Severe Disease Symptoms Research Articles

Varicose veins - diagnostic and treatment methods

Introduction and purpose: Varicose veins of the lower limbs are quite common and common disease. Their presence may be associated with the occurrence of a number of symptoms that negatively affect the quality and comfort of life, such as swelling, leg pain and cosmetic defect.The aim of the study is to review the available literature and articles available in the PubMed database in order to learn about the pathophysiology of varicose veins, methods of diagnosis and the most popular methods of their treatment.
 State of the knowledge: Varicose veins are described as fusiform dilatation of superficial veins with accompanying elongation and characteristic twisting. The main cause of their formation is insufficiency of the venous valve apparatus. Genetic and individual factors such as sex, age, and excessive body weight also have an impact. The diagnosis is based primarily on the physical examination of the patient and the Doppler ultrasound examination of the veins. Management options for varicose veins range from conservative management including pharmacotherapy to invasive and surgical methods, each of which has both advantages and disadvantages.
 Summary: Making a diagnosis of varicose veins usually does not cause many difficulties. There is no one-size-fits-all treatment method. When choosing it, many aspects should be taken into account, such as the patient's preferences, severity of disease symptoms, and the patient's general condition.

Laparoscopic Toupet fundoplication: a safe and effective anti-reflux option in lung transplant recipients.

Fundoplication is known to improve allograft outcomes in lung transplant recipients by reducing retrograde aspiration secondary to gastroesophageal reflux disease, a modifiable risk factor for chronic allograft dysfunction. Laparoscopic Nissen fundoplication has historically been the anti-reflux procedure of choice, but the procedure is associated with discernable rates of postoperative dysphagia and gas-bloat syndrome. Laparoscopic Toupet fundoplication, an alternate anti-reflux surgery with lower rates of foregut complications in the general population, is the procedure of choice on our institution's lung transplant protocol. In this work, we evaluated the efficacy and safety of laparoscopic Toupet fundoplication in our lung transplant recipients. A prospective case series of 44 lung transplant recipients who underwent laparoscopic Toupet fundoplication by a single surgeon between September 2018 and November 2020 was performed. Preoperative and postoperative results from 24-h pH, esophageal manometry, gastric emptying, and pulmonary function studies were collected alongside severity of gastroesophageal reflux disease and other gastrointestinal symptoms. Median DeMeester score decreased from 25.9 to 5.4 after fundoplication (p < 0.0001), while percentage of time pH < 4 decreased from 7 to 1.1% (p < 0.0001). The severity of heartburn and regurgitation were also reduced (p < 0.0001 and p = 0.0029 respectively). Overall, pulmonary function, esophageal motility, gastric emptying, severity of bloating, and dysphagia were not significantly different post-fundoplication than pre-fundoplication. Patients with decreasing rates of FEV1 pre-fundoplication saw improvement in their rate of change of FEV1 post-fundoplication (p = 0.011). Median follow-up was 32.2months post-fundoplication. Laparoscopic Toupet fundoplication provides objective pathologic acid reflux control and symptomatic gastroesophageal reflux improvement in lung transplant recipients while preserving lung function and foregut motility. Thus, laparoscopic Toupet fundoplication is a safe and effective antireflux surgery alternative in lung transplant recipients.

Role of Genetic Polymorphisms in the Efficacy and Adverse Effects of Metformin in the Treatment of Type 2 Diabetes Mellitus

Role of Genetic Polymorphisms in the Efficacy and Adverse Effects of Metformin in the Treatment of Type 2 Diabetes Mellitus

Natural Urease Inhibitors Reduce the Severity of Disease Symptoms, Dependent on the Lifestyle of the Pathogens.

