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Key HIV cure strategies involve reversing immune dysfunction and limiting the proliferation of infected T cells. We evaluate the safety of sirolimus, a mammalian target of rapamycin (mTOR) inhibitor, in people with HIV (PWH) and study the impact of sirolimus on HIV-1 reservoir size and HIV-1-specific immunity in a single-arm study of 20 weeks of treatment in PWH on antiretroviral therapy (ART). Sirolimus treatment does not impact HIV-1-specific CD8 T cell responses but leads to a significant decrease in CD4+ T cell-associated HIV-1 DNA levels at 20 weeks of therapy in the primary efficacy population (n = 16; 31% decline, p = 0.008). This decline persists for at least 12 weeks following cessation of the study drug. Sirolimus treatment also leads to a significant reduction in CD4+ T cell cycling and PD-1 expression on CD8+ lymphocytes. These data suggest that homeostatic proliferation of infected cells, an important mechanism for HIV persistence, is an intriguing therapeutic target.

Background Glycosaminoglycans (GAGs) are a family of polysaccharides found abundantly in the extracellular matrix (ECM) of tissues. Research has indicated that the dysregulation of ECM, including changes and disruptions in GAGs, contributes to various cancer hallmarks such as metabolic reprogramming, persistent growth signals, immunosuppression, angiogenesis, tumor invasion, and metastasis. Objective This systematic review aims to evaluate the diagnostic accuracy of GAGs, including heparan sulfate (HS), chondroitin sulfate (CS), and hyaluronic acid (HA), in early detection of cancer. Method Four databases (PubMed, Scopus, EBSCO, and Ovid) were searched for studies in English within the last 15 years, involving at least 50 human participants. Using a two-stage process: identification and screening, 11 articles were selected and critically appraised using Critical Appraisal Skills Programme (CASP) checklists and Newcastle-Ottawa Scale (NOS) appropriate for each study design. Result Eleven studies met the inclusion criteria, encompassing various cancers like renal cell carcinoma (RCC), upper GI cancer (UGI), ovarian cancer, prostate cancer, breast cancer, lung cancer, colorectal cancer and oral cancer. Methodological quality was assessed using two established tools, with no studies exhibiting a high risk of bias. Heparan sulfate levels showed diagnostic potential in renal cancer with a maximum accuracy of 98.9%, achieving 94.7% specificity and 100% sensitivity. Chondroitin sulfate disaccharides emerged as a promising diagnostic marker in ovarian cancer and showed potential as diagnostic markers in renal cancer. However, there were no statistically significant differences in urinary chondroitin sulfate levels between patients and controls in prostate cancer. In breast cancer, hyaluronic acid showed moderate accuracy (AUC = 0.792) in distinguishing metastatic from non-metastatic disease, and a composite score incorporating multiple markers, including HA, showed even higher accuracy (AUC = 0.901) in detecting metastatic breast cancer. HA demonstrated moderate diagnostic accuracy for UGI cancers. Serum HA levels were significantly elevated in patients with oral cancer and pleural malignant mesothelioma and associated with tumor progression in patients with lung cancer. Elevated low molecular weight form of hyaluronan (~6 k Da HA) levels were found in colorectal cancer tissues. Conclusion GAGs hold potential as early cancer detection biomarkers. Further validation with larger, diverse populations is needed to validate their diagnostic accuracy and clinical utility.

