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Betel quid chewing is a culturally significant practice among the indigenous people (Orang Asli) in Malaysia, but it poses serious health risks, including oral cancer and systemic diseases. Studies on betel quid chewing are limited, making it difficult to develop effective public health interventions. This study aimed to explore the cultural significance, perceived health effects, and misconceptions surrounding betel quid chewing among the indigenous people, assess their awareness of health risks, and explore factors influencing their intentions to quit or reduce betel quid chewing. A qualitative phenomenological design was used, with five groups of Focus Group Discussions conducted with 15 participants from an Orang Asli village in Johor. The discussions revealed that betel quid chewing is deeply embedded in Orang Asli culture, often beginning in childhood and associated with social and ceremonial occasions. However, awareness of health risks, particularly oral cancer, was inconsistent. Social support and personal motivation were critical in influencing quitting behaviors. These findings highlight the need for culturally tailored cessation programs that address the unique social and environmental factors influencing betel quid use in this population.
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Unicameral bone cysts (UBCs) are noncancerous, fluid-containing sacs commonly seen in the metaphysis of long bones among young individuals, mainly affecting the proximal humerus and femur. Since they are painless, 80% of patients do not experience any symptoms from UBCs unless it is complicated by a pathological or stress fracture. These patients usually present with no history of trauma, with mild pain, local tenderness, and occasionally swelling. The diagnosis of UBCS can either be an incidental finding or can be made with the help of clinical features, radiographs, and differential diagnoses of UBCs like aneurysmal bone cyst, fibrous dysplasia, enchondroma, eosinophilic granuloma, and intraosseous ganglia can be ruled out. While identifying these cysts is often straightforward, there is ongoing debate regarding the optimal management approach. We report a case of a 16-year-old female with proximal humerus UBC who presented with a pathological fracture of the right proximal humerus. The patient was initially managed conservatively. However, she sustained a refracture at the same site twice over four years. Due to fracture recurrence and residual deformity, it was treated surgically with curettage, bone grafting, and internal fixation. The normal alignment and function of the right upper limb were restored postoperatively.
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Cadmium, a hazardous heavy metal prevalent in plants and soil, poses a significant threat to human health, particularly as approximately 60% of the global population consumes wheat, which can accumulate high levels of Cd through its roots. This uptake leads to the translocation of Cd to the shoots and grains, exacerbating the potential health risks. However, promising results have been observed with the use of moringa leaf extract (MLE) foliar spray in mitigating the adverse effects of Cd stress. The current experiment was conducted to find out the Cd stress tolerance of wheat varieties V1 = Akbar-19 and V2 = Dilkash-2020 under exogenous spray of MLE. The treatments of this study were T0 = 0% MLE + 0 µM Cd, T1 = 3% MLE + 0 µM Cd, T2 = 0% MLE + 400 µM Cd, and T3 = 3% MLE + 400 µM Cd. Cd stress demonstrated a significant reduction in morphological attributes as shoot and root fresh weight (22%), shoot and root dry weight (24.5%), shoot and root length (22.5%), area of leaf and number of leaves 30.5%, and photosynthetic attributes (69.8%) in comparison with control. Exposure of wheat plants to Cd toxicity cause oxidative stress, increased H2O2, and MDA up to 75% while foliar application of MLE reduced the activities of reactive oxygen species (ROS). The activity of catalase (CAT), superoxide dismutase (SOD), peroxidase (POD), and ascorbic acid (AsA) increased up to 81.5% as well as organic osmolytes such as phenolics, total soluble proteins, and total soluble sugars were improved up to 77% by MLE applications under Cd stress. Higher accumulation of ionic contents root Na+ (22%) and Cd (44%) was documented in plants under Cd stress as compared to control, while uptake of root mineral ions Ca2+ and K+ was 35% more in MLE-treated plants. In crux, Cd toxicity significantly declined the growth, photosynthetic, and biochemical parameters while 3% MLE application was found effective in alleviating the Cd toxicity by improving growth and physiological parameters while declining reactive oxygen species and root Na+ as well as Cd uptake in wheat.
