Increased risk of a herpes zoster attack in patients receiving androgen deprivation therapy for prostate cancer.

This study aimed to examine the association of herpes zoster (HZ) with androgen deprivation therapy (ADT) use among patients with prostate cancer (PC), using a population-based data set. The study sample for this study was retrieved from the Taiwan Longitudinal Health Insurance Database 2005. We selected 877 patients with PC who had received ADT as the study group, while 849 patients with PC who had not received ADT served as the comparison group. Each study patient was individually tracked for a 3-year period to discriminate those who subsequently received a diagnosis of HZ. Of the total 1,726 sampled patients, the incidence rate of HZ per 100 person-years was 1.80 (95% CI: 1.41-2.25) during the 3-year follow-up period. In particular, incidence rates of HZ per 100 person-years were 2.36 (95% CI: 1.75-3.13) and 1.24 (95% CI: 0.81-1.81), respectively, for patients with PC who had and those who had not received ADT. Furthermore, Cox proportional hazard regressions showed that the adjusted hazard ratio for an HZ attack during the 3-year follow-up period for patients with PC who had received ADT was 1.88 (95% CI: 1.13-3.11) than those who had not received ADT. We concluded that patients with PC who had received ADT had an increased risk of HZ.

Novel loci associated with usual sleep duration: the CHARGE Consortium Genome-Wide Association Study.

Usual sleep duration is a heritable trait correlated with psychiatric morbidity, cardiometabolic disease and mortality, although little is known about the genetic variants influencing this trait. A genome-wide association study (GWAS) of usual sleep duration was conducted using 18 population-based cohorts totaling 47 180 individuals of European ancestry. Genome-wide significant association was identified at two loci. The strongest is located on chromosome 2, in an intergenic region 35- to 80-kb upstream from the thyroid-specific transcription factor PAX8 (lowest P=1.1 × 10(-9)). This finding was replicated in an African-American sample of 4771 individuals (lowest P=9.3 × 10(-4)). The strongest combined association was at rs1823125 (P=1.5 × 10(-10), minor allele frequency 0.26 in the discovery sample, 0.12 in the replication sample), with each copy of the minor allele associated with a sleep duration 3.1 min longer per night. The alleles associated with longer sleep duration were associated in previous GWAS with a more favorable metabolic profile and a lower risk of attention deficit hyperactivity disorder. Understanding the mechanisms underlying these associations may help elucidate biological mechanisms influencing sleep duration and its association with psychiatric, metabolic and cardiovascular disease.

Primary skin closure after damage control laparotomy.

BACKGROUND: Damage control laparotomy (DCL) is used widely in the management of patients with traumatic injuries but carries significant morbidity. Surgical-site infection (SSI) also carries potential morbidity, increased costs and prolonged hospital stay. The aim of this study was to determine whether primary skin closure after DCL increases the risk of SSI. METHODS: This was a retrospective institutional review of injured patients undergoing DCL between 2004 and 2012. Outcomes of patients who had primary skin closure at the time of fascial closure were compared with those of patients whose skin wound was left open to heal by secondary intention. The association between skin closure and SSI was evaluated using propensity score-adjusted multivariable logistic regression. RESULTS: Of 510 patients who underwent DCL, primary fascial closure was achieved in 301. Among these, 111 (36.9 per cent) underwent primary skin closure and in 190 (63.1 per cent) the skin wound was left open. Fascial closure at the initial take-back surgery was associated with having skin closure (P < 0.001), and colonic injury was associated with leaving the skin open (P = 0.002). On multivariable analysis, primary skin closure was associated with an increased risk of abdominal SSI (P = 0.020), but not fascial dehiscence (P = 0.446). Of patients receiving skin closure, 85.6 per cent did not develop abdominal SSI and were spared the morbidity of managing an open wound at discharge. CONCLUSION: Primary skin closure after DCL is appropriate but may be associated with an increased risk of SSI.

Use of health care services by patients with psoriasis: a population-based study.

