CD33+ HLA-DR– Myeloid-Derived Suppressor Cells Are Increased in Frequency in the Peripheral Blood of Type1 Diabetes Patients with Predominance of CD14+ Subset

INTRODUCTION: Type 1 Diabetes Mellitus (T1D) is an autoimmune disease that results from the destruction of insulin-producing beta cells of the pancreas by autoreactive T cells. Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of cells that can potently suppress T cell responses.AIM: To detect the presence of MDSCs in T1D and compare their percentage in T1D versus healthy individuals.METHOD: Thirty T1D patients were included in the study. Diabetic patients with nephropathy (n = 18) and diabetic patients without nephropathy (n = 12). A control group of healthy individuals (n = 30) were also included. CD33+ and HLA-DR– markers were used to identify MDSCs by flow cytometry. CD14 positive and negative MDSCs subsets were also identified.RESULTS: MDSCs was significantly increased in T1D than the control group and diabetic patient with nephropathy compared to diabetic patients without nephropathy. M-MDSCs (CD14+ CD33+ HLA–DR−) were the most abundant MDSCs subpopulation in all groups, however their percentage decrease in T1D than the control group.CONCLUSION: MDSCs are increased in the peripheral blood of T1D with a predominance of the CD14+ MDSCs subset. Future studies are needed to test the immune suppression function of MDSCs in T1D

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

The association of modic changes and chronic low back pain: A systematic review

Background: Modic changes (MC) have been proposed as a cause of low back pain (LBP). However, the proposition remains controversial. There is uncertainty over the existence or degree of association between the two and whether, if there is an association, it is a causal relationship. Previous systematic reviews of the evidence have had methodological flaws. Aims: The aim was to synthesize the current evidence to test the hypothesis that there is an association between MC and LBP and if there is, to evaluate the strength of the association. Methods: MEDLINE, EMBASE, and CINAHL were searched for all studies up to 31 December 2018 for cohort, case-control, and cross-sectional studies. Screening, quality assessment, and data extraction were conducted by two independent reviewers. Quality was assessed using the Joanna Biggs Institute tools for observational studies. The clinical heterogeneity among these studies ruled out pooling so a narrative review was undertaken. Results: Fifteen studies met the inclusion criteria, varying in patient characteristics, characteristics of MC, coexisting spinal conditions, and outcomes. The quality of evidence was poor in six and moderate in seven. There was wide clinical heterogeneity amongst the studies. The inclusion ages varied from early teens to over 65s, pain duration varied from under 6 weeks to over three months, and characteristics of the MC chosen for the studies also differed. The results were inconsistent across the studies: the odds ratios varied from showing an inverse relationship [Kovacs] with an odds ratio 0.31 (95% confidence interval, 0.1–0.95) to a very strong positive association 121.4 (11.21–1315.08) [Nakamae]. There was no consistency in associations for: type of MC, lumbar levels affected, position in relation to the vertebra, and presence of co-existing spinal conditions. The associations were possibly spurious arising from potential biases suggested by incomplete reporting: publication bias, selective reporting, and post hoc analysis. Only one study at low risk of bias found a substantial association but it was a small study of a narrow group meaning its results may not be generalizable. Discussion: The inconsistency of findings and the possibility that they were spurious means that no conclusions can be drawn about an association between MC and LBP. Future research should be designed as prospective cohort studies with adherence to reporting guidelines pertaining to observational studies and to MRI. Currently, clinicians should not look for the presence or absence of MC to guide their management of patients with LBP

Streamlined One‐Pot Synthesis of Nitro Fatty Acids

A novel method for the synthesis of nitro fatty acids (NFAs), an intriguing class of endogenously occurring lipid mediators, is reported. This one-pot procedure enables the controlled and stereoselective construction of nitro fatty acids from a simple set of common building blocks in a highly facile manner. Thereby, this methodology offers a streamlined, highly modular access to naturally occurring nitro fatty acids as well as non-natural NFA derivatives

Expression of JAZF1, ABCC8, KCNJ11and Notch2 genes and vitamin D receptor polymorphisms in type 2 diabetes, and their association with microvascular complications

