Association of body mass index and bloodstream infections in patients on extracorporeal membrane oxygenation: a single-centre, retrospective, cohort study.

BACKGROUND: Obesity is associated with poor clinical outcomes in critically ill patients. However, under some clinical conditions, obesity has protective effects. Bloodstream infections (BSI) are among the most common nosocomial infections associated with extracorporeal membrane oxygenation (ECMO). BSI during ECMO is associated with higher mortality rates and poorer clinical outcomes. AIM: To analyse whether body mass index (BMI) is associated with BSI during ECMO or with in-hospital mortality. METHODS: All adult patients who had received ECMO support for >48 h were included in the analysis. The analysis of total duration of ECMO support, in-hospital mortality and BSI was stratified by BMI category. The Cox proportional hazards model was used to compare the risk of BSI among BMI categories. FINDINGS: In total, 473 patients were enrolled in the study. The average age was 56.5 years and 65.3% were men. The total duration of ECMO was approximately 11.8 days, with a mortality rate of 47.1%. The incidence rates of BSI and candidaemia were 20.5% and 5.5%, respectively. The underweight group required ECMO for respiratory support, whereas the overweight and obese groups required ECMO for cardiogenic support (P<0.0001). No significant difference in BSI rate was found (P=0.784). However, after adjusting for clinical factors, patients in Group 4 (BMI 25.0-<30.0 kg/m2) exhibited lower mortality compared with patients in Group 2 (normal BMI) (P=0.004). CONCLUSION: BMI was not associated with risk of BSI, but patients with higher BMI showed lower in-hospital mortality associated with ECMO support.

Impact of tuberculosis on the incidence of osteoporosis and osteoporotic fractures: a nationwide population-based cohort study.

OBJECTIVES: Despite the high prevalence of tuberculosis (TB) and the disease burden of osteoporosis and osteoporotic fractures, there is still a lack of well-designed, large-scale studies demonstrating associations among them. We aimed to investigate the effect of TB on the incidence of osteoporosis and osteoporotic fractures. STUDY DESIGN: This was a nationwide population-based cohort study. METHODS: This study was conducted using the National Health Insurance Service Database of South Korea. We included patients with newly diagnosed TB aged >40 years from January 2006 to December 2017. An uninfected control for each TB patient was randomly extracted by frequency matching for sex, age, income level, residence, and registration date at a 2:1 ratio. The primary outcome was the incidence of osteoporosis and osteoporotic fractures between the two groups, adjusted for sex, age, income level, residence, comorbidities, body mass index, blood pressure, laboratory tests, alcohol drinking, and smoking. The risk factors associated with osteoporosis or osteoporotic fractures were also investigated. RESULTS: A total of 164,389 patients with TB and 328,778 matched controls were included (71.9% males). The mean duration of follow-up was 7.00 ± 3.49 years. The incidence of osteoporosis in patients with TB was 6.1 cases per 1000 person-years, which was significantly higher than that in matched controls (adjusted hazard ratio [aHR] 1.349, 95% confidence interval [CI] 1.302-1.398, P < 0.001). The incidence of osteoporotic fractures was also higher in patients with TB than in controls (aHR 1.392, 95% CI 1.357-1.428, P < 0.001). Among fractures, the risk of hip fracture was the highest (aHR 1.703, 95% CI 1.612-1.798, P < 0.001). CONCLUSIONS: TB independently contributes to the incidence of osteoporosis and osteoporotic fractures, particularly hip fractures.

Comparing the efficacy of different methods of faecal microbiota transplantation via oral capsule, oesophagogastroduodenoscopy, colonoscopy, or gastric tube.

