Knowledge, attitudes and practices regarding respirable silica exposure and personal protective equipment use among brick kiln workers in Nepal.

OBJECTIVES: Brick kiln workers in Nepal are a neglected population who are exposed to high respirable silica concentrations, and few use interventions to reduce exposure. We aimed to characterise the prevalence of respiratory personal protective equipment (PPE) use, understand knowledge and attitudes towards kiln dust and respiratory PPE and identify factors associated with respiratory PPE use. METHODS: We conducted a cross-sectional study in Bhaktapur, Nepal. We used simple random selection to identify 10 out of 64 total kilns and stratified random sampling of 30 households to enrol workers aged ≥14 years within selected kilns. Field workers surveyed participants using structured questionnaires. Our primary outcome was to characterise the prevalence of current respiratory PPE use and secondary outcomes were summaries of knowledge, attitudes and practice of PPE use. RESULTS: We surveyed 83 workers (mean age 30.8 years, 77.1% male). Of these, 28.9% reported current respiratory PPE use at work, 3.6% heard of silicosis prior to the survey and 24.1% correctly identified the best respiratory PPE (N95, compared with surgical masks and barrier face coverings) for reducing dust exposure. Respiratory PPE users had higher income (mean monthly household income US$206 vs US$145; p=0.04) and education levels (25% vs 5.1% completed more than primary school; p=0.02) compared with non-users. CONCLUSIONS: Respiratory PPE use was low. Workers had poor knowledge of kiln dust health effects and proper respiratory PPE. We highlight important barriers to PPE use, particularly knowledge gaps, which can guide future investigations to reduce the silicosis burden among brick kiln workers.

Comprehensive study on pharmacognostic, pharmacological, and toxicological features of Ficus racemosa in Alzheimer's disease using GC-MS and molecular docking analyses.

Background: Alzheimer's disease (AD) presents as a widespread neurodegenerative condition impacting over 55 million individuals globally, with an annual rise of 10 million new cases. Despite its staggering prevalence, the absence of a definitive cure establishes the need for a revisit. Methods: We explore the alternative strategies, focusing on the potential therapeutic efficacy of ethanolic extracts derived from the fruit and leaf of Ficus racemosa Linn. Results: The investigation comprehensively explores pharmacognostic, phytochemical, toxicological, and pharmacological characteristics. In addition to pharmacognostic and physicochemical analyses, toxicological evaluations conducted on experimental animals demonstrated the innocuous nature of the ethanolic extracts (from both fruit and leaf) of F. racemosa, as evidenced by assessments of hemocompatibility, oxidative parameters, and vital organ histology. Phytochemical profiling via GC-MS identified 48 and 80 phytoconstituents in the fruit and leaf extracts, respectively. These constituents were screened for bioactive potential using the "Lipinski Rule of Five," resulting in the selection of 25 and 33 constituents from fruit and leaf extracts, respectively. Subsequent molecular docking studies against the AChE enzyme revealed promising interactions of the selected phytoconstituents. Furthermore, the top-scoring phytoconstituents were subjected to in silico screening to assess their interactions with ß- and γ-secretase enzymes, in addition to the AChE enzyme. The cumulative findings substantiate the therapeutic utility of the plant extracts, particularly in the context of AD. Conclusion: In conclusion, our investigation highlights the promising therapeutic potential of selected phytoconstituents derived from ethanolic extracts of F. racemosa in mitigating AD pathology by targeting key enzyme sites such as AChE, ß-, and γ-secretase.

Validating the temporal performance of genetic biomarkers in an animal model of recurrence/ non-recurrence myocardial infarction persuades by bioinformatics tools.

