Disease-Modifying Antirheumatic Drugs and Dementia Prevention: A Systematic Review of Observational Evidence in Rheumatoid Arthritis.

BACKGROUND: Many observational studies have examined the association of disease-modifying antirheumatic drugs (DMARDs) with dementia risk, but the evidence has been mixed, possibly due to methodological reasons. This systematic review (PROSPERO: CRD42023432122) aims to assess existing observational evidence and to suggest if repurposing DMARDs for dementia prevention merits further investigation. METHODS: Four electronic databases up to October 26, 2023, were searched. Cohort or case-control studies that examined dementia risk associated with DMARDs in people with rheumatoid arthritis were included. Risk of bias was evaluated using the Cochrane Collaboration's Risk of Bias in Nonrandomized Studies of Interventions (ROBINS-I) criteria. Findings were summarized by individual drug classes and by risk of bias. RESULTS: Of 12,180 unique records, 14 studies (4 case-control studies, 10 cohort studies) were included. According to the ROBINS-I criteria, there were 2 studies with low risk of bias, 1 study with moderate risk, and 11 studies with serious or critical risk. Among studies with low risk of bias, one study suggested that hydroxychloroquine versus methotrexate was associated with lower incident dementia, and the other study showed no associations of tumor necrosis factor (TNF) inhibitors, tocilizumab, and tofacitinib, compared to abatacept, with incident dementia. CONCLUSION: Studies that adequately addressed important biases were limited. Studies with low risk of bias did not support repurposing TNF inhibitors, tocilizumab, abatacept or tofacitinib for dementia prevention, but hydroxychloroquine may be a potential candidate. Further studies that carefully mitigate important sources of biases are warranted, and long-term evidence will be preferred.

Clinical and Radiological Presentation of Patients with Smear Positive Pulmonary Tuberculosis.

Chest X-ray is an important diagnostic aid frequently used alongside microscopic smear of sputum for the confirmation of pulmonary tuberculosis (TB). However, there is a dearth of literature investigating the clinical and radiological pattern of sputum positive pulmonary TB among adults in Bangladesh. The current study explored these patterns in presentation. This descriptive cross-sectional study was conducted at outpatients in department of medicine of a tertiary care hospital. A total of 50 newly diagnosed adult cases of smear positive pulmonary TB attending at the Directly Observed Treatment Short-course (DOTS) corners were consecutively included. Informed written consent was taken before inclusion. Data were collected through face-to-face interview. Radiological presentation was explored using chest X-ray. Data were analyzed by SPSS version 26.0. The average age of patients was 41.0±17.12 years and majority were male (78.0%). The most prevalent respiratory symptom was cough (80.0%) followed by constitutional symptom like fever (70.0%) and weight loss (72.0%). Wasting was the predominant sign (60.0%). Radiologically both lungs were involved in 32.0%, left lung were involved in 30.0% cases and right lung were involved in 26.0% of cases. Twelve percent (12.0%) of patients had normal chest X-ray. Upper zone involvement was commonly observed in this study's patients (66.0%). The predominant pattern was consolidation (46.0%) followed by fibrosis (26.0%), nodular opacity (12.0%), collapse (10.0%), cavity (6.0%), pleural effusion (2.0%) and bronchiectasis (2.0%). Findings of this study would help familiarize and identify the common clinical and radiological presentations of sputum positive pulmonary TB patients in day-to-day practice.

Exploring putative enteric methanogenesis inhibitors using molecular simulations and a graph neural network.

Atmospheric methane (CH 4 ) acts as a key contributor to global warming. As CH 4 is a short-lived climate forcer (12 years atmospheric lifespan), its mitigation represents the most promising means to address climate change in the short term. Enteric CH 4 (the biosynthesized CH 4 from the rumen of ruminants) represents 5.1% of total global greenhouse gas (GHG) emissions, 23% of emissions from agriculture, and 27.2% of global CH 4 emissions. Therefore, it is imperative to investigate methanogenesis inhibitors and their underlying modes of action. We hereby elucidate the detailed biophysical and thermodynamic interplay between anti-methanogenic molecules and cofactor F 430 of methyl coenzyme M reductase and interpret the stoichiometric ratios and binding affinities of sixteen inhibitor molecules. We leverage this as prior in a graph neural network to first functionally cluster these sixteen known inhibitors among ∼54,000 bovine metabolites. We subsequently demonstrate a protocol to identify precursors to and putative inhibitors for methanogenesis, based on Tanimoto chemical similarity and membrane permeability predictions. This work lays the foundation for computational and de novo design of inhibitor molecules that retain/ reject one or more biochemical properties of known inhibitors discussed in this study.

