Large-scale Morbidity Research Articles

The Therapeutic Potential Of Date Palm Pollen For Testicular Disorders Induced By Diabetes In Male Diabetic Rats

Diabetes mellitus (DM) is the main cause of large-scale morbidity and mortality. This syndrome has adverse effects on all physiological systems, including the male reproductive system. It affects a large number of men of reproductive age and causes serious reproductive disorders. This study was aimed to examine the protective effect of date palm pollen (DPP) on diabetes-induced testicular disorders in male rats. Rats were divided into 4 groups. The first group represents the negative control, while the second group is the positive control. In contrast, the following two groups represent the treated groups of DPP suspension with a concentration of 130 mg/kg and 160 mg/kg for 4 weeks. At the end of the experiment, the rats were anesthetized, the epididymis and testis were extracted. The positive control group significantly decreased body weight, sex hormones, and sperm count. However, a significant increase in fasting glucose and the number of abnormal sperm. The histological results confirmed tubular degeneration, Leydig cell atrophy, and tubular dilation. Decrease the basement membrane, the semenforuos epithelium, and tubular diameter, while the diameter of the lumen increased. Treatment with DPP suspension showed a significant decrease in the level of fasting glucose and the number of abnormal sperm. While the number of sperm increased significantly. The results of the histological study confirmed that the Seminiferous Tubules treated with DPP were intact, the germinal epithelium dense, seminiferous tubules did not expand. We concluded that the DPP has an influence on protecting testis from diabetes complication.

The effect of the COVID-19 pandemic on community violence in Connecticut

IntroductionNatural disasters may lead to increases in community violence due to broad social disruption, economic hardship, and large-scale morbidity and mortality. The effect of the COVID-19 pandemic on community violence is unknown. MethodsUsing trauma registry data on all violence-related patient presentations in Connecticut from 2018 to 2021, we compared the pattern of violence-related trauma from pre-COVID and COVID pandemic using an interrupted time series linear regression model. ResultsThere was a 55% increase in violence-related trauma in the COVID period compared with the pre-COVID period (IRR: 1.55; 95%CI: 1.34–1.80; p-value<0.001) driven largely by penetrating injuries. This increase disproportionately impacted Black/Latinx communities (IRR: 1.61; 95%CI: 1.36–1.90; p-value<0.001). ConclusionViolence-related trauma increased during the COVID-19 pandemic. Increased community violence is a significant and underappreciated negative health and social consequence of the COVID-19 pandemic, and one that excessively burdens communities already at increased risk from systemic health and social inequities.

Rickettsia Aglow: A Fluorescence Assay and Machine Learning Model to Identify Inhibitors of Intracellular Infection.

Rickettsia is a genus of Gram-negative bacteria that has for centuries caused large-scale morbidity and mortality. In recent years, the resurgence of rickettsial diseases as a major cause of pyrexias of unknown origin, bioterrorism concerns, vector movement, and concerns over drug resistance is driving a need to identify novel treatments for these obligate intracellular bacteria. Utilizing an uvGFP plasmid reporter, we developed a screen for identifying anti-rickettsial small molecule inhibitors using Rickettsia canadensis as a model organism. The screening data were utilized to train a Bayesian model to predict growth inhibition in this assay. This two-pronged methodology identified anti-rickettsial compounds, including duartin and JSF-3204 as highly specific, efficacious, and noncytotoxic compounds. Both molecules exhibited in vitro growth inhibition of R. prowazekii, the causative agent of epidemic typhus. These small molecules and the workflow, featuring a high-throughput phenotypic screen for growth inhibitors of intracellular Rickettsia spp. and machine learning models for the prediction of growth inhibition of an obligate intracellular Gram-negative bacterium, should prove useful in the search for new therapeutic strategies to treat infections from Rickettsia spp. and other obligate intracellular bacteria.

Anemia in Pregnancy: A knowledge, Attitude and Practice Survey Amongst Obstetricians and Gynaecologists in India.

