Chitosan decorated oleosomes loaded propranolol hydrochloride hydrogel repurposed for Candida albicans-vaginal infection.

Aim: Our investigation aims to estimate the antifungal effect of propranolol hydrochloride (PNL). Methods: Oleosomes (OLs) were fabricated by thin-film hydration and evaluated for entrapment efficiency (EE%), particle size (PS), polydispersity index (PDI), zeta potential (ZP), and amount of drug released after 6 h Q6h (%). Results: The optimal OL showed a rounded shape with optimum characteristics. The ex-vivo permeation and confocal laser scanning microscopy verified the prolonged release and well deposition of PNL-loaded OLs-gel. The in-silico assessment demonstrated the good stability of PNL with OLs' ingredients. In vivo evaluations for PNL-loaded OLs-gel showed a good antifungal impact against Candida albicans with good safety. Conclusion: This work highlights the potential of PNL-loaded OLs-gel as a potential treatment for candida vaginal infection.

[Box: see text].

A Comparative Analysis of Polysaccharides and Ethanolic Extracts from Two Egyptian Sweet Potato Cultivars, Abees and A 195: Chemical Characterization and Immunostimulant Activities.

Sweet potato (Ipomoea batatas (L.) Lam.) belongs to family Convolvulaceae. The plant is distributed worldwide and consumed, especially for its edible tubers. Many studies have proved that the plant has variable biological activities such as antidiabetic, anti-cancer, antihypertensive, antimicrobial, and immunostimulant activities. The roots of sweet potatoes are rich in valuable phytochemical constituents that vary according to the flesh color. Our investigation focused on the chemical profiling of two Egyptian sweet potato cultivars, Abees and A 195, using UPLC-QTOF and the analysis of their polysaccharide fractions by GC-MS. Furthermore, we assessed the immunostimulant properties of these extracts in immunosuppressed mice. The study revealed that sweet potato roots contain significant concentrations of phenolic acids, including caffeoylquinic, caffeic, caffeoyl-feruloyl quinic, and p-coumaric acids, as well as certain flavonoids, such as diosmin, diosmetin, and jaceosidin, and coumarins, such as scopoletin and umbelliferone. Moreover, polysaccharides prepared from both studied cultivars were analyzed using GC-MS. Further biological analysis demonstrated that all the tested extracts possessed immunostimulant properties by elevating the level of WBCs, IL-2, TNF, and IFN-γ in the immunosuppressed mice relative to the control group with the highest values in polysaccharide fractions of A195 (the ethanolic extract showed a higher effect on TNF and IFN-γ, while its polysaccharide fraction exhibited a promising effect on IL-2 and WBCs). In conclusion, the roots of the Egyptian sweet potato cultivars Abees and A 195 demonstrated significant immunostimulant activities, which warrants further investigation through clinical studies.

The role of dietitian follow-ups on nutritional outcomes post-bariatric surgery.

BACKGROUND: Current evidence recommends dietary counselling with a registered dietitian (RD) for successful weight loss after metabolic bariatric surgery; however, there are limited data on the effect of RD follow-ups on micronutrient deficiencies. This study evaluated the effects of the number of postoperative RD visits on nutritional outcomes, including weight loss and micronutrient deficiencies. OBJECTIVES: The aim of this study was to evaluate the effects of the number of postoperative registered dietitian visits on nutritional outcomes, including weight loss and micronutrient deficiencies after metabolic and bariatric surgery. SETTING: Cleveland Clinic Abu Dhabi, United Arab Emirates METHODS: This retrospective study included patients who underwent bariatric surgery between September 2015 and June 2020. Demographics, weight loss, micronutrients, and the number of postoperative RD visits were evaluated. Baseline and 12-month postsurgery outcomes were compared based on the number of RD follow-ups. RESULTS: A total of 174 primary and 46 revisions were included. Patients were 73.6% female, with a mean age of 40 years. The initial mean body mass index was 42.8 kg/m2. Number of RD visits were as follows: 0-1 (39 patients), 2 (59 patients), 3 (55 patients), and 4 or more (67 patients). Baseline (pre-operative) micronutrient values were within normal range. In comparison with the reference group (REF = 0-1 post-op RD visits), patients with 3 RD visits had 7% higher total body weight loss (P < .001) and maintained micronutrients within the normal range at 12 months postoperative. Mean differences in postoperative values were statistically significant (P < .05) for weight, vitamin B12, and vitamin D but not for hemoglobin, ferritin, calcium, folate, vitamin B1, copper, and zinc. CONCLUSION: Our study suggests that three or more RD visits during the first 12 months after bariatric surgery are associated with improved outcomes, including significant percent total body weight loss and lower rates of micronutrient deficiencies.

