Heterogeneous Oxidation Products of Fine Particulate Isoprene Epoxydiol-Derived Methyltetrol Sulfates Increase Oxidative Stress and Inflammatory Gene Responses in Human Lung Cells.

Hydroxyl radical (·OH)-initiated oxidation of isoprene, the most abundant nonmethane hydrocarbon in the atmosphere, is responsible for substantial amounts of secondary organic aerosol (SOA) within ambient fine particles. Fine particulate 2-methyltetrol sulfate diastereoisomers (2-MTSs) are abundant SOA products formed via acid-catalyzed multiphase chemistry of isoprene-derived epoxydiols with inorganic sulfate aerosols under low-nitric oxide conditions. We recently demonstrated that heterogeneous ·OH oxidation of particulate 2-MTSs leads to the particle-phase formation of multifunctional organosulfates (OSs). However, it remains uncertain if atmospheric chemical aging of particulate 2-MTSs induces toxic effects within human lung cells. We show that inhibitory concentration-50 (IC50) values decreased from exposure to fine particulate 2-MTSs that were heterogeneously aged for 0 to 22 days by ·OH, indicating increased particulate toxicity in BEAS-2B lung cells. Lung cells further exhibited concentration-dependent modulation of oxidative stress- and inflammatory-related gene expression. Principal component analysis was carried out on the chemical mixtures and revealed positive correlations between exposure to aged multifunctional OSs and altered expression of targeted genes. Exposure to particulate 2-MTSs alone was associated with an altered expression of antireactive oxygen species (ROS)-related genes (NQO-1, SOD-2, and CAT) indicative of a response to ROS in the cells. Increased aging of particulate 2-MTSs by ·OH exposure was associated with an increased expression of glutathione pathway-related genes (GCLM and GCLC) and an anti-inflammatory gene (IL-10).

Morphological Spectrum of Gastritis in Endoscopic Biopsies and Its Association With Helicobacter pylori Infection.

Introduction Helicobacter pylori (H. pylori) infection is the most common cause of gastritis. The consequences of the persistent infection range from acute ulceration to the development of gastric neoplasia. The purpose of the study is to determine the histopathological pattern of gastritis in gastric biopsies and its association with H. pylori. Materials and methods This is a retrospective study of all the gastric biopsies received in the Department of Histopathology, Chughtai Institute of Pathology, Lahore, Pakistan from January 12, 2021 to April 10, 2021. Sections were cut from formalin-fixed, paraffin-embedded (FFPE) tissue blocks. Slides were stained with routine, special and immunohistochemical stains. The cases were then blindly reviewed by two pathologists with a special interest in Gastrointestinal Pathology. Microscopic features based on updated Sydney classification were recorded. The collected data were then analyzed by using SPSS version 20 (IBM Corp., Armonk, NY). Results A total of 429 gastric biopsies were examined. Out of which, 202 (47.1%) were male and 227 (52.9%) were female with a female-to-male ratio of 1.2:1. Their ages ranged from 12 to 100 years and a peak in the fourth decade of life with a mean age of 43 years (median age 49 years). Among gastritis, activity was seen in 194 (45%) and chronicity in 237 (55%) cases. H. pylori was seen in 174 (40.5%) cases and there was a strong statistically significant association between H. pylori infection and severity of gastritis (p<0.001). Other parameters of Sydney classification, such as atrophic changes, were seen in 144 (33%) cases, and intestinal metaplasia in 10 (2.3%) cases. Conclusion H. pylori organism was the most common cause of gastritis in our environment. The severity of gastritis is directly related to the H. pylori infection. If neutrophils are identified on surface epithelium, then H. pylori should be searched with increased attention on morphology and/or on immunohistochemical stain of H. pylori. Chronic inflammation and H. pylori density can also guide treatment which is necessary to avoid complications.

Invasive Micropapillary Carcinoma of the Breast With Solid Papillary Carcinoma: A Case Report.

