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The goal of this study was to assess the anticancer efficacy of chlorojanerin against various cancer cells. The effects of chlorojanerin on cell cytotoxicity, cell cycle arrest, and cell apoptosis were examined using MTT assay, propidium iodide staining, and FITC Annexin V assay. RT-PCR was employed to determine the expression levels of apoptosis-related genes. Furthermore, docking simulations were utilized to further elucidate the binding preferences of chlorojanerin with Bcl-2. According to MTT assay, chlorojanerin inhibited the proliferation of all tested cells in a dose-dependent manner with a promising effect against A549 lung cancer cells with an IC50 of 10 µM. Cell growth inhibition by chlorojanerin was linked with G2/M phase cell cycle arrest in A549 treated cells. Flow cytometry analysis indicated that the proliferation inhibition effect of chlorojanerin was associated with apoptosis induction in A549 cells. Remarkably, chlorojanerin altered the expression of many genes involved in apoptosis initiation. Moreover, we determined that chlorojanerin fit into the active site of Bcl-2 according to the molecular docking study. Collectively, our results demonstrate that chlorojanerin mediated an anticancer effect involving cell cycle arrest and apoptotic cell death and, therefore, could potentially serve as a therapeutic agent in lung cancer treatment.

ABSTRACT INTRODUCTIONKnowledge translation (KT) is a relatively new concept referring to transfers of knowledge into practice in collaboration with multiple sectors that work for the health and wellness of society. Knowledge translation is crucial to identifying and addressing the health needs of immigrants. AIMTo scope the evidence on KT research engaging immigrants in the host country regarding the health and wellness of immigrants. METHODSThis study followed a scoping review approach suggested by Arksey O'Malley. We identified relevant studies from both academic and grey literature using structured criteria, charted the data from the selected studies, collated, summarised and report the results. RESULTSAnalysis of the eligible studies found two types of KT research: integrated KT and end-of-grant KT. Meeting or discussion with community-level knowledge-users were common KT activities among immigrants, but they were involved in the entire research process only if they were hired as members of research teams. Most KT research among immigrants explored cancer screening and used a community-based participatory action research approach. Barriers and enablers usually came from researchers rather than from the community. There was little practice of evaluation and defined frameworks to conduct KT research among immigrants in Canada. CONCLUSIONThis study can help the researchers and other stakeholders of health and wellness of the immigrant population to identify appropriate KT research activities for immigrants and where KT research is required to facilitate the transfer of research knowledge into action.

Background and Aim: Angiotensin-converting enzyme (ACE) is one of the inhibitory enzymes isolated from animals for the treatment of hypertension. ACE inhibitor (ACE-I) peptides can be obtained by hydrolyzing proteins from various animal tissues, including muscle and connective tissues. However, the study on ACE-I activity from collagen of Kacang goat skin has not been conducted. This study explores the potency of collagen from Kacang goat skin as a source of an antihypertensive agent through ACE inhibition. Thermolysin will hydrolyze collagen and produce the peptide classified antihypertensive bioactive peptides. This study aimed to determine the potential of thermolysin to hydrolyze collagen of Kacang goat skin for ACE-I peptide production and to identify the production of ACE-I peptides. Materials and Methods: Collagen from Kacang goat skin was hydrolyzed with thermolysin and incubated at 37°C for 1 h. Molecular weight (MW) evaluation was performed by SDS PAGE; fractionation peptides at 5 kDa was 3.93±0.72 mg/mL, content of 3-5 kDa was 3.81±0.68 mg/mL, and that of

The effects of electronic-cigarette use (vaping), marketed as a healthier alternative to cigarette smoking (CS), on lung function remain equivocal. Therefore, this study assessed and compared the effects of vaping and CS on maximum respiratory pressures (MRP), respiratory function and carboxyhaemoglobin levels. Forty-four young healthy participants were recruited: vapers (n = 12), cigarette smokers (n = 14), and people who had never vaped nor smoked (control) group (n = 18). Spirometry, MRP and carboxyhaemoglobin levels were measured. Both smokers and vapers had a lower Forced expiratory volume in the first second (FEV1), Peak expiratory flow, FEV1/Forced vital capacity (FEV1/FVC), Forced expiratory flow at 25%, 25–75% of FVC, FEF25-75pred% and higher carboxyhaemoglobin% than controls (p

The safety of workers at construction sites is one of the most important aspects that should be considered while performing their required tasks. Many rules and regulations have been implemented in the UAE to reduce injuries and fatalities in the jobsites. However, the number of accidents continues to increase. For instance, an accident category of fall-from-height is considered as the top cause of injuries and fatalities. Thus, this paper develops a novel technique that monitors the workers whether they are complying with a safety standard of the Personal Fall Arrest System (PFAS). This paper establishes a real time detection algorithm based on a Convolutional Neural Network (CNN) model in order to detect two main components of the PFAS that are, safety harness and life-line, in addition to a standard safety measure of using a safety helmet. The YOLOv3 algorithm is adopted for a deep learning network used to train the desired model. The model achieved an accuracy rate of 91.26% and around 99% precision. Moreover, the overall recall of the model was 90.2%. The obtained results verify the effectiveness of our proposed model in construction sites to control potential violations and to avoid unnecessary accidents. The main contribution of this paper is to provide an AI-based image detection framework to mitigate the likelihood of fall-from-height accidents.

Objectives: Staging of pancreatic cancer including vascular staging by use of CT angiography with assessment of presence of direct invasion of surrounding structures or distant metastasis. Patients and Methods: In our study 50 patients with pancreatc cancer were examined with CT angiography to assessresectability and the presence or absence of vascular infiltration of 5 main peri-pancreatc vessels which are celiac artery (CA), superior mesenteric artery (SMA), common hepatic artery (CHA), superior mesenteric vein ( SMV) and portal vein (PV). We assessed five vessels in fifty patientsi.e two hundred and fifty vessels as a whole. Results: Twenty four patients were pre-operatively judged to be resectable or requiring surgical bypass due to jaundice. The remaining 26 patients were judged to be irresectable from the start and referred for chemotherapy or radio-therapy. Conclusion:CT angiography proved to be an important tool in assessing intra abdominal malignancy specially the cancer of the pancreas which in most of cases is missed by abdominal ultrasonography.

Introduction:Pancreatic cancer is one of the worst tumours in prognosis because it is usually already advanced when 1st diagnosed , it is diagnosed late because of difficulty in diagnosis and detection as the pancreas is deeply located in the abdomen and the tumour is ill defined in most cases, when the tumour is located at the head, it obstructs the CBD is most cases causing severe jaundice, so pancreatic head tumours usually presents earlier than tumours at the pancreatic body or tail, early vascular invasion by the tumour also makes the tumourirresectable in most of the cases. In this review article, the roles of imaging with CT in the detection and staging of pancreatic carcinoma will be discussed. The frequently employed techniques using these modality, the common imaging appearances of this tumor, and the limitations of imaging will be addressed.

Extracellular vesicles can carry immunoregulatory cytokines such as TGF-β. Here the authors use CD11b-deficient mice and macrophages to show that such vesicles carrying TGF-β are produced in response to Candida albicans infections and can limit the proinflammatory response partly via a positive feedback on TGF-β production by endothelial cells.

