Dengue Treatment-Seeking Behavior: A Qualitative Study With Costa Rican Residents.

Treatment-seeking behavior (TSB) in relation to dengue infection is a critical aspect of public health, and understanding the factors that influence it is crucial for effective disease management. This research delves into key determinants of dengue TSB by examining the perceptions and behaviors of individuals in Costa Rica, in relation to the Health Belief Model (HBM). This study utilized naturalistic inquiry and incorporated a qualitative research design involving nine students organized into four teams, with at least one student on each team with high Spanish fluency. In total, we initiated 102 semi-structured field interviews with Costa Rican residents in four communities. The interviews were recorded, transcribed verbatim, and coded in several cycles using MAXQDA 2022©. Thematic analysis was used to identify patterns and themes using an inductive approach. We found that several HBM themes influenced dengue TSB among participants. Self-treatment was the most common initial step in managing dengue. Perceived inaccessibility of health care services and perceived ineffective treatment options discouraged medical care-seeking. Ultimately, the prevalence of self-treatment practices suggests a need for interventions that emphasize the importance of timely professional medical attention, while addressing real barriers and perceptions of existing health care services as inaccessible and ineffective. These findings provide a key perspective on dengue TSB, guiding future public health strategies aimed at optimizing health-seeking behaviors and mitigating the negative impacts of dengue on population health.

Effect of dynamic taping on neck pain, disability, and quality of life in patients with chronic non-specific neck pain: a randomized sham-control trial.

Background: In 2020, 203 million people experienced neck pain, with a higher prevalence in women. By 2050, it is predicted that neck pain will affect 269 million people, representing a 32.5% increase. Physical rehabilitation is often employed for the treatment of chronic non-specific neck pain (CNSNP) and the associated functional loss. Taping is frequently used as an adjunct treatment alongside primary physical rehabilitation. Unlike kinesio tape (KT), the therapeutic benefits of dynamic tape (DT) have not been thoroughly explored and documented in non-athletic conditions. Therefore, the aim of this trial was to determine the effects of DT on pain, disability, and overall well-being in individuals experiencing CNSNP. Methods: A prospective parallel-group active controlled trial was conducted at a single center, involving 136 patients with CNSNP, randomly allocated in a 1:1 ratio. The sham taping group (STC) received standard physiotherapy care (n = 67) alongside DT without tension, while the dynamic taping group (DTC) (n = 69) underwent standard cervical offloading technique with appropriate tension in addition to standard physiotherapy care. Demographic information and three patient-reported outcome measures (PROMs), namely the Neck Disability Index (NDI), Visual Analogue Scale (VAS), and the World Health Organization-Five Well-Being Index (WHO-5), were collected for each participant at three time points (baseline, four weeks post-taping, and four weeks follow-up). Results: At baseline, no significant differences were observed between the STC and DTC for any outcome measure. Notably, all three PROMs exhibited a significant improvement from baseline to four weeks post-intervention, with moderate to small effect sizes (NDI ηp2 = 0.21, VAS ηp2 = 0.23, and WHO-55 ηp2 = 0.05). The WHO-5 scores for both groups demonstrated improvement from baseline through follow-up (p < 0.001). The NDI and VAS scores ameliorated from baseline to the four weeks post-taping period, with marginal improvements observed during the four weeks follow-up. Conclusion: The incorporation of DT as an adjunct to standard physiotherapy care yielded enhancements in pain levels, functional disability, and well-being among patients with CNSNP when compared to the sham group. However, the sustainability of these improvements beyond the taping period lacks statistical significance and warrants further validation.

New immune horizons in therapeutics and diagnostic approaches to Preeclampsia.

