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MGMT, the gene coding for the DNA-repair protein O

COVID-19, the human primarily respiratory disease caused by the coronavirus SARS-CoV-2, commonly involves the nervous system, the effects of which may persist for many months. Post-acute sequelae of COVID-19 include relapsing and remitting neurological and neuropsychiatric symptoms that can affect children and adults, including those who had mild acute illness. Since longer-term adverse effects on the central and peripheral nervous system of COVID-19 cannot be excluded, patient and societal health trends should be monitored going forward. Urgent present needs include not only global immunization against SARS-CoV-2 but also the reestablishment of lapsed mass vaccination programs to prevent resurgence of other viral diseases (e.g., measles, polio) that can impact the nervous system. © Spencer P.S., Roman G., Buguet A., Guekht A., Reis J., 2021

The Common Rock Rat Zyzomys argurus is an abundant small- to medium-sized Murid rodent that is endemic to Australia. It is a nocturnal mammal with a mostly herbivorous diet. This species is native to the wet/dry tropics of Northern Australia and can be identified from other rock rats on the basis of its small size and its tail length (which is at least equivalent to its head-body length). Here, we describe the complete mitochondrial genome of Z. argurus and compare it to other Rodentia. The Z. argurus circular mitogenome was 16,261 bp and contained 13 protein-coding genes, two rRNA genes, 22 tRNAs and a control region (D-loop) of 859 bp. Phylogenetic analysis of selected, published sequenced mitogenomes reveal it is most closely related to the Lakeland Downs mouse Leggadina lakedownensis in the order Rodentia.

Unknown environmental factors are thought to contribute to the etiology of sporadic forms of amyotrophic lateral sclerosis (ALS). Strong evidence supporting this view is found in the post-World War decline and disappearance of highincidence ALS in three Western Pacific populations that formerly utilized neurotoxic cycad seed as a traditional source of food and/or medicine. The principal toxins in cycads (cycasin) and in False Morel mushrooms (gyromitrin) generate methyl free radicals that damage DNA and cause mutation and uncontrolled division of cycling cells and degeneration of late-/postmitotic neurons. Since False Morels are scavenged for food in Finland, Russia, Spain, and USA, research studies are underway in Western Europe and USA to determine if the practice is associated with sporadic ALS.

The purpose of this article is to examine risk perception among some specific stakeholders, including international intergovernmental bodies, private western-based corporates, and among European public opinion surveys We also address concerns of the Russian Federation and the impact of China’s Belt and Road Initiative Perception of risks is key to policy decision-making and probably more important than risk assessment We offer a medico-scientific perspective based on factual evidence drawn mostly from official websites and publications Our first goal is to understand if sufficient attention is given to human health, disease prevention and control relative to economic and financial considerations Our second goal is to promote a translational and interprofessional approach to global risk prioritization by cooperation between the medico-scientific community and the financial-economic world To this end, we examine the benefits for the practice of economic risk assessment of engaging biomedical expertise focused on global environmental health Maintenance, expansion and sustainability of the human enterprise require health and wellness Осуществлен анализ представлений, связанных с рисками для здоровья человека, у определенных заинтересованных сторон, в том числе у международных межправительственных организаций, частных западных корпораций, которые отражаются в опросах общественного мнения в европейских странах Также проанализировано восприятие рисков здоровью населения в Российской Федерации, в том числе в связи с китайской инициативой «Один пояс, один путь» Представления о рисках и, следовательно, об иерархии рисков являются ключевыми факторами принятия решений при разработке политики и, возможно, даже более важны, чем оценка риска Авторы смотрят на перспективы анализа рисков как ученые - с позиций науки и медицины, с учетом существующих сведений, взятых большей частью с официальных веб-сайтов и публикаций Первая цель исследования - понять, достаточное ли внимание уделяется вопросам здоровья, предотвращения и контроля заболеваний по сравнению с экономическими и финансовыми вопросами Вторая цель - стимулировать применение поступательного и межпрофессионального подхода к анализу глобальных рисков через взаимодействие медико-научного сообщества и финансово-экономического мира С этих позиций изучены практические преимущества экономической оценки внешнесредовых рисков для здоровья населения с привлечением экспертов в области биомедицины Поддержание, расширение и устойчивое развитие всех аспектов человеческой жизнедеятельности подразумевает здоровье и благосостояние