Abstract Introduction Most of the major cities in the developed western countries are characterized by an increasing multiculturalism brought by the immigrant population. The immigrant communities face challenges in the new environment with their health and wellness related unmet needs. It is imperative to find sustainable ways to empower these diverse communities to champion their health and wellness. Community-based health and wellness literacy initiatives (CBHWLI) focusing on immigrant communities can be an important step towards citizen empowerment in this regard. The aim of the present environmental scan is to identify the key factors that might impact a CBHWLI in immigrant communities in Canada in order to facilitate the process in practice and identify the competencies and training required for its implementation. Methods This study will gather information from existing literature and online sources as well as will capture expert and lay perspectives on the factors that can impact the effectiveness and sustainability of CBHWLIs through conducting a comprehensive environmental scan: (i) a systematic scoping review of published literature and grey literature, (ii) a comprehensive Internet search, (iii) key informant interviews, and (iv) community consultation. Specific methodological and analytical frameworks will guide each step. Ethics and dissemination This study is the first step in establishing a practical base for developing CBHWLI implementation research. Once the initial findings have been generated, the second step will involve inviting experts to provide their input. We first plan to disseminate the results of our scoping review and Internet scan through meetings with key stakeholders, to be followed by journal publications and conference or workshop presentations. Ethical approval is not required for the scoping review or Internet scan; however, approval to conduct interviews with key informants and community consultations in the second stage of the study will be sought from the Conjoint Health Research Ethics Board.

Objective This study was conducted to test the efficiency of genomic selection for milk production traits in a Korean Holstein cattle population. Methods A total of 506,481 milk production records from 293,855 animals (2,090 heads with single nucleotide polymorphism information) were used to estimate breeding value by single step best linear unbiased prediction. Results The heritability estimates for milk, fat, and protein yields in the first parity were 0.28, 0.26, and 0.23, respectively. As the parity increased, the heritability decreased for all milk production traits. The estimated generation intervals of sire for the production of bulls (LSB) and that for the production of cows (LSC) were 7.9 and 8.1 years, respectively, and the estimated generation intervals of dams for the production of bulls (LDB) and cows (LDC) were 4.9 and 4.2 years, respectively. In the overall data set, the reliability of genomic estimated breeding value (GEBV) increased by 9% on average over that of estimated breeding value (EBV), and increased by 7% in cows with test records, about 4% in bulls with progeny records, and 13% in heifers without test records. The difference in the reliability between GEBV and EBV was especially significant for the data from young bulls, i.e. 17% on average for milk (39% vs 22%), fat (39% vs 22%), and protein (37% vs 22%) yields, respectively. When selected for the milk yield using GEBV, the genetic gain increased about 7.1% over the gain with the EBV in the cows with test records, and by 2.9% in bulls with progeny records, while the genetic gain increased by about 24.2% in heifers without test records and by 35% in young bulls without progeny records. Conclusion More genetic gains can be expected through the use of GEBV than EBV, and genomic selection was more effective in the selection of young bulls and heifers without test records.

Treatments that target alterations in gut microbiota may be beneficial for patients with irritable bowel syndrome (IBS). A systematic review and meta-analysis was conducted of randomised clinical trials (RCTs) evaluating the efficacy and safety of probiotics, prebiotics and synbiotics. Factors considered in the analysis included global IBS symptoms and/or abdominal pain, secondary symptoms and the frequency of adverse events. A total of 33 RCTs involving 4,321 patients were identified. Overall, probiotics significantly improved global IBS symptoms compared to placebos (standardised mean difference = −0.32, 95% confidence interval: −0.48 to −0.15; P

ABSTRACT INTRODUCTIONUnderstanding primary care access or health service utilisation challenges among immigrant communities is important for tailoring services to community needs, which is the core of precision population health. AIMWe aim to inventory the primary care access barriers faced by immigrant communities through a comprehensive systematic review and develop a conceptual framework to explain the barriers, using a root cause analysis approach. METHODSAcademic databases of primary research articles and grey literature will be searched using appropriate keywords. Relevant information will be extracted into tabular format from finally selected literature. Our proposed approach of framing the barriers to identify the root causes is adapted from the root cause analysis method, which is the process of identifying and understanding the underlying causes to discover the root causes of problems. RESULTSThe study will produce a systematic, quantified and documented list of the barriers faced by immigrants in a solution-oriented approach. DISCUSSIONThe proposed research, as a first step towards determining possible mitigation strategies for health-care access by immigrants, will provide the background needed to devise and test tailored interventions to improve future access to health care for immigrants. We will follow the integrated knowledge translation or community engagement knowledge mobilization approach, where we are engaged with community-based citizen researchers from the inception of our programme. We plan to disseminate the results of our review through meetings with key stakeholders and social media outreach, followed by journal publications and presentations on relevant platforms.

The interaction between Hen Egg White Lysozyme (HEWL) and 3-[(3-cholamidopropyl) dimethyl-ammonio]-1-propanesulphonate (CHAPS) was examined using biophysical techniques (spectrofluorometric, circular dichroism, and dynamic light scattering) at pH 9.0. The results obtained from multi-techniques showed that CHAPS interact with the HEWL strongly and affects protein conformations. The far-UV CD results suggest that lower as well as higher (1.0–15.0 mM) concentrations of CHAPS are inducing α-helical structure in HEWL. The near-UV CD and fluorescence data indicated that the tertiary structure of HEWL is alter in the presence of CHAPS. The ANS dye binding suggest that the exposure of HEWL tertiary structure is dependent on CHAPS concentration. As the concentrations of CHAPS is increasing the exposure of HEWL tertiary structure is also increasing and maximum exposure was found at 15.0 mM of CHAPS concentrations. The hydrodynamic radii of HEWL is also increase in the presence of sub-micellar and micellar concentrations of CHAPS because the tertiary structure of HEWL is disrupted. Overall, the results suggest that CHAPS is inducing secondary structure and disrupting tertiary structure of HEWL. This study provides detailed interaction of CHAPS with HEWL at the molecular level.

