A detailed transition plan protected most atrial fibrillation patients from strokes and major bleeding when they switched oral anticoagulants, researchers reported in the August issue of the Journal of the American College of Cardiology.

Following such a plan could help patients safely switch anticoagulants in clinical practice, said Dr. Christian Ruff at Harvard Medical School in Boston and his associates.

They reported an analysis from the ENGAGE AF-TIMI 48 (Effective Anticoagulation With Factor Xa Next Generation in Atrial Fibrillation–Thrombolysis in Myocardial Infarction 48) trial, which randomized more than 21,000 AF patients at high risk of stroke to either the investigational factor Xa inhibitor edoxaban or warfarin. Edoxaban was shown noninferior to warfarin in preventing stroke or systemic embolism (N. Engl. J. Med. 2013; 369:2093-104).

In the past, researchers from the ROCKET AF and ARISTOTLE trials reported excess strokes and bleeding events after patients were switched from blinded factor Xa inhibitors to open-label antithrombotics, the investigators said.

In response, ENGAGE AF-TIMI 48 patients and their physicians decided together whether to switch to an open-label vitamin K antagonist (VKA) or a newer oral anticoagulant at the end of the trial, the researchers said. Patients then received a transition kit with a 14-day supply of either a half-dose edoxaban for patients switching from blinded edoxaban to open warfarin, or a placebo for patients switching from blinded to open warfarin. Patients also underwent at least three international normalized ratio (INR) tests during the first 2 weeks of the transition period and were dosed based on a VKA titration algorithm designed to quickly reach therapeutic INR, they said.

Among 13,642 ENGAGE AF-TIMI patients alive at the end of the trial, 68.2% transitioned to a VKA and 31.2% to a new oral anticoagulant, said the researchers.

Thirty days later, rates of therapeutic INR, stroke, and bleeding events were similar regardless of whether patients had taken low-dose edoxaban, high-dose edoxaban, or warfarin during the trial, they reported. In all, 98.7% of patients switched from high-dose edoxaban had at least one INR of 2 or more, compared with 98.9% of patients switched from low-dose edoxaban and 99.4% of patients switched from warfarin, they said (J. Am. Coll. Cardiol. 2014;64:576-84).

Post-transition rates of strokes (1.85% to 1.90% per year) and major bleeding (2.69% to 4.76% per year) also were similar among the three trial groups, they added.

The excess ischemic events in earlier trials probably resulted from relative delays in achieving a therapeutic INR when patients were switched from a newer oral anticoagulant to an open-label VKA, the researchers noted, adding that "VKAs are effective as long as a therapeutic INR can be rapidly reached and maintained."

Daiichi Sankyo funded the ENGAGE AF-TIMI trial. Dr. Ruff reported having been a consultant and receiving honoraria from Daiichi Sankyo. Two coauthors reported financial relationships, six reported having received grant support, and two reported employment with Daiichi Sankyo.

A detailed transition plan protected most atrial fibrillation patients from strokes and major bleeding when they switched oral anticoagulants, researchers reported in the August issue of the Journal of the American College of Cardiology.

Following such a plan could help patients safely switch anticoagulants in clinical practice, said Dr. Christian Ruff at Harvard Medical School in Boston and his associates.

They reported an analysis from the ENGAGE AF-TIMI 48 (Effective Anticoagulation With Factor Xa Next Generation in Atrial Fibrillation–Thrombolysis in Myocardial Infarction 48) trial, which randomized more than 21,000 AF patients at high risk of stroke to either the investigational factor Xa inhibitor edoxaban or warfarin. Edoxaban was shown noninferior to warfarin in preventing stroke or systemic embolism (N. Engl. J. Med. 2013; 369:2093-104).

In the past, researchers from the ROCKET AF and ARISTOTLE trials reported excess strokes and bleeding events after patients were switched from blinded factor Xa inhibitors to open-label antithrombotics, the investigators said.

In response, ENGAGE AF-TIMI 48 patients and their physicians decided together whether to switch to an open-label vitamin K antagonist (VKA) or a newer oral anticoagulant at the end of the trial, the researchers said. Patients then received a transition kit with a 14-day supply of either a half-dose edoxaban for patients switching from blinded edoxaban to open warfarin, or a placebo for patients switching from blinded to open warfarin. Patients also underwent at least three international normalized ratio (INR) tests during the first 2 weeks of the transition period and were dosed based on a VKA titration algorithm designed to quickly reach therapeutic INR, they said.

Among 13,642 ENGAGE AF-TIMI patients alive at the end of the trial, 68.2% transitioned to a VKA and 31.2% to a new oral anticoagulant, said the researchers.

Thirty days later, rates of therapeutic INR, stroke, and bleeding events were similar regardless of whether patients had taken low-dose edoxaban, high-dose edoxaban, or warfarin during the trial, they reported. In all, 98.7% of patients switched from high-dose edoxaban had at least one INR of 2 or more, compared with 98.9% of patients switched from low-dose edoxaban and 99.4% of patients switched from warfarin, they said (J. Am. Coll. Cardiol. 2014;64:576-84).

Post-transition rates of strokes (1.85% to 1.90% per year) and major bleeding (2.69% to 4.76% per year) also were similar among the three trial groups, they added.

The excess ischemic events in earlier trials probably resulted from relative delays in achieving a therapeutic INR when patients were switched from a newer oral anticoagulant to an open-label VKA, the researchers noted, adding that "VKAs are effective as long as a therapeutic INR can be rapidly reached and maintained."

Daiichi Sankyo funded the ENGAGE AF-TIMI trial. Dr. Ruff reported having been a consultant and receiving honoraria from Daiichi Sankyo. Two coauthors reported financial relationships, six reported having received grant support, and two reported employment with Daiichi Sankyo.

A detailed transition plan protected most atrial fibrillation patients from strokes and major bleeding when they switched oral anticoagulants, researchers reported in the August issue of the Journal of the American College of Cardiology.

Following such a plan could help patients safely switch anticoagulants in clinical practice, said Dr. Christian Ruff at Harvard Medical School in Boston and his associates.

They reported an analysis from the ENGAGE AF-TIMI 48 (Effective Anticoagulation With Factor Xa Next Generation in Atrial Fibrillation–Thrombolysis in Myocardial Infarction 48) trial, which randomized more than 21,000 AF patients at high risk of stroke to either the investigational factor Xa inhibitor edoxaban or warfarin. Edoxaban was shown noninferior to warfarin in preventing stroke or systemic embolism (N. Engl. J. Med. 2013; 369:2093-104).

In the past, researchers from the ROCKET AF and ARISTOTLE trials reported excess strokes and bleeding events after patients were switched from blinded factor Xa inhibitors to open-label antithrombotics, the investigators said.

In response, ENGAGE AF-TIMI 48 patients and their physicians decided together whether to switch to an open-label vitamin K antagonist (VKA) or a newer oral anticoagulant at the end of the trial, the researchers said. Patients then received a transition kit with a 14-day supply of either a half-dose edoxaban for patients switching from blinded edoxaban to open warfarin, or a placebo for patients switching from blinded to open warfarin. Patients also underwent at least three international normalized ratio (INR) tests during the first 2 weeks of the transition period and were dosed based on a VKA titration algorithm designed to quickly reach therapeutic INR, they said.

Among 13,642 ENGAGE AF-TIMI patients alive at the end of the trial, 68.2% transitioned to a VKA and 31.2% to a new oral anticoagulant, said the researchers.

Thirty days later, rates of therapeutic INR, stroke, and bleeding events were similar regardless of whether patients had taken low-dose edoxaban, high-dose edoxaban, or warfarin during the trial, they reported. In all, 98.7% of patients switched from high-dose edoxaban had at least one INR of 2 or more, compared with 98.9% of patients switched from low-dose edoxaban and 99.4% of patients switched from warfarin, they said (J. Am. Coll. Cardiol. 2014;64:576-84).

Post-transition rates of strokes (1.85% to 1.90% per year) and major bleeding (2.69% to 4.76% per year) also were similar among the three trial groups, they added.

The excess ischemic events in earlier trials probably resulted from relative delays in achieving a therapeutic INR when patients were switched from a newer oral anticoagulant to an open-label VKA, the researchers noted, adding that "VKAs are effective as long as a therapeutic INR can be rapidly reached and maintained."

Daiichi Sankyo funded the ENGAGE AF-TIMI trial. Dr. Ruff reported having been a consultant and receiving honoraria from Daiichi Sankyo. Two coauthors reported financial relationships, six reported having received grant support, and two reported employment with Daiichi Sankyo.

Slide showing LSCs

Credit: Robert Paulson

Preclinical research suggests that non-steroidal anti-inflammatory drugs (NSAIDs) might help prevent relapse in acute myeloid leukemia (AML).

NSAIDs inhibit 5-lipoxygenase (5-LO), and researchers found this enzyme plays a key role in the survival of leukemic stem cells (LSCs).

In cell cultures and mouse models of AML, NSAIDs selectively and efficiently attacked LSCs.

The researchers detailed these results in Cancer Research.

“These results provide the basis for the potential implementation of 5-LO-inhibitors as stem cell therapeutic agents for a sustained AML cure, although this must be investigated further in preclinical and clinical studies,” said study author Martin Ruthardt, MD, of Goethe University in Frankfurt, Germany.

Recent research suggested 5-LO is critical to the maintenance of LSCs in chronic myeloid leukemia. So Dr Ruthardt and his colleagues hypothesized that 5-LO might be a therapeutic target for AML.

To test that theory, the researchers inhibited 5-LO in a PML/RARα -positive model of AML. As LSC models, the team used Sca-1+/lin- murine hematopoietic stem and progenitor cells (HSPCs), which were retrovirally transduced with PML/RARα.

The group found that inhibiting 5-LO with the NSAIDs CJ-13,610 and zileuton reduced the stem cell capacity of PML/RARα-expressing HSPCs. The NSAIDs also inhibited Wnt signaling.

On the other hand, targeted genetic inhibition of 5-LO did not recapitulate the NSAIDs’ effects on leukemogenic potential and the aberrant stem cell capacity induced by PML/RARα.

