Frequency, management and impact of adverse events on treatment outcomes in patients with multidrug resistant tuberculosis in Balochistan, Pakistan.

Background: Early detection, monitoring, and managing adverse events (AEs) are crucial in optimising treatment for multidrug-resistant tuberculosis (MDR-TB) patients. Objectives: To investigate the incidence, factors, management, and impact of AEs on treatment outcomes in MDR-TB patients. Methods: This study reviewed the medical records of 275 MDR-TB patients at Fatimah Jinnah Institute of Chest Diseases in Quetta, Pakistan. Patient information was collected using a designed data collection form. Mann-Whitney U and Kruskal-Wallis tests examined the difference in AEs occurrences based on patients' characteristics. Multiple binary logistic regression identified factors associated with unsuccessful outcomes, with statistical significance set at a p-value < 0.05. Results: Almost all patients (99.6%) experienced at-least one AE (median = 4/patient, interquartile range:3-6). The most common were GI disturbance (95.3%), arthralgia (80.4%), body pain and headache (61.8%), ototoxicity (61.4%), psychiatric disturbance (44%), hypokalaemia (40.4%), dermatological reactions (26.2%) and hypothyroidism (21.5%). AEs led to treatment modification in 7.3% patients. Educated patients, those with a history of TB treatment, previous use and resistance to any second-line drug had significantly higher number of AEs. A total of 64.0% were declared cured, 3.6% completed treatment, 19.6% died and 12.7.9% were lost to follow-up. Patients' age of 41-60(OR = 9.225) and >60 years(OR = 23.481), baseline body weight of 31-60 kg(OR = 0.180), urban residence(OR = 0.296), and experiencing ototoxicity (OR = 0.258) and hypothyroidism (OR = 0.136) were significantly associated with unsuccessful treatment outcomes. Conclusion: AEs were highly prevalent but did not negatively impact treatment outcomes. Patients at higher risk of developing AEs and unsuccessful outcomes should receive special attention for its early management.

Isotopic evidence of autochthonous organic matter acting as a major sink of anthropogenic heavy metals in modern lacustrine sediments.

The knowledge of major sources, sinks, and the burial fate of various pollutants added to modern aquatic ecosystems under changing environmental conditions is limited but crucial for our sustainability. In this context, the spatial distributions and causative factors of organic matter (OM) and heavy metal accumulations have been explored in modern lacustrine sediments of a large urbanized and protected wetland (ULB: Upper Lake Bhopal) in Central India. For this purpose, geochemical properties, in particular, stable isotopes (δ13C and δ15N) were measured in the ULB surficial sediments (core depth ∼0-1 cm; n = 19), and additionally collected riverbed sediments (n = 2) and atmospheric free-fall dust samples (n = 3) from the lake periphery. The major and trace element data indicate widespread mafic sediment provenance and nearly dysoxic lacustrine conditions. The riverine supply of soil OM from cropped lands and the lake productivity (algae, largely sustained by nutrients from sewage and agricultural runoff) are the major OM sources to the western and eastern lake portions, respectively. The fractional contribution from autochthonous TOC (∼0.19-0.95, mean ∼0.62) predominates that of allochthonous TOC (∼0.05-0.81, mean ∼0.38). Whereas, atmospheric dust deposition is a primary anthropogenic source of heavy metals (Pb and Zn). The lake productivity rather than soil OM or any mineral sorbent is found responsible for the anthropogenic enrichments of Pb and Zn in the ULB surficial sediments, especially on the eastern ULB portion under high anthropogenic pressure. Therefore, the settled OM (primarily autochthonous) being oxidizable acts as a temporary but major sink of anthropogenic heavy metals in modern lacustrine sediments, which are vulnerable to heavy metal efflux to the water column by sediment diagenesis.

Identifying patients with multidrug-resistant tuberculosis who may benefit from shorter durations of treatment.

