A Nationwide Survey Following the Devastating 2022 Floods in Pakistan: Current State of Knowledge, Attitude, and Perception Toward Climate Change and Its Health Consequences.

BACKGROUND:  Climate change (CC) persists as a critical public health concern, vividly demonstrated by Pakistan's severe unprecedented flooding from June to October 2022. The interplay between floods and CC highlights the urgent need to comprehend their complex dynamics. Given Pakistan's significant geographical vulnerability to CC events, assessing public awareness of CC becomes essential. This study aims to evaluate public knowledge, attitudes, and perception (KAP) regarding CC and its implications for overall health, reflecting onto governmental policies and community-based guidelines and enhancing preparedness for future natural calamities of similar magnitude. METHODS:  A nationwide cross-sectional survey of Pakistani adults covering all provinces of the country was conducted from January to March 2023 using a prevalidated questionnaire. A purposive sampling strategy was used to enroll participants in the study. Where appropriate, the chi-square test or Fisher's exact test was used to compare KAP among the sociodemographic groups. Multivariate analysis was used to explore predictors of knowledge. Crude and adjusted odds ratios (ORs) were calculated considering a p value of ≤0.05 as significant. RESULTS:  Among the 714 respondents, 265 (37.1%) of the respondents' residential areas were affected by the floods in Pakistan. A total of 663 (92.9%) of the participants had heard of CC, with 302 (42.3%) choosing "social media/WhatsApp" as their source of information. Increased flooding and changes in rainfall patterns were selected by 679 (95.1%) and 661 (92.6%) participants, respectively, as the most recognized CC. "Deforestation" was the most indicated reason for CC by 675 (94.5%) participants. Multivariate analysis revealed that females (OR: 1.31, 95% CI: 1.16-2.00; p < 0.001), individuals who were affected by recent floods (OR: 1.13, 95% CI: 1.05-3.34; p = 0.003), and individuals who were medical students/healthcare workers (OR: 1.49, 95% CI: 1.24-2.48; p < 0.001) had greater knowledge of CC than their counterparts. CONCLUSIONS:  The study reported an encouraging prevalence of knowledge of CC, positive attitudes, and practices toward CC, with an interest in learning and doing more to address the health effects of CC. With the ongoing global CC and a monsoon season forecast of similar intensity for the years to come in Pakistan, identifying groups with less knowledge of CC warrants a targeted education program to maximize awareness. Based on the study findings, social media platforms and interventions in educational institutes should be essential to mitigate the CC events in Pakistan and other vulnerable regions in the area.

Lung Underdevelopment: Case Reports and a Literature Review.

Lung underdevelopment is a rare congenital anomaly with variable clinical significance and presenting symptoms. It usually manifests during childhood. We present two cases of developmental lung anomaly subtypes and discuss clinical presentation and outcomes in such patient populations. LEARNING POINTS: Pulmonary underdevelopment is a challenging diagnosis and should be considered in patients with unilateral opacification on chest radiograph.Childhood developmental history is critical for diagnosis as delayed, or misdiagnoses are common. Definitive diagnosis can be made by computed tomography scan.Management is watchful waiting with close monitoring, with long term prognosis remaining unclear.

Single-Molecule DNA Methylation Reveals Unique Epigenetic Identity Profiles of T Helper Cells.

Both identity and plasticity of CD4 T helper (Th) cells are regulated in part by epigenetic mechanisms. However, a method that reliably and readily profiles DNA base modifications is still needed to finely study Th cell differentiation. Cytosine methylation in CpG context (5mCpG) and cytosine hydroxymethylation (5hmCpG) are DNA modifications that identify stable cell phenotypes, but their potential to characterize intermediate cell transitions has not yet been evaluated. To assess transition states in Th cells, we developed a method to profile Th cell identity using Cas9-targeted single-molecule nanopore sequencing. Targeting as few as 10 selected genomic loci, we were able to distinguish major in vitro polarized murine T cell subtypes, as well as intermediate phenotypes, by their native DNA 5mCpG patterns. Moreover, by using off-target sequences, we were able to infer transcription factor activities relevant to each cell subtype. Detection of 5mCpG and 5hmCpG was validated on intestinal Th17 cells escaping transforming growth factor ß control, using single-molecule adaptive sampling. A total of 21 differentially methylated regions mapping to the 10-gene panel were identified in pathogenic Th17 cells relative to their nonpathogenic counterpart. Hence, our data highlight the potential to exploit native DNA methylation profiling to study physiological and pathological transition states of Th cells.

