Antiviral Approaches against Influenza Virus.

Preventing and controlling influenza virus infection remains a global public health challenge, as it causes seasonal epidemics to unexpected pandemics. These infections are responsible for high morbidity, mortality, and substantial economic impact. Vaccines are the prophylaxis mainstay in the fight against influenza. However, vaccination fails to confer complete protection due to inadequate vaccination coverages, vaccine shortages, and mismatches with circulating strains. Antivirals represent an important prophylactic and therapeutic measure to reduce influenza-associated morbidity and mortality, particularly in high-risk populations. Here, we review current FDA-approved influenza antivirals with their mechanisms of action, and different viral- and host-directed influenza antiviral approaches, including immunomodulatory interventions in clinical development. Furthermore, we also illustrate the potential utility of machine learning in developing next-generation antivirals against influenza.

mHealth based intervention by social care professionals to support family caregivers to persons with dementia living at home in Sweden (Caregiver Connect): a randomized controlled trial.

BACKGROUND: The majority of persons with dementia in Sweden reside in their own homes with support from family members. Approximately, 12% of persons with dementia have immigrant background. Within the next 20 years, the number of persons with dementia who are non-ethnic Swedes is said to double. Family caregivers with immigrant backgrounds are noted to receive less support in the community than ethnic Swedes and rate their health status lower than ethnic Swedish peers. The Swedish National Board of Health and Welfare have highlighted the importance of follow-up support for family caregivers with immigrant backgrounds as there is a recognized gap in research and available information tailored to meet the needs of this group. PURPOSE OF THE STUDY: The purpose of the study is to test effectiveness of an mHealth based intervention through which community social workers can improve caregiving competence of non-European immigrant family caregivers of people with dementia living at home in Sweden. The overarching aim is to reduce caregiver burden and depressive symptoms, and improve quality of life. METHODS: A randomized controlled trial (RCT) including wait list control group will be performed consisting of an intervention group (A, n = 44) and a wait list control group (B, n = 44), totaling a sample size of 88. On completion of the 10-weeks long intervention in the intervention group, the intervention will be delivered to group B. Effect of the intervention will be analyzed between and within groups over time. The content of the educational component of the intervention is inspired by the iSupport manual developed by the World Health Organization. The contents, in the form of a booklet, aims to equip the family caregivers with structured information on understanding dementia as a condition and its management at home, including self-care guidance designed specifically for family caregivers themselves. DISCUSSION: Similar telephone-delivered intervention studies targeted for family caregivers to persons with dementia are ongoing in Malaysia and will start in India using the same booklet adapted to the local context. These studies will provide evidence on the effectiveness of using digital technologies to deliver support to those who may not be reached or adequately served by the traditional healthcare system. TRIAL REGISTRATION: ISRCTN registry, Registration number ISRCTN64235563.

Musculoskeletal disorders among doctors and nursing officers : an occupational hazard of overstrained healthcare delivery system in western Rajasthan, India.

BACKGROUND: The present study was conducted to estimate the prevalence and distribution of MSDs in different anatomical regions among Doctors and NO and to determine their ergonomic risk factors and predictors. METHODS: This cross-sectional study was conducted in an apex institution in Western India. The socio-demographic information, medical and occupational history, and other personal and work-related attributes were captured using a semi-structured questionnaire, which was developed and finalized by piloting on 32 participants (who were not part of the study). Nordic Musculoskeletal and International Physical Activity Questionnaires were used to assess MSDs and Physical activity. Data were analyzed using SPSS v.23. Prevalence of Musculoskeletal Symptoms (M.S.), Multisite Musculoskeletal Symptoms (MMS), and Widespread Musculoskeletal Symptoms (WMS) were calculated. A comparison was made to estimate the burden and distribution of MSD among Doctors and Nursing officers. Logistic regression was applied to identify the predictors of MSDs and pinpoint the risk factors associated with MSDs. RESULTS: A total of 310 participants, of which 38.7% were doctors, and 61.3% were Nursing Officers (NOs) were included in the study. The mean age of the respondents was 31.63 ± 4.9 years. Almost 73% (95%CI: 67.9-78.1) of participants had MSD in the last 12 months, with approximately 41.6% (95%CI: 36.1-47.3) suffering from MSDs in the previous seven days of the survey. The lower back (49.7%) and the neck (36.5%) were the most affected sites. Working in the same position for a long time (43.5%) and not taking adequate breaks (31.3%) were the highest self-reported risk factors. Females had significantly higher odds of having pain in the upper back [aOR:2.49(1.27-4.85)], neck [aOR:2.15(1.22-3.77)], shoulder [aOR:2.8 (1.54-5.11)], hips [aOR:9.46 (3.95-22.68)] and knee [aOR:3.8(1.99-7.26)]. CONCLUSIONS: Females, who are NOs, work for > 48 h per week, and fall in the obese category were significantly at more risk of developing MSDs. Working in an awkward position, treating an excessive number of patients in a day, working in the same position for a long period, performing repeated tasks, and not having enough rest breaks were significant risk factors for MSDs.