BACKGROUND:. Aviptadil, a synthetic form of human vasoactive intestinal peptide, has entered clinical trials to treat critical coronavirus disease 2019 pneumonia with respiratory failure. Vasoactive intestinal peptide protects the lung against a broad array of injuries by binding to the vasoactive intestinal peptide receptor 1 receptor of alveolar type II cells, the cells that severe acute respiratory syndrome coronavirus 2 binds to. As the role of Aviptadil in treating pregnant patients with critical coronavirus disease 2019 pneumonia is unknown, the authors report successful treatment in such a patient who is ineligible for phase 3 trials of Aviptadil. CASE SUMMARY:. Under an open-label Food and Drug Administration-approved Expanded Access Protocol NCT04453839, a 32-year-old female patient Gravida 6 Para 4 at 27-week gestation, body mass index 42.5 kg/m2, admitted to the ICU of a quaternary care hospital with critical coronavirus disease 2019 was treated in January 2021 and followed for 4 months post-ICU admission. Standard of care included remdesivir, methylprednisolone, enoxaparin, and inhaled epoprostenol. In addition, the patient received three successive 12-hour IV infusions of Aviptadil at 50/100/150 pmol/kg/hr escalating doses, per randomized clinical trial NCT04311697. Human subjects’ protection was overseen by the Institutional Review Board of the Houston Methodist Hospital. The patient was enrolled in the treatment and was given informed consent approved by the Food and Drug Administration and the Institutional Review Board. Data on the patient was incorporated based on her consent for de-identified data to be used in research given at the time of hospital admission in a manner approved by the Institutional Review Board (PRO00025607). Baseline inflammatory markers, arterial blood gases, radiologic imaging, oxygen requirements, Pao2/Fio2, continuous fetal monitoring at baseline, throughout the patient’s treatment with the investigational drug, and throughout the patient’s hospital course. CONCLUSION:. The rapid clinical improvement seen in this patient treated with IV vasoactive intestinal peptide is consistent with the theory that vasoactive intestinal peptide protects the alveolar type II cell, ameliorates cytokine storm, and improves oxygenation in acute lung injury. This specific role of vasoactive intestinal peptide in the lung may be vital to combating the lethal effects of severe acute respiratory syndrome coronavirus 2 infection. In addition, the role of vasoactive intestinal peptide in the human maternal-fetal interface suggests that vasoactive intestinal peptide is a safe treatment of severe coronavirus disease 2019 respiratory failure during pregnancy.

Physiotherapy (PT) is a profession that includes education and close contact for long periods of time with patients for treatment sessions. Globally, smoking is prevalent and is expected to increase in the next decades; thus, smoking cessation (SC) is an important management strategy to mitigate further escalation. Little is known about PT practice in SC, and therefore, this study aimed to systematically review and discuss the published literature about the role of physiotherapists in smoking cessation management, opinions, and prevalence of SC counselling in physiotherapy practice; and to explore barriers towards smoking cessation counselling within physiotherapy practice. A systematic search was conducted through EBSCO, and articles were included if they assessed the role of PTs in SC management. The databases were searched for studies published between 1 January 1970 to 1 April 2022. Articles were excluded if they did not include PTs, if they did not include assessment of SC management/counselling, if they were not cross-sectional studies, if they were not written in the English language, or if they were conference abstracts. Seven studies were included in the review. The search identified no studies that have investigated the role of PTs in vaping cessation. It was found that PTs are not addressing SC counselling and management enough in their practice. In addition, the search revealed that lack of training, time, and knowledge are the most common barriers against including SC counselling in physiotherapy practice and rehabilitation programs. Exploring possibilities of including SC counselling according to the clinical guidelines is encouraged. Additionally, establishing solutions to overcome barriers against SC counselling as part of physiotherapy practice is essential.

Pharmacological interventions of diabetic gastroparesis (DG) constitute an essential element of a patient’s management. This article aimed to systematically review the available pharmacological approaches of DG, including their efficacy and safety. A total of 24 randomised clinical trials (RCTs) that investigated the efficacy and/or safety of medications targeting DG symptoms were identified using several online databases. Their results revealed that metoclopramide was the only approved drug for accelerating gastric emptying and improving disease symptoms. However, this medication may have several adverse effects on the cardiovascular and nervous systems, which might be resolved with a new intranasal preparation. Acceptable alternatives are oral domperidone for patients without cardiovascular risk factors or intravenous erythromycin for hospitalised patients. Preliminary data indicated that relamorelin and prucalopride are novel candidates that have proven to be effective and safe. Future RCTs should be conducted based on unified guidelines using universal diagnostic modalities to reveal reliable and comprehensive outcomes. Keywords: Gastroparesis; Diabetes Mellitus; Diabetes Complications; Randomized Controlled Trial; Metoclopramide; Domperidone; Relamorelin.

Sleep can significantly modulate the immune response to infectious agents. In the current study, changes in sleep quality during COVID-19-induced confinement among adults were investigated. This was a cross-sectional survey study of the public using social media. Participants (n = 1846) were recruited in the study, of which >92% reported a variety of confinement procedures such as self-quarantine, physical distancing, banning of public events, school closure, and lockdown. Majority of the participants (53–59%) reported an increase in most of the sleep parameters except a decrease (49.1%) in daytime sleep. Age was associated with changes in sleeping disturbances during COVID-19 confinement (p < 0.001). Young participants were more likely to experience sleeping disturbance than older ones (p < 0.05). In addition, gender (p < 0.001) is an independent predictor of nighttime sleeping. Being a male is associated with a “decrease” and being a female is associated with an “increase” in nighttime sleeping hours (p < 0.05). Moreover, change in daytime sleeping was related to age, gender, and job type (p < 0.05). In conclusion, changes in sleep quality during COVID-19-induced confinement were reported. Intervention programs and strategies are warranted to further improve sleep during the current and future disease-induced confinement.

Pixel-level depth information is crucial to many applications, such as autonomous driving, robotics navigation, 3D scene reconstruction, and augmented reality. However, depth information, which is usually acquired by sensors such as LiDAR, is sparse. Depth completion is a process that predicts missing pixels’ depth information from a set of sparse depth measurements. Most of the ongoing research applies deep neural networks on the entire sparse depth map and camera scene without utilizing any information about the available objects, which results in more complex and resource-demanding networks. In this work, we propose to use image instance segmentation to detect objects of interest with pixel-level locations, along with sparse depth data, to support depth completion. The framework utilizes a two-branch encoder–decoder deep neural network. It fuses information about scene available objects, such as objects’ type and pixel-level location, LiDAR, and RGB camera, to predict dense accurate depth maps. Experimental results on the KITTI dataset showed faster training and improved prediction accuracy. The proposed method reaches a convergence state faster and surpasses the baseline model in all evaluation metrics.

BackgroundVisceral leishmaniasis (VL), caused by the protozoan parasite Leishmania donovani (L. donovani), is the most severe form of leishmaniasis. It is largely responsible for significant morbidity and mortality in tropical and subtropical countries. Currently, available therapeutics have lots of limitations including high-cost, adverse side-effects, painful route of administration, less efficacy, and resistance. Therefore, it is time to search for cheap and effective antileishmanial agents. In the present work, we evaluated the antileishmanial potential of sesamol against promastigotes as well as intracellular amastigotes. Further, we tried to work out its mechanism of antileishmanial action on parasites through different assays.MethodologyIn vitro and ex vivo antileishmanial assays were performed to evaluate the antileishmanial potential of sesamol on L. donovani. Cytotoxicity was determined by MTT assay on human THP-1-derived macrophages. Sesamol-induced morphological and ultrastructural changes were determined by electron microscopy. H2DCFDA staining, JC-1dye staining, and MitoSOX red staining were performed for reactive oxygen assay (ROS), mitochondrial membrane potential, and mitochondrial superoxide, respectively. Annexin V/PI staining for apoptosis, TUNEL assay, and DNA laddering for studying sesamol-induced DNA fragmentation were performed.ConclusionsSesamol inhibited the growth and proliferation of L. donovani promastigotes in a dose-dependent manner. It also reduced the intracellular parasite load without causing significant toxicity on host-macrophages. Overall, it showed antileishmanial effects through induction of ROS, mitochondrial dysfunction, DNA fragmentation, cell cycle arrest, and apoptosis-like cell death to parasites. Our results suggested the possible use of sesamol for the treatment of leishmaniasis after further in vivo validations.

