Ryzumvi: pioneering advances in countering drug-induced mydriasis.

This article discusses the prevalence and impact of pharmacologically-induced mydriasis, a condition where the pupil becomes excessively dilated due to certain drugs. It highlights the challenges faced by medical professionals in dealing with this condition and the limitations of current treatments, like pilocarpine and dapiprazole, which come with systemic side effects and specific contraindications, limiting their regular use. The article introduces Ryzumvi, a novel ophthalmic solution approved by the US FDA, which effectively reverses mydriasis caused by adrenergic agonists and antimuscarinic drugs. The article provides insights into its mechanism of action, clinical efficacy, pharmacokinetics, safety, and tolerance based on extensive clinical trials. It emphasizes its rapid onset of action and effectiveness in restoring pupils to their initial size. It also underlines the potential for expanded applications, including in pediatric patients, solidifying its importance in the field of ophthalmology. Furthermore, Ryzumvi represents a promising advancement in managing pharmacologically-induced mydriasis, offering swift and effective relief while highlighting the importance of adhering to safety precautions and the continuous research and development efforts in ophthalmology to comprehensively address vision-related disorders and enhance patient outcomes.

Strongyloides causing diarrhea in a Hepatitis B carrier patient: A case report and review of literature.

We report an unusual case of strongyloidiasis in a 62-year-old male, presenting with fever, and acute diarrhea. The patients had concomitant bilateral renal parenchymal disease and carrier for Hepatitis B. Numerous motile larvae were observed in wet mount of the freshly passed stool. The patient responded well to oral ivermectin. Prompt and accurate diagnosis of strongyloidiasis can prevent the consequences associated with hyperinfective syndrome.

Dietary Sources, Stabilization, Health Benefits, and Industrial Application of Anthocyanins-A Review.

Natural phytochemicals are well known to protect against numerous metabolic disorders. Anthocyanins are vacuolar pigments belonging to the parent class of flavonoids. They are well known for their potent antioxidant and gut microbiome-modulating properties, primarily responsible for minimizing the risk of cardiovascular diseases, diabetes, obesity, neurodegenerative diseases, cancer, and several other diseases associated with metabolic syndromes. Berries are the primary source of anthocyanin in the diet. The color and stability of anthocyanins are substantially influenced by external environmental conditions, constraining their applications in foods. Furthermore, the significantly low bioavailability of anthocyanins greatly diminishes the extent of the actual health benefits linked to these bioactive compounds. Multiple strategies have been successfully developed and utilized to enhance the stability and bioavailability of anthocyanins. This review provides a comprehensive view of the recent advancements in chemistry, biosynthesis, dietary sources, stabilization, bioavailability, industrial applications, and health benefits of anthocyanins. Finally, we summarize the prospects and challenges of applications of anthocyanin in foods.

Effectiveness of virtual reality in managing pain and anxiety in adults during periprocedural period: a systematic review and meta-analysis.

PURPOSE: Patients undergoing medical procedures often experience pain and anxiety. These periprocedural outcomes can be overcome by providing a distraction using virtual reality (VR), decreasing their perception. VR has proved effective in reducing pediatric pain and anxiety; however, limited studies have confirmed its effectiveness in adults. We performed a systematic review and meta-analysis on the effectiveness of VR, as opposed to standard care, in reducing periprocedural pain and anxiety in adults. METHODS: A systematic search of randomized controlled trials was conducted using the databases of MEDLINE, Cochrane CENTRAL, and Scopus. Trials involving patients (> 18 years) undergoing elective medical procedures conducted with or without local anesthesia and participating in VR therapy were included. Primary outcomes were pre-procedural anxiety, post-procedural anxiety, and intra-procedural pain. Pre-procedural pain, post-procedural pain, and intra-procedural anxiety were secondary outcomes. RESULTS: Data from 10 studies shortlisted for inclusion revealed no significant association between the use of VR and lower pre-procedural anxiety compared to standard care (p > 0.05) (SMD = -0.02, 95% CI = -0.18 - 0.14, P = 0.81) but demonstrated that the use of VR was significantly associated with a reduction in post-procedural anxiety (SMD = -0.73, 95% CI = -1.08 - -0.39, P < 0.0001), intra-procedural pain (SMD = -0.61, 95% CI = -1.18 - -0.04, P = 0.04), and post-procedural pain (SMD = -0.25, 95% CI = -0.44 - -0.05, P = 0.01). CONCLUSION: The use of VR caused a significant reduction in post-procedural anxiety, intra-procedural pain, and post-procedural pain in adults undergoing medical procedures, although the findings were insignificant concerning pre-procedural anxiety.

Home health care and cardiac rehabilitation following major cardiac surgeries in Pakistan.

