Bowmanjoensen0351

Periodontitis is an inflammatory disease associated with severe alveolar bone loss and is dominantly induced by lipopolysaccharide from Gram-negative bacteria; however, the role of Gram-positive bacteria in periodontal bone resorption remains unclear. In this study, we examined the effects of lipoteichoic acid (LTA), a major cell-wall factor of Gram-positive bacteria, on the progression of inflammatory alveolar bone loss in a model of periodontitis. In coculture of mouse primary osteoblasts and bone marrow cells, LTA induced osteoclast differentiation in a dose-dependent manner. LTA enhanced the production of PGE2 accompanying the upregulation of the mRNA expression of mPGES-1, COX-2 and RANKL in osteoblasts. The addition of indomethacin effectively blocked the LTA-induced osteoclast differentiation by suppressing the production of PGE2. Using ex vivo organ cultures of mouse alveolar bone, we found that LTA induced alveolar bone resorption and that this was suppressed by indomethacin. In an experimental model of periodontitis, LTA was locally injected into the mouse lower gingiva, and we clearly detected alveolar bone destruction using 3D-μCT. We herein demonstrate a new concept indicating that Gram-positive bacteria in addition to Gram-negative bacteria are associated with the progression of periodontal bone loss.The Regulator of G protein signaling 4 (Rgs4) is a member of the RGS proteins superfamily that modulates the activity of G-protein coupled receptors. It is mainly expressed in the nervous system and is linked to several neuronal signaling pathways; however, its role in neural development in vivo remains inconclusive. Here, we generated and characterized a rgs4 loss of function model (MZrgs4) in zebrafish. MZrgs4 embryos showed motility defects and presented reduced head and eye sizes, reflecting defective motoneurons axon outgrowth and a significant decrease in the number of neurons in the central and peripheral nervous system. Forcing the expression of Rgs4 specifically within motoneurons rescued their early defective outgrowth in MZrgs4 embryos, indicating an autonomous role for Rgs4 in motoneurons. We also analyzed the role of Akt, Erk and mechanistic target of rapamycin (mTOR) signaling cascades and showed a requirement for these pathways in motoneurons axon outgrowth and neuronal development. Drawing on pharmacological and rescue experiments in MZrgs4, we provide evidence that Rgs4 facilitates signaling mediated by Akt, Erk and mTOR in order to drive axon outgrowth in motoneurons and regulate neuronal numbers.The lung is severely affected by intestinal ischemia-reperfusion (I-R) injury. Mesna, a thiol compound, possess anti-inflammatory and antioxidant properties. We aimed in the present work to explore the potential beneficial effects of Mesna on the acute lung damage mediated by intestinal I-R in a rat model. Forty male adult albino rats were randomly separated into; control, intestinal I-R, Mesna I and Mesna II groups. Mesna was administered by intraperitoneal injection at a dose of 100 mg/kg, 60 min before ischemia (Mesna I) and after reperfusion (Mesna II). Arterial blood gases and total proteins in bronchoalveolar lavage (BAL) were measured. Lung tissue homogenates were utilized for biochemical assays of proinflammatory cytokines and oxidative stress markers. Lung specimens were managed for examination by light and electron microscopy. Our results revealed that Mesna attenuated the histopathological changes and apoptosis of the lung following intestinal I-R. Mesna also recovered systemic oxygenation. Mesna suppressed neutrophil infiltration (as endorsed by the reduction in MPO level), reduced ICAM-1 mRNA expression, inhibited NF-κB pathway and reduced the proinflammatory cytokines (TNF-α, IL-1β and IL-6) in the lung tissues. Mesna maintained the antioxidant profile as evidenced by the elevation of the tissue GPx and SOD and down-regulation of HSP70 immune-expressions. Accordingly, Mesna treatment can be a promising way to counteract remote injury of the lung resulted from intestinal I-R.COVID 19 is associated with a hypercoagulable state and frequent thromboembolic complications. For how long this acquired abnormality lasts potentially requiring preventive measures, such as anticoagulation remains to be delineated. We used viscoelastic rotational thrombelastometry (ROTEM) in a single center cohort of 13 critical ill patients and performed follow up examinations three months after discharge from ICU. We found clear signs of a hypercoagulable state due to severe hypofibrinolysis and a high rate of thromboembolic complications during the phase of acute illness. Three month follow up revealed normalization of the initial coagulation abnormality and no evidence of venous thrombosis in all thirteen patients. In our cohort the coagulation profile was completely normalized three months after COVID-19. Based on these findings, discontinuation of anticoagulation can be discussed in patients with complete venous reperfusion.In 2001, the German Multiple Sclerosis Society, facing lack of data, founded the German MS Registry (GMSR) as a long-term data repository for MS healthcare research. By the establishment of a network of participating neurological centres of different healthcare sectors across Germany, GMSR provides observational real-world data on long-term disease progression, sociodemographic factors, treatment and the healthcare status of people with MS. This paper aims to illustrate the framework of the GMSR. Structure, design and data quality processes as well as collaborations of the GMSR are presented. The registry's dataset, status and results are discussed. As of 08 January 2021, 187 centres from different healthcare sectors participate in the GMSR. Following its infrastructure and dataset specification upgrades in 2014, more than 196,000 visits have been recorded relating to more than 33,000 persons with MS (PwMS). The GMSR enables monitoring of PwMS in Germany, supports scientific research projects, and collaborates with national and international MS data repositories and initiatives. With its recent pharmacovigilance extension, it aligns with EMA recommendations and helps to ensure early detection of therapy-related safety signals.Bombesin is a putative antibacterial peptide isolated from the skin of the frog, Bombina bombina. Two related (bombesin-like) peptides, gastrin-releasing peptide (GRP) and neuromedin B (NMB) have been found in