The development of new anti-ureolytic compounds is of great interest due to the newly discovered role of urease inhibitors in crop protection. Purine degradation and the generation of ammonium by urease are required for the full virulence of biotrophic and hemibiotrophic fungal plant pathogens. Accordingly, chemicals displaying urease inhibitor activity may be used as a novel class of fungicides. Several urease inhibitors belonging to different chemical classes are known, and some compounds have been developed as urea fertilizer additives. We tested whether the natural urease inhibitors p-benzoquinone (p-HQ) and hydroquinone (HQ), as well as the synthetic inhibitors isopropoxy carbonyl phosphoric acid amide (iCPAA), benzyloxy carbonyl phosphoric acid amide (bCPAA), and dipropyl-hexamino-1,3 diphosphazenium chloride (DDC), prevent or delay plant infection caused by pathogens differing in lifestyles and host plants. p-BQ, HQ, and DCC not only protected maize from infection by the hemibiotroph C. graminicola, but also inhibited the infection process of biotrophs such as the wheat powdery mildew fungus Blumeria graminis f. sp. tritici and the broad bean rust fungus Uromyces viciae-fabae. Interestingly, the natural quinone-based compounds even reduced the symptom severity of the necrotrophic fungi, i.e., the grey mold pathogen B. cinerea and the Southern Leaf Spot fungus C. heterostrophus, to some extent. The urease inhibitors p-BQ, HQ, and DCC interfered with appressorial penetration and confirmed the appropriateness of urease inhibitors as novel fungicidal agents.

The Effect of Job Stress on the Severity of Coronavirus Disease Symptoms in Iranian Hospital Nurses

Introduction: Nurses' job stress during coronavirus disease is very high, which weakens the immune system. Furthermore, job stress plays an important role in the symptoms and clinical severity of this disease. Therefore, this study was conducted to determine the effect of job stress on the severity of coronavirus disease symptoms in hospital nurses in Iran.&#x0D; Materials and Methods: This cross-sectional descriptive-analytical study was carried out on 400 nurses with a history of coronavirus disease in hospitals in Tehran, Iran, in 2021. Demographic and occupational information and clinical status of the subjects were collected from medical records and self-reports. The level of job stress in the subjects was determined using Osipow questionnaire with Cronbach's alpha coefficient of 0.83. Finally, the data were analyzed using ANOVA and the Pearson test in SPSS 19 software.&#x0D; Results: The results of this study showed that the mean level of job stress increases with age, body mass index (BMI), and working hours (P &lt; 0.05). Also, the mean level of job stress was higher in contractual and smoking nurses (P &lt; 0.05). In this study, 20% of the subjects had severe job stress. Job stress decreased blood oxygen and increased the duration of shortness of breath and cough, gastrointestinal disorders, weakness and lethargy, and headache and dizziness in the subjects (P &lt; 0.05).&#x0D; Conclusion: Job stress in nurses experiencing coronavirus disease increases the severity and complete recovery time of coronavirus disease. It also increases the duration of the disease symptoms such as shortness of breath and cough, gastrointestinal disorders, weakness, headache, and vertigo.

Mycobacterium avium subsp. paratuberculosis Antigens Elicit a Strong IgG4 Response in Patients with Multiple Sclerosis and Exacerbate Experimental Autoimmune Encephalomyelitis.

Neuroinflammation can be triggered by microbial products disrupting immune regulation. In this study, we investigated the levels of IgG1, IgG2, IgG3, and IgG4 subclasses against the heat shock protein (HSP)70533-545 peptide and lipopentapeptide (MAP_Lp5) derived from Mycobacterium avium subsp. paratuberculosis (MAP) in the blood samples of Japanese and Italian individuals with relapsing remitting multiple sclerosis (MS). Additionally, we examined the impact of this peptide on MOG-induced experimental autoimmune encephalomyelitis (EAE). A total of 130 Japanese and 130 Italian subjects were retrospectively analyzed using the indirect ELISA method. Furthermore, a group of C57BL/6J mice received immunization with the MAP_HSP70533-545 peptide two weeks prior to the active induction of MOG35-55 EAE. The results revealed a significantly robust antibody response against MAP_HSP70533-545 in serum of both Japanese and Italian MS patients compared to their respective control groups. Moreover, heightened levels of serum IgG4 antibodies specific to MAP antigens were correlated with the severity of the disease. Additionally, EAE mice that were immunized with MAP_HSP70533-545 peptide exhibited more severe disease symptoms and increased reactivity of MOG35-55-specific T-cell compared to untreated mice. These findings provide evidence suggesting a potential link between MAP and the development or exacerbation of MS, particularly in a subgroup of MS patients with elevated serum IgG4 levels.