3-Substituted Coumarins Inhibit NorA and MepA Efflux Pumps of Staphylococcus aureus.

Coumarins are compounds with scientifically proven antibacterial properties, and modifications to the chemical structure are known to improve their effects. This information is even more relevant with the unbridled advances of antibiotic resistance, where Staphylococcus aureus and its efflux pumps play a prominent role. The study's objective was to evaluate the potential of synthetic coumarins with different substitutions in the C-3 position as possible inhibitors of the NorA and MepA efflux pumps of S. aureus. For this evaluation, the following steps took place: (i) the determination of the minimum inhibitory concentration (MIC); (ii) the association of coumarins with fluoroquinolones and ethidium bromide (EtBr); (iii) the assessment of the effect on EtBr fluorescence emission; (iv) molecular docking; and (v) an analysis of the effect on membrane permeability. Coumarins reduced the MICs of fluoroquinolones and EtBr between 50% and 87.5%. Coumarin C1 increased EtBr fluorescence emission between 20 and 40% by reinforcing the evidence of efflux inhibition. The molecular docking results demonstrated that coumarins have an affinity with efflux pumps and establish mainly hydrogen bonds and hydrophobic interactions. Furthermore, C1 did not change the permeability of the membrane. Therefore, we conclude that these 3-substituted coumarins act as inhibitors of the NorA and MepA efflux pumps of S. aureus.

Reduced metal nanocatalysts for selective electrochemical hydrogenation of biomass-derived 5-(hydroxymethyl)furfural to 2,5-bis(hydroxymethyl)furan in ambient conditions.

Selective electrochemical hydrogenation (ECH) of biomass-derived unsaturated organic molecules has enormous potential for sustainable chemical production. However, an efficient catalyst is essential to perform an ECH reaction consisting of superior product selectivity and a higher conversion rate. Here, we examined the ECH performance of reduced metal nanostructures, i.e., reduced Ag (rAg) and reduced copper (rCu) prepared via electrochemical or thermal oxidation and electrochemical reduction process, respectively. Surface morphological analysis suggests the formation of nanocoral and entangled nanowire structure formation for rAg and rCu catalysts. rCu exhibits a slight enhancement in ECH reaction performance in comparison to the pristine Cu. However, the rAg exhibits more than two times higher ECH performance without compromising the selectivity for 5-(HydroxyMethyl) Furfural (HMF) to 2,5-bis(HydroxyMethyl)-Furan (BHMF) formation in comparison to the Ag film. Moreover, a similar ECH current density was recorded at a reduced working potential of 220 mV for rAg. This high performance of rAg is attributed to the formation of new catalytically active sites during the Ag oxidation and reduction processes. This study demonstrates that rAg can potentially be used for the ECH process with minimum energy consumption and a higher production rate.

Calotropis procera accumulates Uzarigenin and Calotropagenin in response to environmental lighting and drought.

Calotropis procera (C. procera) was evaluated as a pharmaceutically useful plant and for its therapeutic effects in the most significant studies. Uzarigenin and Calotropagenin are significant components of this plant that have pharmacological effects on certain systems, including the digestive, immunological, and focal, and peripheral sensory systems. In this study, pathway genes are extracted from high throughput data acc.no. SRR1554320. Seven critical enzymes are involved in studying the effects of sunlight on the formation of Uzaragenin and Calotropagenin in C. procera before and after irrigation. Molecular identification and NCBI submission of six enzyme genes were successful; HSD (acc.no. OQ091761) for 3ß-hydroxystroid dehydrogenase, OR (acc.no. OQ091762) for 5beta-pregnan oxidoreductase, MO (acc.no. OQ091763) for Pregnan monooxygenase, HOX (acc.no. OQ091764) for Steroid hydroxylase, MAT (acc.no. OQ091765) for Melonyletransferase, UHOX (acc.no. OQ091766) for Uzarigenin hydroxylase. During dawn after irrigation, the Uzargenin pathway showed the highest activity, however midday after irrigation was the lowest. The most period that showed high activity for the Uzargenin pathway was dawn after irrigation, however, midday after irrigation was the lowest. This data is confirmed by chromatography analysis (UPLC) to calculate the accumulation of Uzarigenin and Calotropagenin in different periods.