mammals. The history of GRP/bombesin discovery has caused little attention to be paid to the evolutionary relationship of GRP/bombesin and their receptors in vertebrates. We have classified the peptides and their receptors from the phylogenetic viewpoint using a newly established genetic database and bioinformatics. Here we show, by using a clawed frog (Xenopus tropicalis), that GRP is not a mammalian counterpart of bombesin and also that, whereas the GRP system is widely conserved among vertebrates, the NMB/bombesin system has diversified in certain lineages, in particular in frog species. To understand the derivation of GRP system in the ancestor of mammals, we have focused on the GRP system in Xenopus. Gene expression analyses combined with immunohistochemistry and Western blotting experiments demonstrated that GRP peptides and their receptors are distributed in the brain and stomach of Xenopus. We conclude that GRP peptides and their receptors have evolved from ancestral (GRP-like peptide) homologues to play multiple roles in both the gut and the brain as one of the 'gut-brain peptide' systems.Hypertension is a recognized comorbidity for COVID-19. The association of antihypertensive medications with outcomes in patients with hypertension is not fully described. However, angiotensin-converting enzyme 2 (ACE2), responsible for host entry of the novel coronavirus (SARS-CoV-2) leading to COVID-19, is postulated to be upregulated in patients taking angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs). Here, we evaluated the occurrence of pulmonary adverse drug events (ADEs) in patients with hypertension receiving ACEIs/ARBs to determine if disparities exist between individual drugs within the respective classes using data from the FDA Spontaneous Reporting Systems. For this purpose, we proposed the proportional reporting ratio to provide a statistical summary for the commonality of an ADE for a specific drug as compared to the entire database for drugs in the same or other classes. In addition, a statistical procedure, multiple logistic regression analysis, was emy ADEs.High-resolution neurosonography (HRNS) has become a major imaging modality in assessment of peripheral nerve trauma in the recent years. However, the vascular changes of traumatic lesions have not been quantitatively assessed in HRNS. Here, we describe the vascular-ratio, a novel HRNS-based quantitative parameter for the assessment of intraneural vascular alterations in patients with nerve lesions. N = 9 patients suffering from peripheral nerve trauma were examined clinically, electrophysiologically and with HRNS (SonoSite Exporte, Fuji). Image analyses using Fiji included determination of the established fascicular ratio (FR), the cross-section ratio (CSR), and as an extension, the calculation of a vascular ratio (VR) of the healthy versus damaged nerve and a muscle perfusion ratio (MPR) in comparison to a healthy control group. The mean VR in the healthy part of the affected nerve (14.14%) differed significantly (p  less then  0.0001) from the damaged part (VR of 43.26%). This coincides with significant differences in the FR and CSR calculated for the damaged part versus the healthy part and the controls. In comparison, there was no difference between VRs determined for the healthy part of the affected nerve and the healthy controls (14.14% / 17.72%). However, the MPR of denervated muscles was significantly decreased compared to the non-affected contralateral controls. VR and MPR serve as additional tools in assessing peripheral nerve trauma. Image analysis and calculation are feasible. Combined with the more morphologic FR and CSR, the VR and MPR provide a more detailed insight into alterations accompanying nerve trauma.Neuroendocrine prostate cancer (NEPC) is a lethal subtype of prostate cancer that rarely develops de novo in primary tumors and is commonly acquired during the development of treatment resistance. NEPC is characterized by gain of neuroendocrine markers and loss of androgen receptor (AR), making it resistant to current therapeutic strategies targeting the AR signaling axis. Here, we report that MCM2, MCM3, MCM4, and MCM6 (MCM2/3/4/6) are elevated in human NEPC and high levels of MCM2/3/4/6 are associated with liver metastasis and poor survival in prostate cancer patients. MCM2/3/4/6 are four out of six proteins that form a core DNA helicase (MCM2-7) responsible for unwinding DNA forks during DNA replication. Inhibition of MCM2-7 by treatment with ciprofloxacin inhibits NEPC cell proliferation and migration in vitro, significantly delays NEPC tumor xenograft growth, and partially reverses the neuroendocrine phenotype in vivo. Our study reveals the clinical relevance of MCM2/3/4/6 proteins in NEPC and suggests that inhibition of MCM2-7 may represent a new therapeutic strategy for NEPC.Silicosis is a diffuse interstitial lung disease caused by sustained inhalation of silica and silicates. Several cytokines are activated by their inhalation and can mediate the process of pulmonary fibrosis. The identification of biomarkers could allow an early diagnosis before the development of radiological alterations and help monitor the evolution of patients. The objetive of this study was to determine the clinical significance of specific biomarkers, to estimate their association with the development, severity and/or progression of silicosis, and identify determinants of this evolution. We conducted a prospective observational study in patients attending the pulmonology clinic from 2009 to 2018. Serum levels of the following inflammatory mediators were assessed interleukin-6 (IL-6), interleukin 2 receptor subunit alpha (IL2R) interleukin 1 beta (IL1B), interleukin-8 (IL-8), tumour necrosis factor-alpha (TNF-α), transforming growth factor-beta1 (TGF-β1), alpha-1 antitrypsin (AAT), C-reactive protein (CRP), lactate dehydrogenase (LDH) and ferritin in subjects exposed to silica, with and without silicosis. Association between those inflammatory mediators with lung function measurements and radiological severity of disease and their impact on prognosis were analysed. 