The HACE1 E3 ligase mediates RAC1-dependent control of mTOR signaling complexes.

HACE1 is a HECT family E3 ubiquitin-protein ligase with broad but incompletely understood tumor suppressor activity. Here, we report a previously unrecognized link between HACE1 and signaling complexes containing mammalian target of rapamycin (mTOR). HACE1 blocks mTORC1 and mTORC2 activities by reducing mTOR stability in an E3 ligase-dependent manner. Mechanistically, HACE1 binds to and ubiquitylates Ras-related C3 botulinum toxin substrate 1 (RAC1) when RAC1 is associated with mTOR complexes, including at focal adhesions, leading to proteasomal degradation of RAC1. This in turn decreases the stability of mTOR to reduce mTORC1 and mTORC2 activity. HACE1 deficient cells show enhanced mTORC1/2 activity, which is reversed by chemical or genetic RAC1 inactivation but not in cells expressing the HACE1-insensitive mutant, RAC1K147R . In vivo, Rac1 deletion reverses enhanced mTOR expression in KRasG12D -driven lung tumors of Hace1-/- mice. HACE1 co-localizes with mTOR and RAC1, resulting in RAC1-dependent loss of mTOR protein stability. Together, our data demonstrate that HACE1 destabilizes mTOR by targeting RAC1 within mTOR-associated complexes, revealing a unique ubiquitin-dependent process to control the activity of mTOR signaling complexes.

Prevalence of Depressive Symptoms Among an Undergraduate Health Sciences Student Population: A Cross-Sectional Study.

PURPOSE: Undergraduate health sciences students are irrefutably liable to intrapersonal tension that may provoke the almost imperceptible onset and incremental expansion of depressive symptoms. Mental health is often a deplorably neglected topic despite posing as a catalyst in many students' academic demise. Thus, the primary objective of this paper is to provide an insight into a multitude of variables that foster depressive symptoms. In doing so, the scope of subclinical depression that could be hindering a student's academic performance shall be illuminated. METHODOLOGY: A cross-sectional study was conducted among health sciences students comprising both genders, any nationality, students 18 years of age or older, and students within their first three years of undergraduate study. The well-established Patient Health Questionnaire-9 was distributed along with a non-standardized questionnaire that inquires about additional risk factors. The chi-square test method was used to associate the dependent and independent variables, and statistical significance was done at p-value ≤ 0.05. FINDINGS: It was observed that 34.8% of participants suffer depressive symptoms. Participants' sex and marital status, among many other factors, like age, program and year of study, are found to be statistically insignificant. Conversely, nationality, university-related workload, smoking, alcohol intake and more are noted to be significantly associated with the development of depressive symptoms. ORIGINALITY: This study is an original work done by the authors to investigate the prevalence of depressive symptoms among undergraduate health sciences students. The non-standardized questionnaire employed has been reviewed to ensure that it is without discrimination of any gender or biased towards any stakeholders.

Investigation of the phytochemical composition, antioxidant, antibacterial, anti-osteoarthritis, and wound healing activities of selected vegetable waste.