Background: A novel virus known as severe known as severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) primarily targets the respiratory system of infected people. The virus spreads between individuals through respiratory droplets produced during sneezing or coughing. Anyone can contract the virus, but the severity of the disease is often associated with age and pre-existing medical conditions like cancer that may weaken the immune system. Objectives: In this study, we analyzed severe outcomes of SARS-CoV-2 infections among patients with current or prior malignancy. Patients and Methods: Between January 1st and December 31st, 2021, a cross-sectional study was conducted on 100 cancer patients from various medical centers in Baghdad, Iraq. The patients included 50% with solid tumors and 50% with hematologic malignancies. The medical centers involved in the study were the Oncology Teaching Hospital, Baghdad Hematological Center, and Private Nursing Home Hospital in the Medical City Complex. The patients were infected with severe acute respiratory syndrome coronavirus 2. Results: There is a significant correlation between the severity of COVID-19 in cancer patients and their Eastern Cooperative Oncology Group (ECOG) performance status score of ≥1 (10%, P=0.009), the duration of their malignancy being ≥3 years (30%, P=0.017), and the status of their cancer at the time of COVID-19 infection, with patients having was found malignant disease being more likely to develop critical cases. Additionally, patients in remission during their coronavirus infection were found to have developed more critical cases (80%, P=0.001), which was statistically approved. Conclusion: We found that COVID-19 severity parameters, rather than the underlying malignant disease, are the primary factors in morbidity and mortality

Chronic kidney disease (CKD) is a common complication in patients with diabetes mellitus. Recently, the class of sodium-glucose cotransporter 2 inhibitors (SGLT2-Is) has been shown to have cardiovascular and renal benefits. The extent of the use of SGLT2-Is in patients with CKD is unknown. The objective of this study was to describe the prescription pattern of empagliflozin (the only available agent) in patients with CKD at Johns Hopkins Aramco Healthcare. This was a retrospective single-center analysis of patients with CKD over 2 years between January 1, 2020, and December 31, 2021. The prescription pattern of empagliflozin for adults (≥18 years) with CKD was determined quarterly. Among 2528 patients with CKD, 119 (5%) patients were prescribed empagliflozin during the first quarter of 2020. The number of patients steadily increased and reached 16% by the end of the study period. Despite the overwhelming evidence of their benefits, the overall utilization of SGLT2-Is was poor. Physicians' education is paramount to increase awareness about the benefits of SGLT2-Is as renoprotective and lifesaving medications.

Large-scale energy storage systems (ESSs) that can react quickly to energy fluctuations and store excess energy are required to increase the reliability of electricity grids that rely heavily on renewable energy sources (RESs). Hybrid systems, which combine different energy storage technologies such as batteries and supercapacitors, are becoming increasingly popular because no single technology can satisfy all requirements. In this study, a supercapacitor is used to stabilize quickly shifting bursts of power, while a battery is used to stabilize gradually fluctuating power flow. This paper proposes a robust controller for managing the direct current (DC) bus voltage to optimize the performance of ESS. The proposed controller combines a fractional-order proportional integral (FOPI) with a classical PI controller for the first time in the DC microgrid area. The hybrid (FOPI-PI) controller achieves an outstanding and superior performance in all transient and dynamic response specifications compared to other traditional controllers. The parameters of the suggested controller are incorporated with the self-adaptive bonobo optimizer (SaBO) to determine the optimal values. Furthermore, various optimization techniques are applied to the model and the SaBO’s output outperforms other techniques by minimizing the best objective function. In addition, the current study has utilized a novel power management strategy that includes two closed current loops for both batteries and supercapacitors. By using this method, batteries’ lifespans may be increased while still retaining optimal system performance. The suggested controller is implemented in MATLAB/Simulink 2022b, and the outcomes are reported for several case studies. The findings demonstrate that the control technique remarkably improves the transient response, such as transient duration, overshoot/undershoot, and the settling time. The proposed controller (FOPI-PI) with the SaBO optimizer is effective in maintaining the DC bus voltage under load and solar system variation.

