Assessment of the Immune Status and DNA Damage in Goats with Experimentally-Induced Hypocuprosis

Abstract This study was carried out on 16 adult castrated male Baladi goats with age ranged from 1-1.5 years old and weight range of 19±0.82 kg to investigate the biological role of copper deficiency on the modification of immune status and induction of DNA damage. They were randomized into two groups. The first group (six goats) were apparently healthy and kept as control group, whereas the second group (ten goats) were subjected to experimental induction of secondary copper deficiency by dietary addition of Molybdenum ( MO; 10-40 mg/kg DM) and Sulpher (S; 1.5-3 g / Kg dry matter) daily for 24 weeks. Blood samples were collected without anti-coagulant every six weeks for determination of serum copper and ceruloplasmin activity. Heparinized blood samples were used for assessment of immune status, DNA damage and erythrocyte superoxide dismutase (SOD). Results showed significant decrease (P<0.05) in serum copper, ceruloplasmin and erythrocyte SOD activity starting from 6 weeks to 24 weeks after addition of Mo and S. Goats with experimentally-induced copper deficiency have low serum neutralization antibody index (0.5±0.1) against inactivated rift valley fever vaccine which did not reach the protective antibody level (1.7) compared to that of the apparently healthy control group (1.81 ±0.05) which exceeded the protective value. Lymphocyte blastogenesis response of copper deficient goats was decreased although non significantly in comparison with the apparently healthy control group. The results also showed that copper deficiency caused marked increase in the % of DNA fragmentation of blood cells in goats with experimentally-induced copper deficiency compared to the apparently healthy control group. Goats with experimentally-induced copper deficiency have DNA fragmentation as detected by gel electrophoresis and the DNA ladder represented a series of fragments that is multiples of 180-200 bp. Our findings suggest a significant role of copper deficiency in modulation of immune status and induction of DNA damage and cell apoptosis in goats. Hence, copper level should be strictly considered during formulation of rations in farm animal production practice

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

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

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Wiedza, postawa i zasady postępowania pielęgniarek wobec chorych na padaczkę

Background: This work handled three aspects: to assess the nurses’ knowledge and practice with regard to patients with epilepsy, to study the outcome of training of nurses regarding epilepsy. Material and methods: The study conducted at the Department of Neurology at Assiut University Hospital. Data collected from all nurses (n = 35) working at the Department of Neurology. The following tools were used for data collection; a pre-/post-test questionnaire sheet for the assessment of the nurses’ knowledge of epilepsy, an observation checklist sheet for nurses, and the patient’s assessment sheet to assess the nurses’ practice. The work involved nine sessions, each about 30 minutes long, applied to teach nurses about all data necessary for the patients with epilepsy. Results: A good improvement in the mean knowledge and practice scores observed following the implementation of the designed nursing protocol. A significant decrease in complication rate which resulted from bad practice during fit following the implementation of the designed nursing protocol. A reduction in seizure-related complications reported after the training of nurses with the designed nursing protocol which acts as an additional advantage. Conclusion: Improving the nurses’ knowledge and practice with regard to patients with epilepsy will lead to the improvement the health and social conditions of patients with epilepsy.Wprowadzenie: Autorzy opracowania przeanalizowali stan wiedzy i praktykę pielęgniarek w odniesieniu do pacjentów z padaczką, a także wyniki odbytego przez pielęgniarki szkolenia na temat padaczki. Materiał i metody: Badanie przeprowadzono na Oddziale Neurologii Szpitala Uniwersyteckiego w Assiut. Dane zebrano od wszystkich pielęgniarek (n = 35) pracujących na oddziale. Do zbierania danych wykorzystano następujące narzędzia: kwestionariusz przed i po wprowadzeniu programu edukacyjnego służący do oceny stanu wiedzy pielęgniarek na temat padaczki, listę obserwacyjną dla pielęgniarek, formularz oceny stanu pacjenta w celu oceny praktyki pielęgniarek. Szkolenie przeprowadzono w dziewięciu 30-minutowych sesjach, w trakcie których pielęgniarki uzyskały wszelkie informacje potrzebne do opieki nad chorymi z padaczką. Wyniki: Zaobserwowano wyraźną poprawę średniej stanu wiedzy i wyników praktyki pielęgniarskiej po wdrożeniu programu opieki pielęgniarskiej, jak również znaczny spadek liczby powikłań spowodowanych nieprawidłowym postępowaniem z pacjentem podczas napadów padaczkowych. Ponadto stwierdzono zmniejszenie liczby zgłaszanych powikłań ponapadowych po wdrożeniu programu opieki pielęgniarskiej, co stanowi dodatkową jego zaletę. Wnioski: Poprawa stanu wiedzy oraz praktyki pielęgniarek w odniesieniu do chorych na padaczkę doprowadzi do poprawy stanu zdrowia i warunków życia osób z padaczką