Background: We studied JAZF1, ABCC8, KCNJ11and Notch2 gene expression and vitamin D receptor (VDR) polymorphisms (Fok1 and Bsm1) in patients with type 2 diabetes mellitus (T2DM) and tried to find out their association with microvascular complications in these patients. Methods: The study was conducted on 180 patients (93 complicated and 87 noncomplicated) and 150 healthy subjects. Reverse-transcriptase polymerase chain reaction (RT-PCR) was used to assess gene expression and real-time PCR was used to detect VDR genotypes. Serum vitamin D was assessed using Elisa technique. Results: After adjustment for age, sex, body mass index and glycated hemoglobin, altered Notch2 gene expression was found between patients and controls and between complicated and noncomplicated cases ( p = 0.001 and 0.001, respectively) and ABCC8 gene expression showed significant difference between patients and controls only ( p = 0.003), while JAZF1and KCNJ11 expression showed no significant difference between the studied groups ( p = 0.3 and 0.4, respectively). Serum vitamin D level was decreased in patients compared with controls ( p = 0.001), while no difference was detected between complicated and noncomplicated cases ( p = 0.1). Our results revealed no significant difference in VDR Fok1 and Bsm1 genotype distributions ( p = 0.7 and 0.1, respectively) and allele frequencies ( p = 0.4 and 0.1, respectively) between patients and controls. Patients with complications showed increased frequencies of Fok1GG genotype and G allele, while patients without complications showed increased frequencies of AA, then AG Fok1 genotype and A allele ( p = 0.001 and 0.001, respectively). In addition, the frequencies of CC Bsm1 genotype and C allele were significantly higher among patients with complications, while frequencies of TT Bsm1 genotype and T allele were significantly higher among patients without complications ( p = 0.02 and 0.003, respectively). Conclusion: Altered expression of Notch2 and ABCC8 genes may play a role in the pathogenesis of T2DM. Altered expression of Notch2 and VDR polymorphisms may play a role in the development of microvascular complications in diabetic patients. These results may assist in early identification and management of diabetic complications

Novel insights into the synergistic effects of selenium nanoparticles and metformin treatment of letrozole - induced polycystic ovarian syndrome: targeting PI3K/Akt signalling pathway, redox status and mitochondrial dysfunction in ovarian tissue

ABSTRACTPurpose Polycystic ovary syndrome (PCOS) has a series of reproductive and metabolic consequences. Although the link between PCOS, IR, and obesity, their impact on the pathogenesis of PCOS has yet to be determined. Dysfunction of PI3K/AKT pathway has been reported as the main cause of IR in PCOS. This study purposed to explore the effects of selenium nanoparticles (SeNPs) alone and combined with metformin (MET) in a PCOS-IR rat model.Methods After 3 weeks of treatment with SeNPs and/or MET, biochemical analysis of glycemic & lipid profiles, and serum reproductive hormones was performed. Inflammatory, oxidative stress, and mitochondrial dysfunction markers were determined colormetrically. The expression of PI3K and Akt genes were evaluated by Real-time PCR. Histopathological examination and Immunohistochemical analysis of Ki-67 expression were performed.Results The results showed that treatment with SeNPs and/or MET significantly attenuated insulin sensitivity, lipid profile, sex hormones levels, inflammatory, oxidative stress and mitochondrial functions markers. Additionally, PI3K and Akt genes expression were significantly upregulated with improved ovarian histopathological changes.Conclusion Combined SeNPs and MET therapy could be potential therapeutic agent for PCOS-IR model via modulation of the PI3K/Akt pathway, enhancing anti-inflammatory and anti-oxidant properties and altered mitochondrial functions.HighlightsThe strong relationship between obesity, insulin resistance, and polycystic ovarian syndrome.Disturbance of the PI3K/Akt signaling pathway is involved in the progression of polycystic ovary syndrome-insulin resistance (PCOS-IR).In PCOS-IR rats, combined SeNPs and metformin therapy considerably alleviated IR by acting on the PI3K/Akt signaling pathway.The combination of SeNPs and metformin clearly repaired ovarian polycystic pathogenesis and improved hormonal imbalance in PCOS-IR rats

DNA Polymorphisms and mRNA Levels of Immune Biomarkers as Candidates for Inflammatory Postpartum Disorders Susceptibility in Italian Buffaloes