Clinical Characteristics and Outcomes Among Travelers With Severe Dengue : A GeoSentinel Analysis.

Dengue virus is a flavivirus transmitted by Aedes mosquitoes and is an important cause of illness worldwide. Data on the severity of travel-associated dengue illness are limited. To describe the epidemiology, clinical characteristics, and outcomes among international travelers with severe dengue or dengue with warning signs as defined by the 2009 World Health Organization classification (that is, complicated dengue). Retrospective chart review and analysis of travelers with complicated dengue reported to GeoSentinel from January 2007 through July 2022. 20 of 71 international GeoSentinel sites. Returning travelers with complicated dengue. Routinely collected surveillance data plus chart review with abstraction of clinical information using predefined grading criteria to characterize the manifestations of complicated dengue. Of 5958 patients with dengue, 95 (2%) had complicated dengue. Eighty-six (91%) patients had a supplemental questionnaire completed. Eighty-five of 86 (99%) patients had warning signs, and 27 (31%) were classified as severe. Median age was 34 years (range, 8 to 91 years); 48 (56%) were female. Patients acquired dengue most frequently in the Caribbean (n= 27 [31%]) and Southeast Asia (n= 21 [24%]). Frequent reasons for travel were tourism (46%) and visiting friends and relatives (32%). Twenty-one of 84 (25%) patients had comorbidities. Seventy-eight (91%) patients were hospitalized. One patient died of nondengue-related illnesses. Common laboratory findings and signs were thrombocytopenia (78%), elevated aminotransferase (62%), bleeding (52%), and plasma leakage (20%). Among severe cases, ophthalmologic pathology (n= 3), severe liver disease (n= 3), myocarditis (n= 2), and neurologic symptoms (n= 2) were reported. Of 44 patients with serologic data, 32 confirmed cases were classified as primary dengue (IgM+/IgG-) and 12 as secondary (IgM-/IgG+) dengue. Data for some variables could not be retrieved by chart review for some patients. The generalizability of our observations may be limited. Complicated dengue is relatively rare in travelers. Clinicians should monitor patients with dengue closely for warning signs that may indicate progression to severe disease. Risk factors for developing complications of dengue in travelers need further prospective study. Centers for Disease Control and Prevention, International Society of Travel Medicine, Public Health Agency of Canada, and GeoSentinel Foundation.

Sugar Beet Root Storage Properties Are Unaffected by Cercospora Leaf Spot.

Cercospora leaf spot (CLS; causal agent Cercospora beticola Sacc.) is endemic in many sugar beet production regions due to the widespread distribution of C. beticola and the inability of current management practices to provide complete control of the disease. Roots harvested from plants with CLS, therefore, are inevitably incorporated into sugar beet root storage piles, even though the effects of CLS on root storage properties are largely unknown. Research was conducted to determine the effects of CLS on storage properties including root respiration rate, sucrose loss, invert sugar accumulation, loss in recoverable sucrose yield, and changes in sucrose loss to molasses with respect to CLS disease severity and storage duration. Roots were obtained from plants with four levels of CLS severity in each of three production years, stored at 5°C and 95% relative humidity for up to 120 days, and evaluated for storage characteristics after 30, 90, and 120 days storage. No significant or repeatable effects of CLS on root respiration rate, sucrose loss, invert sugar accumulation, loss in recoverable sucrose yield, or change in sucrose loss to molasses were detected after 30, 90, or 120 days storage regardless of the severity of CLS disease symptoms. Therefore, no evidence was found that CLS accelerates sugar beet storage losses, and it is concluded that roots harvested from plants with CLS can be stored without additional or specialized precaution, regardless of CLS symptom severity.

