Molecular insights into expression and silencing of resistance determinants in Staphylococcus aureus.

OBJECTIVE: This study aimed to investigate the status of antimicrobial-resistant strains of Staphylococcus aureus in Pakistan, their association in terms of co-occurrence with the biofilm-forming genes, resistance profiling and associated discrepancies in diagnostic methods. METHODOLOGY: A total of 384 milk samples from bovine was collected by using convenient sampling technique and were initially screened for subclinical mastitis, further preceded by isolation and confirmation of S. aureus. The S. aureus isolates were subjected to evaluation of antimicrobial resistance by phenotypic identification using Kirby-Bauer disc diffusion method, while the genotypic estimation was done by polymerase chain reaction to declare isolates as methicillin, beta-lactam, vancomycin, tetracycline, and aminoglycoside resistant S. aureus (MRSA, BRSA, VRSA, TRSA, and ARSA), respectively. RESULTS: The current study revealed an overall prevalence of subclinical mastitis and S. aureus to be 59.11% and 46.69%, respectively. On a phenotypic basis, the prevalence of MRSA, BRSA, VRSA, TRSA, and ARSA was found to be 44.33%, 58.49%, 20.75%, 35.84%, and 30.18%, respectively. The results of PCR analysis showed that 46.80% of the tested isolates were declared as MRSA, 37.09% as BRSA, and 36.36% as VRSA, while the occurrence of TRSA and ARSA was observed in 26.31% and 18.75%, respectively. The current study also reported the existence of biofilm-producing genes (icaA and icaD) in 49.06% and 40.57% isolates, respectively. Lastly, this study also reported a high incidence of discrepancies for both genotypic and phenotypic identification methods of resistance evaluation, with the highest discrepancy ratio for the accA-aphD gene, followed by tetK, vanB, blaZ, and mecA genes. CONCLUSION: The study concluded that different antibiotic resistance strains of S. aureus are prevalent in study districts with high potential to transmit between human populations. The study also determined that there are multiple resistance determinants and mechanisms that are responsible for the silencing and expression of antibiotic resistance genes.

The therapeutic potential of isosakuranetin against perfluorooctane sulfonate instigated cardiac toxicity via modulating Nrf-2/Keap-1 pathway, inflammatory, apoptotic, and histological profile.

Perfluorooctane sulfonate (PFOS) is a pervasive organic toxicant that damages body organs, including heart. Isosakuranetin (ISN) is a plant-based flavonoid that exhibits a broad range of pharmacological potentials. The current investigation was conducted to evaluate the potential role of ISN to counteract PFOS-induced cardiac damage in rats. Twenty-four albino rats (Rattus norvegicus) were distributed into four groups, including control, PFOS (10 mg/kg) intoxicated, PFOS + ISN (10 mg/kg + 20 mg/kg) treated, and ISN (20 mg/kg) alone supplemented group. It was revealed that PFOS intoxication reduced the expressions of Nrf-2 and its antioxidant genes while escalating the expression of Keap-1. Furthermore, PFOS exposure reduced the activities of glutathione reductase (GSR), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione S-transferase (GST), Heme oxygenase-1 (HO-1) and glutathione (GSH) contents while upregulating the levels of reactive oxygen species (ROS) and malondialdehyde (MDA). Besides, PFOS administration upregulated the levels of creatine kinase-MB (CK-MB), troponin I, creatine phosphokinase (CPK), and lactate dehydrogenase (LDH). Moreover, the levels of tumor necrosis factor-alpha (TNF-α), nuclear factor kappa-B (NF-κB), interleukin-6 (IL-6), and interleukin-1ß (IL-1ß) were increased after PFOS intoxication. Additionally, PFOS exposure downregulated the expression of Bcl-2 while upregulating the expressions of Bax and Caspase-3. Furthermore, PFOS administration disrupted the normal architecture of cardiac tissues. Nonetheless, ISN treatment remarkably protected the cardiac tissues via regulating aforementioned dysregulations owing to its antioxidative, anti-inflammatory, and antiapoptotic properties.

Mitigative potential of kaempferide against polyethylene microplastics induced testicular damage by activating Nrf-2/Keap-1 pathway.

