Phenotypic and genotypic characterization of resistance and virulence in Pseudomonas aeruginosa isolated from poultry farms in Egypt using whole genome sequencing.

Pseudomonas aeruginosa (P. aeruginosa) is an ESKAPE pathogen that can quickly develop resistance to most antibiotics. This bacterium is a zoonotic pathogen that can be found in humans, animals, foods, and environmental samples, making it a One-Health concern. P. aeruginosa threatens the poultry industry in Egypt, leading to significant economic losses. However, the investigation of this bacterium using NGS technology is nearly non-existent in Egypt. In this study, 38 isolates obtained from broiler farms of the Delta region were phenotypically investigated, and their genomes were characterized using whole genome sequencing (WGS). The study found that 100% of the isolates were resistant to fosfomycin and harbored the fosA gene. They were also resistant to trimethoprim/sulfamethoxazole, although only one isolate harbored the sul1 gene. Non-susceptibility (resistant, susceptible with increased dose) of colistin was observed in all isolates. WGS analysis revealed a high level of diversity between isolates, and MLST analysis allocated the 38 P. aeruginosa isolates into 11 distinct sequence types. The most predominant sequence type was ST267, found in 13 isolates, followed by ST1395 in 8 isolates. The isolates were susceptible to almost all tested antibiotics carrying only few different antimicrobial resistance (AMR) genes. Various AMR genes that confer resistance mainly to ß-lactam, aminoglycoside, sulfonamide, and phenicol compounds were identified. Additionally, several virulence associated genes were found without any significant differences in number and distribution among isolates. The majority of the virulence genes was identified in almost all isolates. The fact that P. aeruginosa, which harbors several AMR and virulence-associated factors, is present in poultry farms is alarming and threatens public health. The misuse of antimicrobial compounds in poultry farms plays a significant role in resistance development. Thus, increasing awareness and implementing strict veterinary regulations to guide the use of veterinary antibiotics is required to reduce health and environmental risks. Further studies from a One-Health perspective using WGS are necessary to trace the potential transmission routes of resistance between animals and humans and clarify resistance mechanisms.

Effect of exercise training with laser phototherapy on homeostasis balance resistant to hypercoagulability in seniors with obesity: a randomized trial.

The prevalence of obesity has increased the incidence of obesity-related coagulation disorders. The current study assessed the effectiveness of combined aerobic exercise and laser phototherapy on the coagulation profile and body measurements in older adults with obesity compared to aerobic exercise alone, which has not been adequately explored. We included 76 obese people (50% women and 50% men) with a mean age of 67.83 ± 4.84 years and a body mass index of 34.55 ± 2.67 kg/m2. The participants were randomly assigned to the experimental group (which received aerobic training with laser phototherapy) and the control group (which received aerobic training alone) for three months. From the baseline to the final analysis, the absolute changes in specific coagulation biomarker levels (fibrinogen, fibrin fragment D, prothrombin time, Kaolin-Cephalin Coagulation Time), and contributing parameters (C-reactive protein and total cholesterol), were assessed. In comparison to the control group, the experimental group showed significant improvements in all evaluated measures (p < 0.001). So, in comparison to aerobic exercise alone, combined aerobic exercise and laser phototherapy had superior positive effects on coagulation biomarkers and decreased the risk of thromboembolism throughout a three-month intervention period in senior obese persons. Therefore, we suggest adopting laser phototherapy for individuals with a greater risk of hypercoagulability.The research was entered into the database of clinical trials under the identification NCT04503317.

Efficacy of some avian influenza H5 vaccines against local highly pathogenic avian influenza viruses subtype H5N8 isolated in 2018 and 2020 in Egypt