BACKGROUND: The increasing prevalence of multidrug-resistant organism (MDRO) carriage poses major challenges to medicine as healthcare costs increase. Recently, faecal microbiota transplantation (FMT) has been discussed as a novel and effective method for decolonizing MDRO. AIM: To compare the efficacy of different FMT methods to optimize the success rate of decolonization in patients with MDRO carriage. METHODS: This prospective cohort study enrolled patients with MDRO carriages from 2018 to 2021. Patients underwent FMT via one of the following methods: oral capsule, oesophagogastroduodenoscopy (EGD), colonoscopy, or gastric tube. FINDINGS: A total of 57 patients underwent FMT for MDRO decolonization. The colonoscopy group required the shortest time for decolonization, whereas the EGD group required the longest (24.9 vs 190.4 days, P = 0.022). The decolonization rate in the oral capsule group was comparable to that in the EGD group (84.6% vs 85.7%, P = 0.730). An important clinical factor associated with decolonization failure was antibiotic use after FMT (odds ratio = 6.810, P = 0.008). All four groups showed reduced proportions of MDRO species in microbiome analysis after FMT. CONCLUSION: Compared to other conventional methods, the oral capsule is an effective FMT method for patients who can tolerate an oral diet. The discontinuation of antibiotics after FMT is a key factor in the success of decolonization.

The efficiency of potential food waste-degrading bacteria under harsh conditions.

AIMS: Investigate the impact of highly adapted bacterial strains and their ability in waste degradation under a wide range of temperatures. METHODS AND RESULTS: Bacteria isolated from soil and food waste were grown in various media under fluctuated temperatures. After screening for organic compound degradation, the seven strongest bacterial strains have been selected for further experiments. Their enzyme activities were expressed in terms of the size of the hydrolysis zone in a wide temperature range of 2·5-70°C. The enzyme production assay was carried out for each protease, cellulase and amylase. The waste degradation was determined with a maximum 80% decrease in the volume of food waste in 21 days compared to the control in lab scale with enriched bacterial cultures and soil bacteria as additives at room temperature around 18-20°C. CONCLUSION: These seven bacteria are promising candidates for food waste biodegradation in composting especially in the winter without heating expense for maintaining ambient temperature. SIGNIFICANCE AND IMPACT OF THE STUDY: It is necessary to coax the uncultured bacteria from the various environments into the laboratory for investigating their valuable functions. Herein, using enrichment culture of consortium and additive of soil has illustrated the significant mean in food waste degradation.

Release of extracellular vesicle miR-494-3p by ARPE-19 cells with impaired mitochondria.

BACKGROUND: Mitochondrial function in retinal pigmented epithelial (RPE) cells and extracellular vesicle (EV) formation/release are related through the lysosomal and exocytotic pathways that process and eliminate intracellular material, including mitochondrial fragments. We propose that RPE cells with impaired mitochondria will release EVs containing mitochondrial miRNAs that reflect the diminished capacity of mitochondria within these cells. METHODS: We screened ARPE-19 cells for miRNAs that localize to the mitochondria, exhibit biological activity, and are present in EVs released by both untreated cells and cells treated with rotenone to induce mitochondrial injury. EVs were characterized by vesicle size, size distribution, presence of EV biomarkers: CD81, CD63, and syntenin-1, miRNA cargo, and number concentration of EVs released per cell. RESULTS: We found that miR-494-3p was enriched in ARPE-19 mitochondria. Knockdown of miR-494-3p in ARPE-19 cells decreased ATP production and mitochondrial membrane potential in a dose-dependent manner, and decreased basal oxygen consumption rate and maximal respiratory capacity. Increased number of EVs released per cell and elevated levels of miR-494-3p in EVs released from ARPE-19 cells treated with rotenone were also measured. CONCLUSIONS: ARPE-19 mitochondrial function is regulated by miR-494-3p. Elevated levels of miR-494-3p in EVs released by ARPE-19 cells indicate diminished capacity of the mitochondria within these cells. GENERAL SIGNIFICANCE: EV miR-494-3p is a potential biomarker for RPE mitochondrial dysfunction, which plays a central role in non-neovascular age-related macular degeneration, and may be a diagnostic biomarker for monitoring the spread of degeneration to neighboring RPE cells in the retina.