Family study of haemoglobin Arya in a Malaysian family.

INTRODUCTION: Thalassemia and haemoglobinopathies are relatively common among Malaysians. One of the rare haemoglobinopathies reported is Haemoglobin (Hb) Arya, which occurs due to substitution of aspartic acid at residue 47 of the alpha chain by asparagine. Here, we report the detection of Hb Arya in a Malaysian family, which was detected incidentally during family screening. CASE REPORT: A 16 years-old girl, clinically asymptomatic was noted to have low mean corpuscular haemoglobin (MCV) with normal Hb level. Hb analysis using capillary electrophoresis (CE) showed reduced Hb A of 76.5%, Hb A2 of 1.6% with presence of small peak at Zone 1 likely A2'. There was also a small peak noted at Hb D zone and Hb S zones which quantified as 1.5% and 20% respectively. Supplementary test by high performance liquid chromatography (HPLC) showed a prominent peak at D-window (19.6%) and a small peak at S-window (0.6%). DNA analysis revealed a heterozygous state of α2 codon 47 Hb Arya mutation. Subsequent family study showed a similar mutation in the father and sister of the index case. CONCLUSION: Very few reports are available up to date regarding Hb Arya. This report highlights the rare haemoglobinopathy in a Malay family in Malaysia that contributes to the growing literature of this rare haemoglobin variant.

In vivo assessment of the nephrotoxic effects of the synthetic cannabinoid AB-FUBINACA.

BACKGROUND: The widespread misuse of synthetic cannabinoids (SCs) has led to a notable increase in reported adverse effects, raising significant health concerns. SCs use has been particularly associated with acute kidney injury (AKI). However, the pathogenesis of SCs-induced AKI is not well-understood. METHODS: We investigated the nephrotoxic effect of acute administration of N-[(1S)- 1-(aminocarbonyl)-2-methylpropyl]-1-[(4-fluorophenyl)methyl]-1H-indazole-3-carboxamide (AB-FUBINKA) (3 mg/kg for 5 days) in mice. Various parameters of oxidative stress, inflammation, and apoptosis have been quantified. The expressions of mitochondrial complexes (I-V) in renal tissues were also assessed. RESULTS: Our findings showed that AB-FUBINACA induced substantial impairment in the renal function that is accompanied by elevated expression of renal tubular damage markers; KIM-1 and NGAL. Administration of AB-FUBINACA was found to be associated with a significant increase in the expression of oxidative stress markers (iNOS, NOX4, NOX2, NOS3) and the level of lipid peroxidation in the kidney. The expression of pro-inflammatory markers (IL-6, TNF-alpha, NF-kB) was also enhanced following exposure to AB-FUBINACA. These findings were also correlated with increased expression of major apoptosis regulatory markers (Bax, caspase-9, caspase-3) and reduced expression of mitochondrial complexes I, III, and IV. CONCLUSION: These results indicate that AB-FUBINACA can trigger oxidative stress and inflammation, and activate caspase-dependent apoptosis in the kidney, with these processes being possibly linked to disruption of mitochondrial complexes and could be an underlying mechanism of SCs-induced nephrotoxicity.

Prevalence of plasmid-mediated quinolone resistance genes and biofilm formation in different species of quinolone-resistant clinical Shigella isolates: a cross-sectional study.