With a global towering prevalence of index acute myocardial infarction (nonrecurrent MI, NR-MI), a high incidence of recurrent MI (R-MI) has emerged in recent decades. Despite the extensive occurrence, the promising predictors of R-MI have been elusive within the cohort of survivors. This study investigates and validates the involvement of distinct gene expressions in R-MI and NR-MI. Bioinformatics tools were used to identify DEGs from the GEO dataset, functional annotation, pathway enrichment analysis, and the PPI network analysis to find hub genes. The validation of proposed genes was conceded by qRT-PCR and Western Blot analysis in experimentally induced NR-MI and R-MI models on a temporal basis. The temporal findings based on RT-PCR consequences reveal a significant and constant upregulation of the UBE2N in the NR-MI model out of the proposed three DEGs (UBE2N, UBB, and TMEM189), while no expression was reported in the R-MI model. Additionally, the proteomics study proposed five DEGs (IL2RB, NKG7, GZMH, CXCR6, and GZMK) for the R-MI model since IL2RB was spotted for significant and persistent downregulation with different time points. Further, Western Blot analysis validated these target genes' expressions temporally. I/R-induced NR-MI and R-MI models were confirmed by the biochemical parameters (CKMB, LDH, cTnI, serum nitrite/nitrate concentration, and inflammatory cytokines) and histological assessments of myocardial tissue. These results underscore the importance of understanding genetic mechanisms underlying MI and highlight the potential of UBE2N and IL2RB as biomarkers for non-recurrent and recurrent MI, respectively.

Post-ductal coarctation of aorta aneurysm repair in adult via left antero-axillary thoracotomy with antegrade cerebral perfusion-a case series.

Coarctation of the aorta is a common congenital abnormality that may be associated with serious and rare anomalies like aneurysms. Severe coarctation or interrupted aortic arch in adults is usually managed by percutaneous interventions or extra-anatomic bypass. However, the presence of an aneurysm beyond the coarcted segment implies the opening of a collateral-rich segment of the aorta with redressal of the arch if hypoplastic. We describe our experience in managing three such patients through antero-lateral thoracotomy with antegrade cerebral perfusion. We have found this technique helpful in treating aneurysms of the distal aortic arch or proximal descending thoracic aorta.

An auxin regulated Universal stress protein (TaUSP_3B-1) interacts with TaGolS and provides tolerance under drought stress and ER stress.

A previously identified wheat drought stress responsive Universal stress protein, TaUSP_3B-1 has been found to work in an auxin dependent manner in the plant root tissues in the differentiation zone. We also found a novel interacting partner, TaGolS, which physically interacts with TaUSP_3B-1 and colocalizes in the endoplasmic reticulum. TaGolS is a key enzyme in the RFO (Raffinose oligosaccharides) biosynthesis which is well reported to provide tolerance under water deficit conditions. TaUSP_3B-1 overexpression lines showed an early flowering phenotype under drought stress which might be attributed to the increased levels of AtTPPB and AtTPS transcripts under drought stress. Moreover, at the cellular levels ER stress induced TaUSP_3B-1 transcription and provides tolerance in both adaptive and acute ER stress via less ROS accumulation in the overexpression lines. TaUSP_3B-1 overexpression plants had increased silique numbers and a denser root architecture as compared to the WT plants under drought stress.

Corrigendum: A small molecule inhibitor of Notch1 modulates stemness and suppresses breast cancer cell growth.

[This corrects the article DOI: 10.3389/fphar.2023.1150774.].

Correction to: Post­ductal coarctation of aorta aneurysm repair in adult via left antero­axillary thoracotomy with antegrade cerebral perfusion-a case series.

[This corrects the article DOI: 10.1007/s12055-024-01734-5.].

Brick kiln pollution and its impact on health: A systematic review and meta-analysis.

