The fungicidal effectiveness of 2-Chloro-3-hydrazinylquinoxaline, a newly developed quinoxaline derivative, against Candida species.

BACKGROUND: Candida represents a prevalent fungal infection, notable for its substantial implications on morbidity and mortality rates. In the landscape of prospective treatments, quinoxaline derivatives emerge as a category of compact compounds exhibiting notable potential in addressing infections. These derivatives showcase promising antimicrobial efficacy coupled with favorable pharmacokinetic and safety characteristics. AIMS: The central aim of this investigation was to examine the antifungal characteristics of 2-Chloro-3-hydrazinylquinoxaline against diverse strains of Candida and Aspergillus in vitro. Additionally, we endeavored to assess the in vivo efficacy of 2-Chloro-3-hydrazinylquinoxaline using a murine model for oral candidiasis induced by C. albicans cells ATCC 10231. RESULTS: 2-Chloro-3-hydrazinylquinoxaline demonstrated noteworthy effectiveness when tested against various reference strains of Candida species. It exhibited heightened efficacy, particularly against Candida krusei isolates. However, its performance against Candida albicans, Candida tropicalis, Candida glabrata, Candida parapsilosis, and Candida auris isolates exhibited variability. Notably, 2-Chloro-3-hydrazinylquinoxaline manifests variable efficacy against Aspergillus fumigatus, Aspergillus niger, Aspergillus terreus and Aspergillus flavus and no effect against Aspergillus brasiliensis. In a murine model, 2-Chloro-3-hydrazinylquinoxaline exhibited significant efficacy in combating the C. albicans cells ATCC 10231 strain, underscoring its potential as a viable treatment option. CONCLUSION: 2-Chloro-3-hydrazinylquinoxaline has demonstrated substantial potential in effectively addressing various Candida and Aspergillus species, showcasing dual attributes of antifungal and anti-inflammatory properties. However, to attain a more comprehensive understanding of its therapeutic capabilities, further investigations, incorporating additional tests and experiments, are imperative.

Spinal muscular atrophy type 1: A fatal case in a 1-year-old girl with delayed diagnosis.

Key Clinical Message: Spinal muscular atrophy (SMA) is a growing clinical concern, necessitating higher awareness and early detection. This case study focuses on the difficulties and advances in detecting and treating SMA. It emphasizes the value of early detection, interdisciplinary care, genetic testing, and novel therapeutics in terms of improving outcomes. Abstract: Spinal muscular atrophy type 1 (SMA Type 1) is a rare genetic neuromuscular disease characterized by muscle atrophy and weakness. This case report presents the fatal outcome of a 1-year-old girl with delayed diagnosis of SMA Type 1. The child exhibited symptoms of muscle weakness and respiratory distress, which were initially overlooked. Despite a thorough examination and diagnostic tests, including genetic analysis, SMA Type 1 with a homozygous deletion in the survival motor neuron 1 (SMN1) gene was confirmed. The child received supportive measures and physiotherapy but experienced a progressive deterioration of her condition and eventually succumbed to the disease. This case underscores the challenges of diagnosing SMA and highlights the importance of early identification for appropriate management. Improved awareness, diagnostic protocols, and access to treatment options, including pharmacological drugs and gene therapy, are essential to improve outcomes for SMA Type 1 patients, particularly in resource-limited settings. Early detection through newborn screening programs and timely intervention can significantly impact the prognosis and life expectancy of SMA Type 1 children, emphasizing the need for continued research and clinical trials to establish a definitive cure.

Transient Intraocular Pressure Fluctuations After Intravitreal Bevacizumab Injection in Proliferative Diabetic Retinopathy Patients: A Prospective Study.

