Stimuli-responsive release of active anionophore from RGD-peptide-linked proanionophore.

Integrin-mediated cellular delivery was attempted to optimize practical applications of hydrophobic ionophores. The potent ionophore preferentially transports H+/Cl- across the lipid bilayers following a symport mechanism. The RGD-peptide-appended tag was stimulated by glutathione to generate the active ionophore, prompting the transport of Cl- under the cellular environment.

Genomic characterization of the first mpox and varicella-zoster co-infection in Pakistan (2023) through next-generation sequencing.

The global mpox outbreak spanning 2022-2023 has affected numerous countries worldwide. In this study, we present the first report on the detection, whole-genome sequence, and coinfection of the mpox virus and varicella zoster virus (VZV) from Pakistan. During April-May 2023, samples from 20 suspected cases of mpox were tested at the National Institutes of Health, Islamabad among which 4 tested positive. All four cases had a travel history of Saudi Arabia. All the suspected samples were processed by using a Zymo research kit for DNA extraction, followed by qRT-PCR amplification by using a DaAn Gene detection kit for the mpox virus. Further, two of the positive samples with a low Ct value (<20) were subjected to whole-genome sequencing using a metagenomic approach on the iSeq (Illumina) platform. The sequencing results revealed Clade IIb and genotype A.2.1 of MPXV, which clustered with viruses from Slovenia and the UK in July and June 2022, respectively. Our analysis identified two novel nonsynonymous substitutions in mpox virus, namely V98I in OPG046 and P600S in OPG109. Furthermore, we successfully retrieved the complete genome of VZV from the same sample, belonging to Clade 5. This study represents the first positive case of MPXV in Pakistan and the coinfection of mpox and VZV by using a metagenome approach providing insights into their complete genomes. Our results highlight the importance of surveillance at the point of entries, strengthening lab capacities including next-generation sequencing, and using differential diagnosis for timely and accurate detection of mpox cases.

Quinoline Thiourea-Based Zinc Ionophores with Antibacterial Activity.

The increasing resistance of bacteria to commercially available antibiotics threatens patient safety in healthcare settings. Perturbation of ion homeostasis has emerged as a potential therapeutic strategy to fight against antibacterial resistance and other channelopathies. This study reports the development of 8-aminoquinoline (QN) derivatives and their transmembrane Zn2+ transport activities. Our findings showed that a potent QN-based Zn2+ transporter exhibits promising antibacterial properties against Gram-positive bacteria with reduced hemolytic activity and cytotoxicity to mammalian cells. Furthermore, this combination showed excellent in vivo efficacy against Staphylococcus aureus. Interestingly, this combination prevented bacterial resistance and restored susceptibility of gentamicin and methicillin-resistant S. aureus to commercially available ß-lactam and other antibiotics that had lost their activity against the drug-resistant bacterial strain. Our findings suggest that the transmembrane transport of Zn2+ by QN derivatives could be a promising strategy to combat bacterial infections and restore the activity of other antibiotics.

Clinicopathological profile of peritoneal tuberculosis and a new scoring model for predicting mortality: an international ID-IRI study.

Existing literature about peritoneal tuberculosis (TBP) is relatively insufficient. The majority of reports are from a single center and do not assess predictive factors for mortality. In this international study, we investigated the clinicopathological characteristics of a large series of patients with TBP and determined the key features associated with mortality. TBP patients detected between 2010 and 2022 in 38 medical centers in 13 countries were included in this retrospective cohort. Participating physicians filled out an online questionnaire to report study data. In this study, 208 patients with TBP were included. Mean age of TBP cases was 41.4 ± 17.5 years. One hundred six patients (50.9%) were females. Nineteen patients (9.1%) had HIV infection, 45 (21.6%) had diabetes mellitus, 30 (14.4%) had chronic renal failure, 12 (5.7%) had cirrhosis, 7 (3.3%) had malignancy, and 21 (10.1%) had a history of immunosuppressive medication use. A total of 34 (16.3%) patients died and death was attributable to TBP in all cases. A pioneer mortality predicting model was established and HIV positivity, cirrhosis, abdominal pain, weakness, nausea and vomiting, ascites, isolation of Mycobacterium tuberculosis in peritoneal biopsy samples, TB relapse, advanced age, high serum creatinine and ALT levels, and decreased duration of isoniazid use were significantly related with mortality (p < 0.05). This is the first international study on TBP and is the largest case series to date. We suggest that using the mortality predicting model will allow early identification of high-risk patients likely to die of TBP.