Commercial inactivated avian influenza H5 vaccine is used as an essential control strategy for avian influenza disease in Egypt. Since the initial outbreaks of highly pathogenic avian influenza H5N8, the virus has diverged with new genotypes and variant viruses continuing to emerge which mainly stand behind vaccination failure. In the present work, four different commercial avian influenza vaccines were inoculated in specific pathogenic free chickens for assessing its efficacy against local highly pathogenic avian influenza H5N8 virus isolated in 2018 and 2020. Two hundred and forty specific pathogenic free chickens were clustered into four groups; each group was inoculated with the corresponding vaccine (60 specific pathogenic free chickens/vaccine). Sixty specific pathogenic free chicks were kept as control unvaccinated group. Sera collected from vaccinated chicken groups at 3rd and 4th week post vaccination were examined for calculating neutralizing antibodies using heterologous highly pathogenic avian influenza H5N8 2018 and 2020. At 4th week post vaccination, vaccinated chickens were challenged; moreover, oropharyngeal swabs were collected from challenged vaccinated chickens to calculate the viral shedding. Our findings revealed the groups vaccinated with vaccine code no 1 and 2 that contains two vaccine strains (H5N1 and H5N8) of local origin exhibited the highest hemagglutination inhibition titer, protection (percent) and reduction in viral shedding titer when examined by highly pathogenic avian influenza H5N8 2018 while, vaccine code no 3 induced lower antibody response, protection (percent) and reduction in viral shedding, but still within satisfactory level when compared to previous groups. When highly pathogenic avian influenza H5N8 2020 was used, it was found the seroconversion rate, protection (percent) and mean titer of reduction of viral shedding decreased in comparison to those recorded for highly pathogenic avian influenza H5N8 2018. Vaccine code no 4 was impotent to either highly pathogenic avian influenza 2018 or 2020. Accordingly, it was recommended to update vaccine strain according to epidemiological condition and used the predominant circulating strain isolate in challenge test(AU)

La vacuna comercial inactivada H5 se utiliza como estrategia esencial de control de la enfermedad de la gripe aviar en Egipto. Desde los brotes iniciales de la gripe aviar altamente patógena H5N8, el virus ha variado al aparecer continuamente nuevos genotipos y variantes virales, que son los principales responsables del fracaso de la vacunación. En el presente trabajo, cuatro vacunas comerciales diferentes contra la gripe aviar se inocularon en pollos libres de patógenos específicos para evaluar su eficacia contra cepas del virus local de la gripe aviar altamente patógeno H5N8 aisladas en 2018 y 2020. Se agruparon 240 pollos pollos libres de patógenos específicos en cuatro grupos, cada uno fue inoculado con la vacuna correspondiente (60 pollos pollos libres de patógenos específicos/vacuna). Sesenta pollos SPF se mantuvieron como grupo control sin vacunar. Los sueros de los pollos vacunados recogidos en la 3ª y 4ª semana después de la vacunación se examinaron para calcular los anticuerpos neutralizantes contra la gripe aviar heteróloga H5N8 2018 y 2020. En la cuarta semana después de la vacunación, los pollos vacunados fueron retados; además, se recogieron hisopados orofaríngeos de los pollos vacunados retados para calcular la diseminación viral. Nuestros resultados revelaron que los grupos vacunados con las vacunas con códigos nº 1 y 2, que contienen dos cepas vacunales (H5N1 y H5N8) de origen local, mostraron el mayor título de inhibición de la hemaglutinación, protección (por ciento) y reducción del título de excreción viral cuando se evaluaron contra la gripe aviar altamente patógena H5N8 2018, mientras que la vacuna con código nº 3 indujo menor respuesta de anticuerpos, protección (por ciento) y reducción de la excreción viral, pero todavía dentro de un nivel satisfactorio en comparación con los grupos anteriores. Al utilizar la vacuna contra la gripe aviar altamente patógena H5N8 2020, se observó que la tasa de seronconversión, la protección (por ciento) y el título medio de reducción de la excreción viral disminuyeron en comparación con los registrados para la gripe aviar altamente patógena H5N8 2018. La vacuna con código nº 4 no fue potente para la gripe aviar altamente patógena de 2018 o de 2020. Por consiguiente, se recomendó actualizar la cepa de la vacuna de acuerdo con las condiciones epidemiológicas y utilizar el aislamiento de la cepa circulante predominante en la prueba de reto(AU)

Assessment of mycoplasma vaccine efficacy in reducing infection with Newcastle disease virus