337 exposed to silica (278 with silicosis) and 30 subjects in the control group were included. IL-8, α1AT, ferritin, CRP and LDH levels were higher in silicosis than in those exposed to silica without silicosis. IL-8, LDH and AAT levels were associated with progression of silicosis and IL-6, IL-8, LDH, AAT, ferritin, and CRP with vital status. The results of the ROC analysis indicated the potential of IL-8 as a biomarker in the presence of silicosis and for the prediction of mortality.In this work, we performed an experimental investigation supported by a theoretical analysis, to improve knowledge on the laser ablation of silicon with THz bursts of femtosecond laser pulses. Laser ablated craters have been created using 200 fs pulses at a wavelength of 1030 nm on silicon samples systematically varying the burst features and comparing to the normal pulse mode (NPM). Using bursts in general allowed reducing the thermal load to the material, however, at the expense of the ablation rate. The higher the number of pulses in the bursts and the lower the intra-burst frequency, the lower is the specific ablation rate. However, bursts at 2 THz led to a higher specific ablation rate compared to NPM, in a narrow window of parameters. Theoretical investigations based on the numerical solution of the density-dependent two temperature model revealed that lower lattice temperatures are reached with more pulses and lower intra-burst frequencies, thus supporting the experimental evidence of the lower thermal load in burst mode (BM). This is ascribed to the weaker transient drop of reflectivity, which suggests that with bursts less energy is transferred from the laser to the material. This also explains the trends of the specific ablation rates. Moreover, we found that two-photon absorption plays a fundamental role during BM processing in the THz frequency range.Phenological shifts are among the most obvious biological responses to environmental change, yet documented responses for Southern Ocean marine mammals are extremely rare. Marine mammals can respond to environmental changes through phenological flexibility of their life-history events such as breeding and moulting. Southern elephant seals (Mirounga leonina) undergo an obligatory annual moult which involves the rapid shedding of epidermal skin and hair while seals fast ashore. We quantified the timing (phenology) and duration (the time from arrival ashore to departure) of the moult haulout of 4612 female elephant seals at Marion Island over 32 years. Using linear mixed-effects models, we investigated age, breeding state and environmental drivers of moult timing and haulout duration. We found no clear evidence for a temporal shift in moult phenology or its duration. Annual variation in moult arrival date and haulout duration was small relative to age and breeding effects, which explained more than 90% of the variance in moult arrival date and 25% in moult haulout duration. All environmental covariates we tested explained minimal variation in the data. Female elephant seals moulted progressively later as juveniles, but adults age 4 and older had similar moult start dates that depended on the breeding state of the female. In contrast, moult haulout duration was not constant with age among adults, but instead became shorter with increasing age. Moulting is energetically expensive and differences in the moult haulout duration are possibly due to individual variation in body mass and associated metabolizable energy reserves, although other drivers (e.g. hormones) may also be present. Individual-based data on moult arrival dates and haulout duration can be used as auxiliary data in demographic modelling and may be useful proxies of other important biological parameters such as body condition and breeding history.Lung cancer is one of the deadliest cancers in the world. Two of the most common subtypes, lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC), have drastically different biological signatures, yet they are often treated similarly and classified together as non-small cell lung cancer (NSCLC). LUAD and LUSC biomarkers are scarce, and their distinct biological mechanisms have yet to be elucidated. To detect biologically relevant markers, many studies have attempted to improve traditional machine learning algorithms or develop novel algorithms for biomarker discovery. However, few have used overlapping machine learning or feature selection methods for cancer classification, biomarker identification, or gene expression analysis. This study proposes to use overlapping traditional feature selection or feature reduction techniques for cancer classification and biomarker discovery. The genes selected by the overlapping method were then verified using random forest. The classification statistics of the overlapping method were compared to those of the traditional feature selection methods. The identified biomarkers were validated in an external dataset using AUC and ROC analysis. Gene expression analysis was then performed to further investigate biological differences between LUAD and LUSC. Overall, our method achieved classification results comparable to, if not better than, the traditional algorithms. It also identified multiple known biomarkers, and five potentially novel biomarkers with high discriminating values between LUAD and LUSC. Many of the biomarkers also exhibit significant prognostic potential, particularly in LUAD. Our study also unraveled distinct biological pathways between LUAD and LUSC.Gastrointestinal symptoms are common in COVID-19 patients but the nature of the gut immune response to SARS-CoV-2 remains poorly characterized, partly due to the difficulty of obtaining biopsy specimens from infected individuals. In lieu of tissue samples, we measured cytokines, inflammatory markers, viral RNA, microbiome composition, and antibody responses in stool samples from a cohort of 44 hospitalized COVID-19 patients. SARS-CoV-2 RNA was detected in stool of 41% of patients and more frequently in patients with diarrhea. Patients who survived had lower fecal viral RNA than those who died. Strains isolated from stool and nasopharynx of an individual were the same. Compared to uninfected controls, COVID-19 patients had higher fecal levels of IL-8 and lower levels of fecal IL-10. Stool IL-23 was higher in patients with more severe COVID-19 disease, and we found evidence of intestinal virus-specific IgA responses associated with more severe disease. We provide evidence for an ongoing humeral immune response to SARS-CoV-2 in the gastrointestinal tract, but little evidence of overt inflammation.Childhood arterial ischemic stroke (CAIS) is a rare event. Diverse etiologies, risk factors, symptoms and stroke mimics hamper obtaining a fast diagnosis and implementing immediate recanalization strategies. Over