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BACKGROUND: Hypertension affects 26.7% of Pakistan's population, with only 6% achieving control. This study investigates antihypertensive medication adherence in Multan, focusing on socioeconomic and patient-related factors influencing non-adherence to study the lack of adherence to antihypertensive medications in hypertensive patients and its associated factors at Nishtar Hospital in Multan, Pakistan. METHODS: This cross-sectional study was conducted among hypertensive patients admitted at Nishtar Hospital Multan, Pakistan. Patients under the age of 20 years were excluded from the study. A self-developed questionnaire was used to gather the demographic details of patients. The Hill-Bone Medication Adherence Scale was used via a non-probability convenience sampling technique to deduce the adherence level in patients. Data analysis was done using SPSS (Statistical Package for the Social Sciences) v23 (IBM Corp., Armonk, NY). p-value < 0.05 was considered significant. RESULTS: Out of 217 respondents, most were female, married, unemployed, and residing in urban areas. Most of them had a higher level of education and a monthly income averaging below 30,000 PKR (Pakistani Rupee). The insight into the hypertensive history showed that most of them had a positive family history and comorbid conditions, and were hypertensive for more than five years. The majority of the patients had a complex regimen prescribed to them with multiple doses throughout the day. The minority were smokers and had medications provided to them for free, through public or government-funded institutions. More importantly, adherence to the antihypertensive therapy was negatively correlated with the age of the patients (p = 0.004, r = -0.195), complexity of regimen (p = 0.041), multiple dosing (p = 0.039), and cost of medication (p = 0.043). All of these relations were statistically significant. CONCLUSION: Lack of adherence to antihypertensive medications in hypertensive patients is more common in populations belonging to older age groups, complex regimens, multiple doses, and higher medicine fees.
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INTRODUCTION: Monkeypox (mpox) is an illness caused by the MPX virus and endemic to certain African countries. Historically, sporadic outbreaks have occurred in some non-endemic areas. In 2022, a new variant emerged, clade IIb, causing a global outbreak sustained within sexual networks among men who have sex with men (MSM). To our knowledge, this is the first multi-country study examining mpox epidemiology and clinical features of the 2022-2023 outbreak caused by clade IIb across the Eastern Mediterranean Region (EMR). METHODS: We analyzed datasets of anonymous mpox case-based reports submitted to the World Health Organization (WHO) from May 2022 to December 2023 in the EMR to describe the cumulative incidence, demographics, transmission routes, and clinical outcomes. RESULTS: By the end of 2022, 95 case reports were submitted to the WHO. The first case of mpox was reported in the United Arab Emirates on May 24, 2022. The highest number of cases were reported from Lebanon (27 confirmed cases). Most cases in the EMR were adult males (92 %), 60 % identifying as MSM, and 10 % living with HIV. Most reported symptoms were rash (95.4 %) and fever (69.6 %). No intensive care unit admissions or deaths were reported. CONCLUSION: In this study we investigated the epidemiology, clinical presentation, and outcomes of the mpox outbreak related to clade IIb in the EMR. We raise concerns about the accuracy and completeness of the data, given that the number of cases reported to the WHO from EMR countries appears to be significantly lower than the number of cases documented within the region. This discrepancy could impact the reliability of the reported figures and the region's response strategies. Despite these challenges, collaborative efforts across EMR countries have laid the groundwork for effective outbreak response, underscoring the importance of ongoing regional cooperation to enhance future preparedness strategies.