Brick kiln emissions adversely affect air pollution and the health of workers and individuals living near the kilns; however, evidence of their impacts remains limited. We conducted a systematic review of brick kiln pollution (emissions, source contributions and personal exposures) and its effects on health. We extracted articles from electronic databases and through manual citation searching. We estimated pooled, sample-size-weighted means and standard deviations for personal exposures by job type; computed mean emission factors and pollutant concentrations by brick kiln design; and meta-analyzed differences in means or proportions for health outcomes between brick kiln workers and controls or for participants living near or far away from kilns. We identified 104 studies; 74 were conducted in South Asia. The most evaluated pollutants were particulate matter (PM; n = 48), sulfur dioxide (SO2; n = 24) and carbon monoxide (CO; n = 22), and the most evaluated health outcomes were respiratory health (n = 34) and musculoskeletal disorders (n = 9). PM and CO emissions were higher among traditional than improved brick kilns. Mean respirable silica exposures were only measured in 4 (4%) studies and were as high as 620 µg/m3, exceeding the NIOSH recommended exposure limit by a factor of over 12. Brick kiln workers had consistently worse lung function, more respiratory symptoms, more musculoskeletal complaints, and more inflammation when compared to unexposed participants across studies; however, most studies had a small sample size and did not fully describe methods used for sampling or data collection. On average, brick kiln workers had worse health outcomes when compared to unexposed controls but study quality supporting the evidence was low. Few studies reported silica concentrations or personal exposures, but the few that did suggest that exposures are high. Further research is needed to better understand the relationship between brick kiln pollution and health among workers, and to evaluate exposure mitigation strategies.

Air Quality Monitoring Using Low-Cost Sensors in Urban Areas of Jodhpur, Rajasthan.

Air pollution poses a significant health hazard in urban areas across the globe, with India being one of the most affected countries. This paper presents environmental monitoring study conducted in Jodhpur, Rajasthan, India, to assess air quality in diverse urban environments. The study involved continuous indoor and outdoor air quality monitoring, focusing on particulate matter (PM2.5) levels, bioaerosols, and associated meteorological parameters. Laser sensor-based low-cost air quality monitors were utilized to monitor air quality and Anderson 6-stage Cascade Impactor & Petri Dish methods for bioaerosol monitoring. The study revealed that PM2.5 levels were consistently high throughout the year, highlighting the severity of air pollution in the region. Notably, indoor PM2.5 levels were often higher than outdoor levels, challenging the common notion of staying indoors during peak pollution. The study explored the spatial and temporal diversity of air pollution across various land-use patterns within the city, emphasizing the need for tailored interventions in different urban areas. Additionally, bioaerosol assessments unveiled the presence of pathogenic organisms in indoor and outdoor environments, posing health risks to residents. These findings underscore the importance of addressing particulate matter and bioaerosols in air quality management strategies. Despite the study's valuable insights, limitations, such as using low-cost air quality sensors and the need for long-term data collection, are acknowledged. Nevertheless, this research contributes to a better understanding of urban air quality dynamics and the importance of public awareness in mitigating the adverse effects of air pollution. In conclusion, this study underscores the urgent need for effective air quality management strategies in urban areas. The findings provide valuable insights for policymakers and researchers striving to address air pollution in rapidly urbanizing regions.

A Subjective Assessment of Chemotherapy Drug-Induced Taste and Smell Alteration in Non-head and Neck Cancer Patients: A Questionnaire-Based Cross-Sectional Study.

OBJECTIVE: This study aimed to evaluate alterations in taste and smell perceptions among non-head and neck cancer patients receiving chemotherapy, aiming to identify factors influencing these changes. METHODS: A cohort of 70 non-head and neck cancer patients undergoing one to four cycles or more than four cycles, over a six-month period, from oncology outpatient clinics was recruited. Participants completed structured taste and smell questionnaires with assistance from interviewers. Demographic data, recurrence history, chemotherapy cycles, drug regimens, and taste and smell perceptions were analyzed using descriptive statistics and chi-square tests. RESULTS: The mean age of participants was 46.5 years, with a predominance of females (81.4%) and breast cancer cases (42.9%). Taste changes were more prevalent (62.9%) than smell changes (32.9%) post chemotherapy, particularly among those on combination drug regimens. Salty taste alterations were the most common (30.0%), followed by sweet taste (22.9%) and sour/bitter tastes (14.3%). Moreover, 38.57% of patients reported experiencing dysgeusia, while 30% noted the occurrence of parosmia post chemotherapy. CONCLUSION: Chemotherapy-induced alterations in taste and smell significantly impact the quality of life and nutritional status of cancer patients. Despite often being overlooked, these changes warrant increased attention in oncological practice to inform treatment decisions and enhance symptom management, particularly in palliative care settings. Further research is needed to explore the implications of chemosensory alterations on patient outcomes and treatment strategies.