PRR-HyPred: A two-layer hybrid framework to predict pattern recognition receptors and their families by employing sequence encoded optimal features.

Pattern recognition receptors (PRRs) recognize distinct features on the surface of pathogens or damaged cells and play key roles in the innate immune system. PRRs are divided into various families, including Toll-like receptors, retinoic acid-inducible gene-I-like receptors, nucleotide oligomerization domain-like receptors, and C-type lectin receptors. As these are implicated in host health and several diseases, their accurate identification is indispensable for their functional characterization and targeted therapeutic approaches. Here, we construct PRR-HyPred, a novel two-layer hybrid framework in which the first layer predicts whether a given sequence is PRR or non-PRR using a support vector machine, and in the second, the predicted PRR sequence is assigned to a specific family using a random forest-based classifier. Based on a 10-fold cross-validation test, PRR-HyPred achieved 83.4 % accuracy in the first layer and 95 % in the second, with Matthew's correlation coefficient values of 0.639 and 0.816, respectively. This is the first study that can simultaneously predict and classify PRRs into specific families. PRR-HyPred is available as a web portal at https://procarb.org/PRRHyPred/. We hope that it could be a valuable tool for the large-scale prediction and classification of PRRs and subsequently facilitate future studies.

In silico screening of the effectiveness of natural compounds from algae as SARS-CoV-2 inhibitors: molecular docking, ADMT profile and molecular dynamic studies.

Marine species are known as rich sources of metabolites largely involved in the pharmaceutical industry. This study aimed to evaluate in silico the effect of natural compounds identified in algae on the SARS-CoV-2 Main protease, RNA-dependent-RNA polymerase activity (RdRp), endoribonuclease (NSP15) as well as on their interaction with viral spike protein. A total of 45 natural compounds were screened for their possible interaction on SARS-CoV-2 target proteins using Maestro interface for molecular docking, molecular dynamic (MD) simulation to estimate compounds binding affinities. Among the algal compounds screened in this study, three (Laminarin, Astaxanthin and 4'-chlorostypotriol triacetate) exhibited the lowest docking energy and best interaction with SARS-CoV-2 viral proteins (Main protease, RdRp, Nsp15, and spike protein). The complex of the main protease with laminarin shows the most stable RMSD during a 150 ns MD simulation time. Which indicates their possible inhibitory activity on SARS-CoV-2.Communicated by Ramaswamy H. Sarma.

Comparison of Prophylactic Phenylephrine Infusion Versus Intravenous Ondansetron on Hypotension During Spinal Anesthesia for Cesarean Section.

Background: Multiple methods have been proposed to prevent the incidence of hypotension in women undergoing cesarean section under spinal anesthesia. This study was conducted to compare the efficacy of phenylephrine (50 µg.min-1) versus ondansetron (8 mg) in the prevention of such complications. Patients and Methods: We included a total of 184 full-term pregnant women who were randomly divided into two groups: Group P included 92 cases who were commenced on phenylephrine infusion (50 µg.min-1 given after puncture) and Group O included the other 92 cases who were administered ondansetron (8 mg given 5 min before puncture). Results: Demographic data were not significantly different between the two groups. Maternal hypotension was significantly more encountered in the ondansetron group (51.6% vs. 22%) and ephedrine was used more significantly in that group (19.8% vs. 8.8%). In addition, nausea and skin flushing were more commonly encountered in the same group. The incidence of vomiting and patient discomfort was not significantly different between the two study groups. Conclusion: Phenylephrine is markedly superior to ondansetron in the prevention of maternal hypotension and vasopressor need during cesarean section under spinal anesthesia.

