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Design of the grounding system of power system facilities largely depends on the soil composition and its electrical characteristics, voltage level, dimensions of the object and other factors. This paper presents two calculation procedures intended for the design of the grounding system of a typical distribution transformer station. The first one, frequently used by the designers in Serbia, is based on the application of simple empirical formulas and diagrams, relying on the regulations, national standards and technical recommendations. The second calculation approach is represented by the use of a specialized software, based on modern mathematical methods, the results of which are verified using valid international standards. A comparative analysis of the results obtained using both methodologies, as well as the opportunities they provide to the designer, are presented. Both methodologies can be used when designing new grounding systems, as well as when reconstructing or maintaining the existing ones.

Suppurative portal vein thrombosis (pylephlebitis) is an uncommon condition usually associated with an intra-abdominal infection or inflammatory process. In this study, we aimed to synthesize data on previously published cases according to the PRISMA guidelines. A total of 103 patients were included. Patients were more commonly male (71.8%) and had a mean age of 49 years. The most common infection associated with pylephlebitis was diverticulitis ( n = 29, 28.2%), and Escherichia coli was the most isolated pathogen ( n = 21, 20.4%). Blood cultures were positive in 64 cases (62.1%). The most common site of thrombosis was the main portal vein (PV) in 59 patients (57.3%), followed by the superior mesenteric vein (SMV) in 40 patients (38.8%) and the right branch of the PV in 30 patients (29.1%). Sepsis developed in 60 patients (58.3%). The mortality rate in our review was 8.7%, and independent risk factors for mortality were the presence of pertinent comorbidities (OR 5.5, p = 0.02), positive blood cultures (OR 2.2, p = 0.02), and sepsis (OR 17.2, p = 0.049).

Extraintestinal manifestations of celiac disease (CD) should be considered, even in patients without typical intestinal symptoms. The aim of our study is to examine the literature regarding the occurrence of thrombotic events in CD, and to synthesize the data from case reports and case series. A systematic review of the literature was conducted by searching the Pub-Med/MEDLINE database, from the date of database inception to January 2022, to identify published cases and case series on this topic, in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. A total of 55 cases were included in the study. The majority of patients were previously healthy individuals, with no comorbidities. In less than one-third of the cases (30.91%), the diagnosis of CD was established before the onset of thrombosis, while in the remaining cases (34.54%), thrombosis preceded the diagnosis or was diagnosed concomitantly with CD. The most common sites for thrombosis occurrence were hepatic veins (30.91%), while thrombosis of cerebral blood vessels, deep venous thrombosis of lower extremities, and pulmonary thromboembolism were less frequent. Thrombosis was most commonly isolated to one site only (78.18%). In 69.09% of cases ( n = 38), some form of anticoagulation, along with a gluten-free diet, was initiated.

Yeasts are ubiquitous in temperate forests. While this broad habitat is well-defined, the yeasts inhabiting it and their life cycles, niches, and contributions to ecosystem functioning are less understood. Yeasts are present on nearly all sampled substrates in temperate forests worldwide. They associate with soils, macroorganisms, and other habitats and no doubt contribute to broader ecosystem-wide processes. Researchers have gathered information leading to hypotheses about yeasts' niches and their life cycles based on physiological observations in the laboratory as well as genomic analyses, but the challenge remains to test these hypotheses in the forests themselves. Here, we summarize the habitat and global patterns of yeast diversity, give some information on a handful of well-studied temperate forest yeast genera, discuss the various strategies to isolate forest yeasts, and explain temperate forest yeasts' contributions to biotechnology. We close with a summary of the many future directions and outstanding questions facing researchers in temperate forest yeast ecology. Yeasts present an exciting opportunity to better understand the hidden world of microbial ecology in this threatened and global habitat., (© 2022 John Wiley & Sons, Ltd.)

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a potentially life threatening severe cutaneous drug reaction. Most patients develop eosinophilia, a rash, a fever, lymphadenopathy and variable visceral organ involvement 2-6 weeks following exposure to the inciting medication. Unlike other severe cutaneous drug reactions, internal organ involvement that leads to high mortality is a unique feature of DRESS syndrome. While the liver is the most common internal organ involved, literally every other visceral organ can be affected in this syndrome. The lesser-known gastrointestinal manifestations of this syndrome include esophagitis, gastritis, enteritis, colitis, pancreatitis and a late autoimmune sequela due to pancreatic injury such as fulminant type 1 diabetes mellitus, autoimmune type 1 diabetes mellitus and type 2 diabetes mellitus. While these entities are less common, they are associated with equally severe complications and adverse patient outcomes. In this review, we synthetize data on these rare manifestations using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The liver, the most common visceral organ involved, has been described as part of DRESS elsewhere and is not included in the scope of this article.