Presentation and diagnosis of neonatal tuberous sclerosis complex: A case report and literature review.

Tuberous sclerosis is an uncommon neurocutaneous syndrome characterized by hamartomatous growths with unpredictable progression. Diagnosing and managing neonatal tuberous sclerosis can be challenging. We report a rare case of a 30-day-old male born out of a non-consanguineous marriage who presented with poor suckling and persistent abnormal body movement, required prolonged intensive care, and was diagnosed with tuberous sclerosis with multisystem involvement.

Selenization of Small Molecule Drugs: A New Player on the Board.

There is an urgent need to develop safer and more effective modalities for the treatment of a wide range of pathologies due to the increasing rates of drug resistance, undesired side effects, poor clinical outcomes, etc. Throughout the years, selenium (Se) has attracted a great deal of attention due to its important role in human health. Besides, a growing body of work has unveiled that the inclusion of Se motifs into a great number of molecules is a promising strategy for obtaining novel therapeutic agents. In the current Perspective, we have gathered the most recent literature related to the incorporation of different Se moieties into the scaffolds of a wide range of known drugs and their feasible pharmaceutical applications. In addition, we highlight different representative examples as well as provide our perspective on Se drugs and the possible future directions, promises, opportunities, and challenges of this ground-breaking area of research.

Hemangioblastoma: An Uncommon Cause of Polycythemia in a Child.

Polycythemia is a rare condition in children. Myeloproliferative neoplasms, including polycythemia vera although rare, is an important cause of childhood primary polycythemia. Secondary polycythemia is more common in children due to conditions causing hypoxia or due to pathologic erythropoietin production in malignancies like renal cell carcinoma, Wilms tumor or Hepatocellular carcinoma. Central nervous system hemangioblastoma is one of the rare causes of polycythemia. We report a 13-year-old girl with primarily neurological symptoms identified to be polycythemic during routine evaluation. Clinical examination and neuroimaging subsequently confirmed an intracranial space occupying lesion which was excised. Hemoglobin level normalized after tumor excision. This case report emphasizes the need for thorough systemic evaluation including central nervous system examination in children identified to be polycythemic. Keywords: CNS tumor; hemangioblastoma; polycythemia.

Pharmacological agents targeting drug-tolerant persister cells in cancer.

Current cancer therapy can be effective, but the development of drug resistant disease is the usual outcome. These drugs can eliminate most of the tumor burden but often fail to eliminate the rare, "Drug Tolerant Persister" (DTP) cell subpopulations in residual tumors, which can be referred to as "Persister" cells. Therefore, novel therapeutic agents specifically targeting or preventing the development of drug-resistant tumors mediated by the remaining persister cells subpopulations are needed. Since approximately ninety percent of cancer-related deaths occur because of the eventual development of drug resistance, identifying, and dissecting the biology of the persister cells is essential for the creation of drugs to target them. While there remains uncertainty surrounding all the markers identifying DTP cells in the literature, this review summarizes the drugs and therapeutic approaches that are available to target the persister cell subpopulations expressing the cellular markers ATP-binding cassette sub-family B member 5 (ABCB5), CD133, CD271, Lysine-specific histone demethylase 5 (KDM5), and aldehyde dehydrogenase (ALDH). Persister cells expressing these markers were selected as the focus of this review because they have been found on cells surviving following drug treatments that promote recurrent drug resistant cancer and are associated with stem cell-like properties, including self-renewal, differentiation, and resistance to therapy. The limitations and obstacles facing the development of agents targeting these DTP cell subpopulations are detailed, with discussion of potential solutions and current research areas needing further exploration.