Purpose To reexamine the etiology of a unique retinal pathology (linear and vermiform sub-retinal tubular structures) described among subjects with and without neurodegenerative disease in former high-incidence foci of Western Pacific amyotrophic lateral sclerosis and parkinsonism-dementia complex (ALS/PDC) in Guam (USA) and the Kii peninsula of Honshu island (Japan). Methods Analysis of published and unpublished reports of 1) ALS/PDC and the retinal and cerebellar pathology associated therewith and 2) exogenous neurotoxic factors associated with ALS/PDC and the developing retina and cerebellum. Results ALS/PDC retinal and cerebellar pathology matches persistent retinal and cerebellar dysplasia found in laboratory animals given single in utero or postnatal systemic treatment with cycasin, the principal neurotoxic component in the seed of cycad plants traditionally used for food (Guam) or oral medicine (Kii-Japan), both of which have been linked to the human neurodegenerative disease. Conclusion ALS/PDC-associated retinal and cerebellar dysplasia could arise from in utero exposure to methylazoxymethanol, the genotoxic metabolite of cycasin that results from maternal ingestion of this azoxyglucoside. These results support the environmental toxic etiology of retinal and brain pathology in ALS/PDC.

The deleterious effects of aging on the brain remain to be fully elucidated. In the present study, proteomic changes of young (4-month) and aged (16-month) B6129SF2/J male mouse hippocampus and cerebral cortex were investigated by using nano liquid chromatography tandem mass spectrometry (NanoLC-ESI-MS/MS) combined with tandem mass tag (TMT) labeling technology. Compared with the young animals, 390 hippocampal proteins (121 increased and 269 decreased) and 258 cortical proteins (149 increased and 109 decreased) changed significantly in the aged mouse. Bioinformatic analysis indicated that these proteins are mainly involved in mitochondrial functions (FIS1, DRP1), oxidative stress (PRDX6, GSTP1, and GSTM1), synapses (SYT12, GLUR2), ribosome (RPL4, RPS3), cytoskeletal integrity, transcriptional regulation, and GTPase function. The mitochondrial fission-related proteins FIS1 and DRP1 were significantly increased in the hippocampus and cerebral cortex of the aged mice. Further results in the hippocampus showed that ATP content was significantly reduced in aged mice. A neurotrophin brain-derived neurotrophic factor (BNDF), a protein closely related with synaptic plasticity and memory, was also significantly decreased in the hippocampus of the aged mice, with the tendency of synaptic protein markers including complexin-2, synaptophysin, GLUR2, PSD95, NMDAR2A, and NMDAR1. More interestingly, 8-hydroxydeoxyguanosine (8-OHdG), a marker of DNA oxidative damage, increased as shown by immunofluorescence staining. In summary, we demonstrated that aging is associated with systemic changes involving mitochondrial dysfunction, energy reduction, oxidative stress, loss of neurotrophic factor, synaptic proteins, and ribosomal proteins, as well as molecular deficits involved in various physiological/pathological processes.

It is generally assumed that population supplementation will improve the genetic diversity of the recipient populations. However, the genetic outcomes of supplementations are rarely tested. We used population modelling to predict how the supplementation programme in a translocated Woylie (Bettongia penicillata ogilbyi) population influences their genetic makeup. Our model projections were then compared against real genetic data collected before and after supplementation, to determine whether or not supplementation was effective at increasing genetic diversity and to test the accuracy of the model. Post‐supplementation genetic diversity parameters (heterozygosity and allelic richness) were significantly higher following supplementation, and there was no significant difference from those predicted by the model. These results are encouraging; however, many factors can influence supplementation outcomes and we recommend ongoing monitoring in translocated populations to ensure that population trends are on target.

In this announcement, we report the complete mitogenome of the vulnerable Crest-tailed Mulgara (Dasycercus cristicauda) (Krefft, 1867). The mitogenome was 17,085 bp in length and contained 13 protein-coding genes, two rRNA genes, 22 tRNAs and a 1583 bp variable control region (D-loop). The features of the D. cristicauda mitogenome are consistent with other vertebrate mitogenomes but, in contrast to other marsupials, appears to contain a functional tRNA-Lysine with a UUU anticodon. Phylogenetic analysis of available entire mitogenomes reveals it forms a cluster with other marsupials in the Dasyuromorphia order within the Australidelphian clade, being most closely related to the Northern Quoll and the Tasmanian Devil.