Environmental contamination in the isolation rooms of COVID-19 patients with severe pneumonia requiring mechanical ventilation or high-flow oxygen therapy.

BACKGROUND: Identifying the extent of environmental contamination of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is essential for infection control and prevention. The extent of environmental contamination has not been fully investigated in the context of severe coronavirus disease (COVID-19) patients. AIM: To investigate environmental SARS-CoV-2 contamination in the isolation rooms of severe COVID-19 patients requiring mechanical ventilation or high-flow oxygen therapy. METHODS: Environmental swab samples and air samples were collected from the isolation rooms of three COVID-19 patients with severe pneumonia. Patients 1 and 2 received mechanical ventilation with a closed suction system, while patient 3 received high-flow oxygen therapy and non-invasive ventilation. Real-time reverse transcription-polymerase chain reaction (rRT-PCR) was used to detect SARS-CoV-2; viral cultures were performed for samples not negative on rRT-PCR. FINDINGS: Of the 48 swab samples collected in the rooms of patients 1 and 2, only samples from the outside surfaces of the endotracheal tubes tested positive for SARS-CoV-2 by rRT-PCR. However, in patient 3's room, 13 of the 28 environmental samples (fomites, fixed structures, and ventilation exit on the ceiling) showed positive results. Air samples were negative for SARS-CoV-2. Viable viruses were identified on the surface of the endotracheal tube of patient 1 and seven sites in patient 3's room. CONCLUSION: Environmental contamination of SARS-CoV-2 may be a route of viral transmission. However, it might be minimized when patients receive mechanical ventilation with a closed suction system. These findings can provide evidence for guidelines for the safe use of personal protective equipment.

Time series analysis of delta neutrophil index as the predictor of sepsis in patients with acute poisoning.

Delta neutrophil index (DNI), which reflects the fraction of immature granulocytes, is used to detect infection and sepsis from noninfectious conditions, but few studies have evaluated in the early stage of acute poisoning. This retrospective observational study was performed on acute poisoning patients who visited to the emergency department (ED) and were consecutively admitted in intensive care units over 18-month period. The serial DNI, conventional inflammatory biomarkers, and culture results were obtained in the ED and after admission. The outcomes were the identification of sepsis, bacteremia, and 30-day mortality. Of 166 patients (mean age, 56.0 years) in this cohort, 59 (35.5%) had sepsis and 29 (17.5%) had bacteremia. Initial and peak DNI fractions 24 h after ED admission were strong independent predictors of sepsis development. Analysis of the area under the curve according to multiple receiver operating characteristics showed that DNI had a higher capability to predict sepsis than other parameters (0.815 for DNI, 0.700 for procalcitonin, 0.681 for C-reactive protein, and 0.741 for white blood cell). Using multivariable logistic regression analysis, it was found that DNI was an independent predictor of sepsis (95% confidence interval (CI) of odds: 1.03-1.18) and bacteremia (95% CI: 1.01-1.14). Therefore, initial and serial measurement of DNI may serve as useful risk predictor for development of sepsis or bacteremia in acute poisoning.

Thermal burns of the spectacle associated with supplementary heating in native New Zealand geckos.