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Surtos de Doenças , Mpox , Humanos , Masculino , Adulto , Feminino , Mpox/epidemiologia , Adulto Jovem , Região do Mediterrâneo/epidemiologia , Pessoa de Meia-Idade , Saúde Pública , Adolescente , Incidência , Homossexualidade Masculina/estatística & dados numéricos , Monkeypox virusRESUMO
INTRODUCTION: Social network-based testing approaches (SNAs) encourage individuals ("test promoters") to motivate sexual partners and/or those in their social networks to test for HIV. We conducted a systematic review to examine the effectiveness, acceptability and cost-effectiveness of SNA. METHODS: We searched five databases from January 2010 to May 2023, and included studies that compared SNA with non-SNA. We used random-effects meta-analysis to combine effect estimates. Certainty was assessed using the GRADE approach. RESULTS: We identified 47 studies. SNA may increase uptake of HIV testing compared to non-SNA (RR 2.04, 95% CI: 1.06-3.95, Low certainty). The proportion of first-time testers was probably higher among partners or social contacts of test promoters using SNA compared to non-SNA (RR 1.49, 95% CI: 1.22-1.81, Moderate certainty). The proportion of people who tested positive for HIV may be higher among partners or social contacts of test promoters using SNA compared to non-SNA (RR 1.84, 95% CI: 1.01-3.35, Low certainty). There were no reports of any adverse events or harms associated with SNA. Based on six cost-effectiveness studies, SNA was generally cheaper per person tested and per person diagnosed compared to non-SNA. Based on 23 qualitative studies, SNA is likely to be acceptable to a variety of populations. DISCUSSION: Our review collated evidence for SNA to HIV testing covering the key populations and the general population who may benefit from HIV testing. We summarized evidence for the effectiveness, acceptability and cost-effectiveness of different models of SNA. While we did not identify an ideal model of SNA that could be immediately scaled up, for each setting and population targeted, we recommend various implementation considerations as our meta-analysis showed the effectiveness might differ due to factors which include the testing modality (i.e. use of HIV self-testing), type of test promoters, long or short duration of recruitment and use of financial incentives. CONCLUSIONS: Social network-based approaches may enhance HIV testing uptake, increase the proportion of first-time testers and those testing positive for HIV. Heterogeneity among studies highlights the need for context-specific adaptations, but the overall positive impact of SNA on HIV testing outcomes could support its integration into existing HIV testing services.
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Infecções por HIV , Teste de HIV , Humanos , Infecções por HIV/diagnóstico , Teste de HIV/métodos , Análise Custo-Benefício , Rede Social , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Apoio Social , Parceiros SexuaisRESUMO
A rare histological variant of transitional cell urothelial carcinoma, the plasmacytoid variant, was recently included in the World Health Organization classification of urothelial tract tumors. This variant has a morphological resemblance to other tumors, which poses a diagnostic challenge for identifying this tumor and may often lead to misdiagnosis. Vigilant histopathological analysis and immunostaining are required to delineate the correct diagnosis. The plasmacytoid variant of urothelial carcinoma is an aggressive tumor with a poor prognosis, making correct diagnosis essential for early and appropriate treatment. This paper presents the case of a 46-year-old male with a plasmacytoid variant of high-grade urothelial carcinoma who underwent transurethral resection of a bladder tumor, received chemotherapy, and is currently undergoing follow-up.
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Crystalline ZIF-8 (C-ZIF-8) and amorphous ZIF-8 (Am-ZIF-8) were prepared and investigated to control the germination of Striga hermonthica, a root parasitic plant, which threatens cereal crops production particularly in sub-Saharan Africa. We have demonstrated that Am-ZIF-8 shows a better performance than C-ZIF-8 in inhibiting Striga seed germination. This efficient performance of Am-ZIF-8 materials can be attributed to the incomplete deprotonation of 2 methylimidazole (2MIM) during amorphization, leading to the presence of unsaturated Zn-N coordination with the uncoordinated -NH groups available to undergo hydrogen bonding with the strigolactone analog GR24 forming a more stable Am-ZIF-8···GR24 hydrogen bonded network. We further established that application of ZIF-8 materials generally has no adverse effects on the growth and quality of rice crops.
