Angiogenic protein profiling, phytochemical screening and in silico anti-cancer targets validation of stem, leaves, fruit, and seeds of Calotropis procera in human liver and breast cancer cell lines.

The main focus of anticancer drug discovery is on developing medications that are gentle on normal cells and should have the ability to target multiple anti-cancer pathways. Liver cancer is becoming a worldwide epidemic due to the highest occurring and reoccurring rate in some countries. Calotropis procera is a xerophytic herbal plant growing wildly in Saudi Arabia. Due to its anti-angiogenic and anticancer capabilities, "C. procera " is a viable option for developing innovative anticancer medicines. However, no study has been done previously, to discover angiogenic and anti-cancer targets which are regulated by C. procera in liver cancer. In this study, leaves, stems, flowers, and seeds of C. procera were used to prepare crude extracts and were fractionated into four solvents of diverse polarities. These bioactivity-guided solvent fractions helped to identify useful compounds with minimal side effects. The phytoconstituents present in the leaves and stem were identified by GC-MS. In silico studies were done to predict the anti-cancer targets by major bioactive constituents present in leaves and stem extracts. A human angiogenesis antibody array was performed to profile novel angiogenic targets. The results from this study showed that C. procera extracts are an ideal anti-cancer remedy with minimum toxicity to normal cells as revealed by zebrafish in vivo toxicity screening assays. The novel antiangiogenic and anticancer targets identified in this study could be explored to design medication against liver cancer.

Unveiling photoinduced electron transfer in cobalt(iii)-R-pyridine complexes anchored to anatase nanocrystals: photoluminescence and magnetic studies.

In this study, we synthesized mixed ligand complexes of the cis-[Co(tn)2(Rpy)Br]Br2 type using a novel mechanochemical approach. Characterization involved spectral measurements and single crystal X-ray diffraction analysis, confirming the structure of the cis-[Co(tn)2(4-Mepy)Br]Br2 complex. The single crystal refinement data revealed a monoclinic crystal system with a distorted octahedral geometry. The choice of the sixth ligand influenced the emission and magnetic properties, showing a ferromagnetic character in the Co(iii)-complex environment. We investigated efficient electron transfer to the cobalt(iii) center using TiO2 nanoparticles under UV-light irradiation. The adsorption characteristics of cis-[Co(tn)2(Rpy)Br]Br2 in aqueous 2-propanol varied, leading to surface compound formation. Under UV irradiation, the anatase surface exhibited remarkable adsorption capabilities, facilitating efficient electron transfer to the Co(iii) center and resulting in a high photoefficiency for Co(ii) formation. Our study has put forward a model for interfacial electron transfer (IET), taking into account the overlap between the TiO2 conduction band and the acceptor level of the Co center, as well as the electronic coupling between the donor level of the Ti center and the acceptor level of the Co center. This model sheds light on the accumulation of electrons for reducing the adhered complex ion. The IET process was corroborated by the conversion of 2-propanol into acetone, as verified by 1H NMR technique. Overall, our findings provide novel insights into the role of the Rpy moiety in modifying the structure of the TiO2-cobalt(iii)-Rpy compound and propose a mechanism for IET reactions, thus advancing the field.

Peak Exercise Capacity and Angina Threshold Improvement after Cardiac Rehabilitation in a Patient with Stable Angina and Low Hemoglobin.

Cardiac rehabilitation (CR) is recommended for all patients with stable angina (SA) as an effective treatment. Hemoglobin (Hgb) levels predict exercise performance and may affect symptom threshold in SA patients. A multidisciplinary CR intervention was individually tailored for a 72-year-old patient with a diagnosis of SA, low Hgb (<10 g/dL), and typical chest pain at light-to-moderate exercise (<5 metabolic equivalent task), who was stratified as at high risk for cardiac events during exercise. Two symptom-limited exercise tests were performed before and after 36 sessions of supervised exercise training producing near-optimal accumulated total volume load and chronic training load. In this case report, we show that an individually tailored CR intervention in a patient with SA and low Hgb is feasible, effective, and safe at reducing the burden of symptoms while increasing peak exercise capacity, health-related quality of life, and physical activity engagement.