Case history: Gradual onset of ocular opacity was observed in three gold-striped geckos (Woodworthia chrysosiretica), and five Pacific geckos (Dactylocnemis pacificus) held in two adjacent terrariums in a zoological institution located in the North Island of New Zealand. Ultraviolet light and heat had been provided for the previous 3-4 years by a fluorescent bulb, but in the last 4 weeks of winter a ceramic heat bulb had been added, situated 10 cm above the upper mesh of the cageClinical findings: All eight geckos presented with mostly bilateral lesions of varying severity confined to the central or upper quadrant of the spectacles. These lesions ranged from variable areas of opacity within the stroma of the spectacle to similarly distributed ulcers of the surface epithelium of both spectacles. The spectacle lesions in the Pacific geckos responded well to treatment with topical combined antimicrobial therapy, within 18-29 days. The gold-striped geckos suffered complications including dysecdysis, severe spectacle ulceration and perforation, mycotic spectaculitis, and widespread mycotic dermatitis resulting in death or leading to euthanasia.Pathological findings: In the three gold-striped geckos, there were extensive areas of deep ulceration and replacement of the spectacle with a thick serocellular crust containing large numbers of fungal elements. The affected areas of the stroma were expanded by large deposits of proteinaceous and mucinous material, pyknotic cellular debris and moderate numbers of heterophils and macrophages as well as infiltrating fungal hyphae.Diagnosis: Mycotic spectaculitis with ulceration and perforation, and disseminated mycotic dermatitis likely secondary to thermal burns.Clinical relevance: This is the first report of thermal burns of the spectacle in any reptile. There was species variation in the burn severity with gold-striped geckos showing more severe lesions, possibly due to a mix of behavioural and anatomical factors. The thermal burns to the spectacles in three cases were complicated by delayed healing, perforation, dysecdysis and severe mycotic infection.

Analysis of the number of enlarged pores according to site, age, and sex.

BACKGROUND: Increasing the number of enlarged pores causes cosmetic problems. The difference in the number of enlarged pores according to facial site, age, and sex is unclear. OBJECTIVE: To analyze the distribution of the number of enlarged pores according to facial site, age, and sex. METHODS AND MATERIALS: We analyzed the number of the enlarged pores and the percentage of wrinkles in the nose, forehead, and cheek from 434 polarized images. The measurement results were analyzed according to site, age, and sex. Relationship between enlarged pore counts and wrinkle severity was also analyzed. The study was conducted by using DermaVision,™ which can take cross-polarization, parallel polarization, and ultraviolet light images. RESULTS: The enlarged pores of the nose and forehead were more prominent than in the cheeks. Pore counts were increased with age, and the increment was significant between the 30's and 40's. There was no significant difference by gender. Enlarged pore counts were related to wrinkle severity. CONCLUSIONS: The number of enlarged pores differs depending on body site and increased with age. The enlarged pore counts correlate with wrinkle severity and the correlation varies depending on the body site.

Chronologic Trends in Studies on Fluoride Mechanisms of Action.

Fluoride has been widely used for the prevention of dental caries since the mid-20th century. The aim of this study was to investigate the chronologic trends in studies on fluoride mechanisms of action against dental caries during the years 1950 to 2015. To this aim, queries such as "fluoride," "fluoride and demineralization," "fluoride and remineralization," "fluoride and (plaque or biofilms)," and "fluoride and (bacteria or microbials)" were submitted to PubMed to collect research article information, including titles, abstracts, publication dates, author affiliations, and publication journals. The article information that PubMed produced was then collected by an automatic web crawler and examined through informetrics and linguistic analyses. We found that the number of articles concerned with fluoride mechanisms of action against dental caries was 6,903 and gradually increased over time during the years 1950 to 2015. They were published by 1,136 journals-most notably, Caries Research and Journal of Dental Research. Of the articles published, those related to bacteria/microbials had a higher percentage (44%) than those dealing with plaque/biofilms, demineralization, and remineralization. With regard to the geographic distribution of authors, Europe and North America accounted for 65% of the articles during the years 1987 to 2015, although the number of authors in Asia sharply increased in recent years. Among the fluoride compounds, NaF was mentioned more frequently than SnF2, Na2PO3F, amine fluoride, and acidulated phosphate fluoride during the years 1986 to 2015. Water fluoridation received the most attention among the various fluoride application methods (toothpastes, mouthwashes, fluoride varnishes, and fluoride gels) during the same period. These results, obtained from employing informetrics and linguistic analyses, suggest that in studies on fluoride mechanisms of action, 1) the unbalanced geographic distribution of articles and 2) the heavy concentration of articles on particular fluoride compounds and application methods should be overcome in future research.

cAMP-Response Element-Binding 3-Like Protein 1 (CREB3L1) is Required for Decidualization and its Expression is Decreased in Women with Endometriosis.