INTRODUCTION: The clinical use of intravitreal bevacizumab (IVB), a recombinant humanized monoclonal antibody that functions as an anti-vascular endothelial growth factor (anti-VEGF), has recently increased in patients with retinal ischemic diseases such as proliferative diabetic retinopathy (PDR). The short-term and long-term complications associated with this procedure have not been well established. We aimed to study the possible short-term complication of intraocular pressure (IOP) fluctuations shortly after IVB injection in patients with PDR. MATERIALS AND METHODS: A prospective case series of diabetic patients with PDR who underwent IVB injection was performed in the Department of Ophthalmology, Medical Teaching Institution, Khyber Teaching Hospital, Peshawar, Pakistan, from November 1, 2020, to May 1, 2021. The total number of PDR patients of both sexes included in the study was 101. A slit lamp examination was performed, and IOP readings were recorded before and 30 min after IVB injection using Goldmann applanation tonometry (GAT). IBM Statistical Package for the Social Sciences version 22 for Windows was used to analyze the data. Safety of the procedure, defined as IOP ≤20 mmHg 30 min after IVB injection, was determined and stratified according to sex, age, duration of diabetes, and baseline IOP. A post-stratification chi-square test was applied, and a p-value <0.05 was taken as statistically significant. RESULTS: In this study, 60.4% of the participants were male and 39.6% were female. The age of the patients ranged from 30 to 75 years, with a mean age of 55.66±6.37 years. The mean duration of diabetes among the participants was 7.73±2.94 years and the mean baseline IOP was 15.40±1.77 mmHg. Safety (IOP ≤20 mmHg 30 min after IVB injection) was observed in 90.1% of the patients. CONCLUSION: IVB injections are safe for use in patients with PDR in terms of immediate IOP changes. However, patients with higher baseline IOP (>15 mmHg) are more likely to develop increased IOP post-procedure and prophylaxis may be prudent in such cases.

Evaluation of the Antibacterial Activity of Quinoxaline Derivative Compound Against Methicillin-Resistant Staphylococcus aureus.

Background: While the frequency of methicillin-resistant Staphylococcus aureus (MRSA) continues to rise globally, there is a fear regarding an increase in vancomycin resistance among S. aureus strains. As far back as the 1960s, MRSA was one of the world's most prevalent antibiotic-resistant bacteria. Among hospitalized patients and community members, MRSA is the cause of a significant number of infections. As a result of its resistance to classical beta-lactam and, in some cases, vancomycin antibiotics, efforts must be made as soon as feasible to find a new approach to fighting MRSA. Purpose: This study is designed to evaluate the antibacterial activity of quinoxaline derivative compound against MRSA in comparison with vancomycin as a reference drug. Methods: Sixty MRSA isolates were subjected to susceptibility testing by broth microdilution method for quinoxaline derivative compound and vancomycin. Each drug's minimal inhibitory concentration (MIC) was determined and compared. Results: Among the sixty MRSA isolates, most of the quinoxaline derivative compound MIC findings (56.7%) were 4 µg/mL compared to vancomycin MIC values (63.3%) of 4 µg/mL. In comparison, 20% of quinoxaline derivative compound MIC readings were 2 µg/mL, while the vancomycin MIC results were 6.7%. However, the overall proportion of MIC readings at ≤2 µg/mL for both antibacterial agents was equal (23.3%). None of the isolates were resistant to vancomycin. Conclusion: This experiment revealed that most MRSA isolates were associated with low MICs (1-4 µg/mL) for quinoxaline derivative compound. Overall, the susceptibility of the quinoxaline derivative compound signifies a promising efficacy against MRSA and may set a novel treatment approach.

Assessing the knowledge, attitude, and practice measures against tuberculosis in patients in ambulatory department facilities in Pakistan: a cross-sectional analysis.