a period of 3 years (2015-2017), the data of 164 pediatric patients (> 28 days of life-18 years) with a first episode of AIS were submitted to a hospital-based nationwide surveillance system for rare disorders (ESPED). We report a subgroup analysis of patients who have undergone recanalization therapy and compare these data with those of the whole group. Twenty-eight patients (17%) with a median age of 12.2 years (range 3.3-16.9) received recanalization therapy. Hemiparesis, facial weakness and speech disturbance were the main presenting symptoms. The time from onset of symptoms to confirmation of diagnosis was significantly shorter in the intervention group (4.1 h vs. 20.4 h, p ≤ 0.0001). Only in one patient occurred a minor bleed. Cardiac disease as predisposing risk factor was more common in the recanalization group. Recanalization therapies are feasible and increasingly applied in children with AIS. High awareness, timely diagnosis and a large amount of expertise may improve time to treatment and make hyperacute therapy an option for more patients.Kawasaki disease (KD) is an acute systemic vasculitis that mainly affects infants and young children. The etiology of KD has been discussed for several decades; however, no reproducible risk factors have yet been proven. We used the Japan Environment and Children's Study data to explore the association between the causal effects of exposure during the fetal and neonatal periods and KD onset. The Japan Environment and Children's Study, a nationwide birth cohort study, has followed approximately 100,000 children since 2011. We obtained data on exposures and outcomes from the first trimester to 12 months after birth. Finally, we included 90,486 children who were followed for 12 months. Among them, 343 children developed KD. Multivariate logistic regression revealed that insufficient intake of folic acid during pregnancy (odds ratio [OR], 1.37; 95% CI 1.08-1.74), maternal thyroid disease during pregnancy (OR, 2.03; 95% CI 1.04-3.94), and presence of siblings (OR, 1.33; 95% CI 1.06-1.67) were associated with KD onset in infancy. In this study, we identified three exposures as risk factors for KD. Further well-designed studies are needed to confirm a causal relationship between these exposures and KD onset.Nucleotide-binding domain and leucine-rich repeat (LRR)-containing family protein 3 (NLRP3) regulated the maturation of inflammation-related cytokines by forming NLRP3 inflammasome, which plays pivotal roles in sepsis pathogenesis. In this study, we evaluated the genetic association of NLRP3 polymorphisms with sepsis (640 patients and 769 controls) and characterized the impact of NLRP3 polymorphisms on NLRP3 expression and inflammatory responses. No significant differences were observed in genotype/allelic frequencies of NLRP3 29940G>C between sepsis cases and controls. The G allele was significantly overrepresented in patients with septic shock than those in sepsis subgroup, and the GC/GG genetypes were related to the 28-day mortality of sepsis. Lipopolysaccharide challenge to peripheral blood mononuclear cells showed a significant suppression of NLRP3 mRNA expression and release of IL-1β and TNF-α in CC compared with the GC/GG genotype category. Functional experiments with luciferase reporter vectors containing the NLRP3 3'-UTR with the 29940 G-to-C variation in HUVECs and THP-1 cells showed a potential suppressive effect of miR-146a on NLRP3 transcription in the presence of the C allele. Taken together, these results demonstrated that the 29940 G-to-C mutation within the NLRP3 3'-UTR was a gain-of-function alteration that caused the suppression of NLRP3 expression and downstream inflammatory cytokine production via binding with miR-146a, which ultimately protected patients against susceptibility to sepsis progression and poor clinical outcome.Expansion of various types of water infrastructure is critical to water security in Africa. To date, analysis of adverse disease impacts has focused mainly on large dams. The aim of this study was to examine the effect of both small and large dams on malaria in four river basins in sub-Saharan Africa (i.e., the Limpopo, Omo-Turkana, Volta and Zambezi river basins). The European Commission's Joint Research Center (JRC) Yearly Water Classification History v1.0 data set was used to identify water bodies in each of the basins. Annual malaria incidence data were obtained from the Malaria Atlas Project (MAP) database for the years 2000, 2005, 2010 and 2015. A total of 4907 small dams and 258 large dams in the four basins, with 14.7million people living close ( less then  5 km) to their reservoirs in 2015, were analysed. The annual number of malaria cases attributable to dams of either size across the four basins was 0.9-1.7 million depending on the year, of which between 77 and 85% was due to small dams. The majority of these cases occur in areas of stable transmission. Malaria incidence per kilometre of reservoir shoreline varied between years but for small dams was typically 2-7 times greater than that for large dams in the same basin. Between 2000 and 2015, the annual malaria incidence showed a broadly declining trend for both large and small dam reservoirs in areas of stable transmission in all four basins. In conclusion, the malaria impact of dams is far greater than previously recognized. Small and large dams represent hotspots of malaria transmission and, as such, should be a critical focus of future disease control efforts.The R47H variant of the microglial membrane receptor TREM2 is linked to increased risk of late onset Alzheimer's disease. Human induced pluripotent stem cell derived microglia (iPS-Mg) from patient iPSC lines expressing the AD-linked R47Hhet TREM2 variant, common variant (Cv) or an R47Hhom CRISPR edited line and its isogeneic control, demonstrated that R47H-expressing iPS-Mg expressed a deficit in signal transduction in response to the TREM2 endogenous ligand phosphatidylserine with reduced pSYK-pERK1/2 signalling and a reduced NLRP3 inflammasome response, (including ASC speck formation, Caspase-1 activation and IL-1beta secretion). Apoptotic cell phagocytosis and soluble TREM2 shedding were unaltered, suggesting a disjoint between these pathways and the signalling cascades downstream of TREM2 in R47H-expressing iPS-Mg, whilst metabolic deficits in glycolytic capacity and maximum respiration were reversed when R47H expressing iPS-Mg were exposed to PS+ expressing