Distinct baseline immune characteristics associated with responses to conjugated and unconjugated pneumococcal polysaccharide vaccines in older adults.

Pneumococcal infections cause serious illness and death among older adults. The capsular polysaccharide vaccine PPSV23 and conjugated alternative PCV13 can prevent these infections; yet, underlying immunological responses and baseline predictors remain unknown. We vaccinated 39 older adults (>60 years) with PPSV23 or PCV13 and observed comparable antibody responses (day 28) and plasmablast transcriptional responses (day 10); however, the baseline predictors were distinct. Analyses of baseline flow cytometry and bulk and single-cell RNA-sequencing data revealed a baseline phenotype specifically associated with weaker PCV13 responses, which was characterized by increased expression of cytotoxicity-associated genes, increased frequencies of CD16+ natural killer cells and interleukin-17-producing helper T cells and a decreased frequency of type 1 helper T cells. Men displayed this phenotype more robustly and mounted weaker PCV13 responses than women. Baseline expression levels of a distinct gene set predicted PPSV23 responses. This pneumococcal precision vaccinology study in older adults uncovered distinct baseline predictors that might transform vaccination strategies and initiate novel interventions.

KDM3A, a Novel Blood-Based Biomarker in Colorectal Carcinogenesis.

Colorectal cancer (CRC) is one of the leading causes of cancer-linked deaths globally. The determination of biomarkers is important in the prognosis and treatment of CRC. Previous studies emphasized the relationship between hypoxia and CRC in humans, and there is strong evidence that this process is strongly related to HIF-1. KDM3A is a histone demethylase that could directly bind to HIF-1α, a subunit of HIF-1. This study aimed to reveal whether the expression level of the KDM3A gene could be used as a predictor of CRC. The expression levels of HIF-1α, KDM3A, and Epithelial-Mesenchymal Transition (EMT) genes were evaluated by qRT-PCR in leukocyte samples of 50 CRC patients in different stages and 50 healthy controls. HIF-1α and KDM3A expression levels were significantly higher in the CRC group, compared to the controls. Slug and ZEB-1 genes, the mesenchymal markers, showed the same significance pattern between groups. We acquired 0.664 AUC with 54% sensitivity and 85.4% specificity for separating controls from CRC patients by using the KDM3A expression levels in ROC analysis. This data support that KDM3A could be a novel supplementary biomarker in diagnosis of CRC, which could be noninvasively detected in circulation.

Novel Injury Scoring Tool for Assessing Brain Injury following Neonatal Hypoxia-Ischemia in Mice.

The variability of severity in hypoxia-ischemia (HI)-induced brain injury among research subjects is a major challenge in developmental brain injury research. Our laboratory developed a novel injury scoring tool based on our gross pathological observations during hippocampal extraction. The hippocampi received scores of 0-6 with 0 being no injury and 6 being severe injury post-HI. The hippocampi exposed to sham surgery were grouped as having no injury. We have validated the injury scoring tool with T2-weighted MRI analysis of percent hippocampal/hemispheric tissue loss and cell survival/death markers after exposing the neonatal mice to Vannucci's rodent model of neonatal HI. In addition, we have isolated hippocampal nuclei and quantified the percent good quality nuclei to provide an example of utilization of our novel injury scoring tool. Our novel injury scores correlated significantly with percent hippocampal and hemispheric tissue loss, cell survival/death markers, and percent good quality nuclei. Caspase-3 and Poly (ADP-ribose) polymerase-1 (PARP1) have been implicated in different cell death pathways in response to neonatal HI. Another gene, sirtuin1 (SIRT1), has been demonstrated to have neuroprotective and anti-apoptotic properties. To assess the correlation between the severity of injury and genes involved in cell survival/death, we analyzed caspase-3, PARP1, and SIRT1 mRNA expressions in hippocampi 3 days post-HI and sham surgery, using quantitative reverse transcription polymerase chain reaction. The ipsilateral (IL) hippocampal caspase-3 and SIRT1 mRNA expressions post-HI were significantly higher than sham IL hippocampi and positively correlated with the novel injury scores in both males and females. We detected a statistically significant sex difference in IL hippocampal caspase-3 mRNA expression with comparable injury scores between males and females with higher expression in females.

First Long-term Oncologic Results of the ALPPS Procedure in a Large Cohort of Patients With Colorectal Liver Metastases.