Nodding syndrome (NS) is a progressive encephalopathy of children and adolescents characterized by seizures, including periodic vertical head nodding. Epidemic NS, which has affected parts of East Africa, appears to have clinical overlap with sub-Saharan Nakalanga syndrome (NLS), a brain disorder associated with pituitary dwarfism that appears to have a patchy distribution across sub-Sahara. Clinical stages of NS include inattention and blank stares, vertical head nodding, convulsive seizures, multiple impairments, and severe cognitive and motorsystem disability, including features suggesting parkinsonism. Head nodding episodes occur in clusters with an electrographic correlate of diffuse high-amplitude slow waves followed by an electrodecremental pattern with superimposed diffuse fast activity. Brain imaging reveals differing degrees of cerebral cortical and cerebellar atrophy. Brains of NS-affected children with mild frontotemporal cortical atrophy display neurofibrillary pathology and dystrophic neurites immunopositive for tau, consistent with a progressive neurodegenerative disorder. The etiology of NS and NLS appears to be dominated by environmental factors, including malnutrition, displacement, and nematode infection, but the specific cause is unknown.

Lathyrism is a central motor system disorder recognized since antiquity resulting from prolonged dietary dependence on the grasspea (Lathyrus sativus). The neuropathology underlying the characteristic spastic paraparesis of lathyrism is sketchy. Described here is a landmark but little-known Spanish-language neuropathological study of two patients with lathyrism of recent onset. Due to erroneous interpretations of Filimonov's influential work in 1926, it was assumed that spastic paraparesis of lathyrism was explained by destruction of Betz's pyramidal cells in the motor cortex. Contrary to present understanding, Betz cells and anterior horn cells were preserved, and pathological findings dominated by myelin loss were largely limited to pyramidal tracts in the lumbar cord. Thickening of the adventitia of capillaries and arterioles, together with proliferation of perivascular astrocytes, was found along the length of the spinal cord. Oliveras de la Riva proposed that the segmental spinal pathology arose because distal regions of elongate pyramidal tract axons are distant from their trophic center in the motor cortex, a view not far from the current distal axonopathy concept of lathyrism. In addition, we review the historical circumstances of Filimonov's work in Russia, a summary of the epidemic of lathyrism in Spain following its Civil War (1936-1939), and some historical aspects of the Cajal Institute in Madrid, where Oliveras de la Riva's work was carried out under the supervision of Fernando de Castro, one of Cajal's favorite students.

We address the impact of the tropical environment on the human nervous system using the multifaceted approach characteristic of environmental neurology. First, environmental factors are examined according to their nature (physical, chemical and biological) and in relation to human activity and behavior. Some factors are specific to the tropics (climate and infections), while others are non-specific (chemicals, human communities and their way of life). Second, we examine the major role of human adaptation to the success of Homo sapiens, with emphasis on the linkage between thermoregulation and sleep-wake regulation. Third, we examine the performance of environmental neurology as a clinical discipline in tropical climates, with focus on the diagnostic and therapeutic challenges posed by human African trypanosomiasis. Finally, the prevention, early detection and monitoring of environmental neurological diseases is examined, as well as links with political and economic factors. In conclusion, practitioners of environmental neurology seek a global, multidisciplinary and holistic approach to understanding, preventing and treating neurological disorders within their purview. Environmental neurology integrates an expanded One Health concept by linking health and wellness to the interaction of plants, animals, humans and the ecosystem. Recent epidemics and the current COVID-19 pandemic exemplify the need for worldwide action to protect human health and biodiversity.

The Ghost bat Macroderma gigas is a monotypic bat species that is endemic to northern Australia and named on the basis of the large size of its partially conjoined ears. It is the only carnivorous bat found in Australia and its conservation status is currently listed as Vulnerable. Here, we describe the complete mitochondrial genome of M. gigas and compare it to other vertebrates. The M. gigas circularized mitogenome was 16,661 bp and contained 13 protein-coding genes, two rRNA genes, 22 tRNAs and a control region (D-loop) of 1228 bp. Phylogenetic analysis of available entire mitogenomes reveals that Macroderma gigas is most closely related to the Indian false vampire bat Megaderma lyra in the family Megadermatidae (false vampire bats).