Design and Synthesis of Polyheterocyclic Compounds Containing Pyrazolopyridopyrimidine Nucleus with Antimicrobial Activities.

This study reports the design, synthesis, and antibacterial evaluation of a library of novel polyheterocyclic derivatives featuring a unique fused pyrimidopyridopyrazole moiety. A cyclocondensation reaction between an amino-pyrazolopyridopyrimidine precursor and malonates afforded a series of pyrimidopyridopyrazolopyrimidine derivatives. Further diversification was achieved through nucleophilic cyclocondensation, yielding a collection of complex polyheterocyclic systems encompassing various ring structures. All synthesized compounds were rigorously characterized using spectroscopic techniques and elemental analysis. The antibacterial activity of the newly synthesized compounds was assessed against a panel of Gram-positive and Gram-negative bacteria. Notably, several compounds exhibited promising antibacterial activity, highlighting their potential as leads for the development of novel antibiotics.

Green Synthesis of Zinc Oxide Nanoparticles from Althaea officinalis Flower Extract Coated with Chitosan for Potential Healing Effects on Diabetic Wounds by Inhibiting TNF-α and IL-6/IL-1ß Signaling Pathways.

Background: Diabetes Mellitus is a multisystem chronic pandemic, wound inflammation, and healing are still major issues for diabetic patients who may suffer from ulcers, gangrene, and other wounds from uncontrolled chronic hyperglycemia. Marshmallows or Althaea officinalis (A.O.) contain bioactive compounds such as flavonoids and phenolics that support wound healing via antioxidant, anti-inflammatory, and antibacterial properties. Our study aimed to develop a combination of eco-friendly formulations of green synthesis of ZnO-NPs by Althaea officinalis extract and further incorporate them into 2% chitosan (CS) gel. Method and Results: First, develop eco-friendly green Zinc Oxide Nanoparticles (ZnO-NPs) and incorporate them into a 2% chitosan (CS) gel. In-vitro study performed by UV-visible spectrum analysis showed a sharp peak at 390 nm, and Energy-dispersive X-ray (EDX) spectrometry showed a peak of zinc and oxygen. Besides, Fourier transforms infrared (FTIR) was used to qualitatively validate biosynthesized ZnO-NPs, and transmission electron microscope (TEM) showed spherical nanoparticles with mean sizes of 76 nm and Zeta potential +30mV. The antibacterial potential of A.O.-ZnO-NPs-Cs was examined by the diffusion agar method against Gram-positive (Staphylococcus aureus and Bacillus subtilis) and Gram-negative bacteria (Escherichia coli and Pseudomonas aeruginosa). Based on the zone of inhibition and minimal inhibitory indices (MIC). In addition, an in-silico study investigated the binding affinity of A.O. major components to the expected biological targets that may aid wound healing. Althaea Officinalis, A.O-ZnO-NPs group showed reduced downregulation of IL-6, IL-1ß, and TNF-α and increased IL-10 levels compared to the control group signaling pathway expression levels confirming the improved anti-inflammatory effect of the self-assembly method. In-vivo study and histopathological analysis revealed the superiority of the nanoparticles in reducing signs of inflammation and wound incision in rat models. Conclusion: These biocompatible green zinc oxide nanoparticles, by using Althaea Officinalis chitosan gel ensure an excellent new therapeutic approach for quickening diabetic wound healing.

Multiple-Drug Resistant Shiga Toxin-Producing E. coli in Raw Milk of Dairy Bovine.