BACKGROUND: The purpose of this study was to look into the presence of plasmid-mediated quinolone resistance (PMQR) genes and biofilm formation in several species of clinical Shigella isolates that were resistant to quinolones. METHODS: The stool samples of 150 patients (younger than 10 years) with diarrhea were collected in this cross-sectional study (November 2020 to December 2021). After cultivation of samples on Hektoen Enteric agar and xylose lysine deoxycholate agar, standard microbiology tests, VITEK 2 system, and polymerase chain reaction (PCR) were utilized to identify Shigella isolates. The broth microdilution method was used to determine antibiotic susceptibility. PMQR genes including qnrA, qnrB, qnrC, qnrD, qnrE, qnrS, qnrVC, qepA, oqxAB, aac(6')-Ib-cr, and crpP and biofilm formation were investigated in quinolone-resistant isolates by PCR and microtiter plate method, respectively. An enterobacterial repetitive intergenic consensus polymerase chain reaction (ERIC-PCR) technique was used to determine the clonal relatedness of quinolone-resistant isolates. RESULTS: A total of 95 Shigella isolates including S. sonnei (53, 55.8%), S. flexneri (39, 41.1%), and S. boydii (3, 3.2%) were identified. The highest resistance rates of the isolates were against ampicillin (92.6%, n = 88/95). Overall, 42 of 95 (44.2%) isolates were simultaneously resistant against two or more quinolones including 26 (61.9%) S. sonnei and 16 (38.1%) S. flexneri. All isolates were multidrug-resistant (resistance to more than 3 antibiotics). The occurrence of PMQR genes was as follows: qnrS (52.4%), qnrA and aac(6')-Ib-cr (33.3%), and qnrB (19.0%). The prevalence in species was as follows: 61.5% and 37.5% (qnrS), 19.2% and 56.3% (qnrA), 38.5% and 25.0 (aac(6')-Ib-cr), and 19.2% and 18.8% (qnrB) for S. sonnei and S. flexneri, respectively. The other PMQR genes were not detected. In total, 52.8% (28/53) of quinolone-susceptible and 64.3% (27/42) of quinolone-resistant isolates were biofilm producers. Biofilm formation was not significantly different between quinolone-resistant and quinolone-susceptible isolates (P-value = 0.299). Quinolone-resistant isolates showed a high genetic diversity according to the ERIC-PCR. CONCLUSION: It seems that qnrS, qnrA, and aac(6')-Ib-cr play a significant role in the quinolone resistance among Shigella isolates in our region. Also the quinolone-resistant S. flexneri and S. sonnei isolates had a high genetic diversity. Hence, antibiotic therapy needs to be routinely revised based on the surveillance findings.

Early Outcome of Simultaneous Bilateral Total Knee Arthroplasty Through the Oxford Knee Score in a Developing Country: A Prospective Cohort.

Introduction The most common degenerative joint disease in adults is osteoarthritis. The gold standard treatment option for this aging society with greater functional demands is total knee arthroplasty. The Oxford Knee Score (OKS) assesses factors such as stiffness, pain, function, satisfaction, and quality of life, allowing you to quantify treatment success after surgery. According to published research, there isn't a perfect postoperative timepoint to use the OKS to obtain TKA outcomes. Therefore, at the time of evaluation, the OKS should reflect the best possible outcome for the patient group. This study was conducted to see the OKS in patients who underwent simultaneous bilateral knee replacement at six weeks and six months postoperatively and to see if there was a clinically significant difference in the mean OKS. Methods This prospective cross-sectional study was conducted at the Section of Orthopedic Surgery at Aga Khan University Hospital, a tertiary care center in Karachi, Pakistan. Patients who underwent simultaneous bilateral total knee replacement from October 2023 till December 2023 were included; exclusion criteria included patients who had a recent knee infection and extensor mechanism disruption. OKS was calculated at six weeks and six months postoperatively. Results The total number of patients included in the study was 49 with a mean age of 61.9 +/- 6.1. There were 42 (85.7%) females and 7 (14.3%) males. The mean BMI of our patients was 33.3 +/- 3.8. The radiographic Kellgren Lawrence Grading (KLG) was used and 38 (77.6%) patients were placed in Grade IV KLG, and 11 (22.4%) were placed in Grade III KLG. The mean OKS preoperatively was 12.6 +/- 3.5. At six weeks, the OKS showed improvement, with the mean being 20.6 +/- 3.0. At six months postoperatively, there was a significant improvement in the OKS, with the mean now being 42.7 +/- 2.4. At six weeks post-surgery, the mean improvement in the OKS score was 7.9 +/- 2.71, whereas at six months post-surgery, the mean improvement in the OKS score was 30.1 +/- 3.6. This difference was significant (p-value=0.03). Conclusion Our study showed a clinically significant difference between the mean OKS at the six-week and six-month timeline, with a significant increase in the mean improvement OKS score at six months. OKS should be utilized six months postoperatively to assess the outcome of simultaneous bilateral knee arthroplasty patients.

Factors influencing health-seeking behavior among Sudanese immigrants in Saudi Arabia.