Endometriosis is a major cause of infertility and pelvic pain, affecting more than 10% of reproductive-aged women. Progesterone resistance has been observed in the endometrium of women with this disease, as evidenced by alterations in progesterone-responsive gene and protein expression. cAMPResponse Element-Binding 3-like protein 1 (Creb3l1) has previously been identified as a progesterone receptor (PR) target gene in mouse uterus via high density DNA microarray analysis. However, CREB3L1 function has not been studied in the context of endometriosis and uterine biology. In this study, we validated progesterone (P4) regulation of Creb3l1 in the uteri of wild-type and progesterone receptor knockout (PRKO) mice. Furthermore, we observed that CREB3L1 expression was significantly higher in secretory phase human endometrium compared to proliferative phase and that CREB3L1 expression was significantly decreased in the endometrium of women with endometriosis. Lastly, by transfecting CREB3L1 siRNA into cultured human endometrial stromal cells (hESCs) prior to hormonal induction of in vitro decidualization, we showed that CREB3L1 is required for the decidualization process. Interestingly, phosphorylation of ERK1/2, critical factor for decidualization, was also significantly reduced in CREB3L1-silenced hESCs. It is known that hESCs from patients with endometriosis show impaired decidualization and that dysregulation of the P4-PR signaling axis is linked to a variety of endometrial diseases including infertility and endometriosis. Therefore, these results suggest that CREB3L1 is required for decidualization in mice and humans and may be linked to the pathogenesis of endometriosis in a P4-dependent manner.

Routine endoscopic screening for synchronous esophageal neoplasm in patients with head and neck squamous cell carcinoma: a prospective study.

Early detection of synchronous esophageal squamous cell neoplasm (ESCN) in head and neck squamous cell carcinoma (HNSCC) patients can significantly affect their prognosis. We investigated the prevalence of synchronous ESCN and the risk factors for developing ESCN in patients with HNSCC, and evaluated the effect of routine endoscopic screening in these patients. Subjects who were diagnosed as HNSCC from May 2010 to January 2014 were eligible. All patients underwent conventional white light endoscopic examinations with narrow band imaging and Lugol chromoendoscopy. Among 458 subjects screened, 28 synchronous ESCN were detected in 24 patients (5.2%). The prevalence of ESCN was greatest in patients with hypopharyngeal cancer (20.9%). In multivariate analysis, pyriform sinus involvement was independent risk factor for developing synchronous ESCN (odds ratio 171.2, P < 0.001). During the follow-up period (median, 24 months), the 3-year overall survival rates was significantly lower in patients with ESCN than in patients without ESCN (54.2% vs. 78.3%, P = 0.0013). Routine endoscopic screening for detecting synchronous ESCN should be recommended for patients with HNSCC, especially those with pyriform sinus involvement.

Efficacy and complications of enteral feeding tube insertion after liver transplantation.

BACKGROUND: Adequate nutritional support for patients undergoing major surgery significantly affects postoperative recovery. Data on enteral feeding after liver transplantation (LT) are scarce. The aim of this work was to determine the efficacy and complications of feeding tubes inserted with the use of fluoroscopic assistance, endoscopic assistance, or transperitoneal jejunostomy in patients who underwent LT. METHODS: From January 2008 to August 2013, 2,058 LTs were performed at Asan Medical Center, Seoul, Korea. Enteral feeding tubes were inserted in 155 patients (7.5%) after LT: with the use of fluoroscopic placement in 81 (52%), endoscopic placement in 49 (32%), and transperitoneal jejunostomy in 25 (16%). We retrospectively analyzed the efficacy and complications of enteral feeding tubes. RESULTS: The median age was 55 years (interquartile range [IQR] 49-60). Enteral feeding indications were a high risk of gastric aspiration (n = 90), gastric stasis (n = 27), pneumonia (n = 23), gastrointestinal bleeding (n = 12), and bowel rest (n = 3). Median enteral feeding durations were 14.5 days (IQR 8.0-30.7) for fluoroscopic placement, 20.0 days (IQR 8.0-40.0) for endoscopic placement, and 37.5 days (IQR 18.2-86.2) for transperitoneal jejunostomy. Times to establishment of oral feeding were 13.0 days (IQR 6.2-25.7) for fluoroscopic placement, 24.0 days (IQR 10.5-43.5) for endoscopic placement, and 37.0 days (IQR 17.0-64.2) for transperitoneal jejunostomy. After tube insertion, tube dislocation and blockage occurred in 34 patients (22%) and 16 patients (25%), respectively. CONCLUSIONS: Enteral feeding tube insertion in patients who can not maintain a nasogastric tube or start oral intake for a long time is important for nutritional support after LT. Proper feeding method selection according to patient condition can help patients by improving nutritional support after major operations such as LT.