cells. These findings suggest that R47H-expressing microglia are unable to respond fully to cell damage signals such as phosphatidylserine, which may contribute to the progression of neurodegeneration in late-onset AD.The spatio-temporal variability of fish distribution is important to better manage and protect the populations of endangered species. In this sense, the vertical movements of a vulnerable and protected species, Sciaena umbra, were assessed in a marine protected area (the Réserve Naturelle Marine de Cerbère-Banyuls, south of France) to study the variability of their bathymetric distribution at different time scales. Twenty adults were marked with acoustic transmitters and acoustically monitored over 2.5 years. This revealed that some individuals remained at shallow waters ( less then  8 m) all year round, while others presented vertical segregation at deeper waters during the cold months (mean depth of 22.5 ± 0.04 m) and all aggregated in shallow waters during the warm months. The brown meagre was more active during the night, except in June and July when peaks of activity were observed at dusk. These patterns are likely associated with foraging and reproductive behavior during the cold and warm periods, respectively, and likely regulated by water temperature and the depth of the thermocline. Here, we provide valuable information on when and where in the water column critical periods of S. umbra life cycle are expected to occur, which should be considered in management and protection plans.Nephrotic syndrome arising from monogenic mutations differs substantially from acquired ones in their clinical prognosis, progression, and disease management. Several pathogenic mutations in the COQ8B gene are known to cause nephrotic syndrome. Here, we used the whole-exome sequencing (WES) technology to decipher the genetic cause of nephrotic syndrome (CKD stage-V) in a large affected consanguineous family. Our study exposed a novel missense homozygous mutation NC_000019.9g.41209497C > T; NM_024876.4c.748G > A; NP_079152.3p.(Asp250Asn) in the 9th exon of the COQ8B gene, co-segregated well with the disease phenotype. Our study provides the first insight into this homozygous condition, which has not been previously reported in 1000Genome, ClinVar, ExAC, and genomAD databases. In addition to the pathogenic COQ8B variant, the WES data also revealed some novel and recurrent mutations in the GLA, NUP107, COQ2, COQ6, COQ7 and COQ9 genes. The novel variants observed in this study have been submitted to the ClinVar database and are publicly available online with the accessions SCV001451361.1, SCV001451725.1 and SCV001451724.1. Based on the patient's clinical history and genomic data with in silico validation, we conclude that pathogenic mutation in the COQ8B gene was causing kidney failure in an autosomal recessive manner. We recommend WES technology for genetic testing in such a consanguineous family to not only prevent the future generation, but early detection can help in disease management and therapeutic interventions.Outdoor air pollution has been linked to poor sleep health, but limited studies have investigated the relationship between solid cooking fuels and sleep health in adults. Therefore, we analyzed data from the China Health and Retirement Survey (CHARLS), a national survey of about 17,000 residents aged over 45. Participants were restricted to those who participated in CHARLS 2011, 2013 and 2015 (n = 8,668). Sleep health was indicated by self-reported average sleep hours at night and the numbers of unrested days/week in CHARLS 2015. We analyzed cooking fuel types reported and assessed the duration of solid fuels usage as consistent (indicated use in all three surveys or 6 + years) or inconsistent use (indicated use in one or two surveys or 1-4 years). We found consistent use of solid fuels was associated with a shorter sleep duration (OR = 1.17 95% CI 1.01, 1.35 for ≤ 6 h vs. 7-9 h/day) and higher frequencies of feeling unrested (OR = 1.32 95% CI 1.12, 1.55 for ≥ 5 days/week vs. none) compared with cleaner fuels use. The associations for inconsistent solid fuels use and sleep health were in the similar direction but smaller in magnitude. Further research is needed to confirm our findings and evaluate the exposure impact of specific fuel types to inform intervention strategies.The prevalence of clinically defined problematic substance use among stroke patients is overlooked and its association with post-stroke depression (PSD) is unknown. Our aims were to (1) estimate the proportion of stroke patients with a problematic substance use as defined by clinical screening scales; (2) determine the proportion of PSD at three months of follow-up; (3) explore if the baseline severity in substance use and its evolution are independent predictors of PSD. A cohort of first-ever non-severe stroke adult patients was screened at baseline and three months post-stroke using recommended cut-off scores of standardized scales for tobacco, alcohol and cannabis abuse. PSD was defined using the Center of Epidemiological Studies Depression scale score. Out of the 244 eligible patients, 74 (30.3%) presented a problematic substance use, including 21 (8.6%) polydrug abusers. Among these patients, the prevalence of PSD was 50.8%, including 29.5% of severe depression. The severity of tobacco dependence at baseline was found to double the risk (OR 1.59, 95% CI 1.05-2.43) of presenting a PSD, independently of previously reported risk factors. We found no significant evidence for an effect of the evolution in substance use at follow-up. Addictive disorders are part of the critical unmet needs that should be addressed in the management of PSD.Gastrointestinal (GI) strictures are difficult to treat in a variety of disease processes. Currently, there are no Food and Drug Administration (FDA) approved drugs for fibrosis in the GI tract. One of the limitations to developing anti-fibrotic drugs has been the lack of a reproducible, relatively inexpensive, large animal model of fibrosis-driven luminal stricture. This study aimed to evaluate the feasibility of creating a model of luminal GI tract strictures. Argon plasma coagulation (APC) was applied circumferentially in porcine esophagi in vivo. Follow-up endoscopy (EGD) was performed at day 14 after the APC procedure. We noted high grade, benign esophageal strictures (n = 8). All 8 strictures resembled luminal GI fibrotic strictures in humans. These strictures were