Invasive micropapillary carcinoma and Solid papillary carcinomas are rare histologic subtypes of breast cancer. Co-existence of tumors of the breast like invasive ductal and lobular carcinomas, or invasive ductal carcinoma and mucinous carcinomas have been reported before. But the existence of invasive micropapillary carcinoma with solid papillary carcinoma is a rare occurrence. Here, we are reporting a rare case of a 60-year-old female with a mass in her left breast. The histopathology report showed a tumor containing these two histologic subtypes. Recognition of all tumor subtypes is necessary, as this can impact the treatment strategy.

Interventions to Reduce Opioid Use in Youth At-Risk and in Treatment for Substance Use Disorders: A Scoping Review.

BACKGROUND: Youth and young adults have been significantly impacted by the opioid overdose and health crisis in North America. There is evidence of increasing morbidity and mortality due to opioids among those aged 15-29. Our review of key international reports indicates there are few youth-focused interventions and treatments for opioid use. Our scoping review sought to identify, characterize, and qualitatively evaluate the youth-specific clinical and pre-clinical interventions for opioid use among youth. METHOD: We searched MedLine and PsycInfo for articles that were published between 2013 and 2021. Previous reports published in 2015 and 2016 did not identify opioid-specific interventions for youth and we thus focused on the time period following the periods covered by these prior reports. We input three groups of relevant keywords in the aforementioned search engines. Specifically, articles were included if they targeted a youth population (ages 15-25), studied an intervention, and measured impacts on opioid use. RESULTS: We identified 21 studies that examined the impacts of heterogeneous interventions on youth opioid consumption. The studies were classified inductively as psycho-social-educational, pharmacological, or combined pharmacological-psycho-social-educational. Most studies focused on treatment of opioid use disorder among youth, with few studies focused on early or experimental stages of opioid use. A larger proportion of studies focused heavily on male participants (i.e., male gender and/or sex). Very few studies involved and/or included youth in treatment/program development, with one study premised on previous research about sexual minority youth. CONCLUSIONS: Research on treatments and interventions for youth using or at-risk of opioids appears to be sparse. More youth involvement in research and program development is vital. The intersectional and multi-factorial nature of youth opioid use and the youth opioid crisis necessitates the development and evaluation of novel treatments that address youth-specific contexts and needs (i.e., those that address socio-economic, neurobiological, psychological, and environmental factors that promote opioid use among youth).

"We need to build a better bridge": findings from a multi-site qualitative analysis of opportunities for improving opioid treatment services for youth.

BACKGROUND: Adolescence and young adulthood is an important period for substance use initiation and related harms. In the context of the ongoing opioid crisis, the risks for youth (ages 16-29) who use opioids are particularly heightened. Despite recommendations to adopt a developmentally appropriate and comprehensive approach to reduce opioid-related harms among youth, data continue to show that youth are not adequately engaged in opioid treatments and encounter many barriers. The aim of this study is to identify youth-centered opportunities for improving opioid treatment services. METHODS: This paper reports multi-site qualitative findings from youth participating in the 'Improving Treatment Together' project, a community-based participatory project being conducted in British Columbia and Alberta, two western Canadian provinces that have been dramatically impacted by the opioid crisis. Qualitative data were collected during three workshops with youth who used opioids and accessed opioid treatment services in the prior 12 months. These workshops were conducted in three communities following the core elements of human-centered co-design. A multi-site qualitative analysis was conducted to identify within- and between-site themes surrounding youths' needs for improving opioid treatment service experiences and outcomes. RESULTS: Three overarching needs themes were identified from across the communities. The first reflected youths' difficulties finding and staying connected to opioid treatment services, with the overarching need theme suggesting opportunities to reduce organizational and systems-related barriers to care, such as waiting times and wider information about service availability. The second area of need was rooted in youths' feelings of judgment when accessing services. Consequently, opportunities to increase respectful and empathic interactions were the overarching need. The final theme was more nuanced across communities and reflected opportunities for an individualized approach to opioid treatment services that consider youths' unique basic safety, social, and health needs. CONCLUSIONS: This study identifies fundamental directions for the operationalization and implementation of youth-centered opioid treatment services. These directions are contextualized in youths' lived experiences accessing services in their local communities, with overarching themes from across sites strengthening their transferability to other settings.