Polyethylene microplastics (PE-MPs) are one of the environmental contaminants that instigate oxidative stress (OS) in various organs of the body, including testes. Kaempferide (KFD) is a plant-derived natural flavonol with potential neuroprotective, hepatoprotective, anti-cancer, anti-oxidant and anti-inflammatory properties. Therefore, the present study was designed to evaluate the alleviative effects of KFD against PE-MPs-prompted testicular toxicity in rats. Fourty eight adult male albino rats were randomly distributed into 4 groups: control, PE-MPs-administered (1.5 mgkg-1), PE-MPs (1.5 mgkg-1) + KFD (20 mgkg-1) co-treated and KFD (20 mgkg-1) only treated group. PE-MPs intoxication significantly (P < 0.05) lowered the expression of Nrf-2 and anti-oxidant enzymes, while increasing the expression of Keap-1. The activities of anti-oxidants i.e., catalase (CAT), glutathione reductase (GSR), superoxide dismutase (SOD), hemeoxygene-1 (HO-1) and glutathione peroxidase (GPx) were reduced, besides malondialdehyde (MDA) and reactive oxygen species (ROS) contents were increased significantly (P < 0.05) following the PE-MPs exposure. Moreover, PE-MPs exposure significantly (P < 0.05) reduced the sperm motility, viability and count, whereas considerably (P < 0.05) increased the dead sperm number and sperm structural anomalies. Furthermore, PE-MPs remarkably (P < 0.05) decreased steroidogenic enzymes and Bcl-2 expression, while increasing the expression of Caspase-3 and Bax. PE-MPs exposure significantly (P < 0.05) reduced the levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH) and testosterone, whereas inflammatory indices were increased. PE-MPs exposure also induced significant histopathological damages in the testes. Nevertheless, KFD supplementation significantly (P < 0.05) abrogated all the damages induced by PE-MPs. The findings of our study demonstrated that KFD could significantly attenuate PE-MPs-instigated OS and testicular toxicity, due to its anti-oxidant, anti-inflammatory, androgenic and anti-apoptotic potential.

Amentoflavone mediated hepatoprotection to counteract paraquat instigated hepatotoxicity via modulating Nrf2/keap1 pathway: A biochemical, inflammatory, apoptotic and histopathological study.

Paraquat (PQ) is a ubiquitous and water-soluble herbicide which has potential to cause systematic poisoning. PQ intoxication is known to be associated with various clinical complications including hepatotoxicity. Amentoflavone (AMF) is an active phenolic compound that exhibits a broad range of biological as well as pharmacological activities. This study was designed to determine the hepato-protective potential of AMF against PQ instigated hepatotoxicity in rats. Forty-eight rats were distributed into four groups such as control group, PQ-treated group (5 mg/kg), PQ (5 mg/kg) + AMF (40 mg/kg) exposed group and AMF (40 mg/kg) only supplemented group. It was revealed that PQ exposure reduced nuclear factor erythroid 2-related factor 2 (Nrf2) and antioxidative genes expression whereas increase the expression of Kelch-like ECH-associated protein 1(Keap1). Besides, PQ intoxication reduced the activities of superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GSR), glutathione peroxidase (GPx), Heme- oxygenase-1 (HO-1) & glutathione (GSH) content. Furthermore, the levels of reactive oxygen species (ROS) & malondialdehyde (MDA) were increased. In addition, PQ significantly increased the hepatic serum enzymes including alkaline phosphatase (ALP), aspartate transaminase (AST), & alanine transaminase (ALT) along with inflammatory biomarkers levels such as tumor necrosis- α (TNF- α), nuclear factor- κB (NF-κB), interleukin-6 (IL-6), interleukin 1beta (IL-1ß), & cyclo­oxygenase-2 (COX-2) activity. PQ intoxication increased the expressions of pro-apoptotic markers i.e., Bcl-2-associated X protein (Bax) & Cysteine-aspartic protease-3 (Caspase-3) while reducing the expression of anti-apoptotic protein B-cell lymphoma 2 (Bcl-2). Furthermore, PQ intoxication prompted various histopathological impairments. However, the co-administration of AMF significantly improved the abovementioned hepatic damages induced by PQ. The present study indicated that AMF may be an effective therapeutic candidate to mitigate PQ provoked hepatic impairments due to its anti-apoptotic, antioxidant & anti-inflammatory properties.

Coenzyme Q10 improves the quality and in vitro fertility of post-thawed buffalo (Bubalus bubalis) semen via its antioxidative effect.

