Gastroprotective effects and metabolomic profiling of Chasteberry fruits against indomethacin-induced gastric injury in rats

Vitex agnus castus L. extract (VACE) was investigated for its gastroprotective properties and possible molecular mechanisms in rats. VACE (60 or 120 mg/kg) or Esomeprazole (20 mg/kg) were orally administered for 3 weeks before the induction of gastropathy using indomethacin (30 mg/kg, single oral dose). VACE ameliorated the indomethacin-induced gastric juice acidity and pathological changes. VACE significantly preserved GSH, SOD, NO and PGE2 contents, while decreased lipid-peroxide, TNF-α and MPO contents. Moreover, VACE downregulated NF-κB1, COX-2, Caspase-3 and upregulated Bcl-2 and HSP-70 expression. Ultra-high-performance liquid chromatography (UPLC) coupled with quadrupole high-resolution time of flight mass spectrometry (qTOF-MS) enabled the tentative identification of 87 compounds allocated in seven main classes including flavonoids, glycosylated iridoid and labdane diterpenes. Notably, different agnuside derivatives and diterpenoids were reported in VACE for the first time. In conclusion, VACE contains an arsenal of bioactive metabolites which may exhibit gastroprotection by inhibiting inflammation, oxidative stress, and apoptosis

Novel Sequence Variants in the NPC1 Gene in Egyptian Patients with Niemann-Pick Type C

BACKGROUND: Niemann-Pick disease type C (NPC) is a rare, autosomal recessive, progressive neuro-visceraldisease caused by biallelic mutations in either NPC1gene (95% of cases) or NPC2 gene. AIM: This caseseries study aimed at the molecular analysis of certain hot spots of NPC1 genein NPC Egyptian patients. METHODS: The study included 15 unrelated NPC patients and selected parents,as well as20 healthy controls of matched sex and age. Clinical investigations were performed according to well established clinical criteria. Assessment of the chitotriosidase level, as an initial screening tool for NPC, was done in all cases. Polymerase chain reaction amplification of NPC1 exons (17–25) encountering the hotspot residues (855–1098 and1038–1253) was carried out followed by direct sequencingfor mutational analysis. RESULTS: All includedpatients with mainly neurovisceral involvement were characterized. The onset of the disease varied from early-infantile (58.3%) to late-infantile (26.7%) and juvenile-onset (6.7%). Ahigh chitotriosidase level wasobservedin all patients. Molecular analysis of NPC1 (exons 17–25) confirmed 15 mutant alleles out of 30 studied ones. They included two novel homozygous missense variants (p.Ser1169Arg and p.Ser1197Phe) and previously reportedfour mutations (p.Arg958*, p.Gly910Ser, p.Ala927Glyfs*38, and andp.Cys1011*). CONCLUSION: The two studied amino acid residues (855–1098 and 1038–1253) could beconsidered aspotential hotspot regions in NPC1 Egyptian patients

Post-Thoracotomy Pain: Review Article

Background: Thoracotomy is a very painful surgical procedure that is used to get access into the pleural space, to the lungs, to the heart, to the esophagus or to get access to the thoracic aorta or anterior mediastinum. Objective: To study different modalities of treatment used for post thoracotomy pain control. Recent Findings: Inadequate post-thoracotomy analgesia enhances the postoperative stress response with deleterious effects on respiratory, cardiovascular, gastrointestinal, urinary, immune and coagulation systems. In addition to anxiety and increased risk of Post Thoracotomy Pain Syndrome (PTPS), which can interfere with normal life and may persist for years or even for life?Conclusion: Providing adequate post-thoracotomy analgesia can be challenging, as patients are often elderly or having multiple comorbidities. A multimodal approach is considered in managing post-thoracotomy pain starting with preemptive analgesia and cognitive behavioral modalities in addition to conventional multimodal systemic regimens as opioids, acetaminophen, NSAID, cyclooxygenase (COX)-2-specific inhibitors, gabapentin and pregabalin, steroids, IV lidocaine infusion, ketamine, and many regional analgesic modalities to avoid or decrease adverse effects of systemic regimens. These regional analgesic modalities include thoracic epidural blocks, thoracic paravertebral blocks, intrathecal opioid analgesia, serratus anterior plane blocks, intercostal nerve blocks, interscalene block, erector spinae block and interpleural block

Modulation of steroidogenesis by Actaea racemosa and vitamin C combination, in letrozole induced polycystic ovarian syndrome rat model : promising activity without the risk of hepatic adverse effect