Cytotoxicity and oxidative stress induced by atmospheric mono-nitrophenols in human lung cells.

Nitrophenols (NPs) are hazardous pollutants found in various environmental matrices, including ambient fine particulate matter (PM2.5), agricultural residues, rainwater, wildfires, and industrial wastes. This study showed for the first time the effect of three pure nitrophenols and their mixture on human lung cells to provide basic understanding of the NP influence on cell elements and processes. We identified NPs in ambient PM2.5 and secondary organic aerosol (SOA) particles generated from the photooxidation of monocyclic aromatic hydrocarbons in the U.S. EPA smog chamber. We assessed the toxicity of identified NPs and their equimolar mixture in normal bronchial epithelial (BEAS-2B) and alveolar epithelial cancer (A549) lung cell lines. The inhibitory concentration-50 (IC50) values were highest and lowest in BEAS-2B cells treated with 2-nitrophenol (2NP) and 4-nitrophenol (4NP), respectively, at 24 h of exposure. The lactate dehydrogenase (LDH) assay showed that 4NP, the most abundant NP we identified in PM2.5, was the most cytotoxic NP examined in both cell lines. The annexin-V/fluorescein isothiocyanate (FITC) analysis showed that the populations of late apoptotic/necrotic BEAS-2B and A549 cells exposed to 3NP, 4NP, and NP equimolar mixture increased between 24 and 48 h. Cellular reactive oxygen species (ROS) buildup led to cellular death post exposure to 3NP, 4NP and the NP mixtures, while 2NP induced the lowest ROS buildup. An increased mitochondrial ROS signal following NP exposure occurred only in BEAS-2B cells. The tetramethylrhodamine, methyl ester, perchlorate (TMRM) assay showed that exposed cells exhibited collapse of the mitochondrial membrane potential. TMRM signals decreased significantly only in BEAS-2B cells, and most strongly with 4NP exposures. Our results suggest that acute atmospheric exposures to NPs may be toxic at high concentrations, but not at ambient PM2.5 concentrations. Further chronic studies with NP and NP-containing PM2.5 are warranted to assess their contribution to lung pathologies.

Toxicological Responses of α-Pinene-Derived Secondary Organic Aerosol and Its Molecular Tracers in Human Lung Cell Lines.

Secondary organic aerosol (SOA) is a major component of airborne fine particulate matter (PM2.5) that contributes to adverse human health effects upon inhalation. Atmospheric ozonolysis of α-pinene, an abundantly emitted monoterpene from terrestrial vegetation, leads to significant global SOA formation; however, its impact on pulmonary pathophysiology remains uncertain. In this study, we quantified an increasing concentration response of three well-established α-pinene SOA tracers (pinic, pinonic, and 3-methyl-1,2,3-butanetricarboxylic acids) and a full mixture of α-pinene SOA in A549 (alveolar epithelial carcinoma) and BEAS-2B (bronchial epithelial normal) lung cell lines. The three aforementioned tracers contributed ∼57% of the α-pinene SOA mass under our experimental conditions. Cellular proliferation, cell viability, and oxidative stress were assessed as toxicological end points. The three α-pinene SOA molecular tracers had insignificant responses in both cell types when compared with the α-pinene SOA (up to 200 µg mL-1). BEAS-2B cells exposed to 200 µg mL-1 of α-pinene SOA decreased cellular proliferation to ∼70% and 44% at 24- and 48-h post exposure, respectively; no changes in A549 cells were observed. The inhibitory concentration-50 (IC50) in BEAS-2B cells was found to be 912 and 230 µg mL-1 at 24 and 48 h, respectively. An approximate 4-fold increase in cellular oxidative stress was observed in BEAS-2B cells when compared with untreated cells, suggesting that reactive oxygen species (ROS) buildup resulted in the downstream cytotoxicity following 24 h of exposure to α-pinene SOA. Organic hydroperoxides that were identified in the α-pinene SOA samples likely contributed to the ROS and cytotoxicity. This study identifies the potential components of α-pinene SOA that likely modulate the oxidative stress response within lung cells and highlights the need to carry out chronic exposure studies on α-pinene SOA to elucidate its long-term inhalation exposure effects.