Effective hydrolysis for waste plant biomass impacts sustainable fuel and reduced air pollution generation: A comprehensive review.

Among various natural biowastes availability in the environment, agricultural residues showed great impacts. It is due to huge availability and cheap carbon source, creating big challenges for their utility and systematic reduction. Objective of this review is to address the waste biomass availability and huge quantities issues and also put effort to minimize this nutrient load via biotransforming into value-added products. Different wastes (organic/inorganic) generation with their negative issues are due to numbers of developmental and social activities, reported. Currently, various efforts are found for these wastes minimization via generation of different types of value-added products (biogas, bioH2, alcoholic fuel, organic acids and others products) and these wastes in municipal cities are also reported with production of advanced biofuels as promising outcomes. For hydrolysis of complex organic resources including lignocellulosic biomasses, physicochemical, structural or compositional changes are needed that aid in conversion into sugar and organic compounds such as biofuels. So, efficient and effective pretreatment processes selection (physical, biological, chemical or combined one) is critical to achieve these hydrolysis goals and resultant cellulose or hemicellulose components can be accessible by biological catalysis. These can achieve final hydrolysis and fermentative or monomer sugars. And later, synthesis of fuels or value-added products during microbial fermentation or biotransformation processes can be achieved. This review discusses pretreatment techniques for improved hydrolysis for fermentative sugar with emphasis on reduced quantities of toxic compounds (furfural compound) in hydrolyzed biomasses. Minimum deterioration fuel economy also reported with production of different bioproducts including biofuels. Additionally, impacts of toxic products and gasses emission are also discussed with their minimization.

Analysing the role of gender and place of residence in acceptability and satisfaction towards e-learning among university students' during COVID-19 pandemic in India.

This paper has two broad objectives; the first is to examine the challenges of e-learning faced by the students keeping in view their place of residence and gender in India, particularly during the second-wave of Covid-19. The second objective is to examine the role of place of residence and gender of students in the acceptance and satisfaction towards e-learning. The data has been obtained through an online survey of the students of University of Jamia Millia Islamia, New Delhi, India, in which a total of 490 students participated. Selection of students has been done through stratified sampling technique. Initially the obtained data was analysed and discussed through simple statistical analysis. Later, a chi-square test of independence was applied to find out the dependency of psychological stress, level of acceptance and level of satisfaction towards e-learning on the place of residence and the gender. The major finding of the paper reveals that the gender and the place of residence of the students is significantly associated with their psychological stress, acceptance and satisfaction towards e-learning. Extra money spent on the purchase of online learning resources was greater in case of rural students.

Self-reported antibiotic stewardship and infection control measures from 57 intensive care units: An international ID-IRI survey.

We explored the self-reported antibiotic stewardship (AS), and infection prevention and control (IPC) activities in intensive care units (ICUs) of different income settings. A cross-sectional study was conducted using an online questionnaire to collect data about IPC and AS measures in participating ICUs. The study participants were Infectious Diseases-International Research Initiative (IDI-IR) members, committed as per their institutional agreement form. We analyzed responses from 57 ICUs in 24 countries (Lower-middle income (LMI), n = 13; Upper-middle income (UMI), n = 33; High-income (HI), n = 11). This represented (~5%) of centers represented in the ID-IRI. Surveillance programs were implemented in (76.9%-90.9%) of ICUs with fewer contact precaution measures in LMI ones (p = 0.02); (LMI:69.2%, UMI:97%, HI:100%). Participation in regional antimicrobial resistance programs was more significantly applied in HI (p = 0.02) (LMI:38.4%,UMI:81.8%,HI:72.2%). AS programs are implemented in 77.2% of institutions with AS champions in 66.7%. Infectious diseases physicians and microbiologists are members of many AS teams (59%&50%) respectively. Unqualified healthcare professionals(42.1%), and deficient incentives(28.1%) are the main barriers to implementing AS. We underscore the existing differences in IPC and AS programs' implementation, team composition, and faced barriers. Continuous collaboration and sharing best practices on APM is needed. The role of regional and international organizations should be encouraged. Global support for capacity building of healthcare practitioners is warranted.