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PURPOSE: To investigate retinal capillary plexus capillary flow speed and vessel density in diabetic retinopathy (DR) and normal subjects using variable interscan time analysis (VISTA) optical coherence tomography angiography (OCTA). METHODS: High speed swept source OCTA imaging using multiple interscan times was performed over a 5 mm x 5 mm field-of-view with 600 kHz A-scan rate. Second-generation VISTA OCTA was used to measure a surrogate marker for capillary blood flow speed, VISTA flow speed (VFS), in the superficial and intermediate capillary plexuses, (SCP + ICP)VFS, and deep capillary plexus, DCPVFS. Vessel density was measured using OCTA. RESULTS: Fifty-seven eyes with different DR severity and 37 normal eyes were analyzed. VISTA OCTA provided diverse blood flow speed information, including pseudo-color OCTA and mean flow speed in different regions. Both DCPVFS and DCPVFS/(SCP + ICP)VFS were higher in DR compared to normal eyes. Elevated DCPVFS correlated with decreased DCP vessel density in non-proliferative DR. CONCLUSION: VISTA OCTA can measure a quantitative biomarker for blood flow speed alterations in DR and normal eyes as well as the association with vessel density in different capillary plexuses. VISTA OCTA is promising for studies of pathogenesis and early flow alterations which may precede non-perfusion.
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The yield of pearl millet, a resilient cereal crop crucial for African food security, is severely impacted by the root parasitic weed Striga hermonthica, which requires host-released hormones, called strigolactones (SLs), for seed germination. Herein, we identify four SLs present in the Striga-susceptible line SOSAT-C88-P10 (P10) but absent in the resistant 29Aw (Aw). We generate chromosome-scale genome assemblies, including four gapless chromosomes for each line. The Striga-resistant Aw lacks a 0.7 Mb genome segment containing two putative CARLACTONOIC ACID METHYLTRANSFERASE1 (CLAMT1) genes, which may contribute to SL biosynthesis. Functional assays show that P10CLAMT1b produces the SL-biosynthesis intermediate methyl carlactonoate (MeCLA) and that MeCLA is the precursor of P10-specific SLs. Screening a diverse pearl millet panel confirms the pivotal role of the CLAMT1 section for SL diversity and Striga susceptibility. Our results reveal a reason for Striga susceptibility in pearl millet and pave the way for generating resistant lines through marker-assisted breeding or direct genetic modification.
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Genoma de Planta , Lactonas , Pennisetum , Striga , Striga/genética , Lactonas/metabolismo , Pennisetum/genética , Pennisetum/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Cromossomos de Plantas/genética , Doenças das Plantas/parasitologia , Doenças das Plantas/genética , Metiltransferases/metabolismo , Metiltransferases/genética , Plantas Daninhas/genética , Plantas Daninhas/metabolismo , Resistência à Doença/genética , Reguladores de Crescimento de Plantas/metabolismoRESUMO
AIM AND BACKGROUND: Chronic kidney disease (CKD) is associated with increased cardiovascular morbidity and mortality. This study aimed to assess the frequency of cardiac abnormalities across different stages of CKD, providing insights into the relationship between renal dysfunction and cardiac abnormalities. MATERIAL AND METHODS: A cross-sectional observational study was conducted at Lahore General Hospital's Nephrology Department, enrolling 356 non-dialysis CKD patients (stages I-V) over one year. Participants aged 18-65 years with CKD duration of three months or more were included. Exclusion criteria encompassed dialysis dependency, transplantation, acute kidney injury, and various cardiac conditions. Detailed echocardiographic evaluation of cardiac structure and function was noted. RESULTS: This study included 356 patients with CKD across stages I-V, with the majority in stages III (44.7%) and IV (36.5%). Significant variations were observed in age (p<0.000), hypertension prevalence (p=0.004), and smoking status. Haemoglobin, calcium, and phosphate levels differed significantly across stages (p<0.001). Echocardiographic findings revealed significant differences: left ventricular hypertrophy frequency increased from 12.5% in stages I-II to 60.0% in stage V (p=0.001); diastolic dysfunction worsened, with grades 2-3 dysfunction increasing from 6.2% in stages I-II to 51.4% in stage V (p=0.000); systolic dysfunction increased with reduced ejection fraction (<45%) more common in advanced stages (p=0.000); global longitudinal strain worsened from -18.47% to -15.34% (p=0.000); left atrial volume index and pulmonary hypertension also increased significantly (p=0.049). CONCLUSION: This study demonstrates a significant correlation between the progression of CKD and the severity of echocardiographic abnormalities. As CKD advances, structural and functional cardiac abnormalities increase, underscoring the importance of early cardiac evaluation and intervention to improve cardiovascular outcomes in non-dialysis-dependent CKD patients.