Agri-food wastes, produced following industrial food processing, are mostly discarded, leading to environmental hazards and losing the nutritional and medicinal values associated with their bioactive constituents. In this study, we performed a comprehensive analytical and biological evaluation of selected vegetable by-products (potato, onion, and garlic peels). The phytochemical analysis included UHPLC-ESI-qTOF-MS/MS in combination with molecular networking and determination of the total flavonoid and phenolic contents. Further, the antimicrobial, anti-osteoarthritis and wound healing potentials were also evaluated. In total, 47 compounds were identified, belonging to phenolic acids, flavonoids, saponins, and alkaloids as representative chemical classes. Onion peel extract (OPE) showed the higher polyphenolic contents, the promising antioxidant activity, the potential anti-osteoarthritis activity, and promising antimicrobial activity, especially against methicillin-resistant Staphylococcus aureus (MRSA). Furthermore, OPE revealed to have promising in vivo wound healing activity, restoring tissue physiology and integrity, mainly through the activation of AP-1 signaling pathway. Lastly, when OPE was loaded with nanocapsule based hydrogel, the nano-formulation revealed enhanced cellular viability. The affinities of the OPE major metabolites were evaluated against both p65 and ATF-2 targets using two different molecular docking processes revealing quercetin-3,4'-O-diglucoside, alliospiroside C, and alliospiroside D as the most promising entities with superior binding scores. These results demonstrate that vegetable by-products, particularly, those derived from onion peels can be incorporated as natural by-product for future evaluation against wounds and osteoarthritis.

Pulmonary exacerbations in insured patients with bronchiectasis over 2†years.

Background: Patients with bronchiectasis experience persistent symptoms and frequent pulmonary exacerbations; this study investigated the frequency of exacerbations and all-cause hospitalisation. Methods: This longitudinal, retrospective, claims database study (IBM® MarketScan®) identified patients aged ≥18 years from 1 July 2015 through 30 September 2018. Exacerbations were identified by bronchiectasis inpatient claim or a healthcare interaction, followed by antibiotic prescription within 7 days. Patients with ≥36 months of continuous health plan enrolment (12 months preceding the first bronchiectasis claim, i.e., baseline period and ≥24 months of follow-up) were included. Patients with cystic fibrosis at baseline were excluded. A multivariable logistic regression model identified baseline factors associated with having ≥2 exacerbations over the 2-year follow-up period. Results: In total, 14 798 patients with bronchiectasis were identified; 64.5% were female, 82.7% were aged ≥55 years and 42.7% had ≥2 exacerbations at baseline. Having ≥2 exacerbations after 2 years was positively associated with chronic macrolide use, long-acting ß2 agonist use, gastro-oesophageal reflux disease, heart failure and Pseudomonas aeruginosa. Frequent exacerbations (≥2) at baseline were significantly associated with greater likelihood of experiencing ≥2 exacerbations during the first and second year's follow-up (unadjusted odds ratios 3.35 (95% CI 3.1-3.6) and 2.96 (95% CI 2.8-3.2), respectively). The proportion of patients experiencing ≥1 all-cause hospitalisation cumulatively increased from 41.0% in the first year of follow-up to 51.1% over 2 years' follow-up. Conclusion: Frequent exacerbations in patients with bronchiectasis may increase the likelihood of future exacerbations over 2 years of follow-up, with increased hospitalisation rates over time.

Identifying potentially undiagnosed nontuberculous mycobacterial lung disease among patients with chronic obstructive pulmonary disease: Development of a predictive algorithm using claims data.