BACKGROUND: Health-seeking behavior (HSB) involves any action or inaction taken by individuals who perceive themselves to have a health problem or illness aimed at finding appropriate medical treatments. Studies suggest a positive relationship between the availability and quality of health services and their utilization. This study aimed to identify the factors influencing health-seeking behavior among Sudanese immigrants in Saudi Arabia, to improve healthcare access and health outcomes. METHOD: A cross-sectional study was conducted targeting Sudanese residents of the Kingdom of Saudi Arabia (KSA). Participants were recruited using convenient sampling. A self-administered questionnaire was distributed electronically. A total of 494 participants were recruited for the study. RESULTS: This study showed that the majority of the participants (66.6%) visited a primary healthcare center when faced with a medical problem. However, the prevalence of self-medication in the past three months was 45.7%. Significant factors influencing health-seeking behavior included age (OR [95% CI]: 1.032 [1.000-1.066]) and lack of health insurance (OR = 1.01, 95% CI [1.00-1.02], p = 0.019). CONCLUSIONS: This study emphasizes the importance of understanding healthcare-seeking behavior among immigrant groups, particularly Sudanese immigrants in Saudi Arabia. It highlights the significance of insurance as a determinant of healthcare-seeking behavior and calls for reforming current policies to reduce disparities in accessing healthcare services.

Pressure Sore among Stroke Patients during Hospital Stay: A Cross-Sectional Study in A Tertiary Care Hospital.

Pressure sore is an important post-stroke complication that results in increased morbidity, mortality and poor prognosis of the patients. The objective of the present study was to find out the prevalence and the factors associated with pressure sore among stroke patients. This prospective cross-sectional study includes 50 stroke patients admitted in the Department of Neurology of Dhaka Medical College Hospital, Bangladesh from July to December 2018. Data were collected from the by direct interview of the patients or their relatives or caregiver using a structured case report form. Descriptive statistics were used to represent patients' characteristics and the chi-square test was used to determine the difference between patients' groups. The mean ±SD age of the stroke patients was 59.16±11.53 years and half of them were male. Fifty percent of the patients had been suffering from ischemic stroke and the rest from hemorrhagic stroke. Of all, one-fourth of the patients (24.0%) developed post-stroke pressure sore during the hospital stay and type-specific prevalence was 20.0% in ischemic stroke and 30.0% in hemorrhagic stroke. Common sites of the pressure sore were sacrum (50.0%), buttock (25.0%), heels (17.0%), and greater trochanter (8.0%). Only 8.0% of the patients developed grade IV wounds. Pressure sores of 42.0% of patients healed spontaneously, 25.0% needed conservative management and 25.0% needed a skin graft. This study found that a large portion of stroke patients develop a pressure sore during hospital stay which can deteriorate clinical outcomes and compromise the quality of life of the patients. Adequate preventive measures and proper rehabilitation should be encouraged for better stroke management and to reduce long-term complications.

NF-κB pathway as a molecular target for curcumin in diabetes mellitus treatment: Focusing on oxidative stress and inflammation.

Diabetes mellitus (DM) is a collection of metabolic disorder that is characterized by chronic hyperglycemia. Recent studies have demonstrated the crucial involvement of oxidative stress (OS) and inflammatory reactions in the development of DM. Curcumin (CUR), a natural compound derived from turmeric, exerts beneficial effects on diabetes mellitus through its interaction with the nuclear factor kappa B (NF-κB) pathway. Research indicates that CUR targets inflammatory mediators in diabetes, including tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6), by modulating the NF-κB signaling pathway. By reducing the expression of these inflammatory factors, CUR demonstrates protective effects in DM by improving pancreatic ß-cells function, normalizing inflammatory cytokines, reducing OS and enhancing insulin sensitivity. The findings reveal that CUR administration effectively lowered blood glucose elevation, reinstated diminished serum insulin levels, and enhanced body weight in Streptozotocin -induced diabetic rats. CUR exerts its beneficial effects in management of diabetic complications through regulation of signaling pathways, such as calcium-calmodulin (CaM)-dependent protein kinase II (CaMKII), peroxisome proliferator-activated receptor gamma (PPAR-γ), NF-κB, and transforming growth factor ß1 (TGFB1). Moreover, CUR reversed the heightened expression of inflammatory cytokines (TNF-α, Interleukin-1 beta (IL-1ß), IL-6) and chemokines like MCP-1 in diabetic specimens, vindicating its anti-inflammatory potency in counteracting hyperglycemia-induced alterations. CUR diminishes OS, avert structural kidney damage linked to diabetic nephropathy, and suppress NF-κB activity. Furthermore, CUR exhibited a protective effect against diabetic cardiomyopathy, lung injury, and diabetic gastroparesis. Conclusively, the study posits that CUR could potentially offer therapeutic benefits in relieving diabetic complications through its influence on the NF-κB pathway.