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AIM AND BACKGROUND: This study aimed to evaluate the quality of life (QoL) in end-stage kidney disease (ESRD) patients on maintenance hemodialysis through the Missoula-Vitas Quality of Life Index-15 (MVQOLI-15) to identify factors affecting their well-being. MATERIALS AND METHODS: A cross-sectional study was conducted at the Dialysis Unit of the Nephrology Department, Nishtar Hospital Multan. Over six months, 140 eligible patients were enrolled using non-probability consecutive sampling. Participants aged 18-80 years on maintenance hemodialysis for at least six months were evaluated using the MVQOLI-15 questionnaire assessing symptoms, function, interpersonal, well-being, and transcendence dimensions of QoL. Data were analyzed using the IBM SPSS Statistics for Windows, Version 26 (Released 2019; IBM Corp., Armonk, New York). Inferential statistical tests, including the t-test for comparing two groups and analysis of variance (ANOVA) for comparing multiple groups, were utilized to determine the significance of differences in QoL scores among different demographic and clinical categories. P-values less than 0.05 were considered statistically significant. RESULTS: The study analyzed 140 hemodialysis patients, with a mean age of 52.41 ± 16.31 years and an average hemodialysis duration of 4.55 ± 2.46 years. Most participants were aged 61-80 years (35.7%), had secondary education (44.3%), and were married (67.1%). QoL scores, measured using the MVQOLI, indicated mean values for symptoms at 4.51 ± 10.71, function at 5.77 ± 8.04, interpersonal at 7.49 ± 13.67, well-being at -13.60 ± 7.11, transcendence at 8.24 ± 13.12, and a total score of 16.24 ± 2.75. Significant findings include the following: females had higher symptom scores (p=0.001) and lower well-being scores (p=0.000); younger patients (<30 years) had higher function scores (p=0.054); patients on hemodialysis three times per week had higher function scores (p=0.006); patients taking 1 to 3 pills per day had higher transcendence scores (p=0.000); unmarried patients had higher symptoms scores (p=0.064) and lower well-being scores (p=0.004); and illiterate patients had higher symptoms (p=0.005) and transcendence scores (p=0.034). In total score, patients on hemodialysis once per week reported significantly better scores (p=0.011). CONCLUSION: This study highlights varied QoL experiences among hemodialysis patients, with transcendence scoring the highest and well-being, the lowest. Demographic factors such as age, gender, and education level significantly impact the QoL dimensions. Understanding these findings can guide personalized interventions to improve the well-being of hemodialysis patients.
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Caregiver-assisted testing using HIV self-test (CG-HIVST) kits has been proposed to enhance paediatric HIV case finding and contribute toward ending paediatric HIV/AIDS by 2030. We conducted a systematic review to assess the risks and benefits of CG-HIVST. We searched nine electronic databases and consulted experts to identify relevant articles through 5 February, 2022. Studies comparing CG-HIVST to other testing services among children over 18-months, or to no intervention, were included. Outcomes included uptake, acceptability, diagnostic accuracy, feasibility, HIV positivity, linkage to care, social harm, values and preferences, costs, and cost-effectiveness. Risk of bias was assessed using relevant Cochrane tools and certainty of evidence was evaluated with GRADE. Among 2203 screened articles, nine observational studies from sub-Saharan Africa were included. All studies used and assessed caregiver-assisted testing using oral fluid-based HIVST. In one non-randomized intervention study of 6062 children, overall CG-HIVST uptake was lower than other standard testing services (3.30% vs. 56.71%). In the same study, HIV positivity following CG-HIVST appeared lower or comparable to standard testing (RR = 0.44; 95% CI: 0.06, 3.20). Two single-arm studies reported high linkage to confirmatory testing (97.48%) and treatment initiation (97.7%) among children reported positive with CG-HIVST. Pooled positive predictive value was 36.72% across three non-randomized intervention studies. Reported social harms were rare, and acceptability appeared high among caregivers taking up the intervention, but feasibility was unclear as some reported anxiety in relation to reactive results. Evidence was appraised very low certainty. Average CG-HIVST costs varied widely and were consistently higher than standard testing services. CG-HIVST may be acceptable, but feasibility remains uncertain with potential higher costs. Current evidence favours standard testing for uptake and positivity. Low positive predictive values raise concerns about false positives and potential harm. Programmes should prioritize evidence-based approaches for paediatric case-finding, while research to fully evaluate this approach continues.
