Pan-active imidazolopiperazine antimalarials target the Plasmodium falciparum intracellular secretory pathway.

A promising new compound class for treating human malaria is the imidazolopiperazines (IZP) class. IZP compounds KAF156 (Ganaplacide) and GNF179 are effective against Plasmodium symptomatic asexual blood-stage infections, and are able to prevent transmission and block infection in animal models. But despite the identification of resistance mechanisms in P. falciparum, the mode of action of IZPs remains unknown. To investigate, we here combine in vitro evolution and genome analysis in Saccharomyces cerevisiae with molecular, metabolomic, and chemogenomic methods in P. falciparum. Our findings reveal that IZP-resistant S. cerevisiae clones carry mutations in genes involved in Endoplasmic Reticulum (ER)-based lipid homeostasis and autophagy. In Plasmodium, IZPs inhibit protein trafficking, block the establishment of new permeation pathways, and cause ER expansion. Our data highlight a mechanism for blocking parasite development that is distinct from those of standard compounds used to treat malaria, and demonstrate the potential of IZPs for studying ER-dependent protein processing

Prevalence of noncommunicable diseases and their risk factors among the population residing in the villages under a subcenter in Hassan: A community-based cross-sectional study

INTRODUCTION: In India's rural areas, there is an epidemiological shift toward the prevalence of noncommunicable diseases (NCDs). This study identified the prevalence and associations of risk variables for the development of NCD in Hassan, Karnataka. METHODOLOGY: From February 15, 2022, to April 30, 2022, a community-based cross-sectional survey was conducted among adults (18 years and older) residing in the 11 villages that make up the Hassan Medical College's rural field practice areas. A validated questionnaire was used to collect the data, and the SPSS trial version was used to analyze it. RESULTS: The total population was 765, of which 58.7% were female, 42% were illiterate, 91% were laborers, and 72.5% were from lower socioeconomic status. Among the participants, 59.6% were hypertensive, 7.4% were diabetic, 0.5% had cancer, and 0.3% had a cardiac disorder. Younger people (adjusted odds ratio [AOR] =2.406, confidence interval [CI] =1.747–3.315) and the unemployed (AOR = 2.131, CI = 1.355–3.353) had a higher risk of high blood pressure. Moreover, 9.4% of the participants used tobacco, which was significantly associated with the male gender (AOR = 2.161, CI: 1.289–3.622). About 5.5% consumed alcohol regularly, and being educated was found to be negatively associated with alcohol use (AOR = 0.126, CI = 0.044–0.363). CONCLUSION: Health education to modify lifestyle and improve adherence among patients consuming medicines should start at the individual level. Facilities need to be strengthened in the subcenters under all primary health center

Pacemaker lead related myocardial perforation

Permanent pacemaker (PPM) insertion is widely used to treat cardiac rhythm disorders; approximately 600,000 pacemakers are implanted annually in the US (Wood and Ellenbogen, 2002). Almost 9% of patients who receive a permanent pacemaker, however, experience a variety of medical complications such as infections, battery problems, programming issues, lead migration, or lead fracture (Greenspon et al., 2012). Moreover 1–2% of these patients will encounter severe lead-related problems within 30 days of their pacemaker insertion (Kirkfeldt et al., 2014; Kiviniemi et al., 1999). In this report, we focus on an uncommon but serious complication of PPM insertion: right ventricular lead perforation leading to a pericardial effusion. Although lead perforation is a relatively rare occurrence, this event can be life-threatening, and should be considered in the differential diagnosis when patients present to the emergency department (ED) with relevant symptoms and recent PPM insertion. Specifically, patients who experience complications from pacemaker insertion may present to the ED with a variety of symptoms such as chest pain, syncope, dyspnea, or even dizziness (Squire and Niemann, 2006). Pacemaker complications include pneumothorax, pleural and/or pericardial effusions, and infection, placing the patient at serious risk for significant harm (Squire and Niemann, 2006; Shingaki et al., 2015). The evaluation of a lead-related issue typically involves chest radiography to visualize abnormal lead placement and check for a pneumothorax or pleural effusion, and a 12‑lead electrocardiogram (ECG) to detect pacing errors. We present the case of a patient who presented to the ED three days after his pacemaker insertion with chest pain and dyspnea; he was subsequently diagnosed with a lead perforation into the pericardial space resulting in a pericardial effusion

Case Report - Extensive meningoencephalitis, retrobulbar neuritis, and pulmonary involvement in a patient of neurobrucellosis

We report an unusual case of neurobrucellosis who presented with headache, vision loss, confusional state, retrobulbar neuritis, and left hemiparesis. Neuroimaging studies showed features of ischemic infarct and white matter abnormalities. Pulmonary involvement in form of lobar pneumonia of left basal lobe was another unusual manifestation. Diagnosis was based on the rising titers of antibrucella antibody. Patient showed remarkable improvement on triple drug therapy in form of doxycycline, rifampicin and streptomycin