Hypertensive disorders of pregnancy (HDP) are one of the commonest maladies, affecting 5%-10% of pregnancies worldwide. The American College of Obstetricians and Gynecologists (ACOG) identifies four categories of HDP, namely gestational hypertension (GH), Preeclampsia (PE), chronic hypertension (CH), and CH with superimposed PE. PE is a multisystem, heterogeneous disorder that encompasses 2%-8% of all pregnancy-related complications, contributing to about 9% to 26% of maternal deaths in low-income countries and 16% in high-income countries. These translate to 50 000 maternal deaths and over 500 000 fetal deaths worldwide, therefore demanding high priority in understanding clinical presentation, screening, diagnostic criteria, and effective management. PE is accompanied by uteroplacental insufficiency leading to vascular and metabolic changes, vasoconstriction, and end-organ ischemia. PE is diagnosed after 20 weeks of pregnancy in women who were previously normotensive or hypertensive. Besides shallow trophoblast invasion and inadequate remodeling of uterine arteries, dysregulation of the nonimmune system has been the focal point in PE. This results from aberrant immune system activation and imbalanced differentiation of T cells. Further, a failure of tolerance toward the semi-allogenic fetus results due to altered distribution of Tregs such as CD4+FoxP3+ or CD4+CD25+CD127(low) FoxP3+ cells, thereby creating a cytotoxic environment by suboptimal production of immunosuppressive cytokines like IL-10, IL-4, and IL-13. Also, intracellular production of complement protein C5a may result in decreased FoxP3+ regulatory T cells. With immune system dysfunction as a major driver in PE pathogenesis, it is logical that therapeutic targeting of components of the immune system with pharmacologic agents like anti-inflammatory and immune-modulating molecules are either being used or under clinical trial. Cholesterol synthesis inhibitors like Pravastatin may improve placental perfusion in PE, while Eculizumab (monoclonal antibody inhibiting C5) and small molecular inhibitor of C5a, Zilucoplan are under investigation. Monoclonal antibody against IL-17(Secukinumab) has been proposed to alter the Th imbalance in PE. Autologous Treg therapy and immune checkpoint inhibitors like anti-CTLA-4 are emerging as new candidates in immune horizons for PE management in the future.

Task Sharing for Managing Common Noncommunicable Disease in a Nurse Led Noncommunicable Diseases Clinic in Peri-Urban Community of Chandigarh.

Background: Nurse led noncommunicable diseases (NCD) clinic may address the significant shortage of human resource for health for managing common NCDs. The objective of this study is to assess the feasibility and effectiveness of nurse-led NCD clinic for identification, prevention, and management of common NCDs. Materials and Methods: A quasi experimental study was conducted at a Public Health Dispensary in periurban community of Northern India. Situational analysis and stakeholders' interview were done based on which the clinic was setup and run over a period of 2 months by registered nurses and nursing students to offer screening, health education and appropriate referral. The primary outcome of study was proportion of population screened, prevalence of common NCDs, risk factors modification, medication adherence, and patient satisfaction. Results: It was feasible to run a nurse led clinic in terms of availability of space, equipment to run the clinic and human resource. A total of 455 individuals aged ≥30 years were enrolled using the total enumeration sampling technique. There was a significant increase in screening rates from 0.29% to 3.7% in nurse-led NCD clinic. There was significant mean change in systolic blood pressure (18.75 ± 6.92 mm Hg), diastolic blood pressure (4.4 ± 3.71 mm Hg), random blood sugar (33.36 ± 38.49 mg/dl) Body Mass Index, and waist circumference (P < 0.01) among the population screened. Medication adherence significantly increased from 7.8% to 76.4% (P < 0.01) after 2 months of nurse-led NCD clinic. Conclusion: Task sharing for managing common NCDs in nurse-led NCD clinic was feasible and effective in increasing screening rates, medication adherence, and risk factors modification among studied population.

Exploiting the CRISPR/Cas9 PAM Constraint for Single-Nucleotide Resolution Interventions.

CRISPR/Cas9 is an enabling RNA-guided technology for genome targeting and engineering. An acute DNA binding constraint of the Cas9 protein is the Protospacer Adjacent Motif (PAM). Here we demonstrate that the PAM requirement can be exploited to specifically target single-nucleotide heterozygous mutations while exerting no aberrant effects on the wild-type alleles. Specifically, we target the heterozygous G13A activating mutation of KRAS in colorectal cancer cells and we show reversal of drug resistance to a MEK small-molecule inhibitor. Our study introduces a new paradigm in genome editing and therapeutic targeting via the use of gRNA to guide Cas9 to a desired protospacer adjacent motif.

Transcripts for combined synthetic microRNA and gene delivery.

MicroRNAs (miRNAs) are a class of short noncoding RNAs which are endogenously expressed in many organisms and regulate gene expression by binding to messenger RNA (mRNA). MicroRNAs are either produced from their independent transcription units in intergenic regions or lie in intragenic regions. Intragenic miRNAs and their host mRNAs are produced from the same transcript by the microprocessor and the spliceosome protein complex respectively. The details and exact timing of the processing events have implications for downstream RNA interference (RNAi) efficiency and mRNA stability. Here we engineer and study in mammalian cells a range of synthetic intragenic miRNAs co-expressed with their host genes. Furthermore, we study transcripts which carry the target of the miRNA, thereby emulating a common regulation mechanism. We perform fluorescence microscopy and flow cytometry to characterize the engineered transcripts and investigate the properties of the underlying biological processes. Our results shed additional light on miRNA and pre-mRNA processing but importantly provide insight into engineering transcripts customized for combined delivery and use in synthetic gene circuits.