Diversity of Actinomycetes From Eka Karya Botanical Garden, Bali

A total of 229 strains of actinomycetes were isolated and identified by full sequence of 16S rRNA gene analysis. Samples consisted of 18 soil and 20 leaf-litter were collected from Eka Karya Botanical Garden, Bali Island, Indonesia. Two isolation methods, i.e. SDS-Yeast Extract (SY) and Rehydration-Centrifugation (RC) were used in this study. Based on 16S rRNA gene analysis, isolated actinomycetes may be grouped into 28 genera. Based on molecular analysis of 16S rRNA gene similarities showed that isolated actinomycetes of Eka Karya Botanical Garden origin is diverse. Analysis on 144 isolates from soil samples, resulted in 24 genera and more than 87 species. Streptomyces is the most dominant genus where 65 isolates or 45% from isolated actinomycetes belong to this genus. It was followed by Actinoplanes (25 isolates =17%). From leaf-littersamples, the total number of 85 isolates may be grouped into 9 genera and more than 41 species. The most dominated genus is Actinoplanes (42 isolates =49%) followed by Catenuloplanes (16 isolates=19%)

Tracing controversies in hacker communities: ethical considerations for internet research

This paper reflects on the ethics of internet research on community controversies. Specifically, it focuses on controversies concerning gendered, social interaction in hacking communities. It addresses the question how internet researchers should treat and represent content that individuals controversially discussed online. While many internet sources are likewise technically public, they may yet suggest distinct privacy expectations on the part of involved individuals. In internet research, ethical decision-making regarding which online primary sources may be, e.g., referenced and quoted or require anonymisation is still ambiguous and contested. Instead of generalisable rules, the context dependence of internet research ethics has been frequently stressed. Given this ambiguity, the paper elaborates on ethical decisions and their implications by exploring the case of a controversial hackerspaces.org mailing list debate. In tracing data across different platforms, it analyses the emerging ethico-methodological challenges

Lubiprostone Stimulates Duodenal Bicarbonate Secretion in Rats

Lubiprostone, a bicyclic fatty acid, is used for the treatment of chronic constipation. No published study has addressed the effect of lubiprostone on intestinal ion secretion in vivo. The aim of this study was to test the hypothesis that lubiprostone augments duodenal HCO3 − secretion (DBS). Rat proximal duodenal loops were perfused with pH 7.0 Krebs, control vehicle (medium-chain triglycerides), or lubiprostone (0.1–10 μM). We measured DBS with flow-through pH and CO2 electrodes, perfusate [Cl−] with a Cl− electrode, and water flux using a non-absorbable ferrocyanide marker. Some rats were pretreated with a potent, selective CFTR antagonist, CFTRinh-172 (1 mg/kg, ip), 1 h before experiments. Perfusion of lubiprostone concentration dependently increased DBS, whereas net Cl− output and net water output were only increased at 0.1 μM, compared with vehicle. CFTRinh-172 reduced lubiprostone (10 μM)-induced DBS increase, whereas net Cl− output was also unchanged. Nevertheless, CFTRinh-172 reduced basal net water output, which was reversed by lubiprostone. Furthermore, lubiprostone-induced DBS was inhibited by EP4 receptor antagonist, not by an EP1/2 receptor antagonist or by indomethacin pretreatment. In this first study of the effect of lubiprostone on intestinal ion secretion in vivo, lubiprostone stimulated CFTR-dependent DBS without changing net Cl− secretion. This effect supports the hypothesis that Cl− secreted by CFTR is recycled across the apical membrane by anion exchangers. Recovery of water output during CFTR inhibition suggests that lubiprostone may improve the intestinal phenotype in CF patients. Furthermore, increased DBS suggests that lubiprostone may protect the duodenum from acid-induced injury via EP4 receptor activation

Intramucosal adenocarcinoma of the ileum originated 40 years after ileosigmoidostomy