This study aimed to determine the effects of Coenzyme Q10 (CoQ10) in the freezing medium on functional and oxidative stress parameters and in vitro fertilization (IVF) rate of buffalo sperm. Collected samples were relocated to the laboratory for initial evaluation, gentle dilution in extenders, cooling (4°C, 2 h), equilibration (4°C, 4 h), packaging (straws, 0.5 mL), programmable freezing, and thawing (37°C, 30 s). Statistical analysis depicted that adding CoQ10 (100 µM) in a freezing medium caused a significant augmentation in total motility (%), average path, and straight-line velocities (µm/sec) of buffalo sperm than control. Adding CoQ10 (100 µM) improved sperm progressive motility, rapid velocity, and functional parameters (%) compared to the control and 10 µM of CoQ10. Moreover, CoQ10 in a freezing medium caused a significant augmentation in seminal plasma catalase (U/mL) and glutathione reductase (GSH; nmol/109 ) at 100 µM than control and other treatments. CoQ10 inclusion (100 µM) ameliorates seminal plasma superoxide dismutase (U/mL), glutathione-S-transferase (GST; nmol/mL/min) fructose (µg/mL), and ATP (nmol/million) than control. Furthermore, CoQ10 at 100 µM improved seminal plasma glutathione peroxidase (µM) levels than control, 10 µM, and 20 µM. Lastly, hydrogen peroxide (H2 O2; nM) production was significantly lower at 100 µM than at control and 10 µM. CoQ10 (100 µM) caused a significant augmentation in the un-capacitated pattern followed by a reduction in the capacitated pattern, and apoptosis-like changes (%) than control, and other treatments, whereas viability was increased than control and other treatments. CoQ10 (100 µM) significantly improved the IVF rate in comparison with control, CoQ10 at 10 µM, and 20 µM groups. In conclusion, the addition of CoQ10 (100 µM) in the freezing medium can improve the quality and in vitro fertility of post-thawed buffalo semen via its antioxidative effect. Further studies are needed to evaluate the effect of CoQ10 on the in vivo fertility of buffalo bull semen.

Genotypic insights to Panton-Valentine leukocidin positive methicillin-resistant Staphylococcus aureus isolated from cattle mastitis.

In this research communication we investigate the prevalence and antimicrobial susceptibility of S. aureus harboring virulent genes responsible for mastitis in cattle of Punjab, Pakistan. A total of 690 milk samples were collected from commercial dairy farms for analysis of the prevalence of subclinical and clinical mastitis and isolation of S. aureus. Virulence ability and methicillin resistance in S. aureus (MRSA) was determined by targeting the pvl (the gene for Panton-Valentine leukocidin) and mecA genes, respectively. A total of 175 S. aureus isolates exhibiting prevalence of pvl gene (6.28%) and mecA gene (22.28%) were determined. Antimicrobial susceptibility testing of pvl positive and negative MRSA against different classes of antibiotics revealed 100% resistance against ß-lactams while 100% sensitivity towards tylosin and linezolid.

Determining the cost of acute stroke care for a single stay at a tertiary care centre in Pakistan.

OBJECTIVE: To assess the economic burden of acute stroke, and to determine the average cost of acute stroke care for a single hospital stay in a public tertiary care hospital. METHODS: The cross-sectional study was conducted at the Medical Teaching Institute, Bacha Khan Medical Complex, Swabi, Pakistan, from May 16 to September 19, 2022, and comprised patients of either gender who were hospitalised with an acute stroke for the first time. All costs incurred during the care of the patients were measured using the micro-costing methodology, and the association of the cost with other variables was evaluated. Data was analysed using SPSS 24. RESULTS: Of the 34 patients, 24(70.6%) were males and 10(29.4%) were females. The overall mean age was 66+/-13.00 years. The mean length of hospital stay was 4+/-3.00 days. The mean total cost was 18,156+/-9,068 Pakistani rupees, which was the equivalent of 76.89+/-38.4 United States dollars. The cost of the first day of admission was the highest, declining per day as the stay progressed, and imaging/laboratory investigations formed the highest component of the overall cost (p<0.001). CONCLUSIONS: The cost of acute stroke care was found to be high even in a public hospital. The length of hospital stay was the most important determinant of the overall cost.