INTRODUCTION: Raw milk may contain pathogenic microorganisms harmful to humans, e.g., multidrug-resistant Escherichia coli non-O157:H7, which can cause severe colitis, hemolytic uremia, and meningitis in children. No studies are available on the prevalence of Shiga toxin-producing E. coli (STEC O157:H7) in sick or healthy dairy animals in the Khyber Pakhtunkhwa Province of Pakistan. AIM: This study aimed to isolate, characterize, and detect antibiotic resistance in STEC non-O157:H7 from unpasteurized milk of dairy bovines in this province. MATERIALS AND METHODS: We collected raw milk samples (n = 800) from dairy farms, street vendors, and milk shops from different parts of the Khyber Pakhtunkhwa Province. E. coli was isolated from these samples followed by latex agglutination tests for serotyping. The detection of STEC was conducted phenotypically and confirmed by the detection of virulence genes genotypically. An antibiogram of STEC isolates was performed against 12 antibiotics using the disc diffusion method. RESULTS: A total of 321 (40.12%) samples were found to be positive for E. coli in this study. These samples were processed for the presence of four virulence genes (Stx1, Stx2, ehxA, eae). Forty samples (5.0%) were STEC-positive. Of these, 38%, 25%, 19%, and 18% were positive for Stx1, Stx2, ehxA, and eae, respectively. Genotypically, we found that 1.37% of STEC isolates produced extended-spectrum beta-lactamase (ESBL) and contained the blaCTX M gene. Resistance to various antibiotics ranged from 18% to 77%. CONCLUSION: This study highlights the risk of virulent and multidrug-resistant STEC non-O157:H7 in raw milk and the need for proper quality surveillance and assurance plans to mitigate the potential public health threat.

Synthesis, characterization, molecular modeling, binding energies of ß-cyclodextrin-inclusion complexes of quercetin: Modification of photo physical behavior upon ß-CD complexation.

We prepared a naturally occurring flavanoid namely quercetin from tea leaves and analyzed by Absorption, Emission, FT-IR, 1H, 13C nmr spectra and ESI-MS analysis. The inclusion behavior of quercetin in cyclodextrins like α-, ß-, γ-, per-6-ABCD and mono-6-ABCD cavities were supported such as UV-vis., Emission, FT-IR and ICD spectra and energy minimization studies. From the absorption and emission results, the type of complexes formed were found to depend on stoichiometry of Host:Guest. FT-IR data of CD complexes of quercetin supported inclusion complex formation of the substrate with α-, ß- and γ-CDs. The inclusion of host-guest complexation of quercetin with α-, ß-, γ-CDs, per-6-ABCD and mono-6-ABCDs provides very valuable information about the CD:quercetin complexes, the study also shows that ß-CD complexation improves water solubility, chemical stability and bioavailability of quercetin. Besides, phase solubility studies also supported the formation of 1:1 drug-CD soluble complexes. All these spectral results provide insight into the binding behavior of substrate into CD cavity in the order per-6-ABCD > Mono-6-ABCD > γ-CD > ß-CD > α-CD. The proposed model also finds strong support from the fact with excess CD this exciton coupling disappears indicates the formation of only 1:1 complex.

Interpretation of adsorption isotherm and kinetics behind fluorene degradation.

The gradual release of slow-degrading polycyclic aromatic hydrocarbons into the environment creates a high level of threat to aquatic and terrestrial life worldwide. Remediation of these PAHs should be designed in such a way that it poses as few or no environmental hazards as possible. In our study, we examined the degradation ability of the synthesized MnO2 nanoparticles against fluorene. The MnO2 nanoparticle prepared was found to be spherical from the SEM analysis. XRD analysis confirms the average crystallite size as 31.8652 nm. Further, the characterization of nanoparticles was confirmed by UV-DRS, FT-IR, DLS, and HPLC techniques. The extent of adsorption potential of the synthesized nanoparticles was established from the batch adsorption studies and the kinetic and isotherm model was interpreted. The antimicrobial properties of the synthesized MnO2 nanoparticles were analyzed.

Dysfunctional neutrophil type 1 interferon responses in preschool children with recurrent wheezing and IL-4-mediated aeroallergen sensitization.