Pattern of Prescribing Analgesics and Their Response in Cancer Patients Attending Outpatient Department of Palliative Care Service in Two Teaching Hospitals of Bangladesh.

Palliative care is a valued aspect of clinical care which is an urgent humanitarian need for people worldwide with cancer and other chronic fatal diseases. Patients experience many different symptoms including severe pain in advanced cancer. Palliative care focuses on relief from symptoms, pain and stress by using different analgesics and adjuvant. The goal of palliative care is to improve the quality of life. So, this prospective observational study was carried out to assess pattern of drugs used and their response to pain in cancer patients attending out-patient department of palliative care service in two teaching hospitals of Bangladesh. One hundred forty (140) cancer patients were purposively selected who attended in out-patient department of palliative care unit in Bangabandhu Sheikh Mujib Medical University (BSMMU) and Dhaka Medical College Hospital (DMCH) from July 2018 to June 2019. Outcome variables were commonly presenting complaints, pain intensity, commonly prescribed drugs and analgesic prescription according to WHO three-step analgesic ladder, etc. The mean age ±SD of the respondents was 51.30±15.38 years, male-female ratio 1:1. Common sites of cancer were alimentary origin (20.0%), genitourinary system (17.86%), hepatobiliary system (11.43%), respiratory system (10.71%). The prescribed drugs were analgesics (96.4%), PPIs (74.3%), laxatives (62.1%), anti-emetics (38.6%), multivitamins (32.9%), H2 antagonists (17.1%), sedatives (17.1%), and corticosteroids (8.6%). Level 1 analgesics (Paracetamol or other NSAIDs) were prescribed to 42.65%, level 2 analgesics (Tramadol) were prescribed to 50.00% patients and level 3 analgesics (Morphine) were prescribed to 51.42% patients. The relation between and receiving three levels of analgesic prescriptions was statistically significant. The association between level of analgesic prescription was significant with site of cancer (p<0.001) and intensity of pain (p<0.001). This study showed that morphine was prescribed to more than half of the patients. Other level of analgesics were also used either single or in combination. Younger and male patients were treated more with level III analgesics. Prescribing analgesics were dependent on sites of cancer and intensity of pain.

Multidimensional Measurement of Attitudes Toward Consensual Non-Monogamy.

Despite increased interest in consensual non-monogamy (CNM), significant stigma remains against CNM. Consequently, there is a need for scales to assess attitudes toward CNM. In response to this need we developed the Multidimensional Attitudes toward CNM Scale (MACS). Items were developed in consultation with content experts and data were collected from two samples at two different Canadian Universities. Fit indices of exploratory (Sample A) and confirmatory (Sample B) factor analysis suggested a 16-item scale with three underlying factors: CNM is Dysfunctional, CNM is Immoral, and CNM is Healthy and Satisfying. Validity analyses, conducted using the combined sample (n = 806; 79% women; 67% heterosexual), demonstrated that participants with higher MACS total scores (i.e. more negative attitudes) were less likely to have ever been involved in a CNM relationship and were more likely to report monogamy as their ideal relationship style. Higher MACS scores were also associated with more negative attitudes toward bisexuality and toward women, and higher scores on measures of homophobia and jealousy. In contrast, individuals with higher scores on the CNM is Healthy subscale tended to score higher on measures of empathy. The MACS demonstrates strong psychometric properties and can assist in better understanding attitudes toward CNM relationships in research and clinical settings.

Mechanism and kinetic of piezo-catalytic desulfurization of model and actual fuel samples over CexOy/SrO nanocomposite at room temperature.