Impulse Oscillometry as a measure of airway dysfunction in Sarcoidosis.

BACKGROUND: Sarcoidosis is a systemic inflammatory granulomatous disease which commonly affects intrathoracic lymph nodes, lung parenchyma and airways. OBJECTIVES: To measure respiratory impedance using Impulse Oscillometry (IOS) in patients with pulmonary sarcoidosis and compare the parameters with healthy controls. METHODS: Patients diagnosed with sarcoidosis (n=28); and age and gender matched healthy controls (n=17) were recruited. Lung volumes and capacities were measured by spirometry and respiratory system impedance was assessed using Impulse Oscillometry System (IOS). Measurements were performed before and 15 minutes after inhalation of a short acting bronchodilator. The IOS and spirometric parameters were compared between two groups and correlated. ROC curve analysis was also performed to identify the IOS parameters which can discriminate between sarcoidosis and healthy controls. RESULTS: Resistance at 5 and 20 Hz (R5 and R20), small airway resistance (R5-R20), resonant frequency (FRes) and area of reactance (AX) were significantly higher in Sarcoidosis subjects compared with controls. Reactance at 5 and 20 Hz (X5 and X20) were significantly lower in sarcoidosis. FEV1 (% predicted) and FVC (% predicted) were significantly lower in patients with sarcoidosis while FEV1/FVC ratio and peak expiratory flow rate (PEF) values were comparable. Post bronchodilator inhalation, there was improvement in airway resistance and reactance, but no significant changes observed in spirometric parameters. R5, X5 and R5-R20 are promising parameters to discriminate sarcoidosis from healthy controls. CONCLUSION: Increased airway resistance is a better indicator of airway involvement than airflow limitation by spirometry in pulmonary sarcoidosis.

Stimuli-responsive transmembrane anion transport by AIE-active fluorescent probes.

Anticancer drug resistance implicates multifunctional mechanisms, and hypoxia is one of the key factors in therapeutic resistance. Hypoxia-specific therapy is considered an extremely effective strategy to fight against cancer. The development of small molecule-based synthetic anion transporters has also recently drawn attention for their potential therapeutic applications against several ion-transport-associated diseases, such as cancer and others. Herein, we describe the development of a hypoxia-responsive proanionophore to trigger controlled transport of anions across membranes under pathogenic conditions. Herein, we report the development of tetraphenylethene (TPE)-based anion transporters. The sulfonium-linked p-nitrobenzyl containing TPE-based proanionophore could be converted into a lipophilic fluorescent Cl- ion carrier in a hypoxic or reductive environment. Stimuli such as nitroreductase (NTR) and glutathione (GSH) mediated regeneration of the TPE-based active Cl- ion transporter also showed aggregation-induced emission (AIE) properties. We hypothesize that such hypoxia and reductive stimuli activatable proanionophores have tremendous potential to fight against channelopathies, including cancer.

Vector-borne and zoonotic infections and their relationships with regional and socioeconomic statuses: An ID-IRI survey in 24 countries of Europe, Africa and Asia.