Brittle cornea syndrome (BCS) is a rare recessive condition characterised by extreme thinning of the cornea and sclera. BCS results from loss-of-function mutations in the poorly understood genes ZNF469 or PRDM5. In order to determine the function of ZNF469 and to elucidate pathogenic mechanisms, we used genome editing to recapitulate a human ZNF469 BCS mutation in the orthologous mouse gene Zfp469. Ophthalmic phenotyping showed that homozygous Zfp469 mutation causes significant central and peripheral corneal thinning arising from reduced stromal thickness. Expression of key components of the corneal stroma in primary keratocytes from Zfp469BCS/BCS mice is affected, including decreased Col1a1 and Col1a2 expression. This alters the collagen type I/collagen type V ratio and results in collagen fibrils with smaller diameter and increased fibril density in homozygous mutant corneas, correlating with decreased biomechanical strength in the cornea. Cell-derived matrices generated by primary keratocytes show reduced deposition of collagen type I, offering an in vitro model for stromal dysfunction. Work remains to determine whether modulating ZNF469 activity will have therapeutic benefit in BCS or in conditions such as keratoconus in which the cornea thins progressively. This article has an associated First Person interview with the first author of the paper.

There has been a growing trend of using local anesthesia (LA) compared to general anesthesia (GA) over the last two decades in VR surgery. We aim to answer the following question: what is the institutional benefit of LA versus GA use in operation-room time, anesthesia duration, earlier discharge from an outpatient surgery facility, and the estimated cost savings? We conducted a retrospective analysis of 1476 eyes that underwent vitreoretinal surgery over a 6-year period from a single site; 61.8% of patients received GA and 38.2% received LA for VR surgery. Anesthesia, surgical, and recovery times were significantly shorter with LA (100.49, 66.47, 66.47 mins) vs. GA (145.53, 100.14, 75.08 mins). Anesthesia, surgical, and recovery costs were significantly lower for eyes that received LA, with an estimated adjusted cost reduction of USD 1516 per surgery using LA instead of GA. Use of LA for vitreoretinal surgery is associated with better operational efficiency, earlier patient discharge, and significant cost reduction.

Background: International medical graduates (IMGs) in Canada are individuals who received their medical education and training outside Canada. They undergo a complex licensing procedure in their host country and compete for limited opportunities available to become practicing physicians. Many of them cannot succeed or do not have the resources or interest to undergo this complex and unpredictable career pathway and seek alternative career options. In this study, we aimed to understand how IMGs integrate into the alternative job market, their demographic characteristics, and the types of jobs they undertake after moving to Canada. Methods: An anonymous cross-sectional, online, nationwide, and open survey was conducted among IMGs in Canada. In addition to demographic information, the questionnaire included information on employment status, types of jobs, professional experience, and level of medical education and practice (e.g., specialties, subspecialties, etc.). We conducted a survey of 1740 IMGs in total; however, we excluded responses from those IMGs who are currently working in a clinical setting, thus limiting the number of responses to 1497. Results: Of the respondents, 43.19% were employed and 56.81% were unemployed. Employed participants were more likely to be older males, have stayed longer in Canada, and had more senior-level job experience before moving to Canada. We also observed that the more years that had passed after graduation, the higher the likelihood of being employed. The majority of the IMGs were employed in health-related nonregulated jobs (50.45%). The results were consistent across other demographic characteristics, including different provinces, countries of origin, gender, time since graduation, and length of stay in Canada. Conclusions: This study found that certain groups of IMGs, such as young females, recent immigrants, recent graduates, and less experienced IMGs had a higher likelihood of being unemployed. These findings will inform policymakers, immigrant and professional service organizations, and researchers working for human resources and professional integration of skilled migrants to develop programs and improve policies to facilitate the employment of IMGs through alternative careers.

Objective To report the trends for the use of eye protection methods during retinal laser in clinic and operating room.Methods and analysis Retrospective analysis of a 14-item survey questionnaire submitted to the European Vitreoretinal Society members.Results Responses from 630 members were analysed. Most of the respondents practised in Europe (52.7%), followed by North America (21.0%). The majority of respondents had laser filters in the microscope for the operating surgeon (92.1%), or used protective goggles (6.8%). Only 38.9% of respondents indicated that auxiliary staff in the operative room used protective goggles during laser treatment. Three-dimensional retina viewing system was used by only 22.5% of respondents, of those, 34.5% reported use of laser protection goggles by the operating surgeon. Rates of laser protection by auxiliary staff were 62.9% for indirect laser and 60.8% for slit lamp laser. We found a higher rate for use of laser protection by auxiliary staff in North America-based practices for endolaser (p

Abstract Background Regional National Weather Service (NWS) heat advisory criteria in New York State (NYS) were based on frequency of heat events estimated by sparse monitoring data. These may not accurately reflect temperatures at which specific health risks occur in large geographic regions. The objectives of the study were to use spatially resolved temperature data to characterize health risks related to summertime heat exposure and estimate the temperatures at which excessive risk of heat-related adverse health occurs in NYS. We also evaluated the need to adjust current heat advisory threshold and messaging based on threshold temperatures of multiple health outcomes. Methods We assessed the effect of multi-day lag exposure for maximum near-surface air temperature (Tmax) and maximum Heat Index derived from the gridded National Land Data Assimilation System (NLDAS) reanalysis dataset on emergency department (ED) visits/ hospitalizations for heat stress, dehydration, acute kidney failure (AKF) and cardiovascular diseases (CVD) using a case-crossover analysis during summers of 2008–2012. We assessed effect modification using interaction terms and stratified analysis. Thresholds were estimated using piecewise spline regression. Results We observed an increased risk of heat stress (Risk ratio (RR) = 1.366, 95% confidence interval (CI): 1.347, 1.386) and dehydration (RR = 1.024, 95% CI: 1.021, 1.028) for every 1 °C increase in Tmax on the day of exposure. The highest risk for AKF (RR = 1.017, 95% CI: 1.014, 1.021) and CVD (RR = 1.001, 95% CI: 1.000, 1.002) were at lag 1 and 4 respectively. The increased risk of heat-health effects persists up to 6 days. Rural areas of NYS are at as high a risk of heat-health effects as urban areas. Heat-health risks start increasing at temperatures much lower than the current NWS criteria. Conclusion Reanalysis data provide refined exposure-response functions for health research, in areas with sparse monitor observations. Based on this research, rural areas in NYS had similar risk for health effects of heat. Heat advisories in New York City (NYC) had been reviewed and lowered previously. As such, the current NWS heat advisory threshold was lowered for the upstate region of New York and surrounding areas. Enhanced outreach materials were also developed and disseminated to local health departments and the public.