Many Australian mammal species now only occur on islands and fenced mainland havens free from invasive predators. The range of one species, the banded hare-wallaby (Lagostrophus fasciatus), had contracted to two offshore islands in Western Australia. To improve survival, four conservation translocations have been attempted with mixed success, and all occurred in the absence of genetic information. Here, we genotyped seven polymorphic microsatellite markers in two source (Bernier Island and Dorre Island), two historic captive, and two translocated L. fasciatus populations to determine the impact of multiple translocations on genetic diversity. Subsequently, we used population viability analysis (PVA) and gene retention modelling to determine scenarios that will maximise demographic resilience and genetic richness of two new populations that are currently being established. One translocated population (Wadderin) has undergone a genetic bottleneck and lost 8.1% of its source population&rsquo, s allelic diversity, while the other (Faure Island) may be inbred. We show that founder number is a key parameter when establishing new L. fasciatus populations and 100 founders should lead to high survival probabilities. Our modelling predicts that during periodic droughts, the recovery of source populations will be slower post-harvest, while 75% more animals&mdash, about 60 individuals&mdash, are required to retain adequate allelic diversity in the translocated population. Our approach demonstrates how genetic data coupled with simulations of stochastic environmental events can address central questions in translocation programmes.

IMPORTANCE: The outbreak of coronavirus disease 2019 (COVID-19) in Wuhan, China, is serious and has the potential to become an epidemic worldwide. Several studies have described typical clinical manifestations including fever, cough, diarrhea, and fatigue. However, to our knowledge, it has not been reported that patients with COVID-19 had any neurologic manifestations. OBJECTIVE: To study the neurologic manifestations of patients with COVID-19. DESIGN, SETTING, AND PARTICIPANTS: This is a retrospective, observational case series. Data were collected from January 16, 2020, to February 19, 2020, at 3 designated special care centers for COVID-19 (Main District, West Branch, and Tumor Center) of the Union Hospital of Huazhong University of Science and Technology in Wuhan, China. The study included 214 consecutive hospitalized patients with laboratory-confirmed diagnosis of severe acute respiratory syndrome coronavirus 2 infection. MAIN OUTCOMES AND MEASURES: Clinical data were extracted from electronic medical records, and data of all neurologic symptoms were checked by 2 trained neurologists. Neurologic manifestations fell into 3 categories: central nervous system manifestations (dizziness, headache, impaired consciousness, acute cerebrovascular disease, ataxia, and seizure), peripheral nervous system manifestations (taste impairment, smell impairment, vision impairment, and nerve pain), and skeletal muscular injury manifestations. RESULTS: Of 214 patients (mean [SD] age, 52.7 [15.5] years; 87 men [40.7%]) with COVID-19, 126 patients (58.9%) had nonsevere infection and 88 patients (41.1%) had severe infection according to their respiratory status. Overall, 78 patients (36.4%) had neurologic manifestations. Compared with patients with nonsevere infection, patients with severe infection were older, had more underlying disorders, especially hypertension, and showed fewer typical symptoms of COVID-19, such as fever and cough. Patients with more severe infection had neurologic manifestations, such as acute cerebrovascular diseases (5 [5.7%] vs 1 [0.8%]), impaired consciousness (13 [14.8%] vs 3 [2.4%]), and skeletal muscle injury (17 [19.3%] vs 6 [4.8%]). CONCLUSIONS AND RELEVANCE: Patients with COVID-19 commonly have neurologic manifestations. During the epidemic period of COVID-19, when seeing patients with neurologic manifestations, clinicians should suspect severe acute respiratory syndrome coronavirus 2 infection as a differential diagnosis to avoid delayed diagnosis or misdiagnosis and lose the chance to treat and prevent further transmission.

IntroductionProgressive distal symmetrical axonal neuropathy, a complication of diabetes mellitus (DM), has an unknown cause. Normal physiological metabolism and diabetic dysmetabolism are associated with the generation of γ-diketones. γ-Diketones form pyrroles with protein amines, notably with axonal proteins required for the maintenance of nerve fiber integrity, especially elongate, large-diameter peripheral nerve fibers innervating the extremities. We tested the hypothesis that neuropathy-associated γ-diketone pyrroles are elevated in DM.Research design and methodsWe measured the urinary concentration of γ-diketone pyrroles in age-matched and gender-matched elderly (60–84 years) persons with (n=267) or without (n=267) indicators of DM based in a community population (9411 community older adults aged ≥60 years) in Shenzhen city, Guangdong, China. We used statistical methods, including a generalized linear model, multivariate logistic regression analysis and restricted cubic splines, to assess linear and nonlinear relationships between urinary γ-diketone pyrroles and indicators of DM.ResultsCompared with healthy controls, those with DM had significantly higher levels of fasting blood glucose, glycated hemoglobin A1c, urinary ketone bodies and urinary γ-diketone pyrroles. The median concentration of urinary γ-diketone pyrrole adducts was significantly higher (pConclusionsDiabetic dysmetabolism includes increased generation and excretion of neuropathy-associated γ-diketone pyrroles. These findings form the foundation for studies to test whether γ-diketone pyrrole concentration correlates with quantitative sensory (vibration and temperature) and electrodiagnostic testing.