OBJECTIVES: To analyze long-term oncological outcome along with prognostic risk factors in a large cohort of patients with colorectal liver metastases (CRLM) undergoing ALPPS. BACKGROUND: ALPPS is a two-stage hepatectomy variant that increases resection rates and R0 resection rates in patients with primarily unresectable CRLM as evidenced in a recent randomized controlled trial. Long-term oncologic results, however, are lacking. METHODS: Cases in- and outside the International ALPPS Registry were collected and completed by direct contacts to ALPPS centers to secure a comprehensive cohort. Overall, cancer-specific (CSS), and recurrence-free (RFS) survivals were analyzed along with independent risk factors using Cox-regression analysis. RESULTS: The cohort included 510 patients from 22 ALPPS centers over a 10-year period. Ninety-day mortality was 4.9% and median overall survival, CSS, and RFS were 39, 42, and 15 months, respectively. The median follow-up time was 38 months (95% confidence interval 32-43 months). Multivariate analysis identified tumor-characteristics (primary T4, right colon), biological features (K/N-RAS status), and response to chemotherapy (Response Evaluation Criteria in Solid Tumors) as independent predictors of CSS. Traditional factors such as size of metastases, uni versus bilobar involvement, and liver-first approach were not predictive. When hepatic recurrences after ALPPS was amenable to surgical/ablative treatment, median CSS was significantly superior compared to chemotherapy alone (56 vs 30 months, P < 0.001). CONCLUSIONS: This large cohort provides the first evidence that patients with primarily unresectable CRLM treated by ALPPS have not only low perioperative mortality, but achieve appealing long-term oncologic outcome especially those with favorable tumor biology and good response to chemotherapy.

Evaluation of the accuracy of the mechanical torque wrench by the number of uses and ratchet type.

PURPOSE: To evaluate the accuracy of mechanical torque rachet types based on the number of uses. METHODS: A total of 25 ratchets, including three frictional- and two spring-type torque ratchets from every mechanical torque ratchet group, were used in our study. A digital torque measurement device was used in assessing the efficiency of mechanical torque ratchets. All ratchets were tightened according to the torque values recommended by the companies. The ratchets were tightened 500 times in total. RESULTS: Given the changes in torque delivery by the number of uses, a statistically significant torque loss was observed in the Bego ratchets (P< 0.05), and a statistically significant increase was found in the torque values of the other ratchet groups (P< 0.05). The highest increase in torque values was obtained in the MEDENTIKA ratchet group. CLINICAL SIGNIFICANCE: This study showed that there are changes in the torque values applied based on the number of rachet uses. Thus, clinicians are advised to regularly evaluate the accuracy of the rachets.

Single-incision laparoscopic cholecystectomy: a new retraction technique.

BACKGROUND: Laparo-endoscopic single site cholecystectomy receives great interest from the surgical community. It has potential for reducing postoperative pain, length of hospital stay and improving cosmesis. Minimally invasive surgeons have been forced to develop techniques for providing adequate retraction of the gallbladder. Herein, we describe a new retraction technique to improve the dissection of Calot's triangle. SURGICAL TECHNIQUE: Twelve patients underwent laparo-endoscopic single site laparoscopic cholecystectomy using this retraction technique. An intra-umbilical skin incision was made by pulling out the umbilicus. A SILS port was placed through an open approach. We inserted a 10-mm 30 degrees camera through the SILS port without using any trocar. One suture was knotted in the middle of the gallbladder. Gallbladder retraction was achieved by the use of an EndoClose needle that was inserted into abdominal cavity at the subcostal border. The floppy knot was held by the notched end of the EndoClose needle. This device provided retraction of the gallbladder in every direction. CONCLUSIONS: Adequate retraction greatly simplifies laparo-endoscopic single site cholecystectomy. New retraction techniques will enable wider use of this novel minimally invasive approach. Further work is needed to investigate the advantages of this new technique.

Distinct baseline immune characteristics associated with responses to conjugated and unconjugated pneumococcal polysaccharide vaccines in older adults.