Abstract Background The incidence of type 1 diabetes mellitus (T1DM) in Kuwait is amongst the highest in the world. Vitamin D is considered to be involved in immune modulation and its deficiency contribute to autoimmune destruction of insulin producing beta cells in T1DM patients. Vitamin D has been shown to exert its effects via a nuclear vitamin D receptor (VDR) and therefore, VDR gene may be considered a candidate for T1DM susceptibility. Methods The genotypes of four VDR gene polymorphisms were determined in 253 Kuwaiti Arab T1DM patients and 214 healthy controls by PCR-RFLP analysis. Serum concentrations of three autoantibodies i.e. ICA (Islet cell autoantibody), GADA (Glutamic acid decarboxylase) and INS (Insulin autoantibody) were determined by radio-immunoassays. Results Statistically significant differences were detected between the genotypes of two VDR gene polymorphisms (FokI, C > T, rs10735810 and TaqI, C > T, rs731236) between T1DM patients and controls (P T, rs7975232) and BsmI (A > G, rs1544410) polymorphisms did not show association with T1DM. The homozygous variant genotypes of FokI, ApaI and TaqI polymorphisms show significant differences between various age-of-onset subgroups while no such association was detected in the case of BsmI polymorphism. Significant differences were also noted between heterozygous genotypes of all four polymorphisms especially between 4-6y and > 6y age-of-onset subgroups of T1DM patients. Three autoantibodies, ICA (Islet cell), GADA (glutamate decarboxylase) and INS (insulin) were positively associated to, varying degrees, with T1DM in Kuwaiti Arabs harboring different VDR gene polymorphism genotypes. Conclusions Our results demonstrate a significant effect of two VDR gene polymorphisms (FokI and TaqI) and three autoantibodies on genetic susceptibility of T1DM in Kuwaiti Arabs along with other factors.

Background/Aim: The thoracic injury and related complications are responsible for upto 25% of blunt trauma mortality. This study is designed to compare these two popular ventilation modes in traumatic flail chest. Materials and Method: A total of 30 patients with thoracic trauma, aged 18–60 years, were enrolled in this study for a period of 1 year. The Thoracic Trauma Severity Score (TTSS) was used for assessing the severity of chest injury. Patients were divided into two treatment groups: one recieved endotracheal intubation with mechanical ventilation (ET group, n = 15) and another recieved noninvasive ventilation (NIV group, n = 15). All patients were observed for the duration of ventilatory days, complications such as pneumonia and sepsis, length of the stay in ICU, and mortality. Statistical analysis was done using statistical software SPSS for windows (Version 16.0). Results: There were no significant differences in age, sex, weight, and length of the stay in ICU in between the two groups. Rate of complications was significantly higher in ET group. Oxygenation was significantly improved in NIV group within 24 hr, later it become equivalent to the ET group patients while the pCO2level was significantly lower in ET group compared with NIV group. Analgesia in both the groups is maintained to keep the visual analog scale (VAS) score below 2 and was comparable in both the groups. Conclusions: The endotracheal intubation is also associated with serious complications as compared to NIV. The use of NIV in appropriate patients decreases complications, mortality, length of the stay in ICU, the use of resources, and cost.

Background: Prostate hyperplasia and neoplasia are major illness of men and elderly dogs. Treatment of prostate cancer requires androgen deprivation surgery or therapy to prevent metastases and alleviate pain. Recently, six DNA vaccines have entered clinical trials against prostate cancer in humans with limited success. There is a need for new therapies that delay the establishment of malignancy and prolong survival. Materials and methods: A plasmid DNA vaccine coding for eight gonadotrophin-releasing hormone (GnRH-I) interspersed in eight T-helper epitopes was used. Sexually mature male mice were immunized with the vaccine in hemagglutinating virus of Japanese envelope vector and boosted in nonionized surfactant vesicles in study weeks 0, 3, 6, 9, and 12. Plasma anti-GnRH-I antibody response, serum testosterone concentration, and effect on prostate were evaluated. Results: Results of an indirect enzyme linked immunosorbent assay (ELISA) showed anti-GnRH-I antibody response (OD value) detected in the study week 3 (0.613 ± 0.179) with a highest response in the week 12 (1.205 ± 0.219). Serum testosterone concentration (ng/ml) in vaccinated mice was significantly reduced (P > 0.000, 0.761 ± 0.531) in the study week 24 in contrast to control serum (7.583 ± 1.251). Group average gross combined weight of prostate and seminal vesicles of vaccinated mice was significantly (P

In this paper, step-stress accelerated life test is considered to obtain the failure time data of highly reliable units in specified conditions. It is assumed that the lifetime data of such units follow Lomax distribution with a scale parameter depends on the stress level and the shape parameter remains constant. It is also assumed that failure times occur according to a cumulative exposure model (CEM). Using this model, the maximum likelihood estimators (MLEs) and the respective confidence intervals (CIs) based on the asymptotic normality theory as well as the ones based on parametric bootstrap method are considered. In the context of prediction, point and interval predictions are also addressed. A simulation study has been performed to assess the estimation and prediction methods and a real dataset is analyzed for illustrative purposes.

Recent evidence has revealed that exposing cells to exogenous H 2 S or inhibiting cellular H 2 S synthesis can modulate cell cycle checkpoints, DNA damage and repair, and the expression of proteins involved in the maintenance of genomic stability, all suggesting that H 2 S plays an important role in the DNA damage response (DDR). Here we review the role of H 2 S in the DRR and maintenance of genomic stability. Treatment of various cell types with pharmacologic H 2 S donors or cellular H 2 S synthesis inhibitors modulate the G 1 checkpoint, inhibition of DNA synthesis, and cause p21, and p53 induction. Moreover, in some cell models H 2 S exposure induces PARP-1 and g-H2AX foci formation, increases PCNA, CHK2, Ku70, Ku80, and DNA polymerase-d protein expression, and maintains mitochondrial genomic stability. Our group has also revealed that H 2 S bioavailability and the ATR kinase regulate each other with ATR inhibition lowering cellular H 2 S concentrations, whereas intracellular H 2 S concentrations regulate ATR kinase activity via ATR serine 435 phosphorylation. In summary, these findings have many implications for the DDR, for cancer chemotherapy, and fundamental biochemical metabolic pathways involving H 2 S.

In this paper, we propose a new class of distributions by compounding Lindley distributed random variates with the number of variates being zero-truncated Poisson distribution. This model is called a compound zero-truncated Poisson–Lindley distribution with two parameters. Different statistical properties of the proposed model are discussed. We describe different methods of estimation for the unknown parameters involved in the model. These methods include maximum likelihood, least squares, weighted least squares, Cramer–von Mises, maximum product of spacings, Anderson–Darling and right-tail Anderson–Darling methods. Numerical simulation experiments are conducted to assess the performance of the so obtained estimators developed from these methods. Finally, the potentiality of the model is studied using one real data set representing the monthly highest snowfall during February 2018, for a subset of stations in the Global Historical Climatological Network of USA.