An Unusual Case of Telangiectasias.

BACKGROUND: Telengiectasias are defined as persistent dilatation of small capillaries in the superficial dermis Case : A 26-year-old woman presented with red lesions, epistaxis, joint pains, color changes of the hands, and breathlessness. On clinical examination and investigations, a final diagnosis of mixed connective tissue disease (MCTD), with interstitial lung disease (ILD), with telangiectasias, and epistaxis was made. Telangiectasias and epistaxis are rare presentations of MCTD.

Can urodynamic diagnosis of dysfunctional voiding/external sphincter nonrelaxation be made on two-channel pressure-flow study without video-urodynamics, electromyography, or urethral pressure profilometry? Plateau detrusor pattern in perspective.

AIMS: urodynamic diagnosis of dysfunctional voiding/external-sphincter nonrelaxation (DV/EUSD) needs assistance of specialized testing namely urethral pressure profilometry (UPP), electromyography (EMG), and/or videofluoroscopy (VUDS). We aimed to find a predictive model based on standard pressure-flow study without need for specialized testing. MATERIAL AND METHODS: In this retrospective study (2017-2021), clinical and urodynamic data of adult men and women presenting with voiding dysfunction was collected. Mandatory inclusion criteria were availability of all-(1) findings of clinical examination and neurological status, (2) a valid filling cystometry and pressure-flow study (with active detrusor contraction), (3) a final clinic-urodynamic diagnosis. Voiding cystourethrography (VCUG) was performed to confirm the location of obstruction. RESULTS: Data of 218 participants (178♂, 40♀) was eligible. Plateau detrusor contraction pattern was observed in 89.0% of men and 86% of women with DV/EUSD; whereas only 7.5% men and no women with other obstructions demonstrated this pattern. Forward likelihood Logistic regression analysis revealed presence of plateau pattern, lower bladder outlet obstruction index (BOOI), and smaller difference between Pdetmax and PdetQmax highly predictive of presence of DV/EUSD in men as per the following equation-Y = -9.900 + (0.085 × BOOI) + (0.123 × pdetmax - pdetQmax) + (4.061 × detrusor pattern). A kattan-type nomogram was constructed based on the above equation. In women, presence of plateau pattern alone was highly predictive of DV/EUSD. CONCLUSION: Diagnosis of DV/EUSD can be accurately predicted using parameters of three-channel urodynamics (plateau pattern, BOOI, Pdetmax-pdetQmax) minimizing need for specialized testing.

A prospective interventional study to assess the impact of a 'structured compact training' on knowledge and skills of safe blood transfusion practices among nurses working in a tertiary care institute.