Climate change is altering the frequency and severity of drought events. Recent evidence indicates that drought may produce legacy effects on soil microbial communities. However, it is unclear whether precedent drought events lead to ecological memory formation, i.e., the capacity of past events to influence current ecosystem response trajectories. Here, we utilize a long-term field experiment in a mountain grassland in central Austria with an experimental layout comparing 10 years of recurrent drought events to a single drought event and ambient conditions. We show that recurrent droughts increase the dissimilarity of microbial communities compared to control and single drought events, and enhance soil multifunctionality during drought (calculated via measurements of potential enzymatic activities, soil nutrients, microbial biomass stoichiometry and belowground net primary productivity). Our results indicate that soil microbial community composition changes in concert with its functioning, with consequences for soil processes. The formation of ecological memory in soil under recurrent drought may enhance the resilience of ecosystem functioning against future drought events., (© 2021. The Author(s).)

Background: Direct-acting oral anticoagulants (DOACs) are increasingly used, with studies showing a lower risk of gastrointestinal bleeding (GIB), but overall data for GIB risk remains debatable. The objective was to assess non-fatal and fatal GIB risk in patients on DOACs compared with warfarin from randomized clinical trials (RCTs)., Methods: RCTs comparing warfarin and DOACs for various indications (atrial fibrillation, thromboembolism, insertion of mechanical heart valves) were included. The primary endpoint was any GIB event. Other clinical events, such as fatal GIB, and effects of age (≤60 years or older), time in therapeutic range for warfarin, and choice of individual DOACs on GIB risk, were also assessed., Results: 14 RCTs were included, comprising 87,407 participants (DOACs n=46,223, warfarin control n=41,184). The risk of GIB with DOACs was similar to that of warfarin (relative risk [RR] 1.04, 95% confidence interval [CI] 0.85-1.27). Compared with warfarin, rivaroxaban (RR 1.23, 95%CI 1.03-1.48) and dabigatran (RR 1.38, 95%CI 1.12-1.71) had a higher risk of any GIB, whereas fatal GIB risk was lower in the DOACs group (RR 0.36, 95%CI 0.15-0.82). The risk of DOAC-related fatal GIB was lower in patients aged ≤60 years and in those with poor coagulation control (RR 0.39, 95%CI 0.15-0.98)., Conclusions: DOACs compared with warfarin have a lower risk of fatal GIB, especially in those aged <60 years and those with poor coagulation control. However, the risk of GIB was comparable with warfarin and DOACs, except for rivaroxaban and dabigatran., Competing Interests: Conflict of Interest: None, (Copyright: © Hellenic Society of Gastroenterology.)

Carbohydrate active enzymes (CAZymes) are vital for the lignocellulose-based biorefinery. The development of hypersecreting fungal protein production hosts is therefore a major aim for both academia and industry. However, despite advances in our understanding of their regulation, the number of promising candidate genes for targeted strain engineering remains limited. Here, we resequenced the genome of the classical hypersecreting Neurospora crassa mutant exo - 1 and identified the causative point of mutation to reside in the F-box protein-encoding gene, NCU09899. The corresponding deletion strain displayed amylase and invertase activities exceeding those of the carbon catabolite derepressed strain Δ cre - 1 , while glucose repression was still mostly functional in Δ exo - 1 Surprisingly, RNA sequencing revealed that while plant cell wall degradation genes are broadly misexpressed in Δ exo - 1 , only a small fraction of CAZyme genes and sugar transporters are up-regulated, indicating that EXO-1 affects specific regulatory factors. Aiming to elucidate the underlying mechanism of enzyme hypersecretion, we found the high secretion of amylases and invertase in Δ exo - 1 to be completely dependent on the transcriptional regulator COL-26. Furthermore, misregulation of COL-26, CRE-1, and cellular carbon and nitrogen metabolism was confirmed by proteomics. Finally, we successfully transferred the hypersecretion trait of the exo - 1 disruption by reverse engineering into the industrially deployed fungus Myceliophthora thermophila using CRISPR-Cas9. Our identification of an important F-box protein demonstrates the strength of classical mutants combined with next-generation sequencing to uncover unanticipated candidates for engineering. These data contribute to a more complete understanding of CAZyme regulation and will facilitate targeted engineering of hypersecretion in further organisms of interest., Competing Interests: The authors declare no competing interest.