Background: Idiopathic Nephrotic syndrome (INS) is an immune-mediated disease in which a number of cytokines, including IL-4 and IL-13, have been implicated in the pathogenesis. Cytokine gene polymorphisms might affect their levels and activity. Therefore, may affect INS susceptibility and response to treatment. The aim of the study was to determine the association of IL-4 and IL-13 gene polymorphisms and INS susceptibility and their effects on steroid responsiveness in children.Methods: The polymorphisms in IL-4 and IL-13 genes were detected by PCR-RFLP in 155 INS patients and 64 controls.Results: A total of 132 steroid-sensitive (SS) and 23 steroid resistance (SR) INS patients; mean age 7.3 ± 4.0 years, were included. Male: Female ratio was 2:1. No significant statistical differences were detected in the frequency of CC, CT, and TT genotypes of IL-4 gene compared to controls (P = 0.57, 0.61, and 1.00, respectively). There was no significant difference in the T and C-allele frequencies, in SS and SR subgroups. Analysis of IL-13 gene polymorphism also did not show significant statistical differences in the frequency of QQ, RQ, and RR genotypes compared to controls (P = 0.74, 1.00, and 0.68, respectively). No significant difference was found in the Q and R-allele frequency. However, the heterozygous RQ genotype of the IL13 gene was significantly higher in SS INS patients compared to the SR INS cases (P = 0.04).Conclusion: Our findings did not show an association between IL-4 and IL-13 gene polymorphisms and INS susceptibility. However, IL-13 RQ genotype was expressed more in children with INS who are steroid sensitive.

Enid Lake is one of the largest reservoirs located in Yazoo River Basin, the largest basin in the state of Mississippi. The lake was impounded by Enid Dam on the Yocona River in Yalobusha County and covers an area of 30 square kilometers. It provides significant natural and recreational resources. The soils in this region are highly erodible, resulting in a large amount of fine-grained cohesive sediment discharged into the lake. In this study, a 3D numerical model was developed to simulate the free surface hydrodynamics and transportation of cohesive sediment with a median diameter of 0.0025 to 0.003 mm in Enid Lake. Flow fields in the lake are generally induced by wind and upstream river inflow, and the sediment is also introduced from the inflow during storm events. The general processes of sediment flocculation and settling were considered in the model, and the erosion rate and deposition rate of cohesive sediment were calculated. In this model, the sediment simulation was coupled with flow simulation. In this research, remote sensing technology was applied to estimate the sediment concentration at the lake surface and provide validation data for numerical model simulation. The model results and remote sensing data help us to understand the transport, deposition and resuspension processes of cohesive sediment in large reservoirs due to wind-induced currents and upstream river flows.

Many quinazoline derivatives with pharmacological properties, such as anticancer activity, have been synthesized. Fourteen quinazoline derivatives bearing a substituted sulfonamide moiety (4a–n) were previously synthesized and fully characterized. These compounds exerted antiproliferative activity against cell lines derived from solid tumors. Herein, the antileukemic activities of these compounds (4a–n) against two different leukemia cell lines (Jurkat acute T cell and THP-1 acute monocytic) were investigated. Our investigation included examining their activity in vivo in a zebrafish embryo model. Remarkably, compounds 4a and 4d were the most potent in suppressing cell proliferation, with an IC50 value range of 4–6.5 µM. Flow cytometry analysis indicated that both compounds halted cell progression at the G2/M phase and induced apoptosis in a dose-dependent manner. RT-PCR and Western blot analyses also showed that both compounds effectively induced apoptosis by upregulating the expression of proapoptotic factors while downregulating that of antiapoptotic factors. In vivo animal toxicity assays performed in zebrafish embryos indicated that compound 4d was more toxic than compound 4a, with compound 4d inducing multiple levels of teratogenic phenotypes in zebrafish embryos at a sublethal concentration. Moreover, both compounds perturbed the hematopoiesis process in developing zebrafish embryos. Collectively, our data suggest that compounds 4a and 4d have the potential to be used as antileukemic agents.

Euphorbia cactus Ehrenb ex Boiss. is a plant species reported from central Africa and the southern Arabian Peninsula, belonging to the family of Euphorbiaceae. The plant has ethnobotanical values and is well-known for its milky latex, which has been turned into medicine to treat various ailments. To the best of our knowledge, there have been no literature reports available on phytochemical constituents and antiproliferative mechanism of E. cactus. In the current study, the phytochemical investigation of E. cactus methanolic extract (ECME) resulted in the isolation and characterization of four secondary metabolites, which are reported for the first time from this plant species. In addition, the results of 1,1-diphenyl-2-picrylhydrazyl (DPPH•) and ferrous ion chelating (FIC) assays expressed maximum antioxidant activity by ECME and the isolated phytochemicals. Furthermore, ECME exerted a promising antiproliferative effect against different cancer cell lines, and the A549 lung cancer cells were the most sensitive with an IC50 value of 20 µg/mL. The antiproliferative action of ECME in A549 cells was associated with cell accumulation in the G2/M phase and an increase in early and late apoptosis. In addition, RT-PCR and western blot analysis revealed that ECME decreased the anti-apoptotic (Bcl-2) expression, while the expression of pro-apoptotic (Bax) and caspase-3 were increased. This study provides the first insight into the phytochemical constituents and the antiproliferative mechanism of ECME, implying that it could be exploited as a promising natural source for developing new cancer therapies. Further preclinical research is warranted to support the current results.

In order to investigate for a new effective and safe anticancer drug, we synthesized a novel series of quinazoline containing biologically active substituted-sulfonamide moiety at 3- position 4a–n. The structure of the newly prepared compounds was proved by microanalysis, IR, 1H-NMR, 13C-NMR and mass spectral data. All the synthesized compounds were evaluated for their in vitro cytotoxic activity in numerous cancer cell lines including A549, HepG-2, LoVo and MCF-7 and normal HUVEC cell line. The two most active compounds 4d and 4f were then tested for their apoptosis induction using DNA content and Annexin V-FITC/PI staining. Moreover, apoptosis initiation was also confirmed using RT-PCR and Western blot. To further understand the binding preferences of quinazoline sulfonamides, docking simulations were used. Among the fourteen new synthesized compounds, we found that compounds 4d and 4f exerted the strongest cytotoxicity against MCF-7 cells with an IC50 value of 2.5 and 5 μM, respectively. Flow cytometry data revealed the ability of compounds 4d and 4f to mediate apoptosis and arrest cell cycle growth at G1 phase. Furthermore, RT-PCR and Western blot results suggested that both 4d and 4f activates apoptotic cell death pathway in MCF-7 cells. Molecular docking assessments indicated that compounds 4d and 4f fit perfectly into Bcl2’s active site. Based on the biological properties, we conclude that both compounds 4d and 4f could be used as a new type of anticancer agent, which provides a scientific basis for further research into the treatment of cancer.

Severe novel corona virus disease 2019 (COVID-19) infection is associated with a considerable activation of coagulation pathways, endothelial damage, and subsequent thrombotic microvascular injuries. These consistent observations may have serious implications for the treatment and management of this highly pathogenic disease. As a consequence, the anticoagulant therapeutic strategies, such as low molecular weight heparin, have shown some encouraging results. Cytokine burst leading to sepsis which is one of the primary reasons for acute respiratory distress syndrome (ARDS) drive that could be worsened with the accumulation of coagulation factors in the lungs of COVID-19 patients. However, the obscurity of this syndrome remains a hurdle in making decisive treatment choices. Therefore, an attempt to characterize shared biological mechanisms between ARDS and thrombosis using comprehensive transcriptomics meta-analysis is made. We conducted an integrated gene expression meta-analysis of two independently publicly available datasets of ARDS and venous thromboembolism (VTE). Datasets GSE76293 and GSE19151 derived from National Centre for Biotechnology Information–Gene Expression Omnibus (NCBI-GEO) database were used for ARDS and VTE, respectively. Integrative meta-analysis of expression data (INMEX) tool preprocessed the datasets and effect size combination with random effect modeling was used for obtaining differentially expressed genes (DEGs). Network construction was done for hub genes and pathway enrichment analysis. Our meta-analysis identified a total of 1,878 significant DEGs among the datasets, which when subjected to enrichment analysis suggested inflammation–coagulation–hypoxemia convolutions in COVID-19 pathogenesis. The top hub genes of our study such as tumor protein 53 (TP53), lysine acetyltransferase 2B (KAT2B), DExH-box helicase 9 (DHX9), REL-associated protein (RELA), RING-box protein 1 (RBX1), and proteasome 20S subunit beta 2 (PSMB2) gave insights into the genes known to be participating in the host–virus interactions that could pave the way to understand the various strategies deployed by the virus to improve its replication and spreading.