BACKGROUND: Although psoriasis is seldom life threatening, very few studies have compared differences in health care service use between patients with and without psoriasis. OBJECTIVES: To investigate differences in health care service use between patients with and without psoriasis. METHODS: Patient details and data on their use of health services were retrieved from the Taiwan Longitudinal Health Insurance Database 2000. We included 3649 patients with psoriasis and 3649 without it. Each patient was followed for a 1-year period to estimate their utilization of health care resources. Student t-tests were used to compare differences in health care services use between patients with and without psoriasis. RESULTS: For dermatology services, patients with psoriasis had significantly more outpatient visits (3·5 vs. 0·9), and higher outpatient and total costs (US$148·00 vs. US$12·20 and US$581·60 vs. US$347·20, respectively) than those without psoriasis. For nondermatology services, patients with psoriasis had more outpatient visits (21·3 vs. 17·6), and higher outpatient and total costs (US$904·60 vs. US$663·50 and US$1335·50 vs. US$998·30, respectively) than those without psoriasis. For overall health care service use, patients with psoriasis had significantly more outpatient visits (24·8 vs. 18·5; P < 0·01) and greater total costs (US$1917·10 vs. US$1345·60; P < 0·01) than those without psoriasis. This indicates that the total cost was about 1·4-fold greater for patients with psoriasis than those without it. CONCLUSIONS: Patients with psoriasis used health care services significantly more often than those without psoriasis.

Statin Use Is Associated with Bladder Pain Syndrome/Interstitial Cystitis: A Population-Based Case-Control Study.

INTRODUCTION: Statin may induce epithelial dysfunction of the bladder urothelium. Epithelial dysfunction was proposed as one of the major potential etiologies for bladder pain syndrome/interstitial cystitis (BPS/IC). In this study, we examined the association between statin use and BPS/IC using a population-based study. SUBJECTS AND METHODS: This case-control study used the Taiwan Longitudinal Health Insurance Database. In total, 815 female subjects with BPS/IC and 4075 randomly selected female controls were included. We used a conditional logistic regression to compute the odds ratio (OR) for having previously used statins between cases and controls. RESULTS: A conditional logistic regression analysis showed that the OR of prior statin users for cases was 1.52 (95% confidence interval (CI): 1.19-1.94) compared to controls after adjusting for diabetes, hypertension, coronary heart disease, obesity, chronic pelvic pain, irritable bowel syndrome, fibromyalgia, chronic fatigue syndrome, depression, panic disorder, migraines, sicca syndrome, allergies, endometriosis, and asthma. Furthermore, adjusted ORs of regular and irregular statin use for cases were 1.58 (95% CI: 1.20-2.08) and 1.53 (95% CI: 1.02-2.31), respectively, compared to controls. CONCLUSION: We concluded that there was an association between statin use and BPS/IC.

Oxidative stress/reactive metabolite gene expression signature in rat liver detects idiosyncratic hepatotoxicants.

Previously we reported a gene expression signature in rat liver for detecting a specific type of oxidative stress (OS) related to reactive metabolites (RM). High doses of the drugs disulfiram, ethinyl estradiol and nimesulide were used with another dozen paradigm OS/RM compounds, and three other drugs flutamide, phenacetin and sulindac were identified by this signature. In a second study, antiepileptic drugs were compared for covalent binding and their effects on OS/RM; felbamate, carbamazepine, and phenobarbital produced robust OS/RM gene expression. In the present study, liver RNA samples from drug-treated rats from more recent experiments were examined for statistical fit to the OS/RM signature. Of all 97 drugs examined, in addition to the nine drugs noted above, 19 more were identified as OS/RM-producing compounds-chlorpromazine, clozapine, cyproterone acetate, dantrolene, dipyridamole, glibenclamide, isoniazid, ketoconazole, methapyrilene, naltrexone, nifedipine, sulfamethoxazole, tamoxifen, coumarin, ritonavir, amitriptyline, valproic acid, enalapril, and chloramphenicol. Importantly, all of the OS/RM drugs listed above have been linked to idiosyncratic hepatotoxicity, excepting chloramphenicol, which does not have a package label for hepatotoxicity, but does have a black box warning for idiosyncratic bone marrow suppression. Most of these drugs are not acutely toxic in the rat. The OS/RM signature should be useful to avoid idiosyncratic hepatotoxicity of drug candidates.