Fatal scedosporiosis in multiple solid organ allografts transmitted from a nearly-drowned donor.

Scedosporium spp. is the most common mold infection in pneumonia resulting from near-drowning. Three fatal scedosporiosis cases developed after solid organ transplantation, probably transmitted from the nearly-drowned donor. One heart transplant recipient and two kidney transplant recipients developed fatal scedosporiosis following deceased donor transplantation from the same donor, a nearly-drowned victim of a suicide attempt. Genotypically, indistinguishable strains of Scedosporium auratiacum were recovered from the three recipients. Two liver transplant recipients from the same donor received prophylactic voriconazole without any subsequent signs of infection. To determine the safety of donation from nearly-drowned donors, a national traceback investigation was also performed of the causes of deaths in all transplant recipients who received organs from drowned donors between 2001 and 2013. Over 13 years, 2600 deceased donor transplants were performed in Korea. Among these 2600 deceased donor transplants, 27 (1%) victims of drowning donated their organs. From these 27 donors, 84 patients received organ transplants and 18 died, including the above three. We found no microbiologic evidence of invasive mold transmission from the nearly-drowned donors to the other 15 recipients. Although disseminated infection in the donor could not be demonstrated by culture, undiagnosed disseminated donor infection and transmission of Scedosporium spp. should be considered in near-drowning events.

Comparison of Oven-drying Methods for Determination of Moisture Content in Feed Ingredients.

An accurate assessment of moisture content in feed ingredients is important because moisture influences the nutritional evaluation of feedstuffs. The objective of this study was to evaluate various methods for moisture content determination. In Exp. 1, the weight loss on drying (LOD) of corn, soybean meal (SBM), distillers dried grains with solubles (DDGS), whey permeate, whey powder, spray-dried porcine plasma (SDPP), fish meal, and a mixed diet of these 7 ingredients were measured by oven drying at 135°C for 2 h. Additionally, the samples were dried at 105°C for 3, 6, 9, 12, or 15 h. The LOD contents of the DDGS, whey permeate, and whey powder measured by drying at 135°C for 2 h were greater than the values measured by drying at 105°C for 3 h (p<0.05). All samples except SDPP (p = 0.70) dried at 105°C for 6, 9, 12, or 15 h caused more LOD compared with the samples dried for at 105°C for 3 h (p<0.05). The LOD contents of the individual ingredients were additive when dried at 105°C regardless of drying time. In Exp. 2, moisture contents of corn, SBM, wheat, whey permeate, whey powder, lactose, and 2 sources of DDGS (DDGS1 and DDGS2) were measured by the Karl Fischer method, oven drying at 135°C for 2 h, and oven drying at 125°C, 115°C, 105°C, or 95°C for increasing drying time from 1 to 24 h. Drying samples at 135°C for 2 h resulted in higher moisture content in whey permeate (7.5% vs 3.0%), whey powder (7.7% vs 3.8%), DDGS1 (11.4% vs 7.5%), and DDGS2 (13.1% vs 8.8%) compared with the Karl Fischer method (p<0.05). Whey permeate and whey powder were considerably darkened as the drying time increased. In conclusion, drying samples at 135°C for 2 h is not appropriate for determining the moisture content in whey permeate, whey powder, or DDGS as well as the mixed diet containing these ingredients. The oven-drying method at 105°C for 5 to 6 h appears to be appropriate for whey permeate and whey powder, and at 105°C for 2 to 3 h for DDGS.

