The state of ambient air quality in Pakistan—a review

Background and purpose: Pakistan, during the last decade, has seen an extensive escalation in population growth, urbanization, and industrialization, together with a great increase in motorization and energy use. As a result, a substantial rise has taken place in the types and number of emission sources of various air pollutants. However, due to the lack of air quality management capabilities, the country is suffering from deterioration of air quality. Evidence from various governmental organizations and international bodies has indicated that air pollution is a significant risk to the environment, quality of life, and health of the population. The Government has taken positive steps toward air quality management in the form of the Pakistan Clean Air Program and has recently established a small number of continuous monitoring stations. However, ambient air quality standards have not yet been established. This paper reviews the data being available on the criteria air pollutants: particulate matter (PM), sulfur dioxide, ozone, carbon monoxide, nitrogen dioxide, and lead. Methods: Air pollution studies in Pakistan published in both scientific journals and by the Government have been reviewed and the reported concentrations of PM, SO2, O3, CO, NO2, and Pb collated. A comparison of the levels of these air pollutants with the World Health Organization air quality guidelines was carried out. Results: Particulate matter was the most serious air pollutant in the country. NO2 has emerged as the second high-risk pollutant. The reported levels of PM, SO2, CO, NO2, and Pb were many times higher than the World Health Organization air quality guidelines. Only O3 concentrations were below the guidelines. Conclusions: The current state of air quality calls for immediate action to tackle the poor air quality. The establishment of ambient air quality standards, an extension of the continuous monitoring sites, and the development of emission control strategies are essential. © Springer-Verlag 2009

Impact of Safety-Related Dose Reductions or Discontinuations on Sustained Virologic Response in HCV-Infected Patients: Results from the GUARD-C Cohort.

BACKGROUND: Despite the introduction of direct-acting antiviral agents for chronic hepatitis C virus (HCV) infection, peginterferon alfa/ribavirin remains relevant in many resource-constrained settings. The non-randomized GUARD-C cohort investigated baseline predictors of safety-related dose reductions or discontinuations (sr-RD) and their impact on sustained virologic response (SVR) in patients receiving peginterferon alfa/ribavirin in routine practice. METHODS: A total of 3181 HCV-mono-infected treatment-naive patients were assigned to 24 or 48 weeks of peginterferon alfa/ribavirin by their physician. Patients were categorized by time-to-first sr-RD (Week 4/12). Detailed analyses of the impact of sr-RD on SVR24 (HCV RNA <50 IU/mL) were conducted in 951 Caucasian, noncirrhotic genotype (G)1 patients assigned to peginterferon alfa-2a/ribavirin for 48 weeks. The probability of SVR24 was identified by a baseline scoring system (range: 0-9 points) on which scores of 5 to 9 and <5 represent high and low probability of SVR24, respectively. RESULTS: SVR24 rates were 46.1% (754/1634), 77.1% (279/362), 68.0% (514/756), and 51.3% (203/396), respectively, in G1, 2, 3, and 4 patients. Overall, 16.9% and 21.8% patients experienced ≥1 sr-RD for peginterferon alfa and ribavirin, respectively. Among Caucasian noncirrhotic G1 patients: female sex, lower body mass index, pre-existing cardiovascular/pulmonary disease, and low hematological indices were prognostic factors of sr-RD; SVR24 was lower in patients with ≥1 vs. no sr-RD by Week 4 (37.9% vs. 54.4%; P = 0.0046) and Week 12 (41.7% vs. 55.3%; P = 0.0016); sr-RD by Week 4/12 significantly reduced SVR24 in patients with scores <5 but not ≥5. CONCLUSIONS: In conclusion, sr-RD to peginterferon alfa-2a/ribavirin significantly impacts on SVR24 rates in treatment-naive G1 noncirrhotic Caucasian patients. Baseline characteristics can help select patients with a high probability of SVR24 and a low probability of sr-RD with peginterferon alfa-2a/ribavirin.This study was sponsored by F. Hoffmann-La Roche Ltd, Basel, Switzerland. Support for third-party writing assistance for this manuscript, furnished by Blair Jarvis MSc, ELS, of Health Interactions, was provided by F. Hoffmann-La Roche Ltd, Basel, Switzerland