Background: The innate mechanisms associated with viral exacerbations in preschool children with recurrent wheezing are not understood. Objective: We sought to assess differential gene expression in blood neutrophils from preschool children with recurrent wheezing, stratified by aeroallergen sensitization, at baseline and after exposure to polyinosinic:polycytidylic acid (poly(I:C)) and also to examine whether poly(I:C)-stimulated blood neutrophils influenced airway epithelial gene expression. Methods: Blood neutrophils were purified and cultured overnight with poly(I:C) and underwent next-generation sequencing with Reactome pathway analysis. Primary human small airway epithelial cells were treated with poly(I:C)-treated neutrophil culture supernatants and were analyzed for type 1 interferon gene expression with a targeted array. Symptoms and exacerbations were assessed in participants over 12 months. Results: A total of 436 genes were differently expressed in neutrophils from children with versus without aeroallergen sensitization at baseline, with significant downregulation of type 1 interferons. These type 1 interferons were significantly upregulated in sensitized children after poly(I:C) stimulation. Confirmatory experiments demonstrated similar upregulation of type 1 interferons in IL-4-treated neutrophils stimulated with poly(I:C). Poly(I:C)-treated neutrophil supernatants from children with aeroallergen sensitization also induced a type 1 interferon response in epithelial cells. Children with aeroallergen sensitization also had higher symptom scores during exacerbations, and these symptom differences persisted for 3 days after prednisolone treatment. Conclusions: Type 1 interferon responses are dysregulated in preschool children with aeroallergen sensitization, which is in turn associated with exacerbation severity. Given the importance of type 1 interferon signaling in viral resolution, additional studies of neutrophil type 1 interferon responses are needed in this population.

Characterizing the effects of muscle-specific GSK3α/ß reduction on murine muscle contractility and metabolism in female mice.

Dysregulation of skeletal muscle morphology and metabolism is associated with chronic diseases such as obesity and type 2 diabetes. The enzyme glycogen synthase kinase 3 (GSK3) is highly involved in skeletal muscle physiology and metabolism, acting as a negative regulator of muscle size, strength, adaptive thermogenesis, and glucose homeostasis. Correspondingly, we have shown that partial knockdown (∼40%) of GSK3 specifically in skeletal muscle increases lean mass, reduces fat mass, and activates muscle-based adaptive thermogenesis via sarco(endo)plasmic reticulum Ca2+ (SERCA) uncoupling in male mice. However, the effects of GSK3 knockdown in female mice have yet to be investigated. Here, we examined the effects of muscle-specific GSK3 knockdown on body composition, muscle size and strength, and whole body metabolism in female C57BL/6J mice. Our results show that GSK3 content is higher in the female soleus versus the male soleus; however, there were no differences in the extensor digitorum longus (EDL). Furthermore, muscle-specific GSK3 knockdown did not alter body composition in female mice, nor did it alter daily energy expenditure, glucose/insulin tolerance, mitochondrial respiration, or the expression of the SERCA uncouplers sarcolipin and neuronatin. We also did not find any differences in soleus muscle size, strength, or fatigue resistance. In the EDL, we found that an increase in absolute and specific force production, but there were no differences in fatigability. Therefore, our study highlights sex differences in the response to genetic reduction of gsk3, with most of the effects previously observed in male mice being absent in females.NEW & NOTEWORTHY Here we show that partial GSK3 knockdown has minimal effects on whole body metabolism and muscle contractility in female mice. This is partly inconsistent with previous results found in male mice, which reveal a potential influence of biological sex.

Revolutionizing Psoriasis Topical Treatment: Enhanced Efficacy Through Ceramide/Phospholipid Composite Cerosomes Co-Delivery of Cyclosporine and Dithranol: In-Vitro, Ex-Vivo, and in-Vivo Studies.