The present work recorded the impact of using Mycoplasma gallisepticum vaccines on post-vaccinal response and protection against challenge with Newcastle disease virus. Specific pathogen-free chickens were divided into eight groups of forty chickens each. Group G1 was vaccinated with Mycoplasma gallisepticum live attenuated and Mycoplasma gallisepticum inactivated vaccines. Group G2 was vaccinated with Mycoplasma gallisepticum live attenuated, Mycoplasma gallisepticum inactivated and Newcastle disease inactivated vaccines. Group G3 was vaccinated with Mycoplasma gallisepticum live attenuated vaccine. Group G4 was vaccinated with Mycoplasma gallisepticum live attenuated and Newcastle disease inactivated vaccines. Group G5 was vaccinated with Mycoplasma gallisepticum inactivated vaccine. Group G6 was vaccinated with Mycoplasma gallisepticum inactivated and Newcastle disease inactivated vaccines. Group G7 was vaccinated with Newcastle disease inactivated vaccine. Group G8 was kept as non-vaccinated control. The Newcastle disease hemagglutination inhibition antibodies and mortality percentages were measured. Group G7 recorded the best protective Newcastle disease hemagglutination inhibition antibody titer (7 log2). Group G2 recorded a marginal satisfactory antibody titer (6 log2) after vaccination by the three tested vaccines. The remaining groups revealed unsatisfactory titers ranged from 0-5. The protection levels for G2, G4, G6 and G7 ranged from 70percent to 100percent, but only G2 and G7 were considered protected. G1, G3, G5 and G8 showed typical clinical signs of Newcastle disease. The Mycoplasma gallisepticum vaccines couldn't improve the response to Newcastle disease inactivated vaccine. The results suggest that Mycoplasma gallisepticum vaccination is immunosuppressive rather than immunomodulatory in Newcastle disease vaccination(AU)

En el presente trabajo se registró el impacto de la utilización de vacunas contra Mycoplasma gallisepticum sobre la respuesta posvacunal y la protección frente al reto con el virus de la enfermedad de Newcastle. Pollos libres de patógenos específicos se distribuyeron en ocho grupos de cuarenta pollos cada uno. El grupo G1 se vacunó con vacunas vivas atenuadas e inactivadas contra Mycoplasma gallisepticum. Al grupo G2 se le aplicaron las vacunas: viva atenuada contra Mycoplasma gallisepticum, inactivada contra Mycoplasma gallisepticum e inactivada contra la enfermedad de Newcastle. El grupo G3 se inmunizó con la vacuna viva atenuada contra Mycoplasma gallisepticum; el G4, con las vivas atenuadas contra Mycoplasma gallisepticum e inactivada contra la enfermedad de Newcastle; el G5, con la vacuna inactivada contra Mycoplasma gallisepticum; el G6 con las vacunas inactivadas contra Mycoplasma gallisepticum y la enfermedad de Newcastle; el G7, con la vacuna inactivada contra la enfermedad de Newcastle y el G8 se mantuvo como control no vacunado. Se midieron los anticuerpos de inhibición de la hemaglutinación contra el virus de la enfermedad de Newcastle y los porcentajes de mortalidad. El grupo G7 registró el mejor título de anticuerpos inhibidores de la hemaglutinación contra la enfermedad de Newcastle (7 log2). El grupo G2 registró un título de anticuerpos marginalmente satisfactorio (6 log2) tras la vacunación con las tres vacunas ensayadas. Los demás grupos revelaron títulos insatisfactorios que oscilaban entre 0 y 5. Los niveles de protección de los grupos G2, G4, G6 y G7 oscilaron entre el 70 por ciento y el 100 por ciento, pero sólo G2 y G7 se consideraron protegidos. Los grupos G1, G3, G5 y G8 mostraron signos clínicos típicos de la enfermedad de Newcastle. Las vacunas contra Mycoplasma gallisepticum no pudieron mejorar la respuesta a la vacuna inactivada contra la enfermedad de Newcastle. Los resultados revelan que la vacunación con Mycoplasma gallisepticum es más inmunosupresora que inmunomoduladora en la vacunación contra la enfermedad de Newcastle(AU)

Pathogenicity and vaccine efficacy of two virulent infectious laryngotracheitis virus strains in Egypt.

Infectious laryngotracheitis (ILT) is an economically crucial respiratory disease of poultry that affects the industry worldwide. Vaccination is the principal tool in the control of the disease outbreak. In an earlier study, we comprehensively characterized the circulating strains in Egypt and identified both CEO-like and recombinant strains are dominant. Herein, we investigated the pathogenicity of two virulent strains representing the CEO-like (Sharkia_2018) and recombinant strain (Qalubia_2018). Additionally, we evaluated the efficacy of different commercial vaccines (HVT-LT, CEO, and TCO) against the two isolates in terms of the histopathological lesion scores and the viral (gC) gene load. A total of 270 White Leghorn-specific pathogen-free male chicks were divided into nine groups of 30 birds, each housed in separate isolators. Birds were distributed as follows; one group was non-vaccinated, non-challenged, and served as a negative control. Two groups were non-vaccinated and infected with the two isolates of interest and served as a positive control to test the pathogenicity. Six groups were vaccinated and challenged; two groups were vaccinated with vector vaccine at one day old. The other four groups were vaccinated with either the CEO- or TCO- vaccine (two groups each) at four weeks of age. Three weeks after vaccination, birds were infected with the virulent ILTV isolates. The larynx, trachea, and harderian gland samples were taken at 1, 3, and 7 days post-infection for histopathological lesion score and molecular detection. Notably, The recombinant strain was more virulent and pathogenic than CEO-like ILTV strains. Moreover, the TCO vaccine was less immunogenic than the vector and CEO vaccines.