<p>Abstract</p> <p>Background</p> <p>Small bowel adenocarcinomas (SBAs) are rare carcinomas. They are asymptomatic and usually neither endoscopy nor contrast studies are performed for screening</p> <p>Case presentation</p> <p>A 72-year-old Japanese male had a positive fecal occult blood test at a regular check-up in 2006. He suffered appendicitis and received an ileosigmoidostomy in 1966. A colonoscopy revealed an irregular mucosal lesion with an unclear margin at the ileum side of the anastomosis. A mucosal biopsy specimen showed adenocarcinoma histopathologically. Excision of the anastomosis was performed for this patient. The resected specimen showed a flat mucosal lesion with a slight depression at the ileum adjacent to the anastomosis. Histological examination revealed a well differentiated intramucosal adenocarcinoma (adenocarcinoma in situ). Immunohistological staining demonstrated the overexpression of p53 protein in the adenocarcinoma.</p> <p>Conclusion</p> <p>Adenocarcinoma of the ileum at such an early stage is a very rare event. In this case, there is a possibility that the ileosigmoidostomy resulted in a back flow of colonic stool to the ileum that caused the carcinogenesis of the small intestine.</p

Sonidegib as a Locally Advanced Basal Cell Carcinoma Therapy in Real-life Clinical Setting: A National Multicentre Study

Background: Basal cell carcinoma (BCC) is the most prevalent cancer. A minority of BCCs have an aggressive behaviour (laBCC) and may require hedgehog pathway inhibitors such as sonidegib as its treatment. Objective: To describe the use of sonidegib in a large number of patients and provide more data on its real-life efficacy and safety profile.Methods: We conducted a retrospective and multicentric study that included patients treated with sonidegib. Epidemiological, effectiveness and safety data were collected.Results: A total of 82 patients with a mean age of 73.9 years were included. Ten patients had Gorlin syndrome. Median treatment duration was 6 months. Median follow-up duration was 34.2 months. Globally, 81.7% of the patients showed clinical improvement (52.4% partial response and 29.3% complete response), 12.2% clinical stability and 6.1% disease progression. There was no statistically significant difference in clinical improvement between the 24 h and 48 h sonidegib posology. After 6 months of treatment, 48.8% of the patients discontinued sonidegib. Prior vismodegib treatment and recurrent primary BCC were associated with a poorer response to sonidegib. At 6 months of treatment, 68.3% of the patients experienced at least one adverse effect. Conclusion: Sonidegib shows good effectiveness and acceptable safety profile in usual clinical practice.& COPY; 2023 AEDV. Published by Elsevier Espan & SIM;a, S.L.U.This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Reconfiguration, contestation, and decline: conceptualizing mature large technical systems

Large technical systems (LTS) are integral to modern lifestyles but arduous to analyze. In this paper, we advance a conceptualization of LTS using the notion of mature “phases,” drawing from insights into innovation studies, science and technology studies, political science, the sociology of infra- structure, history of technology, and governance. We begin by defining LTS as a unit of analysis and explaining its conceptual utility and novelty, situating it among other prominent sociotechnical theories. Next, we argue that after LTS have moved through the (overlapping) phases proposed by Thomas Hughes of invention, expansion, growth, momentum, and style,mature LTS undergo the additional (overlapping) phases of reconfiguration, contestation (subject to pressures such as drift and crisis), and eventually stagnation and decline. We illustrate these analytical phases with historical case studies and the conceptual literature, and close by suggesting future research to refine and develop the LTS framework, particularly related to more refined typologies, temporal dimensions, and a broadening of system users. We aim to contribute to theoretical debates about the coevolution of LTS as well as empirical discussions about system-related use, socio- technical change, and policy-making

Polymorphisms in the Mitochondrial Genome Are Associated With Bullous Pemphigoid in Germans

