Association between oral contraceptive use and pancreatic cancer risk: A systematic review and meta-analysis

BACKGROUNDStudies on the association of oral contraceptive (OC) use and pancreatic cancer showed inconsistent findings. AIMTo evaluate the relationship between OC use and pancreatic cancer risk. METHODSA literature search for observational studies (case-control and cohort studies) was conducted up to December 2020. A meta-analysis was performed by calculating pooled relative risks (RRs) and 95% confidence intervals (CIs). Heterogeneity was assessed using Cochran’s chi-square test and I² statistic. Subgroup analyses were performed by study design, source of controls in case-control studies, number of cases of pancreatic cancers, study quality according to Newcastle-Ottawa Scale score, geographical region and menopausal status. All analyses were performed using Review Manager 5.3 (RevMan 5.3).RESULTSA total of 21 studies (10 case-control studies and 11 cohort studies) were finally included in the present meta-analysis, comprising 7700 cases of pancreatic cancer in total. A significant association was observed between the ever use of OC and pancreatic cancer risk in the overall analysis (RR = 0.85; 95%CI = 0.73-0.98; P = 0.03). Duration of OC use (< 1 year, < 5 years, 5-10 years, > 10 years) was not significantly associated with the risk of pancreatic cancer. Subgroup analyses revealed a statistically significant subgroup difference for the geographic region in which the study was conducted (Europe vs Americas vs Asia; P = 0.07). Subgroup analyses showed a statistically significant decrease in pancreatic cancer risk and OC use in high-quality studies, studies conducted in Europe, and in postmenopausal women. CONCLUSIONDespite the suggested protective effects of OC use in this meta-analysis, further epidemiological studies are warranted to fully elucidate the association between the use of OC and pancreatic cancer risk.     

RecQ helicase acts before RuvABC,RecG and XerC proteins during recombination in recBCD sbcBC mutants of Escherichia coli

The RecQ helicase is required by the RecF recombination pathway that is operative in recBC(D) sbcB sbcC(D) mutants of Escherichia coli. Genetic data suggest that RecQ participates in resection of DNA ends during initiation of recombination. In vitro, RecQ can unwind a variety of DNA substrates, including recombination intermediates such as D-loops and Holliday junctions. However, its potential role in processing of recombination intermediates during the late stage of the RecF pathway has not been genetically tested. Here we studied the effect of a recQ mutation on transductional recombination and DNA repair after γ-irradiation in ΔrecBCD ΔsbcB sbcC strains deficient for RuvABC, RecG and XerC proteins. RuvABC and RecG proteins process recombination intermediates in the late stage of recombination, whereas XerC is required to resolve chromosome dimers formed upon recombination. Our results do not reveal any substantial synergistic effect between the recQ mutation, on one hand, and ruvABC, recG and xerC mutations on the other. In addition, the recQ mutation suppresses chromosome segregation defects in γ-irradiated ruvABC recG and xerC mutants. These results suggest that RecQ acts upstream of RuvABC, RecG and XerC proteins, a finding that is compatible with its primary role in initiation of the RecF recombination pathway.     

Non-alcoholic fatty liver disease and obesity: Biochemical,metabolic and clinical presentations

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in the world. Presentation of the disease ranges from simple steatosis to non-alcoholic steatohepatitis (NASH). NAFLD is a hepatic manifestation of metabolic syndrome that includes central abdominal obesity along with other components. Up to 80% of patients with NAFLD are obese, defined as a body mass index (BMI) > 30 kg/m². However, the distribution of fat tissue plays a greater role in insulin resistance than the BMI. The large amount of visceral adipose tissue (VAT) in morbidly obese (BMI > 40 kg/m²) individuals contributes to a high prevalence of NAFLD. Free fatty acids derived from VAT tissue, as well as from dietary sources and de novo lipogenesis, are released to the portal venous system. Excess free fatty acids and chronic low-grade inflammation from VAT are considered to be two of the most important factors contributing to liver injury progression in NAFLD. In addition, secretion of adipokines from VAT as well as lipid accumulation in the liver further promotes inflammation through nuclear factor kappa B signaling pathways, which are also activated by free fatty acids, and contribute to insulin resistance. Most NAFLD patients are asymptomatic on clinical presentation, even though some may present with fatigue, dyspepsia, dull pain in the liver and hepatosplenomegaly. Treatment for NAFLD and NASH involves weight reduction through lifestyle modifications, anti-obesity medication and bariatric surgery. This article reviews the available information on the biochemical and metabolic phenotypes associated with obesity and fatty liver disease. The relative contribution of visceral and liver fat to insulin resistance is discussed, and recommendations for clinical evaluation of affected individuals is provided.     