Circular closure is associated with the lowest rate of surgical site infection following stoma reversal: a systematic review and multiple treatment meta-analysis.

AIM: Stoma reversal is frequently complicated by surgical site infection (SSI). To reduce SSI, several techniques for skin closure have been studied, with no agreement on which is best. The aim of this study was to identify the skin closure technique associated with the lowest rate of SSI following stoma reversal. METHOD: We systematically searched MEDLINE (PubMed and OvidSP), Scopus and clinical registries from 1 January 1980 to 24 March 2012, and included original reports on adult patients following stoma reversal. A network of treatments was created to map the comparisons between skin closure techniques, including primary closure, primary closure with a drain, secondary closure, delayed primary closure, loose primary closure and circular closure. Pairwise meta-analyses were performed for all available direct comparisons of closure types and heterogeneity was assessed. A multiple-treatments meta-analysis was conducted to estimate relative treatment effects between competing closure types (reported as an odds ratio with 95% credible interval, and a probability that each treatment is best). Several sensitivity analyses were performed. RESULTS: Fifteen studies were identified with a total of 2921 cases of stoma reversal. Overall, study quality was poor with observed low (one study), moderate (seven studies) and high (seven studies) risk of bias. Circular closure was associated with the lowest SSI risk (OR 0.12; 95% CI 0.02-0.40) and was the best of six skin closure techniques (probability of being best = 68.9%). Circular closure remained the best after sensitivity analyses. CONCLUSION: This study showed that circular closure is the best skin closure technique after stoma reversal in terms of SSI rate, but the quality of supporting evidence is limited, precluding definite conclusions.

Antibiotic resistance and molecular typing of Photobacterium damselae subsp. damselae, isolated from seafood.

AIM: The objectives of our study is to determinate the antibiotic susceptibility of this organism to different antibiotics to determine the discriminatory power of the molecular typing methods. METHODS AND RESULTS: In this study, 50 Photobacterium damselae subsp. damselae isolates from Scomber australasicus and Rachycentron canadum were collected in Taiwan and their resistance to 15 different antimicrobial agents was determined. In addition, random amplification of polymorphic DNA (RAPD) and pulsed-field gel electrolysis (PFGE) were performed to study the epidemiology and clonal relationship of P. damselae subsp. damselae. The results showed that the 50 isolates generated 25 typeable profiles with multidrug resistance to 3-7 antimicrobials. The results also indicate that the RAPD and PFGE methods have high discriminatory power for molecular subtyping. CONCLUSION: Photobacterium damselae subsp. damselae isolates from fish to examine for multidrug resistance to antimicrobials. RAPD and PFGE methods revealed the high discriminatory power for molecular subtyping and provided information that could be used for risk assessment of P. damselae subsp. damselae infections. SIGNIFICANCE AND IMPACT OF THE STUDY: These results may help in epidemiological investigations of P. damselae subsp. damselae and may be useful in controlling or treating P. damselae subsp. damselae infections in aquaculture and clinical therapy.

Risk factors of involuntary referral by police to ER psychiatric services for patients with a severe mental illness: A GEE analysis.

This study aimed to identify risk factors for involuntary referral by police to emergency room (ER) psychiatric services for community-based patients with a mental illness via a generalized estimating equation (GEE) analysis. The analysis was based on data from the Management Information System of Psychiatric Care (MISPC) system for patients with a severe mental illness in Taipei, Taiwan and registered referral records of the police. Data on 6378 patients aged ≥20 years were used in this study, including 164 patients who were involuntarily referred to the ER by the police and 6214 patients who were not during the period of January 1, 2018 to December 31, 2020. GEEs were utilized to explore possible risk factors of repeated involuntary referral to ER psychiatric services for patients with a severe mental illness. The logistic regressions indicated that patients defined as "severe" according to the Mental Health Act of Taiwan (crude odds ratio (OR): 3.840, 95 % confidence interval (CI): 2.407-6.126), with a disability (crude OR: 3.567, 95 % CI: 1.339-9.501), with two or more family members with a psychiatric disorder (crude OR: 1.598, 95 % CI: 1.002-2.548), with a history of a suicide attempt (crude OR: 25.582, 95 % CI: 17.608-37.167), and with a history of domestic violence (crude OR: 16.141, 95 % CI: 11.539-22.579) were positively associated with involuntary referral to ER psychiatric services. However, age (crude OR: 0.971, 95 % CI: 0.960-0.983) and the MISPC score (crude OR: 0.834, 95 % CI: 0.800-0.869) were inversely associated with involuntary referral to ER psychiatric services. After adjusting for demographics and potential confounders, we found that patients defined as "severe" (Exp (ß): 3.236), with a disability (Exp (ß): 3.715), with a history of a suicide attempt (Exp (ß): 8.706), and with a history of domestic violence (Exp (ß): 8.826), as well as age (Exp (ß): 0.986) and the MISPC score (Exp (ß): 0.902) remained significantly associated with repeated involuntary referral to ER psychiatric services. In conclusion, community-based mentally ill patients with a history of a suicide attempt, with a history of domestic violence, with a severe illness, and with a profound level of disability were highly associated with involuntary referral to ER psychiatric services. We suggest that community mental health case managers identify significant factors associated with involuntary referral to ER psychiatric services to accordingly arrange case management plans.