Cardiovascular disorders are a leading cause of morbidity and mortality globally, and coronary artery bypass graft surgery is one of the most effective procedures for coronary artery disease. Cardiac rehabilitation (CR) has been shown to offer benefits beyond reducing mortality and morbidity rates, including enhancing patients' quality of life and reducing healthcare costs. Home-based CR programs offer personalized plans tailored to individual needs and availability and have been shown to be more effective in sustaining improvements than center-based CR programs. However, there are challenges associated with providing home care services in developing countries, including personnel shortages, lack of financing and policies, and limited access to end-of-life or hospice services. The use of multidisciplinary telehealth and telecare homecare programs that make use of web-based technologies to monitor postoperative outcomes in patients undergoing cardiac surgery may provide a solution to some of these challenges. This manuscript emphasizes the potential of home health care and CR in improving postoperative outcomes in Pakistan and identifies some of the challenges and potential solutions associated with providing home care services.

Role of Ubiquitin-Proteasome and Autophagy-Lysosome Pathways in α-Synuclein Aggregate Clearance.

Synuclein aggregation in neuronal cells is the primary underlying cause of synucleinopathies. Changes in gene expression patterns, structural modifications, and altered interactions with other cellular proteins often trigger aggregation of α-synuclein, which accumulates as oligomers or fibrils in Lewy bodies. Although fibrillar forms of α-synuclein are primarily considered pathological, recent studies have revealed that even the intermediate states of aggregates are neurotoxic, complicating the development of therapeutic interventions. Autophagy and ubiquitin-proteasome pathways play a significant role in maintaining the soluble levels of α-synuclein inside cells; however, the heterogeneous nature of the aggregates presents a significant bottleneck to its degradation by these cellular pathways. With studies focused on identifying the proteins that modulate synuclein aggregation and clearance, detailed mechanistic insights are emerging about the individual and synergistic effects of these degradation pathways in regulating soluble α-synuclein levels. In this article, we discuss the impact of α-synuclein aggregation on autophagy-lysosome and ubiquitin-proteasome pathways and the therapeutic strategies that target various aspects of synuclein aggregation or degradation via these pathways. Additionally, we also highlight the natural and synthetic compounds that have shown promise in alleviating the cellular damage caused due to synuclein aggregation.

Adenine Modification at C7 as a Viable Strategy to Potentiate the Antimalarial Activity of Quinolones.

Although many quinolones have shown promise as potent antimalarials, their clinical development has been slow due to poor performance in vivo. Insights into structural modifications that can improve their therapeutic potential will be very valuable in this vibrant area of research. Our studies involving a library of quinolones which vary in substitution pattern at N1, C3, C6 and C7 positions have shown that the presence of adenine moiety at C7 can bring a noticeable improvement in activity compared to other heterocyclic groups at this location. The most potent compound emerged from this study showed IC50 values of 0.38 µM and 0.75 µM against chloroquine-sensitive and -resistant (W2) strains, respectively. Docking analysis in the Qo site of cytochrome bc1 complex revealed the contribution of a key H-bonding interaction from the adenine unit in target binding. This corroborates with compound-induced loss of mitochondrial functions. These findings not only open avenues for further exploration of antimalarial potential of adenine-modified quinolones, but also suggests broader opportunities during lead-optimization against other antimalarial targets.

Structural-functional diversity of malaria parasite's PfHSP70-1 and PfHSP40 chaperone pair gives an edge over human orthologs in chaperone-assisted protein folding.

Plasmodium falciparum, the human malaria parasite harbors a metastable proteome which is vulnerable to proteotoxic stress conditions encountered during its lifecycle. How parasite's chaperone machinery is able to maintain its aggregation-prone proteome in functional state, is poorly understood. As HSP70-40 system forms the central hub in cellular proteostasis, we investigated the protein folding capacity of PfHSP70-1 and PfHSP40 chaperone pair and compared it with human orthologs (HSPA1A and DNAJA1). Despite the structural similarity, we observed that parasite chaperones and their human orthologs exhibit striking differences in conformational dynamics. Comprehensive biochemical investigations revealed that PfHSP70-1 and PfHSP40 chaperone pair has better protein folding, aggregation inhibition, oligomer remodeling and disaggregase activities than their human orthologs. Chaperone-swapping experiments suggest that PfHSP40 can also efficiently cooperate with human HSP70 to facilitate the folding of client-substrate. SPR-derived kinetic parameters reveal that PfHSP40 has higher binding affinity towards unfolded substrate than DNAJA1. Interestingly, the observed slow dissociation rate of PfHSP40-substrate interaction allows PfHSP40 to maintain the substrate in folding-competent state to minimize its misfolding. Structural investigation through small angle x-ray scattering gave insights into the conformational architecture of PfHSP70-1 (monomer), PfHSP40 (dimer) and their complex. Overall, our data suggest that the parasite has evolved functionally diverged and efficient chaperone machinery which allows the human malaria parasite to survive in hostile conditions. The distinct allosteric landscapes and interaction kinetics of plasmodial chaperones open avenues for the exploration of small-molecule based antimalarial interventions.