In-silico investigation of a novel inhibitors against the antibiotic-resistant Neisseria gonorrhoeae bacteria.

Antibiotics are drugs that are used to treat or prevent bacterial infections. They work by either killing or stopping bacteria from spreading. Nevertheless, it appeared in the last decade, Antibiotic-resistant bacteria are bacteria resistant to antibiotics and cannot be controlled or killed by them. In the presence of an antibiotic, they can live and even reproduce. The Neisseria gonorrhoeae bacteria is appearing to be a multidrug-resistant pathogen. Many factors contribute to antibiotic resistance, including unfettered access to antimicrobials, incorrect drug selection, misuse, and low-quality antibiotics. Here, we investigated in-silico docking screening and analysis for ten natural marine fungus extracted compounds. The resulted data were examined for the best binding affinity, toxicity, and chemical interactions. The most superior compound was elipyrone A with six hydrogen bonds, -8.5 of binding affinity, and preferable results in the SWISS-ADME examination. It is well known that "Declining corporate investment and a lack of innovation in the development of new antibiotics are weakening efforts to battle drug-resistant illnesses," according to the World Health Organization (WHO). So, we extended our effort to predict a new natural compound to overcome the resistance of this bacteria.

First report of triterpenes pathway in Calotropis procera revealed to accumulate beta-amyrin.

The major reports on Calotropis procera (C. procera) indicated the importance of this plant as a resource of pharmaceutically active ingredients as well as its medical advantages. ß-amyrin (BA) is a significant substance in this plant and has a pharmacological effects in some frameworks, like focal and fringe sensory system, digestive and immune systems. In this study, the impact of sunlight before and after irrigation on the BA production in C. procera is studied its pathway with involved eight key enzymes. The eight enzymes' genes were characterized and successfully submitted to NCBI; AAS (acc.no. KU997645) for α-amyrin synthase, BAS (acc.no. MW976955) for ß-amyrin synthase, SE (acc.no. MW976956) for squalene epoxidase, SS (acc.no. MW976957) for squalene synthase, GPPS, (acc.no. MW976958) for geranyl pyrophosphate synthase, FPPS (acc.no. MW976959) for farnasyl pyrophosphate synthase, CAS1, (acc.no. MZ00598) for cycloartenol synthase1 and LS (acc.no. MZ005982) for lupeol synthase. qRT-PCR analysis revealed high expression levels of GPPS, FPPS, SS, SE, and BAS genes at all times specially midday. Otherwise, CAS1, LS and BAS expression levels were very low at all daylight periods. The UPLC ß-amyrin data are in accordance with qRT-PCR results. This indicates that triterpenes biosynthetic pathway in C. procera is going to ß-amyrin accumulation with the highest level at midday.

Rare Adverse Events Associated with BNT162b2 mRNA Vaccine (Pfizer-BioNTech): A Review of Large-Scale, Controlled Surveillance Studies.

Given the increasing anti-vaccine movements erroneously touting vaccine danger, this review has investigated the rare adverse events potentially associated with BNT162b2 (Pfizer-BioNTech), an mRNA vaccine against the severe acute respiratory distress syndrome coronavirus 2 (SARS-CoV-2). Only real-world surveillance studies with at least 0.1 million BNT162b2-vaccinated participants and one unvaccinated control group were selected for review. A total of 21 studies examining the potential association of BNT162b2 with cardiovascular, herpetic, thrombotic or thrombocytopenic, neurological, mortality, and other miscellaneous rare adverse events were described in this review. Only myocarditis is consistently associated with BNT162b2. An unclear direction of association was seen with stroke (hemorrhagic and ischemic), herpes zoster, and paresthesia from BNT162b2, which may require more studies to resolve. Fortunately, most surveillance studies detected no increased risks of the remaining rare adverse events reviewed herein, further reassuring the safety of BNT162b2. In conclusion, this review has concisely summarized the current rare adverse events related and unrelated to BNT162b2, arguably for the first time in sufficient depth, to better communicate vaccine safety to the public.