Peripheral neuropathy associated with chronic occupational and deliberate overexposure to neurotoxic organic solvents results from axonal degeneration in the central and peripheral nervous system. Human and experimental studies show that axonopathy is triggered by the action of neuroprotein-reactive γ-diketone metabolites formed from exposure to certain aliphatic solvents ( n-hexane, 2-hexanone) and aromatic compounds (1,2-diethylbenzene, 1,2-4-triethylbenzene, 6-acetyl-1,1,4,4-tetramethyl-7-ethyl-1,2,3,4-tetralin). Neuroprotein susceptibility is related primarily to their differential content of lysine, the ∊-amino group of which is targeted by γ-diketones. Specific neuroprotein targets have been identified, and the sequence of molecular mechanisms leading to axonal pathology has been illuminated. While occupational n-hexane neuropathy continues to be reported, lessons learned from its experimental study may have relevance to other causes of peripheral neuropathy, including those associated with aging and diabetes mellitus.

Western Pacific Amyotrophic Lateral Sclerosis and Parkinsonism-dementia Complex (ALS/PDC) is a disappearing neurodegenerative disease in three former high-incidence foci of Guam-USA, Papua-Indonesia and Kii Peninsula, Honshu Island, Japan. The latter includes two distinct ALS/PDC-affected regions (Hohara and Kozagawa), where the disorder is known as Muro disease. In Hohara, oral exposure to plant (cycad) neurotoxins used in traditional medical practice has been linked previously to Muro disease. We report new observations that link Kampō medicine to Muro disease in the southern Kozagawa focus. Oral exposure to cycad seed toxins is associated with all three foci of Western Pacific ALS/PDC. Keywords: Amyotrophic Lateral Sclerosis and Parkinsonism-Dementia Complex, Kii peninsula, Honshu, Japan, Traditional/folk medical practice, Cycad seed, Sotetsu

Reductions in genetic diversity and genetic connectivity have been documented in some predatory bird species in response to anthropogenic habitat fragmentation. The Southern Boobook (Ninox boobook) is the most common and widely-distributed owl in Australia but declines in abundance have been observed across its range. We used polymorphic microsatellite loci to investigate landscape-scale patterns of genetic variation and spatial genetic structure in boobooks from a variety of fragmented landscape types and relatively undisturbed landscape types across Western Australia. The maximum distance between collection locations of genetic samples was 1391 km. Indirect estimates of connectivity inferred from these genetic data were complemented by direct estimates of post-breeding dispersal of juvenile boobooks gathered from banding data resulting from this and other studies across Australia. We found high genetic diversity in microsatellite markers, weak spatial genetic structuring and no evidence of genetic erosion associated with inbreeding in heavily fragmented landscapes. Bayesian modelling, spatial autocorrelation analysis and principal coordinates analysis suggested a single large panmictic population across all areas sampled. Within the heavily fragmented landscape of an extensive urban area, band re-sightings and recoveries substantiate the considerable capacity of juvenile boobooks to disperse across areas far greater than the distance between patches. We hypothesise that the genetic homogeneity observed in this species is a consequence of long-distance dispersal capacity in addition to their ability as habitat and dietary generalists to make use of highly altered habitats.

Insular populations are particularly vulnerable to the effects of stochastic events, epidemics, and loss of genetic diversity due to inbreeding and genetic drift. The development of successful management options will require accurate baseline data, establishment of clear objectives, and finally monitoring and implementation of corrective measures, if and when required. This study assessed management options for the genetic rehabilitation of highly inbred woylies obtained from wildlife rehabilitation centers. The study generated genetic data for the woylie Bettongia penicillata from a conservation reserve and calculated measures of genetic diversity and individual relatedness. These data were fed into a population viability analysis (PVA) to test genetic outcomes in relation to different management actions. We demonstrated that a careful selection of the founder cohort produced a population with an expected heterozygosity of ∼70% for a window of approximately 10 years. A proposal to increase the size of the reserve available to the colony was shown to almost double the time at which the colony would retain heterozygosity levels of ≥ 70%. Additionally, developing a regular program of supplementation of unrelated woylies would result in a further improvement in their genetic value. This study demonstrated how the application of molecular techniques in combination with PVA can be beneficial for the management of rehabilitated wildlife otherwise considered of little conservation value. This approach can be applied to the management of breeding programs, but also to small, closed populations such as those found on islands, fenced enclosures, insurance populations, and in zoological collections.