Presence of adult Loa loa in the anterior chamber of the eye along with microfilaremia from nonendemic region: A rare presentation from India.

We report an unusual case of adult Loa loa infection in the anterior chamber of the eye of a 65-year-old female from rural area of Jharkhand, India, with no history of travel to endemic places but the presence of microfilaria of Loa loa in blood. Loiasis is endemic to African countries, with few sporadic cases affecting the Indian population. However, in none of the reports, microfilaremia was detected. This atypical feature in this case adds to the epidemiological variations in parasitic presentations in nonendemic regions.

Protein quality control machinery in intracellular protozoan parasites: hopes and challenges for therapeutic targeting.

Intracellular protozoan parasites have evolved an efficient protein quality control (PQC) network comprising protein folding and degradation machineries that protect the parasite's proteome from environmental perturbations and threats posed by host immune surveillance. Interestingly, the components of PQC machinery in parasites have acquired sequence insertions which may provide additional interaction interfaces and diversify the repertoire of their biological roles. However, the auxiliary functions of PQC machinery remain poorly explored in parasite. A comprehensive understanding of this critical machinery may help to identify robust biological targets for new drugs against acute or latent and drug-resistant infections. Here, we review the dynamic roles of PQC machinery in creating a safe haven for parasite survival in hostile environments, serving as a metabolic sensor to trigger transformation into phenotypically distinct stages, acting as a lynchpin for trafficking of parasite cargo across host membrane for immune evasion and serving as an evolutionary capacitor to buffer mutations and drug-induced proteotoxicity. Versatile roles of PQC machinery open avenues for exploration of new drug targets for anti-parasitic intervention and design of strategies for identification of potential biomarkers for point-of-care diagnosis.

Emergence of non-albicans Candida among candidal vulvovaginitis cases and study of their potential virulence factors, from a tertiary care center, North India.

PURPOSE: The purpose of this study was to determine the prevalence of various Candida species and study some of their virulence factors among thevulvovaginal candidiasis(VVC)patients. STUDY DESIGN AND SETTINGS: The study was conducted in a Tertiary Care University Hospital in North India. MATERIALS AND METHODS: This study was carried out prospectively for a period of 1 year. High vaginal swabs (HVSs) were collected from women in childbearing age group attending the gynecology and obstetrics out-patient departments with the complaints suggestive of vulvovaginitis. Samples were plated on Sabouraud's dextrose agar slope. Candida spp. isolated was further speciated based on microscopy, biochemical tests and culture characteristics on special media. Virulence factors of these strains were determined by biofilm formation and phospholipase activity. RESULT: A total of 464 HVS from 232 patients with the complaints of vulvovaginitis were included in this study. Following laboratory workup, 71 specimens were positive for genus Candida (30.6%). Further speciation showed 32.4% as Candida albicans, 45.07% Candida parapsilosis and 22.53% of Candida glabrata. Biofilm production was shown by 50 candidal strains (70.4%) and phospholipase activity was given by 41 candidal strains (57.74%). CONCLUSION: Our study suggests increasing prevalence of non-albicans Candida among the VVC cases along with their virulence factors. Therefore, we recommend that microbiological investigation upto species level should be mandatory to determine the emergence of non-albicans Candida as a major cause of VVC.

Lymphocutaneous sporotrichosis in an adolescent girl presenting as mycetoma.

A 13-year-old girl presented with multiple painless purulent ulcers with raised borders on the medial aspect of the sole of her right foot associated with inguinal lymphadenopathy for the past 4 years. There was history of local trauma at the site prior to the formation of ulcers. There were no other significant associated signs or symptoms. The patient was initially treated with multiple antibiotics with minimal improvement. Fungal cultures of biopsy specimens demonstrated the presence of colonies of Sporothrix schenckii thus confirming the diagnosis of sporotrichosis. Oral itraconazole at the dose of 100 mg twice daily was initiated with marked response at 4 weeks. This case demonstrated a rare morphological presentation of the lymphocutaneous sporotrichosis as mycetoma. The possible diagnosis of sporotrichosis should be kept in mind in such a clinical presentation not responding to antibiotics. Cutaneous sporotrichosis should be diagnosed and treated as early as possible because untreated cases may disseminate to cause visceral involvement with fatal outcome in immunocompromised patients.