Toxicity of selected airborne nitrophenols on eukaryotic cell membrane models.

Nitroaromatics belong to the group of toxic components of aerosol particles and atmospheric hydrometeors that enter the atmosphere through biomass burning and fuel combustion. In the present work, we report on the cytotoxic effects of a 2-, 3- and 4-nitrophenol mixture on a model eukaryotic-like cell membrane and compared it with in vitro cellular models BEAS-2B (immortalized bronchial epithelial cells) and A549 (cancerous alveolar epithelial cells). A selected model biomembrane comprised of DMPC (1,2-dimyristoyl-sn-glycero-3-phosphocholine), DPPC (1,2-dipalmitoyl-sn-glycero-3-phosphocholine) and POPC (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine) was studied. The electrochemical-based method, combined with atomic force microscopy (AFM) and phase-contrast microscopy imaging, allowed to get insights into the mechanism of cellular function disruption caused by airborne nitrophenols. The efficacy of the method is supported by the data obtained from in vitro experiments performed on cell models. The nitrophenol mixture exhibited cytotoxic effects at concentrations above 100 µg mL-1, as demonstrated by phase-contrast microscopy in real lung cell lines. Electrochemical impedance spectroscopy (EIS) revealed the formation of membrane defects at a nitrophenol concentration of 200 µg mL-1. AFM imaging confirmed the model membrane disintegration and phospholipids rearrangement in the presence of nitrophenols. These observations indicate that particle-bound nitrophenols induce substantial changes in cell membranes and make them more permeable to aerosol, resulting in major cellular damage in the lungs when inhaled. The study provides initial evidence of cellular membrane damage induced by three important nitrated phenols present in the environment.

Diabetic Ketoacidosis: Clinical Characteristics and Precipitating Factors.

INTRODUCTION: Diabetic ketoacidosis (DKA) is a complication of hyperglycemia. Through this study we plan to study the clinical features of DKA and precipitating factors responsible for DKA in type 1 and type 2 diabetes. METHODS: This cross-sectional observational study was conducted in the emergency department of a tertiary care hospital in Sukkur, Pakistan from August 2019 to February 2020. Symptoms and precipitating factors were noted in a self-structured questionnaire. RESULTS: Out of 71 patients, 19 (26.7%) patients had type 1 diabetes mellitus and 52 (73.3%) patients had type 2 diabetes mellitus. The most common clinical symptom was nausea and vomiting (57.7%), followed by pain in abdomen (42.2%) and dehydration (42.2%). We found that the most common precipitating factors were infections (69.0%) and non-compliance to treatment (53.5%). Among various infections, people commonly presented with pneumonia (38.7%) and urinary tract infection (30.6%). CONCLUSION: Diabetic ketoacidosis presents with vague symptoms such as nausea, vomiting, and pain in abdomen. Characteristic findings of DKA such as Kussmaul breathing was present in limited patients. Infections in diabetic patients should be carefully monitored as they are the most common precipitating factors for DKA.

Comparision of Efficacy and Safety of Orlistat vs Placebo in Obese Patients in Pakistan.