characterized, and then successfully dilated. A repeat EGD was performed at day 28 after the APC procedure and found evidence of recurrent, high grade, fibrotic, strictures at all 8 locations in all pigs. Pigs were sacrificed and gross and histologic analyses performed. Histologic examination showed extensive fibrosis, with significant collagen deposition in the lamina propria and submucosa, as well as extensive inflammatory infiltrates within the strictures. In conclusion, we report a porcine model of luminal GI fibrotic stricture that has the potential to assist with developing novel anti-fibrotic therapies as well as endoscopic techniques to address recurring fibrotic strictures in humans.Multi-tracer imaging can provide useful information in the definitive diagnosis and research of medical, biological, and pharmaceutical sciences. Single-photon emission computed tomography (SPECT) is one of the nuclear medicine imaging modalities widely used for diagnosis or medical research and has a multi-tracer imaging capability. One of the drawbacks of multi-tracer imaging is crosstalk from other gamma rays, which affects the reconstructed image. Scattering correction methods, such as the dual- and triple-energy window methods, are used for conventional SPECT imaging to reduce the background caused by the crosstalk. This study proposes another crosstalk reduction method. Some nuclides emit two or more gamma rays through intermediate levels. Thus, detecting these gamma rays with the coincidence method allows us to distinguish a true gamma ray signal and a background signal. The nuclide position can be estimated at the intersection of two gamma rays using collimators. We demonstrate herein simultaneous 111In and 177Lu imaging via the double-photon coincidence method using GAGG detectors and parallel hole collimators. The double-photon coincidence method greatly reduces the background caused by other gamma rays and offers higher-quality images than does conventional imaging.In this study, we show that the discharge voltage pattern of a supercapacitor exhibiting fractional-order behavior from the same initial steady-state voltage into a constant resistor is dependent on the past charging voltage profile. The charging voltage was designed to follow a power-law function, i.e. [Formula see text], in which [Formula see text] (charging time duration between zero voltage to the terminal voltage [Formula see text]) and p ([Formula see text]) act as two variable parameters. We used this history-dependence of the dynamic behavior of the device to uniquely retrieve information pre-coded in the charging waveform pattern. Furthermore, we provide an analytical model based on fractional calculus that explains phenomenologically the information storage mechanism. The use of this intrinsic material memory effect may lead to new types of methods for information storage and retrieval.Endocapillary proliferation occurs in various types of glomerulonephritis (GN), with varying prognoses. We examined 42 renal biopsy samples representing endocapillary proliferative lesions from post-streptococcal acute GN (PSAGN), Henoch-Schönlein purpura nephritis (HSPN), and lupus nephritis (LN). In PSAGN, the glomerular capillary network was maintained, although severe lesions displayed dots or short, curved lines, indicating CD34-positive capillaries and suggesting capillary obstruction. Conversely, patients with LN and HSPN displayed obstruction of CD34-positive capillaries with dissociation from the glomerular basement membrane even in mild lesions. According to computer-assisted morphologic analysis, the cell density did not differ between the diseases. However, in PSAGN, the number of capillary loops was significantly increased, with a larger glomerular capillary luminal area than in the other groups. In addition, the number and frequency of CD163-positive cells (M2 macrophages) tended to be higher in PSAGN, while there were no significant differences in the number of CD68-positive (total) macrophages. These results indicate that in PSAGN, endothelial cell damage is less severe, and angiogenesis may be promoted. The severity of endothelial cell injury in each disease may be associated with differences in infiltrating inflammatory cell phenotypes.Stress can impact perception, especially during use-of-force. Research efforts can thus advance both theory and practice by examining how perception during use-of-force might drive behavior. The current study explored the relationship between perceptual judgments and performance during novel close-combat training. Analyses included perceptual judgments from close-combat assessments conducted pre-training and post-training that required realistic use-of-force decisions in addition to an artificially construed stress-inoculation event used as a training exercise. Participants demonstrated significant reductions in situational awareness while under direct fire, which correlated to increased physiological stress. The initial likelihood of firing upon an unarmed person predicted the perceptual shortcomings of later stress-inoculation training. Subsequently, likelihood of firing upon an unarmed person was reduced following the stress-inoculation training. These preliminary findings have several implications for low or zero-cost solutions that might help trainers identify individuals who are underprepared for field responsibilities.Matrix metalloproteinase13 (MMP13) can be released by keratinocytes and fibroblasts and involved in the pathogenesis of skin disorders. Retinoic acid derivative drugs include tazarotene and acitretin. Tazarotene/acitretin and narrow-band ultraviolet B (NB-UVB) irradiation are common treatment options for psoriasis. However, their impact on MMP13 expression in the context of psoriasis has yet to be determined. The expression of MMP13 was analyzed in patients with psoriasis. The effects of tazarotene/acitretin and NB-UVB on MMP13 expression were also investigated in a mouse model of psoriasis. Human HaCaT keratinocytes were exposed to acitretin or NB-UVB and then assayed for cell proliferation and MMP13 expression levels. We showed that patients with psoriasis had increased levels of MMP13 protein in skin lesions and serum samples. Exposure to acitretin and NB-UVB irradiation alone or in combination led to reduction of cell proliferation and MMP13 expression in HaCaT cells. Consistently, tazarotene treatment or NB-UVB irradiation attenuated imiquimod-induced psoriasis-like