ANTIBACTERIAL EFFICACY OF FIVE NATURAL ESSENTIAL OILS USED IN YEMEN: A COMPARATIVE STUDY

Background and objective: Due to the increasing resistance to synthetic antibiotics and preservatives, there is growing interest in exploring natural alternatives. This study aimed to evaluate the antibacterial potential of five commercially available essential oils in the Yemeni market Azadirachta indica (Neem), Moringa oleifera, Rosmarinus officinalis (Rosemary), Salvia officinalis, and Origanum majorana against selected Gram-positive and Gram-negative bacterial strains. Method: Agar diffusion was used to investigate the antibacterial activity of essential oils from five plants: Azadirachta indica (neem), Moringa oleifera, Rosmarinus officinalis (rosemary), Salvia officinalis, and Origanum majorana. Result:  Significant differences in the inhibitory effects of the plant oils of neem, Moringa oleifera, Rosmarinus officinalis, Salvia officinalis, and Origanum majorana against Gram-positive and Gram-negative bacteria were found during the antimicrobial screening process. Nearing the effectiveness of gentamicin (25 mm), Salvia officinalis and neem oils demonstrated the highest action against Gram-positive Staphylococcus aureus (22 mm and 20 mm inhibition zones, respectively). Rosmarinus officinalis, on the other hand, demonstrated a low level of efficacy (10 mm). Most oils were less effective against Gram-negative organisms, and E. coli showed resistance to all save Rosmarinus officinalis (12 mm). Conclusions: These results demonstrate the potential of oils produced from plants, especially Origanum majorana, neem, and Salvia officinalis, as antibacterial agents against Gram-negative bacteria highlights the need for more research into maximizing their use, either alone or in combination with other antibiotics, despite their encouraging efficacy against Gram-positive bacteria.                     Peer Review History: Received 9 April 2025;   Reviewed 14 May 2025; Accepted 20 June; Available online 15 July 2025 Academic Editor: Dr. Ahmad Najib, Universitas Muslim Indonesia,  Indonesia, [email protected] Reviewers: Antonio José de Jesus Evangelista, Federal University of Ceará, UFC, Brazil, [email protected] Prof. Abdulwahab Ismail Al-kholani, Dean of Faculty of Dentistry at 21 September University, Yemen. [email protected]

QUALITY OF REFRIGERATED RAW MILK FROM BUFFALO COWS (Bubalus bubalis bubalis) IN DIFFERENT FARMS AND SEASONS IN BRAZIL

The present research aimed to examine the chemical and microbiological characteristics of refrigerated raw milk collected from buffalo-only dairy herds from different farms and seasons. Samples were collected from twelve farms producing buffalo milk, located in the Mideast region of São Paulo state, in Brazil, once a month throughout the dairy calendar year from 2011 to 2014. The analysis of fat, protein, lactose, dry extract, and total solids contents were carried out using Infrared Absorption. Residues for antimicrobial analysis were carried out using Delvo Test Kit technique, and both somatic cell count and standard plate count analysis were carried out using Flow Cytometry. The analysis of the chemical components as well as for the microbiological analysis of SPC proved to be statistically significant throughout the period. No antibiotic residues were found in the totality of the sample, hence indicating that the farmers complied with the current sanitary legislation in that country, as well as SCC; however, higher values were found for the SPC. Significant results for all parameters analyzed were found among the farms, indicating that price incentives paid for the quality of raw milk could be an alternative to dairy processing companies, favoring yield and quality of the final product. Keywords: Brazil; chemical parameters; dairy; microbiological parameters; monitoring

A new nail with a locking blade for complex proximal humeral fractures

INTRODUCTION: The objective of this study was to assess the clinical outcome of displaced proximal humerus fracture treated with a new locking blade nail. MATERIALS AND METHODS: This prospective study included a series of 92 patients with acute fracture of the proximal humerus treated in one hospital level I trauma centre with locking blade nail between December 2010 and December 2013. According to the Neer classification, all fractures were two- to four-part fractures. Age adopted Constant score, DASH and visual analogue scores were used as outcome measures. RESULTS: A total of 92 patients were enrolled in the study. However, 29 patients were excluded due to loss to follow-up and death. Ultimately, 63 patients were available for final follow-up and data analysis. The mean duration of follow-up was 22 months (range 16–48 months). On average at 1 year, all fractures had united. The mean weighted Constant score was 84.2 % and the median disabilities of the arm, shoulder and hand (DASH) score was 26, the range of elevation was 115 and range of abduction was 97. The head shaft angle was 130, and pain visual analogue was 1.6. We found that 5 of the 63 patients (8 %) demonstrated complications. Two patients (3 %) displayed secondary displacement and require device removal. Two patients (3 %) had impingement due to prominent metal work, and one patient had a superficial wound infection which was treated with a course of antibiotics. CONCLUSION: Our study shows excellent results with new locking blade nail for displaced proximal humerus fractures. We think the locking blade nail offers stiff triangular fixation of the head fragment and support of the medial calcar region to prevent secondary varus collapse. LEVEL OF EVIDENCE: III

Emergency Response of Indian Hajj Medical Mission to Heat Illness Among Indian Pilgrims in Tent-Clinics at Mina and Arafat During Hajj, 2016