Pneumococcal infections cause serious illness and death among older adults. A capsular polysaccharide vaccine PPSV23 (Pneumovax®) and a conjugated polysaccharide vaccine PCV13 (Prevnar®) are used to prevent these infections, yet underlying responses, and baseline predictors remain unknown. We recruited and vaccinated 39 older adults (>60 years) with PPSV23 or PCV13. Both vaccines induced strong antibody responses at day 28 and similar plasmablast transcriptional signatures at day 10, however, their baseline predictors were distinct. Analyses of baseline flow cytometry and RNA-seq data (bulk and single cell) revealed a novel baseline phenotype that is specifically associated with weaker PCV13 responses, characterized by i) increased expression of cytotoxicity-associated genes and increased CD16+ NK frequency; ii) increased Th17 and decreased Th1 cell frequency. Men were more likely to display this cytotoxic phenotype and mounted weaker responses to PCV13 than women. Baseline expression levels of a distinct gene set was predictive of PPSV23 responses. This first precision vaccinology study for pneumococcal vaccine responses of older adults uncovered novel and distinct baseline predictors that might transform vaccination strategies and initiate novel interventions.

Selectively compromised inner retina function following hypoxic-ischemic encephalopathy in mice: A noninvasive measure of severity of the injury.

The intricate system of connections between the eye and the brain implies that there are common pathways for the eye and brain that get activated following injury. Hypoxia-ischemia (HI) related encephalopathy is a consequence of brain injury caused by oxygen and blood flow deprivation that may result in visual disturbances and neurodevelopmental disorders in surviving neonates. We have previously shown that the tyrosine receptor kinase B (TrkB) agonist/modulator improves neuronal survival and long-term neuroprotection in a sexually differential way. In this study, we tested the hypotheses that; 1) TrkB agonist therapy improves the visual function in a sexually differential way; 2) Visual function detected by electroretinogram (ERG) correlates with severity of brain injury detected by magnetic resonance (MRI) imaging following neonatal HI in mice. To test our hypotheses, we used C57/BL6 mice at postnatal day (P) 9 and subjected them to either Vannucci's rodent model of neonatal HI or sham surgery. ERG was performed at P 30, 60, and 90. MRI was performed following the completion of the ERG. ERG in these mice showed that the a-wave is normal, but the b-wave amplitude is severely abnormal, reducing the b/a wave amplitude ratio. Inner retina function was found to be perturbed as we detected severely attenuated oscillatory potential after HI. No sex differences were detected in the injury and severity pattern to the retina as well as in response to 7,8-DHF therapy. Strong correlations were detected between the percent change in b/a ratio and percent hemispheric/hippocampal tissue loss obtained by MRI, suggesting that ERG is a valuable noninvasive tool that can predict the long-term severity of brain injury.

Acute oxidative stress and antioxidant status responses following an American football match.

AIM: Intense physical activity is known to induce oxidative stress. Though regular physical training enhances the antioxidant defence system, the effects of diminished training periods are unclear. American football is one of the recently popular sports in Türkiye and is defined as a mixed activity. The aim of the research was to examine some markers of oxidative stress and antioxidant status in occasionally competitive American football players following a match, and relations with aerobic power and playing position. METHODS: Twenty two male players volunteered for the study. To determine oxidative stress and antioxidant status from blood samples collected before and immediately following a match, plasma malondialdehyde (MDA) and nitric oxide (NO) levels, erythrocyte superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities, and total antioxidant status (TAS) were assessed, using spectrophotometric methods. Wilcoxon's signed rank test was used to determine the match effect, and Mann-Whitney U test was used to compare playing position and VO2max effects. RESULTS: Plasma MDA (P<0.001) and NO (P<0.05) levels increased significantly following the match. Antioxidant parameters were unchanged following the match when compared with the resting level, except for a VO2max related effect (P<0.05) on TAS. CONCLUSION: Collected data revealed that an American football match caused excessive production of free radicals and oxidative stress. The training loads players underwent were not high enough to cause positive effects on the antioxidant status. To enhance training-induced antioxidant status adaptation, higher amounts of physical activity may be required.

Calcium dobesilate reduces oxidative stress in cardiac surgery.