dermatitis and decreased MMP13 expression in a mouse model. Based on these from HaCaT keratinocytes cells and animal experiments, we suggest that tazarotene/acitretin and NB-UVB irradiation can inhibit the expression of MMP13 in HaCaT keratinocytes and psoriasis mouse models. Blockade of MMP13 activity may have therapeutic potential in improving symptoms of psoriasis.All medically important unicellular protozoans cannot synthesize purines de novo and they entirely rely on the purine salvage pathway (PSP) for their nucleotide generation. Therefore, purine derivatives have been considered as a promising source of anti-parasitic compounds since they can act as inhibitors of the PSP enzymes or as toxic products upon their activation inside of the cell. Here, we characterized a Trypanosoma brucei enzyme involved in the salvage of adenine, the adenine phosphoribosyl transferase (APRT). We showed that its two isoforms (APRT1 and APRT2) localize partly in the cytosol and partly in the glycosomes of the bloodstream form (BSF) of the parasite. RNAi silencing of both APRT enzymes showed no major effect on the growth of BSF parasites unless grown in artificial medium with adenine as sole purine source. To add into the portfolio of inhibitors for various PSP enzymes, we designed three types of acyclic nucleotide analogs as potential APRT inhibitors. Out of fifteen inhibitors, four compounds inhibited the activity of the recombinant APRT1 with Ki in single µM values. The ANP phosphoramidate membrane-permeable prodrugs showed pronounced anti-trypanosomal activity in a cell-based assay, despite the fact that APRT enzymes are dispensable for T. brucei growth in vitro. While this suggests that the tested ANP prodrugs exert their toxicity by other means in T. brucei, the newly designed inhibitors can be further improved and explored to identify their actual target(s).Cilia are protrusions of the cell surface and composed of hundreds of proteins many of which are evolutionary and functionally well conserved. In cells assembling motile cilia the expression of numerous ciliary components is under the control of the transcription factor FOXJ1. Here, we analyse the evolutionary conserved FOXJ1 target CFAP161 in Xenopus and mouse. In both species Cfap161 expression correlates with the presence of motile cilia and depends on FOXJ1. Tagged CFAP161 localises to the basal bodies of multiciliated cells of the Xenopus larval epidermis, and in mice CFAP161 protein localises to the axoneme. Surprisingly, disruption of the Cfap161 gene in both species did not lead to motile cilia-related phenotypes, which contrasts with the conserved expression in cells carrying motile cilia and high sequence conservation. In mice mutation of Cfap161 stabilised the mutant mRNA making genetic compensation triggered by mRNA decay unlikely. However, genes related to microtubules and cilia, microtubule motor activity and inner dyneins were dysregulated, which might buffer the Cfap161 mutation.Recently, we found many immune cells including antigen presenting cells neurally hard wired in the T-cell zone of most lymphoid organs like amongst others, lymph nodes in rats, mice and humans. Single immune cells were reached by single neurites and enclosed with a dense neural meshwork. As it is well known that axons are always accompanied by glial cells, we were able to identify Schwann cells in the hilum, medullary and capsule region, like expected. Unexpected was the result, that we found oligodendrocyte-like cells in these regions, myelinating more than one axon. Likewise important was the finding, that one of the standard glial markers used, a polyclonal GFAP antibody equally bound to desmin and therefore marked nearly all stromal cells in cortical, paracortical and medullary cord regions. More detailed analysis showed that these results also appeared in many other non-lymphoid organs. Therefore, polyclonal GFAP antibodies are only conditionally usable for immunohistochemical analysis in peripheral tissues outside the central nervous system. It remains to be elucidated, if the binding of the GFAP antibody to desmin has its reason in a special desmin variant that can give stromal cells glial character.Despite the global efforts to mitigate the ongoing COVID-19 pandemic, the disease transmission and the effective controls still remain uncertain as the outcome of the epidemic varies from place to place. In this regard, the province-wise data from Nepal provides a unique opportunity to study the effective control strategies. This is because (a) some provinces of Nepal share an open-border with India, resulting in a significantly high inflow of COVID-19 cases from India; (b) despite the inflow of a considerable number of cases, the local spread was quite controlled until mid-June of 2020, presumably due to control policies implemented; and (c) the relaxation of policies caused a rapid surge of the COVID-19 cases, providing a multi-phasic trend of disease dynamics. In this study, we used this unique data set to explore the inter-provincial disparities of the important indicators, such as epidemic trend, epidemic growth rate, and reproduction numbers. Furthermore, we extended our analysis to identify prevention and control policies that are effective in altering these indicators. Our analysis identified a noticeable inter-province variation in the epidemic trend (3 per day to 104 per day linear increase during third surge period), the median daily growth rate (1 to 4% per day exponential growth), the basic reproduction number (0.71 to 1.21), and the effective reproduction number (maximum values ranging from 1.20 to 2.86). Importantly, results from our modeling show that the type and number of control strategies that are effective in altering the indicators vary among provinces, underscoring the need for province-focused strategies along with the national-level strategy in order to ensure the control of a local spread.Orthorexia Nervosa (ON), a condition characterized by a fixation on healthy eating, still does not conform to any consensus concerning diagnostic criteria, notably in regard to a possible body image component. This study investigated the relationship between ON symptomatology, measured with the Eating Habit Questionnaire, and body image attitudes and body image distortion in a non-clinical sample. Explicit body image attitudes and distortion were measured using the Multidimensional Body-Self Relations Questionnaire. Implicit body