Introduction Obesity has become a rising health concern in Pakistan. Several primary measures, such as dietary restrictions and regular exercise, are taken to limit the severe consequences of obesity. Still, such measures alone have been proven to be often short term and therefore, inadequate. In this study, we will evaluate the role of pharmacological management via orlistat in obesity. Methods and Materials A total of 120 patients were enrolled in this study and were divided randomly into two groups (drug arm and placebo arm) of 60 patients each. A standard dose of 120 mg capsules of orlistat given three times a day was administered to the participants of the drug arm group. A placebo was given to the participants in the second group. Baseline investigations were conducted on day 0 of the study, and follow-up visits were planned to take place in week 24 for all participants. Any side effects or adverse events were inquired about and documented in these visits. Results In the orlistat arm, we noted a significant reduction in both body mass index (BMI) (0.04) and waist circumference (0.04). Reduction in weight was more in the orlistat arm than in the placebo arm. However, it is non-significant when compared between day 0 and week 24. Adverse events, such as oily spotting (31.91%), flatus with discharge (27.65%), faecal urgency (25.53%) and fatty stool (35.553%), were significantly higher in the orlistat arm. Conclusion Orlistat has shown positive results in reducing weight, BMI and waist circumference; however, patients should be counselled about potential side effects caused by the mechanism of action of Orlistat.

'Leaving no one behind': a scoping review on the provision of sexual and reproductive health care to nomadic populations.

BACKGRUND: Marginalized groups, such as nomadic populations across the world, have perhaps the least access to modern reproductive health (RH) services. This scoping review aims to identify barriers to access to RH services faced by nomadic populations from the existing literature and to highlight possible opportunities to address them. METHODS: Key databases, including PubMed, Popline, Google Scholar, and Google Advanced were searched for relevant articles published between 2002 and 2019. A total 344 articles were identified through database online searches, and 31 were included in the review. RESULTS: Nomadic people face complex barriers to healthcare access that can be broadly categorized as external (geographic isolation, socio-cultural dynamics, logistical and political factors) and internal (lifestyle, norms and practices, perceptions) factors. To effectively address the needs of nomadic populations, RH services must be available, accessible and acceptable through tailored and culturally sensitive approaches. A combination of fixed and mobile services has proven effective among mobile populations. Low awareness of modern RH services and their benefits is a major barrier to utilization. Partnership with communities through leveraging existing structures, networks and decision-making patterns can ensure that the programmes are effectively implemented. CONCLUSION: Further research is needed to better understand and address the RH needs of nomadic populations. Though existing evidence is limited, opportunities do exist and should be explored. Raising awareness and sensitization training among health providers about the specific needs of nomads is important. Improved education and access to information about the benefits of modern RH care among nomadic communities is needed. Ensuring community participation through involvement of nomadic women and girls, community leaders, male partners, and trained traditional birth attendants are key facilitators in reaching nomads. However, participatory programmes also need to be recognized and supported by governments and existing health systems.

Formulation of active packaging system using Artemisia scoparia for enhancing shelf life of fresh fruits.

An improved active packaging system was developed for fresh fruits using silver nanoparticles (AgNPs) coupled with calcium alginate (Ca-ALG). For the synthesis of AgNPs aqueous, ethanol and methanol extracts of Artemisia scoparia (AS) were used. These AgNP's were characterized using UV-Vis, SEM, EDS, AFM, FTIR and gel electrophoresis. Ethanol extract of AS (ASE) produced AgNPs with smallest size in comparison to aqueous AS (ASA) and methanol extract of AS (ASM). AgNPs synthesized from ASE had a size range of 12.0-23.3 nm and were tested on Human Corneal Epithelial Cells to evaluate their cytotoxicity. At 0.05 ng/mL of AgNP's concentration, no toxic effects were observed on the evaluated cell line. Therefore, 0.05 ng/mL of AgNPs mixed with edible coating of Ca-ALG were applied on strawberries and loquats as active coating to increase their shelf life. Significant improvement was observed in the quality parameters of strawberries and loquats such as microbial analysis, acidity loss, soluble solid content loss, weight loss and quality decay. Ca-ALG coating incorporated with AgNPs enhanced the shelf life of strawberries and loquats in comparison to no treatment and simple Ca-ALG coatings. This study provides an insight to food industry to extend the shelf life of fresh fruits using AgNP's formulated coatings.

Carbon-dot wrapped ZnO nanoparticle-based photoelectrochemical sensor for selective monitoring of H2O2 released from cancer cells.