Bullous pemphigoid (BP) is the most prevalent autoimmune skin blistering disease and is characterized by the generation of autoantibodies against the hemidesmosomal proteins BP180 (type XVII collagen) and BP230. Most intriguingly, BP is distinct from other autoimmune diseases because it predominantly affects elderly individuals above the age of 75 years, raising the question why autoantibodies and the clinical lesions of BP emerges mostly in this later stage of life, even in individuals harboring known putative BP-associated germline gene variants. The mitochondrial genome (mtDNA) is a potential candidate to provide additional insights into the BP etiology; however, the mtDNA has not been extensively explored to date. Therefore, we sequenced the whole mtDNA of German BP patients (n = 180) and age- and sex-matched healthy controls (n = 188) using next generation sequencing (NGS) technology, followed by the replication study using Sanger sequencing of an additional independent BP (n = 89) and control cohort (n = 104). While the BP and control groups showed comparable mitochondrial haplogroup distributions, the haplogroup T exhibited a tendency of higher frequency in BP patients suffering from neurodegenerative diseases (ND) compared to BP patients without ND (50%; 3 in 6 BP with haplogroup T). A total of four single nucleotide polymorphisms (SNPs) in the mtDNA, namely, m.16263T>C, m.16051A>G, and m.16162A>G in the D-loop region of the mtDNA, and m.11914G>A in the mitochondrially encoded NADH:ubiquinone oxidoreductase core subunit 4 gene (MT-ND4), were found to be significantly associated with BP based on the meta-analysis of our NGS data and the Sanger sequencing data (p = 0.0017, p = 0.0129, p = 0.0076, and p = 0.0132, respectively, Peto's test). More specifically, the three SNPs in the D-loop region were negatively, and the SNP in the MT-ND4 gene was positively associated with BP. Our study is the first to interrogate the whole mtDNA in BP patients and controls and to implicate multiple novel mtDNA variants in disease susceptibility. Studies using larger cohorts and more diverse populations are warranted to explore the functional consequences of the mtDNA variants identified in this study on immune and skin cells to understand their contributions to BP pathology

Protein Intake, IGF-1 Concentrations, and Growth in the Second Year of Life in Children Receiving Growing Up Milk – Lite (GUMLi) or Cow's Milk (CM) Intervention

The relationship of protein intake with insulin-like growth factor 1 (IGF-1) concentrations in well-nourished children during the second year of life is poorly understood. The aim of this study was to explore the effect of a reduced-protein Growing Up Milk Lite (GUMLi) or unfortified cow's milk (CM) on protein intake, growth, and plasma IGF-1 at 2 y. An exploratory analysis of a sub-sample of Auckland-based children (n = 79) in the GUMLi trial (a double-blind, randomised control trial, N = 160) completed in Auckland and Brisbane (2015–2017) was conducted. One-year old children were randomised to receive a reduced-protein GUMLi (1.7 g protein/100 mL) or a non-fortified CM (3.1 g protein/100 mL) for 12 months. Blood sampling and anthropometric measurements were made at 1 and 2 y. Diet was assessed using a validated food frequency questionnaire. Total protein intake (g/d) from all cow's milk sources was 4.6 g (95% CI: −6.7, −2.4; p &lt; 0.005) lower in the GUMLi group after 12 months of the intervention, with a significant group-by-time interaction (p = 0.005). Length-for-age (LAZ) and weight-for-length (WLZ) z-scores did not differ between groups, however, mean body fat % (BF%) was 3.2% (95%CI: −6.2, −0.3; p = 0.032) lower in the GUMLi group at 2 y. There was no difference between the intervention groups in relation to IGF-1 and IGF-BP3 (p = 0.894 and 0.698, respectively), with no group-by-sex interaction. After combining the groups, IGF-1 concentration at 2 y was positively correlated with parameters of growth (all p &lt; 0.05), total cow's milk intake (p = 0.032) after adjusting for sex, breastfeeding status, and gestation. Randomisation to a reduced protein GUMLi resulted in small reduction in %BF and lower total protein intakes but had no effect on growth. Plasma IGF-1 concentrations were independently associated with total protein intake from cow's milk at 2 y, highlighting a potential area of the diet to target when designing future protein-related nutrition interventions.Clinical Trial Registration: Australian New Zealand Clinical Trials Registry number: ACTRN12614000918628. Date registered: 27/08/2014