OBJECTIVE: Studying treatment duration for rifampicin-resistant and multidrug-resistant tuberculosis (MDR/RR-TB) using observational data is methodologically challenging. We aim to present a hypothesis generating approach to identify factors associated with shorter duration of treatment. STUDY DESIGN AND SETTING: We conducted an individual patient data meta-analysis among MDR/RR-TB patients restricted to only those with successful treatment outcomes. Using multivariable linear regression, we estimated associations and their 95% confidence intervals (CI) between the outcome of individual deviation in treatment duration (in months) from the mean duration of their treatment site and patient characteristics, drug resistance, and treatments used. RESULTS: Overall, 6702 patients with successful treatment outcomes from 84 treatment sites were included. We found that factors commonly associated with poor treatment outcomes were also associated with longer treatment durations, relative to the site mean duration. Use of bedaquiline was associated with a 0.51 (95% CI: 0.15, 0.87) month decrease in duration of treatment, which was consistent across subgroups, while MDR/RR-TB with fluoroquinolone resistance was associated with 0.78 (95% CI: 0.36, 1.21) months increase. CONCLUSION: We describe a method to assess associations between clinical factors and treatment duration in observational studies of MDR/RR-TB patients, that may help identify patients who can benefit from shorter treatment.

Effect of spin polarization on electron acceleration in magnetized quantum plasma by a surface plasma wave.

The effect of spin-up and spin-down exchange interaction on electron acceleration by a surface plasma wave (SPW) propagating in magnetized quantum plasma has been studied. The SPW was excited over the metal-vacuum interface with maximum amplitude at the interface. The effective dielectric constant was evaluated, considering the effects of quantum Bohm potential, degenerate Fermi pressure, and electron spin. The externally applied magnetic field perturbed the densities of the oppositely spinning electrons, which resulted in spin polarization. The dispersion relation and energy exchange mechanism for the electron acceleration was built, incorporating the effects of spin polarization in the wave-plasma interaction. The energy gain was found to increase with the spin polarization.

Unsuccessful treatment outcome and associated risk factors. A prospective study of DR-TB patients from a high burden country, Pakistan.

INTRODUCTION: Tuberculosis (TB), a curable and preventable infectious disease, becomes difficult to treat if resistance against most effective and tolerable first line anti-TB drugs is developed. The objective of the present study was to evaluate the treatment outcomes and predictors of poor outcomes among drug-resistant tuberculosis (DR-TB) patients treated at a programmatic management unit of drug resistant tuberculosis (PMDT) unit, Punjab, Pakistan. METHODS: This prospective observational study was conducted at a a PMDT unit in Multan, Punjab, Pakistan. A total of 271 eligible culture positive DR-TB patients enrolled for treatment at the study site between January 2016 and May 2017 were followed till their treatment outcomes were recorded. World Health Organization's (WHO) defined criteria was used for categorizing treatment outcomes. The outcomes of cured and treatment completed were collectively placed as successful outcomes, while death, lost to follow-up (LTFU) and treatment failure were grouped as unsuccessful outcomes. Multivariable binary logistic regression analysis was employed for getting predictors of unsuccessful treatment outcomes. A p-value <0.05 was considered statistically significant. RESULTS: Of the 271 DR-TB patients analysed, nearly half (51.3%) were males. The patient's (Mean ± SD) age was 36.75 ± 15.69 years. A total of 69% patients achieved successful outcomes with 185 (68.2%) patients being cured and 2 (0.7%) completed therapy. Of the remaining 84 patients with unsuccessful outcomes, 48 (17.7%) died, 2 (0.7%) were declared treatment failure, 34 (12.5%) were loss to follow up. After adjusting for confounders, patients' age > 50 years (OR 2.149 (1.005-4.592) with p-value 0.048 and baseline lung cavitation (OR 7.798 (3.82-15.919) with p-value <0.001 were significantly associated with unsuccessful treatment outcomes. CONCLUSIONS: The treatment success rate (69%) in the current study participants was below the target set by WHO (>75%). Paying special attention and timely intervention in patients with high risk of unsuccessful treatment outcomes may help in improving treatment outcomes at the study site.

