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BackgroundNo studies have assessed the independent association of methionine homozygosity at codon 129 with the susceptibility to prion diseases, controlling for the effects of the codon 219 polymorphisms and other potential confounders, using a large-scale population-based dataset.MethodsWe conducted a case-control study using a Japanese nationwide surveillance database for prion diseases. The main exposure was methionine homozygosity at codon 129, and the outcome was development of prion diseases. Multivariable logistic regression models were employed for specific disease subtypes (sporadic Creutzfeldt-Jakob disease (CJD), genetic CJD and Gerstmann-Sträussler-Scheinker disease (GSS)).ResultsOf 5461 patients registered in the database, 2440 cases and 796 controls remained for the analysis. The cases comprised 1676 patients with sporadic CJD (69%), 649 with genetic CJD (27%) and 115 with GSS (5%). For patients with methionine homozygosity, potential risk for occurring prion diseases: adjusted OR (95% CI) was 2.21 (1.46 to 3.34) in sporadic CJD, 0.47 (0.32 to 0.68) in genetic CJD and 0.3 (0.17 to 0.55) in GSS. Among patients with specific prion protein abnormalities, the potential risk was 0.27 (0.17 to 0.41) in genetic CJD with 180 Val/Ile, 1.66 (0.65 to 5.58) in genetic CJD with 200 Glu/Lys, 3.97 (1.2 to 24.62) in genetic CJD with 232 Met/Arg and 0.71 (0.34 to 1.67) in GSS with 102 Pro/Leu.ConclusionsMethionine homozygosity at codon 129 was predisposing to sporadic CJD, but protective against genetic CJD and GSS, after adjustment for codon 219 polymorphism effect. However, the impacts differed completely among patients with specific prion protein abnormalities.

Studies on the very early electroencephalography (EEG) features prior to the emergence of generalized periodic discharges (GPDs, generally known as periodic sharp-wave complexes) in Creutzfeldt-Jakob disease (CJD) are rare. Fourteen patients with sporadic CJD (sCJD) (eight with MM1/classic and six with MM2c) were included in this study. The predominant findings of the first EEG were categorized as 1) lateralized periodic discharges (LPDs), 2) central sagittal sporadic epileptiform discharges (CSSEDs) showing midline predominant generalized spike-and-wave complexes and/or sharp waves in the central sagittal regions, or 3) focal epileptiform discharges. Clinical records, magnetic resonance imaging (MRI), and changes in EEG were compared between three groups (LPD in MM1/classic, CSSED in MM1/classic, and focal epileptiform discharge in MM2c). Three (37.5%) and five (62.5%) patients with MM1/classic sCJD were classified into the LPD and CSSED groups, respectively. Patients in the LPD group were accompanied by cortical hyperintensities at the corresponding areas on MRI, while those in the CSSED group showed hyperintensities on MRI at unassociated cortical areas. Follow-up EEG of three (100%) patients in the LPD group and four (80%) in the CSSED group showed transitions to GPDs. All patients with MM1/classic sCJD showed myoclonus on initial EEG, and the symptomatic side was opposite to the hemisphere showing LPDs or higher-amplitude central sagittal epileptiform activity. The periodicity after these EEGs likely contributes to the diagnostic confidence of physicians when patients are in the very early stages of MM1/classic sCJD.

Recent evidence suggests that soluble amyloid-β oligomers (AβOs) act as a key factor in the pathogenetic mechanism of Alzheimer's disease (AD). AβOs induce neurotoxic and synaptotoxic effects probably through binding to certain receptors, however it remains unclarified which receptors are most critically involved. In addition, dysregulation in glutamatergic signaling is implicated in AD. In this study, we used a rat primary cortical neuron model to investigate AβO-induced aberrations of synaptic proteins and binding of extracellular AβOs to candidate receptors in the glutamatergic system. Immunocytochemical analyses showed that both presynaptic (SNAP-25, synapsin I) and postsynaptic (spinophilin, homer 1b/c) proteins appeared to aberrantly dislocate from synapses upon AβO treatment. Double immunofluorescence staining of AβO-treated neurons without permeabilization pretreatment revealed that extracellular AβOs exist over neuronal soma and neurites and clearly colocalized with GluN1 and GluN2B subunits of NMDA receptors and metabotropic glutamate receptor 1 (mGluR1), but not with NMDA GluN2A subunits and mGluR5. AβO treatment altered neither total protein levels nor intracellular localizations of these receptors. These results suggest that extracellular AβOs specifically bind to both NMDA receptors containing GluN2B subunits and mGluR1. It is likely that binding of AβOs to these receptors induces various pathological responses, consequently leading to synaptic disruptions. Our study thus highlights the important roles of GluN2B-containing NMDA receptors and mGluR1 receptors in the synapse pathology in AD.