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Background Chronic respiratory diseases such as chronic obstructive pulmonary disease (COPD) and asthma significantly impair quality of life and impose a substantial burden on healthcare systems. Proper inhalation technique is important for effective management of these diseases, yet remains poorly performed by many patients. This study evaluated the impact of structured counseling and training sessions on inhaler use among patients with COPD and asthma, aiming to enhance technique correctness and disease control. Methodology This cross-sectional study analyzed 150 patients with asthma and COPD who fulfilled the inclusion criteria for inhalation techniques. Patients were counseled regarding the proper seven-step inhalation technique for each inhaler type [metered-dose inhaler (MDI), MDI with spacer, and dry powder inhaler (DPI)] through practical demonstration at baseline visits. Correct use of inhalers was assessed by a predefined checklist for each inhaler device at the baseline visit and after three months. The correctness of the inhalation technique was evaluated by scoring each of the seven steps. The disease control assessment was done using the COPD assessment test (CAT) and asthma control test (ACT) at the baseline visit and after three months. Results In this study of 150 patients, there were 97 (64.7%) males and 53 (35.3%) females. In total, 67 (44.7%) were diagnosed with asthma and 83 (55.3%) with COPD. The mean age was 45.33 ± 12.62 years. Post-counseling improvements in inhaler technique were marked, with MDI users enhancing their technique score from an average of 4.4 to 6.1, MDI with spacer from 4.56 to 6.26, and DPI from 4.92 to 6.24 (p < 0.001 for all). Disease control also showed significant gains; CAT scores decreased for MDI users from 23.4 to 20.5, MDI with spacer from 23.92 to 20.96, and DPI from 24.89 to 21.96. Concurrently, ACT scores increased for MDI users from 16.4 to 18.0 (p = 0.002), MDI with spacer from 17.29 to 19.04, and DPI from 16.42 to 18.37 (p < 0.001 for both), reflecting substantive advances in managing COPD and asthma symptoms. Furthermore, patients with primary education exhibited a significant boost in technique mastery post-counseling (p < 0.001), underscoring the potential of well-crafted counseling to transcend educational barriers in promoting effective inhaler use. Conclusions Post-counseling, inhaler technique improved significantly across all types, with MDI with spacer users demonstrating the most progress. Technique scores increased notably (p < 0.001), and disease control scores for COPD and asthma, measured by CAT and ACT, also showed significant improvements (p < 0.001). Remarkably, primary education level participants exhibited substantial technique gains post-intervention, emphasizing the effectiveness of counseling irrespective of initial educational status in enhancing inhaler use and disease management.
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To maximise the benefits of HIV self-testing (HIVST), it is critical to support self-testers in the testing process and ensure that they access appropriate prevention and care. To summarise systems and tools supporting HIVST (hereafter, 'support systems') and categorise them for future analysis, we synthesised the global data on HIVST support systems and proposed a typology. We searched five databases for articles reporting on one or more HIVST support systems and included 314 publications from 224 studies. Across 189 studies, there were 539 reports of systems supporting HIVST use; while across 115 studies, there were 171 reports of systems supporting result interpretation. Most commonly, these were pictorial instructions, followed by in-person demonstrations and in-person assistance while self-testing or reading self-test results. Less commonly, virtual interventions were also identified, including online video conferencing and smartphone apps. Smartphone-based automated result readers have been used in the USA, China, and South Africa. Across 173 studies, there were 987 reports of systems supporting post-test linkage to care; most commonly, these were in-person referrals/counselling, written referrals, and phone helplines. In the USA, Bluetooth beacons have been trialled to monitor self-test use and facilitate follow-up. We found that, globally, HIVST support systems use a range of methods, including static media, virtual tools, and in-person engagement. In-person and printed approaches were more common than virtual tools. Other considerations, such as linguistic and cultural appropriateness, may also be important in the development of effective HIVST programs.