Contralateral exploration and repair of occult inguinal hernias during laparoscopic inguinal hernia repair: systematic review and Markov decision process.

BACKGROUND: Contralateral clinically occult hernias are frequently noted at the time of laparoscopic unilateral inguinal hernia repair. There is no consensus on the role of contralateral exploration and repair. This systematic review assessed the safety and efficacy of operative repair of occult contralateral inguinal hernias found during unilateral repair. METHODS: PubMed, Embase, and the Cochrane Central Register of Controlled Trials were searched from inception to February 2020. Adults diagnosed with a unilateral inguinal hernia undergoing laparoscopic repair were included. The primary outcome was the incidence of occult contralateral hernias. Summative outcomes of operative and expectant management were reported along with development of a Markov decision process. RESULTS: Thirteen studies (1 randomized trial, 12 observational cohorts) with 5000 patients were included. The incidence of occult contralateral inguinal hernias was 14.6 (range 7.3-50.1) per cent. Among patients who underwent repair, 10.5 (4.3-17.0) per cent experienced a postoperative complication. Of patients managed expectantly, 29 per cent later required elective repair for symptoms. Mean follow-up was 36 (range 2-218) months. Using a Markov decision process, it was calculated that, for every 1000 patients undergoing unilateral inguinal hernia repair, contralateral exploration would identify 150 patients with an occult hernia. Repair would result in 15 patients developing a postoperative complication and 105 undergoing unnecessary repair. Alternatively, expectant management would result in 45 patients requiring subsequent repair. CONCLUSION: Contralateral repair is not warranted in patients with occult hernias diagnosed at the time of elective hernia repair. The evidence is largely based on observational studies at high risk of bias.

A longitudinal study of Taiwanese sialidosis type 1: an insight into the concept of cherry-red spot myoclonus syndrome.

BACKGROUND AND PURPOSE: Sialidosis type 1 (ST-1) is a neurodegenerative disorder with limited long-term follow-up report. This study is to document the chronological profile of ST-1. METHODS: We perform serial analysis of 17 Taiwanese patients with ST-1 focusing on evolution of clinical features, electrophysiological findings, genetic studies, and neuroimage examinations. RESULTS: All patients had a mutation at 554A-->G in exon 3 of the NEU1 gene causing Ser182Gly substitution. Fifteen patients were homozygous. Two patients were heterozygous with novel mutations, 956C-->T causing Ala319Val in one and 163C-->T causing Gln55stop codon in the other. The neuraminidase activity was markedly decreased in all 11 available patients. Only three patients (17.6%) manifested the macular cherry-red spot. The majority of patients (82.3%) developed full-blown manifestation of myoclonus, ataxia, and seizures within 5 years. Abnormal somatosensory evoked potentials with giant cortical waves were found in all patients. Prolonged P100 peak latency of the visual evoked potentials (VEPs) were found in 16 patients (94.1%) in the early stage even without visual symptoms. CONCLUSION: ST-1 in Taiwanese population illustrates distinct characteristics of phenotype with infrequent cherry-red spot. We suggest to screen the NEU1 mutations in patients presenting action myoclonus with abnormal VEPs, even without macular cherry-red spots.