Influence of Manual Diaphragm Release Technique Combined with Inspiratory Muscle Training on Selected Persistent Symptoms in Men with Post-Covid-19 Syndrome: A Randomized Controlled Trial.

OBJECTIVE: To determine whether the addition of manual diaphragm release to an inspiratory muscle training programme is more  effective than inspiratory muscle training alone in reducing blood pressure, dyspnoea, fatigue, and aerobic performance capacity in men with post-COVID-19 syndrome. DESIGN: A prospective, randomized-controlled trial. SETTING: Chest Disease Department, Outpatient Clinic, Cairo University, Egypt. PARTICIPANTS: Fifty-two men with post-COVID-19 syndrome were allocated randomly to the study and control groups. INTERVENTION: The study group underwent diaphragm release plus inspiratory muscle training, whereas the control group received inspiratory muscle training only. OUTCOME MEASURES: All patients were assessed with the following measures at baseline and 6 weeks postintervention: maximum static inspiratory pressure for inspiratory muscle strength, peripheral arterial blood pressure, Modified Medical Research Council scale for dyspnoea, Fatigue Severity Scale, serum lactate level, and 6-min walk test distance for aerobic performance. RESULTS: All outcome measures showed a significant improvement in favour of the study group (p < 0.001) over the control group. However, maximum static inspiratory pressure increased significantly, by 48.17% (p < 0.001) in the study group with no significant change in the control group. CONCLUSION: Addition of manual diaphragm release to an inspiratory muscle training programme potentiates the role of inspiratory muscle training in the management of men with symptomatic post-COVID-19 syndrome.

Genotyping and pathogenicity of fowl adenovirus isolated from broiler chickens in Egypt.

BACKGROUND: Over the past 10 years, inclusion body hepatitis outbreaks, essentially from commercial broiler flocks, have been detected in different geographic regions highlighting the wide distribution of FAdVs around the world resulting in serious economic losses due to increased mortalities as well as poor performance within poultry farms in Assiut province, Egypt. Thus, this study was achieved to detect fowl adenovirus in broiler chicken flocks in Assiut province, Egypt and to recognize the pathogenicity of the isolated virus. RESULTS: The phylogeny of the L1 loop of the hexon gene exposed that the isolated virus clustered and belonged to the reference strains serotype D FAdV. The isolated virus is closely related to inclusion body hepatitis (IBH) strains causing extensive economic losses. The pathogenicity study of the virus showed typical macroscopic lesions with 6% mortality; furthermore, histopathological inspection exhibited severe hepatitis and degenerative changes after 5d from infection in the immune system.  CONCLUSION: Results in this research support the primary pathogenicity and mortality caused by FADV serotype 2 (IBH) alone without immunosuppressive agents thus robust control measures should be implanted against FAdV to evade the serious economic losses in poultry farms.

Trametinib: Could It Be a Promising Drug to Treat Atypical Chronic Myeloid Leukemia?

Atypical chronic myeloid leukemia (aCML) is a rare disease that is currently classified under the myelodysplastic (MDS)/myeloproliferative neoplasm (MPN) disease spectrum. MDS/MPN diseases are characterized by the absence of the Philadelphia (Ph) chromosome and the overlap between bone marrow fibrosis and dysplastic features. The Ph chromosome, resulting from BCR-ABL1 translocation, helps to distinguish aCML from chronic myeloid leukemia (CML). The currently reported incidence of aCML is imprecise because aCML is diagnosed primarily based on morphological features and other unspecified laboratory findings, and there is an especially high chance of under-diagnosis of aCML and other MDS/MPN diseases. Recent advances in next-generation sequencing (NGS) have allowed a greater understanding of the nature of aCML, providing better opportunities to achieve higher diagnostic accuracy and for the use of more targeted treatment to achieve better outcomes. Herein, we present a case of a 68-year-old woman who came to our hospital complaining of shortness of breath, fatigue, and weakness, who was found to have significantly increased leukocytosis, hepatosplenomegaly, and was negative for the Ph chromosome. Further investigations with NGS revealed mutations in ASXL1, GATA2, NRAS, and SRSF2 but not CSF3R. In addition to this, peripheral smear and bone marrow aspiration findings were suggestive of aCML based on specific morphological findings. Since the patient was ineligible for a stem cell transplant (SCT), symptomatic treatment was started with cell transfusion; however, the patient continued to have symptomatic anemia that required multiple transfusions. A trial with trametinib, a mitogen-activated protein kinase kinase (MEK) inhibitor, was later started as a targeted therapy based on one of her genetic mutations. Interestingly, the patient's blood counts stabilized, she reported feeling better, and she did not need any blood transfusions for four consecutive months during treatment with trametinib. Unfortunately, our patient later died from sepsis resulting from secondary infections. In light of the significant advancements in NGS, clinicians should always consider utilizing it as a helpful tool to not only establish a rare diagnosis of aCML but also to offer the best available targeted therapy when applicable. This might alleviate the burden associated with the poor prognosis of aCML.