Public awareness regarding the manufacturer provided information about medicine usage, safety, and adverse drug reactions in Balochistan, Pakistan.

Objectives: This study aimed to analyze the general public's awareness of medicine information, safety, and adverse drug reactions in Quetta, Pakistan. Methods: A cross-sectional descriptive study was conducted using random sampling from April 2020 to April 2021 in Quetta. Samples were collected from respondents who met the inclusion criteria and had visited community pharmacies. The analysis was done using SPSS version 23. Bivariate and multivariate analyses were performed to assess factors associated with good knowledge. Results: Multivariate analysis revealed that purchase on prescription was a determining factor of knowledge regarding knowledge of pharmaceutical products and their provided information, medicines usage and safety, and Medication ADRs. Patients who bought medicines on prescriptions were more likely to have better knowledge. Patients having education were more likely to have better knowledge. Conclusion: Public awareness about medicine information, safety, and the information provided by manufacturers is crucial to ensuring that patients have access to accurate information about their medications and can make informed decisions about their health. Healthcare providers and regulatory bodies must work together to improve access to information and promote safe medication practices.

Evaluation of hypertension control among hemodialysis patients in Pakistan: a prospective follow-up study.

BACKGROUND: Hypertension is highly prevalent and uncontrolled among hemodialysis patients. In Pakistan published data does not provide enough information about the management and factors associated with uncontrolled hypertension in hemodialysis patients. OBJECTIVE: This study was conducted to evaluate the factors influencing the pharmacotherapeutic management and control of hypertension in hemodialysis patients. METHODS: A prospective follow-up study was conducted on hemodialysis patients who were enrolled at study sites between 1 June 2020 and 31 December 2020. The predialysis blood pressure (BP) readings were recorded as mean SBP and DBP at baseline and for each of 6 months. Multivariate analyses were applied to analyze the factors associated with uncontrolled hypertension in hemodialysis patients. RESULTS: The average predialysis BP (SBP and DBP) of study participants at baseline visit was 158.41 and 87.22 mmHg respectively. After 6 months the study participants have 150.27 mmHg and 80.03 mmHg average predialysis SBP and DBP respectively. Only 28.1% of hemodialysis patients were on target BP after 6 months. Results of multivariate analysis have shown that the use of beta-blockers and calcium channel blockers (CCBs) were significantly associated with hypertension control at baseline [odds ratio (OR) = 1.432, P value = 0.034] (OR = 1.499, P value = 0.045) and at after 6 months (OR = 2.824, P value = 0.015) (OR = 1.883, P value = 0.032). CONCLUSION: This study revealed that among the antihypertensive drugs, CCBs and beta-blockers provided better management in controlling hypertension among hemodialysis patients.

A Binary Solution Strategy Enables High-Efficiency Quasi-2D Perovskite Solar Cells with Excellent Thermal Stability.

Quasi-two-dimensional (2D) perovskites are highly promising light-harvesting materials for commercialization of perovskite solar cells (PSCs) owing to the excellent materials stability. However, the coexistence of multiple n-value species in 2D perovskites often causes increased complexities in crystallization that can negatively affect the eventual photovoltaic performance. Herein, we present a binary solution based strategy via introducing nontoxic and widely accessible CH3COOH (HAc) as a co-solvent for preparing high-quality 2D perovskite films. Based on a 2D perovskite model system, (AA)2MA4Pb5I16 (n = 5), we show that the prenucleation and grain growth kinetics are appreciably modified with HAc, which benefits from the strong electron-donating ability of HAc with the key component of PbI2, leading to formation of favorable cluster aggregates and resultant modulation of crystal growth. With the HAc-based method, the devices yield a boosted photovoltaic efficiency of 18.55% with an impressive photovoltage of 1.26 V. The champion cells exhibit a supreme thermal stability, showing <3% efficiency degradation under continuous thermal aging for 800 h.

Cadmium-Free Kesterite Thin-Film Solar Cells with High Efficiency Approaching 12.