SOx emissions are primarily caused by compounds containing sulfur in petroleum and fuels, which lead to severe air pollution. For this reason, it is necessary to develop a fast and simple desulfurization method in order to comply with ever-increasing environmental regulations. The newly discovered piezo-catalyst nanocomposite CexOy/SrO can convert mechanical energy directly into chemical energy, thereby enabling mechanically oxidative sulfur desulfurization. 320 W of bath sonication were used to polarize and activate the prepared piezo-catalyst nanocomposite CexOy/SrO for sulfur removal from thiophene and dibenzothiophene as model fuels and kerosene as a real fuel. Using uniform and spherical CeO2/SrO nanocomposites resulted in the highest desulfurization rates of 95.4 %, 97.3 %, and 59.7 %, respectively, for thiophene and dibenzothiophene. This study examined the effect of several parameters, such as sulfur concentration, pH of fuel, dosage of CexOy/SrO nanocomposite, power and time of ultrasonic, and shaking time, on the piezo-desulfurization of thiophene (TP) and dibenzothiophene (DBTP). To identify the major active species in piezo desulfurization, radical trapping experiments were conducted. This study investigated the possibility of reusing the catalyst, and the piezo-desulfurization activity that was demonstrated in the removal of TP and DBTP after 11 cycles as well as the ability of the catalyst to remove real fuel even after 14 cycles was promising. As the kinetic results show, the reaction follows the second order with K = 0.0050. Also, thermodynamic results showed the oxidation of sulfide to sulfoxide and sulfoxide is endothermic. Activation energy for second order rate constant is (3.824 Kj/mole). 0.0236 mol-1. Sec-1 was calculated for Arrhenius Constant.

Purification and characterization of α-galactosidase isolated from Klebsiella pneumoniae in the human oral cavity.

The enzyme α-Galactosidase (α-D-galactoside galactohydrolase [EC 3.2.1.22]) is an exoglycosidase that hydrolyzes the terminal α-galactosyl moieties of glycolipids and glycoproteins. It is ubiquitous in nature and possesses extensive applications in the food, pharma, and biotechnology industries. The present study aimed to purify α-galactosidase from Klebsiella pneumoniae, a bacterium isolated from the human oral cavity. The purification steps involved ammonium sulfate precipitation (70 %), dialysis, ion exchange chromatography using a DEAE-cellulose column, and affinity monolith chromatography. The sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis was used to determine the molecular weight of the purified enzyme. The kinetic constants, Michaelis constant (Km) and maximal velocity (Vmax), for this enzyme were determined by using p-nitrophenyl-α-D-galactopyranoside as substrate. The results showed that the purification fold, specific activity, and yield were 126.52, 138.58 units/mg, and 21.5 %, respectively. The SDS-PAGE showed that the molecular weight of the purified enzyme was 75 kDa. The optimum pH and temperature of the purified α-galactosidase were detected at pH 6.0 and 50 °C, respectively. The kinetic constants, Michaelis constant (Km) and maximal velocity (Vmax), for this enzyme were 4.6 mM and 769.23 U/ml, respectively. α-galactosidase from Klebsiella pneumoniae was purified and characterized. (SDS-PAGE) analysis showed that the purified enzyme appeared as single band with a molecular weight of 75 kDa.

Different Types of Management for Anastomotic Leak Post Esophagectomy.

Esophagectomy is a critical surgical procedure for managing various esophageal disorders, including malignancies, strictures, and reflux disease. Nonetheless, it is associated with significant postoperative complications, with anastomotic leak being a major concern. An anastomotic leak is defined as an unintended communication failure between the proximal esophageal segment and the conduit after surgery. This review explores evolving strategies for managing anastomotic leaks after esophagectomy, including factors contributing to leaks, such as patient-related, surgical, and perioperative factors. Diagnostic advancements, encompassing clinical evaluation, radiological imaging, and endoscopy, enable rapid and accurate detection, which is crucial for timely intervention. Management approaches have evolved beyond surgical revisions and now include conservative measures, antibiotics, and endoscopic therapies, particularly for high-risk surgical cases. Novel approaches, such as endoscopic stents, tissue sealants, and regenerative therapies, hold promise in revolutionizing treatment and outcomes. Prevention strategies, encompassing patient optimization, surgical techniques, and perioperative care, are key in minimizing leak occurrence. A multidisciplinary approach involving various specialists is essential for tailored treatments and optimized outcomes. In conclusion, anastomotic leaks post esophagectomy remain a significant challenge, and this review provides a comprehensive resource on evolving management strategies, from conservative measures to innovative techniques, assisting clinicians in decision-making for leak management.

Whole genome sequence and comparative genomics analysis of multidrug-resistant Staphylococcus xylosus NM36 isolated from a cow with mastitis in Basrah city.

