A variable neurodegenerative phenotype with polymerase gamma mutation

mtDNA replication and repair, causes mitochondrial diseases including autosomal dominant progressive external ophthalmoplegia (PEO),1 childhood hepato-encephalopathy (Alpers– Huttenlocher syndrome), adult-onset spinocerebellar ataxia, and sensory nerve degeneration with dysarthria and ophthalmoparesis (SANDO)

On thermodynamically consistent Stefan problems with variable surface energy

A thermodynamically consistent two-phase Stefan problem with temperature-dependent surface tension and with or without kinetic undercooling is studied. It is shown that these problems generate local semiflows in well-defined state manifolds. If a solution does not exhibit singularities, it is proved that it exists globally in time and converges towards an equilibrium of the problem. In addition, stability and instability of equilibria is studied. In particular, it is shown that multiple spheres of the same radius are unstable if surface heat capacity is small; however, if kinetic undercooling is absent, they are stable if surface heat capacity is sufficiently large.Comment: To appear in Arch. Ration. Mech. Anal. The final publication is available at Springer via http://dx.doi.org/10.1007/s00205-015-0938-y. arXiv admin note: substantial text overlap with arXiv:1101.376

Disease proportions attributable to environment

Population disease proportions attributable to various causal agents are popular as they present a simplified view of the contribution of each agent to the disease load. However they are only summary figures that may be easily misinterpreted or over-interpreted even when the causal link between an exposure and an effect is well established. This commentary discusses several issues surrounding the estimation of attributable proportions, particularly with reference to environmental causes of cancers, and critically examines two recently published papers. These issues encompass potential biases as well as the very definition of environment and of environmental agent. The latter aspect is not just a semantic question but carries implications for the focus of preventive actions, whether centred on the material and social environment or on single individuals

The impact of the environment on health by country: a meta-synthesis

<p>Abstract</p> <p>Background</p> <p>Health gains that environmental interventions could achieve are main questions when choosing environmental health action to prevent disease. The World Health Organization has recently released profiles of environmental burden of disease for 192 countries.</p> <p>Methods</p> <p>These country profiles provide an estimate of the health impacts from the three major risk factors 'unsafe water, sanitation & hygiene', 'indoor air pollution from solid fuel use' and 'outdoor air pollution'. The profiles also provide an estimate of preventable health impacts by the environment as a whole. While the estimates for the three risk factors are based on country exposures, the estimates of health gains for total environmental improvements are based on a review of the literature supplemented by expert opinion and combined with country health statistics.</p> <p>Results</p> <p>Between 13% and 37% of the countries' disease burden could be prevented by environmental improvements, resulting globally in about 13 million deaths per year. It is estimated that about four million of these could be prevented by improving water, sanitation and hygiene, and indoor and outdoor air alone. The number of environmental DALYs per 1000 capita per year ranges between 14 and 316 according to the country. An analysis by disease group points to main preventions opportunities for each country.</p> <p>Conclusion</p> <p>Notwithstanding the uncertainties in their calculation, these estimates provide an overview of opportunities for prevention through healthier environments. The estimates show that for similar national incomes, the environmental burden of disease can typically vary by a factor five. This analysis also shows that safer water, sanitation and hygiene, and safer fuels for cooking could significantly reduce child mortality, namely by more than 25% in 20 of the lowest income countries.</p

Long‐Term Cognitive Outcome in Anti–N‐Methyl‐D‐Aspartate Receptor Encephalitis

Objective: Cognitive dysfunction is a core symptom of anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis, but detailed studies on prevalence, characteristics of cognitive deficits, and the potential for recovery are missing. Here, we performed a prospective longitudinal study to assess cognitive long-term outcome and identify clinical predictors. Methods: Standardized comprehensive neuropsychological assessments were performed in 43 patients with NMDAR encephalitis 2.3 years and 4.9 years (median) after disease onset. Cognitive assessments covered executive function, working memory, verbal/visual episodic memory, attention, subjective complaints, and depression and anxiety levels. Cognitive performance of patients was compared to that of 30 healthy participants matched for age, sex, and education. Results: All patients had persistent cognitive deficits 2.3 years after onset, with moderate or severe impairment in >80% of patients. Core deficits included memory and executive function. After 4.9 years, significant improvement of cognitive function was observed, but moderate to severe deficits persisted in two thirds of patients, despite favorable functional neurological outcomes (median modified Rankin Scale = 1). Delayed treatment, higher disease severity, and longer duration of the acute phase were predictors for impaired cognitive outcome. The recovery process was time dependent, with greater gains earlier after the acute phase, although improvements were possible for several years after disease onset. Interpretation: Cognitive deficits are the main contributor to long-term morbidity in NMDAR encephalitis and persist beyond functional neurological recovery. Nonetheless, cognitive improvement is possible for several years after the acute phase and should be supported by continued cognitive rehabilitation. Cognition should be included as an outcome measure in future clinical studies