Anemia continues to affect one-third of the global population and is one of the most common reasons for large-scale morbidity and mortality especially among women. The importance of iron-rich diet has always been the backbone of preventing iron deficiency anemia (IDA) in vulnerable age groups followed by oral iron therapy and parenteral iron therapy as the next options in management of iron deficiency. Objective of this survey was to assess the knowledge, attitude and practices of obstetricians and gynaecologists relevant to anemia in pregnancy and identify the practice gaps in management of anemia in pregnancy. This was a knowledge, attitude and practice (KAP) survey involving obstetricians and gynaecologists (ObGyns) across India. A validated questionnaire of twenty questions was used to assess knowledge, attitude and practice about anemia and its management. Results were expressed as percentages. 1974 ObGyns participated in the survey. 88.7% ObGyns screen anemia in first trimester, 53.7% ObGyns perform CBC along with RBC indices. Majority of ObGyns estimate Hb thrice during antenatal period. 50% ObGyns do not consider thalassemia screening routinely and deworming regularly. 92.4% ObGyns believe that iron supplementation is required even if Hb > 11g/dL. Majority of them prefer low-dose iron therapy, 59.9% prefer to use 100mg oral iron daily. Almost half of ObGyns prefer to change iron salt when patients do not respond, instead of escalating to injectable iron. Interestingly 52% ObGyns evaluate serum ferritin before starting intravenous iron therapy. 43.5% perform Hb estimation as early as 2weeks after IV iron therapy. Majority (82.2%) of ObGyns prefer blood transfusion as a treatment of choice when Hb < 5g/dl at 34weeks gestation. Only 40.5% of participants are aware of the exact cut-off for diagnosing postpartum anemia. Majority of the ObGyns are aware of the iron prophylaxis in postpartum period till 3-6months. More than 90% ObGyns consider intravenous iron for severe anemia of postpartum period. The present KAP survey highlights the observation, perception and the practicing behaviour of obstetricians and gynaecologists on anemia in pregnancy and identifies practice gaps in anemia management.

COVID-19 Vaccine Intention among Healthcare Workers in Saudi Arabia: A Cross-Sectional Survey.

The COVID-19 pandemic has caused largescale morbidity and mortality and a tremendous burden on the healthcare system. Healthcare workers (HCWs) require adequate protection to avoid onward transmission and minimize burden on the healthcare system. Moreover, HCWs can also influence the general public into accepting the COVID-19 vaccine. Therefore, determining COVID-19 vaccine intention among HCWs is of paramount importance to plan tailor-made public health strategies to maximize vaccine coverage. A structured questionnaire was administered in February and March 2021 among HCWs in Saudi Arabia using convenience sampling, proceeding the launch of the vaccination campaign. HCWs from all administrative regions of Saudi Arabia were included in the study. In total, 674 out of 1124 HCWs responded and completed the survey (response rate 59.9%). About 65 percent of the HCWs intended to get vaccinated. The intention to vaccinate was significantly higher among HCWs 50 years of age or older, Saudi nationals and those who followed the updates about COVID-19 vaccines (p < 0.05). The high percentage (26 percent) of those who were undecided in getting vaccinated is a positive sign. As the vaccination campaign gathers pace, the attitude is expected to change over time. Emphasis should be on planning healthcare strategies to convince the undecided HCWs into accepting the vaccine in order to achieve the coverage required to achieve herd immunity.

PROSPECTIVE OBSERVATIONAL STUDY TO ASSESS ASSOCIATION OF BLOOD GROUP ANTIGENS AND RISK OF CORONAVIRUS INFECTION CONDUCTED IN A TERTIARY CENTRE.

Purpose: COVID-19 has caused large scale morbidity and mortality. Assessment of frequency of blood groups in COVID-19 to investigate its susceptibility in different blood groups will help in risk stratication and its better understanding. Aims: To assess association between blood group antigens and coronavirus infection. Settings and Design: Blood group of COVID-19 patients was determined and was compared with blood group of blood donors over a period of 23 months. Blood group of both Ccovid-19 positive and negative health care workers was also compared. Methods and Material: Blood group determination was done in 1559 COVID-19 patients, out of which 81 were health care workers. Blood group of 754 COVID-19 negative health care workers was also determined. Gel column technique was used for blood grouping. Blood group frequency of COVID-19 patients was compared with blood group frequency of blood donors over a period of 23 months. Statistical analysis used: Odds ratio, 95% condence limit, z statistic and p value were calculated using online software available at https://www.medcalc.org/calc/odds_ratio.php. p value less than 0.05 was considered signicant. Results: B+ is most prevalent blood group in blood donors hence it was the most frequent blood group encountered in COVID19 patients, No signicant difference was noted in frequency of blood groups of COVID-19 patients and blood donors. Similar results were obtained after comparison of blood group in COVID-19 positive and negative Conclusions: No blood group is immune to SARS-CoV-2. Hence there should be universal compliance of sanitization protocols and vaccination