Cadmium sulfide (CdS) buffer layer is commonly used in Kesterite Cu2 ZnSn(S,Se)4 (CZTSSe) thin film solar cells. However, the toxicity of Cadmium (Cd) and perilous waste, which is generated during the deposition process (chemical bath deposition), and the narrow bandgap (≈2.4 eV) of CdS restrict its large-scale future application. Herein, the atomic layer deposition (ALD) method is proposed to deposit zinc-tin-oxide (ZTO) as a buffer layer in Ag-doped CZTSSe solar cells. It is found that the ZTO buffer layer improves the band alignment at the Ag-CZTSSe/ZTO heterojunction interface. The smaller contact potential difference of the ZTO facilitates the extraction of charge carriers and promotes carrier transport. The better p-n junction quality helps to improve the open-circuit voltage (VOC ) and fill factor (FF). Meanwhile, the wider bandgap of ZTO assists to transfer more photons to the CZTSSe absorber, and more photocarriers are generated thus improving short-circuit current density (Jsc). Ultimately, Ag-CZTSSe/ZTO device with 10 nm thick ZTO layer and 5:1 (Zn:Sn) ratio, Sn/(Sn + Zn): 0.28 deliver a superior power conversion efficiency (PCE) of 11.8%. As far as it is known that 11.8% is the highest efficiency among Cd-free kesterite thin film solar cells.

Pattern, frequency and factors associated with inappropriate high dosing in chronic kidney disease patients at a tertiary care hospital in Pakistan.

BACKGROUND: Patients with chronic kidney diseases (CKD) are susceptible to the toxic drug effects if given unadjusted doses. Although Pakistan harbors a high burden of CKD patients, there is limited information available on the frequency, pattern and factors associated with unadjusted drug doses among CKD patients. METHODS: This cross-sectional study conducted at Sandeman Provincial Hospital, Quetta included 303 non-dialysis ambulatory CKD patients (glomerular filtration rate < 60 ml/min/1.73m2). The patients' data were collected through a purpose designed data collection form. The appropriateness of doses was checked against the renal drug handbook-2018, Kidney Disease Improving Global Outcomes guidelines, British National Formulary-2022, and manufacturer leaflets. Data were analysed by SPSS 23 and multiple binary logistic regression analysis was used to assess the factors associated with receiving inappropriate high doses. A p-value < 0.05 was considered statistically significant. RESULTS: The patients received a total of 2265 prescription lines, with a median of eight different drugs per patient (interquartile range: 6-9 drugs). A total of 34.5% (783/2265) drugs required dose adjustment. Of these, doses were not adjusted for 56.1% (440) drugs in 162 (53.4%) patients. The most common pharmacological class of drugs requiring dose adjustment were antibiotics (79.1%), followed by antidiabetics (59.2%), diuretics (57.0%), angiotensin converting enzyme inhibitors (56.9%), beta blockers (56.9%), analgesics (56.0%), angiotensin receptor blockers (55.2%), domperidone (53.9%) and antihyperlipidmics (46.1%). Patient's age of 41-60 (OR = 5.76) and > 60 years (OR = 9.49), hypertension (OR = 2.68), diabetes mellitus (OR = 3.47) and cardiovascular diseases (OR = 2.82) had statistically significant association (p-value < 0.05) with inappropriate high doses. CONCLUSION: The high frequency of inappropriate high doses suggests an important quality gap in medication dosing for patients with ND-CKD at the study site. Special attention should be paid to the drugs and patients with identified risk factors for receiving inappropriate high doses.

Frequency, types and predictors of drug therapy problems among non-dialysis chronic kidney disease patients at a tertiary care hospital in Pakistan.