image attitudes and distortion were assessed using the reverse correlation technique. Correlational analyses showed that ON is associated with both explicit and implicit attitudes and distortion toward body image. More precisely, multivariate analyses combining various body image components showed that ON is mostly associated with explicit overweight preoccupation, explicit investment in physical health and leading a healthy lifestyle, and implicit muscularity distortion. These findings suggest that ON symptomatology is positively associated with body image attitudes and distortion in a non-clinical sample. However, further studies should be conducted to better understand how ON symptomatology relates to body image, especially among clinical samples.Pregnancy loss directly impairs reproductive performance in dairy cattle. Here, we investigated genetic factors associated with pregnancy loss following detection of a viable embryo around 42 days of gestation. The objectives of this study were to perform whole-genome scans and subsequent gene-set analyses for identifying candidate genes, functional gene-sets and gene signaling pathways implicated in pregnancy loss in US Holstein cows. Data consisted of about 58,000 pregnancy/abortion records distributed over nulliparous, primiparous, and multiparous cows. Threshold models were used to assess the binary response of pregnancy loss. Whole-genome scans identified at least seven genomic regions on BTA2, BTA10, BTA14, BTA16, BTA21, BTA24 and BTA29 associated with pregnancy loss in heifers and lactating cows. These regions harbor several candidate genes that are directly implicated in pregnancy maintenance and fetal growth, such as CHST14, IGF1R, IGF2, PSEN2, SLC2A5 and WNT4. Moreover, the enrichment analysis revealed at least seven significantly enriched processes, containing genes associated with pregnancy loss, including calcium signaling, cell-cell attachment, cellular proliferation, fetal development, immunity, membrane permeability, and steroid metabolism. Additionally, the pathway analysis revealed a number of significant gene signaling pathways that regulate placental development and fetal growth, including Wnt, Hedgehog, Notch, MAPK, Hippo, mTOR and TGFβ pathways. Overall, our findings contribute to a better understanding of the genetic and biological basis of pregnancy loss in dairy cattle and points out novel strategies for improving pregnancy maintenance via marker-assisted breeding.Understanding genotype-by-environment interactions (G × E) is crucial to understand environmental adaptation in mammals and improve the sustainability of agricultural production. Here, we present an extensive study investigating the interaction of genome-wide SNP markers with a vast assortment of environmental variables and searching for SNPs controlling phenotypic variance (vQTL) using a large beef cattle dataset. We showed that G × E contribute 10.1%, 3.8%, and 2.8% of the phenotypic variance of birth weight, weaning weight, and yearling weight, respectively. G × E genome-wide association analysis (GWAA) detected a large number of G × E loci affecting growth traits, which the traditional GWAA did not detect, showing that functional loci may have non-additive genetic effects regardless of differences in genotypic means. Further, variance-heterogeneity GWAA detected loci enriched with G × E effects without requiring prior knowledge of the interacting environmental factors. Functional annotation and pathway analysis of G × E genes revealed biological mechanisms by which cattle respond to changes in their environment, such as neurotransmitter activity, hypoxia-induced processes, keratinization, hormone, thermogenic and immune pathways. We unraveled the relevance and complexity of the genetic basis of G × E underlying growth traits, providing new insights into how different environmental conditions interact with specific genes influencing adaptation and productivity in beef cattle and potentially across mammals.Global climate change is a major threat to reefs by increasing the frequency and severity of coral bleaching events over time, reducing coral cover and diversity. Ocean warming may cause shifts in coral communities by increasing temperatures above coral's upper thermal limits in tropical regions, and by making extratropical regions (marginal reefs) more suitable and potential refugia. We used Bayesian models to project coral occurrence, cover and bleaching probabilities in Southwestern Atlantic and predicted how these probabilities will change under a high-emission scenario (RCP8.5). By overlapping these projections, we categorized areas that combine high probabilities of coral occurrence, cover and bleaching as vulnerability-hotspots. Current coral occurrence and cover probabilities were higher in the tropics (1°S-20°S) but both will decrease and shift to new suitable extratropical reefs (20°S-27°S; tropicalization) with ocean warming. Over 90% of the area present low and mild vulnerability, while the vulnerability-hotspots represent ~ 3% under current and future scenarios, but include the most biodiverse reef complex in South Atlantic (13°S-18°S; Abrolhos Bank). As bleaching probabilities increase with warming, the least vulnerable areas that could act as potential refugia are predicted to reduce by 50%. Predicting potential refugia and highly vulnerable areas can inform conservation actions to face climate change.The popularity and high price of durian make quality control in terms of ripeness very important, which in turn depends heavily on harvesting at an appropriate maturity stage. To date, reports on data-driven methods for maturity prediction are scarce, with many rather focusing on ripeness prediction. Herein, we report the first disclosure of key molecular markers in the liquid extract of durian peduncle that can be a predictive tool for maturity. Multiple chromatographic and spectroscopic techniques including TLC, HPLC, PS-MS, LC-MS/MS, and NMR, were used to characterize chemical profiles of the aqueous extracts from peduncles at different ages. Four compounds that show positive correlations with maturity were identified as sucrose, asparagine, arginine, and pipecolic acid, with asparagine as the most abundant species. This finding paves the way for more research of high impact such as the relationship between biochemical reactions in peduncle and pulp, and the development of accurate and non-destructive sensors for maturity prediction.