IL-17A )rs2275913; G197A) gene polymorphism as predictor for disease severity and its correlation with IL-17 serum levels in COVID-19 patients.

Severity of symptoms in COVID-19 has been shown to result from a cytokine storm. Interleukin (IL)-17 is one of these various cytokines, which results in a proinflammatory response, systemic inflammatory symptoms, inflammatory cell infiltration of lung tissue and thus leads to the massive lung pathology and multiorgan failure. Gene polymorphisms in the regulatory regions of cytokine-encoding genes affect the amounts of cytokines produced and possess a fundamental role in infectious diseases. This study aimed to investigate the role of IL-17A (rs2275913; G197A) gene polymorphism as predictor of disease severity and its correlation with IL-17 serum levels in COVID-19 patients. A group of 70 COVID-19 patients and 17 age and sex-matched control subjects were enrolled in the present work. Patients were classified into two groups moderate, severe and acute respiratory distress (ARDS) cases, defined according to the criteria established by the world health organization. Quantitative real time-polymerase chain reaction was done to detect IL-17A (rs2275913; G197A). Serum IL-17 levels were assessed by an enzyme-linked immunosorbent assay in both patients and controls. The distribution of different IL-17A G/A genotypes among COVID-19 patients were 44.3% for GG genotype, 44.3% for AG genotype and 11.4% for AA genotype. Genotypes among the control group were 43.8% for GG genotype, 50% for AG genotype and 6.3% for AA genotype. G allele distribution was 66.4%, 68.8% in patient and control group, respectively, and A allele was 33.6% and 31.3%, respectively. There was no association between the different genotypes, disease severity or IL-17 serum levels in the patient group. In conclusion, despite the possible role of IL-17 in the pathogenesis of inflammation, there was no association between IL-17 polymorphism and disease severity or IL-17 serum levels among Egyptian COVID-19 patients.

Aerobic Exercise with Mediterranean-DASH Intervention for Neurodegenerative Delay Diet Promotes Brain Cells' Longevity despite Sex Hormone Deficiency in Postmenopausal Women: A Randomized Controlled Trial.

Objective: To investigate the combined impact of aerobic exercise and Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet on brain cells longevity in spite of sex hormones deficiency in obese postmenopausal women. Design: A parallel randomized clinical trial. Subjects/Patients. Sixty-eight eligible postmenopausal women were randomly assigned to one of two groups, one experimental and one control. The participants' age ranged from 60 to 75 years, and their body mass index ranged from 30 to 39.9 kg/m2. Methods: An experimental group whose members followed moderate-intensity treadmill exercise three times/week for three months with MIND diet and a control group whose members followed the MIND diet only. In addition to serum sex hormones, pre- and post-12-week assessments were performed to measure serum sex hormones as well as cognitive and functional levels. Results: The experimental group showed after intervention highly significant changes (p < 0.01) in sex hormones, cognitive functions, and functional levels compared with the control group (p < 0.05). In addition, no correlation was found between the measured variables in both groups after intervention (p > 0.05). Conclusion: Aerobic exercise combined with the MIND diet improves cognitive and functional levels and substitutes sex hormones deficiency in postmenopausal women, which affects the longevity of brain health.

Aerobic exercise with diet induces hormonal, metabolic, and psychological changes in postmenopausal obese women.