Background: Glycosaminoglycans (GAGs) are a family of polysaccharides found abundantly in the extracellular matrix (ECM) of tissues. Research has indicated that the dysregulation of ECM, including changes and disruptions in GAGs, contributes to various cancer hallmarks such as metabolic reprogramming, persistent growth signals, immunosuppression, angiogenesis, tumor invasion, and metastasis. Objective: This systematic review aims to evaluate the diagnostic accuracy of GAGs, including heparan sulfate (HS), chondroitin sulfate (CS), and hyaluronic acid (HA), in early detection of cancer. Method: Four databases (PubMed, Scopus, EBSCO, and Ovid) were searched for studies in English within the last 15 years, involving at least 50 human participants. Using a two-stage process: identification and screening, 11 articles were selected and critically appraised using Critical Appraisal Skills Programme (CASP) checklists and Newcastle-Ottawa Scale (NOS) appropriate for each study design. Result: Eleven studies met the inclusion criteria, encompassing various cancers like renal cell carcinoma (RCC), upper GI cancer (UGI), ovarian cancer, prostate cancer, breast cancer, lung cancer, colorectal cancer and oral cancer. Methodological quality was assessed using two established tools, with no studies exhibiting a high risk of bias. Heparan sulfate levels showed diagnostic potential in renal cancer with a maximum accuracy of 98.9%, achieving 94.7% specificity and 100% sensitivity. Chondroitin sulfate disaccharides emerged as a promising diagnostic marker in ovarian cancer and showed potential as diagnostic markers in renal cancer. However, there were no statistically significant differences in urinary chondroitin sulfate levels between patients and controls in prostate cancer. In breast cancer, hyaluronic acid showed moderate accuracy (AUC = 0.792) in distinguishing metastatic from non-metastatic disease, and a composite score incorporating multiple markers, including HA, showed even higher accuracy (AUC = 0.901) in detecting metastatic breast cancer. HA demonstrated moderate diagnostic accuracy for UGI cancers. Serum HA levels were significantly elevated in patients with oral cancer and pleural malignant mesothelioma and associated with tumor progression in patients with lung cancer. Elevated low molecular weight form of hyaluronan (~6 k Da HA) levels were found in colorectal cancer tissues. Conclusion: GAGs hold potential as early cancer detection biomarkers. Further validation with larger, diverse populations is needed to validate their diagnostic accuracy and clinical utility. [ABSTRACT FROM AUTHOR]

Abstract Expansion of COVID-19 worldwide increases interest in unraveling genomic variations of novel SARS-CoV-2 virus. Metadata of 408,493 SARS-CoV-2 genomes submitted to GISAID database were analyzed with respect to genomic clades and their geographic, age, and gender distributions. Of the currently known SARS-CoV-2 clades, clade GR was the most prevalent worldwide followed by GV then GH. Chronological analysis revealed expansion in SARS-CoV-2 clades carrying D614G mutations with the predominance of the newest clade, GV, in the last three months. D614G clades prevail in countries with more COVID-19 cases. Of them, the clades GH and GR were more frequently recovered from severe or deceased COVID-19 cases. In contrast, G and GV clades showed a significantly higher prevalence among asymptomatic patients or those with mild disease. Metadata analysis showed higher (p

Abstract Antibiotic-resistant Escherichia coli (E. coli) are common in retail poultry products. In this study, we aimed to isolate and characterize multidrug resistant (MDR) E. coli in raw chicken meat samples collected from poultry shops in Sylhet division, Bangladesh, as well as to determine correlation between resistance phenotype and genotype. A total of 600 chicken meat swabs (divided equally between broiler and layer farms, n = 300 each) were collected and the isolates identified as E. coli (n = 381) were selected. Disc diffusion antimicrobial susceptibility assay showed resistance of these isolates to ampicillin, erythromycin, tetracycline, streptomycin, trimethoprim-sulfamethoxazole, chloramphenicol, and gentamicin. Polymerase chain reaction (PCR) identified several antibiotic resistance genes (ARGs) in our isolates. Among these ARGs, the prevalence of tetA (for tetracycline) was the highest (72.58%) in broiler chicken isolates, followed by sul1 (for sulfonamide; 44.16%), aadA1 (for streptomycin; 33.50%), ereA (for erythromycin; 27.41%), aac-3-IV (for gentamicin; 25.38%), and the two genes cmlA (24.87%) and catA1 (8.63%) for chloramphenicol. On the other hand, the respective prevalence in layer chicken isolates were 82.06%, 47.83%, 35.87%, 35.33%, 23.91%, 19.02%, and 5.43%. Furthermore, 49.23% of the isolates from broiler chicken were MDR, with the presence of multiple antibiotic resistance genes, including 3 (40.11%) and 4 (9.13%) genes. On the other hand, 51.09% of layer chicken E. coli isolates were MDR, with 3, 4 or 5 ARGs detected in 36.41%, 14.13%, and 0.54% of the isolates, respectively. We also found that 12.8% of broiler chicken E. coli isolates and 7.61% of layer chicken isolates carried genes coding for extended-spectrum SHV beta-lactamases. Lastly, we report the presence of the AmpC beta-lactamase producing gene (CITM) in 4.56% and 3.26% of broiler and layer chicken E. coli isolates, respectively. We found significant correlations between most of the antimicrobial resistant phenotypes and genotypes observed among the investigated E. coli isolates. Our findings highlight the need for the prudent use of antimicrobials in chickens to minimize the development of antibiotic-resistant bacterial strains.