Learning Hand Kinematics for Parkinson's Disease Assessment Using a Multimodal Sensor Glove.

Hand dysfunctions in Parkinson's disease include rigidity, muscle weakness, and tremor, which can severely affect the patient's daily life. Herein, a multimodal sensor glove is developed for quantifying the severity of Parkinson's disease symptoms in patients' hands while assessing the hands' multifunctionality. Toward signal processing, various algorithms are used to quantify and analyze each signal: Exponentially Weighted Average algorithm and Kalman filter are used to filter out noise, normalization to process bending signals, K-Means Cluster Analysis to classify muscle strength grades, and Back Propagation Neural Network to identify and classify tremor signals with an accuracy of 95.83%. Given the compelling features, the flexibility, muscle strength, and stability assessed by the glove and the clinical observations are proved to be highly consistent with Kappa values of 0.833, 0.867, and 0.937, respectively. The intraclass correlation coefficients obtained by reliability evaluation experiments for the three assessments are greater than 0.9, indicating that the system is reliable. The glove can be applied to assist in formulating targeted rehabilitation treatments and improve hand recovery efficiency.

A Narrative Review on the Potential Role of Vitamin D3 in the Prevention, Protection, and Disease Mitigation of Acute and Long COVID-19.

The coronavirus disease 2019 (COVID-19) pandemic has challenged global health systems and economies from January 2020. COVID-19 caused by the infectious severe acute respiratory syndrome coronavirus (SARS-CoV-2) has acute respiratory and cardiometabolic symptoms that can be severe and lethal. Long-term physiological and psychological symptoms, known as long COVID-19, persist affecting multiple organ systems. While vaccinations support the fight against SARS-CoV-2, other effective mechanisms of population protection should exist given the presence of yet unvaccinated and at-risk vulnerable groups, global disease comorbidities, and short-lived vaccine responses. The review proposes vitamin D3 as a plausible molecule for prevention, protection, and disease mitigation of acute and long COVID-19. Epidemiological studies have shown that individuals who were deficient in vitamin D3 had worse COVID-19 health outcomes and mortality rates. Higher doses of vitamin D3 supplementation may improve health and survivorship in individuals of various age groups, comorbidities, and severity of disease symptoms. Vitamin D3's biological effects can provide protection and repair in multiple organ systems affected by SARS-CoV-2. Vitamin D3 supplementation can potentially support disease-mitigation in acute and long COVID-19.

The Evaluation of Hematological Parameters and Their Correlation with Disease Prognosis in COVID-19 Disease in Iran.

Background: Since 2019, Coronavirus has been a highly contagious disease. The COVID-19 outbreak was declared a pandemic by the World Health Organization in March 2020. Variable laboratory findings are reported in COVID-19 patients, among which elevated levels of D-dimer, lactate dehydrogenase, as well as lymphopenia, have been reported to be associated with increased severity of disease symptoms requiring ventilator support, intensive care unit admission, and mortality. Materials and Methods: In the current study, inclusion criteria were: patient age above 18 years and hospitalization in the Imam Khomeini hospital with COVID-19 disease confirmed with nasopharyngeal swab polymerase chain reaction tests. Levels of white blood cells, neutrophils, lymphocytes, hemoglobin, platelets, D-dimer, C-reactive protein, LDH, and ferritin were measured and their correlation with the final patients' outcome was evaluated. Results: A total of 208 patients were included in the present study. Higher neutrophil to lymphocyte ratio, (WBC count excluding lymphocyte)/lymphocyte, LDH, platelet to lymphocyte ratio, ferritin, and D-dimer were significantly related to O2 dependency. Neutrophil to lymphocyte ratio, (WBC count excluding lymphocyte)/lymphocyte and LDH were significantly related to higher rates of mortality. Higher Hb and lymphocyte count were significantly related to higher rates of survival. Conclusion: Hematological parameters including neutrophil to lymphocyte ratio, (WBC count excluding lymphocyte)/lymphocyte, LDH, platelet to lymphocyte ratio, ferritin, D-dimer, Hb, and lymphocyte count were significantly related to the prognosis of patients with COVID-19 disease. This could help decide which COVID-19 patients have priority for hospitalization and intensive medical care, particularly when the pandemic disease causes limitations in healthcare service.