BACKGROUND: Nontuberculous mycobacterial lung disease (NTMLD) is a debilitating disease. Chronic obstructive pulmonary disease (COPD) is the leading comorbidity associated with NTMLD in the United States. Their similarities in symptoms and overlapping radiological findings may delay NTMLD diagnosis in patients with COPD. OBJECTIVE: To develop a predictive model that identifies potentially undiagnosed NTMLD among patients with COPD. METHODS: This retrospective cohort study developed a predictive model of NTMLD using US Medicare beneficiary claims data (2006 - 2017). Patients with COPD with NTMLD were matched 1:3 to patients with COPD without NTMLD by age, sex, and year of COPD diagnosis. The predictive model was developed using logistic regression modeling risk factors such as pulmonary symptoms, comorbidities, and health care resource utilization. The final model was based on model fit statistics and clinical inputs. Model performance was evaluated for both discrimination and generalizability with c-statistics and receiver operating characteristic curves. RESULTS: There were 3,756 patients with COPD with NTMLD identified and matched to 11,268 patients with COPD without NTMLD. A higher proportion of patients with COPD with NTMLD, compared with those with COPD without NTMLD, had claims for pulmonary symptoms and conditions, including hemoptysis (12.6% vs 1.4%), cough (63.4% vs 24.7%), dyspnea (72.5% vs 38.2%), pneumonia (59.2% vs 13.4%), chronic bronchitis (40.5% vs 16.3%), emphysema, (36.7% vs 11.1%), and lung cancer (15.7% vs 3.5%). A higher proportion of patients with COPD with NTMLD had pulmonologist and infectious disease (ID) specialist visits than patients with COPD without NTMLD (≥ 1 pulmonologist visit: 81.3% vs 23.6%, respectively; ≥ 1 ID visit: 28.3% vs 4.1%, respectively, P < 0.0001). The final model consists of 10 risk factors (≥ 2 ID specialist visits; ≥ 4 pulmonologist visits; the presence of hemoptysis, cough, emphysema, pneumonia, tuberculosis, lung cancer, or idiopathic interstitial lung disease; and being underweight during a 1-year pre-NTMLD period) predicting NTMLD with high sensitivity and specificity (c-statistic, 0.9). The validation of the model on new testing data demonstrated similar discrimination and showed the model was able to predict NTMLD earlier than the receipt of the first diagnostic claim for NTMLD. CONCLUSIONS: This predictive algorithm uses a set of criteria comprising patterns of health care use, respiratory symptoms, and comorbidities to identify patients with COPD and possibly undiagnosed NTMLD with high sensitivity and specificity. It has potential application in raising timely clinical suspicion of patients with possibly undiagnosed NTMLD, thereby reducing the period of undiagnosed NTMLD. DISCLOSURES: Dr Wang and Dr Hassan are employees of Insmed, Inc. Dr Chatterjee was an employee of Insmed, Inc, at the time of this study. Dr Marras is participating in multicenter clinical trials sponsored by Insmed, Inc, has consulted for RedHill Biopharma, and has received a speaker's honorarium from AstraZeneca. Dr Allison is an employee of Statistical Horizons, LLC. This study was funded by Insmed Inc.

Benefit-risk assessment of brensocatib for treatment of non-cystic fibrosis bronchiectasis.

Brensocatib is a novel anti-inflammatory therapy in development for bronchiectasis treatment. Phase 2 WILLOW trial data demonstrate a low number needed to treat and negative number needed to harm, suggesting a favourable benefit-risk profile. https://bit.ly/3SbisW3.

Applying the syndemic framework to cancer research for effective cancer control in low- and middle-income countries.

Cancer burden is increasing rapidly globally, especially in low- and middle-income countries (LMICs), which already face a double burden of infectious diseases and other non-communicable diseases (NCDs). LMICs also struggle with poor social determinants of health, leading to cancer health disparities, such as delayed diagnoses and increased death rates due to cancer. Contextually, relevant research needs to be prioritised in these regions to ensure feasible, evidence-based healthcare planning and delivery for cancer prevention and control. A syndemic framework has been used to study the disease clustering of infectious diseases and NCDs across varied social contexts to understand how diseases interact adversely and how the wider environmental context and other socioeconomic factors contribute to poor health outcomes within specific populations. We propose using this model to study the 'syndemic of cancers' in the disadvantaged population of LMICs and suggest ways for the clear operationalisation of the syndemic framework through multidisciplinary evidence-generation models for the delivery of integrated, socially conscious interventions for effective cancer control.

Attack of the Clones: A Patient With Untreated Aplastic Anemia Presenting With Classical Paroxysmal Nocturnal Hemoglobinuria.

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired X-linked, clonal hematopoietic stem cell disease. Patients with PNH may complain of vague symptomatology that contributes to the challenge of its diagnosis. This is especially true in the clinical context of a coinciding hematologic disorder. Aplastic anemia (AA) is an additional immune-mediated illness that results in the destruction of hematopoietic precursors and pancytopenia. The authors encourage screening for PNH clones in patients initially diagnosed with AA, treating underlying hematologic disease to prevent clonal expansion, and further research to investigate the effectiveness of eculizumab in an unusual "classical" PNH secondary to AA with hypercellular bone marrow.