Symptomatic patent ductus arteriosus (sPDA) is common among preterm infants, and can lead to several complications. This is particularly true for extremely preterm infants, as closure of the ductus arteriosus using cyclooxygenase inhibitors is often difficult. A recent study using a preterm sheep model showed that intimal thickening—required for anatomical closure of the ductus arteriosus—is less developed in twins than in singletons. Therefore, this study primarily aimed to prove that the ductus arteriosus of extremely preterm twins is more resistant to cyclooxygenase inhibitors than those of extremely preterm singletons. Its secondary aim was to assess whether the resistance against cyclooxygenase inhibitors differed according to chorionicity. In this retrospective case–control study, medical records of 162 extremely preterm infants (gestational age

Background : This study aimed to evaluate the association between cognitive impairment and health-related quality of life (HRQOL), fatigue, and depression in Japanese patients with multiple sclerosis (MS). Methods : The Brief International Cognitive Assessment for MS (BICAMS) was performed in 184 Japanese patients with MS. The Functional Assessment of MS (FAMS), Fatigue Severity Scale (FSS), and Beck Depression Inventory-Second Edition (BDI-II) were used to evaluate HRQOL, fatigue, and depression, respectively. Results : Multiple linear regression analysis demonstrated positive correlations of the Symbol Digit Modalities Test (SDMT) with the scores on the FAMS subscales of mobility, symptoms, emotional well-being, and additional concerns and with the total FAMS score even after controlling for the Expanded Disability Status Scale score, age at examination, and duration of education. The SDMT score in the BICAMS battery had negative correlations with the BDI-II score, as revealed by multiple linear regression analysis. None of the three tests in the BICAMS had any correlation with the FSS score. Conclusion : The SDMT has a significant relationship with HRQOL and depression in Japanese patients with MS.

Introduction:the outbreak and rapid spread of the novel SARS-CoV-2, the causative agent of the coronavirus disease 2019 (COVID-19), has evolved into an unprecedented global pandemic. The infection impairs several human organs and systems, however, it is not clear how it affects thyroid function. The study therefore aimed at measuring plasma levels of thyroid hormones and Hs-CRP in COVID-19 patients and apparently healthy uninfected controls to assess the possible effect of SAR-CoV-2 infection on thyroid function. Methods:in this cross-sectional study carried out between May-August 2020, 90 consenting participants comprising 45 COVID-19 patients and 45 apparently healthy uninfected controls were recruited. Plasma FT3, FT4, TSH and Hs-CRP were measured using Enzyme Linked Immunosorbent Assay (ELISA) method. Data was analysed using SPSS version 20 and statistical significance set at p < 0.05. Results:the mean plasma FT3 and TSH concentrations were significantly higher in COVID-19 patients compared to controls (p < 0.001, p < 0.001 respectively). Euthyroidism was observed in all uninfected controls, whereas 35 (77.8%) COVID-19 patients were euthyroid. Sick euthyroid and subclinical hypothyroidism was observed in 7 (15.6%) and 3 (6.7%) COVID-19 patients, respectively. Conclusion:though there was a preponderance of euthyroidism among COVID-19 patients, significantly higher mean plasma levels of TSH and FT3, sick euthyroid syndrome and subclinical hypothyroidism observed among some COVID-19 patients may be indicative of disease-related thyroid function changes. Hence, there is need to pay attention to thyroid function during and after treatment of COVID-19.

Automobile technicians in resource-poor settings often work in poor environments and are exposed to chemicals that put them at risk of ill health and disease. These chemical exposures could affect blood coagulation, leading to bleeding disorders or thrombosis. The present study is aimed at assessing prothrombin test (PT) and activated partial thromboplastin test (aPTT) values, serum zinc (Zn) and copper (Cu) concentrations, and blood lead level (BLL) among occupationally exposed automobile technicians compared to unexposed controls. A total of 140 consenting participants comprising 70 automobile technicians and 70 unexposed controls were recruited for this case–control study. A 6-mL blood sample was drawn from each participant for estimation of BLL, serum Zn and Cu concentrations, and PT and aPTT values. Blood lead level, and serum Zn and Cu concentrations were determined using atomic absorption spectrophotometry, while PT and aPTT values were determined using Innovin PT and Actin FS Activated PTT reagents on the Sysmex CA-101 coagulation analyser. Data were analysed using t-tests, chi-square tests, and logistic and multiple linear regression analyses with statistical significance set at p < 0.05. The mean BLL, serum Zn concentration, and PT and aPTT values were significantly higher in automobile technicians compared to controls. Binary logistic regression showed that automobile technicians had higher odds of elevated PT value (OR = 21.769; p = 0.000), aPTT value (OR = 1.348; p = 0.018), BLL (OR = 1.261; p = 0.000) and serum Zn concentration (OR = 1.063; p = 0.005) than unexposed controls. Linear regression showed significant positive association of PT value with BLL and with serum Zn concentration. Higher PT and aPTT values reflect prolonged blood coagulation time among automobile technicians, which indicates impairment of extrinsic and intrinsic coagulation pathways associated with work-related exposures.