This study reports on a simple approach for the fabrication of an electrode modified with biocompatible C-dot wrapped ZnO nanoparticles for selective photoelectrochemical monitoring of H2O2 released from living cells. The biocompatibility of the ZnO nanoparticles was confirmed through in-vitro cellular testing using the MTT assay on Huh7 cell lines. The ZnO nanoparticles wrapped with dopamine-derived C-dots possess numerous catalytically active sites, excessive surface defects, good electrical conductivity, and efficient separation ability of photo-induced electrons and holes. These properties offer highly sensitive and selective non-enzymatic photo-electrochemical monitoring of H2O2 released from HeLa cells after stimulation with N-formylmethionyl-leucyl-phenylalanine. The sensor has a wide linear range (20-800 nM), low detection limit (2.4 nM), and reliable reproducibility, this implying its suitability for biological and biomedical applications. Graphical abstract Schematic of the fabrication of ZnO nanoparticles by using a plant extract as a reducing agent. Wrapping of ZnO with C-dots enhances the photoelectrocatalytic efficacy. Sensitive and selective photoelectrochemical monitoring of H2O2 released from cancer cells is demonstrated.

Plant exomics: concepts, applications and methodologies in crop improvement.

Molecular breeding has a crucial role in improvement of crops. Conventional breeding techniques have failed to ameliorate food production. Next generation sequencing has established new concepts of molecular breeding. Exome sequencing has proven to be a significant tool for assessing natural evolution in plants, studying host pathogen interactions and betterment of crop production as exons assist in interpretation of allelic variation with respect to their phenotype. This review covers the platforms for exome sequencing, next generation sequencing technologies that have revolutionized exome sequencing and led toward development of third generation sequencing. Also discussed in this review are the uses of these sequencing technologies to improve wheat, rice and cotton yield and how these technologies are used in exploring the biodiversity of crops, providing better understanding of plant-host pathogen interaction and assessing the process of natural evolution in crops and it also covers how exome sequencing identifies the gene pool involved in symbiotic and other co-existential systems. Furthermore, we conclude how integration of other methodologies including whole genome sequencing, proteomics, transcriptomics and metabolomics with plant exomics covers the areas which are left untouched with exomics alone and in the end how these integration will transform the future of crops.

Adult seafood allergy in the Texas Medical Center: A 13-year experience.

There is a paucity of data regarding prevalence and characteristics of adult seafood allergy in United States cohorts. This study was designed to determine the characteristics of patient-reported seafood allergy in a large allergy referral adult population. Retrospective analysis was performed of laboratory and clinical characteristics of seafood-allergic patients in three allergy clinics in the Texas Medical Center between January 1, 1997 and January 30, 2010. Of 5162 patients seen in this adult allergy referral population, 159 had physician-diagnosed seafood allergy with an average age of diagnosis of 50.2 (18-81 years) years. Shellfish allergy (59.1%) was more frequent than fish allergy (13.8%). Crustacean allergy (82.6%) was more frequent than mollusk allergy (7.2%). Shrimp (72.5%), crab (34.8%), and lobster (17.4%) were the most common shellfish allergies and tuna (28.6%), catfish (23.8%), and salmon (23.8%) were the most common fish allergies. One-third of seafood-allergic patients reported reactions to more than one seafood. Shellfish-allergic adults were more likely to experience respiratory symptoms than fish-allergic adults (p < 0.05). The likelihood of having anaphylaxis (32%) was not statistically different between shellfish- and fish-allergic subjects. Severe reactions were 12.9 times more likely to occur within the 1st hour of ingestion compared with nonsevere reactions (p < 0.005). The percentage of seafood allergy in this adult allergy referral population was 3.08%.

Child and adolescent mental health services in Pakistan: current situation, future directions and possible solutions.

Worldwide, mental disorders are on the increase (Gadit, 2007) and an estimated 10-20% of children have one or more mental or behavioural problems (Park, 2002). There is an urgent and serious need to pay attention to the mental health needs of children in low- and middle-income countries (Rahman et al, 2000). The initial survey for the World Health Organization's Atlas project (Sherer, 2002) showed that 41% of countries surveyed had no mental health policy and 28% had no separate budget for mental health.