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The clinical, neuroanatomical, and neuropathologic phenotype of TBK1-associated frontotemporal dementia: A longitudinal case report
No full textAbstractIntroductionMutations in the TANK-binding kinase 1 (TBK1) gene have recently been shown to cause frontotemporal dementia (FTD). However, the phenotype of TBK1-associated FTD is currently unclear.MethodsWe performed a single case longitudinal study of a patient who was subsequently found to have a novel A705fs mutation in the TBK1 gene. He was assessed annually over a 7-year period with a series of clinical, cognitive, and magnetic resonance imaging assessments. His brain underwent pathological examination at postmortem.ResultsThe patient presented at the age of 64 years with an 18-month history of personality change including increased rigidity and obsessiveness, apathy, loss of empathy, and development of a sweet tooth. His mother had developed progressive behavioral and cognitive impairment from the age of 57 years. Neuropsychometry revealed intact cognition at first assessment. Magnetic resonance imaging showed focal right temporal lobe atrophy. Over the next few years his behavioral problems progressed and he developed cognitive impairment, initially with anomia and prosopagnosia. Neurological examination remained normal throughout without any features of motor neurone disease. He died at the age of 72 years and postmortem showed TDP-43 type A pathology but with an unusual novel feature of numerous TAR DNA-binding protein 43 (TDP-43)–positive neuritic structures at the cerebral cortex/subcortical white matter junction. There was also associated argyrophilic grain disease not previously reported in other TBK1 mutation cases.DiscussionTBK1-associated FTD can be associated with right temporal variant FTD with progressive behavioral change and relatively intact cognition initially. The case further highlights the benefits of next-generation sequencing technologies in the diagnosis of neurodegenerative disorders and the importance of detailed neuropathologic analysis
Parkin elimination of mitochondria is important for maintenance of lens epithelial cell ROS levels and survival upon oxidative stress exposure
No full textAbstractAge-related cataract is associated with oxidative stress and death of lens epithelial cells (LECs) whose survival is dependent on functional mitochondrial populations. Oxidative stress-induced depolarization/damage of LEC mitochondria results in increased reactive oxygen species (ROS) levels and cell death suggesting the need for a LEC mechanism to remove mitochondria depolarized/damaged upon oxidative stress exposure to prevent ROS release and LEC death. To date, a mechanism(s) for removal of depolarized/damaged LEC mitochondria has yet to be identified and the importance of eliminating oxidative stress-damaged mitochondria to prevent LEC ROS release and death has not been established. Here, we demonstrate that Parkin levels increase in LECs exposed to H2O2-oxidative stress. We establish that Parkin translocates to LEC mitochondria depolarized upon oxidative stress exposure and that Parkin recruits p62/SQSTM1 to depolarized LEC mitochondria. We demonstrate that translocation of Parkin results in the elimination of depolarized/damaged mitochondria and that Parkin clearance of LEC mitochondria is dependent on its ubiquitin ligase activity. Importantly, we demonstrate that Parkin elimination of damaged LEC mitochondria results in reduced ROS levels and increased survival upon oxidative stress exposure. These results establish that Parkin functions to eliminate LEC mitochondria depolarized/damaged upon oxidative stress exposure and that elimination of damaged mitochondria by Parkin is important for LEC homeostasis and survival. The data also suggest that mitochondrial quality control by Parkin could play a role in lens transparency
Topics in differential geometry associated with position vector fields on Euclidean submanifolds
No full textAbstractThe position vector field is the most elementary and natural geometric object on a Euclidean submanifold. The purpose of this article is to survey six research topics in differential geometry in which the position vector field plays very important roles. In this article we also explain the relationship between position vector fields and mechanics, dynamics, and D’Arcy Thompson’s law of natural growth in biology
“Vaginella massiliensis” gen. nov., sp. nov., a new genus cultivated from human female genital tract