Electronic waste generation has been increasing at a rate three times faster than that of general waste stream. Developing nations like Nigeria bear the consequences as it is estimated that 500 containers, each carrying about 500,000 used computers and other electronic equipment, enter Nigeria’s ports every month from the United States, Europe and Asia. To this effect, The United Nations Environmental Programme (UNEP) and the Federal Government of Nigeria have announced a $15 million initiative to establish an electronic system in Nigeria, which will pioneer safe e-waste recycling in the country. It is against this background that this study was conducted to determine the households’ awareness and practice towards the recycling of e-waste, as well as the most suitable collection pattern within Kano Metropolis. The data for this study was collected using Open Data Kit (ODK) mobile phone platform, which contained questions on households’ characteristics, current practices regarding disposal and recycling of electronic waste as well as their awareness dimension on the recycling of e-waste. Statistical Package for Social Sciences (SPSS) was used to estimate the average number of unused households’ appliances and also to analyse household awareness and practice. The awareness dimension of the surveyed households about recycling of electronic waste was determined and 97% of the households are aware of the significance of electronic waste recycling. The positive statements presented about awareness indicates a positive awareness dimension about the significance of recycling electronic waste. Among the sampled households, 23% engage in e-waste recycling, and they all do this by selling their wastes (electronic waste, inclusive) to house-to-house scavengers. Majority of the households (77.4%) do not recycle electronic waste. They either keep them at home for decoration, give them out for free, burn them or dispose them in open dumpsites. The average quantity of e-waste prese

北海道屈斜路カルデラとその周辺は，約40 kaから続いている後カルデラ期に活発な火山活動と地形変化が生じてきた。とくに約20～23 kaのアトサヌプリカルデラ形成時に噴出したアトサヌプリ軽石（Ap）とおよそ7.6 kaの摩周カルデラより噴出した摩周f（Ma-f）は噴火規模が大きく，火砕流台地を形成するとともに釧路川を閉塞し屈斜路湖の水位を上昇させた。湖水位の上昇と火砕流二次堆積物の供給によって屈斜路湖岸および釧路川河岸には複数の段丘が形成された。また，このような地形面形成と並行して屈斜路湖東岸のアトサヌプリ火山群周辺では激しい隆起運動が生じ，隆起速度は最大2 m/kyr程度以上に至る。そしてこの隆起運動に伴い断層群が形成され，一部はA級活断層に匹敵する変位速度に達している。

Infections caused by Chromobacterium violaceum are extremely rare but can be relatively fatal in septicemia. We report a case of a 76 year old female who presented with pustules in the skin and later developed into septicemia. She succumbed to the illness despite escalating the antibiotic therapy to meropenem. To the best of our knowledge this is the 16th case report from India.

Background/Aim: To report cases in which we achieved sufficient width of the keratinized gingiva using a coronally advanced flap in combination with a subepithelial connective tissue graft (SCTG) obtained by the ‘CO(2) laser de-epithelization technique’ (CODE). Patients and Methods: Eleven patients with 21 Miller Class I, II, and III gingival recessions had surgery. To prepare SCTG, free gingival grafts were harvested and de-epithelialized extra-orally. De-epithelialization was conducted by irradiation of CO(2) laser. Postoperative examinations were performed at 12 months. Results: At 12 months, statistically highly significant root coverage was achieved in all recessions. Complete root coverage was obtained in 7 of the 21 recessions. The treatment yielded mean root coverage of 41.0%, and was associated with a mean gain of keratinized gingiva of 2.9±0.3 mm. Conclusion: The use of CODE allows harvesting grafts of excellent quality and quantity and increases the keratinization of the overlying mucosal epithelium.