Cognitive functioning in women with breast cancer: psychometric properties of the Arabic version of the Functional Assessment of Cancer Therapy-Cognitive Function Tool.

BACKGROUND: The Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog) evaluates perceived cognitive functioning and their impact on quality of life. This study was designed to evaluate the factors associated with cognitive functioning in a sample of women with breast cancer (BC) in Lebanon. We also sought to explore the psychometric properties of the FACT-Cog Arabic version. METHODS: A cross-sectional study was carried out between March and August 2020 among women with BC. Socio-demographic and clinical characteristics were collected. In addition, patients were asked to complete the FACT-Cog Arabic version as well as the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire 30, the Patient Health Questionnaire (PHQ-9), and the Generalized Anxiety Disorder (GAD-7). The internal consistency of the FACT-Cog tool was evaluated using Cronbach's alpha. Content, convergent, and known group validity of the FACT-Cog Arabic version were also evaluated. All statistical analyses were performed using SPSS version 23.0. RESULTS: A sample of 134 women with BC was collected. Internal consistencies of the FACT-cog total scale and its subscales were high (Cronbach's α between 0.83 and 0.95). The convergent validity of the FACT-Cog Arabic version was supported by the positive correlation with the EORTC-cognitive functioning subscale. Moreover, negative correlations were found between FACT-Cog scale and fatigue, pain, anxiety, as well as depression. Known-group validity was supported by the statistically significant mean differences of the FACT-Cog total scale between patients in early (I &II) and late (III & IV) BC stages. Unmarried BC patients as well as those having higher depressive symptoms and a lower quality of life were found to be at higher risk of cognitive impairment. CONCLUSION: The FACT-Cog Lebanese Arabic version is a valid and reliable tool for assessing perceived cognitive functioning in BC women. Higher level of depression and impaired quality of life were associated with a decline in cognitive functioning.

Brazilian Butt Lift Gone Wrong: A Case Series of Non-Tuberculous Mycobacterial Gluteal Infection After Brazilian Butt Lifts.

Cosmetic surgeries are very popular and glamorized by the mainstream media and celebrities. Many individuals perceive certain bodily features as appealing for physical attraction and will attempt to obtain these features by surgery. However, these surgeries are not without risk, and significant consequences can occur if not performed by qualified medical professionals under sterile procedures. The authors present novel cases of two healthy young female patients who underwent a Brazilian butt lift (BBL) procedure a week apart by the same plastic surgeon in Mexico and developed dark painful lesions secondary to Mycobacterium abscessus (M. abscessus), a multidrug-resistant non-tuberculous mycobacterium (NTM). The literature review shows a paucity of data concerning NTM infections via surgical procedures of this type. The first case was of a 31-year-old woman who underwent a BBL and presented with bilateral dark painful buttock lesions weeks later. The patient returned to the plastic surgeon, who drained some lesions and prescribed oral antibiotics. The patient's clinical status continued to deteriorate and presented to the hospital for further assessment. The patient was initially started on broad-spectrum antibiotic therapy. The patient was found to have an HIV infection with a relatively preserved CD4 lymphocyte count and was started on antiretroviral therapy (ART). Intraoperative excisional tissue sample cultures grew M. abscessus. The patient was started on empiric tigecycline, cefoxitin, and linezolid. Preliminary culture susceptibilities showed resistance to linezolid. Linezolid was discontinued, amikacin was started, and cefoxitin and tigecycline were continued. Tigecycline, cefoxitin, and amikacin were continued and final susceptibilities showed sensitivity to the current treatment. The patient received a total of four months of treatment with tigecycline, cefoxitin, and amikacin. The second case was of a 28-year-old woman who underwent a BBL a week after the first patient by the same surgeon and developed multiple gluteal and body abscesses. The patient underwent bilateral thigh and gluteal, right chest wall, and breast surgical debridements with intraoperative cultures at a different hospital facility, which grew M. abscessus. Susceptibilities were not performed there. The patient was transferred to our facility for further care. Intraoperative cultures remained negative, and the patient was treated with a six-month course of tigecycline, cefoxitin, and amikacin.