Altered paired associative stimulation-induced plasticity in NMDAR encephalitis

Objective: To determine whether neurophysiological mechanisms indicating cortical excitability, long-term potentiation (LTP)-like plasticity, GABAergic and glutamatergic function are altered in patients with anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis and whether they can be helpful as markers of diagnostic assessment, disease progression, and potentially therapy response. Methods: Neurophysiological characterizations of patients with NMDAR encephalitis (n = 34, mean age: 28 ± 11 years; 30 females) and age/gender-matched healthy controls (n = 27, 28.5 ± 10 years; 25 females) were performed using transcranial magnetic stimulation-derived protocols including resting motor threshold, recruitment curve, intracortical facilitation, short intracortical inhibition, and cortical silent period. Paired associative stimulation (PAS) was applied to assess LTP-like mechanisms which are mediated through NMDAR. Moreover, resting state functional connectivity was determined using functional magnetic resonance imaging. Results: PAS-induced plasticity differed significantly between groups (P = 0.0056). Cortical excitability, as assessed via motor-evoked potentials after PAS, decreased in patients, whereas it increased in controls indicating malfunctioning of NMDAR in encephalitis patients. Lower PAS-induced plasticity significantly correlated with the modified Rankin Scale (mRS) (r = −0.41; P = 0.0031) and was correlated with lower functional connectivity within the motor network in NMDAR encephalitis patients (P < 0.001, uncorrected). Other neurophysiological parameters were not significantly different between groups. Follow-up assessments were available in six patients and demonstrated parallel improvement of PAS-induced plasticity and mRS. Interpretation: Assessment of PAS-induced plasticity may help to determine NMDAR dysfunction and disease severity in NMDAR encephalitis, and might even aid as a sensitive, noninvasive, and well-tolerated “electrophysiological biomarker” to monitor therapy response in the future.Clinical Trial Registration: ClinicalTrials.gov: Identifier: NCT0186557

Diseases due to unhealthy environments: an updated estimate of the global burden of disease attributable to environmental determinants of health

The update of the global burden of disease attributable to the environment is presented. The study focuses on modifiable risks to show the potential health impact from environmental interventions.; Systematic literature reviews on 133 diseases and injuries were performed. Comparative risk assessments were complemented by more limited epidemiological estimates, expert opinion and information on disease transmission pathways. Population attributable fractions were used to calculate global deaths and global disease burden from environmental risks.; Twenty-three percent (95% CI: 13-34%) of global deaths and 22% (95% CI: 13-32%) of global disability adjusted life years (DALYs) were attributable to environmental risks in 2012. Sixty-eight percent of deaths and 56% of DALYs could be estimated with comparative risk assessment methods. The global disease burden attributable to the environment is now dominated by noncommunicable diseases. Susceptible ages are children under five and adults between 50 and 75 years. Country level data are presented.; Nearly a quarter of global disease burden could be prevented by reducing environmental risks. This analysis confirms that eliminating hazards and reducing environmental risks will greatly benefit our health, will contribute to attaining the recently agreed Sustainable Development Goals and will systematically require intersectoral collaboration to be successful

Long‐Term Cognitive Outcome in Anti–N‐Methyl‐D‐Aspartate Receptor Encephalitis

Objective Cognitive dysfunction is a core symptom of anti–N‐methyl‐D‐aspartate receptor (NMDAR) encephalitis, but detailed studies on prevalence, characteristics of cognitive deficits, and the potential for recovery are missing. Here, we performed a prospective longitudinal study to assess cognitive long‐term outcome and identify clinical predictors. Methods Standardized comprehensive neuropsychological assessments were performed in 43 patients with NMDAR encephalitis 2.3 years and 4.9 years (median) after disease onset. Cognitive assessments covered executive function, working memory, verbal/visual episodic memory, attention, subjective complaints, and depression and anxiety levels. Cognitive performance of patients was compared to that of 30 healthy participants matched for age, sex, and education. Results All patients had persistent cognitive deficits 2.3 years after onset, with moderate or severe impairment in >80% of patients. Core deficits included memory and executive function. After 4.9 years, significant improvement of cognitive function was observed, but moderate to severe deficits persisted in two thirds of patients, despite favorable functional neurological outcomes (median modified Rankin Scale = 1). Delayed treatment, higher disease severity, and longer duration of the acute phase were predictors for impaired cognitive outcome. The recovery process was time dependent, with greater gains earlier after the acute phase, although improvements were possible for several years after disease onset. Interpretation Cognitive deficits are the main contributor to long‐term morbidity in NMDAR encephalitis and persist beyond functional neurological recovery. Nonetheless, cognitive improvement is possible for several years after the acute phase and should be supported by continued cognitive rehabilitation. Cognition should be included as an outcome measure in future clinical studies. ANN NEUROL 2021;90:949–961Bundesministerium für Bildung und Forschung http://dx.doi.org/10.13039/501100002347Deutsche Forschungsgemeinschaft http://dx.doi.org/10.13039/501100001659Peer Reviewe