Importance of the physical exam: double-blind randomized controlled trial of radiologic interpretation of ventral hernias after selective clinical information.

PURPOSE: Increasingly, radiologic imaging is obtained as part of the pathway in diagnosing ventral hernias. Often, radiologists receive incomplete or incorrect clinical information from clinicians. OBJECTIVE: The aim of the study is to determine if clinical exam findings alter radiological interpretation of ventral hernias on CT. METHODS: This is a single-institution double-blind, randomized trial. All patients with a recent abdominal/pelvic CT scan seen in various surgical clinics were enrolled. A surgeon blinded to the CT scan findings performed a standardized physical examination and assessed for the presence of a ventral hernia. Seven independent radiologists blinded to the study design reviewed the scans. Each radiologist received one of three types of clinical exam data per CT: accurate (correct), inaccurate (purposely incorrect), or none. Allocation was random and stratified by the presence of clinical hernia. The primary outcome was the proportion of radiologic hernias detected, analyzed by chi square. RESULTS: 115 patients were enrolled for a total of 805 CT scan reads. The proportion of hernias detected differed by up to 25% depending on if accurate, no, or inaccurate clinical information was provided. Inaccurate clinical data in patients with no hernia on physical exam led to a significant difference in the radiologic hernia detection rate (54.3% versus 35.7%, p = 0.007). No clinical data in patients with a hernia on physical exam led to a lower radiologic hernia detection rate (75.0% versus 93.8%, p = 0.001). CONCLUSIONS: The presence and accuracy of clinical information provided to radiologists impacts the diagnosis of abdominal wall hernias in up to 25% of cases. Standardization of both clinical and radiologic examinations for hernias and their reporting are needed. TRIAL REGISTRATION: Clinicaltrials.gov, Number NCT03121131, https://clinicaltrials.gov/ct2/show/NCT03121131.

Disposition, metabolism, and excretion of [14C]doripenem after a single 500-milligram intravenous infusion in healthy men.

In this open-label, single-center study, eight healthy men each received a single 500-mg dose of [(14)C]doripenem, containing 50 microCi of [(14)C]doripenem, administered as a 1-h intravenous infusion. The concentrations of unchanged doripenem and its primary metabolite (doripenem-M-1) resulting from beta-lactam ring opening were measured in plasma and urine by a validated liquid chromatography method coupled to a tandem mass spectrometry assay. Total radioactivity was measured in blood, plasma, urine, and feces by liquid scintillation counting. Further metabolite profiling was conducted on urine samples using liquid chromatography coupled to radiochemical detection and high-resolution mass spectrometry. Unchanged doripenem and doripenem-M-1 accounted for means of 80.7% and 12.7% of the area under the plasma total-radioactivity-versus-time curve (area under the concentration-time curve extrapolated to infinity) and exhibited elimination half-lives of 1.1 and 2.5 h, respectively. Total clearance of doripenem was 16 liters/h, and renal clearance was 12.5 liters/h. At 7 days after the single dose, 95.3% of total doripenem-related radioactivity was recovered in urine and 0.72% in feces. A total mean of 97.2% of the administered dose was excreted in the urine as unchanged doripenem (78.7% +/- 5.7%) and doripenem-M-1 (18.5% +/- 2.6%). Most of the urinary recovery occurred within 4 h of dosing. Three additional minor metabolites were identified in urine: the glycine and taurine conjugates of doripenem-M-1 and oxidized doripenem-M-1. These results show that doripenem is predominantly eliminated in urine as unchanged drug, with only a fraction metabolized to doripenem-M-1 and other minor metabolites.

Role of NBCe1 and AE2 in secretory ameloblasts.

The H(+)/base transport processes that control the pH of the microenvironment adjacent to ameloblasts are not currently well-understood. Mice null for the AE2 anion exchanger have abnormal enamel. In addition, persons with mutations in the electrogenic sodium bicarbonate co-transporter NBCe1 and mice lacking NBCe1 have enamel abnormalities. These observations suggest that AE2 and NBCe1 play important roles in amelogenesis. In the present study, we aimed to understand the roles of AE2 and NBCe1 in ameloblasts. Analysis of the data showed that NBCe1 is expressed at the basolateral membrane of secretory ameloblasts, whereas AE2 is expressed at the apical membrane. Transcripts for AE2a and NBCe1-B were detected in RNA isolated from cultured ameloblast-like LS8 cells. Our data are the first evidence that AE2 and NBCe1 are expressed in ameloblasts in vivo in a polarized fashion, thereby providing a mechanism for ameloblast transcellular bicarbonate secretion in the process of enamel formation and maturation.