No full textAbstractWe relate the main characteristics of “Vaginella massiliensis” strain Marseille P2517 (= DSM 102346=CSUR P2517), a new member of the Flavobacteriaceae family. The strain Marseille P2517 was cultivated from a vaginal swab from a healthy 22-year-old woman
Further development of an in vitro model for studying the penetration of chemicals through compromised skin
No full textAbstractA new in vitro model based on the electrical resistance properties of the skin barrier has been established in this laboratory. The model utilises a tape stripping procedure in dermatomed pig skin that removes a specific proportion of the stratum corneum, mimicking impaired barrier function observed in humans with damaged skin. The skin penetration and distribution of chemicals with differing physicochemical properties, namely; Benzoic acid, 3-Aminophenol, Caffeine and Sucrose has been assessed in this model. Although, skin penetration over 24h differed for each chemical, compromising the skin did not alter the shape of the time course profile, although absorption into receptor fluid was higher for each chemical. Systemic exposure (receptor fluid, epidermis and dermis), was marginally higher in compromised skin following exposure to the fast penetrant, Benzoic acid, and the slow penetrant Sucrose. The systemically available dose of 3-Aminophenol increased to a greater extent and the absorption of Caffeine was more than double in compromised skin, suggesting that Molecular Weight and Log Pow, are not the only determinants for assessing systemic exposure under these conditions. Although further investigations are required, this in vitro model may be useful for prediction of dermal route exposure under conditions where skin barrier is impaired
A case report of laparoscopic duodenal atresia repair in a neonate using a novel miniature stapling device
No full textAbstractIntroductionLaparoscopic duodenal atresia repair is an advanced procedure performed in select pediatric surgical centers. Recently, sub–6mm endosurgical staplers have been introduced, facilitating and accelerating the creation of intracorporeal intestinal anastomoses.Presentation of caseWe performed a laparoscopic duodenojejunostomy in a one-day-old child with duodenal atresia due to annular pancreas using a novel 5.8mm articulating endostapler with excellent outcome. The technical details are reported.DiscussionLaparoscopic duodenojejunostomy is a technically demanding procedure due to difficulty in hand-sewn anastomosis in a small and restricted space. With this novel 5.8mm articulating endostapler, we were able to perform a quicker and easier anastomosis.ConclusionWe report a case of laparoscopic duodenal atresia repair in a neonate using a novel miniature stapling device. This new technique is a safe, quick and easier way to perform laparoscopic duodenal atresia repair
Evaluation of aerial microbial pollutants in Al-Haram Al-Nabawi during pilgrimage of 2013
No full textAbstractAl-Madinah Al-Munawwarah is the second holiest site in Islam. The possibility of new emerging microbes is valid due to the increased number of pilgrims. The objectives of the current study were to estimate the numbers of fungi and bacteria inside and outside Al-Haram Al-Nabawi and to find whether new bacterial and fungal species have emerged compared to previous studies. Air samples were collected twice a day from 12 spots and four directions during the pilgrim year of 2013 for four consecutive weeks by using the sedimentation method. Thirty five genera and fifty eight species were identified. The most recovered bacterial genera were Staphylococcus, Micrococcus, Bacillus, and Dermacoccus with 32.47%, 18.18%, 12.85%, and 11.23%, respectively. Fifty nine isolates of fungi were molecularly identified. Aspergillus species had the highest percentage (78%). The other fungal genera identified (Alternaria triticina, Emericella nidulans, Emericella striata, Mucor circinelloides, Penicillium chrysogenum, Penicillium minioluteum, Rhizopus arrhizus, Rhizopus oryzae, and Syncephalastrum racemosum) had less than 5% frequency. In places such as Al-Haram Al-Nabawi, a large and crowded public (millions) exist especially during pilgrimages and Ramadan, thus, exposure to microorganisms is high. On the other hand, microorganism infectivity depends on many factors including their virulence, landing site, and person’s immunity. For those reasons, many aspects should be considered to avoid aerosol contaminants
Maintaining rigor in research: flaws in a recent study and a reanalysis of the relationship between state abortion laws and maternal mortality in Mexico