Further investigation revealed that Wnt and LSC inhibition is mediated by the enzymatically inactive form of 5-LO, which hinders the nuclear translocation of ß-catenin. So it seems 5-LO inhibitors also inhibit Wnt signaling due to the generation of a catalytically inactive form of 5-LO, which assumes a new function.

“[T]here are plans for further molecular biological studies with the objective of understanding exactly how the 5-LO inhibitors act on the leukemic cells,” said study author Thorsten J. Maier, MD, PhD, of Aarhus University in Denmark.

Slide showing LSCs

Credit: Robert Paulson

Preclinical research suggests that non-steroidal anti-inflammatory drugs (NSAIDs) might help prevent relapse in acute myeloid leukemia (AML).

NSAIDs inhibit 5-lipoxygenase (5-LO), and researchers found this enzyme plays a key role in the survival of leukemic stem cells (LSCs).

In cell cultures and mouse models of AML, NSAIDs selectively and efficiently attacked LSCs.

The researchers detailed these results in Cancer Research.

“These results provide the basis for the potential implementation of 5-LO-inhibitors as stem cell therapeutic agents for a sustained AML cure, although this must be investigated further in preclinical and clinical studies,” said study author Martin Ruthardt, MD, of Goethe University in Frankfurt, Germany.

Recent research suggested 5-LO is critical to the maintenance of LSCs in chronic myeloid leukemia. So Dr Ruthardt and his colleagues hypothesized that 5-LO might be a therapeutic target for AML.

To test that theory, the researchers inhibited 5-LO in a PML/RARα -positive model of AML. As LSC models, the team used Sca-1+/lin- murine hematopoietic stem and progenitor cells (HSPCs), which were retrovirally transduced with PML/RARα.

The group found that inhibiting 5-LO with the NSAIDs CJ-13,610 and zileuton reduced the stem cell capacity of PML/RARα-expressing HSPCs. The NSAIDs also inhibited Wnt signaling.

On the other hand, targeted genetic inhibition of 5-LO did not recapitulate the NSAIDs’ effects on leukemogenic potential and the aberrant stem cell capacity induced by PML/RARα.

Further investigation revealed that Wnt and LSC inhibition is mediated by the enzymatically inactive form of 5-LO, which hinders the nuclear translocation of ß-catenin. So it seems 5-LO inhibitors also inhibit Wnt signaling due to the generation of a catalytically inactive form of 5-LO, which assumes a new function.

“[T]here are plans for further molecular biological studies with the objective of understanding exactly how the 5-LO inhibitors act on the leukemic cells,” said study author Thorsten J. Maier, MD, PhD, of Aarhus University in Denmark.

Slide showing LSCs

Credit: Robert Paulson

Preclinical research suggests that non-steroidal anti-inflammatory drugs (NSAIDs) might help prevent relapse in acute myeloid leukemia (AML).

NSAIDs inhibit 5-lipoxygenase (5-LO), and researchers found this enzyme plays a key role in the survival of leukemic stem cells (LSCs).

In cell cultures and mouse models of AML, NSAIDs selectively and efficiently attacked LSCs.

The researchers detailed these results in Cancer Research.

“These results provide the basis for the potential implementation of 5-LO-inhibitors as stem cell therapeutic agents for a sustained AML cure, although this must be investigated further in preclinical and clinical studies,” said study author Martin Ruthardt, MD, of Goethe University in Frankfurt, Germany.

Recent research suggested 5-LO is critical to the maintenance of LSCs in chronic myeloid leukemia. So Dr Ruthardt and his colleagues hypothesized that 5-LO might be a therapeutic target for AML.

To test that theory, the researchers inhibited 5-LO in a PML/RARα -positive model of AML. As LSC models, the team used Sca-1+/lin- murine hematopoietic stem and progenitor cells (HSPCs), which were retrovirally transduced with PML/RARα.

The group found that inhibiting 5-LO with the NSAIDs CJ-13,610 and zileuton reduced the stem cell capacity of PML/RARα-expressing HSPCs. The NSAIDs also inhibited Wnt signaling.

On the other hand, targeted genetic inhibition of 5-LO did not recapitulate the NSAIDs’ effects on leukemogenic potential and the aberrant stem cell capacity induced by PML/RARα.

Further investigation revealed that Wnt and LSC inhibition is mediated by the enzymatically inactive form of 5-LO, which hinders the nuclear translocation of ß-catenin. So it seems 5-LO inhibitors also inhibit Wnt signaling due to the generation of a catalytically inactive form of 5-LO, which assumes a new function.

“[T]here are plans for further molecular biological studies with the objective of understanding exactly how the 5-LO inhibitors act on the leukemic cells,” said study author Thorsten J. Maier, MD, PhD, of Aarhus University in Denmark.

Prescription drugs

Credit: CDC

The introduction of expedited drug approvals in the US coincides with an increase in black box warnings and market withdrawals, a new study shows.

The researchers could not establish a causal link between the events, but they still believe physicians and patients should exercise caution when considering the use of drugs approved since 1992.

That’s when Congress passed a law allowing the Food and Drug Administration (FDA) to collect fees to expedite drug approvals.

The researchers found that drugs approved after the law—the Prescription Drug User Fee Act (PDUFA)—was enacted were significantly more likely than previously approved drugs to acquire a black box warning or be withdrawn for safety reasons.

“Our findings raise concern that the FDA is rushing its review of new drugs and allowing potentially unsafe medicines onto the market,” said Karen Lasser, MD, MPH, of Boston University School of Medicine and Boston Medical Center.

“As a primary care doctor, I’m wary of prescribing brand new drugs unless they’re really a breakthrough, since their full risks are often unknown. And patients should be wary too.”

Dr Lasser and her colleagues expressed this viewpoint and described the research supporting it in Health Affairs.

The researchers collected information on new molecular entities (active ingredients that have never before been marketed in the US in any form) approved by the FDA between 1975 and 2009.

Of these 748 drugs, 114 (15.2%) received one or more black box warnings, and 32 (4.3%) were withdrawn from the market for safety reasons.

Very few of the 32 withdrawn drugs had clearly unique benefits at the time of approval, but all had unique risks that eventually led to their withdrawal.

Half of all black box warnings appeared after a drug had been on the market for 12 years, and safety withdrawals have occurred as late as 30 years after a drug’s initial release.

Drugs approved after the enactment of PDUFA were significantly more likely to receive a black box warning or withdrawal than drugs approved before PDUFA’s enactment—26.7 out of 100 drugs vs 21.2 out of 100 drugs (P<0.05) at up to 16 years of follow-up.

Since the law was enacted, the average approval time for all drugs has fallen from 34 months to 16 months.

“Since PDUFA, the review times for the drugs that are eventually banned have decreased enormously,” said study author Sidney Wolfe, MD, founder of Public Citizen’s Health Research Group and author of Worst Pills, Best Pills.

“These shorter review times, combined with increased FDA authority to require further studies after approval—rather than settling safety issues before approval—possibly contributes to the increased rate of withdrawals and black box warnings.”

The researchers noted that they could not determine with certainty whether PDUFA caused the increase in drug withdrawals and black box warnings. It’s possible that other factors caused or contributed to the decrease in safety observed in recent years.

Prescription drugs

Credit: CDC

The introduction of expedited drug approvals in the US coincides with an increase in black box warnings and market withdrawals, a new study shows.

The researchers could not establish a causal link between the events, but they still believe physicians and patients should exercise caution when considering the use of drugs approved since 1992.

That’s when Congress passed a law allowing the Food and Drug Administration (FDA) to collect fees to expedite drug approvals.

The researchers found that drugs approved after the law—the Prescription Drug User Fee Act (PDUFA)—was enacted were significantly more likely than previously approved drugs to acquire a black box warning or be withdrawn for safety reasons.

“Our findings raise concern that the FDA is rushing its review of new drugs and allowing potentially unsafe medicines onto the market,” said Karen Lasser, MD, MPH, of Boston University School of Medicine and Boston Medical Center.

“As a primary care doctor, I’m wary of prescribing brand new drugs unless they’re really a breakthrough, since their full risks are often unknown. And patients should be wary too.”

Dr Lasser and her colleagues expressed this viewpoint and described the research supporting it in Health Affairs.

The researchers collected information on new molecular entities (active ingredients that have never before been marketed in the US in any form) approved by the FDA between 1975 and 2009.

Of these 748 drugs, 114 (15.2%) received one or more black box warnings, and 32 (4.3%) were withdrawn from the market for safety reasons.

Very few of the 32 withdrawn drugs had clearly unique benefits at the time of approval, but all had unique risks that eventually led to their withdrawal.

Half of all black box warnings appeared after a drug had been on the market for 12 years, and safety withdrawals have occurred as late as 30 years after a drug’s initial release.

Drugs approved after the enactment of PDUFA were significantly more likely to receive a black box warning or withdrawal than drugs approved before PDUFA’s enactment—26.7 out of 100 drugs vs 21.2 out of 100 drugs (P<0.05) at up to 16 years of follow-up.

Since the law was enacted, the average approval time for all drugs has fallen from 34 months to 16 months.

“Since PDUFA, the review times for the drugs that are eventually banned have decreased enormously,” said study author Sidney Wolfe, MD, founder of Public Citizen’s Health Research Group and author of Worst Pills, Best Pills.

“These shorter review times, combined with increased FDA authority to require further studies after approval—rather than settling safety issues before approval—possibly contributes to the increased rate of withdrawals and black box warnings.”

The researchers noted that they could not determine with certainty whether PDUFA caused the increase in drug withdrawals and black box warnings. It’s possible that other factors caused or contributed to the decrease in safety observed in recent years.

Prescription drugs

Credit: CDC

The introduction of expedited drug approvals in the US coincides with an increase in black box warnings and market withdrawals, a new study shows.

The researchers could not establish a causal link between the events, but they still believe physicians and patients should exercise caution when considering the use of drugs approved since 1992.

That’s when Congress passed a law allowing the Food and Drug Administration (FDA) to collect fees to expedite drug approvals.

The researchers found that drugs approved after the law—the Prescription Drug User Fee Act (PDUFA)—was enacted were significantly more likely than previously approved drugs to acquire a black box warning or be withdrawn for safety reasons.