INTRODUCTION: There is scarce information on the baseline knowledge and practices of nursing officers in relation to administration of blood components. We set out to evaluate the influence of training on their knowledge and skills through Kirkpatrick's levels of Training Evaluation. MATERIALS AND METHODS: This interventional cross sectional study of 7 months duration conducted in a tertiary care teaching institute involved 200 nursing officers. Hundred were assigned to study/intervention group and 100 were assigned to control/ comparison group by systematic random sampling. Knowledge was tested in different domains-blood components, pre-transfusion checks, transfusion process, post-transfusion process and blood administration practice. RESULTS: The baseline knowledge scores of intervention and control group were similar-15.16 ± 4.11 and 15.02 ± 4.75 (p = 0.831). Post-intervention (phase I) after 1 month, the scores improved significantly for domain A, B, C, D and E to 4.3 ± 2.21 (p = 0.0001), 3.46 ± 2.15 (p = 0.0001), 7.02 ± 3.55 (p = 0.0001), 2.51 ± 1.46 (p = 0.0012), and 5.86 ± 3.61 (p = 0.0018) respectively. In phase II, after 3 months of training, and the scores were significantly better from baseline for all domains except E. For domain A, B, C, D and E, scores were 3.82 ± 2.46 (p = 0.0001), 3.53 ± 1.98 (p = 0.0001), 7.38 ± 3.87 (p = 0.0001), 2.48 ± 1.55 (p = 0.0035), and 5.86 ± 3.61 (p = 0.95) respectively. CONCLUSIONS: Our study showed that baseline scores were low in the nursing officers. No significant difference was found in baseline scores in subject and control population. However, post-intervention, a significant improvement in scores was observed in the study group across all domains.

Gene networks determine predisposition to AMD.

PURPOSE: AMD genetic studies have revealed various genetic loci as causal to AMD pathology. We have described the genetic complexity of Indian AMD by describing the interaction of genotypes and subsequent changes in protein expression under the influence of environmental factors. This can be utilized to enhance the diagnostic and therapeutic efficacy in AMD patients. DESIGN: Genotype association was studied in 464 participants (AMD =277 & controls = 187) for eight genetic variants and their corresponding protein expression METHODS: SNP analysis and protein expression analysis was carried out in AMD and controls in tandem with longitudinal assessment of protein levels during the course of AMD pathology. ANCOVA and contrast analysis were used to examine the genotypic interactions and corresponding alterations in protein levels. In order to identify the important genetic variants Logistic Regression (LR) modeling was carried out and to authenticate the model Area under the Receiver Operating Characteristic curve (AUROC) were also computed. RESULTS: We have found genetic variants of rs5749482 (TIMP-3), rs11200638 (HTRA1), rs769449 (APOE) and rs6795735 (ADAMTS9) to be associated with AMD, concomitant with significant alterations of studied proteins levels. Analysis also revealed that the genetic interaction between APOE-HTRA1 genotypes and changes in LIPC levels (>6 pg/ug) by one unit change in SNP, play a crucial role in AMD. LR model suggested that the seven factors (including both genetic and environmental) can be utilized to predict the AMD cases with 88% efficacy and 95.6% AUROC. CONCLUSION: Results suggest that diagnostic and therapeutic strategy for Indian AMD must include estimation of genetic interaction and concomitant changes in expression levels of proteins under influence of environmental factors.

Pharmaco-immunomodulatory interventions for averting cytokine storm-linked disease severity in SARS-CoV-2 infection.

The year 2020 is characterised by the COVID-19 pandemic that has quelled more than half a million lives in recent months. We are still coping with the negative repercussions of COVID-19 pandemic in 2021, in which the 2nd wave in India resulted in a high fatality rate. Regardless of emergency vaccine approvals and subsequent meteoric global vaccination drives in some countries, hospitalisations for COVID-19 will continue to occur due to the propensity of mutation in SARS-CoV-2 virus. The immune response plays a vital role in the control and resolution of infectious diseases. However, an impaired immune response is responsible for the severity of the respiratory distress in many diseases. The severe COVID-19 infection persuaded cytokine storm that has been linked with acute respiratory distress syndrome (ARDS), culminates into vital organ failures and eventual death. Thus, safe and effective therapeutics to treat hospitalised patients remains a significant unmet clinical need. In that state, any clue of possible treatments, which save patients life, can be treasured for this time point. Many cohorts and clinical trial studies demonstrated that timely administration of immunomodulatory drugs on severe COVID-19 patients may mitigate the disease severity, hospital stay and mortality. This article addresses the severity and risk factors of hypercytokinemia in COVID-19 patients, with special emphasis on prospective immunomodulatory therapies.