Effect of high advanced-collagen tripeptide on wound healing and skin recovery after fractional photothermolysis treatment.

BACKGROUND: Collagens have long been used in pharmaceuticals and food supplements for the improvement of skin. AIM: We evaluated the efficacy of high advanced-collagen tripeptide (HACP) on wound healing and skin recovery. METHODS: Using an in vitro model, we performed HaCaT cell migration assays and collagen gel contraction assays using HACP concentrations of 1, 10 and 100 µg/mL. In this pilot study, eight healthy volunteers were randomly divided into two groups. Both the control and experimental groups received fractional photothermolysis treatment, but in the experimental group, four subjects received 3 g/day of oral collagen peptide (CP) for 4 weeks. To assess transepidermal water loss in each patient before and after the treatment, we used a Corneometer and a Cutometer, and we also assessed the patient's Erythema Index. RESULTS: The cell migration assay showed that HACP enhanced wound closure, but not in a dose-dependent manner. The collagen gel contraction assay showed increased contractility when patients were treated with 100 µg/mL HACP, but the results were not significantly different from those of controls. We found that post-laser erythema resolved faster in the experimental group than in the control group (P < 0.05). In addition, the recovery of skin hydration after fractional laser treatment was greater in the experimental group than in the control group by day 3 (P < 0.05), and the experimental group showed significantly improved post-treatment skin elasticity compared with the controls by day 14 (P < 0.05). CONCLUSIONS: Collagen tripeptide treatment appears to be an effective and conservative therapy for cutaneous wound healing and skin recovery after fractional photothermolysis treatment.

P42 Ebp1 regulates the proteasomal degradation of the p85 regulatory subunit of PI3K by recruiting a chaperone-E3 ligase complex HSP70/CHIP.

The short isoform of ErbB3-binding protein 1 (Ebp1), p42, is considered to be a potent tumor suppressor in a number of human cancers, although the mechanism by which it exerts this tumor-suppressive activity is unclear. Here, we report that p42 interacts with the cSH2 domain of the p85 subunit of phosphathidyl inositol 3-kinase (PI3K), leading to inhibition of its lipid kinase activity. Importantly, we found that p42 induces protein degradation of the p85 subunit and further identified HSP70/CHIP complex as a novel E3 ligase for p85 that is responsible for p85 ubiquitination and degradation. In this process, p42 couples p85 to the HSP70/CHIP-mediated ubiquitin-proteasomal system (UPS), thereby promoting a reduction of p85 levels both in vitro and in vivo. Thus, the tumor-suppressing effects of p42 in cancer cells are driven by negative regulation of the p85 subunit of PI3K.

HIV-associated neurocognitive disorder in HIV-infected Koreans: the Korean NeuroAIDS Project.