“Our findings raise concern that the FDA is rushing its review of new drugs and allowing potentially unsafe medicines onto the market,” said Karen Lasser, MD, MPH, of Boston University School of Medicine and Boston Medical Center.

“As a primary care doctor, I’m wary of prescribing brand new drugs unless they’re really a breakthrough, since their full risks are often unknown. And patients should be wary too.”

Dr Lasser and her colleagues expressed this viewpoint and described the research supporting it in Health Affairs.

The researchers collected information on new molecular entities (active ingredients that have never before been marketed in the US in any form) approved by the FDA between 1975 and 2009.

Of these 748 drugs, 114 (15.2%) received one or more black box warnings, and 32 (4.3%) were withdrawn from the market for safety reasons.

Very few of the 32 withdrawn drugs had clearly unique benefits at the time of approval, but all had unique risks that eventually led to their withdrawal.

Half of all black box warnings appeared after a drug had been on the market for 12 years, and safety withdrawals have occurred as late as 30 years after a drug’s initial release.

Drugs approved after the enactment of PDUFA were significantly more likely to receive a black box warning or withdrawal than drugs approved before PDUFA’s enactment—26.7 out of 100 drugs vs 21.2 out of 100 drugs (P<0.05) at up to 16 years of follow-up.

Since the law was enacted, the average approval time for all drugs has fallen from 34 months to 16 months.

“Since PDUFA, the review times for the drugs that are eventually banned have decreased enormously,” said study author Sidney Wolfe, MD, founder of Public Citizen’s Health Research Group and author of Worst Pills, Best Pills.

“These shorter review times, combined with increased FDA authority to require further studies after approval—rather than settling safety issues before approval—possibly contributes to the increased rate of withdrawals and black box warnings.”

The researchers noted that they could not determine with certainty whether PDUFA caused the increase in drug withdrawals and black box warnings. It’s possible that other factors caused or contributed to the decrease in safety observed in recent years.

Lab mouse

Results of a new study contradict previous research suggesting mice do not make suitable models for human inflammatory conditions.

The original study, published in PNAS in February 2013, indicated that genomic responses to different acute inflammatory stressors—trauma, burns, sepsis, and infection—are highly similar in humans but poorly reproduced in corresponding mouse models.

The new study, published in PNAS yesterday, suggests that is not the case.

The original study was conducted by Junhee Seok, PhD, of Northwestern University, and his colleagues. It garnered a lot of attention from the scientific community and the general public, reigniting the debate over mouse models’ suitability for medical research.

Tsuyoshi Miyakawa, PhD, of Fujita Health University in Japan, was among those who argued that mice are suitable models, and Dr Seok’s findings were likely incorrect.

So Dr Miyakawa and his colleague, Keizo Takao, PhD, of the National Institute for Physiological Sciences in Japan, reanalyzed the data from Dr Seok’s study using the bioinformatics tool NextBio. 

Dr Seok’s group had compared the expression levels of genes that were altered in a particular human condition between humans and mice.

A comparison of the genomic response between humans and mice, including those genes altered in one species but not in another, obscures the correlation between homologous genes of humans and mice to nearly 0, as the team showed.

The group’s comparison of the gene expression patterns between human burn victims and mouse models of burns, trauma, sepsis, and infection revealed a Pearson’s correlation coefficient (R) that ranged from 0.14 to 0.28. And the percentage of genes whose expression changed in the same direction was 55% to 61%.

In the new analysis based on the same data, Drs Miyakawa and Takao found the R values ranged from 0.36 to 0.59. And 77% to 93% of the genes changed in the same directions between the human condition and the mouse models.

Non-parametric ranking analysis using NextBio showed the pattern of the gene expression changes in mouse models was highly similar to that in human burn conditions—a significant correlation (P = 6.5 x 10^-11 to 1.2 x 10^-35).

Drs Miyakawa and Takao noted that many molecular pathways are commonly dysregulated in human diseases and mouse models. And focusing on the commonalities between human diseases and mouse models will allow us to derive useful information for studying the pathophysiology and pathogenesis of human diseases, as well as aid treatment development.

Lab mouse

Results of a new study contradict previous research suggesting mice do not make suitable models for human inflammatory conditions.

The original study, published in PNAS in February 2013, indicated that genomic responses to different acute inflammatory stressors—trauma, burns, sepsis, and infection—are highly similar in humans but poorly reproduced in corresponding mouse models.

The new study, published in PNAS yesterday, suggests that is not the case.

The original study was conducted by Junhee Seok, PhD, of Northwestern University, and his colleagues. It garnered a lot of attention from the scientific community and the general public, reigniting the debate over mouse models’ suitability for medical research.

Tsuyoshi Miyakawa, PhD, of Fujita Health University in Japan, was among those who argued that mice are suitable models, and Dr Seok’s findings were likely incorrect.

So Dr Miyakawa and his colleague, Keizo Takao, PhD, of the National Institute for Physiological Sciences in Japan, reanalyzed the data from Dr Seok’s study using the bioinformatics tool NextBio. 

Dr Seok’s group had compared the expression levels of genes that were altered in a particular human condition between humans and mice.

A comparison of the genomic response between humans and mice, including those genes altered in one species but not in another, obscures the correlation between homologous genes of humans and mice to nearly 0, as the team showed.

The group’s comparison of the gene expression patterns between human burn victims and mouse models of burns, trauma, sepsis, and infection revealed a Pearson’s correlation coefficient (R) that ranged from 0.14 to 0.28. And the percentage of genes whose expression changed in the same direction was 55% to 61%.

In the new analysis based on the same data, Drs Miyakawa and Takao found the R values ranged from 0.36 to 0.59. And 77% to 93% of the genes changed in the same directions between the human condition and the mouse models.

Non-parametric ranking analysis using NextBio showed the pattern of the gene expression changes in mouse models was highly similar to that in human burn conditions—a significant correlation (P = 6.5 x 10^-11 to 1.2 x 10^-35).

Drs Miyakawa and Takao noted that many molecular pathways are commonly dysregulated in human diseases and mouse models. And focusing on the commonalities between human diseases and mouse models will allow us to derive useful information for studying the pathophysiology and pathogenesis of human diseases, as well as aid treatment development.

Lab mouse

Results of a new study contradict previous research suggesting mice do not make suitable models for human inflammatory conditions.

The original study, published in PNAS in February 2013, indicated that genomic responses to different acute inflammatory stressors—trauma, burns, sepsis, and infection—are highly similar in humans but poorly reproduced in corresponding mouse models.

The new study, published in PNAS yesterday, suggests that is not the case.

The original study was conducted by Junhee Seok, PhD, of Northwestern University, and his colleagues. It garnered a lot of attention from the scientific community and the general public, reigniting the debate over mouse models’ suitability for medical research.

Tsuyoshi Miyakawa, PhD, of Fujita Health University in Japan, was among those who argued that mice are suitable models, and Dr Seok’s findings were likely incorrect.

So Dr Miyakawa and his colleague, Keizo Takao, PhD, of the National Institute for Physiological Sciences in Japan, reanalyzed the data from Dr Seok’s study using the bioinformatics tool NextBio. 

Dr Seok’s group had compared the expression levels of genes that were altered in a particular human condition between humans and mice.

A comparison of the genomic response between humans and mice, including those genes altered in one species but not in another, obscures the correlation between homologous genes of humans and mice to nearly 0, as the team showed.

The group’s comparison of the gene expression patterns between human burn victims and mouse models of burns, trauma, sepsis, and infection revealed a Pearson’s correlation coefficient (R) that ranged from 0.14 to 0.28. And the percentage of genes whose expression changed in the same direction was 55% to 61%.

In the new analysis based on the same data, Drs Miyakawa and Takao found the R values ranged from 0.36 to 0.59. And 77% to 93% of the genes changed in the same directions between the human condition and the mouse models.

Non-parametric ranking analysis using NextBio showed the pattern of the gene expression changes in mouse models was highly similar to that in human burn conditions—a significant correlation (P = 6.5 x 10^-11 to 1.2 x 10^-35).

Drs Miyakawa and Takao noted that many molecular pathways are commonly dysregulated in human diseases and mouse models. And focusing on the commonalities between human diseases and mouse models will allow us to derive useful information for studying the pathophysiology and pathogenesis of human diseases, as well as aid treatment development.

Emmanuel Farber, MD, PhD

Emmanuel Farber, MD, PhD, a renowned pathologist who made fundamental contributions to our understanding of chemical carcinogenesis, passed away on August 3 at the age of 95.

Dr Farber’s studies in experimental pathology demonstrated that chemical carcinogens are capable of binding to nucleic acids, in turn generating specific DNA adducts.

These early studies led to the observation that chemical carcinogenesis is a sequential process.

Dr Farber later proved this theory by showing that cancer could be induced through a series of step-by-step chemical treatments in the liver. He served on the Surgeon General’s first Advisory Committee on Smoking and Health from 1961 to 1964.

The committee was responsible for issuing the 1964 Surgeon General’s Report, which has now done more to prevent tobacco-related disease than any other preventive measure.

Throughout his career, Dr Farber promoted the concept that to understand carcinogenesis, one must also understand the cellular, genetic, metabolic, and molecular changes that are occurring during the process. This mindset, along with Dr Farber’s energy and enthusiasm in exploring the nature of cancer, has served as a source of inspiration and guidance for cancer researchers worldwide.

Dr Farber was born in Toronto, Canada, on October 19, 1918. He obtained his medical degree from the Faculty of Medicine, University of Toronto in 1942.

After completing his residency training in pathology at the Hamilton General Hospital in Ontario, Canada, he served in the Royal Canadian Army Medical Corps and later obtained a doctorate in biochemistry from the University of California, Berkeley.

His academic career began at Tulane University in New Orleans, Louisiana. It continued with his appointment as Professor and Chairman of Pathology and Professor of Biochemistry at the University of Pittsburgh School of Medicine and at the Fels Research Institute, Temple University School of Medicine, in Philadelphia, Pennsylvania, where he was Professor of Pathology and Biochemistry and Director of the Institute.