BACKGROUND: In this cross-sectional, international study, we aimed to analyze vector-borne and zoonotic infections (VBZI), which are significant global threats. METHOD: VBZIs' data between May 20-28, 2018 was collected. The 24 Participatingcountries were classified as lower-middle, upper-middle, and high-income. RESULTS: 382 patients were included. 175(45.8%) were hospitalized, most commonly in Croatia, Egypt, and Romania(P = 0.001). There was a significant difference between distributions of VBZIs according to geographical regions(P < 0.001). Amebiasis, Ancylostomiasis, Blastocystosis, Cryptosporidiosis, Giardiasis, Toxoplasmosis were significantly more common in the Middle-East while Bartonellosis, Borreliosis, Cat Scratch Disease, Hantavirus syndrome, Rickettsiosis, Campylobacteriosis, Salmonellosis in Central/East/South-East Europe; Brucellosis and Echinococcosis in Central/West Asia; Campylobacteriosis, Chikungunya, Tick-borne encephalitis, Visceral Leishmaniasis, Salmonellosis, Toxoplasmosis in the North-Mediterranean; CCHF, Cutaneous Leishmaniasis, Dengue, Malaria, Taeniasis, Salmonellosis in Indian Subcontinent; Lassa Fever in West Africa. There were significant regional differences for viral hemorrhagic fevers(P < 0.001) and tick-borne infections(P < 0.001), and according to economic status for VBZIs(P < 0.001). The prevalences of VBZIs were significantly higher in lower-middle income countries(P = 0.001). The most similar regions were the Indian Subcontinent and the Middle-East, the Indian Subcontinent and the North-Mediterranean, and the Middle-East and North-Mediterranean regions. CONCLUSIONS: Regional and socioeconomic heterogeneity still exists for VBZIs. Control and eradication of VBZIs require evidence-based surveillance data, and multidisciplinary efforts.

Presenting Characteristics, Comorbidities, and Outcomes Among Patients With COVID-19 Hospitalized in Pakistan: Retrospective Observational Study.

BACKGROUND: COVID-19 became a pandemic rapidly after its emergence in December 2019. It belongs to the coronavirus family of viruses, which have struck a few times before in history. Data based on previous research regarding etiology and epidemiology of other viruses from this family helped played a vital role in formulating prevention and precaution strategies during the initial stages of this pandemic. Data related to COVID-19 in Pakistan were not initially documented on a large scale. In addition, due to a weak health care system and low economic conditions, Pakistan's population, in general, already suffers from many comorbidities, which can severely affect the outcome of patients infected with COVID-19. OBJECTIVE: COVID-19 infections are coupled with a manifestation of various notable outcomes that can be documented and characterized clinically. The aim of this study was to examine these clinical manifestations, which can serve as indicators for early detection as well as severity prognosis for COVID-19 infections, especially in high-risk groups. METHODS: A retrospective observational study involving abstraction of demographic features, presenting symptoms, and adverse clinical outcomes for 1812 patients with COVID-19 was conducted. Patients were admitted to the four major hospitals in the Rawalpindi-Islamabad region of Pakistan, and the study was conducted from February to August 2020. Multivariate regression analysis was carried out to identify significant indicators of COVID-19 severity, intensive care unit (ICU) admission, ventilator aid, and mortality. The study not only relates COVID-19 infection with comorbidities, but also examines other related factors, such as age and gender. RESULTS: This study identified fever (1592/1812, 87.9%), cough (1433/1812, 79.1%), and shortness of breath (998/1812, 55.1%) at the time of hospital admission as the most prevalent symptoms for patients with COVID-19. These symptoms were common but not conclusive of the outcome of infection. Out of 1812 patients, 24.4% (n=443) required ICU admission and 21.5% (n=390) required ventilator aid at some point of disease progression during their stay at the hospital; 25.9% (n=469) of the patients died. Further analysis revealed the relationship of the presented symptoms and comorbidities with the progression of disease severity in these patients. Older adult patients with comorbidities, such as hypertension, diabetes, chronic kidney disease, and asthma, were significantly affected in higher proportions, resulting in requirement of ICU admission and ventilator aid in some cases and, in many cases, even mortality. CONCLUSIONS: Older adult patients with comorbidities, such as hypertension, diabetes, asthma, chronic obstructive pulmonary disorder, and chronic kidney disease, are at increased risk of developing severe COVID-19 infections, with an increased likelihood of adverse clinical outcomes.