Autophagy in antitumor activity of aloin for breast cancer cells compared with doxorubicin

252-264Breast cancer is the most commonly diagnosed cancer and is one of the leading causes of cancer mortality in women worldwide. Natural product compounds have attracted significant attention for their potent effects against human cancers. Aloin, a natural phytochemical anthraquinone glycoside extracted from Aloe sp., has been previously reported for its antitumor activity. Autophagy is a highly conserved process that mediates the degradation of dysfunctional cellular components, such as senescent proteins and organelles. In the present study, we verified the involvement of autophagy in tolerance to aloin, especially in breast cancer cells with negative estrogen receptors, and as an alternative pathway to promote cell death in cells expressing mutant p53 status, which often limits the efficacy and accounts for resistance to chemotherapy. We studied the effect of aloin on 2 types of breast cancer cell lines, estrogen receptor-positive (T47D) and triple negative (MDA-MB231), and compared to an anthraquinone analog, doxorubicin (Dox) as a reference compound. Aloin inhibited the cell growth of both T47D and MDA-MB231 cancer cells, in a time- and dose-dependent manner with a more pronounced effect in the 72 h exposure regimen, and in the ERα+ breast cell line. The autophagic activity of aloin was emphasized by the formation of autophagosomes and autolysophagosomes, as early and late autophagic compartments, respectively, as well as the accumulation of acidic vesicular organelles in the tumor cells. Also, upregulation in the protein expression of some marker genes of autophagy such as beclin 1 and LC3BII/LC3I, and conversely down-regulation in pmTOR and p62 was recorded. The results suggest that autophagy can be regarded as one of the mechanistic modes of aloin cytotoxicity in breast cancer cells that evade apoptosis through genetic mutations in p53

Correlations between beclin-1 and transforming growth factor-β1 in letrozole induced polycystic ovary syndrome

332-340In the pathogenesis of polycystic ovary syndrome (PCOS), despite the importance of autophagy and transforming growth factor-β1 (TGF-β1), there is scarce information about their inter-relationship. Therefore, here we assessed the correlations between beclin-1, a cornerstone in autophagy, and TGF-β1 in a letrozole-induced PCOS rat model. Accordingly, a total of 45 female adult albino Wistar rats were randomly assigned into control, vehicle (carboxymethyl cellulose), and PCO groups. To establish the PCOS model, letrozole (1.0 mg/kg body wt., p.o.) was given once daily for three successive weeks. Circulating levels of luteinizing hormone, follicle-stimulating hormone, testosterone, estradiol, and progesterone were assayed along with ovarian total antioxidant capacity (TAC), protein carbonyl content (PCC), beclin-1 level, and TGF-β1 level. Ovarian morphology and ultrastructure were examined by hematoxylin and eosin staining and electron microscopy, respectively. Compared to control groups, hormonal levels and ovarian morphology in the letrozole-exposed animals indicated the successful construction of the PCOS model. Further, the PCO group exhibited an oxidative stress status reflected by a significant decrease in ovarian TAC and a significant elevation in the PCC. Moreover, ovarian beclin-1 and TGF-β1 levels were significantly increased with an enhancement of autophagy as revealed by electron microscopy. In multiple linear regression models, only TGF-β1 was observed in the final model where it explained the 62.3% variability of Beclin-1. In conclusion, the ovarian level of TGF-β1 might be a determinant factor of beclin-1 level in PCOS which may provide new insight into the pathophysiology and therapy of the disease