Physical activity and diet are recommended lifestyle strategies to improve human health. Consequently, this study aimed to investigate the impact of aerobic exercise combined with dietary restriction on hormonal, metabolic, and psychological variables in postmenopausal women. Eligible 60 women were enrolled and assigned into two equal groups; the experimental group performed aerobic exercise three times per week for 12 weeks with diet restriction, and the control group only received the same diet program. Serum levels of sex hormones, insulin resistance, and depression scores were measured before and after the intervention. Results: All measured variables were significantly changed in the experimental group compared to the control group (P = 0.001). Conclusion: Changes in sex hormones are a biological marker of metabolic complications such as insulin resistance, which can be reduced with exercise and diet. In addition, they are effective therapeutic interventions in the treatment of mild depression. Trial registration: Registration identifier number of this study is: NCT05136742 on https://register.ClinicalTrials.gov.

Hashimoto's Thyroiditis Presents as an Acute Encephalopathy: A Case Report of Unusual Presentation.

Hashimoto's thyroiditis is the most common thyroid disorder in the United States. Hashimoto encephalopathy is a rare presentation of Hashimoto's thyroiditis that is frequently misdiagnosed. We present the case of a 71-year-old female who had normal mental status at baseline. She presented with acute alteration in mental status. Further evaluation with brain MRI showed a hyperintense signal in the bilateral centrum. Spinal fluid analysis revealed elevated protein. Thyroid peroxidase (TPO) antibody was elevated at 59.7 and TSH was elevated at 4.9. Her mental status improved dramatically after treatment with steroids and levothyroxine. This diagnosis should be suspected when the patient develops acute encephalopathy with positive serum thyroid antibody settings with a complete return to normal mental status after treatment with steroids.

The Effect of Laser Therapy Along With Mediterranean Diet Versus Mediterranean Diet Only on Older Adults With Non-alcoholic Fatty Liver Disease: A Randomized Clinical Trial.

Introduction: Obesity is the major pathogenesis of the non-alcoholic fatty liver disease (NAFLD). The combination of low-level laser therapy (LLLT) and Mediterranean diet (MD) is a new approach for improving liver function. Methods: 60 obese older adults (65-75 years old) with NAFLD were randomly assigned equally to two groups: a study group and a control group. The study group received LLLT and MD, while the control group followed MD only. These findings evaluated the changes in the level of liver enzymes, serum lipid profile, and anthropometric measurements (body mass index [BMI] and waist circumference [WC]) after 12 weeks of intervention. Results: Both study and control groups showed a significant reduction in the levels of liver enzymes, serum lipid profile, BMI, and WC (P < 0.001 and P < 0.01 respectively); however, the study group showed more significant results compared to the control group (P < 0.01). Conclusion: LLLT and MD may be considered as a treatment approach for NAFLD in older adults to improve their liver function, control dyslipidemia, and help in losing weight.

Current Updates on the Management of AL Amyloidosis.

Systemic immunoglobulin light chain (AL) amyloidosis is a rare but fatal disease. It results from clonal proliferation of plasma cells with excessive production of insoluble misfolded proteins that aggregate in the extracellular matrix, causing damage to the normal architecture and function of various organs. For decades, treatment for AL amyloidosis was based mainly on therapeutic agents previously studied for its more common counterpart, multiple myeloma. As the prevalence and incidence of AL amyloidosis have increased, ongoing research has been conducted with treatments typically used in myeloma with varying success. In this review, we focus on current treatment strategies and updates to clinical guidelines and therapeutics for AL amyloidosis.

Expression of NKG2A inhibitory receptor on cytotoxic lymphocytes as an indicator of severity in Corona Virus Disease 2019 (COVID-19) patients.

NK group 2 member A (NKG2A) receptor transduces inhibitory signaling; suppressing NK and T-cell cytokine secretion and cytotoxic function. This study aimed to assess the expression of NKG2A inhibitory receptor on natural killer (NK) cells and CD8+ T lymphocytes in COVID-19 patients and correlate the results with disease severity defined according to the criteria established by the world health organization, in a trial to understand the immunological response towards COVID-19 infection. The study enrolled 30 COVID-19 patients classified into 2 groups that comprised 15 subjects each; moderate and severe based on clinical, radiological, and laboratory findings. Ten age and sex matched apparently healthy individuals were included in this study as a control group. About 1 ml EDTA anti-coagulated blood samples were collected for measuring expression of NKG2A/CD159a on CD56+ CD3- NK and CD3+CD8+ T cells by flow cytometry. Results revealed that COVID-19 patients had significantly lower NK and CD8+ T cell counts compared to healthy subjects. Severe cases had significantly lower CD8+ T counts compared to moderate ones. Percentages of NK and CD8+T cells expressing NKG2A receptor were significantly higher in cases compared to controls. Comparison between severe and moderate cases revealed that although the percentages of NK cells expressing NKG2A receptor were not significantly higher in severe cases, the mean fluorescence intensity was significantly higher. The percentages of CD8 +T cells expressing NKG2A receptor were significantly higher in severe cases with higher mean fluorescence intensity. In conclusion, our results indicate that elevated NKG2A expression on cytotoxic lymphocytes correlates with disease severity in COVID-19 patients, and may serve as a potential marker for prognosis. Additionally, the blockade of NKG2A should be investigated as means of enhancing NK cell and cytotoxic T cells antiviral immunity in patients with severe COVID-19 infection.