No full textAbstractObjectiveA recent publication [Koch E, Chireau M, Pliego F, Stanford J, Haddad S, Calhoun B, Aracena P, Bravo M, Gatica S, Thorp J. Abortion legislation, maternal healthcare, fertility, female literacy, sanitation, violence against women and maternal deaths: a natural experiment in 32 Mexican states. BMJ Open 2015;5(2):e006013] claimed that Mexican states with more restrictive abortion laws had lower levels of maternal mortality. Our objectives are to replicate the analysis, reanalyze the data and offer a critique of the key flaws of the Koch study.Study designWe used corrected maternal mortality data (2006–2013), live births, and state-level indicators of poverty. We replicate the published analysis. We then reclassified state-level exposure to abortion on demand based on actual availability of abortion (Mexico City versus the other 31 states) and test the association of abortion access and the maternal mortality ratio (MMR) using descriptives over time, pooled chi-square tests and regression models. We included 256 state-year observations.ResultsWe did not find significant differences in MMR between Mexico City (MMR=49.1) and the 31 states (MMR=44.6; p=.44). Using Koch's classification of states, we replicated published differences of higher MMR where abortion is more available. We found a significant, negative association between MMR and availability of abortion in the same multivariable models as Koch, but using our state classification (beta=−22.49, 95% CI=−38.9; −5.99). State-level poverty remains highly correlated with MMR.ConclusionKoch makes errors in methodology and interpretation, making false causal claims about abortion law and MMR. MMR is falling most rapidly in Mexico City, but our main study limitation is an inability to draw causal inference about abortion law or access and maternal mortality. We need rigorous evidence about the health impacts of increasing access to safe abortion worldwide.ImplicationsTransparency and integrity in research is crucial, as well as perhaps even more in politically contested topics such as abortion. Rigorous evidence about the health impacts of increasing access to safe abortion worldwide is needed
Focal osteoporosis defects play a key role in hip fracture
No full textAbstractBackgroundHip fractures are mainly caused by accidental falls and trips, which magnify forces in well-defined areas of the proximal femur. Unfortunately, the same areas are at risk of rapid bone loss with ageing, since they are relatively stress-shielded during walking and sitting. Focal osteoporosis in those areas may contribute to fracture, and targeted 3D measurements might enhance hip fracture prediction. In the FEMCO case-control clinical study, Cortical Bone Mapping (CBM) was applied to clinical computed tomography (CT) scans to define 3D cortical and trabecular bone defects in patients with acute hip fracture compared to controls. Direct measurements of trabecular bone volume were then made in biopsies of target regions removed at operation.MethodsThe sample consisted of CT scans from 313 female and 40 male volunteers (158 with proximal femoral fracture, 145 age-matched controls and 50 fallers without hip fracture). Detailed Cortical Bone Maps (c.5580 measurement points on the unfractured hip) were created before registering each hip to an average femur shape to facilitate statistical parametric mapping (SPM). Areas where cortical and trabecular bone differed from controls were visualised in 3D for location, magnitude and statistical significance. Measures from the novel regions created by the SPM process were then tested for their ability to classify fracture versus control by comparison with traditional CT measures of areal Bone Mineral Density (aBMD). In women we used the surgical classification of fracture location (‘femoral neck’ or ‘trochanteric’) to discover whether focal osteoporosis was specific to fracture type. To explore whether the focal areas were osteoporotic by histological criteria, we used micro CT to measure trabecular bone parameters in targeted biopsies taken from the femoral heads of 14 cases.ResultsHip fracture patients had distinct patterns of focal osteoporosis that determined fracture type, and CBM measures classified fracture type better than aBMD parameters. CBM measures however improved only minimally on aBMD for predicting any hip fracture and depended on the inclusion of trabecular bone measures alongside cortical regions. Focal osteoporosis was confirmed on biopsy as reduced sub-cortical trabecular bone volume.ConclusionUsing 3D imaging methods and targeted bone biopsy, we discovered focal osteoporosis affecting trabecular and cortical bone of the proximal femur, among men and women with hip fracture