On-farm epidemiology, virulence profiling, and molecular characterization of methicillin-resistant Staphylococcus aureus at goat farms.

Antimicrobial resistance (AMR) becomes a challenging issue that limits the therapeutic options for both veterinary and public health professionals. The current study aimed to investigate the on-farm epidemiology, antibiotics resisting profiling, virulence analysis, and molecular detection of methicillin-resistant Staphylococcus aureus (MRSA) at the caprine-human interface. A total of 768 goat milk samples and 94 skin swabs from farm personnel were collected from 30 goat flocks and processed for isolation of S. aureus. The study isolates were confirmed as MRSA based on the oxacillin and cefoxitin disc diffusion test and the presence of mecA gene. MRSA isolates of goats and human origin were characterized and further evaluated for the presence of virulence genes responsible for intramammary infections and public health hazards. The results revealed 26.82 % and 27.79 % goat milk samples and human samples positive for S. aureus, respectively. A higher MRSA prevalence of 35.92 % and 10.71 % was found in goat and human isolates respectively. The phylogenetic analysis revealed a lesser extent of homology in mecA gene of S. aureus isolates at the caprine-human interface. Moreover, this study revealed strong evolutionary connection between the study isolates and MRSA isolates of Pakistani cattle and buffalo while the in-silico protein analysis showed that all sequences have the same protein motifs resembling penicillin binding protein 2a. The risk factors analysis revealed that teat length, drainage system, hygienic measures during milking, use of teat dip, teat injury, and veterinary services were significantly associated with subclinical mastitis in goats. A total of 43.24 % of local MRSA isolates showed multi-drug resistance (MDR). The isolates showed higher resistance to oxytetracycline followed by gentamicin and vancomycin while moxifloxacin, and linezolid were among the susceptible antibiotics. Local MRSA isolates carried virulence markers (nuc and coag genes) and biofilm-associated icaA (43.24 %) and icaD (29.73 %) genes which are responsible for the intramammary infection. The local isolates also carried the virulence genes of public health concern including the enterotoxin C (sec) gene (24.3 %), enterotoxins B (seb) gene (5.41 %), and enterotoxin D (sed) gene (2.7 %). Enterotoxins A (sea) and E (see) genes were not detected in any isolate. The study concluded that MRSA is an emerging and prevailing pathogen in dairy goats with a high potential to transmit to associated human beings. The presence of a variety of virulence factors as well as the associated antibiotic resistance makes MRSA a potential threat at animal-human interface and thus demands further research.

Discrepancies between phenotypic and genotypic identification methods of antibiotic resistant genes harboring Staphylococcusaureus.

Antimicrobial resistance is a global issue that limits therapeutic options for infections. S. aureus being a member of the ESKAPE group is capable of "escaping" the biocidal action of antimicrobial agents. There are phenotypic and genotypic methods used for the identification of antibiotic resistant genes harboring S. aureus but these methods do not always show concordant results. To address these discrepancies, a total of 335 equine nasal swab samples from four districts of Punjab were collected using a convenient sampling technique. These samples were first subjected to common microbial techniques to identify S. aureus. The disc diffusion assay was performed for the phenotypic identification of antibiotic resistant S. aureus by using discs of oxacillin, penicillin, vancomycin, gentamycin, and tetracycline. After this, PCR was performed by targeting mecA, blaZ, vanB, aaca-aphd, and tetK genes for genotypic identification of respective antibiotic-resistant S. aureus. Phenotypic discrepancies (number of antibiotic resistant isolates found from disc diffusion who appeared to be negative for the resistant gene), and genotypic discrepancies (number of antibiotic sensitive isolates found from disc diffusion who appeared to be positive for the resistant gene) were calculated. The discrepancy ratio for mecA, blaZ, vanB, aaca-aphd, and tetK genes were 3.09, 1.96, 2.67, 1.93, and 1.67 respectively. These discrepant results indicate that the absence or presence of only one gene is not a true marker of resistant or sensitive isolates. There are multiple resistance determinants and resistance mechanisms. This study also highlighted the phenomenon of silencing of antibiotic resistance determinants.

Attenuative effect of astilbin on polystyrene microplastics induced testicular damage: Biochemical, spermatological and histopathological-based evidences.