Undifferentiated Pleomorphic Sarcoma Presenting With Cardiac Tamponade: A Case Report and Review.

Soft tissue sarcomas (STS) comprise a large group of heterogeneous malignant tumors that form approximately 1% of all adult malignancies. Most sarcomas originate from soft tissue and the rest arise from the bone. Undifferentiated pleomorphic sarcoma (UPS) is an aggressive tumor that usually presents as an asymptomatic subcutaneous mass that exhibits rapid growth with unremarkable skin findings. The diagnosis is usually made with histopathology or immunohistochemistry; once the diagnosis is confirmed, evaluation and workup of the primary tumor, lymph nodes, and metastasis should be made. Treatment is stage-dependent but generally involves en-bloc resection followed by a review of pathology with a discussion of the benefits of adjuvant radiation or chemotherapy. Here, we discuss a case of a 77-year-old patient who presented with a large mass over the right shoulder and echocardiographic findings of cardiac tamponade.

Improvement in Primary Autoimmune Myelofibrosis Following a Short Course of Steroids and Intravenous Immunoglobulins.

Bone marrow fibrosis (BMF) is a histopathological finding appreciated in a multitude of conditions such as myeloproliferative diseases and malignant neoplasms, along with autoimmune disorders. Autoimmune myelofibrosis (AIMF) is a particularly uncommon etiology of benign BMF. AIMF may be primary with serologic evidence of autoantibodies or secondary to an underlying autoimmune disease. The authors aim to emphasize the importance of distinguishing between primary versus secondary causes owing to significant prognostic and therapeutic discrepancies and in hopes of expediting the diagnostic journey. Research has recommended a treatment strategy of high-dose steroids followed by a steroid taper. However, our patient responded positively to a short course of high-dose steroids and intravenous immunoglobulins (IVIG) as evidenced by an improvement in cytopenias and bone marrow fibrosis grading. This outcome warrants further research on the necessity of steroid tapers in AIMF.

Cancer research in Pakistan: Opportunities, challenges and the way forward.

Chronic disease disparities, in low and middle income countries (LMICs), need to be addressed through research to improve health equity. Most LMICs including Pakistan have a huge burden of non communicable disease (NCDs) like cancer and a high number of deaths due to cancer. National Cancer Control Programmes are recommended for countries with high cancer burden like Pakistan to ensure systematic implementation of evidence based strategies for cancer control however there is limited capacity for evidence generation through research. We describe the existing status for cancer registries and research in Pakistan and suggest a syndemic framework to prioritize contextually relevant research which can advance cancer health equity for Pakistani population.

A digital score of tumour-associated stroma infiltrating lymphocytes predicts survival in head and neck squamous cell carcinoma.

The infiltration of T-lymphocytes in the stroma and tumour is an indication of an effective immune response against the tumour, resulting in better survival. In this study, our aim was to explore the prognostic significance of tumour-associated stroma infiltrating lymphocytes (TASILs) in head and neck squamous cell carcinoma (HNSCC) through an AI-based automated method. A deep learning-based automated method was employed to segment tumour, tumour-associated stroma, and lymphocytes in digitally scanned whole slide images of HNSCC tissue slides. The spatial patterns of lymphocytes and tumour-associated stroma were digitally quantified to compute the tumour-associated stroma infiltrating lymphocytes score (TASIL-score). Finally, the prognostic significance of the TASIL-score for disease-specific and disease-free survival was investigated using the Cox proportional hazard analysis. Three different cohorts of haematoxylin and eosin (H&E)-stained tissue slides of HNSCC cases (n = 537 in total) were studied, including publicly available TCGA head and neck cancer cases. The TASIL-score carries prognostic significance (p = 0.002) for disease-specific survival of HNSCC patients. The TASIL-score also shows a better separation between low- and high-risk patients compared with the manual tumour-infiltrating lymphocytes (TILs) scoring by pathologists for both disease-specific and disease-free survival. A positive correlation of TASIL-score with molecular estimates of CD8+ T cells was also found, which is in line with existing findings. To the best of our knowledge, this is the first study to automate the quantification of TASILs from routine H&E slides of head and neck cancer. Our TASIL-score-based findings are aligned with the clinical knowledge, with the added advantages of objectivity, reproducibility, and strong prognostic value. Although we validated our method on three different cohorts (n = 537 cases in total), a comprehensive evaluation on large multicentric cohorts is required before the proposed digital score can be adopted in clinical practice. © 2021 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Immunomodulatory effect of Noni fruit and its isolates: insights into cell-mediated immune response and inhibition of LPS-induced THP-1 macrophage inflammation.