Comparable exposure to SARS-CoV-2 in young children and healthcare workers in Zambia

Background:Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an ongoing global health crisis that has caused large scale morbidity and mortality. We aimed to determine the exposure to SARS-CoV-2 among young children and healthcare workers by measurement of anti-S1 antigen (spike protein) specific immunoglobulin G (IgG) using an in-house optimized indirect enzyme-linked immunosorbent assay (ELISA) method.Methods:Plasma samples were collected from cohorts of healthcare workers (n = 287) and young children aged from 6 weeks to 2 years old (n = 150) pre-COVID-19 pandemic between September 2018 and November 2019 and post-COVID-19 pandemic between August and December 2020 were simultaneously tested for anti-SARS-CoV-2 S1 specific IgG. The arithmetic mean of natural logarithm-transformed ELISA relative absorbance reading + (3 x standard deviation) of pre-pandemic plasma was used as the cut-off to determine SARS-CoV-2 IgG seropositivity of post-pandemic plasma.Results:There was no reactivity to SARS-CoV-2 S1 antigen detected in pre-pandemic plasma but in post pandemic plasma an 8.0% (23/287) IgG seropositivity in healthcare workers’ and 6.0% (9/150) seropositivity in children aged 2 years old was detected.Conclusions:Comparable levels of SARS-CoV-2 IgG seropositivity in healthcare workers and children suggest widespread exposure to SARS-CoV-2 in Zambia during the first wave of the pandemic. This finding has implications for continued acquisition and transmission of infection in the healthcare setting, household, and wider community.

Bloodstream infections in cancer patients: Analysis from a tertiary cancer hospital in Bhubaneswar, Odisha, India

Background: Bloodstream infections (BSIs) account for large-scale morbidity and mortality among cancer patients requiring a rational antibiotic policy. In India, there is a paucity of data regarding incidence and pattern of BSI in such patients. Aim: The study was conducted to evaluate the pattern of BSI in cancer patients and their sensitivity and resistance toward antibiotic. Materials and Methods: All the blood culture-confirmed infections among cancer patients treated at a tertiary care institute in Bhubaneswar, Odisha, India, were retrospectively analyzed during the year 2018. Results: A total of 82 patients/episodes had confirmed BSI. Gram-negative bacteria accounted for 43 (52.4%) cases, followed by Gram positive 38 (46.4%) cases and 1 case of candida species. The most common organisms isolated were Klebsiella pneumoniae and Staphylococcus aureus consisting of 17 cases each. The Gram-negative bacterial isolates (n = 43) were sensitive to cefoperazone plus sulbactam, piperacillin plus tazobactam, carbapenem, and colistin in 18 (41.9%), 19 (44.2%), 29 (67.4%), and 40 (93%) episodes, respectively. The sensitivity of Gram-positive bacteria (n = 38) to vancomycin, linezolid, and teicoplanin was seen in 37 (97.3%), 37 (97.3%), and 35 (92.1%) episodes, respectively. Multidrug-resistant bacteria accounted for 17 (39.5%) cases of Gram-negative isolates and 9 (53%) of which were K. pneumoniae. Extended-spectrum beta-lactamase activity was seen in 11 of 26 episodes of Enterobacteriaceae. Four of 17 S. aureus and 3 of 11 coagulase-negative Staphylococci were methicillin resistant, and 1 of 2 cases of Enterococcus was vancomycin resistant. Conclusion: Gram-negative bacteria are the predominant cause of BSI in cancer patients and development of a high degree of resistance to commonly used antibiotics is challenging.