Tuberculosis (TB), at present, is the leading infectious etiology of death globally. In Pakistan, there are approximately 510,000 new cases annually, with more than 15,000 of them developing into drug-resistant TB, making the nation the fifth-leading country in TB prevalence in the world. Due to the ongoing COVID-19 pandemic, the focus has drifted away from TB screening, diagnostic and health awareness campaigns, and therapeutic measures endangering knowledge, attitude, and practices (KAP) towards TB in our population. We conducted a cross-sectional descriptive study in Pakistan to assess the KAP of Pakistani residents attending the adult outpatient departments of public hospitals for any health-related concerns. Our sample size was 856 participants, with a median age of 22 years. Occupation-wise, those who were employed had better knowledge of TB than those who were unemployed [odds ratio (OR): 1.011; 95% confidence interval (CI): 1.005-1.8005]. No differences were observed in TB knowledge between those adherents to common preventive practices versus those not adherent (OR: 0.875; 95% CI: 0.757-1.403). More than 90% of participants agreed that TB is dangerous for the community, and the majority opted against stigmatizing TB patients (79.1%). People who could read and write were 3.5 times more likely to have a good attitude towards TB compared to those who could not (OR: 3.596; 95% CI: 1.821-70.230; p=0.037). Similarly, employed subjects had better attitudes compared to unemployed ones (OR: 1.125; 95% CI: 0.498-1.852; p=0.024) and those with better knowledge of TB had a better attitude grade (OR: 1.749; 95% CI: 0.832-12.350; p=0.020). Age, occupation, and educational status were statistically significant among the two groups (p=0.038, p=0.023, p=0.000). Literate subjects had three times better practice towards TB than illiterate subjects (OR: 3.081; 95% CI: 1.869-4.164; p=0.000). Future education and awareness programs should target specific groups, such as the unemployed and illiterate, with practice-focused approaches. Our study outcomes can enable the concerned officials and authorities to take appropriate evidence-based steps to direct the efforts efficiently to curtail the burden of TB in Pakistan and to limit its progression, which could potentially lead our nation to become a multi drug-resistant TB endemic territory.

Transition Zone Pull-through in Patients with Hirschsprung Disease: Is Redo Surgery Beneficial for the Long-term Outcomes?

INTRODUCTION: Transition zone pull-through (TZPT) is incomplete removal of the aganglionic bowel/transition zone (TZ) in patients with Hirschsprung disease (HD). Evidence on which treatment generates the best long-term outcomes is lacking. The aim of this study was to compare the long-term occurrence of Hirschsprung associated enterocolitis (HAEC), requirement of interventions, functional outcomes and quality of life between patients with TZPT treated conservatively to patients with TZPT treated with redo surgery to non-TZPT patients. METHODS: We retrospectively studied patients with TZPT operated between 2000 and 2021. TZPT patients were matched to two control patients with complete removal of the aganglionic/hypoganglionic bowel. Functional outcomes and quality of life was assessed using Hirschsprung/Anorectal Malformation Quality of Life questionnaire and items of Groningen Defecation & Continence together with occurrence of Hirschsprung associated enterocolitis (HAEC) and requirement of interventions. Scores between the groups were compared using One-Way ANOVA. The follow-up duration lasted from time at operation until follow-up. RESULTS: Fifteen TZPT-patients (six treated conservatively, nine receiving redo surgery) were matched with 30 control-patients. Median duration of follow-up was 76 months (range 12-260). No significant differences between groups were found in the occurrence of HAEC (p = 0.65), laxatives use (p = 0.33), rectal irrigation use (p = 0.11), botulinum toxin injections (p = 0.06), functional outcomes (p = 0.67) and quality of life (p = 0.63). CONCLUSION: Our findings suggest that there are no differences in the long-term occurrence of HAEC, requirement of interventions, functional outcomes and quality of life between patients with TZPT treated conservatively or with redo surgery and non-TZPT patients. Therefore, we suggest to consider conservative treatment in case of TZPT.

O-GlcNAc transferase modulates the cellular endocytosis machinery by controlling the formation of clathrin-coated pits.