BACKGROUND: Drug therapy problems (DTPs) are common among patients suffering from chronic kidney disease (CKD). However, there is a lack of information about DTPs and its predictors among CKD patients from Pakistan. OBJECTIVES: To evaluate the frequency, type and predictors of various types of DTPs among CKD patients at a tertiary-care hospital in Pakistan. METHODOLOGY: This was a cross-sectional study carried out at Sandeman Provincial Hospital, Quetta between 1-11-2020 and 31-1-2021. It included 303 non-dialysis ambulatory patients of CKD-stage 3 and above. Cipolle et al., criterion was used for classifying the DTPs and a clinician at the study site checked the identified DTPs for accuracy. Data were analyzed by SPSS 23. Multivariate analysis was conducted to find the predictors of individual types of DTPs. A p-value <0.05 was considered statistically significant. RESULTS: The patients received a total of 2265 drugs with a median of eight drugs per patient (range: 3-15 drugs). A total of 576 DTPs were identified among 86.1% patients with a median of two DTPs (interquartile range 1-3) per patient. Dosage too high (53.5%) was the most common DTP followed by adverse drug reactions (ADRs) (50.5%) and need of additional drug therapy (37.6%). In multivariate analysis, patients' age of >40 years emerged as a predictor of unnecessary drug therapy and dosage too high. The odds of needing a different drug product was significantly high in patients with cardiovascular diseases (CVD) and diabetes mellitus (DM). The dosage too low had significant association with CVD. The risk of ADRs was significantly high in elderly patients (>60 years) and those with CVD. The presence of hypertension, DM and CKD stage-5 emerged as predictors of dosage too high. CONCLUSION: This study revealed a high prevalence of DTPs among CKD patients. Targeted interventions in high risk patients may reduce the frequency of DTPs at the study site.

Cudraflavone B induces human glioblastoma cells apoptosis via ER stress-induced autophagy.

BACKGROUND: Glioblastoma (GBM) is the most common malignant intracranial tumor with a low survival rate. However, only few drugs responsible for GBM therpies, hence new drug development for it is highly required. The natural product Cudraflavone B (CUB) has been reported to potentially kill a variety of tumor cells. Currently, its anit-cancer effect on GBM still remains unknown. Herein, we investigated whether CUB could affect the proliferation and apoptosis of GBM cells to show anti-GBM potential. RESULTS: CUB selectively inhibited cell viability and induced cell apoptosis by activating the endoplasmic reticulum stress (ER stress) related pathway, as well as harnessing the autophagy-related PI3K/mTOR/LC3B signaling pathway. Typical morphological changes of autophagy were also observed in CUB treated cells by microscope and scanning electron microscope (SEM) examination. 4-Phenylbutyric acid (4-PBA), an ER stress inhibitor, restored the CUB-caused alteration in signaling pathway and morphological change. CONCLUSIONS: Our finding suggests that CUB impaired cell growth and induced cell apoptosis of glioblastoma through ER stress and autophagy-related signaling pathways, and it might be an attractive drug for treatment of GBM.

Combined effects of vitamin C and cold atmospheric plasma-conditioned media against glioblastoma via hydrogen peroxide.

Glioblastoma is the most lethal intracranial malignant tumor, for which the five-year overall survival rate is approximately 5%. Here we explored the therapeutic combination of vitamin C and plasma-conditioned medium on glioblastoma cells in culture and as subcutaneous or intracranial xenografts in mice. The combination treatment reduced cell viability and proliferation while promoting apoptosis, and the effects were significantly stronger than with either treatment on its own. Similar results were obtained in the two xenograft models. Vitamin C appeared to upregulate aquaporin-3 and enhance the uptake of extracellular H2O2, while the combination treatment increased intracellular levels of reactive oxygen species including H2O2 and activated the JNK signaling pathway. The cytotoxic effects of the combination treatment were partially reversed by the specific JNK signaling inhibitor SP600125. Our results suggest that the combination of vitamin C and plasma-conditioned medium has therapeutic potential against glioblastoma, and they provide mechanistic insights that may help investigate this and other potential therapies in greater depth.

Treatment Outcomes of Childhood TB Patients in Four TB High Burden States of Malaysia: Results from a Multicenter Retrospective Cohort Study.