Evaluating the Effect of a Bruton’s Tyrosine Kinase Inhibitor in a Murine Experimental Autoimmune Encephalomyelitis Model of Multiple Sclerosis (P2-3.012)

<h3>Objective:</h3> To characterize a central nervous system (CNS)-penetrant, tolebrutinib-like Bruton’s tyrosine kinase inhibitor (BTKi) in murine experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis (MS) for its potential to modulate disease progression and expression of genes linked to disease-associated microglia (DAM). <h3>Background:</h3> BTK inhibition may slow disease progression in people with MS by targeting microglia-driven neuroinflammation in the CNS. We previously showed that a structural analogue of the BTKi tolebrutinib can reduce BTK-dependent inflammatory signalling in microglia in the mouse brain, using the cuprizone-mediated model of demyelination. <h3>Design/Methods:</h3> Female C57BL/6 mice were immunized with MOG_35–55 peptide (250 μg/mouse; two subcutaneous injections in the lower back) to induce EAE. Animals were randomized to receive vehicle (n=15) or oral BTKi (15 mg/kg; n=15), starting at clinical score of 1.0–1.5. Treatment groups were blinded until after final data analysis. Cohorts were monitored daily for development and severity of disease symptoms. After 10 days of treatment, spinal cord and plasma samples were taken for transcriptome analysis and neurofilament heavy chain (NfH) concentration measurement, respectively. <h3>Results:</h3> BTK inhibition significantly reduced the clinical score in the EAE mice, with significant differences between treatment groups starting after two days of treatment and continuing until end of study (Day 10). BTK inhibition significantly reduced plasma Nfh concentrations. A BTK-dependent transcriptional signature was identified, with BTK inhibition found to modulate pathways relevant to MS pathology. BTK inhibition modulated mRNA expression of genes that had previously been linked to DAM and/or are associated with BTK-signalling. <h3>Conclusions:</h3> We extended our previous <i>in vivo</i> findings from a demyelination model by demonstrating that dosing with a BTKi halted disease progression in an immune-mediated model of MS. This therapeutic benefit was accompanied by modulated expression of genes associated with activated microglia, which could abrogate microglia-driven neuroinflammation implicated in disease progression in MS. <b>Disclosure:</b> Dr. Gruber has received personal compensation for serving as an employee of Sanofi. Dr. Gruber has received stock or an ownership interest from Sanofi. Dr. Blazier has received personal compensation for serving as an employee of Sanofi. Lan Lee has nothing to disclose. Dr. Ryan has nothing to disclose. Dr. Cheong has received personal compensation for serving as an employee of Sanofi. Ms. Havari has received personal compensation for serving as an employee of sanofi. Timothy J. Turner has received personal compensation for serving as an employee of Sanofi. Timothy J. Turner has received stock or an ownership interest from Sanofi. Timothy J. Turner has received intellectual property interests from a discovery or technology relating to health care. Dimitry Ofengeim has received personal compensation for serving as an employee of Sanofi. Dimitry Ofengeim has received stock or an ownership interest from Sanofi. Dimitry Ofengeim has received personal compensation in the range of $500-$4,999 for serving as a Study Section Reveiwer with NIH.

Efficacy of Biological Control Agents and Resistance Inducer for Control of Mal Secco Disease.