AIM: Calcium dobesilate (CD) is a synthetic benzene sulfonate derivative and an angioprotective agent used orally. It can be used in patients who have diabetic retinopathy or chronic venous insufficiency. The aim of this study was to investigate the effect of CD on the reduction of oxidative stress during coronary artery bypass graft operations on cardiopulmonary bypass. METHODS: A double-blind prospective randomized study was carried out on 30 patients who underwent coronary artery bypass operations. The control and study groups were composed of 15 patients each. Pretreatment with CD started two weeks before the operation. Serial blood samples for superoxide dismutase, glutathione peroxidase were collected for the serum concentration measurements of the major endogenous antioxidant enzyme systems and malondialdehyde for scavenging capacity. RESULTS: After the release of cross clamp levels of superoxide dismutase and glutathione peroxidase. they were significantly higher in the study group than in the control group (P<0.05). Malondialdehyde levels in the study group were significantly lower than those of the control group (P<0.05). The cardiac function after aortic declamping was affected by CD, indicating contribution of CD to myocardial injury from ischemia/reperfusion. CONCLUSIONS: The study suggests that pretreatment with CD alleviates malondialdehyde production and preserves endogenous antioxidant capacity during cardiopulmonary bypass and cardioplegic arrest.

Can SUVmax values of Ga-68-PSMA PET/CT scan predict the clinically significant prostate cancer?

PURPOSE: The intensity of prostate-specific membrane antigen (PSMA) expression increases as the tumor grade increases and the uptake of Ga-68-PSMA is higher in high-grade tumors. The aim of the present study was to evaluate the correlation of preoperative tracer uptake of primary tumor to Gleason Score in patients who underwent prostatectomy. PATIENTS AND METHODS: We retrospectively evaluated 141 patients who had Ga-68-PSMA positron emission tomography/computed tomography (PET/CT) imaging and who underwent prostatectomy. All patients had a diagnosis of prostate cancer on the basis of 10-24 cores transrectal ultrasound-guided biopsy (TRUS-Bx). Histological assessment was performed according to the New Contemporary Prostate Cancer Grading System. All patients had a prostate-specific antigen (PSA) level measurement within maximum of 28 days before Ga-68-PSMA PET/CT. Region of interests were drawn manually around the prostate gland, avoiding the bladder activity, to calculate the maximum standardized uptake values (SUVmax) values. RESULTS: The median PSA values for all patients were 10.0 ng/ml. PSA values for low-risk patients were significantly lower than those of high-risk patients (P<0.001). There were 41.1% upgrades and 7.8% downgrades following prostatectomy in terms of Grade Groups. According to the final pathology reports, 21% (n=16) of patients moved from a low-risk level (grade groups 1+2) to a high-risk level (grade groups 3+4+5). The median SUVmax value was 8.8, ranging from 2.1 to 62.4. There was a strong correlation between SUVmax values and grade groups (Pearson ρ=0.66) (P<0.001). The mean SUVmax values of high-risk patients were significantly higher than those of low-risk patients (18.9±12.1 vs. 7.16±6.2, respectively) (P<0.001). Receiver operation characteristic curve analysis of SUVmax at the cut-off value of 9.1 showed a high sensitivity (78%) and specificity (81%) for detection of high risk disease. CONCLUSION: SUVmax values correlate significantly with the grade groups of the primary tumor. The intraprostatic accumulation sites may predict clinically significant cancer and potentially serve as a target for biopsy sampling in conjunction with mpMRI in selected patients.

Outpatient follow-up'' or ''Active clinical observation'' in patients with nonspecific abdominal pain in the Emergency Department. A randomized clinical trial.

AIM: The aim of this study was to determine whether it is safe and cost-effective to discharge nonspecific abdominal pain (NSAP) patients from the Emergency Department (ED) and re-evaluate diagnosis later. METHODS: Patients aged between 18 and 65 years were enrolled into the study. They had been admitted to the ED for acute abdominal pain with an indefinitive diagnosis after clinical examination and base-line investigations. The patients were randomly assigned into two groups: 1) active clinical observation (ACO), comprising those admitted to the ED observation room; 2) outpatient group (OG), comprising those discharged and asked to return for re-evaluation at 8-12 hours intervals over the following three days. Each patient was examined by an ED physician and a consultant general surgeon. Demographics, blood tests, morbidity and mortality, number of operations, together with 6-month follow-up results were noted. Finally, a patient satisfaction questionnaire was administered. RESULTS: A total of 105 patients were enrolled into the study; 50 were randomized to the ACO group and 55 to the OG. There were no statistically significant differences in demographics and blood parameters between the two groups. Overall agreement of ED diagnosis with final diagnosis was 91.4%. Total morbidity was 10% in the ACO group and 7.2% in the OG. There were no statistically differences in morbidities and usage of diagnostic imaging modalities between the two groups (P>0.05). No deaths occurred in either group during the study period. The patients in the ACO group were more keen on returning for re-evaluation and willing to recommend our hospital services to other people (P< or =0.05). CONCLUSION: Outpatient evaluation of patients with an ED diagnosis of NSAP may be an option, seems to be safe, is not accompanied by an increased incidence of complications and is efficient if patients are selected properly.