Zygotic development without functional mitotic centrosomes.

The centrosome is the dominant microtubule-organizing center in animal cells. At the onset of mitosis, each cell normally has two centrosomes that lie on opposite sides of the nucleus. Centrosomes nucleate the growth of microtubules and orchestrate the efficient assembly of the mitotic spindle. Recent studies in vivo and in vitro have shown that the spindle can form even in the absence of centrosomes and demonstrate that individual cells can divide without this organelle. However, since centrosomes are involved in multiple processes in vivo, including polarized cell divisions, which are an essential developmental mechanism for producing differentiated cell types, it remains to be shown whether or not a complete organism can develop without centrosomes. Here we show that in Drosophila a centrosomin (cnn) null mutant, which fails to assemble fully functional mitotic centrosomes and has few or no detectable astral microtubules, can develop into an adult fly. These results challenge long-held assumptions that the centrosome and the astral microtubules emanating from it are essential for development and are required specifically for spindle orientation during asymmetric cell divisions.

Oxygen-independent intracellular and oxygen-dependent extracellular killing of Escherichia coli S15 by human polymorphonuclear leukocytes.

Effective killing of bacteria by polymorphonuclear leukocytes (PMN) is generally assumed to require intracellular sequestration and, depending on the bacterial species, can be both O2-dependent or O2-independent. Killing of several strains of Salmonella typhimurium and Escherichia coli by rabbit PMN does not require O2 and is apparently due to a granule-associated bactericidal/permeability-increasing protein (BPI) present in rabbit and human PMN. In this study we examined the O2 dependence of the killing of E. coli (S15) by human PMN. Ingested and noningested E. coli were separated by centrifugation after incubation with PMN in room air or under N2. In the presence of heat-treated serum approximately 50% of E. coli (10 bacteria/PMN) were taken up by PMN and rapidly (5-15 min) killed both in room air and under N2. The remaining extracellular bacteria (approximately 50%) were killed during 30-60 min of incubation in room air but not under N2. When uptake of E. coli by PMN was increased to approximately 80% by the use of C6-depleted serum (retaining heat-labile opsonins), bacterial survival under N2 was reduced from 54 +/- 7.6% to 13 +/- 5.5%. PMN from a patient with chronic granulomatous disease killed PMN-associated but not extracellular E. coli. BPI was detected, by indirect immunofluorescence, on the surface of PMN-associated E. coli within 5 min of incubation of E. coli with PMN both in room air and under N2. In contrast, at no time was BPI detected on the surface of extracellular E. coli, indicating that the non-PMN-associated E. coli had not been previously ingested. Thus, killing of ingested E. coli S15 by human as well as rabbit PMN does not require O2 and appears to be BPI-mediated. However, when ingestion is limited, extracellular bacteria can also be killed but principally by O2-dependent mechanisms.

Interactions between the ankyrin repeat-containing protein Akr1p and the pheromone response pathway in Saccharomyces cerevisiae.

Akr1p, which contains six ankyrin repeats, was identified during a screen for mutations that displayed synthetic lethality with a mutant allele of the bud emergence gene BEM1. Cells from which AKR1 had been deleted were alive but misshapen at 30 degrees C and inviable at 37 degrees C. During a screen for mutants that required one or more copies of wild-type AKR1 for survival at 30 degrees C, we isolated mutations in GPA1, which encodes the G alpha subunit of the pheromone receptor-coupled G protein. (The active subunit of this G protein is G beta gamma, and G alpha plays an inhibitory role in G beta gamma-mediated signal transduction.) AKR1 could serve as a multicopy suppressor of the lethality caused by either loss of GPA1 or overexpression of STE4, which encodes the G beta subunit of this G protein, suggesting that pheromone signaling is inhibited by overexpression of Akr1p. Mutations in AKR1 displayed synthetic lethality with a weak allele of GPA1 and led to increased expression of the pheromone-inducible gene FUS1, suggesting that Akr1p normally (and not just when overexpressed) inhibits signaling. In contrast, deletion of BEM1 resulted in decreased expression of FUS1, suggesting that Bem1p normally facilitates pheromone signaling. During a screen for proteins that displayed two-hybrid interactions with Akr1p, we identified Ste4p, raising the possibility that an interaction between Akr1p and Ste4p contributes to proper regulation of the pheromone response pathway.

