Dietary Habits and Their Impact on Gastroesophageal Reflux Disease (GERD).

Introduction Gastroesophageal reflux disease (GERD) is marked by the frequent occurrence of stomach acid flowing back into the esophagus, causing symptoms such as heartburn and acid regurgitation at least once a week. When reflux leads to troublesome symptoms and esophageal damage and adversely affects quality of life, it is diagnosed as GERD. Age, gender, ethnicity, genetic predispositions, and aspects of diet and lifestyle, including factors like obesity and smoking, are associated with GERD. Methodology This cross-sectional study was conducted within the Departments of General Medicine, Surgery, and Gastroenterology at Khyber Teaching Hospital (KTH) in Peshawar, spanning from January 2024 to June 2024. Patients who visited these departments or the Outpatient Department within the specified period with GERD were included in the study. A non-probability purposive sampling technique was used. For the analysis, we utilized IBM SPSS Statistics version 21. Results This study consists of 280 participants. The mean age of the participants in this study was 44.60 years. GERD has a significant association with obesity (69.99) and lack of exercise (80%), and a negative association was found between other gastrointestinal conditions (55.71%) and smoking (64.28). Common symptoms among GERD patients were swallowing difficulty, regurgitation, heartburn, and chest pain. Conclusion Our study is the first to examine the relationship between lifestyle factors and GERD among Pakistani patients. Our findings highlight significant associations between GERD and several factors, including gender, BMI, dietary habits, and lack of exercise. Notably, cultural and regional differences appear to influence GERD prevalence and its risk factors, as demonstrated by the minimal impact of alcohol consumption in our study population.

Defluoridation by positive single-pulse current electrocoagulation from photovoltaic wastewater: Energy consumption assessment and mechanism analysis.

The presence of fluoride ions (F-) in photovoltaic (PV) wastewater significantly affects the integrity of the ecological environment. In contrast to direct current electrocoagulation (DC-EC), positive single-pulse electrocoagulation (PSPC-EC) shows a significant reduction in both the formation of passivation films on electrodes and the consumption of electrical energy. Under the experimental conditions of an Al-Al-Al-Al electrode combination, an electrode spacing of 1.0 cm, a NaCl concentration of 0.05 mol L-1, an initial pH of 5.6, an initial F- concentration of 5 mg L-1, a current density of 5 A m-2, a pulse frequency of 500 Hz, and a 40 % duty cycle, the achieved equilibrium F- removal efficiencies were 84.0 % for DC-EC and 88.0 % for PSPC-EC, respectively, accompanied by power consumption of 0.0198 kWh·mg-1 and 0.0073 kWh·mg-1. The flocs produced in the PSPC-EC process were characterized using scanning electron microscopy, X-ray diffraction, Fourier transform infrared spectroscopy, and X-ray photoelectron spectroscopy and it is revealed that the F- removal mechanisms in the PSPC-EC process include co-precipitation, hydrogen bond complexation, and ion exchange. When the actual PV wastewater was finally subjected to treatment under the optimal PSPC-EC conditions, the F- concentration in the wastewater was reduced from 4.6 mg L-1 to 1.4 mg L-1. This paper provides both a theoretical framework and a technological basis for the application of PSPC-EC in the advanced treatment of PV wastewater.

Catalytic ozonation of reverse osmosis membrane concentrates by catalytic ozonation: Properties and mechanisms.