177Lu-DOTATATE therapy in patients with neuroendocrine tumours including high-grade (WHO G3) neuroendocrine tumours: response to treatment and long-term survival update.

PURPOSE: Upon diagnosis, distant metastases are encountered in 21-50% of neuroendocrine tumours (NETs). However, few systemic treatment options are available for the well-differentiated NETs in the metastatic stage. Lu-DOTATATE is one of the most effective treatments in this limited patient group. We retrospectively investigated its efficacy and effect on the survival in patients with both well-differentiated and grade III NETs who had high uptake in pretherapeutic Ga-DOTATATE PET/computed tomography scans. PATIENTS AND METHODS: Patients with metastatic NETs treated with Lu-DOTATATE between January 2010 and November 2015 in our department were included in this retrospective cohort. Toxicity and adverse effects were evaluated according to SWOG criteria. Progression-free survival (PFS) and overall survival (OS) rates were calculated considering the first date of treatment. Response was evaluated according to RECIST criteria. Potential predictors of survival and response were analysed. RESULTS: Patients (n=186) with metastatic NETs originating from various primary sites (bronchial, pancreatic, nonpancreatic gastroenteropancreatic-NETs, pheochromocytoma-paraganglioma and unknown primary) were treated with 1107 courses of Lu-DOTATATE treatment (median: 6; range: 3-12). Among 160 patients whose responses to treatment could be evaluated according to the RECIST criteria, 28.1% (n=45) had a progressive disease, 21.9% (n=35) had a stable disease, 46.9% (n=75) had a partial response and 3.1% (n=5) had a complete response. Median follow-up was 30.6 months. The Kaplan-Meier estimated median PFS was 36.4 months, mean PFS was 38 months and the mean OS was 55 months. The disease control rates in patients with WHO grades I, II and III were 74, 73 and 60%, respectively, and the OS rates were 61.9, 52.2 and 38.4 months, respectively. We observed no major renal toxicity except a minor increase (11.1%) in average serum creatinine levels. In 33.9% (n=56) of the patients, grade I toxicity; in 9.1% (n=15), grade II; and in 1.2% (n=2), grade III toxicity were observed. CONCLUSION: Lu-DOTATATE therapy is an important treatment option in somatostatin receptor type-2-positive pancreatic, nonpancreatic gastroenteropancreatic-NETs, and lung NETs including metastatic NETs with an unknown primary site and significantly contributed to patients' OS. Additionally, peptide receptor radionuclide therapy may have a role in a selected subgroup of patients with grade III NET with high somatostatin receptor type-2 expression.

Icodextrin and Seprafilm do not interfere with colonic anastomosis in rats.

BACKGROUND: Physical barriers and instilled solutions have been studied to prevent intra-abdominal adhesions. However, undesirable side effects of these substances on the healing of intestinal anastomoses may limit their use. This study was designed to compare the effects of antiadhesives on the healing of colonic anastomosis in rats. METHODS: Sixty female Sprague-Dawley rats were divided into 3 groups of 20. The animals received isotonic saline and 7.5% icodextrin, intraperitoneally after standard left colonic anastomosis. In group 3, Seprafilm was wrapped around the anastomosis and also laid over the abdominal viscera. Half of the animals from each group were killed on postoperative day (POD) 4 and the remaining half on POD 21. Adhesion scoring, bursting pressure and tissue hydroxyproline measurements and histopathological assessment were performed. RESULTS: Mean hydroxyproline levels were significantly higher in groups receiving icodextrin and Seprafilm compared with the control group, whereas mean bursting pressures were significantly higher in the group that received icodextrin (p < 0.05). Intraperitoneal administration of icodextrin resulted in significant reduction of adhesion formation on POD 21 (p < 0.05). CONCLUSIONS: Seprafilm does not prevent formation of adhesions as much as icodextrin does, but its effect on the healing of colonic anastomoses is similar.

Folate and vitamin B12 levels in abnormal pap smears: a case control study.