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Infecções por HIV , Autoteste , Humanos , Infecções por HIV/diagnóstico , Teste de HIV/métodosRESUMO
INTRODUCTION: The underlying mechanisms of gastric cancer (GC) remain unknown. Therefore, in this study, we employed a comprehensive approach, combining computational and experimental methods, to identify potential key genes and unveil the underlying pathogenesis and prognosis of GC. METHODS: Gene expression profiles from GEO databases (GSE118916, GSE79973, and GSE29272) were analyzed to identify DEGs between GC and normal tissues. A PPI network was constructed using STRING and Cytoscape, followed by hub gene identification with CytoHubba. Investigations included expression and promoter methylation analysis, survival modeling, mutational and miRNA analysis, gene enrichment, drug prediction, and in vitro assays for cellular behaviors. RESULTS: A total of 83 DEGs were identified in the three datasets, comprising 41 up-regulated genes and 42 down-regulated genes. Utilizing the degree and MCC methods, we identified four hub genes that were hypomethylated and up-regulated: COL1A1, COL1A2, COL3A1, and FN1. Subsequent validation of their expression and promoter methylation on clinical GC samples through targeted bisulfite sequencing and RT-qPCR analysis further confirmed the hypomethylation and overexpression of these genes in local GC patients. Furthermore, it was observed that these hub genes regulate tumor proliferation and metastasis in in vivo and exhibited mutations in GC patients. CONCLUSION: We found four potential diagnostic and prognostic biomarkers, including COL1A1, COL1A2, COL3A1, and FN1 that may be involved in the occurrence and progression of GC.
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Metilação de DNA , Regulação Neoplásica da Expressão Gênica , Neoplasias Gástricas , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Humanos , Metilação de DNA/genética , Regiões Promotoras Genéticas/genética , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Simulação por Computador , Prognóstico , Linhagem Celular Tumoral , Perfilação da Expressão Gênica , Mapas de Interação de Proteínas/genética , Redes Reguladoras de Genes , Bases de Dados Genéticas , Biologia Computacional , Proliferação de Células/genética , MicroRNAs/genética , MicroRNAs/metabolismo , Fibronectinas , Colágeno Tipo IRESUMO
OBJECTIVES: Being a checkpoint, the expression level of V-set immunoregulatory receptor (VSIR) serves as an indicator of the extent of immunosuppression. Our objective was to undertake a pan-cancer analysis to examine the expression, genetic alterations, prognosis, and immunologic features associated with VSIR. METHODS: The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), GEPIA2, UALCAN, OncoDB, Human Protein Atlas (HPA), STRING, DAVID, cell culture, clinical sample collection, and reverse transcription quantitative polymerase chain reaction (RT-qPCR) were used. RESULTS: This study comprehensively assessed VSIR across 33 cancers using TCGA and GTEx databases. Differential expression analysis revealed elevated VSIR in several cancers, notably in cholangiocarcinoma, esophageal carcinoma, kidney renal cell carcinoma, and liver hepatocellular carcinoma, while decreased expression was observed in various others. Prognostic analysis highlighted its significant association with reduced overall survival (OS) in ESCA and LIHC. Investigation into cancer stages demonstrated a correlation between VSIR expression and stage in ESCA and LIHC. Promoter methylation analysis indicated decreased VSIR methylation levels in tumors, implicating a role in oncogenesis. Furthermore, subcellular localization predictions, Tumor Mutational Burden (TMB), and Microsatellite Instability (MSI) correlations revealed intriguing insight into VSIR's function. Notably, a positive correlation was identified between VSIR expression and various immune cells in both cancers. Protein-protein interaction (PPI) network construction and gene enrichment analysis elucidated VSIR-associated dysregulated pathways, emphasizing its possible involvement in diverse pathways. Finally, experimental validation using LIHC clinical samples and cell lines confirmed elevated VSIR expression, supporting its oncogenic role. CONCLUSION: Collectively, these findings present a comprehensive understanding of VSIR's diverse roles and potential clinical implications in ESCA and LIHC.