Low Platinum-Loaded Molybdenum Co-catalyst for the Hydrogen Evolution Reaction in Alkaline and Acidic Media.

Developing an efficient catalytic system for electrolysis with reduced platinum (Pt) loading while maintaining performance comparable to bulk platinum metal is important to decrease costs and improve scalability of the hydrogen fuel economy. Here we report the performance of a novel sputter-deposited molybdenum (Mo) thin film with an extremely low co-loading of Pt, where Pt atoms were dispersed on Mo (Ptd-Mo) as an electrocatalyst for the hydrogen evolution reaction (HER) in either alkaline or acidic media. The Ptd-Mo electrocatalyst presents similar catalytic activity to bulk Pt in alkaline media, while the performance is only slightly decreased in acidic media. Differential electrochemical mass spectrometry (DEMS) results confirm that the Ptd-Mo electrocatalyst produced hydrogen at a rate comparable with that of a pristine Pt sample at the same potential. A comparison with Pt-loaded degenerately doped p-type doped silicon (Ptd-Si) suggests that Mo and Pt work synergistically to boost the performance of Ptd-Mo catalysts. Cyclic voltammetry (CV) and X-ray photoelectron spectroscopy (XPS) before and after 1000 cycles of continuous operation confirm the significant durability of the Ptd-Mo performance. Overall, the Ptd-Mo electrocatalyst, with comparable HER activity to bulk Pt despite an ultra-low Pt loading, could be a strong candidate for hydrogen production in either acidic or basic conditions.

A case of horizontal gaze palsy with progressive scoliosis.

Horizontal gaze palsy with progressive scoliosis is a rare entity with few cases in the literature. Despite the fact the patient will not present with typical symptoms of this syndrome, clinical suspicion should be raised particularly in terms of imaging findings. Imaging findings are characteristic to flag the possibility of this syndrome. Keeping in mind such congenital abnormalities on magnetic resonance imaging particularly for radiologists might help in the management process. Multidisciplinary teams play a crucial role in terms of communication to find the clinical, radiological and genetic studies to reach the diagnosis.

Review: Geometric interpretation of reflection and transmission RHEED patterns.

Reflection high-energy electron diffraction (RHEED) is widely used to characterize the surface structure of single crystals. Moreover, RHEED has become a standard tool to monitor thin film growth in molecular beam epitaxy and is used to monitor other vapor deposition techniques including evaporation, sputtering, and pulsed laser deposition. With the rapid development of the fabrication methods and use of nanoparticles, RHEED operating in the transmission mode is being applied to characterize nanoparticles on surfaces. In this review, the fundamentals needed to interpret RHEED patterns from the top few atomic layers, in its reflection mode, and from nanoparticles and nanofeatures, in its transmission mode, are discussed based on the geometric kinematic approximation. Examples are provided on the interpretation of RHEED patterns from unreconstructed and 2 × 1-reconstructed Si(100), InP(100), highly oriented pyrolytic graphite, indium nanoparticles, and indium growth on Si(100)- 2 × 1.

Gastric Cancer and Viruses: A Fine Line between Friend or Foe.

Gastric cancer (GC) is a significant health concern worldwide, with a GLOBOCAN estimate of 1.08 million novel cases in 2020. It is the leading cause of disability-adjusted life years lost to cancer, with the fourth most common cancer in males and the fifth most common cancer in females. Strategies are pursued across the globe to prevent gastric cancer progression as a significant fraction of gastric cancers have been linked to various pathogenic (bacterial and viral) infections. Early diagnosis (in Asian countries), and non-invasive and surgical treatments have helped manage this disease with 5-year survival for stage IA and IB tumors ranging between 60% and 80%. However, the most prevalent aggressive stage III gastric tumors undergoing surgery have a lower 5-year survival rate between 18% and 50%. These figures point to a need for more efficient diagnostic and treatment strategies, for which the oncolytic viruses (OVs) appear to have some promise. OVs form a new therapeutic agent class that induces anti-tumor immune responses by selectively killing tumor cells and inducing systemic anti-tumor immunity. On the contrary, several oncogenic viruses have been shown to play significant roles in malignancy progression in the case of gastric cancer. Therefore, this review evaluates the current state of research and advances in understanding the dual role of viruses in gastric cancer.