OBJECTIVE: This study aimed to explore the risk of abnormal cervical cytology in relation to serum folate and vitamin B12 levels, and demographic characteristics. PATIENTS AND METHODS: A case-control study was carried out among women attending the gynecology clinic for cervical cytology screening. At the follow-up clinic visit, fasting blood samples were collected from 103 cases with abnormal cervical cytology of the cervix and 175 controls with cytological normal smears and serum folate and vitamin B12 levels were measured. Data from cases and controls were compared. Logistic regression analysis was used to estimate the relative odds of abnormal cytology with increasing vitamin B12 levels. RESULTS: There were no significant differences between cases and controls in demographic characteristics and mean folate levels (p > 0.05). The mean vitamin B12 level of cases was significantly lower than that of controls (p < 0.001). Dichotomized logistic regression analyses of vitamin B12 levels were significantly different (p < 0.001). The predicted percentages at a cut-off value of 0.5 were as follows: sensitivity 70.0%, specificity 74.6%, positive predictive value 71.8% and negative predictive value 72.6%. The logistic regression analysis of the 1st and the 4th quartiles of vitamin B12 levels showed a significant difference p < 0.001, OR: 1.525 (CI, 1.175-1.875). CONCLUSION: The results of this study suggest that lower vitamin B12 levels are associated with abnormal cervical cytology. It is recommended that women should consume not only folate-rich foods such as fruits and vegetables but also vitamin B12-rich foods such as meat, fish, milk products and eggs in a balanced way.

Assessment of mTOR pathway molecules during implantation in rats.

Mammalian target of rapamycin (mTOR) is a member of the PI3K/Akt/mTOR signaling pathway that participates in cell growth, proliferation, protein synthesis, transcription, angiogenesis, apoptosis and autophagy. We investigated the role of mTOR and other signaling molecules in the rat uterus during implantation. Female pregnant rats were divided into three groups: embryonic days (ED) 4.5, 5.5 and 6.5 according to vaginal smears. Immunohistochemical staining of mTORC1, mTORC2, IGF1, PI3K, pAkt1/2/3, ERK1 and pERK1/2 was performed on formalin fixed, paraffin embedded uterine tissue samples. pAkt1/2/3 and ERK1 also were analyzed using western blotting. We found that PI3K/Akt/mTOR and ERK/pERK were increased during the implantation period. Different amounts of mTORC1, mTORC2, IGF1, PI3K, pAKT1/2/3, ERK1 and pERK1/2 were expressed in luminal epithelium, decidual cells, embryoblast and trophoblast cells during implantation. We suggest that mTOR and associated signaling molecules may participate in implantation.

Anxiety disorder in patients with non-specific chest pain in the emergency setting.

OBJECTIVES: Many patients who have been discharged from the emergency department (ED) with a diagnosis of "non-specific chest pain" (NSCP) have anxiety disorder (AD), a commonly missed entity in acute care. The objective of this study was to delineate characteristic properties that could enhance recognition of AD in ED patients admitted with NSCP. METHODS: All patients between 18 and 65 years of age diagnosed with NSCP were enrolled. The Hospital Anxiety and Depression Scale (HADS) anxiety subscale was used as a screening test for AD. The patients with high HADS scores (> or = 10) were evaluated by a psychiatrist for AD. RESULTS: In total, 157 patients were enrolled in the study. HADS scores were found to be "high" (> or = 10) in 49 patients (31.2%). Patients with high HADS scores had a higher frequency of associated symptoms (p = 0.004). Dizziness or lightheadedness, chills or hot flushes, and fear of dying were found to have been reported more frequently by patients with high anxiety scores. Of the group with high score, 33 patients (67.3%) were interviewed by a psychiatrist, and 23 (69.7%) of these patients were diagnosed with AD. Associated symptoms were described by 21 patients with AD (91.3%). Of those with AD, 18 (78.3%) had been previously admitted to the ED with chest pain. Atypical chest pain was described by 21 patients (91.3%). CONCLUSIONS: Physicians should always consider AD in patients presenting to the ED with chest pain after ruling out organic aetiology. Patients' definition of atypical pain, recurrent admissions to ED, and presence of associated symptoms such as dizziness, chills or hot flushes, and fear of dying could aid in considering AD.

Evaluation of X Chromosome Inactivation with Respect to HLA Genetic Susceptibility in Rheumatoid Arthritis and Systemic Sclerosis.