Purpose: Improving the treatment of psoriasis is a serious challenge today. Psoriasis is an immune-mediated skin condition affecting 125 million people worldwide. It is commonly treated with cyclosporine-A (CsA) and dithranol (DTH). CsA suppresses the activation of T-cells, immune cells involved in forming psoriatic lesions. Meanwhile, DTH is a potent anti-inflammatory and anti-proliferative drug that effectively reduces the severity of psoriasis symptoms such as redness, scaling, and skin thickness. CsA and DTH belong to BCS class II with limited oral bioavailability. We aim to develop a drug delivery system for topical co-delivery of CsA and DTH, exploring its therapeutic potential. Methods: Firstly, we developed a niosomal drug delivery system based on ceramide IIIB to form Cerosomes. Cerosomes were prepared from a mixture of Ceramide, hyaluronic acid, and edge activator using a thin-film hydration technique. To co-deliver CsA and DTH topically for the treatment of psoriasis. These two hydrophobic drugs encapsulated into our synthesized positively charged particle cerosomes. Results:  Cerosomes had an average particle size of (222.36 nm± 0.36), polydispersity index of (0.415±0.04), Entrapment Efficiency of (96.91%± 0.56), and zeta potential of (29.36±0.38mV) for selected formula. In vitro, In silico, in vivo, permeation, and histopathology experiments have shown that cerosomes enhanced the skin penetration of both hydrophobic drugs by 66.7% compared to the CsA/DTH solution. Imiquimod (IMQ) induced psoriatic mice model was topically treated with our CsA/DTH cerosomes. We found that our formulation enhances the skin penetration of both drugs and reduces psoriasis area and severity index (PASI score) by 2.73 times and 42.85%, respectively, compared to the CsA/DTH solution. Moreover, it reduces the levels of proinflammatory cytokines, TNF-α, IL-10, and IL-6 compared to CsA/DTH solution administration. Conclusion: The Cerosomes nano-vesicle-containing CsA/DTH represents a more promising topical treatment for psoriasis, giving new hope to individuals with psoriasis, compared to commercial and other conventional alternatives.

A systematic review on Nb2O5-based photocatalysts: Crystallography, synthetic methods, design strategies, and photocatalytic mechanisms.

With the increasing popularity of photocatalytic technology and the highly growing issues of energy scarcity and environmental pollution, there is an increasing interest in extremely efficient photocatalytic systems. The widespread immense attention and applicability of Nb2O5 photocatalysts can be attributed to their multiple benefits, including strong redox potentials, non-toxicity, earth abundance, corrosion resistance, and efficient thermal and chemical stability. However, the large-scale application of Nb2O5 is currently impeded by the barriers of rapid recombination loss of photo-activated electron/hole pairs and the inadequacy of visible light absorption. To overcome these constraints, plentiful design strategies have been directed at modulating the morphology, electronic band structure, and optical properties of Nb2O5. The current review offers an extensive analysis of Nb2O5-based photocatalysts, with a particular emphasis on crystallography, synthetic methods, design strategies, and photocatalytic mechanisms. Finally, an outline of future research directions and challenges in developing Nb2O5-based materials with excellent photocatalytic performance is presented.

Magnitude of health expenditure induced removable poverty in India: Some reflections of Ayushman Bharat.

The authors have measured the health expenditure-induced removable poverty in India using nationally representative consumer expenditure surveys of three quinquennial rounds conducted by the National Sample Survey Organization (NSSO). This study has also focused on the reflections of Ayushman Bharat-Pradhan Mantri Jan Arogya Yojana (AB-PMJAY), the world's largest Government-funded health insurance scheme, on these poverty rates in the country. The study has used headcount, payment gap, and concentration index to measure the economic burden and impoverishment impact of out-of-pocket (OOP) health expenditure. The analysis shows that the incidence and depth of poverty are substantially understated because of overlooking OOP health expenditure in the country's standard poverty measure. Outpatient care contributes almost four times more than inpatient care to health expenditure-induced impoverishment in India, though this care has not been covered in the AB-PMJAY. Muslims, among all religious groups, Scheduled Castes among social groups, and casual labourers among different household types are more vulnerable to OOP health expenditure-induced removable poverty in the country. Poverty, in general, has dropped significantly, but the share of health expenditure-induced poverty in general poverty has increased substantially. It has risen considerably in rural areas and among India's most vulnerable sections of society in the past 20 years. We emphasised that universal health insurance coverage is needed in India. Implementing comprehensive health insurance schemes that cover both inpatient and outpatient care can help alleviate the financial burden of healthcare expenses on households and contribute to reducing poverty rates.

Women's attitudes, prevalence, related factors, and perceived barriers of birth companionship in Saudi Arabia.