Production landscapes, where activities such as timber harvesting, grazing, and resource extraction take place, have considerably reduced the extent of natural habitats. The ecological restoration of these landscapes is, in many cases, the best remaining option to protect biodiversity. However, it is unclear whether restoration designed to avert biodiversity loss in restored landscapes can also maintain genetic diversity in recolonizing faunal populations. We employed core concepts in the field of population genetics to address questions of genetic diversity and gene flow in recolonizing faunal populations, using a small and vagile marsupial (Antechinus flavipes) inhabiting a mined landscape under restoration. We did not detect a disruption of gene flow that led to genetic substructuring, suggesting adequate levels of gene flow across the landscape. Parameters of neutral genetic diversity were high in groups of individuals sampled in both restored and unmined sites. Our results are encouraging as they indicate that ecological restoration has the potential to not just increase available habitat, but also to maintain genetic diversity. However, there is evidence that past anthropogenic disturbances affected the genetics of the population at the regional level. Although restoration at the local level may seem to be successful, it is necessary to manage populations at larger spatial scales than where restoration is conducted, and over long temporal scales, if genetic diversity is to be maintained in restored landscapes. The field of population genetics is an underused tool in ecological restoration yet can provide important insights into how well restoration achieves its goals.

International audience; A role for environmental factors in the etiology of amyotrophic lateral sclerocis (ALS) has been suspected for many years. A large body of work has implicated common exposures, conjugal cases, at-risk activities, heavy metals, organic solvents, and electric shocks, among others. One of the most demonstrative relationships between ALS and the environment is spatial clustering. We reviewed the most important and recent spatial clusters in a given area, whatever the geographical size, with either substantial epidemiological approaches or with highly significant associations, and with precise hypotheses. We present a broad, albeit incomplete overview of investigations in different areas, including examples of the difficulties and contradictions of some approaches. Most of the time, the implication of neurotoxins is suspected and, although not always strictly identified, some candidates are emerging: cycasin, MAM, L-BMAA, hydrazine, for example. One other important point is the possibility of interaction among risk/causal factors that increase the complexity of investigation. Additionally, with the exception of Western Pacific ALS, studies of spatial clustering are lacking a major methodological approach, namely a large cohort analysis extended over a long period of time, and probably for decades. Nevertheless, any spatial cluster needs to be identified, described and studied as deeply as possible to illuminate knowledge of the origin of this devastating disorder and to promote primary or secondary disease prevention.

The human environment and exposures arising therefrom are major contributors to neurological disorders ranging from stroke to neurodegenerative diseases. Reduction of exposure to environmental risk factors, with the goal of disease prevention or control, is addressed at the individual as well as the societal level and in recognition of differential subject vulnerability. We examine some practical solutions in high-income countries that may allow a better adaptation to environmental risks and reduce their adverse impact on the nervous system. We consider the citizen's role in reducing unhealthy exposures and explore new approaches to treatment.

Decision-making in environmental health policy is a complex procedure even in well-known conditions. Thus, in the case of uncertainty, decision-making becomes a hurdle race. We address scientific uncertainty, methods to reduce uncertainty, biomedical doubt and science communication, and the role of stakeholders, activists, lobbies and media that together influence policy decisions. We also consider the major responsibility and role of the medico-scientific community in this process. This community can and should teach the principle of scientific uncertainty to all stakeholders, advise policy-makers and underline the ethical issues, considering that our brains are not only the deposit of our humanity but also the route to environmental health and societal harmony.