Nurses' awareness and adherence with national ethical guidelines for research in North India.

BACKGROUND: A large number of nurse researchers do not adhere to ethical standards while performing the research. Moreover, there is far less data on knowledge of existing national ethical guidelines. This study was, therefore, done to assess awareness and adherence to current national ethical guidelines among nursing students and faculty members. METHODS: A cross-sectional descriptive study was done among nursing faculty members and theses carried out by postgraduate nursing students between 2012 and 2017. Using the convenience sampling technique, seven states of North India were selected. In each of the selected seven states, one government and one private nursing college was selected. Thus, a sample of 14 nursing colleges was selected. Then, using simple random sampling, a total of 140 nursing faculty members and 280 postgraduate nursing theses were selected from all the chosen institutes to be part of the study. Data analysis was done using descriptive statistics. ETHICAL CONSIDERATIONS: The study has been approved by the institutional ethical committee (ECR/737/Inst/UK/2018/RR-18). In addition, written permission from the head of each nursing institute was obtained before conducting the study. After participants read the Participation Information Sheet, they were asked for written informed consent before data collection. Confidentiality of the information and anonymity of the participants were maintained throughout the study. RESULTS: The majority (81.8%) of the participants were females. It was found that compared to private nurses, government college nurses were more adhered to the research guidelines on research project approval (68.6% vs 22.1%), informed consent guidelines (74.3% vs 25%), providing patient information sheets (55.7% vs 10%), maintaining information confidentiality (82.9% vs 72.1%), maintaining anonymity (76.4% vs 22.9%) and obtaining custodian permission (97.8 vs 89.3%). It was also shown that nurses were more aware of the informed consent process domain (4.3 ± 0.3) followed by the general ethical principles domain (3.8 ± 0.8). CONCLUSION: Government college nurses adhered more to the research guidelines as compared to those employed in private settings. Most of the faculty members were not part of any clinical trials and had no research ethics training at all. Therefore, it is needed to provide an instructional programme to raise awareness of the research ethical standards.

The prevalence of alcohol use disorders using alcohol use disorders identification test (AUDIT) in the Indian setting: - a systematic review and meta-analysis.

There is a wide discrepancy in the epidemiology of alcohol use disorders (AUDs) due to diverse scales and survey approaches. We estimated the prevalence of AUDs by comparing the pooled prevalence based on the alcohol use disorders identification test (AUDIT) Vs. non-AUDIT (all scales other than AUDIT). This review searched the community-based prevalence of AUDs in PubMed, Web of Science, PsycINFO, Scopus, Ovid, and Google Scholar. Articles published during the years from 2000 to 2020 were included. The methodological quality of each study was scored, and data were extracted from the published reports. Pooled prevalence was estimated, and the publication bias was evaluated. Twenty-one studies conducted in different states of India included 73997 community-based respondents, which estimated the overall prevalence of AUDs as 12.5% (95% CI: 9 to 17.3%). The pooled prevalence based on AUDIT was 12.4% (AUDIT ≥8; 95% CI: 8.8 to 17.1%) in which the magnitude of hazardous and harmful alcohol use (8.6%; 95% CI: 5.7 to 12.8%; AUDIT 8-19) was significantly higher than dependent alcohol use (2.3%; 95% CI: 1.1 to 4.8%; AUDIT ≥ 20). The pooled prevalence using the non-AUDIT tool was 14.2(95%; CI: 6-30%). Our findings further reveal that about one in twelve of the population of India have AUDs, and there is a gross variation in the patterns of alcohol use across the country. The high prevalence of AUDs suggests developing a national policy to benefit alcohol use, justifying regional variations.

Neuroplasticity in Depression: A Narrative Review with Evidence-Based Insights.