In 1975, Dr Farber moved back to his native city to take the post of Professor and Chairman of the Department of Pathology and Professor in the Department of Biochemistry at the University of Toronto. At his death, he held the title of Chairman Emeritus and Professor in the Department of Pathology at the University of Toronto.

Dr Farber is survived by his daughter Naomi Farber, son-in-law Steven Grosby, and grandson Samuel Grosby, who wish to extend their sincere appreciation to those who enriched his personal and professional life and joined his tireless search for scientific truth.

Emmanuel Farber, MD, PhD

Emmanuel Farber, MD, PhD, a renowned pathologist who made fundamental contributions to our understanding of chemical carcinogenesis, passed away on August 3 at the age of 95.

Dr Farber’s studies in experimental pathology demonstrated that chemical carcinogens are capable of binding to nucleic acids, in turn generating specific DNA adducts.

These early studies led to the observation that chemical carcinogenesis is a sequential process.

Dr Farber later proved this theory by showing that cancer could be induced through a series of step-by-step chemical treatments in the liver. He served on the Surgeon General’s first Advisory Committee on Smoking and Health from 1961 to 1964.

The committee was responsible for issuing the 1964 Surgeon General’s Report, which has now done more to prevent tobacco-related disease than any other preventive measure.

Throughout his career, Dr Farber promoted the concept that to understand carcinogenesis, one must also understand the cellular, genetic, metabolic, and molecular changes that are occurring during the process. This mindset, along with Dr Farber’s energy and enthusiasm in exploring the nature of cancer, has served as a source of inspiration and guidance for cancer researchers worldwide.

Dr Farber was born in Toronto, Canada, on October 19, 1918. He obtained his medical degree from the Faculty of Medicine, University of Toronto in 1942.

After completing his residency training in pathology at the Hamilton General Hospital in Ontario, Canada, he served in the Royal Canadian Army Medical Corps and later obtained a doctorate in biochemistry from the University of California, Berkeley.

His academic career began at Tulane University in New Orleans, Louisiana. It continued with his appointment as Professor and Chairman of Pathology and Professor of Biochemistry at the University of Pittsburgh School of Medicine and at the Fels Research Institute, Temple University School of Medicine, in Philadelphia, Pennsylvania, where he was Professor of Pathology and Biochemistry and Director of the Institute.

In 1975, Dr Farber moved back to his native city to take the post of Professor and Chairman of the Department of Pathology and Professor in the Department of Biochemistry at the University of Toronto. At his death, he held the title of Chairman Emeritus and Professor in the Department of Pathology at the University of Toronto.

Dr Farber is survived by his daughter Naomi Farber, son-in-law Steven Grosby, and grandson Samuel Grosby, who wish to extend their sincere appreciation to those who enriched his personal and professional life and joined his tireless search for scientific truth.

Emmanuel Farber, MD, PhD

Emmanuel Farber, MD, PhD, a renowned pathologist who made fundamental contributions to our understanding of chemical carcinogenesis, passed away on August 3 at the age of 95.

Dr Farber’s studies in experimental pathology demonstrated that chemical carcinogens are capable of binding to nucleic acids, in turn generating specific DNA adducts.

These early studies led to the observation that chemical carcinogenesis is a sequential process.

Dr Farber later proved this theory by showing that cancer could be induced through a series of step-by-step chemical treatments in the liver. He served on the Surgeon General’s first Advisory Committee on Smoking and Health from 1961 to 1964.

The committee was responsible for issuing the 1964 Surgeon General’s Report, which has now done more to prevent tobacco-related disease than any other preventive measure.

Throughout his career, Dr Farber promoted the concept that to understand carcinogenesis, one must also understand the cellular, genetic, metabolic, and molecular changes that are occurring during the process. This mindset, along with Dr Farber’s energy and enthusiasm in exploring the nature of cancer, has served as a source of inspiration and guidance for cancer researchers worldwide.

Dr Farber was born in Toronto, Canada, on October 19, 1918. He obtained his medical degree from the Faculty of Medicine, University of Toronto in 1942.

After completing his residency training in pathology at the Hamilton General Hospital in Ontario, Canada, he served in the Royal Canadian Army Medical Corps and later obtained a doctorate in biochemistry from the University of California, Berkeley.

His academic career began at Tulane University in New Orleans, Louisiana. It continued with his appointment as Professor and Chairman of Pathology and Professor of Biochemistry at the University of Pittsburgh School of Medicine and at the Fels Research Institute, Temple University School of Medicine, in Philadelphia, Pennsylvania, where he was Professor of Pathology and Biochemistry and Director of the Institute.

In 1975, Dr Farber moved back to his native city to take the post of Professor and Chairman of the Department of Pathology and Professor in the Department of Biochemistry at the University of Toronto. At his death, he held the title of Chairman Emeritus and Professor in the Department of Pathology at the University of Toronto.

Dr Farber is survived by his daughter Naomi Farber, son-in-law Steven Grosby, and grandson Samuel Grosby, who wish to extend their sincere appreciation to those who enriched his personal and professional life and joined his tireless search for scientific truth.

You love Dr. Baumann’s Cosmeceutical Critique column in Skin & Allergy News, and soon that content will be expanded in a new book entitled "Cosmeceuticals and Cosmetic Ingredients," available this November via Amazon.com. Meet Dr. Baumann at the Skin Disease Education Foundation (SDEF)/Skin & Allergy News Booth #1500 from 12:00-12:30 p.m. on Saturday, Aug. 9 at the 2014 Summer Academy Meeting in Chicago. And be sure to pick up a copy of her latest column from Skin & Allergy News, the leading news publication for aesthetic, medical, and surgical dermatology.

In addition, you can visit Dr. Baumann at her booth (#1716) during the meeting.

Read Dr. Baumann’s columns online at edermatologynews.com.

[email protected]

You love Dr. Baumann’s Cosmeceutical Critique column in Skin & Allergy News, and soon that content will be expanded in a new book entitled "Cosmeceuticals and Cosmetic Ingredients," available this November via Amazon.com. Meet Dr. Baumann at the Skin Disease Education Foundation (SDEF)/Skin & Allergy News Booth #1500 from 12:00-12:30 p.m. on Saturday, Aug. 9 at the 2014 Summer Academy Meeting in Chicago. And be sure to pick up a copy of her latest column from Skin & Allergy News, the leading news publication for aesthetic, medical, and surgical dermatology.

In addition, you can visit Dr. Baumann at her booth (#1716) during the meeting.

Read Dr. Baumann’s columns online at edermatologynews.com.

[email protected]

You love Dr. Baumann’s Cosmeceutical Critique column in Skin & Allergy News, and soon that content will be expanded in a new book entitled "Cosmeceuticals and Cosmetic Ingredients," available this November via Amazon.com. Meet Dr. Baumann at the Skin Disease Education Foundation (SDEF)/Skin & Allergy News Booth #1500 from 12:00-12:30 p.m. on Saturday, Aug. 9 at the 2014 Summer Academy Meeting in Chicago. And be sure to pick up a copy of her latest column from Skin & Allergy News, the leading news publication for aesthetic, medical, and surgical dermatology.

In addition, you can visit Dr. Baumann at her booth (#1716) during the meeting.

Read Dr. Baumann’s columns online at edermatologynews.com.

[email protected]

Among women who undergo minimally invasive hysterectomy with electric power morcellation, the rate of uterine cancer is 27 cases per 10,000 women at the time of the procedure, according to a recent study published in the Journal of the American Medical Association.¹ That figure translates into approximately one case of undetected uterine cancer in every 368 women undergoing hysterectomy. Earlier this year the US Food and Drug Administration (FDA) estimated the prevalence of uterine sarcoma at one case in every 352 women.²

Leading up to publication of this study in late July, there had been concern and considerable discussion—including a 2-day hearing convened by the FDA— about whether power morcellation may result in the spread of undetected malignancies and, if so, how often that may occur.

Although power morcellators have been available commercially for two decades, accurate estimates of the prevalence of malignancy at the time of power morcellation have been lacking.

Jason D. Wright, MD, and colleagues from Columbia University used the Perspective database, a large insurance database, to investigate the prevalence of underlying cancer in women who underwent uterine morcellation during minimally invasive hysterectomy from 2006 to 2012. This database is an “all-payer” database that includes more than 500 hospitals in the United States, many of them urban teaching centers.

The cohort included 232,882 women who underwent minimally invasive hysterectomy, including 36,470 (15.7%) who had uterine morcellation during the procedure. Among women who underwent morcellation, 99 cases of uterine cancer were identified, a prevalence of 27 cases per 10,000 women (95% confidence interval [CI], 22–32).

Among women who underwent power morcellation, the prevalence of underlying cancer and endometrial hyperplasia increased with age. For example, compared with women younger than 40 years, the prevalence ratio for uterine malignancy was:

• 4.97 (95% CI, 1.91–12.93) in women aged 50 to 54 years
• 19.37 (95% CI, 7.66–48.95) in those aged 55 to 59 years
• 21.36 (95% CI, 7.22–63.21) in women aged 60 to 64
• 35.97 (95% CI, 14.14–91.53) in women aged 65 or older. 

“Prevalence information is the first step in determining the risk of spreading cancer with morcellation,” Wright and colleagues observe. “Patients considering morcellation should be adequately counseled about the prevalence of cancerous and precancerous conditions prior to undergoing the procedure.”

Among women who undergo minimally invasive hysterectomy with electric power morcellation, the rate of uterine cancer is 27 cases per 10,000 women at the time of the procedure, according to a recent study published in the Journal of the American Medical Association.¹ That figure translates into approximately one case of undetected uterine cancer in every 368 women undergoing hysterectomy. Earlier this year the US Food and Drug Administration (FDA) estimated the prevalence of uterine sarcoma at one case in every 352 women.²

Leading up to publication of this study in late July, there had been concern and considerable discussion—including a 2-day hearing convened by the FDA— about whether power morcellation may result in the spread of undetected malignancies and, if so, how often that may occur.

Although power morcellators have been available commercially for two decades, accurate estimates of the prevalence of malignancy at the time of power morcellation have been lacking.

Jason D. Wright, MD, and colleagues from Columbia University used the Perspective database, a large insurance database, to investigate the prevalence of underlying cancer in women who underwent uterine morcellation during minimally invasive hysterectomy from 2006 to 2012. This database is an “all-payer” database that includes more than 500 hospitals in the United States, many of them urban teaching centers.