Clathrin-mediated endocytosis (CME) controls the internalization and function of a wide range of cell surface proteins. CME occurs by the assembly of clathrin and many other proteins on the inner leaflet of the plasma membrane into clathrin-coated pits (CCPs). These structures recruit specific cargo destined for internalization, generate membrane curvature, and in many cases undergo scission from the plasma membrane to yield intracellular vesicles. The diversity of functions of cell surface proteins controlled via internalization by CME may suggest that regulation of CCP formation could be effective to allow cellular adaptation under different contexts. Of interest is how cues derived from cellular metabolism may regulate CME, given the reciprocal role of CME in controlling cellular metabolism. The modification of proteins with O-linked ß-GlcNAc (O-GlcNAc) is sensitive to nutrient availability and may allow cellular adaptation to different metabolic conditions. Here, we examined how the modification of proteins with O-GlcNAc may control CCP formation and thus CME. We used perturbation of key enzymes responsible for protein O-GlcNAc modification, as well as specific mutants of the endocytic regulator AAK1 predicted to be impaired for O-GlcNAc modification. We identify that CCP initiation and the assembly of clathrin and other proteins within CCPs are controlled by O-GlcNAc protein modification. This reveals a new dimension of regulation of CME and highlights the important reciprocal regulation of cellular metabolism and endocytosis.

Deaths caused by medication in persons not using illicit narcotic drugs: An autopsy study from Western Denmark.

Information regarding deaths caused by poisoning or adverse effects of medication in Danish persons not using illicit narcotic drugs (PNUIDs) is sparse. To characterize aetiology, demographics, and death scene, we reviewed all legal autopsies performed at Aarhus University from 2017 to 2019 and isolated 96 deaths caused by medications in PNUIDs. Suicides caused by medication overdose accounted for 38%. Opioids and psychotropic medications were the main cause of death in 48% and 35% of the 96 cases, respectively. Morphine, tramadol, and quetiapine were the most commonly involved individual medications. A single medication caused death in 50% of cases, and multiple substances were involved in 50%. The median total number [interquartile range] of detected medications was 5 [4-6], with a higher number in females (5 [4-7]) than males (4 [2-5]), p = 0.009. Median age was 51 [42.5-61.5] years, and 57% were female. Scene of death most frequently involved a body on a bed or couch in the decedent's own home (72%). In conclusion, opioids and psychotropic medications dominated by morphine, tramadol and quetiapine most frequently caused medication-related deaths in PNUIDs. Monitoring this type of death may yield important knowledge to direct prophylactic initiatives regarding medication use and prescription.

Plasmodium falciparum resistance and malaria presentation in children at Dongola specialist hospital: A prospective cohort study.

OBJECTIVE: To provide evidence about the susceptibility of anti-malarial drugs, and to identify the clinical features of the disease in children. Methods: The prospective observational comparative study was conducted at the Dongola Specialist Hospital, Dunqulah, Sudan, from February 2016 to February 2017, and comprised children aged <16 years with bodyweight >5kg who had malaria. The subjects were enrolled into group 1, which received treatment based on physician's discretion, and group 2, which received treatment in accordance with the national guidelines. The follow-up was conducted on days 3, 7 and 14 to identify cases as early treatment failure, late treatment failure, or treatment success. Data were analysed in terms of frequencies and percentages using statistical analysis software R version 3.1.2. RESULTS: Of the 120 children, 60(50%) were in each of the two groups. Overall, 63(52.5%) were aged 1-6 years, 66(55%) were males, and 42(35%) were exposed to malaria for the first time. Post-treatment test was negative for all 120(100%) the subjects in both the groups. showing no inter-group difference. Conclusion: Although resistance to combination therapy was not detected, it remains extremely important to remain vigilant for the emergence of resistance in the future.

Optical Trocar Causing Aortic Injury: A Potentially Fatal Complication of Minimal Access Surgery.

Trocar injury to abdominal aorta is uncommon and even rare with optical trocars. Such injury, resulting from umbilical trocar insertion, is potentially fatal. It often causes on-table death due to torrential life-threatening haemorrhage and unavailability of expert vascular help. We present a rare case of an injury to infra-renal abdominal aorta, caused by optical trocar insertion for bariatric surgery. Immediate recognition of the injury, deployment of life-saving manoeuvres, timely resuscitation, followed by definitive repair of aorta by vascular surgeon was life-saving for this patient. The recovery phase was uneventful and patient had no residual clinical problems during follow-up.