Data regarding treatment outcomes among childhood TB patients are lacking in Malaysia. The present study aimed to evaluate the treatment outcomes and predictors of unsuccessful treatment outcomes among childhood TB patients in four TB high-burden states of Malaysia. This was a retrospective cohort study conducted at 13 healthcare centers in four states of Malaysia, namely, Sabah, Sarawak, Selangor, and Penang. During the study period, a total of 8932 TB patients were enrolled for treatment at the study sites, of whom 206 (2.31%) were children. The majority of the childhood TB patients were female (52.9%) and belonged to the age group of 6-10 years (42.7%). Pulmonary TB accounted for 70.9% of childhood TB. Among childhood PTB patients, 50% were sputum smear negative. One hundred and seventy-eight patients (86.4%) were successfully treated (87 were cured and 91 completed treatment). Among 28 (13.6%) patients with unsuccessful treatment outcomes, 13 (6.3%) died, 3 (1.5%) failed treatment, 9 (4.4%) defaulted, and 3 (1.5%) were transferred out. Multivariate analysis revealed that patients' age (5-14 years) (OR = 0.279, p-value = 0.006) and male gender (OR = 0.390, p-value = 0.046) had a statistically significant negative association with unsuccessful treatment outcomes. The prevalence of childhood TB in the current study was comparable to the recently published national estimates. The study sites reached the WHO target of treatment success. Special attention to patients with identified risk factors can improve treatment outcomes.

Doctors' adherence to guidelines recommendations and glycaemic control in diabetic patients in Quetta, Pakistan: Findings from an observational study.

Background: Poor control of diabetes mellitus (DM) is partly attributed to doctors' poor adherence to guidelines. Objective: To evaluate doctors' adherence to pharmacotherapeutic recommendations of DM management guidelines and factors associated with guidelines adherence and glycaemic control. Methods: This prospective observational study included 30 doctors who were treating DM patients in their private clinics in Quetta, Pakistan. On visit 1, a total of 600 prescriptions written by 30 enrolled doctors (20 patients per doctor) were noted along with patients' sociodemographic and clinical characteristics. American Diabetes Association guidelines was used as a reference. The prescriptions noted were judged for guidelines compliance. Of 600 enrolled patients, 450 patients (15 patients per doctor) were followed for one more visit and included in final analysis. Glycated hemoglobin (HbA1c) level noted one visit 2 was related with the respective prescription on visit 1. Data were analyzed by SPSS (version 23). A p-value <0.05 was considered statistically significant. Results: Patients received a median of two antidiabetic drugs (range: 1-5). A total of 73.1% patients were on polytherapy. Metformin was the most frequently prescribed (88.4%) antidiabetic followed by gliptins (46.2%). A total of 41.6% prescriptions were judged guidelines compliant. In multivariate binary logistic regressions (MVBLR) analysis, chronic kidney disease (CKD) (OR = 0.422) and polytherapy (OR = 0.367) had statistically significant negative associations (p-value <0.05) with guidelines' compliant prescriptions. The group of doctors comprised of specialists and consultants wrote significantly (p-value = 0.004) high number of guidelines adherent prescriptions (mean rank = 20.25) than the group comprised of medical officers (mean rank = 11.34). On visit 2, only 39.5% patients were on goal glycemic levels. In MVBLR analysis, suffering from dyslipidemia (OR = 0.134) and CKD (OR = 0.111), receiving sulfonylurea (OR = 0.156) and guidelines' compliant prescription (OR = 4.195) were significantly (p-value <0 .05) associated with glycemic control. Conclusion: Although guidelines compliant prescriptions produced better glycemic control, but doctors' adherence to guidelines and glycemic control were poor. Polytherapy and CKD emerged as risk factors for guidelines divergent prescriptions. Dyslipidemia, CKD and reception of sulfonylureas had negative association with glycemic control.

Magnetoelectric core-shell CoFe2O4@BaTiO3 nanorods: their role in drug delivery and effect on multidrug resistance pump activity in vitro.