Polystyrene microplastics (PS-MPs) are the potential environmental pollutants that possess the ability to induce testicular damage. Astilbin (ASB) is a dihydroflavonol, abundantly reported in multiple plants that has various pharmacological properties. This research elucidated the mitigative potential of ASB against PS-MPs-instigated testicular toxicity. 48 adult male rats (200 ± 10 g) were distributed into 4 groups (n = 12): control, PS-MPs received (0.01 mg/kg), PS-MPs + ASB received (0.01 mg/kg + 20 mg/kg) and ASB supplemented group (20 mg/kg). After 56th day of the trial, animals were sacrificed and testes were harvested for the estimation of biochemical, hormonal, spermatogenic, steroidogenic, apoptotic and histological profiles. PS-MPs intoxication significantly (P < 0.05) lowered glutathione peroxidase (GPx), superoxide dismutase (SOD), glutathione reductase (GSR) as well as catalase (CAT) activities, whereas elevated MDA as well as ROS levels. Besides, the levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), nuclear factor kappa-B (NF-κB) along with cyclooxygenase-2 (COX-2) activity were raised. PS-MPs treatment reduced luteinizing hormone (LH), plasma testosterone and follicle-stimulating hormone (FSH) level besides decreased epididymal sperm number, viability, motility as well as the count of HOS coil-tailed spermatozoa and increased sperm morphological irregularities. PS-MPs exposure lowered steroidogenic enzymes (17ß-HSD, 3ß-HSD and StAR protein along with Bcl-2 expression, besides increasing Caspase-3 and Bax expressions and histopathological alterations in testicular tissues. However, ASB treatment significantly reversed PS-MPs mediated damage. In conclusion, ASB administration is protective against PS-MPs-instigated testicular damage owing to its anti-inflammatory, anti-apoptotic, antioxidant and androgenic nature.

Antioxidant, anti-inflammatory, and anti-apoptotic effects of genkwanin against aflatoxin B1-induced testicular toxicity.

Aflatoxin B1 (AFB1) is the most hazardous aflatoxin that causes significant damage to the male reproductive system. Genkwanin (GNK) is a bioactive flavonoid that shows antioxidant and anti-inflammatory potential. Therefore, the current study was planned to evaluate the effects of GNK against AFB1-induced testicular toxicity. Forty-eight male rats were distributed into four groups (n = 12 rats). AFB1 (50 µg/kg) and GNK (20 mg/kg) were administered to the rats for eight weeks. Results of the current study revealed that AFB1 exposure induced adverse effects on the Nrf2/Keap1 pathway and reduced the expressions and activities of antioxidant enzymes. Additionally, it increased the levels of oxidative stress markers. Furthermore, expressions of steroidogenic enzymes were down-regulated by AFB1 intoxication. Besides, AFB1 exposure reduced the levels of gonadotropins and plasma testosterone, which subsequently reduced the epididymal sperm count, motility, and hypo-osmotic swelled (HOS) sperms, while increasing the number of dead sperms and causing morphological anomalies of the head, midpiece, and tail of the sperms. In addition, AFB1 decreased the activities of testicular function marker enzymes and the levels of inflammatory markers. Moreover, it severely affected the apoptotic profile by up-regulating the expressions of Bax and Casp3, while down-regulating the Bcl2 expression. Besides, AFB1 significantly damaged the histoarchitecture of testicular tissues. However, GNK treatment reversed all the AFB1-induced damages in the rats. Taken together, the current study reports the potential use of GNK as a therapeutic agent to prevent AFB1-induced testicular toxicity due to its antioxidant, anti-inflammatory, and anti-apoptotic properties.

Therapeutic and immunomodulatory role of probiotics in breast cancer: A mechanistic review.

Breast cancer has become the most prevalent and noxious type of malignancy around the globe (Giaquinto et al., 2022). Multiple clinical strategies including chemotherapy, radiotherapy, and immunotherapy have been in practice to manage breast cancer. Besides the protective roles of conventional remedial approaches, and non-reversible and deteriorative impacts like healthy cell damage, organ failure, etc., the world scientific community is in a continuous struggle to find some alternative biocompatible and comparatively safe solutions. Among novel breast cancer management/treatment options, the role of probiotics has become immensely important. The current review encompasses the prevalence statistics of breast cancer across the globe concerning developed and undeveloped counties, intestinal microbiota linkage with breast cancer, and association of breast microbiome with breast carcinoma. Furthermore, this review also narrates the role of probiotics against breast cancer and their mode of action. In Vivo and In Vitro studies under breast cancer research regarding probiotics are mechanistically explained. The current review systematically explains the immunomodulatory role of probiotics to prevent breast cancer. Last, but not the least, current review concludes the use of probiotics in the treatment of breast cancer through various mechanisms and future recommendations for molecular basis studies.

