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Human mitochondrial DNA is a small circular double-stranded molecule that is essential for cellular energy production. A specialized protein machinery replicates the mitochondrial genome, with DNA polymerase γ carrying out synthesis of both strands. According to the prevailing mitochondrial DNA replication model, the two strands are replicated asynchronously, with the leading heavy-strand initiating first, followed by the lagging light-strand. By using purified recombinant forms of the replication proteins and synthetic DNA templates, it is possible to reconstitute mitochondrial DNA replication in vitro. Here we provide details on how to differentially reconstitute replication of the leading- and lagging-strands.Ulcer disease in excluded segments after Roux-Y gastric bypass (RYGB) is rare but can evolve into a life-threatening situation. The excluded segments exhibit a different behavior from that of non-altered anatomy; perforated ulcers do not result in pneumoperitoneum or free fluid, and therefore must be met with a low threshold for surgical exploration. The anatomical changes after RYGB impede routine access to the remnant stomach and duodenum. There are various options to address bleeding or perforated ulcers. While oversewing and drainage preserves the anatomy and forgoes resection, remnant gastrectomy offers a definitive solution. The importance of traditional risk factors such as smoking or use of non-steroidal anti-inflammatory drugs is unclear. Eradication of Helicobacter pylori and secondary prophylaxis with proton-pump inhibitors is advisable, albeit in double-dose.

Currently, there is little consensus on management of the in situ gallbladder of patients undergoing gastric bypass. Our aim was to evaluate outcomes of selective concomitant cholecystectomy (CCY) and long-term biliary outcomes after Roux-en-Y gastric bypass (RYGB).

We performed a retrospective analysis of patients undergoing laparoscopic RYGB (LRYGB) between 2008 and 2018. Chi-square, Fisher's exact, or Wilcoxon rank-sum tests were used to compare outcomes. Concomitant CCY was performed on a selective basis.

Three thousand and four patients underwent a RYGB (LRYGB n = 2458, open RYGB n = 546). Fifty-two percent (n = 1670) of patients had undergone CCY at any stage. Thirty-one percent of patients (n = 933) had CCY prior to RYGB, 13% (n = 403) had a concomitant CCY and 13% (n = 214) of the remainder required interval CCY. In the LRYGB subgroup, 29.9% (n = 735) had a prior CCY; 12.9% (n = 202) of those with an in situ gallbladder required interval CCY. Those who underwent concomitant CCY/LRYGB (n = 328) were compared with LRYGB alone (n = 1231). The concomitant CCY group was significantly older and had higher percentage of females, higher preoperative BMI, higher Charlson Comorbidity Index, and a higher medication count. There was no significant difference in BMI nadir, length of stay, complications, or mortality. Interval CCY had a higher incidence of CCY-related complications.

Our study suggests a higher percentage of bariatric patients with in situ gallbladders will undergo interval CCY than documented in recently published guidelines. Concomitant CCY can be performed without an increase in length of stay or complications. Interval CCY may be associated with a higher complication rate.

Our study suggests a higher percentage of bariatric patients with in situ gallbladders will undergo interval CCY than documented in recently published guidelines. Concomitant CCY can be performed without an increase in length of stay or complications. Interval CCY may be associated with a higher complication rate.Celiac disease (CD) is an immune-mediated systemic disorder triggered by gluten and related prolamins in genetically predisposed individuals. Here, we described a case of a 31-year-old Caucasian woman who exhibited cerebellar and psychiatric dysfunctions. The patient underwent single-photon emission computed tomography (SPECT-CT) before and after a gluten-free diet (GFD). There was an improvement in cerebellar perfusion accompanied by a remission of cerebellar manifestations. The maintenance of the psychiatric manifestations was related to the persistence of the hypoperfusion in the frontal lobes. The patient's psychiatric symptoms did not change after 4 months under a GFD in the hospital. To our knowledge, this is the first case that shows the relationship between improvement in cerebellar perfusion and remission of cerebellar clinical manifestations in a CD patient under a GFD.Parkinson's disease (PD) patients are at risk for developing bone health problems, and freezing of gait (FOG) in PD is associated with a high risk of falling and fracture. This study aimed to determine the association between FOG and bone mineral density (BMD) in patients with PD. We included 148 PD patients. FOG was assessed using the FOG Questionnaire (FOG-Q), and BMD was measured by dual-energy X-ray absorptiometry. Of 148 PD patients, 102 (68.9%) had FOG. PD patients with FOG were older and had longer disease duration, higher levodopa equivalent dose, higher modified Hoehn and Yahr stage, higher Unified PD Rating Scale motor score, higher FOG-Q score, higher total Non-Motor Symptom Scale score, and lower BMD scores in the femoral neck area than those without FOG. Pearson correlation analysis revealed that age, sex, body mass index, and age at onset were significantly correlated with areal BMDs in all areas. FOG-Q scores correlated negatively with areal BMDs in the total hip area and femoral neck, but not with areal BMD in the lumbar spine. Multivariate regression analysis showed that FOG-Q score was significantly correlated with areal BMD in the femoral neck, but not with areal BMDs in the lumbar spine or total hip. FOG in PD patients correlates significantly with BMD in the femoral neck area. Therefore, PD patients with FOG should be screened for osteoporosis.