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The rice Zaxinone Synthase (ZAS) gene encodes a carotenoid cleavage dioxygenase (CCD) that forms the apocarotenoid growth regulator zaxinone in vitro. Here, we generated and characterized constitutive ZAS-overexpressing rice lines, to better understand ZAS role in determining zaxinone content and regulating growth and architecture. ZAS overexpression enhanced endogenous zaxinone level, promoted root growth and increased the number of productive tillers, leading to about 30% higher grain yield per plant. Hormone analysis revealed a decrease in strigolactone (SL) content, which we confirmed by rescuing the high-tillering phenotype through application of a SL analogue. Metabolomics analysis revealed that ZAS overexpressing plants accumulate higher amounts of monosaccharide sugars, in line with transcriptome analysis. Moreover, transgenic plants showed higher carbon (C) assimilation rate and elevated root phosphate, nitrate and sulphate level, enhancing the tolerance towards low phosphate (Pi). Our study confirms ZAS as an important determinant of rice growth and architecture and shows that ZAS regulates hormone homoeostasis and a combination of physiological processes to promote growth and grain yield, which makes this gene an excellent candidate for sustainable crop improvement.
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Background Chronic liver disease (CLD) is associated with a variety of consequences, including thrombocytopenia and esophageal varices, which significantly impact patient prognosis and management. Thrombocytopenia, frequently observed in patients with CLD, may correlate with the severity of esophageal varices, a critical complication leading to variceal bleeding. Methodology A cross-sectional study was carried out in the Department of Medicine and Gastroenterology, Pak Emirates Military Hospital, Rawalpindi, from October 2021 to March 2022. The study enrolled 94 patients, aged 18-70 years, diagnosed with CLD, regardless of the cause. These patients were categorized into four groups based on platelet count: <50,000/uL, 50,000-99,999/uL, 100,000-150,000/uL, and >150,000/uL. Pearson's correlation was utilized to evaluate the association between the severity of thrombocytopenia and the grading of esophageal varices. Results A total of 94 patients were enrolled in the study, with 53 (56.4%) males and 41 (43.6%) females. The mean age of patients was 51.06 ±11.09 years. Seventeen (18.1%) had no esophageal varices, 16 (17.0%) were diagnosed with Grade I varices, 35 (37.2%) with Grade II varices, and 26 (27.7%) had Grade III varices. Most patients without varices had a platelet count above 150 x 103 (17, 18.1%). Conversely, most patients with Grade III varices (19, 20.2%) had platelet counts below 50 x 103. Patients with no esophageal varices had a mean platelet count of 173.70 ± 37.48 x 103. Among the patients, those with Grade III esophageal varices exhibited the lowest mean platelet count, recorded at 78.54 ± 24.14 x 103. These findings indicate a statistically significant difference in mean platelet counts across the various esophageal varices grades (P = 0.000). There was an inverse correlation of platelet count with the grading of esophageal varices (r = -0.645, P < 0.000). Conclusions A negative correlation was observed between the platelet count and the grading of esophageal varices, implying that as the severity of esophageal varices increased, the platelet counts proportionally decreased.
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A relatively recent approach in molecular graph theory for analyzing chemical networks and structures is called a modified polynomial. It emphasizes the characteristics of molecules through the use of a polynomial-based procedure and presents numerical descriptors in algebraic form. The Quantitative Structure-Property Relationship study makes use of Modified Polynomials (M-Polynomials) as a mathematical tool. M-Polynomials used to create connections between a material's various properties and its structural characteristics. In this study, we calculated several modified polynomials and gave a polynomial description of the magnesium iodide structure. Particularly, we computed first, second and modified Zagreb indices based M-polynomials. Randic index, and inverse Randic indices based M-polynomials are also computed in this work.