Ni-Mn@KL ozone catalyst was prepared for the efficient treatment of reverse osmosis membrane concentrates. The working conditions and reaction mechanism of the ozone-catalyzed oxidation by Ni-Mn@KL were systematically studied. Then, a comprehensive CRITIC weighting-coupling coordination evaluation model was established. Ni-Mn@KL was characterized by scanning electron microscopy, BET, X-ray diffraction, X-ray photoelectron spectroscopy, energy-dispersive spectrometry, and X-ray fluorescence spectrometry and found to have large specific surface area and homogeneous surface dispersion of striped particles. Under the optimum working conditions with an initial pH of 7.9 (raw water), a reaction height-to-diameter ratio of 10:1, an ozone-aeration intensity of 0.3 L/min, and a catalyst filling rate of 10%, the maximum COD removal rate was 60.5%. Free-radical quenching experiments showed that OH oxidation played a dominant role in the Ni-Mn@KL-catalyzed ozone-oxidation system, and the reaction system conformed to the second-order reaction kinetics law. Ni-Mn@KL catalysts were further confirmed to have good catalytic performance and mechanical performance after repeated utilization. PRACTITIONER POINTS: Ni-Mn@KL catalyst can achieve effective treatment of RO film concentrated liquid. High COD removal rate of RO membrane concentrated liquid was obtained at low cost. Ni-Mn@KL catalyst promotes ozone decomposition to produce ·OH and O2 -· oxidized organic matter. The Ni-Mn@KL catalyst can maintain good stability after repeated use. A CRITIC weight-coupling coordination model was established to evaluate the catalytic ozonation.

KRAS as a Prognostic and Predictive Marker in Metastatic Non-Small Cell Lung Carcinoma: A Systematic Review.

Metastatic non-small cell lung cancer (NSCLC) poses a significant clinical challenge, prompting a focused investigation into the role of KRAS mutations in prognosis and treatment response. Targeted therapies offer promising avenues for intervention, motivating a comprehensive analysis of existing evidence. Conducted in June 2023, our review delved into MEDLINE (Medical Literature Analysis and Retrieval System Online), Embase, Scopus, and the Cochrane Register of Controlled Trials. Rigorous inclusion and exclusion criteria guided the selection of 12 articles, comprising two randomized controlled trials (RCTs) and 10 observational studies. Multiple investigators independently executed data extraction, evaluating prognostic factors (overall and progression-free survival) and predictive outcomes (treatment and objective response). The Newcastle-Ottawa Scale (NOS) and modified Jadad scores were used for study quality assessment of observational studies and RCTs, respectively. From an initial pool of 120 articles, the 12 selected studies, spanning 2013 to 2022, encompassed 2,845 metastatic NSCLC patients. KRAS mutations, particularly the G12C variant, emerged as a pivotal factor influencing treatment response. Notably, KRAS wild type patients displayed enhanced responses to platinum-based chemotherapy, while those with KRAS mutations exhibited favourable outcomes with immune checkpoint inhibitors (ICIs). The role of KRAS mutations as prognostic indicators in metastatic NSCLC is underscored by this systematic review, with implications for both survival and treatment response. The discernment between KRAS wild type and mutant patients offers insights into tailored therapeutic strategies, with platinum-based chemotherapy and immune checkpoint inhibitors emerging as context-dependent options. Nevertheless, more research is required to solidify the predictive role of KRAS and explore the efficacy of KRAS inhibitors and other targeted therapies, paving the way for refined and personalized interventions in the management of metastatic NSCLC.

Global epidemiology of cannabis use disorders and its trend from 1990 to 2019: Benchmarking analysis of the global burden of disease study.

Introduction: Cannabis is one of the most widely used psychoactive substances globally, with an increasing trend in its legalization for both medical and recreational purposes in various countries. While cannabis offers potential therapeutic benefits, its regular use can lead to the development of Cannabis Use Disorders (CUDs). Understanding the epidemiology of CUDs is crucial in assessing the public health burden associated with cannabis use. Methods: Epidemiological parameters of CUDs were assessed using the Global Burden of Disease (GBD) methodology across different age-groups, years, sexes, and locations worldwide from 1990-2019. Results: Globally, for both sexes combined, prevalent cases of CUDs increased steadily from 17.1 million(95%UI=12.7-22.8million) in 1990 to 23.8-million(95%UI=17.8-30.9 million) in 2019. All age-adjusted highest number of incidence observed in High-Income-North-America(HINA)(121/100,000), followed by Australasia(100/100,000), Oceania(83.97/100,000), Tropical Latin America(69.59/100,000). Globally, age-standardized disability-adjusted life years rate(ASDR) observed higher in HINA, followed by Australasia, and Western-Europe. In male, all-age incidence counts increased from 1.7 million(95%UI=1.3-2.4million) in 1990 to 2.4 million(95%UI=1.8-3.2 million) in 2019. The highest annual percentage of change in age-standardized incidence rate(ASIR) was found in East-Asia (22%) followed by Middle-East and North-Africa(MENA)(15%). The age group of 15-24 years exhibited the highest burden of CUDs. Conclusion: The widespread occurrence of CUDs on a global scale poses a substantial challenge to public health. Understanding the impact of CUDs and implementing evidence-based interventions is crucial in mitigating the associated individual, societal, and economic burdens. Continued research, collaboration, and knowledge dissemination are essential to inform policies, prevention efforts, and treatment strategies aimed at addressing CUDs on a global-scale.