Acinetobacter baumannii is an opportunistic microorganism commonly found in intensive care units (ICUs), and it is responsible for a broad span of hospital-acquired infections. Persistence of nosocomial infection caused by multidrug-resistant (MDR) A. baumannii is an alarming health care issue in Egypt, and at present, colistin remains the treatment of choice for the management of MDR A. baumannii infections. A. baumannii possesses great capacity to develop and acquire resistance to a broad range of antibiotics. The acquisition and dissemination of antibiotic-resistant determinants in A. baumannii strains are mediated by integrons, especially class I integrons. This study focuses on the characterization of some genetic mechanisms underlying the multidrug-resistant phenotypes of A. baumannii isolates in Egypt. Forty-eight A. baumannii specimens were isolated from different hospitalized patients; least resistance was observed against amikacin and tigecycline, with 60% and 58.5% of the isolates resistant, respectively, whereas 62.5% of the isolates were resistant to imipenem and meropenem. The highest sensitivity was found for colistin. Genetic analysis revealed that blaoxa-51 was detected in all isolates, the blaoxa-23-like gene was detected in 80% of the isolates, and blaoxa-24 and blaoxs-58 were not detected in any isolate. Finally, PCR analysis revealed that 6.6% of isolates carried the class I integron gene.

Abstract Background Levothyroxine is a synthetic thyroxine and is the treatment of choice for hypothyroidism. It is a prohormone with minimal intrinsic activity. The drug is de-iodinated in peripheral tissue to form triiodothyronine, which is the active thyroid hormone. On initiation of treatment, levothyroxine is titrated, and usually it is extremely well tolerated in the vast majority of patients. We report a case of a patient with self-limiting levothyroxine-induced liver injury, a rare adverse effect of this drug. Case presentation We report a case of a 34-year-old Mediterranean woman diagnosed with post-thyroidectomy hypothyroidism. She was commenced on levothyroxine and developed liver injury confirmed by noninvasive liver investigations. Complete recovery of the patient’s liver tests occurred upon cessation of the drug. Triiodothyronine was an appropriate treatment alternative. Conclusion Levothyroxine-induced liver injury is a rare, and in the present case report, a self-limiting, adverse effect. The diagnosis of our patient was confirmed via noninvasive diagnostic methods. Knowledge of this rare adverse effect is important in the differential diagnosis of patients who have commenced on levothyroxine and have deranged liver enzymes in the context of hypothyroidism.