OBJECTIVES: HIV-associated neurocognitive disorder (HAND) is an independent predictor of early mortality and is associated with many difficulties in activities of daily living. We sought to determine the prevalence of and risk factors for HAND in HIV-infected Koreans. In addition, we investigated the performance of screening tools and components of neuropsychological (NP) tests for diagnosing HAND. METHODS: HIV-infected patients were enrolled consecutively from two different urban teaching hospitals in Seoul, South Korea between March 2012 and September 2012. Participants completed a detailed NP assessment of six cognitive domains commonly affected by HIV. The Frascati criteria were used for diagnosing HAND. Four key questions, the International HIV Dementia Scale (IHDS) and Montreal Cognitive Assessment (MoCA)-K were also assessed as potential tools for screening for HAND. RESULTS: Among the 194 participants, the prevalence of HAND was 26.3%. Asymptomatic neurocognitive impairment and minor neurocognitive disorder accounted for 52.9 and 47.1% of the patients with HAND, respectively. In multivariate analysis, haemoglobin (Hb) level ≤ 13 g/dL (P = 0.046) and current use of a protease inhibitor-based regimen (P = 0.031) were independent risk factors for HAND. The sensitivity and specificity of the IHDS were 72.6 and 60.8%, and those of MoCA-K were 52.9 and 73.4%, respectively. The IHDS (P < 0.001) and MoCA-K (P < 0.001) were both useful for screening for HAND. Among NP tests, the sensitivity and specificity of the Grooved Pegboard Test were 90.2 and 72.0%, and those of the Wisconsin Card Sorting Test were 61.2 and 84.4%, respectively. CONCLUSIONS: HAND is a prevalent comorbidity in HIV-infected Koreans. Active screening and diagnosis with effective tools, such as the IHDS, MoCA-K and Grooved Pegboard Test, could be used to identify this important complication.

Double-blind, randomized non-inferiority trial of a novel botulinum toxin A processed from the strain CBFC26, compared with onabotulinumtoxin A in the treatment of glabellar lines.

BACKGROUND: Botulinum toxins have been widely used in cosmetic dermatology. Neurotoxin from the CBFC26 strain (NTC) is a recently developed botulinum toxin type A product manufactured through refined procedures. OBJECTIVE: A double-blinded, randomized, multicentre-designed, phase III trial to investigate the non-inferiority of NTC to existing botulinum toxin A, onabotulinumtoxin A in the treatment of moderate to severe glabellar lines. METHODS: A total of 272 subjects were randomized in a 1 : 1 ratio to receive 20 U of NTC or onabotulinumtoxin A. The primary endpoint was the response rate of physicians' assessment (PA) using the Facial Wrinkle Scale at week 4. The secondary endpoints included the response rate of PA at weeks 8, 12 and 16, and photographic assessment at weeks 4, 8, 12 and 16. Subjects' improvement assessment and subjective self-satisfaction levels were also investigated. RESULTS: Response rates for maximum frown were 89.3% in the NTC group and 81.9% in the onabotulinumtoxin A group at week 4. NTC also resulted in comparable results for both the response rates of the other evaluation points and incidence of adverse events compared to those of onabotulinumtoxin A. In subjects' improvement assessment and photographic evaluations, NTC even demonstrated better results compared with onabotulinumtoxin A in the early phase after treatment. Analysis of these results strongly supports the non-inferiority of NTC to onabotulinumtoxin A in the efficacy and safety. CONCLUSION: NTC is as effective as onabotulinumtoxin A in the treatment of glabellar lines, and both products were well tolerated.

Endoscopic submucosal dissection for sessile, nonampullary duodenal adenomas.

Although endoscopic submucosal dissection (ESD) is increasingly utilized to treat early neoplasms of the gastrointestinal tract, its use for duodenal neoplasms is limited by the thin wall and narrow lumen of the duodenum. We have reviewed cases where ESD was used to treat sessile, nonampullary duodenal neoplasms. To do this, we retrospectively reviewed the medical records of patients treated with ESD for adenomas of the duodenum from January 2001 to December 2010, assessing the curative outcomes and complication rates. A total of 14 cases were reviewed. Mean patient age was 56.4 years. The mean size of tumors and mean size of the specimens were 17.1 mm and 26.4 mm, respectively. The en bloc resection rate with ESD was 78.6%, and the complete (R0) resection rate was 85.7%. No patient in the study experienced major bleeding. However, second-look endoscopy revealed minor bleeding requiring endoscopic homeostasis in one case (7.1%). Perforations were observed in five cases (35.7%). Two of the five patients with perforation underwent surgery. The ESD methods yielded acceptable curative resection rates for duodenal adenomas, although ESD was associated with a higher rate of perforation. Therefore, duodenal ESD should be performed with care and only in selected patients to avoid serious complications.