Performance Improvement Program Review of Institutional Massive Transfusion Protocol Adherence: An Opportunity for Improvement.

BACKGROUND: Given the acuity of patients who receive MTPs and the resources they require, MTPs are a compelling target for performance improvement. This study evaluated adherence with our MTP's plasma:red blood cell ratio (FFPR) of 1:2 and platelet:red blood cell ratio (PLTR) of 1:12, to test the hypothesis that ratio adherence is associated with lower inpatient mortality. MATERIALS AND METHODS: The registry of an urban level I trauma center was queried for adult patients who received at least 6 units of packed red blood cells within 4 hours of presentation. Patients were excluded for interfacility transfer, cardiac arrest during the prehospital phase or within one hour of arrival, or for head AIS ≥5. Univariate analysis and multiple logistic regressions were performed to identify variables associated with early transfusion protocol noncompliance and the effect on inpatient mortality. RESULTS: Three hundred and eighty-three patients were included, with mean ISS of 25.9 ± 13.3 and inpatient mortality of 28.5%. Increasing age, ISS, INR, and total units of blood product transfused were associated with increased odds of mortality, while an increase in revised trauma score was associated with a decreased odds ratio of mortality. Achieving our goal ratios were protective against mortality, with OR of .451 (P = .013) and .402 (P=.003), respectively. DISCUSSION: Large proportions of critically injured patients were transfused fewer units of plasma and platelets than our MTP dictated; failure to achieve intended ratios at 4 hours was strongly associated with inpatient mortality. MTP processes and outcomes should be critically assessed on a regular basis as part of a mature performance improvement program to ensure protocol adherence and optimal patient outcome.

Preparation of composite coagulant for the removal of microplastics in water.

In this work, a composite flocculant (polyferric titanium sulfate-polydimethyldiallylammonium chloride [PFTS-PDMDAAC]) with a rich spatial network structure was prepared for the treatment of simulated wastewater containing polystyrene (PS) micro-nanoparticles. Characterization results showed that the surface of the PFTS-PDMDAAC was a three-dimensional network polymer of chain molecules that exhibited good thermal stability and formed an amorphous polymer containing multiply hydroxyl-bridged titanium and iron. When n(OH- ) : n(Fe) = 1:2, n(PO4 3- ) : n(Fe) = 0.35, n(Ti) : n(Fe) = 1:8, n(DMDAAC) : n(Fe) = 5:100, and the polymerization temperature is 60°C, the prepared composite flocculant has the best effect. The effects of dosage, pH, and agitation intensity on the flocculation properties of PFTS-PDMDAAC were also studied. The optimal removal rates of PS-µm and haze by PFTS-PDMDAAC were 85.60% and 90.10%, respectively, at a stirring intensity of 200 rpm, a pH of 9.0, and a PFTS-PDMDAAC dosage of 20 mg/L. The flocs produced by the PFTS-PDMDAAC flocculation were large and compact in structure, and the flocculation mechanism was mainly based on adsorption bridging. Kaolin played a promoting role in the process of PS-µm removal by PFTS-PDMDAAC floc and accelerated the formation of large and dense flocs. This study provided a reference for the coagulation method to remove micro-nanopollutants in the actual water treatment process. PRACTITIONER POINTS: A composite flocculant with rich spatial network structure (PFTS-PDMDAAC) was prepared. PFTS-PDMDAAC can effectively remove micro-nano polystyrene (PS) in wastewater. The floc produced by PFTS-PDMDAAC is large and compact in structure. The flocculation mechanism of PFTS-PDMDAAC is mainly adsorption bridging.