Major Depressive Disorder (MDD) is one of the leading causes of disability worldwide. The current pharmacological treatment options for MDD, which rely on the mono-amine hypothesis, has their limitations with respect to treatment non-response, partial response etc. This propels for a search for a novel neurobiological understanding of MDD that can lead to novel treatment options. A literature search strategy was thus employed using relevant keywords pertaining to the topic in PubMed, Embase and Google Scholar. Systematic reviews and meta-analyses, narrative reviews and clinical trials were reviewed to incorporate the most robust evidence-based literature available. A total of 37 publications were narrowed down based upon the topic. Alterations in brain neuroplasticity, as evidenced by changes in neurotrophic factors and from neuroimaging, has been found to be a strong patho-mechanism for MDD. This link has been exploited to stimulate psychopharmacological research to treat MDD.

AMPA induced cognitive impairment in rats: Establishing the role of endoplasmic reticulum stress inhibitor, 4-PBA.

Glutamate excitotoxicity and endoplasmic reticulum (ER) recently have been found to be instrumental in the pathogenesis of various neurodegenerative diseases. However, the paucity of literature deciphering the inter-linkage among glutamate receptors, behavioral alterations, and ER demands thorough exploration. Reckoning the aforesaid concerns, a prospective study was outlined to delineate the influence of ER stress inhibition via 4-phenylbutyric acid (PBA) on α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) excitotoxicity-induced behavioral aspects and possible ER stress-glutamate linkage. Male SD rats were randomly divided into four groups namely sham (surgical control+vehicle, group 1), AMPA-induced excitotoxic group 2 receive a single intra-hippocampal injection of 10 mM AMPA, group 3 received AMPA along with PBA (i.p, 100 mg/kg body weight) for 15 days, and group 4 received PBA alone. Behavioral analyses were performed prior to the sacrifice of animals and hippocampus was extracted thereafter for further analysis. AMPA-induced excitotoxicity exhibited significant impairment of locomotion as well as cognitive functions. The levels of neurotransmitters such as dopamine, homo vanillic acid (HVA), norepinephrine, and serotonin were reduced accompanied by reduced expression of GLUR1 and GLUR4 (glutamate receptor) as well as loss of neurons in different layers of hippocampus. ER stress markers were upregulated upon AMPA excitotoxicity. However, chemical chaperone PBA supplementation remarkably mitigated the behavioral alterations along with expression of glutamate and ER stress intermediates/markers in AMPA excitotoxic animals. Therefore, the present exploration convincingly emphasizes the significance of ER stress and its inhibition via PBA in combating cognitive impairment as well as improving locomotion in excitotoxic animals.

Safety and efficacy study of the wound care 360° SiteSeal® vascular closure device in percutaneous cardiac catheterization procedures.

OBJECTIVES: Vascular access site complications after percutaneous transfemoral cardiovascular procedures remain a common cause of morbidity and mortality. We evaluated the SiteSeal® VCD for achieving hemostasis following diagnostic cardiac catheterization. METHODS: We conducted a prospective case control single center study to assess the safety and efficacy of SiteSeal® VCD compared to standard manual compression following diagnostic cardiac catheterization. Forty patients were enrolled in study to receive either SiteSeal® device or manual compression (20 in each group). RESULTS: Patients in the SiteSeal® group achieved hemostasis in a significantly shorter time (4 ± 2.4 vs. 19 ± 2.4 min, P < 0.001), had shorter time from hemostasis to ambulation (95 ± 44 vs. 388 ± 63 min, P < 0.001) and significantly earlier device deployment to discharge time compared to the manual compression group (4.7 ± 1.1 vs. 8.9 ± 4.8 h, P = 0.001). There was one non-major bleeding event in the SiteSeal® group which occurred >24 h after discharge from the hospital and was managed conservatively. In the remaining device patients, there was no clinical or Doppler ultrasound evidence of major or minor vascular complication with good overall patient comfort at discharge, 7 days and 30 days follow-up. CONCLUSIONS: In this first clinical experience, the SiteSeal® VCD achieved safe and efficient hemostasis, allowed for earlier ambulation and faster discharge compared to manual compression.

Is the retropharyngeal lymph node the first echelon node for carcinoma tonsil? Prospective evaluation and literature review.