This case-control study adds to the growing body of knowledge on the medical, nutritional, and environmental factors associated with Nodding Syndrome (NS), a seizure disorder of children and adolescents in northern Uganda. Past research described a significant association between NS and prior history of measles infection, dependence on emergency food and, at head nodding onset, subsistence on moldy maize, which has the potential to harbor mycotoxins. We used LC-MS/MS to screen for current mycotoxin loads by evaluating nine analytes in urine samples from age-and-gender matched NS cases (n = 50) and Community Controls (CC, n = 50). The presence of the three mycotoxins identified in the screening was not significantly different between the two groups, so samples were combined to generate an overall view of exposure in this community during the study. Compared against subsequently run standards, α-zearalenol (43 ± 103 µg/L in 15 samples > limit of quantitation (LOQ); 0 (0/359) µg/L), T-2 toxin (39 ± 81 µg/L in 72 samples > LOQ; 0 (0/425) µg/L) and aflatoxin M1 (4 ± 10 µg/L in 15 samples > LOQ; 0 (0/45) µg/L) were detected and calculated as the average concentration ± SD; median (min/max). Ninety-five percent of the samples had at least one urinary mycotoxin; 87% were positive for two of the three compounds detected. While mycotoxin loads at NS onset years ago are and will remain unknown, this study showed that children with and without NS currently harbor foodborne mycotoxins, including those associated with maize.

Nodding syndrome is a pediatric epileptic encephalopathy of apparent environmental origin that was first described in Tanzania, with recent epidemics in South Sudan and Uganda. Following a brief description of the medical geography, setting and case definition of this progressive brain disorder, we report recent advances relating to etiology, diagnosis and treatment described in papers given at the 2nd International Conference on Nodding Syndrome held in July 2015 in Gulu, Uganda. The target audience for this report includes: anthropologists, entomologists, epileptologists, health care workers, helminthologists, medical researchers, neuroepidemiologists, neurologists, neuroscientists, neuropathologists, nurses, nutritional scientists, primary health care physicians, psychiatrists, public health practitioners, toxicologists, and virologists.•Update on medical geography and need for case definition revision•New hypotheses for disease etiology: metabolic, toxic, viral•Advances in clinical neurophysiology and effective treatment•Neuropathological description needed to define nodding syndrome•Commitment to collaborate locally, nationally and internationally.

A comprehensive review of the neurological disorders reported during the current COVID-19 pandemic demonstrates that infection with SARS-CoV-2 affects the central nervous system (CNS), the peripheral nervous system (PNS) and the muscle. CNS manifestations include: headache and decreased responsiveness considered initial indicators of potential neurological involvement; anosmia, hyposmia, hypogeusia, and dysgeusia are frequent early symptoms of coronavirus infection. Respiratory failure, the lethal manifestation of COVID-19, responsible for 264,679 deaths worldwide, is probably neurogenic in origin and may result from the viral invasion of cranial nerve I, progressing into rhinencephalon and brainstem respiratory centers. Cerebrovascular disease, in particular large-vessel ischemic strokes, and less frequently cerebral venous thrombosis, intracerebral hemorrhage and subarachnoid hemorrhage, usually occur as part of a thrombotic state induced by viral attachment to ACE2 receptors in endothelium causing widespread endotheliitis, coagulopathy, arterial and venous thromboses. Acute hemorrhagic necrotizing encephalopathy is associated to the cytokine storm. A frontal hypoperfusion syndrome has been identified. There are isolated reports of seizures, encephalopathy, meningitis, encephalitis, and myelitis. The neurological diseases affecting the PNS and muscle in COVID-19 are less frequent and include Guillain-Barré syndrome; Miller Fisher syndrome; polyneuritis cranialis; and rare instances of viral myopathy with rhabdomyolysis. The main conclusion of this review is the pressing need to define the neurology of COVID-19, its frequency, manifestations, neuropathology and pathogenesis. On behalf of the World Federation of Neurology we invite national and regional neurological associations to create local databases to report cases with neurological manifestations observed during the on-going pandemic. International neuroepidemiological collaboration may help define the natural history of this worldwide problem., Highlights • SARS-CoV-2 has definitive neurogenic capacity. • After binding to ACE2 receptors in nasal epithelium it invades the olfactory nerve and bulb progressing to invade the brainstem respiratory centers. • Irreversible respiratory failure may be the reason for the dismal prognosis of COVID-19 respirator-dependent patients. • SARS-CoV-2 binds to ACE2 receptors in endothelial cells causing endotheliitis. • Stroke occurs as a result of the pro-thrombotic state caused by endotheliitis. • Multi-organ failure occurs secondary to virus invasion of ACE2 receptors in lung, kidney, intestines, and brain.