In today’s dynamic and turbulent business environment, diversification has become a catalyst for achieving competitive advantages and the creation of synergy in market operations. This is because manufacturing companies operate in a highly competitive environment, especially among firmsthat produce the same or similar goods. This study examines the effect of a diversification strategy on an organization’s performance in the manufacturing sector. A quasi-experimental study with an ex-post facto research design were used for the study. The respondent populationconsists of thirty-one organizations listed in Nigerian Stock Exchange (NSE) for a period of 20 years (1997-2017), while the sample size is comprised of six organizations purposively selected based on their life-span and level of diversification. Three hypotheses were formulated and tested using ratio analysis, while performance was measured in terms of ROA, ROI and ROE; organization size, organizationvalue and growth; as well asleverage and liquidity. Data was drawn from the financial reports of the selected organizations, with E-View version 9 used for the data analysis. The study revealed that diversified organizations outperformundiversified ones in terms of ROA and ROI. While related diversified organizations were discovered to be positive in terms of ROA (26.8%), unrelated and hybrid diversified organizations were positive in ROE (81.7% and 20.5%). A diversification strategy leads to growth and profitability (20%) and a strong capital structure to cover liabilities (26%). The study concluded that diversification is a strategic tool for achieving strategic relevance and spontaneous performance.

Biometrics form a key characteristic of a species. Here, we provide a summary of biometrics held by the South African Bird Ringing Scheme (SAFRING), which was initiated in 1948, including measures ...

Purpose Mouse in vitro spermatogenesis is possible with classical organ culture methods, by placing the testis tissue at the interphase between culture medium and air. In this condition, however, a tissue piece tends to round up to be compact, whose central region suffers from shortage of nutrients and oxygen. In this study, the authors improved the culture condition by spreading each tissue thin and flat, by which they were able to get better access to the oxygen and nutrients. Methods Immature mouse testis tissues placed on agarose gel block were forced to spread flat by covering with a polydimethylsiloxane (PDMS) ceiling chip (PC chip). They were then cultured for weeks and evaluated by the transgene expression of Acr‐Gfp, which reflects the progression of spermatogenesis. Results Testis tissues covered with PC chip initiated and maintained spermatogenesis in its wider region than those without PC chip covering. Flow cytometric analysis demonstrated that the PC method yielded more numerous meiotic germ cells than those without PC. Immunohistochemical examination confirmed the authentic histological figure of spermatogenesis from spermatogonia up to round or elongating spermatids. Conclusions The PC chip method is simple and effective to improve the efficiency of in vitro spermatogenesis in the organ culture system.

TGF-β–activated kinase 1 (TAK1) is known to play vital roles for innate and adaptive immunity; however, little is known about its potential role in limiting biological responses such as inflammation. In this study, we report that macrophage TAK1 participates in negatively regulating inflammation by restraining proinflammatory cell death. Macrophages from TAK1-deficient mice underwent cell death in response to LPS and poly(I:C), which took place in a manner dependent on TLR/TRIF-induced active Caspase8-mediated cleavage of gasdermin D, known as an executioner of pyroptosis. Likewise, TNF-α induced Caspase8-dependent gasdermin D processing following cell death in TAK1-deficient macrophages. Importantly, we demonstrated that this type of proinflammatory macrophage death is linked to susceptibility to septic shock in mice lacking TAK1 in macrophages in a TNF-α–independent fashion. Taken together, our data revealed that TAK1 acts as a signaling checkpoint to protect macrophages from unique proinflammatory cell death, ensuring the maintenance of innate immune homeostasis.

This study sought to examine the effect of organization structure on organization strategy. Survey research design was employed through the administration of structured questionnaire to staff of Nestle Nigeria PLC, Unilever Nigeria PLC and PZ (Cussons) PLC. The findings revealed that, organization structure positively and significantly affects strategy implementation (F stat 107.52* 0.000) and that organization structure account for 53% (Adjusted R2= 0.5312) variation in organization strategy. It can therefore be concluded that, organization structure plays a significant role in strategy formulation and implementation in Nigeria multinational enterprises. It could be seen that, global matrix structure and product division structure are the most critical elements of organization structure driving strategy implementation in a multinational firm. It is therefore recommended that, multinational firms in Nigeria should employ matrix structure towards the enhancement of their organization strategy. This is because matrix structure has the highest effect on organization strategy.