Seminal parameters before and during combined antiviral (pegylated interferon α-2a and ribavirin) treatment in chronic hepatitis C virus patients in upper Egypt

Background Some reports suggest that chronic hepatitis C virus (HCV) infection and its combined antiviral therapy could alter seminal parameters, and so chronic HCV infection may influence male fertility. Aim The aim of this study was to evaluate seminal parameters before and during combined antiviral (pegylated interferon α-2a+ribavirin) treatment in chronic HCV patients. Because of the possible teratogenic effect of ribavirin, contraception is mandatory during therapy. This study was conducted on 40 male chronic HCV patients (PCR based), age 20-58 years: 30 patients were given combined therapy (group 1) and 10 were not given treatment (group 2); 10 normal controls were included (group 3). The seminal fluid (volume, concentration, motility, and morphology) was analyzed. Parameters were determined at the beginning, and in group 1, they were reassessed after 12 weeks of therapy. Results Semen abnormalities were common at baseline with further impairment during antiviral therapy in group 1: oligoasthenoteratozoospermia was detected in 15 patients, asthenozoospermia in six, and athenoteratozoospermia in six (sperm density: BL, 59.2 ± 40.7 × 106/ml; week 12, 26.7 ± 22.4 × 106/ml; progressive motility: BL, 44.5 ± 15.2%; week 12, 31.2 ± 12.5%). The proportion of sperm without motility reached its peak after 12 weeks of therapy. The percentage of abnormal forms was BL 14 ± 0.04% and week 12 16.8 ± 5.2%, with further increase during therapy. In group 2, oligoasthenoteratozoospermia was present in three patients, asthenozoospermia in three, and athenoteratozoospermia in two. The density was 46.7 ± 32.4 × 106/ml, and the progressive motility 40 ± 10.7%. The percentage of abnormal forms was 13.5 ± 1.6%. In group 3, there was no oligoasthenoteratozoospermia, one patient had asthenozoospermia, and one had athenoteratozoospermia. The density was 95.2 ± 28.7 × 106/ml, and the progressive motility 57.2 ± 18.2%. The percentage of abnormal forms was 9.5 ± 2.8%. Conclusion Semen abnormalities were common in chronic HCV patients, with further impairment during combined antiviral therapy

Probiotic-prebiotic-synbiotic modulation of (YAP1, LATS1 and NF2 mRNAs/miR-1205/lncRNA SRD5A3-AS1) panel in NASH animal model

Aim: To investigate the prophylactic efficacy of gut microbiota-based treatments on nonalcoholic steatohepatitis (NASH) management via modulation of Hippo signaling pathway-related genes (YAP1, LATS1 and NF2), and their epigenetic regulators (miR-1205 and lncRNA SRD5A3-AS1) retrieved from in-silico data analysis. Materials &amp; methods: Histopathological, biochemical, molecular and immunohistochemistry analyses were used to assess the effects of multistrain probiotic mixture and prebiotic inulin fiber on high sucrose high fat (HSHF) diet-induced NASH in rats. These treatments were administered orally either alone or in combination, along with HSHF diet. Results: Both probiotic mixture and prebiotic inulin fiber attenuated steatosis, inflammation and fibrosis grades in HSHF diet-induced NASH rats. Moreover, the applied treatments significantly prevented the elevation of serum liver enzymes and improved lipid panel. At the molecular level, both treatments down-regulated hepatic YAP1 mRNA and miR-1205 expressions, and concomitantly up-regulated the expression of hepatic LATS1& NF2 mRNAs and the lncRNA SRD5A3-AS1. At the protein level, both treatments decreased the hepatic content of the inflammatory marker IL6 and the fibrotic marker TGFβ1. Moreover, an observable reduction in α-SMA together with noticeable elevation in LATS1/2 protein expression levels were detected in liver sections compared to the untreated rats. Conclusion: Probiotic mixture and prebiotic inulin fiber, either alone or in combination, attenuated NASH progression and ameliorated both fibrosis and hepatic inflammation in the applied animal model. The produced effect was correlated with modulation of the retrieved (YAP1, LATS1 and NF2) – (miR-1205) – (lncRNA SRD5A3-AS1) RNA panel