BACKGROUND: Staphylococcus xylosus is a coagulase-negative, gram-positive coccus that is found in the environment and as a commensal organism on the skin and mucosal surfaces of animals. Despite the fact that S. xylosus is considered a nonpathogenic bacterium, several studies have linked S. xylosus to opportunistic infections in both animals and humans. During an investigation of mastitis-causing agents in the governorate of Basrah, Iraq, we identified an antibiotic-resistant strain of S. xylosus NM36 from a milk sample from a cow with chronic mastitis. In addition to robust biofilm formation, multiple antibiotic resistance phenotypes were found. To further understand the genetic background for these phenotypes, the full genome of S. xylosus NM36 was analyzed. RESULTS: The genome consisted of a single circular 2,668,086 base pairs chromosome containing 32.8% G + C. There were 2454 protein-coding sequences, 4 ribosomal RNA (rRNA) genes, and 50 transfer RNA (tRNA) genes in the genome. In addition, genetic variation was studied by searching sequence data against a representative reference genome. Consequently, single-nucleotide polymorphism analysis was conducted and showed that there were 46,610 single-nucleotide polymorphisms (SNPs), 523 insertions, and 551 deletions. In order to overcome antibiotics, S. xylosus NM36 had been armed with several antibiotic resistance genes from several groups and families. The genome annotation service in PathoSystems Resource Integration Center (PATRIC) and Rapid Annotation using Subsystem Technology (RAST) annotation servers showed that there are multiple antimicrobial resistance elements, including antibiotic inactivation enzymes (BlaZ family, FosB), antibiotic resistance gene clusters (TcaB, TcaB2, TcaR), proteins involved in methicillin resistance (LytH, FmtA, FemC, HmrB, HmrA), TetR family transcriptional regulators, and efflux pumps conferring antibiotic resistance (NorA). In addition, we investigated and categorized the biofilm and quorum-sensing elements of the NM36 strain and found that it has multiple subsets of biofilm regulators, confirming its pathogenic nature. CONCLUSIONS: These findings necessitate a reevaluation of microbial and clinical interventions when dealing with coagulase-negative staphylococci, particularly in the context of studies pertaining to public health. This is the first time, to our knowledge, that the entire genome of S. xylosus has been sequenced in Iraq.

Occurrence of some common carbapenemase genes in carbapenem-resistant Klebsiella pneumoniae isolates collected from clinical samples in Tabriz, northwestern Iran.

OBJECTIVES: This study aimed to evaluate the antibiotic resistance patterns and prevalence of carbapenemase genes in Klebsiella pneumoniae isolates in different clinical samples from Tabriz city, northwestern Iran. RESULTS: This cross-sectional study was conducted in the Department of Microbiology, Islamic Azad University, Ahar Branch, Iran, in 2020. K. pneumoniae isolates were collected from different clinical samples, including blood, wounds, sputum, and urine. The isolates were identified using a series of standard bacteriological tests. Antibiotic resistance was determined by the disc diffusion method. The presence of blaVIM, blaNDM, blaKPC, blaOXA, and blaIMP genes were screened by polymerase chain reaction (PCR). A total of 100 non-duplicated K. pneumoniae isolates were collected from 57 urine samples, 27 blood samples, 13 wound samples, and 3 sputum samples. Overall, 70.0% of the samples were from inpatients, while 30.0% were from outpatients. The most resistance rate was related to ampicillin (94.0%), while the lowest resistance rate was related to imipenem (18.0%) and meropenem (20.0%). Overall, 25.0% of the isolates were carbapenem-resistant, of which 13.0% were resistant to both imipenem and meropenem. The PCR showed the total prevalence of 23.0% for carbapenemase genes, including 18.0% for blaKPC, 3.0% for blaVIM, 1.0% for blaIMP, and 1.0% for blaOXA gene. The blaNDM gene was not detected in any isolate. The prevalence of carbapenemase-producing K. pneumoniae isolates was relatively lower in northwestern Iran than in other regions of the country. However, special attention should be paid to the proper use of antibiotics, particularly carbapenems, to prevent further spread of antibiotic resistance and its related genes.

Primary Thymic Hodgkin Lymphoma Coexisting with Thymoma and Myasthenia Gravis: A Case Report.