E-cigarettes (e-cigs) release toxic chemicals known to increase blood pressure (BP) levels. The effects of e-cigs on BP, however, remain unknown. Studying BP may help characterize potential cardiovascular risks of short- and long-term e-cig use. We summarized published studies on the association of e-cig use with BP endpoints.

Thirteen e-cig trials (12 cross-over designs) and 1 observational study evaluated systolic and diastolic blood pressure (SBP and DBP). All trials included at least one e-cig arm with nicotine, 6 a no-nicotine e-cig arm, and 3 a placebo arm. SBP/DBP increased in most nicotine e-cig arms, in some non-nicotine e-cig arms, and in none of the placebo arms. The observational study followed e-cig users and nonsmokers for 3.5years with inconsistent findings. The use of e-cigs with and without nicotine may result in short-term elevations of both SBP and DBP. Prospective studies that investigate the long-term cardiovascular impact of e-cig use are needed.

Thirteen e-cig trials (12 cross-over designs) and 1 observational study evaluated systolic and diastolic blood pressure (SBP and DBP). All trials included at least one e-cig arm with nicotine, 6 a no-nicotine e-cig arm, and 3 a placebo arm. SBP/DBP increased in most nicotine e-cig arms, in some non-nicotine e-cig arms, and in none of the placebo arms. The observational study followed e-cig users and nonsmokers for 3.5 years with inconsistent findings. The use of e-cigs with and without nicotine may result in short-term elevations of both SBP and DBP. Prospective studies that investigate the long-term cardiovascular impact of e-cig use are needed.

Hepatitis C virus (HCV) has become an easily treatable disease after the introduction of sofosbuvir-based direct-acting antiviral (DAA) regimens. This is a large single center experience of changing severity and outcome profile of HCV-related liver disease after availability of DAAs.

A retrospective analysis of prospectively collected liver transplantation (LT) database of adults (age > 18years at the time of LT) was performed from June 2010 to July 2018. A total of 410 patients (including 26 co-infection with hepatitis B) underwent LT for hepatitis C-related decompensated cirrhosis and/or hepatocellular carcinoma (HCC) out of 1754 adult transplantation in the defined period.

The study group comprised of 296 males and 114 females aged 52.1 ± 7.9years. HCV-related decompensated cirrhosis and/or HCC as indication of LT was present in 289/1016 (28.4%) during 2010-2014, which was reduced to 121/738 (16.3%) during2015-2018 (p = 0.000). The LT recipients for HCV-related cirrhosis had significantly lower Child's and model for end-stage liver disease (MELD) score during 2015-2018 as compared to that during2010-2014; Child's score was 7.9 ± 2.2 vs. 8.6 ± 2.1, p = 0.003; MELD scorewas 13.9 ± 5.3 vs. 17.1 ± 5.8, p = 0.000, respectively. There was a trend towards better survival in HCV patients during 2015-2018 as compared to that during 2010-2014. Significantly more patients had HCV RNA negative status before LT during 2015-2018 (38.8% vs. 13%, p = 0.000); moreover, the proportion of LT for decompensated cirrhosis (without HCC) decreased significantly in the latter period, 64.0% vs. 42.1% (p = 0.000).

In the DAA era, HCV as an indication for LT has decreased and patients have less severe disease at transplantation. Biricodar solubility dmso There is a trend towards better patient survival.

In the DAA era, HCV as an indication for LT has decreased and patients have less severe disease at transplantation. There is a trend towards better patient survival.Micrometastatic disease that is present at the time of surgery is responsible for the overwhelming majority of deaths in patients with what is otherwise perceived to be local and regional colon cancer. The goal of perioperative therapy is to eliminate microscopic residual disease that would otherwise be left behind following surgery. A secondary goal specific to neoadjuvant (preoperative) therapy is to downstage tumors deemed potentially not amenable to an R0 resection on the basis of a suspected T4b primary (locally invading into a surrounding structure). In this landmark series paper, we review the current standard for perioperative therapy in patients with colon cancer.

Hepatic artery infusion (HAI) chemotherapy is associated with overall survival (OS) in patients with resected colon cancer liver metastases (CLM). The prognostic impact of primary tumor location in CLM following hepatic resection in patients receiving regional HAI is unknown. This study seeks to investigate the prognostic impact of HAI in relation to laterality in this patient population.

Consecutive patients with resected CLM, with known primary tumor site treated with and without HAI, were reviewed from a prospective institutional database. Correlations between HAI, laterality, other clinicopathological factors, and survival were analyzed, and Cox proportional hazard regressionwas used to determine whether laterality was an independent prognostic factor.

From 1993 to 2012, 487 patients [182 with right colon cancer (RCC),305 with left colon cancer (LCC)] were evaluated with a median follow-up of 6.5years. Fifty-seven percent(n = 275) received adjuvant HAI. Patients with RCC had inferior 5-year OS compared with LCC (56% vs.