Outcomes and risk factors for death in patients with coronavirus disease-2019 (COVID-19) pneumonia admitted to the intensive care units of an Egyptian University Hospital. A retrospective cohort study.

BACKGROUND: The characteristics, outcomes, and risk factors for in-hospital death of critically ill intensive care unit (ICU) patients with coronavirus disease-2019 (COVID-19) have been described in patients from Europe, North America and China, but there are few data from COVID-19 patients in Middle Eastern countries. The aim of this study was to investigate the characteristics, outcomes, and risk factors for in-hospital death of critically ill patients with COVID-19 pneumonia admitted to the ICUs of a University Hospital in Egypt. METHODS: Retrospective analysis of patients with COVID-19 pneumonia admitted between April 28 and July 29, 2020 to two ICUs dedicated to the isolation and treatment of patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in Cairo University Hospitals. Diagnosis was confirmed in all patients using real-time reverse transcription polymerase chain reaction on respiratory samples and radiologic evidence of pneumonia. RESULTS: Of the 177 patients admitted to the ICUs during the study period, 160 patients had COVID-19 pneumonia and were included in the analysis (mean age: 60 ± 14 years, 67.5% males); 23% of patients had no known comorbidities. The overall ICU and hospital mortality rates were both 24.4%. The ICU and hospital lengths of stay were 7 (25-75% interquartile range: 4-10) and 10 (25-75% interquartile range: 7-14) days, respectively. In a multivariable analysis with in-hospital death as the dependent variable, ischemic heart disease, history of smoking, and secondary bacterial pneumonia were independently associated with a higher risk of in-hospital death, whereas greater PaO2/FiO2 ratio on admission to the ICU was associated with a lower risk. CONCLUSION: In this cohort of critically ill patients with COVID-19 pneumonia, ischemic heart disease, history of smoking, and secondary bacterial pneumonia were independently associated with a higher risk of in-hospital death.

The Latest Advancement in Pancreatic Ductal Adenocarcinoma Therapy: A Review Article for the Latest Guidelines and Novel Therapies.

Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer deaths in the US, and it is expected to be the second leading cause of cancer deaths by 2030. The lack of effective early screening tests and alarming symptoms with early undetectable micro-metastasis at the time of presentation play a vital role in the high death rate from pancreatic cancer. In addition to this, the low mutation burden in pancreatic cancer, low immunological profile, dense tumorigenesis stroma, and decreased tumor sensitivity to cytotoxic drugs contribute to the low survival rates in PDAC patients. Despite breakthroughs in chemotherapeutic and immunotherapeutic drugs, pancreatic cancer remains one of the solid tumors that exhibit meager curative rates. Therefore, researchers must dedicate more effort to understanding the pathology and immunological behavior of PDAC, in addition to properly utilizing more advanced screening modalities and new therapeutic agents. In our review, we focus mainly on the latest updates from clinical guidelines and novel therapies that have been recently investigated or are under investigation for PDAC. We used PubMed as a search tool for finding original research articles addressing the latest developments in diagnosing and treating PDAC. Additionally, we also used the clinical trials published on clinicaltrialsgov as sources for our data.

Impact of Combined Photo-Biomodulation and Aerobic Exercise on Cognitive Function and Quality-of-Life in Elderly Alzheimer Patients with Anemia: A Randomized Clinical Trial.