Comparative study on elder abuse and neglect among geriatric population in the rural and urban field practice areas of a medical college

Background: Elder abuse is a multidimensional problem of public importance. According to the World Health Organization (WHO), 16% of older people were victims of elder abuse. A study conducted by HelpAge India in 2018 showed that Mangaluru ranks the highest in elder abuse (47%). Given the scarce literature, this study sought to determine the prevalence of elder abuse and its associated sociodemographic factors. Material and Methods: A community-based cross-sectional study was conducted among the senior population in the rural and urban field practice a medical college in Mangaluru for one and a half years. The sample size was 280. Results: Most of the study population was in the age group of fewer than 75 years (75.4%), with 50.4% females, 60% Hindus, 56.4% married, 39.3% illiterate, and 88.9% of them retired. The prevalence of elder abuse was 44.6% (rural = 50.7% and urban = 38.6%). Binary logistic regression showed that elder abuse was statistically significant among the unemployed, extended family members, and staying with children. Conclusions: The study brings to light the sociodemographic factors that play a role in detecting elder abuse. It also shows the importance of awareness of elder mistreatment among older people. These elements must be considered for implementing and enforcing laws and legislation to help curb elder abuse

Alginate oligosaccharide postharvest treatment preserve fruit quality and increase storage life via Abscisic acid signaling in strawberry

Abscisic acid (ABA) has been advocated to play substantial role on ripening of non-climacteric fruit. Here we report that alginate oligosaccharide (AOS) postharvest treatments delayed the accumulation of ABA and ABA-conjugates and restrained the expression of ABA signaling genes, resulting enlarged storage life of strawberry. In addition, AOS postharvest treatments also increased the quality and reduced the degradation of cell wall components and repressed the expression of cell wall degradation genes. AOS treated fruits exhibited significant delays of hardness, decay percentage, titratable acidity, pH, total soluble solids and vitamin C content compared to untreated fruits. Moreover, AOS had a positive effect on retaining higher amount of anthocyanin, total phenol and flavonoids contents. The finding of this study suggests that AOS postharvest treatments are very useful for preserving fruit quality and enhancing shelf life by delayed ABA accretion, restrained the gene expression related to ABA signaling and cell wall degeneration

Exploration of drug addiction prevalence among young generation of Pabna district, Bangladesh

Drug addiction has spread at a frightening rate in the whole world, especially in the South Asian countries such as Bangladesh which needs to be analyzed, discussed and eradicated. This present survey based study was conducted with an aim to discover the scenery of drug addiction in northern region of Bangladesh. Researchers also uncovered the factors, problems and effects of drug addiction, age of first drug used, source of money to buy drugs and effective measures to prevent this problem etc. Total 600 youngsters from Pabna, a northern part of Bangladesh were directly interviewed by using self-construct questionnaire. Age range of the participants was between 12 and 35. Result showed, low income participants were highly addicted (58.62%) and family problems (43.93%) were the most prevalent cause of addiction. Participants involved in sports had lower drug addiction propensity (36.38%). Addicted young consumed more nicotine (95.04%), alcohol (63.93%) and marijuana (44.28%). Among addicts, youngs started using drugs mostly between 15 to 18 years age. Parent’s income (42%) was the prime source of money to buy drugs and 91% of addicted young faced complications. Counseling (71.2%) and systematic penalty (66.4%) were the best preventive measures for drug addiction. The young generations of Bangladesh are cankering their crucial youth time in addiction and they should be rescued by counseling, monitoring and treating them with care and affection from the parents, society and government. Keywords: Drug Addiction, Survey, Young People, Pabna, Banglades

Rapid Chagas Disease Drug Target Discovery Using Directed Evolution in Drug-Sensitive Yeast

Recent advances in cell-based, high-throughput phenotypic screening have identified new chemical compounds that are active against eukaryotic pathogens. A challenge to their future development lies in identifying these compounds' molecular targets and binding modes. In particular, subsequent structure-based chemical optimization and target-based screening require a detailed understanding of the binding event. Here, we use directed evolution and whole-genome sequencing of a drug-sensitive S. cerevisiae strain to identify the yeast ortholog of TcCyp51, lanosterol-14-alpha-demethylase (TcCyp51), as the target of MMV001239, a benzamide compound with activity against Trypanosoma cruzi, the etiological agent of Chagas disease. We show that parasites treated with MMV0001239 phenocopy parasites treated with another TcCyp51 inhibitor, posaconazole, accumulating both lanosterol and eburicol. Direct drug-protein binding of MMV0001239 was confirmed through spectrophotometric binding assays and X-ray crystallography, revealing a binding site shared with other antitrypanosomal compounds that target Cyp51. These studies provide a new probe chemotype for TcCyp51 inhibition