BACKGROUND: The World Health Organization recommends companionship as a critical element of respectful maternity care. However, there is paucity of literature regarding women's attitudes, related factors, and barriers of implementation in Saudi Arabia. OBJECTIVE: This study aimed to assess women's attitudes toward birth companionship during labor and delivery, related factors, and barriers of implementing labor companionship in Saudi Arabia. DESIGN/METHODS: This study was carried out in Al Ahsa, Saudi Arabia, using a cross-sectional design. The data collection took place over a period of approximately 6 months, specifically from 16 August 2021 to 20 February 2022. A total of 418 women who had given birth at three governmental hospitals and three private hospitals in Al Ahsa participated in the survey. The study included women between the ages of 18 and 49 years who had delivered during the study period. RESULTS: The study revealed that while around 82.8% of mothers expressed a desire for companionship during labor, only 43.2% actually had a labor companion present during delivery. The primary obstacle to labor companionship reported by 21.5% of respondents was hospital policies. Other barriers identified included husbands' fear of being present during labor (4.7%) and limited availability of time for companionship (3.8%). CONCLUSION: The study concludes that birth companionship is highly desired by women in the study area. However, various physical, emotional, and institutional barriers, such as hospital policies and regulations, impede its implementation. Addressing these barriers and promoting supportive policies are essential to facilitate the provision of birth companionship and improve the childbirth experience for women in Al Ahsa.

Assessment of antidiabetic, anti-inflammatory, antioxidant and anticancer activity competence of methonolic extracts of Trianthema ortulacastrum and Andrographis paniculata.

An in-vitro investigation was performed to evaluate and compare the phytochemical, antioxidant, antidiabetic, anti-inflammatory, and anti-lung cancer activities of methanol extracts of aerial parts of Andrographis paniculata and Trianthema portulacastrum. Furthermore studied major functional groups of phytochemicals present in the methanol extracts of these plants through Fourier transform infrared (FTIR) analysis. The results showed that the methanol extract of A. paniculata contain more number of pharmaceutically valuable phytochemicals such as alkaloids, flavonoids, terpenoids, saponin, glycoside, phytosterol, and tannin than T. portulacastrum. Similar way the methanol extract of A. paniculata showed considerable dose dependent antioxidant (DPPH: 63%), antidiabetic (α-amylase: 82.31% and α-glucosidase inhibitions: 72.34%), and anti-inflammatory (albumin-denaturation inhibition: 76.3% and anti-lipoxygenase: 61.2%) activities (at 900 µg mL-1 concentration) than T. portulacastrum. However, the anti-lung cancer activities of these test plants against A549 cells were not considerable. According to FTIR analysis, the A. paniculata methanol extract has a larger number of characteristic peaks attributed to the active functional groups of pharmaceutically valuable bioactive components that belong to different types of phytochemicals. These findings imply that A. paniculata methanol extracts can be used for additional research, such as bioactive compound screening and purification, as well as assessing their potential biomedical uses in various in-vitro and in-research settings.

Antimicrobial and anti-diabetic efficiency of Polyalthia longifolia leaf extracts and major compounds characterization.

This research was performed to investigate the bactericidal and fungicidal competence of extracts (methanol and petroleum ether extract) of Polyalthia longifolia leaf. Moreover, the major active compounds present in the effective crude extract (either methanol or petroleum ether extract) was determined through initially with UV-Vis spectra, FTIR, and GC-MS analyses. The methanol extract alone showed remarkable bactericidal and fungicidal activity against the bacterial (S. pyogenes > E. coli > S. aureus > S. pneumoniae > C. difficile > P. aeruginosa) and fungal (A. clavatus > C. albicans > A. niger > A. fumigatus > C. tropicalis > C. auris) pathogens at increased concentration (12.5 mg mL-1) than petroleum ether extract. The MIC and MBC values of methanol extract were found as 10-20 mg mL-1 and 30-40 mg mL-1 respectively. The MFC value of methanol extract was found as 10-20 mg mL-1. These MIC, MBC, and MFC values of methanol extract were considerably greater than petroleum ether extract. The FTIR and GC-MS characterization studies revealed that the presence of more acre functional groups belonging to bioactive compounds such as Z)-7-Hexadecenal, Aromandendrene, α-Curcumene, Caryophyllene, Methyl 14-methyl Pentadecanoat, Methyl trans-13-Octadecenoate, 9-Octadecenoic acid (Z)-, and 2-hydroxy-1- (hydroxymethyl)ethyl. As a result of these findings, it is possible that P. longifolia leaf methanol extract contains medicinally important bioactive substances with bactericidal and fungicidal properties.