PLK1 as a cooperating partner for BCL2-mediated antiapoptotic program in leukemia.

The deregulation of BCL2 family proteins plays a crucial role in leukemia development. Therefore, pharmacological inhibition of this family of proteins is becoming a prevalent treatment method. However, due to the emergence of primary and acquired resistance, efficacy is compromised in clinical or preclinical settings. We developed a drug sensitivity prediction model utilizing a deep tabular learning algorithm for the assessment of venetoclax sensitivity in T-cell acute lymphoblastic leukemia (T-ALL) patient samples. Through analysis of predicted venetoclax-sensitive and resistant samples, PLK1 was identified as a cooperating partner for the BCL2-mediated antiapoptotic program. This finding was substantiated by additional data obtained through phosphoproteomics and high-throughput kinase screening. Concurrent treatment using venetoclax with PLK1-specific inhibitors and PLK1 knockdown demonstrated a greater therapeutic effect on T-ALL cell lines, patient-derived xenografts, and engrafted mice compared with using each treatment separately. Mechanistically, the attenuation of PLK1 enhanced BCL2 inhibitor sensitivity through upregulation of BCL2L13 and PMAIP1 expression. Collectively, these findings underscore the dependency of T-ALL on PLK1 and postulate a plausible regulatory mechanism.

Toxic effects of aging mask microplastics on E. coli and dynamic changes in extracellular polymeric matter.

Contamination of disposable medical masks has become a growing problem globally in the wake of Covid-19 due to their widespread use and improper disposal. Three different mask layers, namely the outer layer, the meltblown (MB) filler layer and the inner layers release three different types of microplastics, whose physical and chemical properties change after prolonged environmental weathering. In this study, physical and chemical changes of mask microplastics before and after aging were characterized by different characterization techniques. The toxic effect and mechanism of aged mask microplastics on Escherichia coli (E. coli) were studied by measuring the growth inhibition of mask microplastics, the change in ATPase activity, the change in malondialdehyde content and reactive oxygen species production, and the release of the chemical composition of exopolymeric substances (EPS). The microplastics of the aged MB filter layer had the most significant inhibitory effect on E. coli growth, reaching 19.2 % after 36 h. Also, under the influence of mask microplastics, ATPase activity of E. coli was inhibited and a large amount of EPS was released. The chemical composition of EPS has also changed. This study proposed the possible toxicity mechanism of mask microplastics and the self-protection mechanism of E. coli, and provided a reference for future research on the toxic effects of mask microplastics on environmental organisms.

One-step hydrothermal generation of oxygen-deficient N-doped blue TiO2-Ti3C2 for degradation of pollutants and antibacterial properties.

In this study, TiO2 was generated in situ on the surface of Ti3C2 by a hydrothermal process, and urea was added to form N-doped TiO2-Ti3C2. The surface morphology and functional group properties of the prepared materials were analyzed by SEM, TEM, XRD, XPS, etc. The results showed that anatase TiO2 formed on the surface of the Ti3C2 monolayer. Nitrogen-doped nanomaterials show good phenol degradation and good recyclability under visible light. At a urea content of 0.5 g, the photocatalytic degradation of phenol under visible light is best, reaching 88.9% in 3 h, with ·OH and ·O2- holes playing the leading role. However, at lower pH and higher ion concentration, the degradability of N-TiO2-Ti3C2 for phenol is reduced. Furthermore, the material prepared in this work is a two-dimensional layered material, and the adsorption of phenol best fits the Langmuir adsorption isotherm model and the pseudo-second-order kinetic equation. In terms of the antibacterial performance of the material, the N-doped TiO2-Ti3C2 nanomaterial made with 0.2 g of urea has an Escherichia coli scavenging efficiency of about 97.86%, which is an excellent antibacterial material. This study shows that the N-TiO2-Ti3C2 produced in this experiment can be used for environmental applications.

Fever in the returning traveler.

Evaluation of febrile illness in a returning traveler is challenging as it requires careful history taking and knowledge of local epidemiology of endemic and epidemic diseases. Incorporating information of host characteristics for susceptibility of infections is also important for endemic mycosis apart from history of tick bites and animal exposures. Laboratory tests directed by clinical and laboratory parameters will help to reach final diagnosis.