The Influence of Etiologic Factors on Clinical Outcome in Patients with Peptic Ulcer Bleeding

Background

Peptic ulcer bleeding remains an important cause of morbidity and mortality.

Aim

The aim of this study was to evaluate the prevalence of non-steroidal anti-inflammatory drugs (NSAID) use, Helicobacter pylori infection and non-H. pylori?Cnon-NSAIDs causes of peptic ulcer bleeding and to identify the predictive factors influencing the rebleeding rate and in-hospital mortality in patients with bleeding peptic ulcer.

Methods

A total of 1,530 patients with endoscopically confirmed peptic ulcer bleeding were evaluated consecutively between January 2005 and December 2009. The 30-day mortality and clinical outcome were related to patient??s demographic data, endoscopic and clinical characteristics.

Results

The age-standardized 1-year cumulative incidence for peptic ulcer bleeding was 40.4 cases/100,000 people. The proportion of patients over 65?years increased from 45.7?% in 2005 to 61.4?% in 2009 (p?=?0.007). Overall 30-day mortality rate was 4.6?%, not significantly different for conservatively and surgically treated patients (4.9 vs. 4.1?%, p?=?0.87). Mortality was significantly higher in patients over 65?years of age and those with in-hospital bleeding recurrence. Patients with non-H. pylori?Cnon-NSAID idiopathic ulcers had significantly higher 30-day mortality rate than those with H. pylori ulcers and NSAID?CH. pylori ulcers (7.1 vs. 0 vs. 0.8?%, p?=?0.001 and p?=?0.007, respectively). There was no statistically significant difference between patients with NSAID ulcers and non-H. pylori?Cnon-NSAID idiopathic ulcers in terms of 30-day mortality rate (5.3 vs. 7.1?%, p?=?0.445).

Conclusion

The incidence of peptic ulcer bleeding has not changed over a 5-year observational period. The overall 30-day mortality was positively correlated to older age, underlying comorbid illnesses, in-hospital bleeding recurrence and the absence of H. pylori infection.     

Survivin gene promoter polymorphism -31G/C as a risk factor for keratocystic odontogenic tumor development

Several single nucleotide polymorphisms in survivin gene promoters, notably -31G/C, have been shown to modulate the expression and activity of the survivin protein. Consequently, the -31G/C polymorphism has been identified as a risk factor for the development of several types of tumors. The aim of this study was to investigate a possible association between the -31G/C polymorphism and the risk for keratocystic odontogenic tumor (KCOT) development. DNA from 52 biopsy specimens of KCOTs and from 82 buccal swabs of healthy individuals was subjected to PCR restriction fragment length polymorphism analysis to identify individual genotypes. The distribution of genotypes in KCOT and control groups, respectively, was: GG: 30 (57.7%) vs. 26 (31.7%); CG: 17 (32.7%) vs. 45 (54.9%); and CC: 5 (9.6%) vs. 11 (13.4%), respectively. These differences were statistically significant. The G allele was more common in the KCOT group than in the control group: 76 (74%) vs. 96 (59%), respectively. Logistic regression analysis showed that GC heterozygotes had a considerably decreased susceptibility for KCOTs compared with GG homozygotes. The same was true for GC+CC vs. GG. The GG genotype of the -31G/C polymorphism might be a risk factor for KCOT development.     