Delayed admissions and efficacy of steroid use in patients with critical and severe COVID-19: an apprehensive approach.

BACKGROUND: Inadvertent delays in access to appropriate therapeutic interventions in high-risk group coronavirus disease 2019 (COVID-19) patients contribute to mortality in patients with severe/critical disease presentation. OBJECTIVES: The aim of this study was to determine the effect of timely admission to the hospital on mortality of patients with severe/critical COVID-19. Another secondary aspect of this study was to observe the efficacy of time-dependent use of corticosteroids on mortality of critical/severe COVID-19 patients. METHODS: Clinical data of 659 patients with severe/critical COVID-19, admitted to four major tertiary care hospitals from the Islamabad-Rawalpindi region of Pakistan was retrospectively collected from a period February-August 2020. Multivariate logistic regression analysis was carried out to determine the predictors of mortality in severe/critical COVID-19 patients. RESULTS: Out of a total of 659 patients, 469 (71.2%) patients died. Age > 60 years, presence of hypertension, heart disease and kidney disease along with late admission (>5 days) were significant predictors of mortality in patients with severe/critical COVID-19. CONCLUSIONS: The study highlights the importance of well-timed provision of appropriate medical interventions control COVID-19-associated mortality.

Profiles of multidrug-resistant organisms among patients with bacteremia in intensive care units: an international ID-IRI survey.

Evaluating trends in antibiotic resistance is a requisite. The study aimed to analyze the profile of multidrug-resistant organisms (MDROs) among hospitalized patients with bacteremia in intensive care units (ICUs) in a large geographical area. This is a 1-month cross-sectional survey for blood-borne pathogens in 57 ICUs from 24 countries with different income levels: lower-middle-income (LMI), upper-middle-income (UMI), and high-income (HI) countries. Multidrug-resistant (MDR), extensively drug-resistant (XDR), or pan-drug-resistant isolates were searched. Logistic regression analysis determined resistance predictors among MDROs. Community-acquired infections were comparable to hospital-acquired infections particularly in LMI (94/202; 46.5% vs 108/202; 53.5%). Although MDR (65.1%; 502/771) and XDR (4.9%; 38/771) were common, no pan-drug-resistant isolate was recovered. In total, 32.1% of MDR were Klebsiella pneumoniae, and 55.3% of XDR were Acinetobacter baumannii. The highest MDR and XDR rates were in UMI and LMI, respectively, with no XDR revealed from HI. Predictors of MDR acquisition were male gender (OR, 12.11; 95% CI, 3.025-15.585) and the hospital-acquired origin of bacteremia (OR, 2.643; 95%CI, 1.462-3.894), and XDR acquisition was due to bacteremia in UMI (OR, 3.344; 95%CI, 1.189-5.626) and admission to medical-surgical ICUs (OR, 1.481; 95% CI, 1.076-2.037). We confirm the urgent need to expand stewardship activities to community settings especially in LMI, with more paid attention to the drugs with a higher potential for resistance. Empowering microbiology laboratories and reports to direct prescribing decisions should be prioritized. Supporting stewardship in ICUs, the mixed medical-surgical ones in particular, is warranted.

An Overview of the Treatment Options Used for the Management of COVID-19 in Pakistan: Retrospective Observational Study.

