Role of high resolution computed tomography (HRCT) of the chest in the diagnosis of lymphangioleiomyomatosis (LAM) – A serial study of 15 patients

AbstractAim of workTo highlight the characteristic high resolution computed tomography (HRCT) findings in 15 patients diagnosed with lymphangioleiomyomatosis (LAM), narrowing the wide range of ILD and allowing accurate diagnosis preventing unnecessary interventional procedures.Patients and methods15 female patients ranged in age from 17 to 55years (mean age=40.33years). ILD was suspected based on clinical examination and chest radiographs. They were referred to do HRCT chest for further assessment. A 64 MSCT scanner was used.ResultsAll patients showed bilateral multiple cysts showing upper lobar predominance in 13.3% of cases and lower lobar one in 6.7%. The size of the cysts ranged from few mms to 3cm with variable wall thickness. Pneumothorax was reported in three patients and pulmonary hypertension in 15 cases.ConclusionHRCT is a valued diagnostic tool for diagnosis of LAM showing characteristic features for the disease

Detection of Helicobacter pylori oipA and dupA genes among dyspeptic patients with chronic gastritis

Helicobacter pylori (H. pylori): is a microbe with wide genetic diversity that infects the stomach of most people in developing countries, leading to several clinical outcomes among different individuals such as gastritis, ulcers, or gastric cancer. Outer inflammatory protein A (oipA) and duodenal ulcer promoting (dupA) genes are among the possible virulence factors which determine the patient outcome. Aim: To detect oipA and dupA genes of H. pylori among dyspeptic Egyptian patients, and to investigate their correlation with the varying degrees of the associated chronic gastritis. Methods: The study enrolled 50 patients with dyspepsia, attending the Gastrointestinal Endoscopy unit of the Gastroenterology and Tropical Departments at Ain Shams University Hospital for upper gastrointestinal endoscopy, in the period between, June and, December 2019. Four antral gastric biopsies were taken from each patient for polymerase chain reaction assay to detect the virulence genes oipA, dupA, and cagA and for histopathological assessment. Results: Forty patients were H. pylori positive by histopathology and PCR. cagA, oipA, and dupA were identified in 6 (15%), 13 (32.5%), 9 (22.5%) of biopsies, respectively. Both cagA and oipA genes were highly significantly associated with increasing the severity of gastritis. Only oipA virulence gene showed a highly significant association with gastroduodenitis. There was a highly significant moderate association between cagA and oipA genes. Conclusion: oipA could be a virulence biomarker that serves a great value in predicting the progress of gastric mucosal damage in patients with chronic gastritis, and targeting antimicrobial therapy in those patients to prevent severe gastroduodenal diseases

Scaffold hopping of α-rubromycin enables direct access to FDA-approved cromoglicic acid as a SARS-CoV-2 M^Pro inhibitor

The COVID-19 pandemic is still active around the globe despite the newly introduced vaccines. Hence, finding effective medications or repurposing available ones could offer great help during this serious situation. During our anti-COVID-19 investigation of microbial natural products (MNPs), we came across α-rubromycin, an antibiotic derived from Streptomyces collinus ATCC19743, which was able to suppress the catalytic activity (IC50 = 5.4 µM and Ki = 3.22 µM) of one of the viral key enzymes (i.e., MPro). However, it showed high cytotoxicity toward normal human fibroblasts (CC50 = 16.7 µM). To reduce the cytotoxicity of this microbial metabolite, we utilized a number of in silico tools (ensemble docking, molecular dynamics simulation, binding free energy calculation) to propose a novel scaffold having the main pharmacophoric features to inhibit MPro with better drug-like properties and reduced/minimal toxicity. Nevertheless, reaching this novel scaffold synthetically is a time-consuming process, particularly at this critical time. Instead, this scaffold was used as a template to explore similar molecules among the FDA-approved medications that share its main pharmacophoric features with the aid of pharmacophore-based virtual screening software. As a result, cromoglicic acid (aka cromolyn) was found to be the best hit, which, upon in vitro MPro testing, was 4.5 times more potent (IC50 = 1.1 µM and Ki = 0.68 µM) than α-rubromycin, with minimal cytotoxicity toward normal human fibroblasts (CC50 > 100 µM). This report highlights the potential of MNPs in providing unprecedented scaffolds with a wide range of therapeutic efficacy. It also revealed the importance of cheminformatics tools in speeding up the drug discovery process, which is extremely important in such a critical situation

Mostafa Ahmed Hammamand Heba Abd Elmordy. Topical Use of Systemic Drugs in Dermatology

Abstract: Objective: Review the topical usage of systemic drugs in dermatological diseases. Data Sources: From previous Literatures, reviews and studies as well as medical websites (PubMed, MD consult, Medscape) and Scientific Journals data-bases were searched from the start date of each data-base. Study Selection: Selection was done by supervisors for studying new advancement in topical use of systemic drugs in dermatology and studies that addressed topical therapy in dermatology and systemic drugs used topically in dermatology. Data Extraction: Data from published studies were manually extracted and summarized. Study quality assessment included whether ethical approval was gained, prospective design, eligibility criteria specified, appropriate controls used, adequate follow-up achieved and defined outcome measures. Data synthesis: In this review the data found that several studies of the topical usage of systemic drugs in dermatological diseases to know which systemic drug can used topically. Findings: A total of 44 studies were included in the review as they were deemed eligible by fulfilling the inclusion criteria. Of these 44 articles, included in this review, 32 were Topical usage of systemic drugs in dermatological diseases and 12 were topical therapy. Studies indicate that some of systemic drugs can used topically in the treatment of some dermatological diseases. Conclusion: Extemporaneous compounding helps physicians to individualize treatment to the patient's specific needs and to create topical preparations that are not otherwise commercially available. However, comparative effectiveness studies are needed to determine whether or not topical use of systemic therapeutics is more beneficial than existing therapies