Sustainable healthcare education: integrating planetary health into clinical education

Sustainable healthcare education: integrating planetary health into clinical education

Expression of HA1 antigen of H5N1 influenza virus as a potent candidate for vaccine in bacterial system.

The impending influenza virus pandemic requires global vaccination to prevent large-scale mortality and morbidity, but traditional influenza virus vaccine production is too slow for rapid responses. In this study, bacterial system has been developed for expression and purification of properly folded HA1 antigen as a rapid response to emerging pandemic strains. Here, a recombinant H5N1 (A/Indonesia/05/05) hemagglutinin globular domain, the synthesized HA1 (1-320 amino acids), was amplified and cloned into pET-28a bacterial expression vector. Then, his-tagged HA1 protein was expressed in Escherichia coli BL21 under 1 mM IPTG induction. The protein expression was optimized under a time-course induction study and further purified using Ni-NTA chromatography. Migration size of protein was detected at 40 KDa by Western blot using anti-His tag monoclonal antibody and demonstrated no discrepancy compared to its calculated molecular weight. Since most antigenic sites are in the HA1 domain of HA, using this domain of influenza virus as antigen is of great importance in vaccine development. The ability of the antibody stimulation against HA1 expressed in bacterial cells is also examined using enzyme-linked immunosorbent assay (ELISA) analysis. Upon immunization of rabbits, oligomeric HA1 elicited potent neutralizing antibodies and high levels of serum antibody binding to HA1. Our findings suggest that HA1-based vaccines can be produced efficiently in bacterial systems and can be easily upscaled in response to a pandemic influenza virus threat.

70,489 primary care encounters: retrospective analysis of morbidity at a primary care centre in Ireland.

While considerable changes are happening in primary care in Ireland and considerable potential exists in intelligence derived from practice-based data to inform these changes, relatively few large-scale general morbidity surveys have been published. To examine the most common reasons why people attend primary care, specifically 'reasons for encounter' (RFEs) among the general practice population and among specific demographic groups (i.e., young children and older adults). We retrospectively examined clinical encounters (which had a diagnostic code) over a 4-year time period. Descriptive analyses were conducted on anonymised data. 70,489 RFEs consultations were recorded (mean 13.53 recorded RFEs per person per annum) and consultations involving multiple RFEs were common. RFE categories for which codes were most commonly recorded were: 'general/unspecified' (31.6%), 'respiratory' (15.4%) and 'musculoskeletal' (12.6%). Most commonly recorded codes were: 'medication renewal' (6.8%), 'cough' (6.6%), and 'health maintenance/prevention' (5.8%). There was considerable variation in the number of RFEs recorded per age group. 6239 RFEs (8.9%) were recorded by children under 6 years and 15,295 RFEs (21.7%) were recorded by adults aged over 70. RFEs recorded per calendar month increased consistently through the study period and there was a marked seasonal and temporal variation in the number of RFEs recorded. Practice databases can generate intelligence on morbidity and health service utilisation in the community. Future research to optimise diagnostic coding at a practice level and to promote this activity in a more representative sample of practices is a priority.

The role of Wnt/β-catenin pathway and LRP5 protein in metabolism of bone tissue and osteoporosis etiology

Osteoporosis is a metabolic bone disease, manifested by decreased bone mineral density microarchitectural disturbances of bone tissue, and increased risk of bone fractures. Owing to large-scale morbidity particularly among postmenopausal women, nowadays osteoporosis constitutes a significant global health problem. In recent years, much attention has been paid to the role of signaling Wnt/β-catenin pathway and LRP protein in the pathomechanism of osteoporosis, indicating a possible contribution of polymorphic variants of the candidate LRP5 gene to disease development. The goal of our study is to present contemporary research on signaling Wnt/β-catenin pathway and mechanism of LRP protein action in the process of bone tissue metabolism and etiology of osteoporosis.

Diabetes-induced oxidative DNA damage alters p53-p21CIP1/Waf1 signaling in the rat testis.