Nanoparticle mediated targeted drug delivery has become a widespread area of cancer research to address premature drug delivery problems. We report the synthesis of magneto-electric (ME) core-shell cobalt ferrite-barium titanate nanorods (CFO@BTO NRs) to achieve "on demand" drug release in vitro. Physical characterizations confirmed the formation of pure CFO@BTO NRs with appropriate magnetic and ferroelectric response, favorable for an externally controlled drug delivery system. Functionalization of NRs with doxorubicin (DOX) and methotrexate (MTX) achieved up to 98% drug release in 20 minutes, under a 4 mT magnetic field (MF). We observed strong MF and dose dependent cytotoxic response in HepG2 and HT144 cells and 3D spheroid models (p < 0.05). Cytotoxicity was characterized by enhanced oxidative stress, causing p53 mediated cell cycle arrest, DNA damage and cellular apoptosis via downregulation of Bcl-2 expression. In addition, MF and dose dependent inhibition of Multidrug Resistance (MDR) pump activity was also observed (p < 0.05) indicating effectivity in chemo-resistant cancers. Hence, CFO@BTO NRs represent an efficient carrier system for controlled drug delivery in cancer nanotherapeutics, where higher drug uptake is a prerequisite for effective treatment.

Comparative effectiveness of individualized longer and standardized shorter regimens in the treatment of multidrug resistant tuberculosis in a high burden country.

Objective: To compare the effectiveness of second line injectables containing shorter (duration 9-12 months) and longer treatment regimens (LTR, duration ≥ 20 months) among multidrug-resistant tuberculosis (MDR-TB) patients with no documented resistance and history of treatment with any second-line anti-TB drug (SLD) for ≥ 1 month. Methods: This was an observational cohort study of MDR-TB patients treated at eight PMDT units in Pakistan. Patients' data from baseline until treatment outcomes were collected from Electronic Nominal Recording and Reporting System. The treatment outcomes of "cured" and "treatment completed" were grouped together as successful, whereas "death," "treatment failure," and "lost to follow-up" were collectively grouped as unsuccessful outcomes. Time to sputum culture conversion (SCC) was analyzed using the Kaplan-Meier method and the differences between groups were compared through the log-rank test. Multivariate Cox proportional hazards and binary logistic regression analyses were used to find predictors of time to SCC and unsuccessful treatment outcomes. A p-value < 0.05 was considered statistically significant. Results: A total 701 eligible MDR-TB patients [313 treated with shorter treatment regimen (STR) and 388 treated with LTR at eight centres in Pakistan were evaluated]. Time to achieve SCC was significantly shorter in STR group [mean: 2.03 months, 95% confidence interval (CI):1.79-2.26] than in LTR group (mean: 2.69 months, 95% CI: 2.35-3.03) (p-value<0.001, Log-rank test). Treatment success was higher in STR (83.7%) than in LTR (73.2%) group (p-value <0.001) due to high cure (79.9% vs. 70.9%, p-value = 0.006) and low death (9.9% vs. 18.3%, p-value = 0.002) rates with STR. Treatment with STR emerged the only predictor of early SCC [adjusted Hazards ratio (aHR) = 0.815, p-value = 0.014], whereas, patient's age of 41-60 (OR = 2.62, p-value<0.001) and >60 years (OR = 5.84, p-value<0.001), baseline body weight of 31-60 (OR = 0.36, p-value = 0.001) and >60 kg (OR = 0.23, p-value <0.001), and treatment with LTR (OR = 1.88, p-value = 0.001) had statistically significant association with unsuccessful treatment outcomes. Conclusion: STR exhibited superior anti-microbial activity against MDR-TB. When compared LTR, treatment with STR resulted in significantly early SCC, high cure, and lower death rates among MDR-TB patients who had no documented resistance and history of treatment with any SLD ≥ 1 month.

The molecular mechanisms of ferroptosis and its role in glioma progression and treatment.