Natural Immunomodulators Treat the Cytokine Storm in SARS-CoV-2

Recently, the world has been dealing with a destructive global pandemic Coronavirus disease 2019 (COVID-19) infection, since 2020; there were millions of infections and hundreds of thousands of deaths worldwide. With sequencing generations of the virus, around 60% are expected to become infected during the pandemic. Unfortunately, no drug or vaccine has been approved because no real evidence from clinical trials in treatment was reached. According to current thinking, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mortality is caused by a cytokine storm syndrome in patients with hyper-inflammatory conditions, resulting in acute respiratory distress and finally death. In this review, we discuss the various types of natural immune-modulatory agents and their role in the management of SARS-CoV-2, and cytokine storm syndrome. For example, Polyphenols as natural products can block the binding of SARS-CoV-2 spike protein to host cell receptor ACE2, stop viral entry into the host cell and block viral RNA replication. Also, saikosaponins (A, B2, C, and D), triterpene glycosides, which are isolated from medicinal plants exert antiviral action against HCoV-22E9, and Houttuynia cordata water extract has antiviral effects on SARS-CoV. Moreover, eucalyptus oil has promising potential for COVID-19 prevention and treatment. There is an urgent need for research to improve the function of the human immune system all over the world. As a result, actions for better understanding and improving the human immune system are critical steps toward mitigating risks and negative outcomes. These approaches will be strongly recommended for future emerging viruses and pathogens

Reliability of Spectrum-Efficient Mixed Satellite-Underwater Systems

The combination of radio-frequency (RF) communication and underwater optical wireless communication (UOWC) plays a vital role in the underwater Internet of Things (UIoT). This correspondence proposes a dual-hop hybrid satellite underwater system that exploits non-orthogonal multiple access (NOMA) as a spectrum-efficient access technique. The RF link from the satellite to the relay on an oil platform is presumptively subject to a Shadowed-Rician (SR) fading, while the UOWC channels from the relay to the underwater destinations are suggested to follow Exponential-Generalized Gamma (EGG) distributions. The reliability of the system is characterized in terms of both underwater destinations and system outage probabilities (OPs). We derive new closed-form expressions for the OPs under imperfect successive interference cancellation (SIC) conditions. Furthermore, the asymptotic OP and the diversity order (DO) are obtained to learn more about the system’s performance. The results are verified through an extensive representative Monte-Carlo simulation. Also, we investigate the performance against the turbulence of the salty water, air bubbles level (BL), temperature gradients (TG), shadowing parameters, and satellite pointing errors due to satellite motion, even if the beam is pointed at the center of the directive antenna relay, the beam will randomly oscillate. Finally, we contrast our approach with the conventional orthogonal multiple access (OMA) scheme to demonstrate its superiority

Metabolomic profile, anti-trypanosomal potential and molecular docking studies of <i>Thunbergia grandifolia</i>

Trypanosomiasis is a protozoan disease transmitted via Trypanosoma brucei. This study aimed to examine the metabolic profile and anti-trypanosomal effect of methanol extract of Thunbergia grandifolia leaves. The liquid chromatography-high resolution electrospray ionisation mass spectrometry (LC-HRESIMS) revealed the identification of fifteen compounds of iridoid, flavonoid, lignan, phenolic acid, and alkaloid classes. The extract displayed a promising inhibitory activity against T. brucei TC 221 with MIC value of 1.90 μg/mL within 72 h. A subsequent in silico analysis of the dereplicated compounds (i.e. inverse docking, molecular dynamic simulation, and absolute binding free energy) suggested both rhodesain and farnesyl diphosphate synthase as probable targets for two compounds among those dereplicated ones in the plant extract (i.e. diphyllin and avacennone B). The absorption, distribution, metabolism, excretion, and toxicity (ADMET) profiling of diphyllin and avacennone were calculated accordingly, where both compounds showed acceptable drug-like properties. This study highlighted the antiparasitic potential of T. grandifolia leaves

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Burnout among surgeons before and during the SARS-CoV-2 pandemic: an international survey

Background: SARS-CoV-2 pandemic has had many significant impacts within the surgical realm, and surgeons have been obligated to reconsider almost every aspect of daily clinical practice. Methods: This is a cross-sectional study reported in compliance with the CHERRIES guidelines and conducted through an online platform from June 14th to July 15th, 2020. The primary outcome was the burden of burnout during the pandemic indicated by the validated Shirom-Melamed Burnout Measure. Results: Nine hundred fifty-four surgeons completed the survey. The median length of practice was 10&nbsp;years; 78.2% included were male with a median age of 37&nbsp;years old, 39.5% were consultants, 68.9% were general surgeons, and 55.7% were affiliated with an academic institution. Overall, there was a significant increase in the mean burnout score during the pandemic; longer years of practice and older age were significantly associated with less burnout. There were significant reductions in the median number of outpatient visits, operated cases, on-call hours, emergency visits, and research work, so, 48.2% of respondents felt that the training resources were insufficient. The majority (81.3%) of respondents reported that their hospitals were included in the management of COVID-19, 66.5% felt their roles had been minimized; 41% were asked to assist in non-surgical medical practices, and 37.6% of respondents were included in COVID-19 management. Conclusions: There was a significant burnout among trainees. Almost all aspects of clinical and research activities were affected with a significant reduction in the volume of research, outpatient clinic visits, surgical procedures, on-call hours, and emergency cases hindering the training. Trial registration: The study was registered on clicaltrials.gov "NCT04433286" on 16/06/2020

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P &lt; 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely