Paraoxonase 1 gene (Gln192–Arg) polymorphism and the risk of coronary artery disease in type 2 diabetes mellitus

AbstractBackgroundParaoxonase 1 (PON1) is reported to have antioxidant and cardioprotective properties. Recently, an association of glutamine (Gln) or type A/arginine (Arg) or type B polymorphism at position 192 of PON1 gene has been suggested with coronary artery disease (CAD) among patients with diabetes mellitus (DM). However, conflicting results have also been reported.ObjectivesTo investigate the relationship between PON1 gene (Gln192–Arg) polymorphism and the presence, extent and severity of CAD in type 2 DM.MethodsThe study comprised 180 patients recruited from those undergoing coronary angiography for suspected CAD, who were divided according to the presence or absence of CAD and DM into four groups: Group I (n=40 patients) nondiabetic subjects without CAD, Group II (n=45 patients) diabetic patients without CAD, Group III (n=47 patients) nondiabetic patients with CAD and Group IV (n=48 patients) diabetic patients with CAD. PON1(Gln192–Arg) genotype was assessed using polymerase chain reaction (PCR) followed by AlwI digestion.ResultsThe frequency of Gln allele (type A) was significantly higher in Group I and Group II compared to Group III and Group IV (62.5%, 60% vs. 38.3%, 31.25%, respectively, p<0.001) while the frequency of Arg allele (type B+type AB) was significantly higher in ischemic groups (III and IV) compared to nonischemic groups (I and II) (61.7%, 68.75% vs. 37.5%, 40%, respectively, p<0.001). Patients with CAD and DM (Group IV) have significantly higher severity score and vessel score than those with CAD only (Group III) (9.7±2.97, 2.44±0.56 vs. 6.99±3.71, 1.67±0.89, respectively, p<0.001) Patients with vessel score 3 had significantly higher severity score and higher Arg allele frequency than patients with vessel score 2, the latter group had also significantly higher severity score and Arg allele frequency than patients with vessel score 1 (8.9±2.79 vs. 5.21±2.13 and 80.49% vs. 67.86%), (5.21±2.13 vs. 3.11±0.89 and 67.86% vs. 53.85%), p<0.001 for all. In multivariate logistic regression analysis of different variables for prediction of CAD, age [OR 2.99, CI (1.11–10.5), p<0.01], smoking [OR 4.13, CI (1.37–11.7), p<0.001], low-density lipoprotein (LDL) cholesterol>100mg/dL [OR 4.31, CI (1.25–12.5), p<0.001], high-density lipoprotein (HDL) cholesterol<40mg/dL [OR 5.11, CI (1.79–16.33), p<0.001] and PON1 192 Arg allele [OR 4.62, CI (1.67–13.57), p<0.001] were significantly independent predictors of CAD.ConclusionArg allele of PON1 192 gene polymorphism is an independent risk factor for CAD and is associated not only with the presence of CAD but also with its extent and severity and its impact is clearly more pronounced in diabetic patients

Oxidative Stress and Anti-Oxidant Markers in Premature Infants with Respiratory Distress Syndrome

BACKGROUND: Neonatal respiratory distress syndrome (RDS) caused by decreased surfactant and structural lung immaturity. The imbalance between oxidative status and antioxidant defence system was suggested to be an important trigger for lung affection with RDS. AIM: The goal of the current research was to elucidate the significance of the oxidant/ antioxidant status in the pathogenesis of RDS in preterm infants. PATIENTS AND METHODS: This controlled study included 31 preterm neonates with RDS and 36 healthy preterm neonates. Quantification level of oxidative stress biomarkers; malondialdehyde (MDA) &amp; hydrogen peroxide (H2O2) along with antioxidant enzymes activity; catalase (CAT) &amp; superoxide dismutase (SOD) in plasma of healthy premature neonates compared with those with RDS. RESULTS: status of oxidative stress markers (MDA &amp; H2O2) showed a significant increase with decreased levels of antioxidant enzymes activity (CAT &amp; SOD) in neonates with RDS when compared to healthy prematures. CONCLUSION: The results obtained in this study indicate that the increased oxidative stress accompanied by reduced antioxidant defences may play a significant role in the pathogenesis of respiratory distress in preterm newborns