Targeting altered glycosylation in secreted tumor glycoproteins for broad cancer detection.

There is an urgent need to develop new tumor biomarkers for early cancer detection, but the variability of tumor-derived antigens has been a limitation. Here we demonstrate a novel anti-Tn antibody microarray platform to detect Tn+ glycoproteins, a near universal antigen in carcinoma-derived glycoproteins, for broad detection of cancer. The platform uses a specific recombinant IgG1 to the Tn antigen (CD175) as a capture reagent and a recombinant IgM to the Tn antigen as a detecting reagent. These reagents were validated by immunohistochemistry in recognizing the Tn antigen using hundreds of human tumor specimens. Using this approach, we could detect Tn+ glycoproteins at subnanogram levels using cell lines and culture media, serum, and stool samples from mice engineered to express the Tn antigen in intestinal epithelial cells. The development of a general cancer detection platform using recombinant antibodies for detection of altered tumor glycoproteins expressing a unique antigen could have a significant impact on cancer detection and monitoring.

Different weathering conditions affect the release of microplastics by masks.

A generation of microplastics caused by improper disposal of disposable masks has become a non-negligible environmental concern. In order to investigate the degradation mechanisms of masks and the release of microplastics under different environmental conditions, the masks are placed in 4 common environments. After 30 days of weathering, the total amount and release kinetics of microplastics released from different layers of the mask were studied. The chemical and mechanical properties of the mask were also discussed. The results showed that the mask released 25141±3543 particles/mask into the soil, which is much more than the sea and river water. The release kinetics of microplastics fit the Elovich model better. All samples correspond to the release rate of microplastics from fast to slow. Experiments show that the middle layer of the mask is released more than the other layers, and the amount of release was highest in the soil. And the tensile capacity of the mask is negatively correlated with its ability to release microplastics in the following order, which are soil > seawater > river > air > new masks. In addition, during the weathering process, the C-C/C-H bond of the mask was broken.

Application of Size Exclusion Chromatography with Multiangle Light Scattering in the Analytical Development of a Preclinical Stage Gene Therapy Program.

To provide safe recombinant adeno-associated viruses (rAAV) to patients, scalable manufacturing processes are required. However, these processes may introduce impurities that impact the performance and quality of the final drug product. Empty rAAV capsids are product-related impurities. Regulatory guidance requires that accurate analytical methods be implemented early in product development to measure the level of empty capsids. A process confirmation vector, produced from 200 L production, was used to develop and optimize a size exclusion chromatography with UV and multiangle light scattering (SEC-MALS) method. Vector produced from a 500 L production was used to assess the full-to-empty ratio using the following analytical methods: sedimentation velocity analytical ultracentrifugation (SV-AUC), droplet digital PCR (ddPCR) with capsid enzyme-linked immunosorbent assay (ELISA), bulk absorbance at 260/280 nm, cryogenic electron microscopy, and SEC-MALS. This test article was used for a 30-day, non-Good Laboratory Practices animal study that assessed biodistribution of the product (STRX-330). SEC-MALS outperformed the other methods and correlated well with SV-AUC values of full-to-empty particles. In addition, SEC-MALS agreed with ddPCR and ELISA measurements for vector genomes/mL and capsid particles/mL, respectively. SEC-MALS was linear, accurate, and precise while achieving chromatography quality control (QC) recommendations. Compared to other stability-indicating assays, SEC-MALS performed similarly to ddPCR, capsid ELISA, and infectivity assays in accelerated stress studies. In response to alkaline, but not acidic stress, SEC-MALS indicated distinct changes in the DNA content of the monomer Adeno-associated viruses (AAV) peak for STRX-330, which was supported by ddPCR data. Conversely, acidic treatment resulted in more aggregated vector, but did not impact the DNA content. This work indicates that SEC-MALS is a valuable analytical tool in the analytical development and QC testing of AAV. In addition, this work suggests that SEC-MALS can provide fundamental understanding of AAV in response to environmental stress. This may impact steps of the manufacturing process to minimize conditions that reduce performance.

