The polymorphism of XRCC1 Arg399Gln (rs25487) and male infertility risk: a meta-analysis of 1,407 cases and 974 control studies.

X-ray repair cross-complementing group 1 (XRCC1) is a scaffold protein and a key element in DNA base excision repair process. Although, the role of XRCC1 polymorphisms in male infertility has been studied broadly, it is still a matter of debate. Hence, in order to shed light on the problem, we performed a meta-analysis to evaluate the overall effect of XRCC1 polymorphisms in male infertility risk. Databases, Web of Science, PubMed, Scopus, and Google Scholar were searched until September 15, 2018. Afterwards, the genotypes' distribution, genotyping methods, and ethnicity groups were extracted, and overall analyses were conducted. A total number of five researches on 1,407 subjects and 974 controls were found to meet our criteria in this meta-analysis. The XRCC1 Arg399Gln (rs25487) polymorphism was analyzed. This is the first meta-analysis to investigate the association of XRCC1 polymorphisms (codon 399) and male infertility risk. Our results indicated that the XRCC1 Arg399Gln polymorphism was not associated with male infertility risk in the total studied populations (Tab. 2, Fig. 3, Ref. 26). Keywords: meta-analysis; male infertility; polymorphism; XRCC1 Arg399Gln.

Microbes: possible link between modern lifestyle transition and the rise of metabolic syndrome.

The rapid decrease in infectious diseases globally has coincided with an increase in the prevalence of obesity and other components of metabolic syndrome. Insulin resistance is a common feature of metabolic syndrome and can be influenced by genetic and non-genetic/environmental factors. The emergence of metabolic syndrome epidemics over only a few decades suggests a more prominent role of the latter. Changes in our environment and lifestyle have indeed paralleled the rise in metabolic syndrome. Gastrointestinal tract microbiota, the composition of which plays a significant role in host physiology, including metabolism and energy homeostasis, are distinctly different within the context of metabolic syndrome. Among humans, recent lifestyle-related changes could be linked to changes in diversity and composition of 'ancient' microbiota. Given the co-adaptation and co-evolution of microbiota with the immune system over a long period of time, it is plausible that such lifestyle-related microbiota changes could trigger aberrant immune responses, thereby predisposing an individual to a variety of diseases. Here, we review current evidence supporting a role for gut microbiota in the ongoing rise of metabolic syndrome. We conclude that population-level shifts in microbiota can play a mediatory role between lifestyle factors and pathogenesis of insulin resistance and metabolic syndrome.

Colonic immune cells in irritable bowel syndrome: A systematic review and meta-analysis.

BACKGROUND & AIMS: Increases in mucosal immune cells have frequently been observed in irritable bowel syndrome (IBS) patients. However, this finding is not completely consistent between studies, possibly due to a combination of methodological variability, population differences and small sample sizes. We performed a meta-analysis of case-control studies that compared immune cell counts in colonic biopsies of IBS patients and controls. METHODS: PubMed and Embase were searched in February 2017. Results were pooled using standardized mean difference (SMD) and were considered significant when zero was not within the 95% confidence interval (CI). Heterogeneity was assessed based on I2 statistics where I2  ≤ 50% and I2  > 50% indicated fixed and random effect models, respectively. KEY RESULTS: Twenty-two studies on 706 IBS patients and 401 controls were included. Mast cells were increased in the rectosigmoid (SMD: 0.38 [95% CI: 0.06-0.71]; P = .02) and descending colon (SMD: 1.69 [95% CI: 0.65-2.73]; P = .001) of IBS patients. Increased mast cells were observed in both constipation (IBS-C) and diarrhea predominant IBS (IBS-D). CD3+ T cells were increased in the rectosigmoid (SMD: 0.53 [95% CI: 0.21-0.85]; P = .001) and the descending colon of the IBS patients (SMD: 0.79, 95% CI [0.28-1.30]; P = .002). This was possibly in relation to higher CD4+ T cells in IBS (SMD: 0.33 [95% CI: 0.01-0.65]; P = .04) as there were no differences in CD8+ T cells. CONCLUSIONS & INFERENCES: Mast cells and CD3+ T cells are increased in colonic biopsies of patients with IBS vs non-inflamed controls. These changes are segmental and sometimes IBS-subtype dependent. The diagnostic value of the quantification of colonic mucosal cells in IBS requires further investigation.

Toll-like receptor expression in crypt epithelial cells, putative stem cells and intestinal myofibroblasts isolated from controls and patients with inflammatory bowel disease.

The aim of our studies was to investigate the expression of Toll-like receptor (TLR)-2 and TLR-4 (and in some studies TLR-5) in myofibroblasts and small and large intestinal crypt epithelial cells from control patients and those affected by Crohn's disease and ulcerative colitis. Isolated and disaggregated crypt epithelial cells and monolayers of myofibroblasts were used for studies by reverse transcription-polymerase chain reaction (RT-PCR), real-time RT-PCR, flow cytometry, immunocytochemistry and Western blot analysis. Compared to control cells, crypt epithelial cells isolated from active ulcerative colitis and Crohn's disease colonic mucosal samples showed significantly higher expression of TLR-2 and TLR-4 transcripts and protein (on the cell surface). There was also enhanced expression of TLR-4 in crypt cells from ileal Crohn's disease. Expression of TLR-2 and TLR-4 transcripts in crypt epithelial cells isolated from inflamed mucosa of distal ulcerative colitis did not differ significantly from such cells obtained from the normal proximal colon. Crypt epithelial cells with side population characteristics (putative stem cells) also expressed transcripts and protein for TLR-2, TLR-4 and TLR-5. Colonic myofibroblast expression of these TLRs was much weaker than in crypt epithelial cells. In conclusion, enhanced TLR-2 and TLR-4 expression by crypt epithelial cells in active inflammatory bowel disease likely reflects greater ability to respond to microbial products. Results from our studies using mucosal samples from patients with distal ulcerative colitis suggest that the enhanced expression of these TLRs could be constitutive. TLR-2, TLR-4 and TLR-5 expression by stem cells imply ability to respond to distinct bacterial products.