Neurological Alterations in Type 1 Diabetes Mellitus Among Adolescents

BACKGROUND: Diabetes mellitus (DM) is a group of chronic disorders of metabolism characterised by high blood glucose levels. There is an increased prevalence of Type 1 DM in children and adolescents with its adverse complications especially microvascular ones (retinopathy, nephropathy and neuropathy) that might cause multiple organ damage. AIM: To study the relation between DM and neurological affection. METHODS: Fifty-nine children with type I DM, divided randomly into 2 groups, aged 8-18 years old of both sexes were enrolled in this cross-sectional study. All children were subjected to full history taking, physical, neurological and systemic examination. RESULTS: There was an affection of motor power in both upper limbs as well as lower limbs. Also, we found that there was an affection of the superficial peripheral sensation affecting both upper and lower limbs. CONCLUSION: Neurological assessment of children with diabetes mellitus type I should be a routine to early discover these manifestations which can have a deteriorating effect on the child’s health

Pentraxin 3: A Potential Novel Predictor for Neonatal Pulmonary Hypertension

BACKGROUND: Persistent pulmonary hypertension of the newborn (PPHN) is a serious neonatal problem which has a high mortality rate even with advanced modes of mechanical ventilation. Pentraxin 3 is one of the long pentraxins, which plays an essential role in regulation of cell proliferation and angiogenesis. AIM: This study aims to assess serum pentraxin 3 levels in neonates with pulmonary arterial hypertension and compare them in those who have other congenital heart diseases and healthy neonates. Also, we intended to evaluate serum levels of CRP as a mediator of inflammation in the studied groups. METHODS: The study is a case-control study. Cases were recruited from El Galaa Teaching Hospital, classified into three groups; each group had thirty cases. The first one: cases with pulmonary hypertension (PHT), the second one: cases with congenital heart diseases (CHD) without pulmonary hypertension and the third group included healthy neonates. All participants were subjected to full history taking and full clinical examination. Diagnosis of congenital heart disease and pulmonary hypertension was made according to echocardiographic ï¬ndings by pediatric cardiologist using echocardiography machine. Laboratory investigations included measurement of serum pentraxin 3, Routine CBC, CRP. RESULTS: This study found that the mean serum pentraxin 3 in PHT neonates was significantly higher than that of the control and CHD neonates (p ≤ 0.001, p = 0.02 respectively). Also, the mean Pentraxin3 of the CHD neonates was significantly higher than that of the control (p = 0.06). Also, the mean CRP of the PHT neonates was significantly higher than that of the control (p = 0.01). Regression analysis showed that Pentraxin3 was the main predictor of PAP (P = 0.01). CONCLUSION: Serum pentraxin 3 is significantly elevated in neonates with pulmonary hypertension, so measurement of pentraxin 3 levels in neonates may be valuable as a predictor for pulmonary hypertension in neonates

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

The impact of immediate breast reconstruction on the time to delivery of adjuvant therapy: the iBRA-2 study

Background: Immediate breast reconstruction (IBR) is routinely offered to improve quality-of-life for women requiring mastectomy, but there are concerns that more complex surgery may delay adjuvant oncological treatments and compromise long-term outcomes. High-quality evidence is lacking. The iBRA-2 study aimed to investigate the impact of IBR on time to adjuvant therapy. Methods: Consecutive women undergoing mastectomy ± IBR for breast cancer July–December, 2016 were included. Patient demographics, operative, oncological and complication data were collected. Time from last definitive cancer surgery to first adjuvant treatment for patients undergoing mastectomy ± IBR were compared and risk factors associated with delays explored. Results: A total of 2540 patients were recruited from 76 centres; 1008 (39.7%) underwent IBR (implant-only [n = 675, 26.6%]; pedicled flaps [n = 105,4.1%] and free-flaps [n = 228, 8.9%]). Complications requiring re-admission or re-operation were significantly more common in patients undergoing IBR than those receiving mastectomy. Adjuvant chemotherapy or radiotherapy was required by 1235 (48.6%) patients. No clinically significant differences were seen in time to adjuvant therapy between patient groups but major complications irrespective of surgery received were significantly associated with treatment delays. Conclusions: IBR does not result in clinically significant delays to adjuvant therapy, but post-operative complications are associated with treatment delays. Strategies to minimise complications, including careful patient selection, are required to improve outcomes for patients