Introduction: Extreme heat claims more lives than all other weather-related exposures combined. Hajj rituals at Mina, Arafat, and Muzdalifah involve a minimally-clothed, moving assemblage of 3.5 million pilgrims who are exposed to a harsh, hot, desert climate during physically challenging outdoor rituals and unsheltered night stays, rendering them prone to heat illness, dehydration, and sunburn. This cross-sectional study assessed the emergency response of the Indian Hajj Medical Mission to overwhelming heat illnesses in Mina and Arafat among Indian pilgrims during Hajj, 2016. Methods: In 2016, 88 patients affected by the heat were brought to central tent-clinics at 36 maktabs in Mina and Arafat that were established by the Indian Hajj Medical Mission. Patients were offered rapid external evaporative cooling (wet towels) and cold intravenous saline infusion on patient couches and wheelchairs. Results: The incidence of heat illness among Indian pilgrims in 2016 was 0.62/1000. The ratio of males to females was 1.8:1. Mean ages of males and females were 62.2 ± 7.43 and 52.6 ± 9.3, respectively. Pre-existing conditions, such as diabetes mellitus and hypertension, were present in 93.2% of the patients. The most common presentations included hyperthermia, fatigue, and restlessness. Heatstroke presented in five patients and resulted in one fatality. Twenty-eight patients were referred to Saudi hospitals, and 12 of them were institutionalized. Exertion related to the stoning of Satan ritual during late morning and afternoon hours was the leading cause of heat illness. Conclusion: The overwhelming incidence of heat illness among Indian pilgrims in the critical five-day period of the Hajj represents the tip of the iceberg as the Hajj attracts over 3.5 million pilgrims from 200 countries annually. Heat illness is difficult to manage in the presence of pre-existing comorbidities and mandates clientele education and outreach warning systems to enhance resilience capital amongst Hajj pilgrims, sportspersons, outdoor enthusiasts, and military personnel

Functional Analysis of the Cathepsin-Like Cysteine Protease Genes in Adult Brugia malayi Using RNA Interference

Filarial nematodes are an important group of human pathogens, causing lymphatic filariasis and onchocerciasis, and infecting around 150 million people throughout the tropics with more than 1.5 billion at risk of infection. Control of filariasis currently relies on mass drug administration (MDA) programs using drugs which principally target the microfilarial life-cycle stage. These control programs are facing major challenges, including the absence of a drug with macrofilaricidal or permanent sterilizing activity, and the possibility of the development of drug-resistance against the drugs available. Cysteine proteases are essential enzymes which play important roles in a wide range of cellular processes, and the cathepsin-like cysteine proteases have been identified as potential targets for drug or vaccine development in many parasites. Here we have studied the function of several of the cathepsin-like enzymes in the filarial nematode, B. malayi, and demonstrate that these cysteine proteases are involved in the development of embryos, show similar functions to their counterparts in C. elegans, and therefore, provide an important target for future drug development targeted to eliminate filariasis

An Integrated Disease/Pharmacokinetic/Pharmacodynamic Model Suggests Improved Interleukin-21 Regimens Validated Prospectively for Mouse Solid Cancers

Interleukin (IL)-21 is an attractive antitumor agent with potent immunomodulatory functions. Yet thus far, the cytokine has yielded only partial responses in solid cancer patients, and conditions for beneficial IL-21 immunotherapy remain elusive. The current work aims to identify clinically-relevant IL-21 regimens with enhanced efficacy, based on mathematical modeling of long-term antitumor responses. For this purpose, pharmacokinetic (PK) and pharmacodynamic (PD) data were acquired from a preclinical study applying systemic IL-21 therapy in murine solid cancers. We developed an integrated disease/PK/PD model for the IL-21 anticancer response, and calibrated it using selected “training” data. The accuracy of the model was verified retrospectively under diverse IL-21 treatment settings, by comparing its predictions to independent “validation” data in melanoma and renal cell carcinoma-challenged mice (R2>0.90). Simulations of the verified model surfaced important therapeutic insights: (1) Fractionating the standard daily regimen (50 µg/dose) into a twice daily schedule (25 µg/dose) is advantageous, yielding a significantly lower tumor mass (45% decrease); (2) A low-dose (12 µg/day) regimen exerts a response similar to that obtained under the 50 µg/day treatment, suggestive of an equally efficacious dose with potentially reduced toxicity. Subsequent experiments in melanoma-bearing mice corroborated both of these predictions with high precision (R2>0.89), thus validating the model also prospectively in vivo. Thus, the confirmed PK/PD model rationalizes IL-21 therapy, and pinpoints improved clinically-feasible treatment schedules. Our analysis demonstrates the value of employing mathematical modeling and in silico-guided design of solid tumor immunotherapy in the clinic

A Pro-Cathepsin L Mutant Is a Luminal Substrate for Endoplasmic-Reticulum-Associated Degradation in C. elegans

Endoplasmic-reticulum associated degradation (ERAD) is a major cellular misfolded protein disposal pathway that is well conserved from yeast to mammals. In yeast, a mutant of carboxypeptidase Y (CPY*) was found to be a luminal ER substrate and has served as a useful marker to help identify modifiers of the ERAD pathway. Due to its ease of genetic manipulation and the ability to conduct a genome wide screen for modifiers of molecular pathways, C. elegans has become one of the preferred metazoans for studying cell biological processes, such as ERAD. However, a marker of ERAD activity comparable to CPY* has not been developed for this model system. We describe a mutant of pro-cathepsin L fused to YFP that no longer targets to the lysosome, but is efficiently eliminated by the ERAD pathway. Using this mutant pro-cathepsin L, we found that components of the mammalian ERAD system that participate in the degradation of ER luminal substrates were conserved in C. elegans. This transgenic line will facilitate high-throughput genetic or pharmacological screens for ERAD modifiers using widefield epifluorescence microscopy