The cohort included 232,882 women who underwent minimally invasive hysterectomy, including 36,470 (15.7%) who had uterine morcellation during the procedure. Among women who underwent morcellation, 99 cases of uterine cancer were identified, a prevalence of 27 cases per 10,000 women (95% confidence interval [CI], 22–32).

Among women who underwent power morcellation, the prevalence of underlying cancer and endometrial hyperplasia increased with age. For example, compared with women younger than 40 years, the prevalence ratio for uterine malignancy was:

• 4.97 (95% CI, 1.91–12.93) in women aged 50 to 54 years
• 19.37 (95% CI, 7.66–48.95) in those aged 55 to 59 years
• 21.36 (95% CI, 7.22–63.21) in women aged 60 to 64
• 35.97 (95% CI, 14.14–91.53) in women aged 65 or older. 

“Prevalence information is the first step in determining the risk of spreading cancer with morcellation,” Wright and colleagues observe. “Patients considering morcellation should be adequately counseled about the prevalence of cancerous and precancerous conditions prior to undergoing the procedure.”

Among women who undergo minimally invasive hysterectomy with electric power morcellation, the rate of uterine cancer is 27 cases per 10,000 women at the time of the procedure, according to a recent study published in the Journal of the American Medical Association.¹ That figure translates into approximately one case of undetected uterine cancer in every 368 women undergoing hysterectomy. Earlier this year the US Food and Drug Administration (FDA) estimated the prevalence of uterine sarcoma at one case in every 352 women.²

Leading up to publication of this study in late July, there had been concern and considerable discussion—including a 2-day hearing convened by the FDA— about whether power morcellation may result in the spread of undetected malignancies and, if so, how often that may occur.

Although power morcellators have been available commercially for two decades, accurate estimates of the prevalence of malignancy at the time of power morcellation have been lacking.

Jason D. Wright, MD, and colleagues from Columbia University used the Perspective database, a large insurance database, to investigate the prevalence of underlying cancer in women who underwent uterine morcellation during minimally invasive hysterectomy from 2006 to 2012. This database is an “all-payer” database that includes more than 500 hospitals in the United States, many of them urban teaching centers.

The cohort included 232,882 women who underwent minimally invasive hysterectomy, including 36,470 (15.7%) who had uterine morcellation during the procedure. Among women who underwent morcellation, 99 cases of uterine cancer were identified, a prevalence of 27 cases per 10,000 women (95% confidence interval [CI], 22–32).

Among women who underwent power morcellation, the prevalence of underlying cancer and endometrial hyperplasia increased with age. For example, compared with women younger than 40 years, the prevalence ratio for uterine malignancy was:

• 4.97 (95% CI, 1.91–12.93) in women aged 50 to 54 years
• 19.37 (95% CI, 7.66–48.95) in those aged 55 to 59 years
• 21.36 (95% CI, 7.22–63.21) in women aged 60 to 64
• 35.97 (95% CI, 14.14–91.53) in women aged 65 or older. 

“Prevalence information is the first step in determining the risk of spreading cancer with morcellation,” Wright and colleagues observe. “Patients considering morcellation should be adequately counseled about the prevalence of cancerous and precancerous conditions prior to undergoing the procedure.”

Older veterans with traumatic brain injury (TBI) are 60% more likely to develop dementia later in life, compared with veterans without TBI, according to a study published online ahead of print June 25 in Neurology. The study involved 188,764 veterans ages 55 and older. At the study’s outset, each participant was free of dementia and had at least one inpatient or outpatient visit to a health care facility at baseline (2000 to 2003) and during the follow-up (2003 to 2012). A total of 1,229 veterans had a TBI diagnosis; 196 veterans with TBI (16%) developed dementia, and 18,255 (10%) of those without TBI developed dementia. On average, veterans with TBI developed dementia two years earlier than those without TBI. “If we assume that this relationship is causal, it seems likely that the same increased risk probably occurs with TBI in the civilian population as well,” said the researchers.

Higher levels of depressive symptoms, stress, and hostility are associated with a significantly increased risk of stroke or transient ischemic attack (TIA) in middle-aged and older adults, according to a study published online ahead of print July 10 in Stroke. Researchers used data from the Multi-Ethnic Study of Atherosclerosis (MESA) to determine how psychologic factors might influence the risk for chronic disease. The investigators examined data for 6,749 adults (ages 45 to 84; 53% women) as they completed questionnaires assessing chronic stress, depressive symptoms, anger, and hostility during a two-year period. Hazard ratios indicated a significantly elevated risk of stroke or TIA for the highest scoring group, compared with the lowest scoring group, for depressive symptoms (HR, 1.86), chronic stress (HR, 1.59), and hostility (HR, 2.22). No significant increased risk was associated with anger.

Patients with mild to moderate Parkinson’s disease can improve their symptoms with regular walking, according to a study published online ahead of print July 2 in Neurology. Investigators included 60 individuals who participated in a randomized trial of various exercise regimens for six months. Eighty-one percent of participants completed the study with a mean attendance of 83.3%. Subjects took additional tests to gauge their aerobic fitness, tiredness, and other factors. Brisk walking reduced tiredness by 11%, improved motor function and mood by 15%, improved attention and response control scores by 14%, and increased aerobic fitness and gait speed by 7%. With regard to motor function, participants improved by an average of 2.8 points. “The results of our study suggest that walking may provide a safe and easily accessible way of improving the symptoms of Parkinson’s disease and improve quality of life,” stated the researchers.

Mild traumatic brain injury (TBI) may result in brain damage and memory and thinking problems, according to a study published online ahead of print July 16 in Neurology. Fifty-three patients (44 with mild TBI and nine with moderate TBI) were compared with 33 participants without brain injury. Each subject underwent testing to assess his or her memory and thinking skills. Participants also had diffusion tensor imaging scans. Those with injuries had brain damage in white matter that consisted of disruption to nerve axons. Researchers also determined that scores on the verbal letter fluency task were 25% lower in individuals with injury than in individuals without injury. “We studied patients who had suffered clinically mild injuries, often from common accidents such as falling from a bicycle, or slow-speed car accidents. This finding is especially important, as 90% of all TBIs are mild to moderate,” said the researchers.

Patients with a traumatic brain injury (TBI) who received erythropoietin (EPO) or maintained a higher hemoglobin concentration through blood transfusion did not have an improved neurologic outcome at six months, according to a study published in the July 2 issue of JAMA. The randomized study included 200 patients (erythropoietin, n = 102; placebo, n = 98) with a closed head injury at neurosurgical intensive care units in two US level I trauma centers between May 2006 and August 2012. Patients were enrolled within six hours of injury and had to be unable to follow commands after initial stabilization. Overall, transfusing at higher hemoglobin concentrations was associated with a higher risk of adverse events. Researchers also observed a higher incidence of thromboembolic events for the transfusion threshold of 10 g/dL (21.8%) versus the threshold of 7 g/dL (8.1%)

Frontline Medical Communications and the National Organization for Rare Disorders (NORD) have signed a partnership agreement to develop educational programs about rare diseases for health care providers. Frontline and NORD also seek to improve awareness, recognition, and understanding of rare diseases among health care providers to accelerate diagnosis and promote optimal care for patients, facilitate the sharing of information among health care providers and rare disease medical experts, and update health care providers on new treatment options and clinical care standards. “Innovative multichannel educational programs, developed by both organizations and funded by commercial sponsors, will be distributed to more than 1.2 million health care providers using Frontline’s portfolio of 30 journal brands, corresponding websites, eNewsletters, and live events,” according to Frontline.

Upsher-Smith Laboratories (Maple Grove, Minnesota) announced that Qudexy XR (topiramate) extended-release capsules are now available in the United States. Qudexy XR, a broad-spectrum, once-daily antiepileptic drug is engineered to deliver a smooth pharmacokinetic profile. The FDA approved Qudexy XR in March 2014 as an initial monotherapy in patients 10 and older with primary generalized tonic-clonic seizures and partial-onset seizures. The drug also was approved as adjunctive therapy in patients 2 and older with primary generalized tonic-clonic seizures, partial-onset seizures, and seizures associated with Lennox-Gastaut syndrome. Overall, results from Upsher-Smith’s phase III trial showed that Qudexy XR is generally well tolerated and effective.

Transplanted brain cells producing dopamine remain viable in patients with Parkinson’s disease for several years, according to a study published June 26 in Cell Reports. The study included five patients with Parkinson’s disease who received transplants of fetal tissue-derived, dopamine-producing neurons four to 14 years earlier. Their transplanted dopamine neurons showed no signs of Parkinson’s disease–associated deterioration and appeared healthy. Researchers believe the findings provide further support for stem cells as a source for transplant-ready dopamine neurons. The investigators noted that the neuronal transplant has proven to be a durable treatment for many patients with Parkinson’s disease, with some improving for years without a need for standard medications. The study authors called the new finding “extremely encouraging,” adding that the long life of the transplanted neurons bodes well “for advancing [the technique] as a restoration therapy for Parkinson’s disease.”

Women may recover more quickly than men after a concussion, according to a study published online ahead of print May 6 in Radiology. Researchers examined the medical records and imaging results of 69 patients diagnosed with mild traumatic brain injury (TBI) between 2006 and 2013. The cohort included 47 men, 22 women, and 21 controls (10 men; median age of men, 17; median age of women, 16). Of the 47 men with TBI, 32 (68%) were injured while playing a sport, as were 10 of the 22 women (45%). Although all participants underwent the same evaluation, diffusion tensor imaging scans revealed that compared with the female patients with mild TBI, the male patients with mild TBI had significantly decreased uncinate fasciculus fractional anisotropy values. The average recovery time for all patients with concussion was 54 days. However, compared with women, who recovered in an average of 26.3 days, recovery was significantly longer for men (66.9 days).