The Role of Oxidative Stress and NADPH Oxidase P22phox Polymorphism in Acute Kidney Injury Patients The Role of Oxidative Stress and NADPH Oxidase P22phox Polymorphism in Acute Kidney Injury Patients

Abstract: Acute kidney injury (AKI) is a common condition with significant associated morbidity and mortality. Although several studies have been done to understand the molecular and biochemical mechanisms of kidney injury. Results were static over the last 30 years. Increased production of reactive oxygen species (ROS) is thought to play a major role in the pathogenesis of AKI and its complications. The NADPH oxidase complex is an important source of ROS in AKI. Its p22 subunit is polymorph with a C242T variant that changes histidine-72 for a tyrosine in the potential heme binding site. The aim of this study was to investigate the occurrence of this polymorphism in 75 patients with AKI and correlate the genotype to the extent of the load of the circulating ROS and its association with the unfavorable course of the disease. This study included 75 hospitalized patients in the Internal Medicine Department Menofiya University Hospital with established AKI. We had done genotyping for the C242T polymorphism of the p22 subunit of the NADPH oxidase gene using restriction fragment length polymorphism (RFLP) technique. The extent of the ROS load was estimated by measuring the level of plasma nitrotyrosine level and then correlation to the severity of the course of the disease and its outcome was made. The results revealed that, compared to CC group, the T-allele carrier was associated with higher levels of serum urea, creatinine and plasma nitrotyrosine (p&lt;0.01) and the levels of plasma nitrotyrosine are correlated with age of the patient and length of hospital stay. Also the T-allele carries (CT and TT groups) showed higher cumulative probability of remaining hospitalized, while there was no significant difference concerning requirement for dialysis, for ICU admission and dialysis dependency. It is concluded that the polymorphism C242T in the gene encoding p22phox of NADPH oxidase is associated with the severity of the course of the disease and the adverse outcome in cases with AKI

Origin and Global Expansion of Complex Lineage 3.

complex (MTBC) Lineage 3 (L3) strains are abundant in world regions with the highest tuberculosis burden. To investigate the population structure and the global diversity of this major lineage, we analyzed a dataset comprising 2682 L3 strains from 38 countries over 5 continents, by employing 24-loci mycobacterial interspersed repetitive unit-variable number of tandem repeats genotyping (MIRU-VNTR) and drug susceptibility testing. We further combined whole-genome sequencing (WGS) and phylogeographic analysis for 373 strains representing the global L3 genetic diversity. Ancestral state reconstruction confirmed that the origin of L3 strains is located in Southern Asia and further revealed multiple independent introduction events into North-East and East Africa. This study provides a systematic understanding of the global diversity of L3 strains and reports phylogenetic variations that could inform clinical trials which evaluate the effectivity of new drugs/regimens or vaccine candidates

The proportion of different BCR-ABL1 transcript types in chronic myeloid leukemia. An international overview

There are different BCR-ABL1 fusion genes that are translated into proteins that are different from each other, yet all leukemogenic, causing chronic myeloid leukemia (CML) or acute lymphoblastic leukemia. Their frequency has never been systematically investigated. In a series of 45503 newly diagnosed CML patients reported from 45 countries, it was found that the proportion of e13a2 (also known as b2a2) and of e14a2 (also known as b3a2), including the cases co-expressing e14a2 and el 3a2, was 37.9% and 62.1%, respectively. The proportion of these two transcripts was correlated with gender, e13a2 being more frequent in males (39.2%) than in females (36.2%), was correlated with age, decreasing from 39.6% in children and adolescents down to 31.6% in patients &gt;= 80 years old, and was not constant worldwide. Other, rare transcripts were reported in 666/34561 patients (1.93%). The proportion of rare transcripts was associated with gender (2.27% in females and 1.69% in males) and with age (from 1.79% in children and adolescents up to 3.84% in patients &gt;= 80 years old). These data show that the differences in proportion are not by chance. This is important, as the transcript type is a variable that is suspected to be of prognostic importance for response to treatment, outcome of treatment, and rate of treatment-free remission