Mal secco, caused by Plenodomus tracheiphilus, is an economically important fungal vascular disease in citrus-growing countries of the Mediterranean basin. Preventing fungal infections usually requires a high number of copper treatments but European legislation imposes the minimization of their accumulation in soil. In our study, biological control agents (BCAs) and a plant resistance inducer (PRI), tested in four different experiments on citrus seedlings under controlled conditions, have resulted in promising strategies to control mal secco disease. Foliar (Experiment I) and soil (Experiment II) applications of two formulations of Bacillus amyloliquefaciens strain D747 (Amylo-X® LC and Amylo-X® WG) provided similar performances in reducing the disease amount (incidence and symptoms severity) over time compared to the untreated control, whereas copper hydroxide (Kocide Opti®) used as standard was the most effective treatment over time. In the third experiment, Pythium oligandrum strain M1 (Polyversum®) and Trichoderma asperellum strain ICC012 + Trichoderma gamsii strain ICC080 (Remedier®) were able to reduce disease incidence and symptoms severity compared to the untreated control. Remedier® provided the best performances in reducing the disease amount, whereas the Polyversum® application was the least effective treatment over time. The effectiveness of the Trichoderma spp. formulation in reducing P. tracheiphilus infections did not significantly differ from the standard copper compound (Kocide Opti®). Comprehensively, in the last experiment (IV), acibenzolar-S-methyl (ASM) alone and in mixture with metalaxyl-M proved as effective as B. amyloliquefaciens strain FZB24, with no dose-response relationships observed. These findings provide important insight for the integrated management of mal secco disease.

Optimising Decision Making in Chronic Venous Disease Management with Micronised Purified Flavonoid Fraction.

Evidence-based medicine favours randomised controlled trials to limit bias and establish the effects of a treatment with statistical rigour. However, the controlled conditions and careful patient selection of randomised trials may produce results that cannot be generalised to a more diverse patient population in clinical practice. Therefore, there is growing recognition of the importance of supplementing randomised trial data with real-world evidence. Micronised purified flavonoid fraction has been investigated in several large-scale real-world studies, including the RELIEF and DECIDE studies, each of which included more than 1000 patients with chronic venous disease. These studies demonstrated a significant reduction in the prevalence and severity of chronic venous disease symptoms, and an improvement in quality of life. The chronic VEnous dIsorders maNagement and treatment effectivenesS evaluaTion in chronic vEnous disease, an international Program (VEINSTEP) study (NCT04574375), is currently underway in more than 6000 patients with chronic venous disease in nine countries. Preliminary data from one country (Morocco) indicate that chronic venous disease drug treatment, which was micronised purified flavonoid fraction in 75.7% of patients, was associated with a statistically significantly reduction in symptoms and improved quality of life. The overall results are awaited with interest. International chronic venous disease guidelines grade the evidence for micronised purified flavonoid fraction highly, as the benefits of micronised purified flavonoid fraction have been proven in randomised clinical trials and meta-analyses. Real-world studies demonstrate that the randomised evidence for micronised purified flavonoid fraction is generalisable to a clinical practice setting. Treatment decisions in chronic venous disease should consider evidence-based recommendations, including real-world data, as well as patient goals of symptom relief, functional improvement and/or better quality of life.

Integrated systems immunology approach identifies impaired effector T cell memory responses as a feature of progression to severe dengue fever