PURPOSE: Few data are available on the positive impact of photo-biomodulation (PBM) using low-level laser therapy as a complementary treatment for improving the cognitive function and optimizing the hemoglobin (Hb) level and oxygen carrying capacity in anemic elderly patients and consequently improving the quality-of-life. The present study aimed to evaluate a new, safe, and easy therapeutic approach to improve Alzheimer's disease-related symptoms that interfere with the whole life activities and social interaction of elderly patients. PATIENTS AND METHODS: In this placebo-controlled clinical trial, 60 elderly patients suffering from anemia and mild cognitive dysfunction were randomly assigned into two equal groups to receive active or placebo low-level laser in addition to a moderate-intensity aerobic exercise over a 12-week period. Hb level as well as cognitive and functional tests were reassessed for any change after 12 weeks of intervention. RESULTS: By the end of this study, both groups showed significant improvements in Hb level, Montreal Cognitive Assessment Scale (MoCa - B basic), Quality-of-Life for Alzheimer's Disease scale, and Berg Balance scale scores along with significant reduction in body mass index (BMI) and waist-hip ratio (WHR) (P<0.0001). The experimental group which received active low-level laser in addition to moderate-intensity aerobic exercise showed more significant results compared to the control group which received placebo low-level laser in addition to moderate-intensity aerobic exercise in all the measured outcomes (P<0.001). CONCLUSION: Combined low-level laser therapy and moderate-intensity aerobic exercises are more effective in improving the cognitive function and quality-of-life of Alzheimer's disease patients. CLINICAL TRIAL REGISTRATION: www.ClinicalTrials.gov, identifier NCT04496778.

Effect of chitosan nanoparticles on quorum sensing-controlled virulence factors and expression of LasI and RhlI genes among Pseudomonas aeruginosa clinical isolates.

Antibiotic-resistant strains of Pseudomonas aeruginosa (P. aeruginosa) pose a major threat for healthcare-associated and community-acquired infections. P. aeruginosa is recognized as an opportunistic pathogen using quorum sensing (QS) system to regulate the expression of virulence factors and biofilm development. Thus, meddling with the QS system would give alternate methods of controlling the pathogenicity. This study aimed to assess the inhibitory impact of chitosan nanoparticles (CS-NPs) on P. aeruginosa virulence factors regulated by QS (e.g., motility and biofilm formation) and LasI and RhlI gene expression. Minimum inhibitory concentration (MIC) of CS-NPs against 30 isolates of P. aeruginosa was determined. The CS-NPs at sub-MIC were utilized to assess their inhibitory effect on motility, biofilm formation, and the expression levels of LasI and RhlI genes. CS-NPs remarkably inhibited the tested virulence factors as compared to the controls grown without the nanoparticles. The mean (±SD) diameter of swimming motility was decreased from 3.93 (±1.5) to 1.63 (±1.02) cm, and the mean of the swarming motility was reduced from 3.5 (±1.6) to 1.9 (±1.07) cm. All isolates became non-biofilm producers, and the mean percentage rate of biofilm inhibition was 84.95% (±6.18). Quantitative real-time PCR affirmed the opposition of QS activity by lowering the expression levels of LasI and RhlI genes; the expression level was decreased by 90- and 100-folds, respectively. In conclusion, the application of CS-NPs reduces the virulence factors significantly at both genotypic and phenotypic levels. These promising results can breathe hope in the fight against resistant P. aeruginosa by repressing its QS-regulated virulence factors.

Mortality Prediction of Microalbuminuria in Septic Patients.

BACKGROUND: Huge number of pro-inflammatory and anti-inflammatory markers is produced during the process of sepsis. Its mortality prediction value needs to be determined. AIM: To assess the prognostic value of Albumin creatinine ratio (ACR) in septic patients and its ability to predict mortality in comparison with Acute physiology and chronic health evaluation II score (APACHE II). METHODS: Seventy-five Septic patients were included within 24 hours of sepsis diagnosis and were admitted to the intensive care unit (ICU). ACR values were obtained within 6 hours of ICU admission for all patients. Prognostic scoring systems [APACHE II and Sequential organ failure assessment (SOFA) scores] were calculated. RESULTS: Twenty percent of enrolled patients died within 28 days of hospital admission. ACR was significantly higher in non-survivor in comparison to survivors (55.1 ± 20.5 versus 30.2 ± 35.7, p = 0.006). ACR ≥ 40 (mg/gm creatinine) was the cut-off point for predicting mortality with a sensitivity of 90.7% and specificity of 71.8% with total accuracy of 66% and AUC 0.75 (CI 0.62-0.88). Mean APACHE II score was significantly higher in non-survivors than survivor groups (21.4 versus 10.8, p < 0.001). ACR was positively correlated with highest SOFA score (r = 0.3, P < 0.05). CONCLUSION: ACR is a simple prognostic marker in septic patient and could be used as a mortality predictor, particularly in early (within 6 hours) septic patients.