Intestinal stem cell imaging in colorectal cancer screening.

Colorectal cancer (CRC) is a common cancer and cause of cancer-related death worldwide. Although, the step-wise genetic alteration in the course of adenoma-carcinoma progression is well-understood, the mechanism of the tumour initiation and promotion is yet to be elucidated. Murine studies indicate that intestinal tumour originates from normal intestinal stem cells which acquire the oncogenic hits. It is plausible to consider the abnormality of the stem cell compartment as the earliest potentially detectable phenotypic change in the course of intestinal tumourigenesis. Hereby, it is hypothesised that imaging of the abnormal state of the intestinal stem cell compartment could potentially be integrated in CRC screening strategy.

First-trimester screening for chromosomal abnormalities by integrated application of nuchal translucency, nasal bone, tricuspid regurgitation and ductus venosus flow combined with maternal serum free ß-hCG and PAPP-A: a 5-year prospective study.

OBJECTIVE: To investigate the performance of first-trimester screening for chromosomal abnormalities by integrated application of nuchal translucency thickness (NT), nasal bone (NB), tricuspid regurgitation (TR) and ductus venosus (DV) flow combined with maternal serum free ß-human chorionic gonadotropin (fß-hCG) and pregnancy-associated plasma protein-A (PAPP-A) at a one-stop clinic for assessment of risk (OSCAR). METHODS: In total, 13,706 fetuses in 13,437 pregnancies were screened for chromosomal abnormalities during a period of 5 years. Maternal serum biochemical markers and maternal age were evaluated in combination with NT, NT + NB, NT + NB + TR, and NT + NB + TR + DV flow data in 8581, 242, 236 and 4647 fetuses, respectively. RESULTS: In total, 51 chromosomal abnormalities were identified in the study population, including 33 cases of trisomy 21, eight of trisomy 18, six of sex chromosome abnormality, one of triploidy and three of other unbalanced abnormalities. The detection rate and false-positive rate (FPR) for trisomy 21 were 93.8% and 4.84%, respectively, using biochemical markers and NT, and 100% and 3.4%, respectively, using biochemical markers, NT, NB, TR and DV flow. CONCLUSION: While risk assessment using combined biochemical markers and NT measurement has an acceptable screening performance, it can be improved by the integrated evaluation of secondary ultrasound markers of NB, TR and DV flow. This enhanced approach would decrease the FPR from 4.8 % to 3.4 %, leading to a lower number of unnecessary invasive diagnostic tests and subsequent complications, while maintaining the maximum level of detection rate. Pre- and post-test genetic counseling is of paramount importance in either approach.

Recurrent severe anion gap metabolic acidosis secondary to episodic ethylene glycol intoxication.

Acute ethylene glycol toxicity and its attendant metabolic derangement is a well described clinical entity. Recurrent severe anion gap metabolic acidosis consequent to episodic ingestion of ethylene glycol has not been previously reported. We present a patient who developed severe anion gap metabolic acidosis with no osmolar gap and hypokalemia, consequent to episodic ethylene glycol ingestion. Modest artifactual elevation of the serum lactic acid level and rapid response to intravenous bicarbonate infusion may serve as diagnostic clues. Consideration of these aberrant features should be included in the clinical assessment of severe anion gap metabolic acidosis.

[Results of corrective osteotomy of malunited extension fractures of the radius at the usual site]. / Ergebnisse der Korrekturosteotomie fehlverheilter Extensionsfrakturen der Speiche an typischer Stelle.

BACKGROUND: There is an increasing interest in the corrective osteotomy for the malunited distal radius fracture. Already in the seventies we developed an operative technique for the correction of the malunited Colles' fracture. The technique is based on a special plate, which facilitates precise restoration of the angulation of the joint surface and the length of the radius. The purpose of our study is to investigate the results of our method and to compare them with results in the literature. PATIENTS AND METHODS: We examined retrospectively the patients with a malunited Colles' fracture corrected by our technique until August 1996. The investigated criteria were range of motion, grip strength, pain relief, and X-ray findings. RESULTS: Until August 1996, we have performed 124 corrective osteotomies for malunited Colles' fractures; 115 were carried out by our technique; 91 of them could be examined. The mean follow-up time was 4.5 years. The range of motion has improved in all planes, especially for flexion. Grip strength increased but still remained below the level of the opposite side. On X-ray, average dorsal tilt of the radiocarpal joint was 24 degrees preoperatively and was reduced to an almost normal palmar tilt of 7 degrees. Ulnar-plus variance was reduced from 6 mm to less than 1 mm. CONCLUSION: Corrective osteotomy of the distal radius is of great benefit and leads to improved hand function and diminished pain. The use of our special plate facilitates this ambitious operation considerably.