Patients with mesial temporal lobe epilepsy who cannot be controlled with medication can now opt for a minimally invasive laser procedure performed under MRI guidance, according to a study published in the June issue of Neurosurgery. Researchers used an MRI-guided stereotactic laser amygdalohippocampotomy in 13 adult patients with epilepsy (median age, 24). During this procedure, a saline-cooled fiber-optic laser probe was targeted at the amygdalohippocampal complex. Using real-time MRI guidance, a neurosurgeon pinpointed the area of the brain responsible for seizure activity and destroyed this tissue without harming nearby brain tissue. Sixty percent of the amygdalohippocampal complex was destroyed, and the average length of the ablated area was 2.5 cm. “Such minimally invasive techniques may be more desirable to patients and result in increased use of epilepsy surgery among the large number of medically intractable epilepsy patients,” according to the investigators.

Researchers identified 10 proteins in the blood that can predict the onset of Alzheimer’s disease, according to a study published online ahead of print July 3 in Alzheimer’s & Dementia. In the international study of 1,148 individuals (220 with mild cognitive impairment [MCI], 452 elderly controls without dementia, and 476 with Alzheimer’s disease), blood samples were analyzed for 26 proteins previously associated with Alzheimer’s disease. Investigators found 16 of the 26 proteins to be strongly associated with brain shrinkage in Alzheimer’s disease or MCI. The researchers conducted a second series of tests to establish which of these proteins could predict the progression from MCI to Alzheimer’s disease. The study authors identified a combination of 10 proteins capable of predicting whether individuals with MCI would develop Alzheimer’s disease within a year with 87% accuracy. “Memory problems are common, but the challenge is identifying who is likely to develop dementia,” according to the researchers.

An international team of researchers has reviewed the diagnostic criteria for Alzheimer’s disease developed by the International Working Group (IWG) and US National Institute on Aging–Alzheimer’s Association, according to a study published in the June issue of Lancet Neurology. The team considered the strengths and weakness of the IWG criteria and proposed advances to improve the diagnostic framework. The investigators asserted that the diagnosis of Alzheimer’s disease can be simplified by requiring the presence of an appropriate clinical Alzheimer’s disease phenotype (typical or atypical) and a pathophysiologic biomarker consistent with the presence of Alzheimer’s pathology. “We propose that downstream topographic biomarkers of the disease, such as volumetric MRI and fluorodeoxyglucose PET, might better serve in the measurement and monitoring of the course of disease,” the team stated

—Kimberly D. Williams

Older veterans with traumatic brain injury (TBI) are 60% more likely to develop dementia later in life, compared with veterans without TBI, according to a study published online ahead of print June 25 in Neurology. The study involved 188,764 veterans ages 55 and older. At the study’s outset, each participant was free of dementia and had at least one inpatient or outpatient visit to a health care facility at baseline (2000 to 2003) and during the follow-up (2003 to 2012). A total of 1,229 veterans had a TBI diagnosis; 196 veterans with TBI (16%) developed dementia, and 18,255 (10%) of those without TBI developed dementia. On average, veterans with TBI developed dementia two years earlier than those without TBI. “If we assume that this relationship is causal, it seems likely that the same increased risk probably occurs with TBI in the civilian population as well,” said the researchers.

Higher levels of depressive symptoms, stress, and hostility are associated with a significantly increased risk of stroke or transient ischemic attack (TIA) in middle-aged and older adults, according to a study published online ahead of print July 10 in Stroke. Researchers used data from the Multi-Ethnic Study of Atherosclerosis (MESA) to determine how psychologic factors might influence the risk for chronic disease. The investigators examined data for 6,749 adults (ages 45 to 84; 53% women) as they completed questionnaires assessing chronic stress, depressive symptoms, anger, and hostility during a two-year period. Hazard ratios indicated a significantly elevated risk of stroke or TIA for the highest scoring group, compared with the lowest scoring group, for depressive symptoms (HR, 1.86), chronic stress (HR, 1.59), and hostility (HR, 2.22). No significant increased risk was associated with anger.

Patients with mild to moderate Parkinson’s disease can improve their symptoms with regular walking, according to a study published online ahead of print July 2 in Neurology. Investigators included 60 individuals who participated in a randomized trial of various exercise regimens for six months. Eighty-one percent of participants completed the study with a mean attendance of 83.3%. Subjects took additional tests to gauge their aerobic fitness, tiredness, and other factors. Brisk walking reduced tiredness by 11%, improved motor function and mood by 15%, improved attention and response control scores by 14%, and increased aerobic fitness and gait speed by 7%. With regard to motor function, participants improved by an average of 2.8 points. “The results of our study suggest that walking may provide a safe and easily accessible way of improving the symptoms of Parkinson’s disease and improve quality of life,” stated the researchers.

Mild traumatic brain injury (TBI) may result in brain damage and memory and thinking problems, according to a study published online ahead of print July 16 in Neurology. Fifty-three patients (44 with mild TBI and nine with moderate TBI) were compared with 33 participants without brain injury. Each subject underwent testing to assess his or her memory and thinking skills. Participants also had diffusion tensor imaging scans. Those with injuries had brain damage in white matter that consisted of disruption to nerve axons. Researchers also determined that scores on the verbal letter fluency task were 25% lower in individuals with injury than in individuals without injury. “We studied patients who had suffered clinically mild injuries, often from common accidents such as falling from a bicycle, or slow-speed car accidents. This finding is especially important, as 90% of all TBIs are mild to moderate,” said the researchers.

Patients with a traumatic brain injury (TBI) who received erythropoietin (EPO) or maintained a higher hemoglobin concentration through blood transfusion did not have an improved neurologic outcome at six months, according to a study published in the July 2 issue of JAMA. The randomized study included 200 patients (erythropoietin, n = 102; placebo, n = 98) with a closed head injury at neurosurgical intensive care units in two US level I trauma centers between May 2006 and August 2012. Patients were enrolled within six hours of injury and had to be unable to follow commands after initial stabilization. Overall, transfusing at higher hemoglobin concentrations was associated with a higher risk of adverse events. Researchers also observed a higher incidence of thromboembolic events for the transfusion threshold of 10 g/dL (21.8%) versus the threshold of 7 g/dL (8.1%)

Frontline Medical Communications and the National Organization for Rare Disorders (NORD) have signed a partnership agreement to develop educational programs about rare diseases for health care providers. Frontline and NORD also seek to improve awareness, recognition, and understanding of rare diseases among health care providers to accelerate diagnosis and promote optimal care for patients, facilitate the sharing of information among health care providers and rare disease medical experts, and update health care providers on new treatment options and clinical care standards. “Innovative multichannel educational programs, developed by both organizations and funded by commercial sponsors, will be distributed to more than 1.2 million health care providers using Frontline’s portfolio of 30 journal brands, corresponding websites, eNewsletters, and live events,” according to Frontline.

Upsher-Smith Laboratories (Maple Grove, Minnesota) announced that Qudexy XR (topiramate) extended-release capsules are now available in the United States. Qudexy XR, a broad-spectrum, once-daily antiepileptic drug is engineered to deliver a smooth pharmacokinetic profile. The FDA approved Qudexy XR in March 2014 as an initial monotherapy in patients 10 and older with primary generalized tonic-clonic seizures and partial-onset seizures. The drug also was approved as adjunctive therapy in patients 2 and older with primary generalized tonic-clonic seizures, partial-onset seizures, and seizures associated with Lennox-Gastaut syndrome. Overall, results from Upsher-Smith’s phase III trial showed that Qudexy XR is generally well tolerated and effective.

Transplanted brain cells producing dopamine remain viable in patients with Parkinson’s disease for several years, according to a study published June 26 in Cell Reports. The study included five patients with Parkinson’s disease who received transplants of fetal tissue-derived, dopamine-producing neurons four to 14 years earlier. Their transplanted dopamine neurons showed no signs of Parkinson’s disease–associated deterioration and appeared healthy. Researchers believe the findings provide further support for stem cells as a source for transplant-ready dopamine neurons. The investigators noted that the neuronal transplant has proven to be a durable treatment for many patients with Parkinson’s disease, with some improving for years without a need for standard medications. The study authors called the new finding “extremely encouraging,” adding that the long life of the transplanted neurons bodes well “for advancing [the technique] as a restoration therapy for Parkinson’s disease.”

Women may recover more quickly than men after a concussion, according to a study published online ahead of print May 6 in Radiology. Researchers examined the medical records and imaging results of 69 patients diagnosed with mild traumatic brain injury (TBI) between 2006 and 2013. The cohort included 47 men, 22 women, and 21 controls (10 men; median age of men, 17; median age of women, 16). Of the 47 men with TBI, 32 (68%) were injured while playing a sport, as were 10 of the 22 women (45%). Although all participants underwent the same evaluation, diffusion tensor imaging scans revealed that compared with the female patients with mild TBI, the male patients with mild TBI had significantly decreased uncinate fasciculus fractional anisotropy values. The average recovery time for all patients with concussion was 54 days. However, compared with women, who recovered in an average of 26.3 days, recovery was significantly longer for men (66.9 days).

Patients with mesial temporal lobe epilepsy who cannot be controlled with medication can now opt for a minimally invasive laser procedure performed under MRI guidance, according to a study published in the June issue of Neurosurgery. Researchers used an MRI-guided stereotactic laser amygdalohippocampotomy in 13 adult patients with epilepsy (median age, 24). During this procedure, a saline-cooled fiber-optic laser probe was targeted at the amygdalohippocampal complex. Using real-time MRI guidance, a neurosurgeon pinpointed the area of the brain responsible for seizure activity and destroyed this tissue without harming nearby brain tissue. Sixty percent of the amygdalohippocampal complex was destroyed, and the average length of the ablated area was 2.5 cm. “Such minimally invasive techniques may be more desirable to patients and result in increased use of epilepsy surgery among the large number of medically intractable epilepsy patients,” according to the investigators.

Researchers identified 10 proteins in the blood that can predict the onset of Alzheimer’s disease, according to a study published online ahead of print July 3 in Alzheimer’s & Dementia. In the international study of 1,148 individuals (220 with mild cognitive impairment [MCI], 452 elderly controls without dementia, and 476 with Alzheimer’s disease), blood samples were analyzed for 26 proteins previously associated with Alzheimer’s disease. Investigators found 16 of the 26 proteins to be strongly associated with brain shrinkage in Alzheimer’s disease or MCI. The researchers conducted a second series of tests to establish which of these proteins could predict the progression from MCI to Alzheimer’s disease. The study authors identified a combination of 10 proteins capable of predicting whether individuals with MCI would develop Alzheimer’s disease within a year with 87% accuracy. “Memory problems are common, but the challenge is identifying who is likely to develop dementia,” according to the researchers.