The immunological genes that may interact with inflammatory postpartum diseases in Italian buffaloes were examined in this study. A total number of 120 female Italian buffaloes (60 normal and 60 with inflammatory reproductive diseases) were employed. Each buffalo’s jugular vein was pierced to get five milliliters of blood. To obtain whole blood and extract DNA and RNA, the blood was placed within tubes containing sodium fluoride or EDTA anticoagulants. The immunological (IKBKG, LGALS, IL1B, CCL2, RANTES, MASP2, HMGB1, and S-LZ) genes’ nucleotide sequence differences between healthy buffaloes and buffaloes affected by inflammatory reproductive diseases were found by employing PCR-DNA sequencing. According to Fisher’s exact test (p ˂ 0.01), there were noticeably different probabilities of all major nucleotide changes spreading among buffalo groups with and without reproductive problems. Buffaloes were significantly more likely to express the examined genes when they had inflammatory reproductive diseases. The outcomes might support the significance of these markers’ nucleotide variations and gene expression patterns as indicators of the prevalence of inflammatory reproductive disorders and provide a workable buffalo management policy

Accuracy of the Traditional COVID-19 Phone Triaging System and Phone Triage-Driven Deep Learning Model

Objectives: During the COVID-19 pandemic, a quick and reliable phone-triage system is critical for early care and efficient distribution of hospital resources. The study aimed to assess the accuracy of the traditional phone-triage system and phone triage-driven deep learning model in the prediction of positive COVID-19 patients. Setting: This is a retrospective study conducted at the family medicine department, Cairo University. Methods: The study included a dataset of 943 suspected COVID-19 patients from the phone triage during the first wave of the pandemic. The accuracy of the phone triaging system was assessed. PCR-dependent and phone triage-driven deep learning model for automated classifications of natural human responses was conducted. Results: Based on the RT-PCR results, we found that myalgia, fever, and contact with a case with respiratory symptoms had the highest sensitivity among the symptoms/ risk factors that were asked during the phone calls (86.3%, 77.5%, and 75.1%, respectively). While immunodeficiency, smoking, and loss of smell or taste had the highest specificity (96.9%, 83.6%, and 74.0%, respectively). The positive predictive value (PPV) of phone triage was 48.4%. The classification accuracy achieved by the deep learning model was 66%, while the PPV was 70.5%. Conclusion: Phone triage and deep learning models are feasible and convenient tools for screening COVID-19 patients. Using the deep learning models for symptoms screening will help to provide the proper medical care as early as possible for those at a higher risk of developing severe illness paving the way for a more efficient allocation of the scanty health resources

Impact of the International Nosocomial Infection Control Consortium (INICC)’s multidimensional approach on rates of ventilator-associated pneumonia in intensive care units in 22 hospitals of 14 cities of the Kingdom of Saudi Arabia

To analyze the impact of the International Nosocomial Infection Control Consortium (INICC) Multidimensional Approach (IMA) and use of INICC Surveillance Online System (ISOS) on ventilator-associated pneumonia (VAP) rates in Saudi Arabia from September 2013 to February 2017. A multicenter, prospective, before–after surveillance study on 14,961 patients in 37 intensive care units (ICUs) of 22 hospitals. During baseline, we performed outcome surveillance of VAP applying the definitions of the CDC/NHSN. During intervention, we implemented the IMA and the ISOS, which included: (1) a bundle of infection prevention practice interventions, (2) education, (3) outcome surveillance, (4) process surveillance, (5) feedback on VAP rates and consequences and (6) performance feedback of process surveillance. Bivariate and multivariate regression analyses were performed using generalized linear mixed models to estimate the effect of intervention. The baseline rate of 7.84 VAPs per 1000 mechanical-ventilator (MV)-days―with 20,927 MV-days and 164 VAPs―, was reduced to 4.74 VAPs per 1000 MV-days―with 118,929 MV-days and 771 VAPs―, accounting for a 39% rate reduction (IDR 0.61; 95% CI 0.5–0.7; P 0.001). Implementing the IMA was associated with significant reductions in VAP rates in ICUs of Saudi Arabia