Background: Sonic hedgehog (Shh) and Nrf2 play a critical role in chemotherapeutic resistance. These two genes have been found to be dysregulated in head and neck squamous cell carcinomas (HNSCC). The purpose of this study was to analyze the expression, function and clinical prognostic relationship of Shh and Nrf2 in HNSCC in the context of therapeutic resistance and cancer stem cells (CSCs). Methods: We analyzed a cohort of patients with HNSCC to identify potential therapeutic biomarkers correlating with overall survival (OS) as well as disease-free survival (DFS) from our own data and validated these results using The Cancer Genome Atlas dataset. Expression of Shh and Nrf2 was knocked down by siRNA and cell growth, sphere growth and chemotherapeutic resistance were evaluated. Results: Widespread abundant expression of Shh and Nrf2 proteins were associated with shorter OS and DFS. The combination of Shh and Nrf2 expression levels was found to be a significant predictor of patient DFS. The tumor stromal index was correlated with Shh expression and inversely associated with shorter OS and DFS. Inhibition of Shh by siRNA or cyclopamine resulted in the attenuation of resistant CSC self-renewal, invasion, clonogenic growth and re-sensitization to the chemotherapeutic agents. Concomitant upregulation of Shh and Nrf2 proved to be an independent predictor of poor OS and DFS in patients with HNSCC. Conclusions: These findings suggest that Shh and Nrf2 could serve as therapeutic targets as well as promising dual prognostic therapeutic biomarkers for HNSCC.

Protozoan parasites of the Leishmania donovani complex – L. donovani and L. infantum – cause the fatal disease visceral leishmaniasis. We present the first comprehensive genome-wide global study, with 151 cultured field isolates representing most of the geographical distribution. L. donovani isolates separated into five groups that largely coincide with geographical origin but vary greatly in diversity. In contrast, the majority of L. infantum samples fell into one globally-distributed group with little diversity. This picture is complicated by several hybrid lineages. Identified genetic groups vary in heterozygosity and levels of linkage, suggesting different recombination histories. We characterise chromosome-specific patterns of aneuploidy and identified extensive structural variation, including known and suspected drug resistance loci. This study reveals greater genetic diversity than suggested by geographically-focused studies, provides a resource of genomic variation for future work and sets the scene for a new understanding of the evolution and genetics of the Leishmania donovani complex.

Background: Congenital kyphosis results from the failed formation of the vertebrae during the embryonic period and may be associated with cardiac, urogenital, or spinal cord anomalies. Surgical treatment is the best choice through anterior, posterior, or both approaches. Objectives: This study aims to evaluate the effect of posterior gradual correction using the “in situ” bender to correct severe thoracolumbar congenital kyphosis with or without osteotomy or excision of the vertebra. Methods: Twenty-five patients with an age range of 2–23 (mean ± SD = 12.58 ± 6.03) years with severe thoracolumbar kyphosis were treated surgically at our institution between 2004 and 2013. Pedicle screwing, osteotomy, and gradual “in situ” bending through the single posterior approach were the choices of treatment. Cobb’s angle, patient’s height, and SRS-22r were used to evaluate the patients preoperatively and postoperatively. Follow-up periods were 35–136 months. Result: Cobb’s angle pre-surgery range was 35–180 (81.48 ± 39.1) degrees improved post-surgery to 0–45 (21.72 ± 13.47) degrees ( p -value

We have developed and applied a relatively simple disaggregation scheme that uses spatial patterns of Land Surface Temperature (LST) from MODIS warm-season composites to improve the spatial characterization of daily maximum and minimum air temperatures. This down-scaling model produces qualitatively reasonable 1 km daily maximum and minimum air temperature estimates that reflect urban and coastal features. In a 5-city validation, the model was shown to provide improved daily maximum air temperature estimates in the three coastal cities, compared to 12 km NLDAS-2 (North American Land Data Assimilation System). Down-scaled maximum temperature estimates for the other two (non-coastal) cities were marginally worse than the original NLDAS-2 temperatures. For daily minimum temperatures, the scheme produces spatial fields that qualitatively capture geographic features, but quantitative validation shows the down-scaling model performance to be very similar to the original NLDAS-2 minimum temperatures. Thus, we limit the discussion in this paper to daily maximum temperatures. Overall, errors in the down-scaled maximum air temperatures are comparable to errors in down-scaled LST obtained in previous studies. The advantage of this approach is that it produces estimates of daily maximum air temperatures, which is more relevant than LST in applications such as public health. The resulting 1 km daily maximum air temperatures have great potential utility for applications such as public health, energy demand, and surface energy balance analyses. The method may not perform as well in conditions of strong temperature advection. Application of the model also may be problematic in areas having extreme changes in elevation.

Bilateral spontaneous hyphemas are a rare ophthalmic event. Aplastic anemia is a hematologic condition with well-documented manifestations in the posterior segment but not the anterior segment. We present a patient with aplastic anemia without obvious risk factors for hyphema who developed bilateral spontaneous hyphemas. To our knowledge, this is the first reported case of bilateral spontaneous hyphemas in a patient with aplastic anemia.

Behavioral interventions utilizing community health workers (CHWs) have demonstrated effectiveness in improving hypertension disparities in ethnic minority populations in the United States, but few have focused on Asian Americans. We assessed the efficacy of a CHW intervention to improve hypertension management among Filipino Americans with uncontrolled blood pressure (BP) in New York City (NYC) from 2011 to 2013. A total of 240 Filipino American individuals (112 in the treatment group and 128 in the control group) with uncontrolled hypertension (SBP ≥ 140 mmHg and/or DBP ≥ 90 mmHg) were recruited from community-based settings in NYC. Using a community-based participatory research approach, treatment participants received 4 educational workshops and 4 one-on-one visits with CHWs over a 4-month period, while control group participants received 1 educational workshop. Main outcome measures included BP control, changes in SBP and DBP, and changes in appointment keeping at 8-months. At 8-months, BP was controlled among a significantly greater percentage of treatment group participants (83.3%) compared to the control group (42.7%). The adjusted odds of controlled BP for the treatment group was 3.2 times the odds of the control group (P