Background: Complementary remedies such as the Chinese herb 'Sheng Ma' (Black cohosh; Actaea racemosa 'AR') are being sought to overcome the shortcomings of conventional hormonal and surgical therapies developed for the treatment of polycystic ovary syndrome (PCOS). However, AR-induced hepatotoxicity necessitates a cautionary warning to be labeled on its products as recommended by the United States Pharmacopeia, where four out of seven hepatotoxic cases in Sweden were possibly associated with black cohosh products. Methods: We investigated the effects, safety, and molecular targets of black cohosh ethanolic extract and/or vitamin C on ovarian functionality and oxidative response in hyperandrogenism-induced PCOS rats. A well-established rat model using oral letrozole, daily, for 21 days was employed. The rats then received the AR extract with and without vitamin C for 28 days. The hormonal evaluation, antioxidant status, histopathological examination, immunohistochemical analysis, cell proliferation, and the expression ratio of the aromatase (Cyp19α1) gene were evaluated. Additionally, holistic profiling of the AR arsenal of secondary metabolites was performed using ultra-high-performance liquid chromatography (UHPLC) coupled with quadrupole high-resolution time of flight mass spectrometry (QTOF-MS). Results: Beneficial effects were exerted by AR in PCOS rats as antioxidant status, hormonal profile, lipid profile, glucose level, liver functions, and the induced Ki-67 expression in the granulosa, theca cell layers and interstitial stromal cells were all improved. Notably, the combination of AR with vitamin C was not only more effective in reversing the dysregulated levels of testosterone, luteinizing hormone, and mRNA level of Cyp19α1 gene in the PCOS rat, but also safer. The combination regulated both ovarian and hepatic malondialdehyde (MDA) and glutathione (GSH) levels with histological improvement observed in the liver and ovaries. In addition, the untargeted metabolomic profiling enabled the identification of 61 metabolites allocated in five major chemical classes. Conclusion: This study demonstrated the benefit of the combinatorial effects of AR and vitamin C in mitigating the reproductive and metabolic disorders associated with PCOS with the elimination of AR hepatotoxic risk

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

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 < 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

Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication

Activating Transcription Factor 1 (ATF1) Immunohistochemical Marker Distinguishes HCCC from MEC

The study aimed to compare 15 cases of mucoepidermoid carcinoma (MEC) and 15 cases of hyalinizing clear cell carcinoma (HCCC) using immunohistochemical staining and molecular analysis. Thirty samples were examined, and markers, including p63, CK5/6, SOX10, CK7, ATF1, and FISH probes specific to EWSR1 and MAML2, were used. Clear cell differentiation was observed in all MEC cases to some extent, with clear cell MEC showing the most prominent findings. Clear cell features were also present in conventional MEC, oncocytic MEC, and Warthin-like MEC, although to a lesser extent. The majority of cases were classified as low-grade MECs. MAML2 rearrangement was detected in all cases (except cases 11 and 14), while EWSR1 rearrangement was observed in a single case of clear cell MEC. These findings helped identify distinct subtypes within the mucoepidermoid carcinoma spectrum. The study emphasized the importance of utilizing immunohistochemical profiles, histopathological features, and molecular analysis for accurate diagnosis and classification of salivary gland neoplasms. HCCC was also discussed, and ATF1 was proposed as a marker to distinguish HCCC from morphologically similar neoplasms. The study concluded that a comprehensive approach combining immunohistochemistry, histopathology, and clinical correlation is essential for accurate diagnosis and classification, considering the variable expression of markers and potential overlap with other tumor types

Immunomodulatory Role of Dietary Thyme against Saprolegnia parasitica Infection in Cultured Nile tilapia (Oreochromis niloticus)

The fish industry has grown considerably worldwide, and fungal infections represent a significant aspect that increases economic losses and challenges through high mortality rates. The Egyptian aquaculture industry is particularly vulnerable to Saprolegnia parasitica, a deadly fish pathogen. Using phytobiotics as immunomodulators, antioxidants, and health promoters in aquaculture have been proven recently as an alternative strategy for banned malachite green. This research aimed to examine the thyme effect (Thymus vulgaris) on the immune status of cultured Nile tilapia against Saprolegniasis. A total of 50 fish (Oreochromis niloticus) with skin lesions were gathered from a private fish farm in Alexandria, Egypt. Skin swabs, gill swabs, and muscle tissue were obtained from each fish. After the mycological examination, results revealed that 35 isolates out of 150 examined samples (23.33%) were positive for fungal growth, of which 15 (10%) isolates were identified as Saprolegnia species. In addition, other fungi were detected; 5 (3.33%), 8 (5.33%), 4 (2.67%), and 3 (2%) isolates were identified as Penicillium species, Aspergillus flavus, Alternaria species, and Fusarium species, respectively. To evaluate the immunomodulatory effect of thyme, 300 healthy Nile tilapia fish with a mean weight of 30 ± 5 gm were brought to be experimentally designed; they were distributed into four groups (with three replicates) and were fed on an experimental diet including 0.0, 0.5, 1.0, and 1.5 thyme oil (gm/100gm diet) continuously for two months. Then fish were infected with S. parasitica zoospores, which were thoroughly mixed with their diet. According to results, after two months of feeding, catalase (CAT), serum lysozyme activity, and total protein dramatically increased according to the levels of thyme added; the acquisition was for the group fed on a 1.5 gm/100gm diet. Additionally, the expression of interleukin-10 (IL-10) and interleukin-1β (IL-1β) in liver tissues increased similarly. Hence, it is concluded that employing thyme would improve the well-being and yield of the farmed Nile tilapia