Interaction Analysis of MRP1 with Anticancer Drugs Used in Ovarian Cancer: In Silico Approach.

Multidrug resistance (MDR) is one of the major therapeutic challenges that limits the efficacy of chemotherapeutic response resulting in poor prognosis of ovarian cancer (OC). The multidrug resistance protein 1 (MRP1) is a membrane-bound ABC transporter involved in cross resistance to many structurally and functionally diverse classes of anticancer drugs including doxorubicin, taxane, and platinum. In this study, we utilize homology modelling and molecular docking analysis to determine the binding affinity and the potential interaction sites of MRP1 with Carboplatin, Gemcitabine, Doxorubicin, Paclitaxel, and Topotecan. We used AutoDock Vina scores to compare the binding affinities of the anticancer drugs against MRP1. Our results depicted Carboplatin < Gemcitabine < Topotecan < Doxorubicin < Paclitaxel as the order of binding affinities. Paclitaxel has shown the highest binding affinity whereas Carboplatin displayed the lowest affinity to MRP1. Interestingly, our data showed that Carboplatin, Paclitaxel, and Topotecan bind specifically to Asn510 residue in the transmembrane domains 1 of the MRP1. Our results suggest that Carboplatin could be an appropriate therapeutic choice against MRP1 in OC as it couples weakly with Carboplatin. Further, our findings also recommend opting Carboplatin with Gemcitabine as a combinatorial chemotherapeutic approach to overcome MDR phenotype associated with recurrent OC.

Revealing the Effect of MnO2, Activated Carbon and MnO2/Activated Carbon on Chitosan Polymer Host Fabricated Co NPs: Antibacterial Performance and Degradation of Organic Compounds.

MnO2 and MnO2 blended with 1 and 2 weight percent of activated carbon (AC), MnO2/AC1 and MnO2/AC2 were synthesized through the sol-gel method. The pure chitosan (CS) films were cast in the form of films. Similarly, 5 weight% of each MnO2, AC, MnO2/AC1 and MnO2/AC2 was intermingled with the CS to produce different films, such as CS-AC, CS-MnO2, CS-MnO2/AC1 and CS-MnO2/AC2. Zero-valent Co NPs were then supported on these films through the chemical reduction method and expressed as CS@Co, CS-AC@Co, CS-MnO2@Co, CS-MnO2/AC1@Co and CS-MnO2/AC2@Co NPs. All the catalysts were characterized by field emission scanning electron microscopy (FESEM), energy-dispersive spectroscopy (EDS) and X-ray diffraction (XRD) techniques. The synthesized catalysts were used as a dip catalyst against the hydrogenation of 4-nitrophenol (4NP), and for the degradation of methyl orange (MO) and Congo red (CR) dyes. The kapp and R2 values were deduced from pseudo-first-order kinetics for 4NP and MO and zero-order kinetics for CR dye. The kapp values of CS-AC@Co and CS-MnO2/AC1@Co NPs for 4NP hydrogenation were higher than those for any other member of the series, at 1.14 × 10-1 and 1.56 × 10-1 min-1 respectively. Similarly, the rate of CR degradation was highest with CS-AC@Co. The R2 values for 4NP, MO and CR dyes were above 0.9, which indicated that the application of pseudo-first- and zero-order models were appropriate for this study. Furthermore, the antibacterial activity of all the catalysts was evaluated against Pseudomonas aeruginosa and Escherichia coli. The CS-AC@Co NPs exhibited the highest zone of inhibition compared to other catalysts against P. aeruginosa, while all the catalysts were inactive against E. coli. This study reveals that the catalyst can be used for the degradation of other pollutants and for microbial inhibition.