Diabetes is increasingly becoming a major cause of large-scale morbidity and mortality. Diabetes-induced oxidative stress alters numerous intracellular signaling pathways. Although testicular dysfunction is a major concern in diabetic men, the mechanistic alterations in the testes that lead to hypogonadism are not yet clear. Oxidative mitochondrial DNA damage, as indicated by 7,8-dihydro-8-oxo-2'-deoxyguanosine, and phosphorylation of p53 at ser315 residue (p-p53ser315) increased in a stage- and cell-specific manner in the testes of rats that were diabetic for 1 month (DM1). Prolongation of diabetes for 3 months (DM3) led to an increase in nuclear oxidative DNA damage in conjunction with a decrease in the expression of p-p53ser315. The nuclei of pachytene and preleptotene spermatocytes, steps 1, 11, and 12 spermatids, secondary spermatocytes and the Sertoli cells, and the meiotic figures showed an increase in the expression of p-p53ser315. An increase in the expression of a downstream target of p53 and protein 21(cyclin-dependent kinase interacting protein 1/wild-type p53-activated factor 1) (p21(CIP1/Waf1)) in both diabetic groups did not show any time-dependent effects but occurred concurrent with an upregulation of p-p53ser315 in DM1 and a downregulation of the protein in DM3. In diabetic groups, the expression of p21(CIP1/Waf1) was mainly cytoplasmic but also perinuclear in pachytene spermatocytes and round spermatids. The cytoplasmic localization of p21(CIP1/Waf1) may be suggestive of an antiapoptotic role for the protein. The perinuclear localization is probably related to the cell cycle arrest meant for DNA damage repair. Diabetes upregulates p21(CIP1/Waf1) signaling in testicular germ cells in association with alteration in p-p53ser315 expression, probably to counteract DNA damage-induced cell death.

Circulation : Cardiovascular Imaging

<i>Circulation</i> : <i>Cardiovascular Imaging</i>

Results From a Carotid Intima-Media Thickness Trial as a Decision Tool for Launching a Large-Scale Morbidity and Mortality Trial

Trials with carotid intima-media thickness (CIMT) as primary end point may improve the efficiency of the evaluation of new therapies targeting atherosclerosis considerably, and the results of CIMT trials may be used as a decision tool to help in the choice to launch or not to launch a large-scale morbidity and mortality (M&M) trial. We evaluated the literature to provide evidence to support or refute this proposition. PubMed Medline was systematically searched on May 1, 2012, for randomized double-blind controlled CIMT trials. The agreement between the results from CIMT and M&M trials was assessed, and positive and negative predictive values were calculated. Forty-eight CIMT trials were included. CIMT trials (n=20) on lipid-level modifying therapies are all, except one, in agreement with the M&M trial findings. For blood pressure-lowering trials (n=13), 3 were not congruent with the M&M trial. The positive and negative predictive value (95% confidence interval) of a CIMT trial to predict the outcome of a M&M trial are 96% (80-99%) and 83% (64-93%), respectively. The predictive values are higher for lipid-level modifying therapies than for other therapies. A CIMT trial positioned before an M&M trial may considerably improve the efficiency of the evaluation of new drug therapies on atherosclerosis and cardiovascular disease risk. Hence, the results of a CIMT trial should be seen as a decision tool to support or refute the start of a large-scale M&M trial on drugs targeting atherosclerosis.