Morinda citrifolia L. is a plant of the family Rubiaceae and is known as Indian mulberry or Noni in India. It is a perennial herb native to Southeast Asia and has been used over the years as a food supplement and medicinal plant. Noni fruits are reported to possess anticancer, fungicidal, antiviral and antiarthritic effects. The objective of our study is the screening of the immunomodulatory activity of the total extract, fractions, and isolated compounds of Noni fruits to identify their bioactive compounds. To achieve our goal, an ethanol extract (EE) was prepared from Noni fruits. Fractionation and purification of the EE were accomplished. The cell-mediated immune (CMI) response in prednisolone-induced immunosuppression rats was evaluated. The toxicity of the EE, fractions and isolated compounds on the differentiated THP-1 macrophage was assessed using the MTT viability assay. Moreover, the inflammation-related immune responses in lipopolysaccharide (LPS)-induced THP-1 macrophage activation were evaluated. Fractionation of the EE gave three fractions, dichloromethane (DCMF), water (WF) and methanol (MF). Purification of DCMF yielded stigmast-7-ene-3-ol (M1), 28-hydroxy-3ß-acetoxy-9-dehydrogramisterol (M2), 3ß-acetoxy-taraxast-20(30)-ene-21-ol (M3), 22-dehydroclerosterol (M4) and 22-dehydroclerosterol-3-O-ß-d-glucopyranoside (M5), while purification of MF yielded quercetin (M6), hesperidin (M7), naringin (M9) and gallic acid (M8). The results revealed that DCMF elicited an increase in paw edema to the extent of 35.8%. All the tested samples had no cytotoxic effect on THP-1 macrophages. Co-treatment of the LPS-induced macrophages with DCMF, M2, M3, and M6 decreased the production of TNF-α, IL-1ß, and IL-6/IL-10. The expression of iNOS, COX-2, and NF-κB decreased to 0.14 ± 0.02, 0.15 ± 0.02, and 0.17 ± 0.03, respectively, after co-treatment with LPS and DCMF. M2 attenuated the expression of iNOS and NF-κB to 0.18 ± 0.03 and 0.17 ± 0.03, respectively. Additionally, M3 attenuated the expression of iNOS to 0.18 ± 0.03, and after co-treatment with M6 and LPS, the expression of COX-2 and NF-κB was down-regulated to 0.2 ± 0.03. Our study proves the immunomodulatory effect of Noni fruits and specifies for the first time the compounds responsible for their activity.

Biodegradation of aflatoxin by bacterial species isolated from poultry farms.