The rising antimicrobial resistance is particularly alarming for Acinetobacter baumannii, calling for the discovery and evaluation of alternatives to treat A. baumannii infections. Some bacteriophages produce a structural protein that depolymerizes capsular exopolysaccharide. Such purified depolymerases are considered as novel antivirulence compounds. We identified and characterized a depolymerase (DpoMK34) from Acinetobacter phage vB_AbaP_PMK34 active against the clinical isolate A. baumannii MK34. In silico analysis reveals a modular protein displaying a conserved N-terminal domain for anchoring to the phage tail, and variable central and C-terminal domains for enzymatic activity and specificity. AlphaFold-Multimer predicts a trimeric protein adopting an elongated structure due to a long α-helix, an enzymatic β-helix domain and a hypervariable 4 amino acid hotspot in the most ultimate loop of the C-terminal domain. In contrast to the tail fiber of phage T3, this hypervariable hotspot appears unrelated with the primary receptor. The functional characterization of DpoMK34 revealed a mesophilic enzyme active up to 50 °C across a wide pH range (4 to 11) and specific for the capsule of A. baumannii MK34. Enzymatic degradation of the A. baumannii MK34 capsule causes a significant drop in phage adsorption from 95% to 9% after 5 min. Although lacking intrinsic antibacterial activity, DpoMK34 renders A. baumannii MK34 fully susceptible to serum killing in a serum concentration dependent manner. Unlike phage PMK34, DpoMK34 does not easily select for resistant mutants either against PMK34 or itself. In sum, DpoMK34 is a potential antivirulence compound that can be included in a depolymerase cocktail to control difficult to treat A. baumannii infections.

Abstract There is limited data on methicillin-resistant Staphylococcus aureus (MRSA) carriage in dental clinics. 1300 specimens from patients, health personnel, and environmental surfaces of a dental clinic in Egypt were tested for MRSA. Antibiotic susceptibility, biofilm formation, Staphylococcal protein A (spa) typing, SCCmec typing, and PCR-based assays were used to detect mecA, mecC, vanA, Panton-Valentine Leukocidin toxin (PVL), and toxic shock syndrome toxin-1 (tst) genes. Among 34 mecA-positive MRSA isolates, five (14.7%) were PVL-positive, seventeen (50%) were tst-positive, ten (29.4%) were vanA-positive, while none harboured mecC. MRSA hand carriage rates in patients, nurses, and dentists were 9.8%, 6.6%, and 5%. The respective nasal colonization rates were 11.1%, 6.7%, and 9.7%. 1.3% of the environmental isolates were MRSA-positive. Strong and moderate biofilm-forming isolates represented 23.5% and 29.4% of MRSA isolates. 24 MRSA isolates (70.6%) were multi-resistant and 18 (52.9%) harboured SCCmec IV. Among eight spa types, t223 (26.5%), t267 (23.5%), and t14339 (23.5%) were predominant. We noted an alarming genetic relatedness between 7 (20.6%) MRSA isolates and the epidemic EMRSA-15 clone, as well as a combined occurrence of tst and PVL in 3 (8.8%) isolates. Results suggest high MRSA pathogenicity in dental wards highlighting the need for more efficient surveillance/infection control strategies.

The Study dealing with the influence of heavy metal(Pb) separately in the growth of the algae Microcystis & chroococcus (cyanophyta)under lab. Conditions,the parameters were total cell count by slid chamber.The results indicates that the toxic effect of studied heavy metals depend upon metal construction,lowest total cell count . lead ions was added to the culture media as aconcetration (0.5, 1, 2,4)mg/l . the (4)mg/l concentration was more toxicity for both algae , the minimum chroococcus colonies count was (62) colony and (66) colony in microcystis at (4) mg/l concentration. By measuring inhibit rate for both algae,found , Microcystis was more resistant lead than other algae.Obsorved increase toxisity increased period was concentration of 4% toxcisity for both algae.

This paper presents an experimental study conducted on model piled rafts in partially saturated sandy soil. The aim of the experimental program is to study the effect of matric suction on the load carrying capacity of piled rafts embedded within partially saturated sandy soil .The influence of number of piles are presented and discussed in this study. The piled raft is arranged in different configurations of piles (single, double and triple piled raft with spacing 3.5D c/c) with the same area ratio (raft area to the cross section area of piles) to avoid different contact pressure area and to show the effect of different piles number and its group action. The influence of matric suction (i.e., capillary stresses) in partially saturated zone is typically not taken into account in the conventional design of both shallow and deep foundations so that the present research study the determination and contribution of matric suction towards the load carrying capacity of piled raft. The experimental work consist of 3 models of footing "single piled raft (8.3 x 5) cm, double piled (16.6 x 5) cm and triple piled raft (25 x 5) cm". All these models are loaded and tested under both of fully saturated condition (i.e., matric suction equals to 0kPa) and unsaturated conditions (i.e., matric suction value equals to 6kPa , 8kPa and 10kPa), which are achieved by predetermined lowering of water table.