PURPOSE: Tonsil cancer being predominantly treated by non-surgical means, there is a paucity of data on lymph nodal drainage pathways and histo-pathologically confirmed metastatic rates. This study assesses the retropharyngeal lymph node (RPLN) in N0 squamous cell carcinoma tonsil as a possible first echelon node and a site for occult metastasis. METHODS: Prospective study involving treatment naïve N0 carcinoma tonsil treated by primary surgery and adjuvant treatment from June 2017 to March 2019. In-vivo lymph nodal drainage patterns were assessed by sentinel node mapping by preoperative SPECT-CT and intra-operative hand-held Gamma probe. All patients had a subsequent Level I-III/IV sampling neck dissection supplemented with RPLN dissection. Histological evaluation of sentinel nodes and RPLN involved step-serial sectioning and pan-cytokeratin immunohistochemistry. A comprehensive literature review was performed with keywords "retropharyngeal lymph node", "oropharynx", "tonsil", "squamous cell carcinoma" to determine the incidence of RPLN positivity in previously published series. RESULTS: Sentinel node was successfully identified by SPECT-CT in all 17 patients (ipsilateral level 2a-13/17, 2b-1/17, 3-1/17; bilateral 2a-1/17; isolated contralateral retropharyngeal node-1/17). 8/17 had occult neck metastasis. In no patient was an ipsilateral RPLN identified as the sentinel node. Histological sampling did not indicate metastatic tumor in the RPLN in any patient (0/17). A systematic literature review further confirmed that RPLN metastasis in oropharyngeal cancer is noted only in the presence of pN + disease at other neck levels, and isolated RPLN metastasis is extremely rare (1.2%). CONCLUSION: The ipsilateral RPLN is not identified either as the first echelon node or as a site of occult metastatic disease in N0 tonsil cancer. CTRI REGISTRATION: CTRI/2019/06/019551.

Cross-cultural validation of Hindi version Knee Injury and Osteoarthritis Outcome Score (KOOS) in osteoarthritis knee.

PURPOSE: To assess the reliability, validity and responsiveness of the Hindi version of the Knee Injury and Osteoarthritis Outcome Score (H-KOOS) in osteoarthritic knee. METHODS: Two hundred and fourteen patients of osteoarthritis knee (OA) between 40 and 80 years of age were evaluated with H-KOOS, Short form health survey (SF12v2) and the WHOQOL-BREF questionnaire. The H-KOOS was re-evaluated after 48 h in 125 patients to assess the test-retest reliability. For responsiveness, 40 patients were treated with the intra-articular hyaluronic acid injection, and the effect was assessed after 6 weeks. RESULTS: Most of the domains in H-KOOS did not show a ceiling effect. The floor values were observed in 3.75% of patients in sports/recreation function and 2.75% of patients in Quality of life (QoL). The test-retest reliability was excellent with the Intraclass-Correlation-Coefficient (ICC) ranging from 0.89 to 0.94. Internal consistency as assessed using Cronbach's alpha coefficient was acceptable for pain, activities of daily living (ADL) and sport/recreation function (range 0.86-0.93); however, symptoms and QoL had weak internal consistency. There were moderate to strong correlations (r = 0.35 to 0.6) between domains measuring similar constructs in H-KOOS, SF12v2 and WHOQOL-BREF indicating good convergent construct validity. The responsiveness as measured by the effect size (ES) and standardized response mean (SRM) was large for pain (ES 0.9, SRM 0.8), moderate for Sport/Rec (ES 0.66, SRM 0.2) and small for ADL, QoL and Symptoms subscales. CONCLUSION: The Hindi version KOOS is a valid, reliable and responsive measure to evaluate osteoarthritis knee with minimal ceiling and floor effects. LEVEL OF EVIDENCE: Prospective cohort study, level II.

Monitoring an ungagged coastal marsh to analyze the salinity interaction of the marsh with Lake Erie.