BackgroundTypical symptoms of uncomplicated dengue fever (DF) include headache, muscle pains, rash, cough, and vomiting. A proportion of cases progress to severe dengue hemorrhagic fever (DHF), associated with increased vascular permeability, thrombocytopenia, and hemorrhages. Progression to severe dengue is difficult to diagnose at the onset of fever, which complicates patient triage, posing a socio-economic burden on health systems.MethodsTo identify parameters associated with protection and susceptibility to DHF, we pursued a systems immunology approach integrating plasma chemokine profiling, high-dimensional mass cytometry and peripheral blood mononuclear cell (PBMC) transcriptomic analysis at the onset of fever in a prospective study conducted in Indonesia.ResultsAfter a secondary infection, progression to uncomplicated dengue featured transcriptional profiles associated with increased cell proliferation and metabolism, and an expansion of ICOS+CD4+ and CD8+ effector memory T cells. These responses were virtually absent in cases progressing to severe DHF, that instead mounted an innate-like response, characterised by inflammatory transcriptional profiles, high circulating levels of inflammatory chemokines and with high frequencies of CD4low non-classical monocytes predicting increased odds of severe disease.ConclusionsOur results suggests that effector memory T cell activation might play an important role ameliorating severe disease symptoms during a secondary dengue infection, and in the absence of that response, a strong innate inflammatory response is required to control viral replication. Our research also identified discrete cell populations predicting increased odds of severe disease, with potential diagnostic value.

High non-compliance rate among presumptive tuberculosis cases referred from peripheral health facilities in silti district of Southern Ethiopia: a mixed methods study

BackgroundFor presumptive Tuberculosis (TB) case referral to be effective, most of the referred cases need to present themselves to health facilities for assessment and testing. Otherwise, cases of TB could be missed, and these cases are at an increased risk of delayed diagnosis, complications and death. Further, their care incurs significantly higher costs. This study assessed referral compliance as well as factors attributable to compliance/non-compliance to referral of presumptive TB cases in Silti district, Southern Ethiopia.MethodWe applied a mixed design involving both quantitative and qualitative methods. A randomly selected sample of 384 presumptive TB cases referred between January, 2014 and July 2021 were included in this study from the records of 12 health posts. Purposefully selected presumptive TB cases and Health Extension Workers were also interviewed to get in-depth information on the reasons for compliance and non-compliance to referral. STATA version 14 was employed to model the data using logistic regression. Qualitative data were analyzed using thematic content analysis.ResultsOf the 384 referred presumptive TB cases, close to 49% did not present themselves to the referral facilities. About 66% (n = 249) of the referred cases were women, and 62% (n = 119) of those who complied to referral were women. In multivariate analysis, cough [AOR = 3.4, 95%CI: 1.54–7.32], and chest pain [AOR = 2.7, 95%CI: 1.45–5.05] were independent predictors of compliance to referral. Nearly 5.5% (n = 21) of TB cases of all types were identified. The qualitative data analysis revealed that severe disease symptoms, HEW’s recommendations, and social issues as reasons improving compliance while personal and social factors, financial problems, lack of awareness about TB and transportation were reasons impeding compliance to referral.ConclusionOur study showed a high level of non-compliance to referral among referred presumptive TB cases. We also found that more women were referred and also complied with the referral. Strengthening community awareness about the disease symptoms and the existence of free treatment, addressing misconceptions about TB, supporting the elderly and disabled, and checkup house visits after referral could improve compliance to referral.

Relationship between the ABO blood group and Rhesus factors with COVID-19 susceptibility

ABSTRACT Introduction The molecular research has raised copious hypotheses about different molecular effects on the variable expression of the current virus on the human body. The present prospective study aims to determine clinically as well as statistically, the relation between ABO blood groups and Rhesus (Rh) factor and the severity of the Covid-19 virus. Research design and methods We conducted a prospective, single-centered study at The Combined Military Hospital Lahore, Pakistan. Details of only those patients who exhibit COVID-19 symptoms were included. The odds ratios with a 95% confidence interval and the chi-square test of blood groups and Rhesus factor was also conducted individually with the severity of disease, outcomes, and respiratory symptoms. P-values less than 0.05 was considered significant. Results The chi-square test and odd ratio yielded no significant results when the covid-19 status was compared with the Rhesus factor (p-value > 0.05). However, the results were found to be significant when associations were run between Covid-19 status and all the blood groups (p-value < 0.05). Conclusion According to the analytical results of the present study, protective nature of all the blood antigens (A, B, AB, none) was observed in patients presenting with Covid-19 symptoms of varying severity.