Zonulopathy is a major concern if found during cataract surgery as it can cause further complications. Such complications may occur during continuous curvilinear capsulorhexis (CCC), lens fragmentation and intraocular lens (IOL) implantation. Femtosecond laser-assisted cataract surgery (FLACS) devices, such as the LenSX (Alcon Laboratories) are advantageous because they can detect the area and largest point of zonulopathy via anterior segment optical coherent tomography (AS-OCT) before the manual part of the procedure. CCC and lens fragmentation can also minimize further zonular stress. A symmetrical CCC is ideal for IOL implantation in the sulcus with optic capture. In the present study, we did not detect significant zonular dehiscence preoperatively in either of the eyes of our 68-year-old patient when using AS-OCT (CASIA2 Tomey). However, LenSx AS-OCT revealed zonular dehiscence in both eyes, perioperatively. We created CCC and lens fragmentation without causing stress to the zonules. In the subsequent manual part of procedure, we found zonular dehiscence in the same area as indicated by LenSx AS-OCT, which extended to approximately 200° in the right eye and 180° in the left. After lens fragmentation by LenSx, we successfully removed the lens without further zonular dialysis. However, zonular dialysis (>180°) in the right eye was too large to insert an IOL, either in the capsule or the sulcus. Therefore, we performed scleral IOL implantation. In the left eye, we avoided using capsular tension ring (CTR) for IOL placement to avoid further iatrogenic damage to the zonule. Instead, an IOL was inserted into the sulcus with optic capture to reduce the possibility of further stress to the zonula and phimosis. Post-surgically, the patient regained good eyesight in both eyes. This case illustrates the advantages of FLACS in addressing zonulopathy. The consistent creation of CCC and lens fragmentation by FLACS may increase success rates, even in unexpectedly challenging cases.

Tumefactive multiple sclerosis (tumefactive MS) is an atypical variant of MS characterized by a large isolated demyelinating lesion. Because tumefactive MS mimics high grade astrocytoma clinically and radiologically, it is difficult to distinguish between the two using only traditional diagnostic modalities, such as routine magnetic resonance imaging. [11C] methionine positron emission tomography (MET PET) has been known as a useful diagnostic tool for glioma. However, it has not been established as a diagnostic tool for tumefactive MS yet. Therefore, the objective of this study was to evaluate the performance of MET PET in differentiating tumefactive MS from high grade astrocytoma. We studied patients with tumefactive MS [six patients (three men, three women), 7 lesions] and 77 patients with astrocytoma (World Health Organization grade II: 13 patients, grade III: 28 patients, and grade IV: 36 patients), and we compared MET uptake of tumefactive demyelinating lesions and astrocytoma. For MET PET analysis, Lesion/Normal region ratios (L/N ratios) were calculated and compared between tumefactive demyelinating lesions and astrocytoma. On MET PET, the L mean/N ratio of tumefactive MS was 1.18 ± 0.50, which was significantly lower than that of high-grade glioma (astrocytoma grade III: 1.95 ± 0.62, P = 0.006; grade IV: 2.35 ± 0.54, P

The important of electric power distribution is to have centralized plants distributing electricity through Distributed generation (DG) which reduces the cost of maintenance on transmission and distribution station and also improve voltage profile. This research paper present the application of generation based on Biogas power renewable energy source to the Distribution network and how it stabilizes the network by normalizing the fluctuating voltage profile at the distribution end of power system. A Particle Swarm Optimization (PSO) model was performed and evaluation of the impact of the DG by stimulating the developed model in the system. A mathematical formulation and optimization algorithm was performed using the MATLAB/Simulink program. The results obtained were correction of the faulty buses voltages and stable power supply which is 29.4% better than the conventional one. The result shows the implementation of the optimisation technique has improved the energy efficiency of the distribution network.

Innate lymphoid cells (ILCs), composed of heterogeneous populations of lymphoid cells, contribute critically to immune surveillance at mucosal surfaces. ILC subsets develop from common lymphoid progenitors through stepwise lineage specification. However, the composition and temporal regulation of the transcription factor network governing such a process remain incompletely understood. Here, we report that deletion of the transcription factor interferon regulatory factor 2 (IRF-2), known also for its importance in the maturation of conventional NK cells, resulted in an impaired generation of ILC1, ILC2 and ILC3 subsets with lymphoid tissue inducer (LTi)-like cells hardly affected. In IRF-2-deficient mice, PD-1hi ILC precursors (ILCPs) that generate these three ILCs but not LTi-like cells were present at normal frequency, while their sub-population expressing high amounts of PLZF, another marker for ILCPs, was severely reduced. Notably, these IRF-2-deficient ILCPs contained normal quantities of PLZF-encoding Zbtb16 messages, and PLZF expression in developing invariant NKT cells within the thymus was unaffected in these mutant mice. These results point to a unique, cell-type selective role for IRF-2 in ILC development, acting at a discrete step critical for the generation of functionally competent ILCPs.