Determination of histological and genotoxic parameters of Nile Tilapia, Oreochromis niloticus exposed to lead (Pb).

This study investigates the hazardous effects of lead on the histological and genotoxic parameters of the fish, Oreochromis niloticus. Present work was conducted in a series of three steps. In first step, acute toxicity, LC50 and lethal lead concentration were measured using Probit analysis method. LC50 value and lethal concentration for O. niloticus was measured as 77.673 mgL-1 and 150.924 mgL-1, respectively. In second step, histological changes were assessed by preparing slides of tissues of the gills, liver and kidney of both control and Pb-stressed O. niloticus and examining the respective tissues under the light microscope. The inferences showed significant histological alterations (p<0.05) in the gills of Pb-exposed fish including necrosis, edema, vascular congestion, shortening and curling and lifting of the epithelium of secondary lamella in gills. The cellular degeneration and dilation of sinusoids in liver and loss of hemopoietic tissue, necrosis and edema in kidney was observed. Histomorphometry of the liver showed a decrease in diameter of the central vein and hepatocyte along with an increase in width of sinusoids. The histomorphometry of kidney showed an increase in the diameter of renal corpuscle, glomerulus, proximal and distal convoluted tubules. The nuclear anomalies were studied in the RBCs of fish. Non-parametric Mann-Whitney U-test was conducted to compare nuclear abnormalities and the frequency of micronuclei among the control and lead-treated fish groups. Results declared an increased micronucleus, notched and de-shaped nuclei frequency, in RBCs of fish exposed to lead as compared to control group.

Attenuative effects of tamarixetin against polystyrene microplastics-induced hepatotoxicity in rats by regulation of Nrf-2/Keap-1 pathway.

Polystyrene microplastics (PS-MPs) are environmental contaminants due to their potential to induce damages in multiple organs specifically liver. Tamarixetin (TMT) is a naturally occurring flavonoid present in Tamarix ramosissima plant that exhibits multiple pharmacological properties. Therefore, the present research was designed to evaluate the palliative role of TMT against PS-MPs instigated liver dysfunction in rats. The exposure to PS-MPs reduced the expressions of nuclear factor erythroid 2-related factor 2 and antioxidant genes, while increasing the expression of Kelch-like ECH-associated protein 1. PS-MPs exposed rats exhibited considerably (p < .05) higher alkaline phosphatase (ALP), aspartate aminotransferase (AST) as well as alanine aminotransferase (ALT) contents. Additionally, PS-MPs treatment resulted in a notable decrease in anti-oxidants activity, that is, glutathione S-transferase (GST), superoxide dismutase (SOD), heme oxygenase-1 (HO-1), glutathione reductase (GSR), glutathione peroxidase (GPx), catalase (CAT) and glutathione (GSH) content, whereas upregulating reactive oxygen species (ROS) and malondialdehyde (MDA) contents. Moreover, PS-MPs intoxication noticeably increased (p < .05) the inflammatory indices (interleukin-1ß [IL-1ß], nuclear factor kappa B [NF-κB], interleukin-6 [IL-6], tumor necrosis factor-α [TNF-α] levels, and cyclooxygenase-2 [COX-2] activity). Besides, Caspase-3 and Bax expressions were upregulated and Bcl-2 expression was decreased after PS-MPs exposure. Additionally, the histomorphological examination revealed notable hepatic damage in PS-MPs treated group. However, TMT treatment substantially (p < .05) recovered all the PS-MPs-induced damages and histopathological changes. Taken together, it can be deduced that TMT might be used as a pharmacological agent to ameliorate hepatic damage.

Contextual factors influencing incomplete immunization and investigation of its geospatial heterogeneity in Pakistan: a cross-sectional study based on PDHS (2017-18).