BACKGROUND Myasthenia gravis is a neuromuscular disorder that is strongly associated with thymoma. Although the presence of myasthenia gravis with other tumors is uncommon, approximately 50% of patients with thymoma have myasthenia gravis. Thymic Hodgkin lymphoma should be considered due to the multiple reported cases of patients with myasthenia gravis and Hodgkin lymphoma. In this report, we present the case of 24-year-old woman with myasthenia gravis who was incidentally found to have coexisting thymoma with thymic Hodgkin lymphoma. CASE REPORT A 24-year-old woman with a known case of vitiligo presented with a 2-year history of diplopia and incidental anterior mediastinal mass. Following investigations, myasthenia gravis was diagnosed and managed by pyridostigmine, prednisolone, and azathioprine. Regarding the anterior mediastinal mass, thymoma was suspected based on the presence of myasthenia gravis and radiological findings. She underwent extended transsternal thymectomy. The final histopathological report of the dissected thymus disclosed Hodgkin lymphoma pathology coexisting with thymoma. After the diagnosis of Hodgkin lymphoma nodular sclerosis type IIA was confirmed, 6 cycles of chemotherapy were administered. Four years of follow-up revealed no evidence of Hodgkin lymphoma. However, her symptoms of myasthenia gravis persisted despite Hodgkin lymphoma remission. CONCLUSIONS There is an unclear association between myasthenia gravies and Hodgkin lymphoma. Prior reports revealed regression of myasthenia gravies following Hodgkin lymphoma management, which suggests that myasthenia could be a complication of Hodgkin lymphoma. However, in our case, myasthenia gravis persisted after Hodgkin lymphoma management; therefore, further studies are needed to explore this association.

The Five Basic Human Senses Evoke Electrodermal Activity.

Electrodermal activity (EDA) usually relates to variations in the electrical properties of palmar or plantar skin sites. EDA responses, namely skin conductance responses (SCRs), skin potential responses (SPRs) and skin susceptance responses (SSRs) are shown to be sensitive indexes of sympathetic nervous system activation and are studied in many research projects. However, the association between EDA responses and the five basic human senses has not been investigated yet. Our study aimed to explore the relationship between the three EDA responses (SCRs, SSRs and SPRs) and the five basic human senses. These three EDA responses were measured simultaneously at the same skin site on each of the 38 volunteers. The tested five senses were sight, hearing, touch, taste and smell. The results showed that the different tested senses led to different degrees of EDA responses due to activation of the sympathetic nervous system and corresponding secretion of sweat. Although a controlled study on the degree of EDA as a function of the strength of each stimulus was not performed, we noted that the largest EDA responses were typically associated with the smell sense test. We conclude that EDA responses could be utilized as measures for examining the sensitivity of the human senses. Hence, EDA devices may have important roles in sensory systems for future clinical applications.

Preventive treatment of coronavirus disease-2019 virus using coronavirus disease-2019-receptor-binding domain 1C aptamer by suppress the expression of angiotensin-converting enzyme 2 receptor.

The cause of the worldwide coronavirus disease-2019 (COVID-19) pandemic is the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). It is known to employ the same entry portal as SARS-CoV, which is the type 1 transmembrane angiotensin-converting enzyme 2 (ACE2) receptor. The receptor-binding domain (RBD) is located on the spike S-protein's S1 subunit of the spike glycoprotein. The most important and effective therapy method is inhibiting the interaction between the ACE2 receptor and the S-spike RBD. An aptamer is a small, single-chain oligonucleotide that binds strongly to the target molecule. Recently, a CoV-2-RBD-1C aptamer-based system with a 51-base hairpin structure was discovered to have substantial binding affinity against the SARS-CoV-2RBD with similar binding sites at ACE. In the current study, we will study the aptamer's effect as a SARS-CoV-2 spike blocker and inhibit its ACE2 receptors' binding by studying the toxicity of aptamer for this cell line by calcein assay and the inhibition test of CoV-2-RBD-1C aptamers on spike RBD-ACE2 binding. The results show the half-maximum inhibitory concentration of CoV-2-RBD-1C aptamer is 0.08188 µM. The inhibition effect of CoV-2-RBD-1C aptamer on spike RBD-ACE2 binding was determined at half-maximal effective concentration of 0.5 µM concentration. The percentage of spike-ACE2 binding inhibition in A549-hACE2 cells in the D614G variant after 30 s was 77%. This percentage is higher than D614 and N501Y and equals 55% and 65%, respectively, at 0.15 µM of CoV-2-RBD-1C aptamer. The CoV-2-RBD-1C aptamer prevents virus entrance through spike inhibition, which results in a 90% reduction in spike D614 virus transduction at 1.28 µM. In conclusion, the CoV-2-RBD-1C aptamer might be an effective treatment against COVID-19 infection because it directly affects the virus by blocking the S-spike of SARS-CoV-2 and preventing ACE2 receptor binding.