An international team of researchers has reviewed the diagnostic criteria for Alzheimer’s disease developed by the International Working Group (IWG) and US National Institute on Aging–Alzheimer’s Association, according to a study published in the June issue of Lancet Neurology. The team considered the strengths and weakness of the IWG criteria and proposed advances to improve the diagnostic framework. The investigators asserted that the diagnosis of Alzheimer’s disease can be simplified by requiring the presence of an appropriate clinical Alzheimer’s disease phenotype (typical or atypical) and a pathophysiologic biomarker consistent with the presence of Alzheimer’s pathology. “We propose that downstream topographic biomarkers of the disease, such as volumetric MRI and fluorodeoxyglucose PET, might better serve in the measurement and monitoring of the course of disease,” the team stated

—Kimberly D. Williams

Older veterans with traumatic brain injury (TBI) are 60% more likely to develop dementia later in life, compared with veterans without TBI, according to a study published online ahead of print June 25 in Neurology. The study involved 188,764 veterans ages 55 and older. At the study’s outset, each participant was free of dementia and had at least one inpatient or outpatient visit to a health care facility at baseline (2000 to 2003) and during the follow-up (2003 to 2012). A total of 1,229 veterans had a TBI diagnosis; 196 veterans with TBI (16%) developed dementia, and 18,255 (10%) of those without TBI developed dementia. On average, veterans with TBI developed dementia two years earlier than those without TBI. “If we assume that this relationship is causal, it seems likely that the same increased risk probably occurs with TBI in the civilian population as well,” said the researchers.

Higher levels of depressive symptoms, stress, and hostility are associated with a significantly increased risk of stroke or transient ischemic attack (TIA) in middle-aged and older adults, according to a study published online ahead of print July 10 in Stroke. Researchers used data from the Multi-Ethnic Study of Atherosclerosis (MESA) to determine how psychologic factors might influence the risk for chronic disease. The investigators examined data for 6,749 adults (ages 45 to 84; 53% women) as they completed questionnaires assessing chronic stress, depressive symptoms, anger, and hostility during a two-year period. Hazard ratios indicated a significantly elevated risk of stroke or TIA for the highest scoring group, compared with the lowest scoring group, for depressive symptoms (HR, 1.86), chronic stress (HR, 1.59), and hostility (HR, 2.22). No significant increased risk was associated with anger.

Patients with mild to moderate Parkinson’s disease can improve their symptoms with regular walking, according to a study published online ahead of print July 2 in Neurology. Investigators included 60 individuals who participated in a randomized trial of various exercise regimens for six months. Eighty-one percent of participants completed the study with a mean attendance of 83.3%. Subjects took additional tests to gauge their aerobic fitness, tiredness, and other factors. Brisk walking reduced tiredness by 11%, improved motor function and mood by 15%, improved attention and response control scores by 14%, and increased aerobic fitness and gait speed by 7%. With regard to motor function, participants improved by an average of 2.8 points. “The results of our study suggest that walking may provide a safe and easily accessible way of improving the symptoms of Parkinson’s disease and improve quality of life,” stated the researchers.

Mild traumatic brain injury (TBI) may result in brain damage and memory and thinking problems, according to a study published online ahead of print July 16 in Neurology. Fifty-three patients (44 with mild TBI and nine with moderate TBI) were compared with 33 participants without brain injury. Each subject underwent testing to assess his or her memory and thinking skills. Participants also had diffusion tensor imaging scans. Those with injuries had brain damage in white matter that consisted of disruption to nerve axons. Researchers also determined that scores on the verbal letter fluency task were 25% lower in individuals with injury than in individuals without injury. “We studied patients who had suffered clinically mild injuries, often from common accidents such as falling from a bicycle, or slow-speed car accidents. This finding is especially important, as 90% of all TBIs are mild to moderate,” said the researchers.

Patients with a traumatic brain injury (TBI) who received erythropoietin (EPO) or maintained a higher hemoglobin concentration through blood transfusion did not have an improved neurologic outcome at six months, according to a study published in the July 2 issue of JAMA. The randomized study included 200 patients (erythropoietin, n = 102; placebo, n = 98) with a closed head injury at neurosurgical intensive care units in two US level I trauma centers between May 2006 and August 2012. Patients were enrolled within six hours of injury and had to be unable to follow commands after initial stabilization. Overall, transfusing at higher hemoglobin concentrations was associated with a higher risk of adverse events. Researchers also observed a higher incidence of thromboembolic events for the transfusion threshold of 10 g/dL (21.8%) versus the threshold of 7 g/dL (8.1%)

Frontline Medical Communications and the National Organization for Rare Disorders (NORD) have signed a partnership agreement to develop educational programs about rare diseases for health care providers. Frontline and NORD also seek to improve awareness, recognition, and understanding of rare diseases among health care providers to accelerate diagnosis and promote optimal care for patients, facilitate the sharing of information among health care providers and rare disease medical experts, and update health care providers on new treatment options and clinical care standards. “Innovative multichannel educational programs, developed by both organizations and funded by commercial sponsors, will be distributed to more than 1.2 million health care providers using Frontline’s portfolio of 30 journal brands, corresponding websites, eNewsletters, and live events,” according to Frontline.

Upsher-Smith Laboratories (Maple Grove, Minnesota) announced that Qudexy XR (topiramate) extended-release capsules are now available in the United States. Qudexy XR, a broad-spectrum, once-daily antiepileptic drug is engineered to deliver a smooth pharmacokinetic profile. The FDA approved Qudexy XR in March 2014 as an initial monotherapy in patients 10 and older with primary generalized tonic-clonic seizures and partial-onset seizures. The drug also was approved as adjunctive therapy in patients 2 and older with primary generalized tonic-clonic seizures, partial-onset seizures, and seizures associated with Lennox-Gastaut syndrome. Overall, results from Upsher-Smith’s phase III trial showed that Qudexy XR is generally well tolerated and effective.

Transplanted brain cells producing dopamine remain viable in patients with Parkinson’s disease for several years, according to a study published June 26 in Cell Reports. The study included five patients with Parkinson’s disease who received transplants of fetal tissue-derived, dopamine-producing neurons four to 14 years earlier. Their transplanted dopamine neurons showed no signs of Parkinson’s disease–associated deterioration and appeared healthy. Researchers believe the findings provide further support for stem cells as a source for transplant-ready dopamine neurons. The investigators noted that the neuronal transplant has proven to be a durable treatment for many patients with Parkinson’s disease, with some improving for years without a need for standard medications. The study authors called the new finding “extremely encouraging,” adding that the long life of the transplanted neurons bodes well “for advancing [the technique] as a restoration therapy for Parkinson’s disease.”

Women may recover more quickly than men after a concussion, according to a study published online ahead of print May 6 in Radiology. Researchers examined the medical records and imaging results of 69 patients diagnosed with mild traumatic brain injury (TBI) between 2006 and 2013. The cohort included 47 men, 22 women, and 21 controls (10 men; median age of men, 17; median age of women, 16). Of the 47 men with TBI, 32 (68%) were injured while playing a sport, as were 10 of the 22 women (45%). Although all participants underwent the same evaluation, diffusion tensor imaging scans revealed that compared with the female patients with mild TBI, the male patients with mild TBI had significantly decreased uncinate fasciculus fractional anisotropy values. The average recovery time for all patients with concussion was 54 days. However, compared with women, who recovered in an average of 26.3 days, recovery was significantly longer for men (66.9 days).

Patients with mesial temporal lobe epilepsy who cannot be controlled with medication can now opt for a minimally invasive laser procedure performed under MRI guidance, according to a study published in the June issue of Neurosurgery. Researchers used an MRI-guided stereotactic laser amygdalohippocampotomy in 13 adult patients with epilepsy (median age, 24). During this procedure, a saline-cooled fiber-optic laser probe was targeted at the amygdalohippocampal complex. Using real-time MRI guidance, a neurosurgeon pinpointed the area of the brain responsible for seizure activity and destroyed this tissue without harming nearby brain tissue. Sixty percent of the amygdalohippocampal complex was destroyed, and the average length of the ablated area was 2.5 cm. “Such minimally invasive techniques may be more desirable to patients and result in increased use of epilepsy surgery among the large number of medically intractable epilepsy patients,” according to the investigators.

Researchers identified 10 proteins in the blood that can predict the onset of Alzheimer’s disease, according to a study published online ahead of print July 3 in Alzheimer’s & Dementia. In the international study of 1,148 individuals (220 with mild cognitive impairment [MCI], 452 elderly controls without dementia, and 476 with Alzheimer’s disease), blood samples were analyzed for 26 proteins previously associated with Alzheimer’s disease. Investigators found 16 of the 26 proteins to be strongly associated with brain shrinkage in Alzheimer’s disease or MCI. The researchers conducted a second series of tests to establish which of these proteins could predict the progression from MCI to Alzheimer’s disease. The study authors identified a combination of 10 proteins capable of predicting whether individuals with MCI would develop Alzheimer’s disease within a year with 87% accuracy. “Memory problems are common, but the challenge is identifying who is likely to develop dementia,” according to the researchers.

An international team of researchers has reviewed the diagnostic criteria for Alzheimer’s disease developed by the International Working Group (IWG) and US National Institute on Aging–Alzheimer’s Association, according to a study published in the June issue of Lancet Neurology. The team considered the strengths and weakness of the IWG criteria and proposed advances to improve the diagnostic framework. The investigators asserted that the diagnosis of Alzheimer’s disease can be simplified by requiring the presence of an appropriate clinical Alzheimer’s disease phenotype (typical or atypical) and a pathophysiologic biomarker consistent with the presence of Alzheimer’s pathology. “We propose that downstream topographic biomarkers of the disease, such as volumetric MRI and fluorodeoxyglucose PET, might better serve in the measurement and monitoring of the course of disease,” the team stated

—Kimberly D. Williams

Hematopoietic stem cells
in the bone marrow

A new study helps explain how blood production declines with age and why older individuals are not suitable donors for hematopoietic stem cell (HSC) transplant.