Tailed bacteriophages (phages) are one of the most abundant life forms on Earth. They encode highly efficient molecular machines to infect bacteria, but the initial interactions between a phage and a bacterium that then lead to irreversible virus attachment and infection are poorly understood. This information is critically needed to engineer machines with novel host specificities in order to combat antibiotic resistance, a major threat to global health today. The tailed phage T4 encodes a specialized device for this purpose, the long tail fiber (LTF), which allows the virus to move on the bacterial surface and find a suitable site for infection. Consequently, the infection efficiency of phage T4 is one of the highest, reaching the theoretical value of 1. Although the atomic structure of the tip of the LTF has been determined, its functional architecture and how interactions with two structurally very different Escherichia coli receptor molecules, lipopolysaccharide (LPS) and outer membrane protein C (OmpC), contribute to virus movement remained unknown. Here, by developing direct receptor binding assays, extensive mutational and biochemical analyses, and structural modeling, we discovered that the ball-shaped tip of the LTF, a trimer of gene product 37, consists of three sets of symmetrically alternating binding sites for LPS and/or OmpC. Our studies implicate reversible and dynamic interactions between these sites and the receptors. We speculate that the LTF might function as a "molecular pivot" allowing the virus to "walk" on the bacterium by adjusting the angle or position of interaction of the six LTFs attached to the six-fold symmetric baseplate.

Abstract Background Systemic lupus erythematosus (SLE) is an autoimmune inflammatory disease which involves the loss of self-tolerance with hyperactivation of autoreactive T- and B-cells. Protein tyrosine phosphatase non-receptor type 22 (PTPN22) encodes for lymphoid specific phosphatase (LYP) which is a key negative regulator of T lymphocyte activation. The aim of this study was to investigate the association between PTPN22 gene functional variant R620W and systemic lupus erythematosus (SLE) by comparing its prevalence in Kuwaiti SLE patients and controls. Methods The study included 134 SLE patients and 214 controls from Kuwait. The genotypes of PTPN22 gene functional variant R620W were determined by PCR-RFLP and confirmed by DNA sequence analysis in both SLE patients and the controls. Results A relatively high prevalence of the variant 620 W (T-allele) of the PTPN22 gene was detected in the SLE patients from Kuwait. 35.7% of the SLE patients had at least one variant allele (T-allele) compared to 15.9% in the controls. A statistically significant difference was detected in the frequency of variant genotypes, TT and CT between SLE patients and the controls (p

Janerin is a cytotoxic sesquiterpene lactone that has been isolated and characterized from different species of the Centaurea genus. In this study, janerin was isolated form Centaurothamnus maximus, and its cytotoxic molecular mechanism was studied in THP-1 human leukemic cells. Janerin inhibited the proliferation of THP-1 cells in a dose-dependent manner. Janerin caused the cell cycle arrest at the G2/M phase by decreasing the CDK1/Cyclin-B complex. Subsequently, we found that janerin promoted THP-1 cell death through apoptosis as indicated by flow cytometry. Moreover, apoptosis induction was confirmed by the upregulation of Bax, cleaved PARP-1, and cleaved caspase 3 and the downregulation of an anti-apoptotic Bcl-2 biomarker. In addition, immunoblotting indicated a dose dependent upregulation of P38-MAPK and ERK1/2 phosphorylation during janerin treatment. In conclusion, we have demonstrated for the first time that janerin may be capable of inducing cell cycle arrest and apoptosis through the MAPK pathway, which would be one of the mechanisms underlying its anticancer activity. As a result, janerin has the potential to be used as a therapeutic agent for leukemia.

Endophthalmitis is a serious ophthalmologic condition involving purulent inflammation of the intraocular spaces. The underlying etiology of infectious endophthalmitis is typically bacterial or fungal. The mechanism of entry into the eye is either exogenous, involving seeding of an infectious source from outside the eye (e.g., trauma or surgical complications), or endogenous, involving transit of an infectious source to the eye via the bloodstream. The most common organism for fungal endophthalmitis is Candida albicans. The most common clinical manifestation of fungal endophthalmitis is vision loss, but other signs of inflammation and infection are frequently present. Fungal endophthalmitis is a clinical diagnosis, which can be supported by vitreous, aqueous, or blood cultures. Treatment involves systemic and intravitreal antifungal medications as well as possible pars plana vitrectomy. In this review, we examine these essential elements of understanding fungal endophthalmitis as a clinically relevant entity, which threatens patients’ vision.

There is a well-documented association between ambient fine particulate matter air pollution (PM2.5) and cardiovascular disease (CVD) morbidity and mortality. Exposure to PM2.5 can cause premature death and harmful and chronic health effects such as heart attack, diabetes, and stroke. The Environmental Protection Agency sets annual PM2.5 standards to reduce these negative health effects. Currently above an annual average level of 12.0 µg/m is considered unhealthy. Methods. We examined the association of long-term exposure to PM2.5 and CVD in a cohort of 44,610 individuals who resided in 12 states recruited into the Southern Community Cohort Study (SCCS). The SCCS was designed to recruit Black and White participants who received care from Federally Qualified Health Centers; hence, they represent vulnerable individuals from low-income families across this vast region. This study tests whether SCCS participants who lived in locations exposed to elevated ambient levels of PM2.5 concentrations were more likely to report a history of CVD at enrollment (2002–2009). Remotely sensed satellite data integrated with ground monitoring data provide an assessment of the average annual PM2.5 in urban and rural locations where the SCCS participants resided. We used multilevel logistic regression to estimate the associations between self-reported CVD and exposure to elevated ambient levels of PM2.5. Results. We found a 13.4 percent increase in the odds of reported CVD with exposure to unhealthy levels of PM2.5 exposure at enrollment. The SCCS participants with medical histories of hypertension, hypercholesterolemia, and smoking had, overall, 385 percent higher odds of reported CVD than those without these clinical risk factors. Additionally, Black participants were more likely to live in locations with higher ambient PM2.5 concentrations and report high levels of clinical risk factors, thus, they may be at a greater future risk of CVD. Conclusions: In the SCCS participants, we found a strong relation between exposures to high ambient levels of PM2.5 and self-reported CVD at enrollment.

Since the beginning of 2020, the world has been in a race to develop vaccines that can control the COVID-19 pandemic. More than 250 projects have been initiated for this purpose, but only 14 of them have been authorized for use, despite being in phase 3 clinical trials. More than 40 other vaccines are also in phase 1/2 clinical trials and show promising outcomes. Regarding the appropriate choice of vaccines for each country or region, we reviewed the currently used vaccines in light of the different influencing parameters. These factors include the mode of action, dosage protocol, age group of the vaccinee, side effects, storage conditions, mounted immune response, and cost. Technically, there are seven types of vaccines developed against SARS-CoV-2: messenger RNA (mRNA), nonreplicating and replicating vectors, inactivated viruses, protein subunits, viral-like particles, DNA vaccines, and live attenuated vaccines. The mRNA type is being used for the first time in humans. Unfortunately, mutated variants of SARS-CoV-2 have started to appear worldwide, and researchers are investigating the effects of the currently used vaccines on them. There are many concerns regarding the long-term protection afforded by these vaccines and their side effects, and whether they require future modifications to be effective against the mutated variants. The development of new vaccines using more advanced technology is paramount for overcoming the difficulties in controlling the COVID-19 pandemic across the world.