BACKGROUND: Immunization is one of the most effective public health initiatives, saving millions of lives and lowering the risk of diseases such as diphtheria, tetanus, influenza, and measles. Immunization saves an estimated 2-3 million lives per year. A study of the regional variations in incomplete immunization will be useful in identifying gaps in the performance of immunization programs that are not noticed by standard vaccination programs monitoring. The primary goal of this study was to identify factors influencing child immunization status and to examine regional variations in incomplete immunization among children aged 12 to 23 months in Pakistan. METHODS: For the current study, the data were taken from the Demographic and Health Survey for Pakistan (PDHS 2017-2018). Ever-married women who had children aged 12-23 months were included in this study. The immunization status of children was used as an outcome variable. In order to determine the effects of different factors on incomplete immunization, multilevel logistic model was used. To study the geographical variation of incomplete immunization, hotspot analysis was done using ArcGIS 10.7 and SaTScan software and to identify significant predictors of incomplete immunization, GWR 4 software was used. RESULTS: Place of delivery, gender of child, mother's educational level and region were identified as significant determinants of incomplete immunization of children in Pakistan. Chances of incomplete immunization of children were found significantly lower for educated mothers (AOR = 0.52, 95% CI 0.34-0.79) and mothers who had delivered children in the health facilities (AOR = 0.51, 95% CI 0.32-0.83). Female children were more likely (AOR = 1.44, 1.95% CI 1.04-1.99) to be incompletely immunized as compared to male children. FATA (AOR = 11.19, 95% CI 4.89-25.6), and Balochistan (AOR = 10.94, 95% CI 5.08-23.58) were found at the highest risk of incomplete immunization of children as compared to Punjab. The significant spatial heterogeneity of incomplete immunization was found across Pakistan. The spatial distribution of incomplete immunization was clustered all over Pakistan. The high prevalence of incomplete immunization was observed in Balochistan, South Sindh, North Sindh, South KPK, South FATA, Gilgit Baltistan, Azad Jammu Kashmir, South and East Punjab. Drang and Harcho were identified as hotspot areas of incomplete immunization in Gilgit Baltistan. Secondary clusters with a high risk of incomplete immunization were found in regions Balochistan, Sindh and FATA. CONCLUSION: Gender biasedness towards female children, regarding complete immunization of children prevailed in Pakistan. Spatial heterogeneity was also found for incomplete immunization of children. To overcome the problem access to health facilities is the foremost step. Government should target hotspot areas of incomplete immunization of children to provide primary health care facilities by opening health care units in these areas. The government in collaboration with the media should launch awareness campaigns in those areas to convince people that complete immunization is the right of every child regardless of gender.

Eriodictyol attenuates Furan induced testicular toxicity in Rats: Role of oxidative stress, steroidogenic enzymes and apoptosis.

Furan (C4H4O) is a naturally occurring organic compound. It develops as a result of the thermal processing of food and stimulates critical impairments in male reproductive tract. Eriodictyol (Etyol) is a natural dietary flavonoid possessing diverse pharmacological potentials. The recent investigation was proposed to ascertain the ameliorative potential of eriodictyol against furan-instigated reproductive dysfunctions. Male rats (n = 48) were classified into 4 groups: untreated/control, furan (10 mg/kg), furan+ eriodictyol (10 mg/kg + 20 mg/kg) and eriodictyol (20 mg/kg). At the 56th day of the trial, the protective effects of eriodictyol were evaluated by assessing various parameters. Results of the study revealed that eriodictyol attenuated furan-induced testicular toxicity in the biochemical profile by increasing catalase (CAT), glutathione peroxidase (GPx), superoxide dismutase (SOD) along with glutathione reductase (GSR) activities, whereas reduced the reactive oxygen species (ROS) along with malondialdehyde (MDA) levels. It also restored the normal state of sperm motility, viability, the count of hypo-osmotic tail swelled sperm as well as epididymal sperm number along with reduced sperm anomalies (morphological) tail, mid-piece and head. Furthermore, it elevated the decreased levels of luteinizing hormone (LH), plasma testosterone and follicle-stimulating hormone (FSH) as well steroidogenic enzymes (17ß-HSD, StAR protein & 3ß-HSD) and testicular anti-apoptotic marker (Bcl-2) expression, whereas, down-regulating apoptotic markers (Bax & Caspase-3) expression. Eriodictyol treatment also effectively mitigated the histopathological damages. The outcomes of the current study provide fundamental insights into the ameliorative potential of eriodictyol against furan-instigated testicular toxicity.