Biological Control of Hyalomma Ticks in Cattle by Fungal Isolates.

Ticks pose a major threat to cattle health and production in Pakistan because they transmit pathogens of diseases like Babesiosis and Theileriosis. Hyalomma spp., found across Africa, Asia, and Europe, are especially problematic. This study explored biocontrol of Hyalomma spp. using spore-free fungal culture filtrates collected from dairy farm soil in Kohat, Pakistan. Three fungal species of the genera Alternaria, Aspergillus, and Penicillium were isolated, and their filtrates were tested against tick adults and larvae. Filtrate concentrations were prepared at different strengths. Data were taken after the exposure of adults and larvae ticks to various concentrations of the fungal filtrates. Results indicated that at 100% concentration, all fungal filtrates induced 100% mortality in adults and larvae. Decreasing filtrate concentration lowered tick mortality. The lowest concentration caused the least mortality. The effect was time- and dose-dependent. In conclusion, spore-free fungal culture filtrates can provide biocontrol of Hyalomma spp. in a time- and concentration-dependent manner. Further research should explore the active compounds causing mortality and optimal application methods. The process outlined here provides a natural biocontrol alternative to chemical pesticides to reduce tick infestations and associated cattle diseases in Pakistan.

Influence of metabolic stress and metformin on synaptic protein profile in SH-SY5Y-derived neurons.

Insulin resistance (IR) is associated with reductions in neuronal proteins often observed with Alzheimer's disease (AD), however, the mechanisms through which IR promotes neurodegeneration/AD pathogenesis are poorly understood. Metformin (MET), a potent activator of the metabolic regulator AMPK is used to treat IR but its effectiveness for AD is unclear. We have previously shown that chronic AMPK activation impairs neurite growth and protein synthesis in SH-SY5Y neurons, however, AMPK activation in IR was not explored. Therefore, we examined the effects of MET-driven AMPK activation with and without IR. Retinoic acid-differentiated SH-SY5Y neurons were treated with: (1) Ctl: 24 h vehicle followed by 24 h Vehicle; (2) HI: 100 nM insulin (24 h HI followed by 24 h HI); or (3) MET: 24 h vehicle followed by 24 h 2 mM metformin; (4) HI/MET: 24 h 100 nM insulin followed by 24 h 100 nM INS+2 mM MET. INS and INS/MET groups saw impairments in markers of insulin signaling (Akt S473, mTOR S2448, p70s6k T389, and IRS-1S636) demonstrating IR was not recovered with MET treatment. All treatment groups showed reductions in neuronal markers (post-synaptic marker HOMER1 mRNA content and synapse marker synaptophysin protein content). INS and MET treatments showed a reduction in the content of the mature neuronal marker NeuN that was prevented by INS/MET. Similarly, increases in cell size/area, neurite length/area observed with INS and MET, were prevented with INS/MET. These findings indicate that IR and MET impair neuronal markers through distinct pathways and suggest that MET is ineffective in treating IR-driven impairments in neurons.

Transmissibility of severe acute respiratory syndrome coronavirus 2 among household contacts of coronavirus disease 2019-positive patients: A community-based study in India.