Phragmites growth in a marsh watershed due to increased salinity has been a crucial issue across the world. The objective of this study was to investigate the salinity movement in the ungagged Mentor Marsh of Ohio, USA, where the salinity had increased due to a number of potential sources causing a decline in the native vegetation and leading to the increased invasive phragmites growth. In this study, we conducted a detailed bathymetric survey and established several monitoring stations to record hourly environmental data in Mentor Marsh. Since Mentor Marsh has a complex hydrologic characteristic, which interacts with Lake Erie due to the backwater effect, a hydrodynamic model, Environmental Fluid Dynamic Code (EFDC +), was developed to simulate the western Mentor Marsh wetland's salinity distribution. We evaluated the model performance by comparing water level, temperature, and salinity using statistical measures for a duration from December 2019 to March 2020. The model was calibrated using the measured time-series data of water temperatures, water levels, and water salinity from monitoring stations in the western basin. The model performance for salinity calibration (R2 = 0.82, RMSE = 0.041, and Pbias = - 1.05%) and validation (R2 = 0.84, RMSE = 0.066, and Pbias = - 2.05%) was good. In the next step, the calibrated model was utilized to investigate the salinity distributions under different inflow and lake level rise conditions. Our analysis suggested that during high-flow conditions, the advection of the saline water from Marsh Creek was vigorous in comparison to the diffusion of salinity mixing by tidal influence pushing the salinity towards Mentor Marsh and resulting in the lower salinity distribution within the model domain. Similarly, when the lake level rise occurred, the model predicted a significant decrease in the salinity of Mentor Marsh near Lake Erie. The average decrease of salinity from the salinity during the base run was - 45.8% near Lake Erie, - 29.7% at the junction of Mentor Marina and Mentor Marsh, - 21.2% in Mentor Marsh, and - 4.4% in Marsh Creek. The analysis further suggested that under high-flow conditions from Marsh Creek, the salinity moved towards Mentor Marsh, especially when lake level rise conditions were considered. This is mainly because the high water level of Lake Erie pushed March Creek towards Mentor Marsh. However, the salinity moved towards Lake Erie from Marsh Creek during low-flow conditions. Presumably, the phragmites growth in the western section seems to be due to the road salt used in winter for deicing purposes.

Expectations of healthcare personnel from infection prevention and control services for preparedness of healthcare organisation in view of COVID-19 pandemic.

BACKGROUND: During infectious outbreaks like COVID-19, it is essential that every healthcare personnel (HCP) strictly adheres to infection prevention and control (IPC) policies. To boost IPC measures, training to reinforce preventive practices, which are pertinent to needs and encompass the expectations of the HCP, is indispensable. Thus, these expectations of the HCP should be explored. METHODS: In this cross-sectional descriptive survey, we used convenience sampling technique to ask the participants to list their expectations on of covid-19 IPC training paper based forms. Using the category construction approach, we organised the expectations and grouped the participants on the basis of their work and place of work to analyse the association using the chi-square test. RESULTS: Many participants expected to learn about the use of PPE and masks, hand hygiene, physical distancing, cleaning and disinfection, basic precautions for personal protection during the training. Expectations also included various administrative queries, sample collection and clinical skills for diagnosis and management. There was significant association of many categories of expectations with the nature and place of work in the hospital. CONCLUSION: When planning IPC training, these expectations of the HCP may be carefully addressed. Information about causative agent, transmission and clinical aspects may will give a contextual meaning to IPC training. Some important preventive measures, which few participants expected to learn must be analysed in detail to understand the attitude of the HCP towards them. Efforts to appraise the HCP for the importance of these measures and promoting its practice may play a vital role to curb the spread of infectious diseases.

Hijacking of multiple phospholipid biosynthetic pathways and induction of membrane biogenesis by a picornaviral 3CD protein.

RNA viruses induce specialized membranous structures for use in genome replication. These structures are often referred to as replication organelles (ROs). ROs exhibit distinct lipid composition relative to other cellular membranes. In many picornaviruses, phosphatidylinositol-4-phosphate (PI4P) is a marker of the RO. Studies to date indicate that the viral 3A protein hijacks a PI4 kinase to induce PI4P by a mechanism unrelated to the cellular pathway, which requires Golgi-specific brefeldin A-resistance guanine nucleotide exchange factor 1, GBF1, and ADP ribosylation factor 1, Arf1. Here we show that a picornaviral 3CD protein is sufficient to induce synthesis of not only PI4P but also phosphatidylinositol-4,5-bisphosphate (PIP2) and phosphatidylcholine (PC). Synthesis of PI4P requires GBF1 and Arf1. We identified 3CD derivatives: 3CDm and 3CmD, that we used to show that distinct domains of 3CD function upstream of GBF1 and downstream of Arf1 activation. These same 3CD derivatives still supported induction of PIP2 and PC, suggesting that pathways and corresponding mechanisms used to induce these phospholipids are distinct. Phospholipid induction by 3CD is localized to the perinuclear region of the cell, the outcome of which is the proliferation of membranes in this area of the cell. We conclude that a single viral protein can serve as a master regulator of cellular phospholipid and membrane biogenesis, likely by commandeering normal cellular pathways.