Ferroptosis is one of the programmed modes of cell death that has attracted widespread attention recently and is capable of influencing the developmental course and prognosis of many tumors. Glioma is one of the most common primary tumors of the central nervous system, but effective treatment options are very limited. Ferroptosis plays a critical role in the glioma progression, affecting tumor cell proliferation, angiogenesis, tumor necrosis, and shaping the immune-resistant tumor microenvironment. Inducing ferroptosis has emerged as an attractive strategy for glioma. In this paper, we review ferroptosis-related researches on glioma progression and treatment.

A novel CuBi2O4/polyaniline composite as an efficient photocatalyst for ammonia degradation.

A novel polyaniline (PANI) coupled CuBi2O4 photocatalyst was successfully synthesized via in situ polymerization of aniline with pre-synthesized CuBi2O4 composites. The structure and morphology of the synthesized CuBi2O4/PANI composite photocatalyst were characterized by X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR) and the photocatalytic performance were evaluated through degradation process of ammonia in water under visible light irradiation. The resultant CuBi2O4/PANI composite showed exceptional stability as its structure and morphology persisted even after being immersed in water for 2 days. The composite photocatalyst exhibited improved charge transport properties due to the electrical conductivity of the PANI protective layer, leading to enhanced photoelectrochemical activity in water and removal of ammonia. PANI with CuBi2O4 (10% wt) heterostructure was applied for photodegradation of ammonia and exhibited a 96% ammonia removal efficiency (30 mg/l with 0.1 g photocatalyst and 180 min), as compared to PANI (78%) and CuBi2O4 (70%). The degradation was attributed to the efficient charge transfer (e- and h+) and formation of reactive oxygen species upon simulated sunlight exposure. The present work suggests that the CuBi2O4/PANI photocatalyst can be synthesized in a simple process and provides an excellent adsorption capacity, high photocatalytic activity, long term stability, and reusability making it a promising alternative for ammonia removal from wastewater.

Genetic Analysis of HIV-1 vpr Sequences from HIV-Infected Older Patients on Long-Term Antiretroviral Therapy.

BACKGROUND: Many HIV-infected individuals have achieved undetectable viral load and increased CD4 T cell counts due to the success of Antiretroviral Therapy (ART). However, HIV persists in resting T cells, monocytes/macrophages and other quiescent cells. Furthermore, the HIV- 1 vpr accessory gene may play an important role in the persistence of HIV in these infected patients. OBJECTIVES: Therefore, we characterized the HIV-1 vpr gene from PBMC DNA of 14 HIV-infected older patients on long-term ART with mostly undetectable viral load and increased CD4 T cell counts. METHODS: Peripheral Blood Mononuclear Cells (PBMC) were isolated from 14 HIV-infected individuals, followed by extraction of genomic DNA, amplification of HIV-1 vpr gene by polymerase chain reaction (PCR), cloning of vpr gene in TOPO vector and characterization of correct size recombinant inserts containing vpr genes. An average of 13 clones were sequenced from each patient, followed by sequence analysis by bioinformatic tools. RESULTS: Phylogenetic analysis of 182 vpr sequences demonstrated that the vpr sequences of each patient were well separated and discriminated from other patients' sequences and formed distinct clusters. The vpr sequences showed a low degree of viral heterogeneity, lower estimates of genetic diversity and about half of the patients' sequences were under positive selection pressure. While the majority of the vpr deduced amino acid sequences from most patients contained intact open reading frames, several sequences, mostly from two patients, had stop codons. Numerous patient-specific and common amino acid motifs were found in deduced vpr sequences. The functional domains required for vpr activity, including virion incorporation, nuclear import of pre-integration complex and cell cycle arrest, were generally conserved in most vpr sequences. Several of the known Cytotoxic T-lymphocytes (CTL) epitopes in vpr showed variation in our patients' sequences. CONCLUSION: In summary, a low degree of genetic variability, conservation of functional domains and variations in CTL epitopes were the features of vpr sequences from the 14 HIV-infected older patients with controlled viremia on long-term ART.