BACKGROUND: Autoimmune diseases, including rheumatoid arthritis (RA) and systemic sclerosis (SSc) are characterized by a strong genetic susceptibility from the Human Leucocyte Antigen (HLA) locus. Additionally, disorders of epigenetic processes, in particular non-random X chromosome inactivation (XCI), have been reported in many female-predominant autoimmune diseases. Here we test the hypothesis that women with RA or SSc who are strongly genetically predisposed are less susceptible to XCI bias. METHODS: Using methylation sensitive genotyping of the androgen receptor (AR) gene, XCI profiles were performed in peripheral blood mononuclear cells from 161 women with RA, 96 women with SSc and 100 healthy women. HLA-DRB1 and DQB1 were genotyped. Presence of specific autoantibodies was documented for patients. XCI skewing was defined as having a ratio ≥ 80:20 of cells inactivating the same X chromosome. RESULTS: 110 women with RA, 68 women with SSc, and 69 controls were informative for the AR polymorphism. Among them 40.9% of RA patients and 36.8% of SSc patients had skewed XCI compared to 17.4% of healthy women (P = 0.002 and 0.018, respectively). Presence of RA-susceptibility alleles coding for the "shared epitope" correlated with higher skewing among RA patients (P = 0.002) and such correlation was not observed in other women, healthy or with SSc. Presence of SSc-susceptibility alleles did not correlate with XCI patterns among SSc patients. CONCLUSION: Data demonstrate XCI skewing in both RA and SSc compared to healthy women. Unexpectedly, skewed XCI occurs more often in women with RA carrying the shared epitope, which usually reflects severe disease. This reinforces the view that loss of mosaicism in peripheral blood may be a consequence of chronic autoimmunity.

Age and gender dependent alterations in the activities of glutathione related enzymes in healthy subjects.

OBJECTIVES: Oxidative stress as a result of increased free radical production is implicated in the pathogenesis of several diseases. Specific antioxidant enzymes have a crucial role in the prevention of these deleterious effects. Since the activities of these enzymes differ significantly in different populations and seem to be affected by various environmental factors, in this study we aimed to determine the reference values of glutathione related antioxidant enzyme activities in the erythrocytes of healthy subjects and to investigate the possible variations as a function of age and gender in a healthy Turkish Mediterranean population. DESIGN AND METHODS: 130 healthy subjects (12-90 yr, 82 females, 48 males) were divided into six different age groups. Erythrocyte glutathione peroxidase (GSH-PX), glutathione reductase (GR) and glutathione-s-transferase (GST) activities were measured on a Hitachi 704 autoanalyser by the modification of previously described manual UV spectrophotometric methods. RESULTS: No significant differences were observed in erythrocyte GSH-PX, GR and GST activities between different age groups. Overall, GST activities were significantly higher in females compared with males (8.08 +/- 1.39, 6.88 +/- 1.51 U/g Hb respectively, mean +/- SD, p < 0.001). A significant positive correlation between GSH-PX and GR activities was observed (r = 0.49, p < 0.001). CONCLUSION: The results of this study suggested that the activities of GSH-PX, GR and GST did not depend. GST activities overall were higher in females. The reference values that we obtained were different than the previous reports. This situation implies that each population should determine its own reference values and should investigate the influence of environmental factors and life style habits on the activities of these enzymes that constitute a major part of the antioxidant defense system in the human organism.

Laparoscopic repair of an internal supravesical hernia: a rare hernia causing small bowel obstruction.

The application of diagnostic laparoscopy in emergency surgery has facilitated a wide range of endoscopic operative procedures. We report an extremely rare case of a patient who had a bowel obstruction caused by an internal supravesical hernia that was repaired via a minimally invasive technique. Abdominal computed tomography (CT) showed signs of small bowel obstruction: the cause was thought to be an invagination due to a small bowel tumor. Laparoscopic exploration of the dilated small bowel segments allowed the diagnosis of supravesical hernia. Reduction was performed with slight traction, and the hernial orifice was closed with intracorporeal sutures. To our knowledge, this is the first repair of an internal supravesical hernia ever to receive herniorraphy based on laparoscopic techniques. The mean starting time for bowel-function and mean hospital stay following the laparoscopic release of the intestinal obstruction were significantly shorter than is typically seen with standard techniques.