Benefits of PDE5 inhibition in patients with diastolic heart failure

The occurrence of signs and symptoms of heart failure (HF) with normal left ventricular ejection fraction and predominant anomalies of left ventricular (LV) relaxation and stiffness (i.e. diastolic HF) is increasingly recognized. Notably, in recent years survival rate of systolic HF has improved, whereas the prognosis for diastolic HF remains unchanged. This may be in part attributable to the lack of additional benefits by treatments’ options used as standard care of systolic HF. PDE5 inhibition is an emerging therapy proposed for HF treatment that enhances NO signaling by increasing the cyclic guanosine monophosphate (cGMP) availability. This pharmacological property seems especially attractive for patients with left ventricular hypertrophy and diastolic HF [1]. In experimental models of failing hearts due to pressure overload and diastolic dysfunction, PDE5 inhibition has been shown to promote a reverse left ventricular (LV) chamber remodeling by modulating LV hypertrophy and fibrosis [2]. Preliminary observations in humans confirm the ability of long-term PDE5 inhibition administration by sildenafil to improve cardiac geometry, LV mass and diastolic function [3]. Recent community based studies [4] have highlighted that a considerable number of patients with diastolic HF present with left-sided Group 2 pulmonary hypertension suggesting a tight pathophysiological relationship between LV hypertrophy, increasing LV filling pressures and abnormalities of pulmonary vascular tone and permeability. Interestingly, development of pulmonary hypertension strongly discriminates survival rate. Although in these patients alterations of many signaling pathways may be unique to the heart or pulmonary vasculature, downregulation of the NO-cGMP pathway seems to be a common finding in both locations. Accordingly, in an effort to better understand the combined role of this pathway in both the heart and the lung vasculature, we recently performed a study aimed at testing the hypothesis that diastolic HF patients at higher risk for the unfavorable upstream effects of an increased left atrial pressure would benefit of chronic PDE5 inhibition with sildenafil. Specifically, we hypothesized that sildenafil would modulate pulmonary vascular tone and RV hemodynamic burden. A significant improvement in pulmonary hemodynamics, right ventricular contractility and chamber dimensions were observed at 6 and 12 months of follow-up. These effects were paralleled by an improvement in quality of life and clinical status [5]. Although the available experimental and clinical data seem promising, further large-scale morbidity and mortality studies are necessary to provide a definitive appreciation onto whether PDE5 inhibition may effectively impact the natural history of HF due to diastolic origin.

Human Adenovirus 14a: A New Epidemic Threat

Human Adenovirus 14a: A New Epidemic Threat

Intubation training in the real world: a defence of the Northwick Park drill

Intubation training in the real world: a defence of the Northwick Park drill

Anthrax: From Antiquity to Answers

be guided by pathogenesis studies. Anthrax continues to occupy its position atop the category A agent bioterrorism threat list [2], in large part because of the potential for large-scale morbidity and mortality associated with its use as an aerosolized weapon [3]. Selected antimicrobials, although they have activity against the organism, do not prevent the pathogenic consequences of infection, because systemic illness results from the effects of protein exotoxins produced by the pathogen during infection. Individuals with inhalational anthrax appear to reach a critical threshold beyond which death, despite the use of appropriate antimicrobials, is expected [4]. Two discrete exotoxins are responsible for the pathogenic sequelae of anthrax: lethal toxin (LT), which is composed of a heptameric protective antigen (PA) bound to lethal factor, and edema toxin (ET), which is composed of PA bound to edema factor [5]. Much has been learned in the recent past, especially since 2001, concerning the molecular and cellular processes involved in anthrax intoxication [6]. LT has been the focus of substantial in-

The strange case of Dr HDL and Mr HDL: Does a NO’s story illuminate the mystery of HDL’s dark side uncovered by Dr HDL’s drug targeting CETP?

Recently, the first large-scale morbidity and mortality trial (ILLUMINATE) to evaluate the cardiovascular end points of a CETP inhibitor (torcetrapib) has been prematurely stopped because the mortality was significantly increased in the treated group. Why torcetrapib caused excess death is not known. Based on the fact that HDL interacts with endothelial nitric oxyde synthase (eNOS) and nitric oxide (NO) secretion, which partly controlled blood pressure and than torcetrapib could increase blood pressure among some patients, we hypothesize that CETP inhibition could have significantly inhibit eNOS. CETP inhibition would have enlarged HDL size resulting in a deficit in the interaction between HDL and the Scavenger Receptor class B type I (SR-BI), which is an important link between HDL and eNOS activation. We suggest than the deficit in NO secretion would have been sufficient among all patients to induce a destabilization of the plaques of atheroma, but could have induced a pathogenic increase in blood pressure only in patients whose eNOS activity was naturally weak due to genetic polymorphisms of this enzyme. We also hypothesize that the increase in HDL levels, induced by CETP inhibition, coupled with the capacity of HDL to induce endothelin-1 secretion would have aggravated the cardiovascular risks under this CETP inhibitor treatment.