The research also reveals a potential approach for mitigating

the negative effects of aging on the blood, which can lead to anemia,

bone marrow failure, and myeloid malignancies.

The study, conducted in mice, suggests HSCs falter with age because they lose the ability to replicate their DNA accurately and efficiently during cell division.

Emmanuelle Passegué, PhD, of the University of California San Francisco, and her colleagues reported this discovery in Nature.

The researchers analyzed old HSCs in mice and found a scarcity of protein components needed to form the mini-chromosome maintenance helicase. This molecular machine unwinds double-stranded DNA so the cell’s genetic material can be duplicated and allocated to daughter cells later in cell division.

The HSCs were stressed by the loss of this machine’s activity. As a result, they had an increased risk for DNA damage and death when forced to divide.

On the other hand, the cells tended to survive unless they were confronted with a “strong replication challenge” like transplantation.

The researchers also discovered that even after the stress associated with DNA replication, old HSCs retained molecular tags on histones, a feature often associated with DNA damage.

However, these old survivors could repair induced DNA damage as efficiently as young stem cells.

“Old stem cells are not just sitting there with damaged DNA ready to develop cancer, as it has long been postulated,” Dr Passegué said.

Of course, not all was well in the old, surviving HSCs. The molecular tags accumulated on genes needed to make ribosomes.

Dr Passegué said she will further explore the consequences of reduced protein production as part of her ongoing research. She hopes it might be possible to prevent declining stem cell populations by developing a drug to prevent the loss of the helicase components needed to unwind and replicate DNA, thereby avoiding immune system failure.

Hematopoietic stem cells
in the bone marrow

A new study helps explain how blood production declines with age and why older individuals are not suitable donors for hematopoietic stem cell (HSC) transplant.

The research also reveals a potential approach for mitigating

the negative effects of aging on the blood, which can lead to anemia,

bone marrow failure, and myeloid malignancies.

The study, conducted in mice, suggests HSCs falter with age because they lose the ability to replicate their DNA accurately and efficiently during cell division.

Emmanuelle Passegué, PhD, of the University of California San Francisco, and her colleagues reported this discovery in Nature.

The researchers analyzed old HSCs in mice and found a scarcity of protein components needed to form the mini-chromosome maintenance helicase. This molecular machine unwinds double-stranded DNA so the cell’s genetic material can be duplicated and allocated to daughter cells later in cell division.

The HSCs were stressed by the loss of this machine’s activity. As a result, they had an increased risk for DNA damage and death when forced to divide.

On the other hand, the cells tended to survive unless they were confronted with a “strong replication challenge” like transplantation.

The researchers also discovered that even after the stress associated with DNA replication, old HSCs retained molecular tags on histones, a feature often associated with DNA damage.

However, these old survivors could repair induced DNA damage as efficiently as young stem cells.

“Old stem cells are not just sitting there with damaged DNA ready to develop cancer, as it has long been postulated,” Dr Passegué said.

Of course, not all was well in the old, surviving HSCs. The molecular tags accumulated on genes needed to make ribosomes.

Dr Passegué said she will further explore the consequences of reduced protein production as part of her ongoing research. She hopes it might be possible to prevent declining stem cell populations by developing a drug to prevent the loss of the helicase components needed to unwind and replicate DNA, thereby avoiding immune system failure.

Hematopoietic stem cells
in the bone marrow

A new study helps explain how blood production declines with age and why older individuals are not suitable donors for hematopoietic stem cell (HSC) transplant.

The research also reveals a potential approach for mitigating

the negative effects of aging on the blood, which can lead to anemia,

bone marrow failure, and myeloid malignancies.

The study, conducted in mice, suggests HSCs falter with age because they lose the ability to replicate their DNA accurately and efficiently during cell division.

Emmanuelle Passegué, PhD, of the University of California San Francisco, and her colleagues reported this discovery in Nature.

The researchers analyzed old HSCs in mice and found a scarcity of protein components needed to form the mini-chromosome maintenance helicase. This molecular machine unwinds double-stranded DNA so the cell’s genetic material can be duplicated and allocated to daughter cells later in cell division.

The HSCs were stressed by the loss of this machine’s activity. As a result, they had an increased risk for DNA damage and death when forced to divide.

On the other hand, the cells tended to survive unless they were confronted with a “strong replication challenge” like transplantation.

The researchers also discovered that even after the stress associated with DNA replication, old HSCs retained molecular tags on histones, a feature often associated with DNA damage.

However, these old survivors could repair induced DNA damage as efficiently as young stem cells.

“Old stem cells are not just sitting there with damaged DNA ready to develop cancer, as it has long been postulated,” Dr Passegué said.

Of course, not all was well in the old, surviving HSCs. The molecular tags accumulated on genes needed to make ribosomes.

Dr Passegué said she will further explore the consequences of reduced protein production as part of her ongoing research. She hopes it might be possible to prevent declining stem cell populations by developing a drug to prevent the loss of the helicase components needed to unwind and replicate DNA, thereby avoiding immune system failure.

Plasmodium parasite in a

red blood cell; Credit: St Jude

Children’s Research Hospital

Scientists have uncovered a number of potential targets for a blood-stage malaria vaccine.

The team assessed how antibodies from a group of malaria-infected children responded to a library of proteins from the Plasmodium falciparum parasite.

This revealed antigens that had not previously been identified as possible vaccine targets and provided new insight into the ways antigens could be used in combination to increase protection from malaria.

“Resistance to malaria drugs is an increasing problem, so vaccines are desperately needed to battle the Plasmodium falciparum parasite before it has a chance to make people sick,” said Faith Osier, MBChB, of the Kenya Medical Research Institute in Nairobi City.

“This study presents us with a large number of new vaccine candidates that offer real hope for the future.”

Dr Osier and her colleagues described the study in Science Translational Medicine.

The researchers generated a library of correctly folded, full-length proteins from the P falciparum parasite. They then tested antibody reactivity against these proteins in a cohort of Kenyan children who were monitored for clinical episodes of malaria over 6 months.

This revealed antibodies that provide protection against clinical episodes of malaria. Some were equivalent or superior to current leading malaria vaccine candidates.

In fact, combinations consisting of 5 of the 10 top-ranked antigens (PF3D7_1136200, MSP2, RhopH3, P41, MSP11, MSP3, PF3D7_0606800, AMA1, Pf113, and MSRP1) could provide 100% protection against clinical episodes of malaria.

The researchers said these results add further weight to the theory that a successful blood-stage vaccine needs to target multiple antigens.

The team’s next step will be to generate antibodies against all of the proteins in the library and test them in different combinations to see whether combinations that appear to provide protection can directly prevent parasite invasion.

Plasmodium parasite in a

red blood cell; Credit: St Jude

Children’s Research Hospital

Scientists have uncovered a number of potential targets for a blood-stage malaria vaccine.

The team assessed how antibodies from a group of malaria-infected children responded to a library of proteins from the Plasmodium falciparum parasite.

This revealed antigens that had not previously been identified as possible vaccine targets and provided new insight into the ways antigens could be used in combination to increase protection from malaria.

“Resistance to malaria drugs is an increasing problem, so vaccines are desperately needed to battle the Plasmodium falciparum parasite before it has a chance to make people sick,” said Faith Osier, MBChB, of the Kenya Medical Research Institute in Nairobi City.

“This study presents us with a large number of new vaccine candidates that offer real hope for the future.”

Dr Osier and her colleagues described the study in Science Translational Medicine.

The researchers generated a library of correctly folded, full-length proteins from the P falciparum parasite. They then tested antibody reactivity against these proteins in a cohort of Kenyan children who were monitored for clinical episodes of malaria over 6 months.

This revealed antibodies that provide protection against clinical episodes of malaria. Some were equivalent or superior to current leading malaria vaccine candidates.

In fact, combinations consisting of 5 of the 10 top-ranked antigens (PF3D7_1136200, MSP2, RhopH3, P41, MSP11, MSP3, PF3D7_0606800, AMA1, Pf113, and MSRP1) could provide 100% protection against clinical episodes of malaria.

The researchers said these results add further weight to the theory that a successful blood-stage vaccine needs to target multiple antigens.

The team’s next step will be to generate antibodies against all of the proteins in the library and test them in different combinations to see whether combinations that appear to provide protection can directly prevent parasite invasion.

Plasmodium parasite in a

red blood cell; Credit: St Jude

Children’s Research Hospital

Scientists have uncovered a number of potential targets for a blood-stage malaria vaccine.

The team assessed how antibodies from a group of malaria-infected children responded to a library of proteins from the Plasmodium falciparum parasite.

This revealed antigens that had not previously been identified as possible vaccine targets and provided new insight into the ways antigens could be used in combination to increase protection from malaria.

“Resistance to malaria drugs is an increasing problem, so vaccines are desperately needed to battle the Plasmodium falciparum parasite before it has a chance to make people sick,” said Faith Osier, MBChB, of the Kenya Medical Research Institute in Nairobi City.

“This study presents us with a large number of new vaccine candidates that offer real hope for the future.”

Dr Osier and her colleagues described the study in Science Translational Medicine.

The researchers generated a library of correctly folded, full-length proteins from the P falciparum parasite. They then tested antibody reactivity against these proteins in a cohort of Kenyan children who were monitored for clinical episodes of malaria over 6 months.

This revealed antibodies that provide protection against clinical episodes of malaria. Some were equivalent or superior to current leading malaria vaccine candidates.

In fact, combinations consisting of 5 of the 10 top-ranked antigens (PF3D7_1136200, MSP2, RhopH3, P41, MSP11, MSP3, PF3D7_0606800, AMA1, Pf113, and MSRP1) could provide 100% protection against clinical episodes of malaria.

The researchers said these results add further weight to the theory that a successful blood-stage vaccine needs to target multiple antigens.

The team’s next step will be to generate antibodies against all of the proteins in the library and test them in different combinations to see whether combinations that appear to provide protection can directly prevent parasite invasion.