Venetoclax-Resistant T-ALL Cells Display Distinct Cancer Stem Cell Signatures and Enrichment of Cytokine Signaling.

Therapy resistance remains one of the major challenges for cancer treatment that largely limits treatment benefits and patient survival. The underlying mechanisms that lead to therapy resistance are highly complicated because of the specificity to the cancer subtype and therapy. The expression of the anti-apoptotic protein BCL2 has been shown to be deregulated in T-cell acute lymphoblastic leukemia (T-ALL), where different T-ALL cells display a differential response to the BCL2-specific inhibitor venetoclax. In this study, we observed that the expression of anti-apoptotic BCL2 family genes, such as BCL2, BCL2L1, and MCL1, is highly varied in T-ALL patients, and inhibitors targeting proteins coded by these genes display differential responses in T-ALL cell lines. Three T-ALL cell lines (ALL-SIL, MOLT-16, and LOUCY) were highly sensitive to BCL2 inhibition within a panel of cell lines tested. These cell lines displayed differential BCL2 and BCL2L1 expression. Prolonged exposure to venetoclax led to the development of resistance to it in all three sensitive cell lines. To understand how cells developed venetoclax resistance, we monitored the expression of BCL2, BCL2L1, and MCL1 over the treatment period and compared gene expression between resistant cells and parental sensitive cells. We observed a different trend of regulation in terms of BCL2 family gene expression and global gene expression profile including genes reported to be expressed in cancer stem cells. Gene set enrichment analysis (GSEA) showed enrichment of cytokine signaling in all three cell lines which was supported by the phospho-kinase array where STAT5 phosphorylation was found to be elevated in resistant cells. Collectively, our data suggest that venetoclax resistance can be mediated through the enrichment of distinct gene signatures and cytokine signaling pathways.

Review of Impact of COVID-19 on Maternal, Neonatal Outcomes, and Placental Changes.

Coronavirus disease (COVID-19), caused by SARS-CoV-2, is a disease that has caused a global impact. COVID-19 is transmitted through airborne droplets, respiratory secretions, and direct contact. The pandemic has affected individuals of different ages, and studying the impact of COVID-19 on maternal and newborn outcomes is critical. In this review, we highlight the impact of COVID-19 infection in pregnancy and its repercussion in the maternal-fetal binomial. Physiological changes that occur during pregnancy have significant effects on the immune system, cardiopulmonary system, and coagulation, and these changes can result in an altered response to COVID-19 infection. The symptoms, risk factors, and maternal health consequences of COVID-19 were discussed. In addition, the impact of newborns born to mothers with COVID-19 was reviewed. Finally, placental changes and vertical transmission of COVID-19 during pregnancy were also discussed in this review.

Dental Caries and Oral Health Status of Psychoactive Substance Abusers.

Substance-abuse disorders are universally associated with comorbid illness. Tobacco is a widely abused substance across the globe and presents a critical public health problem. The precise correlation between tobacco use and dental caries remains unclear. Thus, the present study aimed to evaluate the correlation between tobacco use and dental caries. METHODOLOGY: Based on selection criteria, a total of 270 (age 20-50 years) participants were included in the study, and were categorized as group A (n = 135), consisting of tobacco users, and group B (n = 135), comprising healthy controls (non-users). The Decayed, Missing, and Filled index (DMFT) was used to measure caries status. The Simplified Oral Hygiene index was used to evaluate oral health. RESULTS: The tobacco group reported the use of cigarettes; smokeless tobacco in indigenous forms, such as gutka (areca nut, tobacco, and slaked lime), betel nut chewing; and a combination. Individuals with tobacco habits had a higher prevalence of dental caries (Mean DMFT 4.73 ± 4.32) compared to the non-habit group (Mean DMFT 3.17 ± 3.11 (p = 0.001). The Oral Hygiene index was significantly higher (indicating bad/poor oral hygiene) in tobacco abusers than those of non-users (p = 0.0001). Duration and frequency of tobacco use were correlated with the levels of moderate and severe caries (p = 0.001). CONCLUSION: Psychoactive substance abuse, such as smoking/smokeless tobacco consumption, is associated with higher prevalence of dental caries.