Mechanistic insight into the protective and pathogenic immune-responses against SARS-CoV-2.

COVID-19 is a severe respiratory illness that has emerged as a devasting health problem worldwide. The disease outcome is heterogeneous, which is most likely dependent on the immunity of an individual. Asymptomatic and mildly/moderate symptomatic (non-severe) patients likely develop an effective early immune response and clear the virus. However, severe symptoms dominate due to a failure in the generation of an effective and specific early immune response against SARS-CoV-2. Moreover, a late surge in pathogenic inflammation involves dysregulated innate and adaptive immune responses leading to local and systemic tissue damage and the emergence of severe disease symptoms. In this review, we describe the potential mechanisms of protective and pathogenic immune responses in "mild/moderate" and "severe" symptomatic SARS-CoV-2 infected people, respectively, and discuss the immune components that are currently targeted for therapeutic intervention.

Development of Highly Efficient Resistance to Beet Curly Top Iran Virus (Becurtovirus) in Sugar Beet (B. vulgaris) via CRISPR/Cas9 System.

Beet Curly Top Iran Virus (BCTIV, Becurtovirus) is a dominant and widespread pathogen responsible for great damage and yield reduction in sugar beet production in the Mediterranean and Middle East. CRISPR-based gene editing is a versatile tool that has been successfully used in plants to improve resistance against many viral pathogens. In this study, the efficiency of gRNA/Cas9 constructs targeting the expressed genes of BCTIV was assessed in sugar beet leaves by their transient expression. Almost all positive control sugar beets revealed systemic infection and severe disease symptoms (90%), with a great biomass reduction (68%) after BCTIV agroinoculation. On the other hand, sugar beets co-agronioculated with BCTIV and gRNA/Cas9 indicated much lower systemic infection (10-55%), disease symptoms and biomass reduction (13-45%). Viral inactivation was also verified by RCA and qPCR assays for gRNA/Cas9 treated sugar beets. PCR-RE digestion and sequencing assays confirmed the gRNA/Cas9-mediated INDEL mutations at the target sites of the BCTIV genome and represented high efficiencies (53-88%), especially for those targeting BCTIV's movement gene and its overlapping region between capsid and ssDNA regulator genes. A multiplex CRISPR approach was also tested. The most effective four gRNAs targeting all the genes of BCTIV were cloned into a Cas9-containing vector and agroinoculated into virus-infected sugar beet leaves. The results of this multiplex CRISPR system revealed almost complete viral resistance with inhibition of systemic infection and mutant escape. This is the first report of CRSIPR-mediated broad-spectrum resistance against Becurtovirus in sugar beet.

Potential predictive value of CT radiomics features for treatment response in patients with COVID-19.

This study aims to explore the predictive value of CT radiomics and clinical characteristics for treatment response in COVID-19 patients. Data were collected from clinical/auxiliary examinations and follow-ups of COVID-19 patients. Whole lung radiomics feature extraction was performed at baseline chest CT. Radiomics, clinical, and combined features (nomogram) were evaluated for predicting treatment response. Among 36 COVID-19 patients, mild, common, severe, and critical disease symptoms were found in 1, 21, 13, and 1 of them, respectively. Twenty-five (1 mild, 18 common, and 6 severe) patients showed a good response to treatment and 11 poor/fair responses. The clinical classification (p = 0.025) and serum creatinine (p = 0.010) on admission and small area emphasis (p = 0.036) from radiomics analysis significantly differed between the two groups. Predictive models were constructed based on the radiomics, clinical features, and nomogram showing an area under the curve of 0.651, 0.836, and 0.869, respectively. The nomogram achieved good calibration. This new, non-invasive, and low-cost prediction model that combines the radiomics and clinical features is useful for identifying COVID-19 patients who may not respond well to treatment.