Antimicrobial resistance is a major health problem, particularly in developing countries like Bangladesh, where there is a paucity of information on resistance patterns and prevalence of antimicrobial determinants. Therefore, the aims of this study were to investigate the prevalence of resistance, including multi-drug resistance (MDR), and the associated genetic determinants in Escherichia coli isolates from cloacal swabs of live broiler chickens in Bangladesh. Altogether, 400 cloacal swabs (200 from Rajshahi and 200 from Dhaka divisions) were randomly collected from individual chickens in 50 broiler farms. E. coli was isolated and identified using conventional bacteriological culture and biochemical methods. The isolates were further confirmed using genus-specific 16S rRNAtargeted polymerase chain reaction (PCR) primers. Antimicrobial susceptibilities and MDR of the isolates against nine different antimicrobial agents (ampicillin, erythromycin, tetracycline, gentamicin, ciprofloxacin, levofloxacin, trimethoprim-sulfamethoxazole, colistin sulphate, and streptomycin) were determined using the Kirby-Bauer disc diffusion method. Resistance determinants of E. coli to ampicillin (blaTEM), streptomycin (aadA1), erythromycin [ere(A)], trimethoprim (dfrA1), and tetracycline [tet(A), tet(B)] were screened using PCR. Our results showed that all swab samples were positive for E. coli. The isolates were uniformly resistant to ampicillin, tetracycline, streptomycin, ciprofloxacin, erythromycin, and trimethoprim-sulphamethoxazole. The isolates exhibited highest susceptibility to colistin sulphate (73.5%), followed by gentamicin (49%), and levofloxacin (17%). All isolates were resistant to three classes of antibiotics, 204 isolates (51%) were resistant to four classes, and 56 isolates (14%) were resistant to five. The highest prevalence of antimicrobial resistance gene was recorded for tetracycline (tet(A):95.25%; tet(B):95.25%) followed by ampicillin (blaTEM:91.25%), streptomycin (aadA1:88.25%), erythromycin (ere(A):84.75%), and trimethoprim (dfrA1:65.5%). In conclusion, surveillance for MDR bacteria in poultry is a critical piece of knowledge, which would be useful for optimizing empiric antimicrobial treatments and exploring alternative antimicrobial agents.

Mimusops laurifolia is a native species restricted to the Red Sea mountains and Gulf of Aden. Its leaves contain saponins with wide range of biological activities. The presented research aimed to prepare saponins-rich extract from n -butanol fraction of M. laurifolia leaves and screen it for promising antimicrobial activities. Minimum inhibitory concentration (MIC) of the prepared saponins against Candida albicans , and their potential anti-pathogenic and antivirulence effects were determined. Different concentrations of the saponins-rich extract were investigated for their antimicrobial potential, particularly against C. albicans , using the agar well diffusion method. To assess the potential antivirulence and antipathogenic effects, we carried out molecular docking of the bioactive saponins against four key enzymes in C. albicans , which are involved in virulence and/or pathogenicity. Different concentrations of the investigated mixture showed notable antifungal activity against C. albicans with an MIC value of 6.4 μg ml−1. Docking analysis of the investigated saponins showed their affinity toward the docked enzymes, particularly saponin 1 with secreted aspartic proteinase 3 and saponin 6 with secreted aspartic proteinase 5. Thereafter, the stability of these two protein-ligand interactions was investigated using molecular dynamics (MD) simulation. The molecular interactions between saponins and the enzymes' active sites were analyzed and discussed. [ABSTRACT FROM AUTHOR]