Rational Design and Synthesis of Isatin-Chalcone Hybrids Integrated with 1H-1,2,3-Triazole: Anti-Proliferative Profiling and Molecular Docking Insights.

In this study, a series of isatin-chalcone linked triazoles were synthesized using Cu-promoted Azide-Alkyne Cycloaddition (CuAAC) reaction and evaluated for their cytotoxicity against various cancer cell lines. The most potent compound displayed approximately 2.5 times greater activity compared to both reference compounds against ovarian cancer cell lines. These findings were supported by caspase-mediated apoptosis and molecular docking analyses. Docking revealed comparable VEGFR-2 affinities for 5 b and 5-FU but highlighted stronger interaction of 5 b with EGFR, evident from its lower docking score. Overall, these results signify the notable anti-proliferative potential of most synthesized hybrids, notably emphasizing the efficacy of compound 5 b in suppressing cancer cell growth.

Transcriptional regulation of tomato fruit ripening.

An intrinsic and genetically determined ripening program of tomato fruits often depends upon the appropriate activation of tissue- and stage-specific transcription factors in space and time. The past two decades have yielded considerable progress in detailing these complex transcriptional as well as hormonal regulatory circuits paramount to fleshy fruit ripening. This non-linear ripening process is strongly controlled by the MADS-box and NOR family of proteins, triggering a transcriptional response associated with the progression of fruit ripening. Deepening insights into the connection between MADS-RIN and plant hormones related transcription factors, such as ERFs and ARFs, further conjugates the idea that several signaling units work in parallel to define an output fruit ripening transcriptome. Besides these TFs, the role of other families of transcription factors such as MYB, GLK, WRKY, GRAS and bHLH have also emerged as important ripening regulators. Other regulators such as EIN and EIL proteins also determine the transcriptional landscape of ripening fruits. Despite the abundant knowledge of the complex spectrum of ripening networks in the scientific domain, identifying more ripening effectors would pave the way for a better understanding of fleshy fruit ripening at the molecular level. This review provides an update on the transcriptional regulators of tomato fruit ripening.

Aerosol drug therapy in critically ill patients (Aero-in-ICU study): A multicentre prospective observational cohort study.

BACKGROUND: In recent years, a significant understanding of delivering optimal aerosol therapy and the availability of various drugs and devices have led to an increase in its use in clinical practice. There are only a few studies available regarding their use in critically ill patients from a few parts of the world. We aimed to study the practice pattern of aerosol therapy in critically ill patients from Indian intensive care units (ICUs). METHODS: After ethical approval, this multi-centric prospective observational study was performed over a study period of four weeks. Newly admitted adult patients considered who had an artificial airway and/or ventilation (including non-invasive). Patients were followed up for the next 14 days or until ICU discharge/death (whichever came first) for details of each aerosol therapy, including ongoing respiratory support, drug type, and aerosol-generating device. RESULTS: From the nine participating centers across India, 218 patients were enrolled. Of 218 enrolled patients, 72.48% received 4884 aerosols with 30.91 ± 27.15 (95%CI: 26.6-35.1) aerosols per patient over 1108 patient days. Approximately 62.7% during IMV, 30.2% during NIV, 2.3% in spontaneously breathing patients with an artificial airway during weaning, and 4.7% were given without an artificial airway after weaning or decannulation. In 59%, a single drug was used, and bronchodilators were the most frequent. The jet nebulizer was the most common, followed by the ultrasonic and vibrating mesh aerosol generator. The ventilator setting was changed in only 6.6% of the aerosol sessions with IMV and none with NIV. CONCLUSION: Aerosol therapy is frequently used with a wide variation in practices; bronchodilators are the most commonly used drugs, and jet nebulizers are the most widely used.