Multiple poliovirus-induced organelles suggested by comparison of spatiotemporal dynamics of membranous structures and phosphoinositides.

At the culmination of poliovirus (PV) multiplication, membranes are observed that contain phosphatidylinositol-4-phosphate (PI4P) and appear as vesicular clusters in cross section. Induction and remodeling of PI4P and membranes prior to or concurrent with genome replication has not been well studied. Here, we exploit two PV mutants, termed EG and GG, which exhibit aberrant proteolytic processing of the P3 precursor that substantially delays the onset of genome replication and/or impairs virus assembly, to illuminate the pathway of formation of PV-induced membranous structures. For WT PV, changes to the PI4P pool were observed as early as 30 min post-infection. PI4P remodeling occurred even in the presence of guanidine hydrochloride, a replication inhibitor, and was accompanied by formation of membrane tubules throughout the cytoplasm. Vesicular clusters appeared in the perinuclear region of the cell at 3 h post-infection, a time too slow for these structures to be responsible for genome replication. Delays in the onset of genome replication observed for EG and GG PVs were similar to the delays in virus-induced remodeling of PI4P pools, consistent with PI4P serving as a marker of the genome-replication organelle. GG PV was unable to convert virus-induced tubules into vesicular clusters, perhaps explaining the nearly 5-log reduction in infectious virus produced by this mutant. Our results are consistent with PV inducing temporally distinct membranous structures (organelles) for genome replication (tubules) and virus assembly (vesicular clusters). We suggest that the pace of formation, spatiotemporal dynamics, and the efficiency of the replication-to-assembly-organelle conversion may be set by both the rate of P3 polyprotein processing and the capacity for P3 processing to yield 3AB and/or 3CD proteins.

Does conserved domain SOD1 mutation has any role in ALS severity and therapeutic outcome?

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative fatal disease that can affect the neurons of brain and spinal cord. ALS genetics has identified various genes to be associated with disease pathology. Oxidative stress induced bunina and lewy bodies formation can be regulated through the action of SOD1 protein. Hence, in the present study we aim to analyse the structural and functional annotation of various reported SOD1 variants throughout and their putative correlation with the location of mutation and degree of ALS severity by inferring the structural and functional alterations in different SOD1 variants. METHODS: We have retrieved around 69 SNPs of SOD1 gene from Genecards. Structural annotation of SOD1 variants were performed using SWISS Model, I-Mutant 2.0, Dynamut, ConSurf. Similarly, the functional annotation of same variants were done using SIFT, PHP-SNP, PolyPhen2, PROVEAN and RegulomeDB. Ramachandran plot was also obtained for six synonymous SNPs to compare the amino acid distribution of wild-type SOD1 (WT SOD1) protein. Frequency analysis, Chi square analysis, ANOVA and multiple regression analysis were performed to compare the structural and functional components among various groups. RESULTS AND CONCLUSION: Results showed the mutations in conserved domain of SOD1 protein are more deleterious and significantly distort the tertiary structure of protein by altering Gibb's free energy and entropy. Moreover, significant changes in SIFT, PHP-SNP, PolyPhen2, PROVEAN and RegulomeDB scores were also observed in mutations located in conserved domain of SOD1 protein. Multiple regression results were also suggesting the significant alterations in free energy and entropy for conserved domain mutations which were concordant with structural changes of SOD1 protein. Results of the study are suggesting the biological importance of location of mutation(s) which may derive the different disease phenotypes and must be dealt accordingly to provide precise therapy for ALS patients.