In vivo assessment of DNA damage induced in oral mucosa cells by fixed and removable metal prosthodontic appliances

Given long-term effect on oral tissues due to contact with dental appliances, the biocompatibility studies of casting alloys are of great importance. It has been previously documented that metal dental appliances, due to corrosion, might induce genotoxic and mutagenic effects in cells. Therefore, the aim of presented study was to examine the genotoxicity of two dental casting alloys (Co-Cr-Mo and Ni-Cr) commonly used in fixed and removable prosthodontic appliances that are in contact with the oral epithelium for 5 years or more. For that purpose, 55 age-matched subjects were included in the study; 30 wearers of prosthodontic appliances and 25 controls. Buccal cells of oral mucosa were collected and processed for further analysis. The cell viability has been assessed by trypan blue exclusion test, while genotoxic effect of metal ions on DNA in oral mucosa cells was studied by use of alkaline comet assay. Results have shown significantly higher comet assay parameters (tail length and percentage DNA in the tail) in the group wearing metal appliances. Both subjects with Co-Cr-Mo alloy and Ni-Cr alloy showed significantly higher comet assay parameters when compared with controls. It has been confirmed that metal ions released by the two base metal dental casting alloys examined in this study, might be responsible for DNA damage of oral mucosa cells. Therefore, the results of this study emphasize the importance of the in vivo evaluation of dental materials with respect to their genotoxicity, which is of major importance to ensure long-term biocompatibility.     

A case of postpartum eosinophilic gastroenteritis and review of the literature

Eosinophilic gastroenteritis (EG) is a rare disease of unknown etiology that can involve any area of the gastrointestinal (GI) tract. It can be classified into three major types: predominantly mucosal, muscularis, or subserosal form. Diagnosis of EG is confirmed after the exclusion of other disorders having similar features, such as parasitic infection, carcinoma, allergy, and autoimmune conditions such as Churg-Strauss disease. Correct diagnosis hinges on the presence of eosinophilic infiltration of one or more areas of the GI tract, without extraintestinal involvement. We present the case of a 30-year-old female with symptoms of EG 26 days after delivery. After corticosteroid and montelukast treatment for 2 weeks, all symptoms and objective clinical findings disappeared. Although numerous cases of this disorder have been described, to our knowledge this is the first case of postpartum EG. This case highlights the need to include this entity in the differential diagnosis of postpartum GI disorders.     

Management of Smell Dysfunction

Olfaction is an essential chemosensory system in the living world. Although less appreciated in humans, smell impairment significantly affects many aspects of quality of life. Smell disorders may be caused by an impaired nasal airway or by lesions in the olfactory system, leading to reduced or distorted smell perception. The most common causes of smell disorders are aging, upper respiratory tract infection, sinonasal disease, and head trauma. Recovery is rarely complete. Counseling is important in progressive or severe smell loss. In patients with distorted smell perception, antidepressant medication is sometimes necessary. Best response to treatment is achieved for nasal obstruction and sinonasal inflammatory disease. Treatment of olfactory impairment caused by sinonasal disease includes medication with topical and systemic steroids, or surgery for refractory cases. Although there are reports that surgical resection of olfactory neurons may lead to reinnervation and recovery of smell, adequate treatment of the smell loss remains an unmet need.     

The lack of influence of IVS5-91 G>A polymorphism of the SCN1A gene on efficacy of lamotrigine in patients with focal epilepsy

ABSTRACT

Background: IVS5-91G>A (rs3812718) polymorphism of the sodium voltage-gated channel alpha subunit 1 (SCN1A) gene has been associated with inadequate responsiveness to common antiepileptic drugs which act as sodium channel blockers. This study was performed to investigate the effect of IVS5-91G>A (rs3812718) polymorphism on lamotrigine (LTG) efficacy in a cohort of patients with non-lesional focal epilepsy taking LTG as monotherapy.

Methods: A total of 100 of patients with non-lesional focal epilepsy on LTG monotherapy was included in this prospective interventional study. After reaching a stable dose of LTG patients were followed-up for 12 consecutive months. LTG responsiveness was defined as a 75% or more reduction in seizure frequency on a stable dose of LTG. Genotyping was performed at the end of the study using standard procedures and data were correlated with clinical data.

Results: There were no significant differences in the prevalence of responsiveness to LTG between carriers of different genotypes. Average maintenance LTG doses in the responder group differed by genotype in the order AA>GA>GG, but these differences did not reach statistical significance.

Conclusion: Our data suggest lack of association between SCN1A IVS5-91G>A (rs3812718) polymorphism and response to LTG.