A Novel Traffic Prediction Method Using Machine Learning for Energy Efficiency in Service Provider Networks.

This paper presents a systematic approach for solving complex prediction problems with a focus on energy efficiency. The approach involves using neural networks, specifically recurrent and sequential networks, as the main tool for prediction. In order to test the methodology, a case study was conducted in the telecommunications industry to address the problem of energy efficiency in data centers. The case study involved comparing four recurrent and sequential neural networks, including recurrent neural networks (RNNs), long short-term memory (LSTM), gated recurrent units (GRUs), and online sequential extreme learning machine (OS-ELM), to determine the best network in terms of prediction accuracy and computational time. The results show that OS-ELM outperformed the other networks in both accuracy and computational efficiency. The simulation was applied to real traffic data and showed potential energy savings of up to 12.2% in a single day. This highlights the importance of energy efficiency and the potential for the methodology to be applied to other industries. The methodology can be further developed as technology and data continue to advance, making it a promising solution for a wide range of prediction problems.

A New COVID-19 Detection Method Based on CSK/QAM Visible Light Communication and Machine Learning.

This article proposes a novel method for detecting coronavirus disease 2019 (COVID-19) in an underground channel using visible light communication (VLC) and machine learning (ML). We present mathematical models of COVID-19 Deoxyribose Nucleic Acid (DNA) gene transfer in regular square constellations using a CSK/QAM-based VLC system. ML algorithms are used to classify the bands present in each electrophoresis sample according to whether the band corresponds to a positive, negative, or ladder sample during the search for the optimal model. Complexity studies reveal that the square constellation N=22i×22i,(i=3) yields a greater profit. Performance studies indicate that, for BER = 10-3, there are gains of -10 [dB], -3 [dB], 3 [dB], and 5 [dB] for N=22i×22i,(i=0,1,2,3), respectively. Based on a total of 630 COVID-19 samples, the best model is shown to be XGBoots, which demonstrated an accuracy of 96.03%, greater than that of the other models, and a recall of 99% for positive values.

A New Internet of Things Hybrid VLC/RF System for m-Health in an Underground Mining Industry.

This paper proposes a new system based on the Industrial Internet of Things (IIoT) for the monitoring of Mobile Health (m-Health) of workers in the underground mining industry. The proposed architecture uses a hybrid model in data transmission. Visible Light Communication (VLC) is used for downlink because of its narrow coverage, which aids in worker positioning. Radio frequency (RF) communication technology is used to send data for primary vital signs in the uplink, which is more efficient in transmission and is a viable solution according to the problem raised. The results obtained in terms of coverage and transmission for the downlink and uplink links show the feasibility of implementing the proposed system.

Screening of Active Ingredients from Wendan Decoction in Alleviating Palmitic Acid-Induced Endothelial Cell Injury.

(1) Objective: Traditional Chinese medicine (TCM) plays an important role in the treatment of numerous illnesses. As a classic Chinese medicine, Wendan Decoction (WDD) encompasses a marvelous impact on the remedy of hyperlipidemia. It is known that hyperlipidemia leads to cardiovascular injury, therefore anti-vascular endothelial cell injury (AVECI) may be an underlying molecular mechanism of WDD in the cure of hyperlipidemia. However, there is no relevant research on the effect of WDD on vascular endothelial cells and its pharmacodynamic substances. Therefore, the purpose of this study was to investigate the protective effect of WDD on vascular endothelial cells. (2) Methods: The chemical constituents of WDD were determined by LC-MS/MS technology. The protective effects of 16 batches of WDD on samples from human umbilical vein endothelial cells (HUVECs) were evaluated. Finally, gray relation analysis (GRA) and partial least squares regression (PLSR) were used to analyze the potential correlation between chemical ingredients and AVECI. (3) Results: The results indicated that WDD had apparent protective effect on endothelial cells, and pharmacological properties in 16 batches of WDD tests were apparently discrepant. The GRA and PLSR showed that trigonelline, liquiritin, hesperidin, hesperetin, scopoletin, morin, quercetin, isoliquiritigenin, liquiritigenin and formononetin may be the active ingredients of AVECI in WDD. (4) Conclusions: WDD has a protective effect on endothelial cell injury induced by palmitic acid, which may be related to its component content. This method was suitable for the search of active components in classical TCM.