BACKGROUND: This study identified the risk factors for severe acute respiratory syndrome coronavirus 2 infection among household contacts of index patients and determined the incubation period (IP), serial interval, and estimates of secondary infection rate in Kerala, India. METHODS: We conducted a cohort study in three districts of Kerala among the inhabitants of households of reverse transcriptase polymerase chain reaction-positive coronavirus disease 2019 patients between January and July 2021. About 147 index patients and 362 household contacts were followed up for 28 days to determine reverse transcriptase polymerase chain reaction positivity and the presence of total antibodies against SARS-CoV-2 on days 1, 7, 14, and 28. RESULTS: The mean IP, serial interval, and generation time were 1.6, 3, and 3.9 days, respectively. The secondary infection rate at 14 days was 43.0%. According to multivariable regression analysis persons who worked outside the home were protected (adjusted odds ratio [aOR], 0.45; 95% confidence interval [CI], 0.24-0.85), whereas those who had kissed the coronavirus disease 2019-positive patients during illness were more than twice at risk of infection (aOR, 2.23; 95% CI, 1.01-5.2) than those who had not kissed the patients. Sharing a toilet with the index patient increased the risk by more than twice (aOR, 2.5; 95% CI, 1.42-4.64) than not sharing a toilet. However, the contacts who reported using masks (aOR, 2.5; 95% CI, 1.4-4.4) were at a higher risk of infection in household settings. CONCLUSIONS: Household settings have a high secondary infection rate and the changing transmissibility dynamics such as IP, serial interval should be considered in the prevention and control of SARS-CoV-2.

The Burden of Neonatal Referrals on a Pediatric Cardiology Service: A Local Center Experience.

BACKGROUND: Congenital heart disease (CHD) is a common occurrence in live births, with some exhibiting critical congenital heart disease; therefore, cardiology services should be available around the clock to ensure timely diagnosis and management. This study aims to describe the workload and the need for pediatric cardiac services in a maternity hospital for newborn referrals. Moreover, the study describes the indications for neonatal cardiology consultations. METHODS: The prospective cohort study was conducted over four months, from January to April 2022, in the Prince Sultan Cardiac Center Al Qassim region of Saudi Arabia. Prince Sultan Cardiac Center's pediatric cardiology department provides cardiac services to the Maternity and Children Hospital Buraidah Al Qassim. Out of the total 2,606 live births during the study period, the cardiology team evaluated 352 neonates. Neonates less than 30 days of age who were born in the maternity hospital were enrolled in the study. The outborn babies referred from other centers as suspected congenital heart disease for whom a cardiac evaluation was done were excluded. In addition, babies assessed in the emergency room and born elsewhere were excluded. Only new consultations have been considered, excluding follow-up consultations. STATISTICAL ANALYSIS: Data about patients' demographic, clinical and echocardiographic findings were recorded on Google Forms and converted to a Google spreadsheet. The Google spreadsheet's inbuilt statistical software was used for analysis. Categorical data were presented as percentages, and numerical data as median and range. RESULTS: The cardiology team evaluated 352 neonates from 2,606 live births over four months, accounting for 13.5 per 100 live births. The median weight was 2.8 kilograms, with a 0.5-4.3 kilogram range. Males comprised 187 (53%), and females comprised 165 (47%). Moreover, full-term, preterm, and post-term accounted for 236 (67%), 113 (32%), and 3 (0.8%) of patients, respectively. The common indications for neonatal cardiac referral were respiratory distress 60 (17%), infants born to diabetic mothers 50 (14%), abnormal fetal echocardiogram 49 (13.9%), family history of abortion or neonatal death 31 (8.8%), and congenital anomalies 30 (8.5%). Systolic murmur was the commonest clinical finding that prompted cardiology referrals 82 (23.2%), followed by desaturation 38 (10.7%) and dysmorphic features 31 (8.8%). Among the congenital cardiac defects, an isolated atrial septal defect (ASD) was seen in 66 (18.5%), isolated patent ductus arteriosus in 50 (14.2%), and ventricular septal defect in 21 (5.9%). Moreover, 13 (4.4%) lesions were critical CHDs. Finally, 27 (7.6%) had a diagnosis of pulmonary hypertension. CONCLUSION: Knowing the burden of neonatal cardiac assessment on pediatric cardiology services in any maternity center may help the healthcare authorities to allocate resources and optimize the delivery of cardiac services among the neonatal population. Properly allocating pediatric cardiologists to the needed centers may optimize neonatal cardiac services. Moreover, it may decide on the number of pediatric cardiologists that need to be trained each year to meet the requirements of neonatal cardiac services.