Mitochondrial dysfunction is implicated in the pathogenesis of Alzheimer’s disease (AD). However, the precise mitochondrial molecular deficits in AD remain poorly understood. Mitochondrial and nuclear proteomic analysis in mature male triple transgenic AD mice (PS1M146V/APPSwe/TauP301L) by two-dimensional fluorescence difference gel electrophoresis (2D-DIGE) coupled with MALDI-TOF-MS/MS, bio-informatics analysis and immunofluorescent staining were performed in this study. In addition to impaired spatial memory impairment and intracellular accumulation of amyloid 1–42 (Aβ1–42) in the 3xTg-AD mice, a well-accepted mouse model of the human disease, we also found significantly increased DNA oxidative damage in entorhinal cortex, hippocampal CA1, CA3 and dental gyrus (DG), as evidenced by the positive staining of 8-hydroxyguanosine, a biomarker of mild cognitive impairment early in AD. We identified significant differences in 27 hippocampal mitochondrial proteins (11 increased and 16 decreased), and 37 hippocampal nuclear proteins (12 increased and 25 decreased) in 3xTg-AD mice compared with the wild-type (WT) mice. Differentially expressed mitochondrial and nuclear proteins were mainly involved in energy metabolism (>55%), synapses, DNA damage, apoptosis and oxidative stress. Two proteins were differentially expressed in both hippocampal mitochondria and nuclei, namely electron transport chain (ETC)-related protein ATP synthase subunit d (ATP5H) was significantly decreased, and apoptosis-related dynamin-1 (DYN1), a pre-synaptic and mitochondrial division-regulated protein that was significantly increased. In sum, perturbations of hippocampus mitochondrial energy metabolism-related proteins responsible for ATP generation via oxidation phosphorylation (OXPHOS), especially nuclear-encoded OXPHOS proteins, correlated with the amyloid-associated cognitive deficits of this murine AD model. The molecular changes in respiratory chain-related proteins and DYN1 may represent novel biomarkers of AD.

This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited., In threatened wildlife populations, it is important to determine whether observed low genetic diversity may be due to recent anthropogenic pressure or the consequence of historic events. Historical size of the Irrawaddy dolphin (Orcaella brevirostris) population inhabiting the Mekong River is unknown and there is significant concern for long-term survival of the remaining population as a result of low abundance, slow reproduction rate, high neonatal mortality, and continuing anthropogenic threats. We investigated population structure and reconstructed the demographic history based on 60 Irrawaddy dolphins samples collected between 2001 and 2009. The phylogenetic analysis indicated reciprocal monophyly of Mekong River Orcaella haplotypes with respect to haplotypes from other populations, suggesting long-standing isolation of the Mekong dolphin population from other Orcaella populations. We found that at least 85% of all individuals in the two main study areas: Kratie and Stung Treng, bore the same mitochondrial haplotype. Out of the 21 microsatellite loci tested, only ten were polymorphic and exhibited very low levels of genetic diversity. Both individual and frequency-based approaches suggest very low and non-significant genetic differentiation of the Mekong dolphin population. Evidence for recent bottlenecks was equivocal. Some results suggested a recent exponential decline in the Mekong dolphin population, with the current size being only 5.2% of the ancestral population. In order for the Mekong dolphin population to have any potential for long-term survival, it is imperative that management priorities focus on preventing any further population fragmentation or genetic loss, reducing or eliminating anthropogenic threats, and promoting connectivity between all subpopulations.

Nodding syndrome represents a complex encephalopathy in previously healthy children and adolescents that occurs in hot spots of South Sudan, northern Uganda and southern Tanzania. The core feature of this neurological disorder is a repetitive forward bobbing of the head towards the chin of a variable length of time associated with other features such generalized epileptic seizures, psychiatric symptoms/signs, stunted growth, wasting and reduced sexual development, among others. The etiology of this neuropediatric disorder so far has remained obscure, but there seems to be some evidence in support of a post-measles disorder as well as an involvement of the parasite Onchocerca volvulus which can cause skin and eye disease (river blindness). While discussing potential etiology and pathogenesis of nodding syndrome, we also explore reasons while funding for research on nodding syndrome has been so scarce and compare it to other similarly neglected diseases. Furthermore, we discuss the inclusion of nodding syndrome in the WHO list of neglected tropical diseases with the aim of creating a disease specific lobby, thereby supporting financing and collaboration on research and development for nodding syndrome. In the last paragraph we examine a global health approach to nodding syndrome via the sustainable development goals and conclude that by investing in some of the goals concerning health, poverty alleviation and quality education, among others, individuals suffering from nodding syndrome and their families may derive clear benefits which eventually can lead to an overall reduction in morbidity and mortality. However, other diseases will also benefit from employment of the sustainable development goals and therefore awareness of nodding syndrome needs to be raised, so that it will not be forgotten.