BACKGROUND: Since the first reports of COVID-19 infection, the foremost requirement has been to identify a treatment regimen that not only fights the causative agent but also controls the associated complications of the infection. Due to the time-consuming process of drug discovery, physicians have used readily available drugs and therapies for treatment of infections to minimize the death toll. OBJECTIVE: The aim of this study is to provide a snapshot analysis of the major drugs used in a cohort of 1562 Pakistani patients during the period from May to July 2020, when the first wave of COVID-19 peaked in Pakistan. METHODS: A retrospective observational study was performed to provide an overview of the major drugs used in a cohort of 1562 patients with COVID-19 admitted to the four major tertiary-care hospitals in the Rawalpindi-Islamabad region of Pakistan during the peak of the first wave of COVID-19 in the country (May-July 2020). RESULTS: Antibiotics were the most common choice out of all the therapies employed, and they were used as first line of treatment for COVID-19. Azithromycin was the most prescribed drug for treatment. No monthly trend was observed in the choice of antibiotics, and these drugs appeared to be a random but favored choice throughout the months of the study. It was also noted that even antibiotics used for multidrug resistant infections were prescribed irrespective of the severity or progression of the infection. The results of the analysis are alarming, as this approach may lead to antibiotic resistance and complications in immunocompromised patients with COVID-19. A total of 1562 patients (1064 male, 68.1%, and 498 female, 31.9%) with a mean age of 47.35 years (SD 17.03) were included in the study. The highest frequency of patient hospitalizations occurred in June (846/1562, 54.2%). CONCLUSIONS: Guidelines for a targeted treatment regime are needed to control related complications and to limit the misuse of antibiotics in the management of COVID-19.

Building better tuberculosis control systems in a post-COVID world: learning from Pakistan during the COVID-19 pandemic.

OBJECTIVES: All countries impacted by COVID-19 have had to change routine health service delivery. Although this has reversed some of the progress made in reducing the global burden of tuberculosis (TB) disease, there is an opportunity to incorporate lessons learned to improve TB programmes going forward. APPROACH: We use Pakistan as a case study to discuss three important adaptations in light of COVID-19: bringing care closer to patients; strengthening primary health care systems; and proactively addressing stigma and fear. FINDINGS: COVID-19 control in Pakistan has restricted people's ability to travel and this has forced the TB programme to reduce the need for in-person health facility visits and bring care closer to patients' homes. Strategies that may be useful for providing more convenient care to patients in the future include: : remote treatment support using telemedicine; collaborating with private healthcare providers; and establishing community medicine collection points. As part of the response to COVID-19 in Pakistan, the out-patient departments of major tertiary and secondary care hospitals were closed, and this highlighted the importance of strengthening primary healthcare for both better pandemic and TB control. Finally, stigma associated with COVID-19 and TB can be addressed using trusted community-based health workers, such as Lady Health Workers in Pakistan.

Translation and cross-cultural adaptation of WHOQOL-HIV Bref among people living with HIV/AIDS in Pakistan.

BACKGROUND: Reliable Health-Related Quality of Life (HRQoL) assessment will be useful in identifying health issues and in identifying health care actions. Due to the lack of a psychometrically valid tool in Urdu, we aim to translate and examine the psychometric and cross-cultural adaptation of WHOQOL HIV Bref among people living with HIV/AIDS (PLWHA) in Pakistan. METHODS: The standard forward-backwards translation technique was used to convert English version of the WHOQOL HIV Bref into Urdu. After cognitive debriefing, final Urdu version of instrument was developed. Based on the principle of at least 5 subjects for each item, a sample of 182 patients was used using a universal random sampling technique from the Pakistan Institute of Medical Sciences, Islamabad. The Cronbach's alpha and intra-class correlation coefficients (ICC) were estimated to assess internal validity and reliability of the translated version. Exploratory factor analysis was carried out to determine the factor structure and independent associations between the instrument domains and CD-4T-cell count were assessed using multivariable linear regression RESULTS: High Cronbach alpha 0.93 was found for all WHOQOL HIV Bref facets. The test-retest reliability demonstrated a statistically significant ICC ranged from 0.88 to 0.98 (p < 0.001). In known group validity, lower CD-4 lymphocytes count was significantly related to poor scores for all six domains (p < 0.001). Similarly, symptomatic subjects had significantly lower scores compared to asymptomatic subjects on the physical, psychological, social relationship and independence domains (p < 0.05). Statistically significant positive correlation of all six domains of instrument with CD4 cells count (p < 0.001), exhibiting patients with higher CD-4 cells will have higher mean scores of all domains. Factor analysis revealed 5 domains, including physical health, psychological health, social relationship, environmental, and spiritual health. Multivariable linear regression analysis reported; only physical, psychological health and environment health domains were found significantly associated with higher CD-4 lymphocytes count (Beta = 0.121, p < 0.001, Beta = 0.103, p = 0.002, and Beta = 0.032, p = 0.032). CONCLUSION: Findings suggested that the Urdu version of WHOQOL HIV Bref is a psychometrically valid and culturally well-adapted HRQoL measurement tool for PLWHA in Pakistan.