A novel DNA-binding protein bound to the mitochondrial inner membrane restores the null mutation of mitochondrial histone Abf2p in Saccharomyces cerevisiae.

The yeast mitochondrial HMG-box protein, Abf2p, is essential for maintenance of the mitochondrial genome. To better understand the role of Abf2p in the maintenance of the mitochondrial chromosome, we have isolated a multicopy suppressor (YHM2) of the temperature-sensitive defect associated with an abf2 null mutation. The function of Yhm2p was characterized at the molecular level. Yhm2p has 314 amino acid residues, and the deduced amino acid sequence is similar to that of a family of mitochondrial carrier proteins. Yhm2p is localized in the mitochondrial inner membrane and is also associated with mitochondrial DNA in vivo. Yhm2p exhibits general DNA-binding activity in vitro. Thus, Yhm2p appears to be novel in that it is a membrane-bound DNA-binding protein. A sequence that is similar to the HMG DNA-binding domain is important for the DNA-binding activity of Yhm2p, and a mutation in this region abolishes the ability of YHM2 to suppress the temperature-sensitive defect of respiration of the abf2 null mutant. Disruption of YHM2 causes a significant growth defect in the presence of nonfermentable carbon sources such as glycerol and ethanol, and the cells have defects in respiration as determined by 2,3,5,-triphenyltetrazolium chloride staining. Yhm2p may function as a member of the protein machinery for the mitochondrial inner membrane attachment site of mitochondrial DNA during replication and segregation of mitochondrial genomes.

Foreign material erosion after laparoscopic Roux-en-Y gastric bypass: findings and treatment.

BACKGROUND: Patients after laparoscopic Roux-en-Y gastric bypass (LRYGB) can have nonspecific, upper gastrointestinal (UGI) complaints. During postoperative endoscopy, we have noted the erosion of nondissolvable material, such as Peri-Strips or silk sutures, into the gastric pouch. This study reports the incidence and presentation of foreign material erosion into the gastric pouch after a LRYGB and the outcome after therapeutic endoscopy. METHODS: From a prospective LRYGB database, postoperative endoscopies from February 2002 to June 2005 that found foreign material in the gastric pouch were reviewed. Presenting symptoms, time until endoscopy, and patient outcomes were evaluated. A therapeutic endoscopy was performed by using endo-shears and biopsy forceps to remove the foreign material. RESULTS: A total of 23 patients underwent 29 therapeutic endoscopies. From February 2002 to November 2004, 208 LRYGB were performed using silk suture for the outer layer of the gastrojejunostomy, and 21 patients (10%) had silk suture found on endoscopy. Peri-Strips were used from February 2002 to December 2003 (n = 153) and 6 patients (4%) had erosions. Since converting to Vicryl suture and Seamguard, we have had 173 and 228 patients, respectively, without pouch erosion. The most common presenting symptom was abdominal pain (n = 15, 65%). Other symptoms included nausea (n = 13, 57%), vomiting (n = 12, 52%), dysphagia (n = 5, 22%), and melena (n = 3, 13%). Foreign material was found by a mean of 34 weeks. Of 29 therapeutic endoscopies, 20 resulted in resolution of symptoms (69%), 4 led to improvements (14%), and 5 had no effect (17%). There were no endoscopic complications and no anastomotic leaks. CONCLUSIONS: Nonabsorbable material used during a LRYGB can migrate into the gastric pouch and cause UGI complaints. A therapeutic endoscopy will resolve most UGI symptoms. Using absorbable material in the creation of the gastric pouch and the gastrojejunostomy will avoid foreign material erosion.