Aflatoxins are carcinogenic compounds produced by certain Aspergillus spp and naturally contaminate poultry rations. Exposure to low levels of Aflatoxin B1 (AFB1) in poultry feeds is the second most threatening issue facing the poultry industry in Egypt; it can cause a reduction in growth, egg production, and compromised immune functions, resulting in significant economic loss. Hence, a safe, effective and eco-friendly detoxification method is strongly required. Biological decontamination is a promising approach to reduce aflatoxin levels within threshold limits. This study explores the biodegradation capacity of bacteria isolated from the moldy feed, soil and poultry feces in various poultry farms against AFB1 (100 ppb), G1 (100 ppb), B2 (30 ppb), G2 (30 ppb). Sixty-five bacterial isolates were initially screened using coumarin media with a concentration of (0.01%-0.5%) coumarin. Only one soil isolate (SZ1) grew at the highest concentration (0.5%). Coumarin and Aflatoxin degradation rates of ten promising isolates were measured using spectrophotometry and HPLC. Six isolates reduced AFG1 by more than 90% in the liquid medium, five reduced AFB2 while only four did the same with AFB1& AFG2. Impressively, isolate SZ1 (identified as Pseudomonas fluorescens) exhibited the best degradation capacity to both coumarin and aflatoxin with 100% degradation of AFG1 and 99% degradation of AFB1, AFB2 and AFG2. Biochemical and molecular identification of the ten isolates revealed that they belong to four genera; Bacillus (6), Pseudomonas (2), Enterococcus (1) and Stenotrophomonas (1). Factors affecting Pseudomonas fluorescens SZ1 degradation activity was further investigated. Optimum temperature, time and pH for maximum aflatoxin degradation were at 37 °C, 72 h and 7, respectively. Treatment with proteinase K reduced the degradation activity of G1 (31% ± 1.438), B1 (42% ± 1.438), G2 (19% ± 1.097), and B2 (25% ± 1.732), suggesting that the effective component in aflatoxin degradation may be protein in nature. Our study suggests the biocontrol potential of several different species isolated from poultry farms; B. haynesii, B. licheniformis, B. tequilensis, B. subtilis, B. amyloliquefaciens, Pseudomonas fluorescens, Enterococcus casseliflavus, and Stenotrophomonas maltophilia. The results proposed Pseudomonas fluorescens SZ1 as an excellent candidate for bioremediation and decontamination of aflatoxin in feed matrices. To the best of our knowledge, this is the first report identifying B. haynesii, Enterococcus casseliflavus, B. tequilensis and B. amyloliquefaciens with aflatoxin degradation activity.

Repurposed Antiviral Drugs for Covid-19 - Interim WHO Solidarity Trial Results.

BACKGROUND: World Health Organization expert groups recommended mortality trials of four repurposed antiviral drugs - remdesivir, hydroxychloroquine, lopinavir, and interferon beta-1a - in patients hospitalized with coronavirus disease 2019 (Covid-19). METHODS: We randomly assigned inpatients with Covid-19 equally between one of the trial drug regimens that was locally available and open control (up to five options, four active and the local standard of care). The intention-to-treat primary analyses examined in-hospital mortality in the four pairwise comparisons of each trial drug and its control (drug available but patient assigned to the same care without that drug). Rate ratios for death were calculated with stratification according to age and status regarding mechanical ventilation at trial entry. RESULTS: At 405 hospitals in 30 countries, 11,330 adults underwent randomization; 2750 were assigned to receive remdesivir, 954 to hydroxychloroquine, 1411 to lopinavir (without interferon), 2063 to interferon (including 651 to interferon plus lopinavir), and 4088 to no trial drug. Adherence was 94 to 96% midway through treatment, with 2 to 6% crossover. In total, 1253 deaths were reported (median day of death, day 8; interquartile range, 4 to 14). The Kaplan-Meier 28-day mortality was 11.8% (39.0% if the patient was already receiving ventilation at randomization and 9.5% otherwise). Death occurred in 301 of 2743 patients receiving remdesivir and in 303 of 2708 receiving its control (rate ratio, 0.95; 95% confidence interval [CI], 0.81 to 1.11; P = 0.50), in 104 of 947 patients receiving hydroxychloroquine and in 84 of 906 receiving its control (rate ratio, 1.19; 95% CI, 0.89 to 1.59; P = 0.23), in 148 of 1399 patients receiving lopinavir and in 146 of 1372 receiving its control (rate ratio, 1.00; 95% CI, 0.79 to 1.25; P = 0.97), and in 243 of 2050 patients receiving interferon and in 216 of 2050 receiving its control (rate ratio, 1.16; 95% CI, 0.96 to 1.39; P = 0.11). No drug definitely reduced mortality, overall or in any subgroup, or reduced initiation of ventilation or hospitalization duration. CONCLUSIONS: These remdesivir, hydroxychloroquine, lopinavir, and interferon regimens had little or no effect on hospitalized patients with Covid-19, as indicated by overall mortality, initiation of ventilation, and duration of hospital stay. (Funded by the World Health Organization; ISRCTN Registry number, ISRCTN83971151; ClinicalTrials.gov number, NCT04315948.).