A cross sectional study to assess nasal carriage of methicillin resistant Staphylococcus aureus in healthcare professionals in a tertiary care hospital.

OBJECTIVE: To determine the nasal carriage of staphylococcus aureus and methicillin-resistant staphylococcus aureus among healthcare workers in a tertiary care setting. METHODS: The cross-sectional study was conducted at the Pakistan Institute of Medical Sciences, Islamabad, Pakistan, from April to July 2018, and comprised healthcare workers at the institution. Nasal swabs were collected and cultured on Mannitol salt agar. Mannitol fermenting colonies which were gram-positive cocci, catalase-positive and coagulase-positive were identified as staphylococcus aureus. Antibiotic susceptibility test was performed by modified Kirby-Bauer disc diffusion method. Methicillin resistance was detected using cefoxitin disc diffusion method. Data was analysed using SPSS 23. RESULTS: Of the 210 nasal swabs, 52(24.76%) had a staphylococcus aureus growth, and of them, 15(7.1%) were methicillin-resistant. No association could be established with either any single category of healthcare worker or an inter-department variation (p>0.05). Likewise, there was no association with age, gender, duration of service, smoking, co-morbidities, use of antibiotics in the preceding six months, treating a patient with methicillin-resistant staphylococcus aureus in the preceding six months and hospitalisation in the preceding year (p>0.05). CONCLUSIONS: The frequency of nasal carriage of methicillin resistant staphylococcus aureus amongst healthcare workers was regardless of the nature of their professional engagement.

Inhibition of immunosuppressive indoleamine 2,3-dioxygenase by targeting the heme and apo-form.

Inhibition of immunomodulating enzyme indoleamine 2,3-dioxygenase 1 (IDO1) is considered one of the potential approaches in the fight against cancer and other diseases. Comprehensive biophysical and cellular studies have shown that quinine derivatives effectively inhibit the activity of IDO1. Mechanistic studies revealed that the potent quinine derivatives compete with heme for binding to apo-IDO1 and perturb its reversible binding propensity to apo-IDO1 via the formation of a heme-inhibitor complex. This IDO1 inhibitory pathway could provide new avenues to immunotherapy-based drug discovery strategies.

Multi-stimuli controlled release of a transmembrane chloride ion carrier from a sulfonium-linked procarrier.

In recent times, anion transporters have received substantial consideration due to their ability to disrupt the ionic equilibrium across membrane bilayers. While numerous Cl- ion transporters were developed for channelopathies, unfortunately, poor aqueous solubility precluded their bioapplicability. Herein, we demonstrate the development of a multi-stimuli activatable anion transport approach to induce regulated transport of Cl- ions across membranes under specific conditions. The sulfonium-based procarrier was initially inactive, but the transmembrane transport of Cl- ions was activated in the presence of stimuli such as glutathione (GSH), reactive oxygen species (ROS) and light. The release of the hydrophobic anionophore from the aqueous-soluble procarrier under specific conditions leads to the successful transport of Cl- ions. Under physiological conditions, these anion carriers follow an antiport exchange mechanism to transport Cl- ions across lipid bilayers. Such multi-stimuli activatable procarriers have great potential to combat various types of channelopathies, including cancer, cystic fibrosis, kidney stones, myotonia, and others.