Background: Fungal enzymes are vital for industrial biotechnology, including the conversion of plant biomass to biofuels and bio-based chemicals. In recent years, there is increasing interest in using enzymes from thermophilic fungi, which often have higher reaction rates and thermal tolerance compared to currently used fungal enzymes. The thermophilic filamentous fungus Thermoascus aurantiacus produces large amounts of highly thermostable plant cell wall-degrading enzymes. However, no genetic tools have yet been developed for this fungus, which prevents strain engineering efforts. The goal of this study was to develop strain engineering tools such as a transformation system, a CRISPR/Cas9 gene editing system and a sexual crossing protocol to improve the enzyme production., Results: Here, we report Agrobacterium tumefaciens -mediated transformation (ATMT) of T. aurantiacus using the hph marker gene, conferring resistance to hygromycin B. The newly developed transformation protocol was optimized and used to integrate an expression cassette of the transcriptional xylanase regulator xlnR , which led to up to 500% increased xylanase activity. Furthermore, a CRISPR/Cas9 gene editing system was established in this fungus, and two different gRNAs were tested to delete the pyrG orthologue with 10% and 35% deletion efficiency, respectively. Lastly, a sexual crossing protocol was established using a hygromycin B- and a 5-fluoroorotic acid-resistant parent strain. Crossing and isolation of progeny on selective media were completed in a week., Conclusion: The genetic tools developed for T. aurantiacus can now be used individually or in combination to further improve thermostable enzyme production by this fungus., Competing Interests: Competing interestsThe authors declare that they have no competing interests., (© The Author(s) 2020.)

Objectives: Study national hospitalization trends for colorectal cancer in patients younger than 50 years of age., Methods: Patients under age 50 years hospitalized for colorectal cancer were studied using the national inpatient sample databases (2010-2014), using validated ICD-CM-9 codes and hospitalizations represented per 100,000 total inpatient population., Results: Colorectal cancer hospitalizations demonstrated a significant uptrend in the 41-50 years age group, with Caucasians and females most affected, stratifying for age and excluding those with a family history of colorectal cancer (p trend < 0.001)., Conclusions: Younger colorectal cancer patients aged 41-50 years (especially younger Caucasian females) are burdened with increasing hospitalization rates.

Considering an increase in the life expectancy leading to a rise in the elderly population, it is important to recognize the changes that occur along the process of aging. Gastrointestinal (GI) changes in the elderly are common, and despite some GI disorders being more prevalent in the elderly, there is no GI disease that is limited to this age group. While some changes associated with aging GI system are physiologic, others are pathological and particularly more prevalent among those above age 65 years. This article reviews the most important GI disorders in the elderly that clinicians encounter on a daily basis. We highlight age-related changes of the oral cavity, esophagus, stomach, small and large bowels, and the clinical implications of these changes. We review epidemiology and pathophysiology of common diseases, especially as they relate to clinical manifestation in elderly. Details regarding management of specific disease are discussed in detail if they significantly differ from the management for younger groups or if they are associated with significant challenges due to side effects or polypharmacy. Cancers of GI tract are not included in the scope of this article.

BACKGROUND Drug-induced liver injury (DILI) can present clinically as a spectrum that includes asymptomatic elevation of transaminases, acute or chronic hepatitis, and acute liver failure. Idiosyncratic DILI is more likely to affect individuals with comorbidities, and to have a wide range of clinical presentations. Although antibiotics are associated with DILI, the fluoroquinolone, ciprofloxacin, is a rarely reported cause. Two cases of idiosyncratic DILI following ciprofloxacin treatment are described, including a review of the literature. CASE REPORT Case 1: A 35-year-old man was treated with ciprofloxacin for periorbital cellulitis. On the second day of ciprofloxacin treatment, he developed abdominal pain, nausea, vomiting and increased serum levels of liver transaminases, aspartate aminotransferase (AST), and alanine aminotransferase (ALT). Further investigations excluded infectious hepatitis, autoimmune disease, or structural liver disease. Exclusion of other causes of DILI and cessation of ciprofloxacin resulted in clinical improvement and normalization of liver function tests (LFTs). Case 2: An 82-year-old man was treated with ciprofloxacin for osteomyelitis. On the tenth day of ciprofloxacin treatment, he developed jaundice and abnormal LFTs, including increased AST, ALT, alkaline phosphatase (ALP), and total bilirubin. Further investigations excluded infectious hepatitis, autoimmune disease, or structural liver disease. Exclusion of other causes of DILI and cessation of ciprofloxacin resulted in clinical improvement and normalization of LFTs. CONCLUSIONS Idiosyncratic DILI due to ciprofloxacin treatment is rare. These two cases have shown that timely diagnosis and discontinuation of ciprofloxacin can prevent the progression of DILI, reduce liver damage, and reduce mortality rates from DILI.

In obesity and the early stages of type 2 diabetes (T2D), proinflammatory cytokines are mildly elevated in the systemic circulation. This low-grade systemic inflammation exposes pancreatic islets to these circulating cytokines at much lower levels than seen within the islet during insulitis. These low-dose effects have not been well described. We examined mouse islets treated overnight with a low-dose cytokine combination commonly associated with inflammation (TNF-alpha, IL-1 beta, and IFN-gamma). We then examined islet function primarily using intracellular calcium ([Ca(2+)](i)), a key component of insulin secretion and cytokine signaling. Cytokine-treated islets demonstrated several features that suggested dysfunction including excess [Ca(2+)](i) in low physiological glucose (3mM), reduced responses to glucose stimulation, and disrupted [Ca(2+)](i) oscillations. Interestingly, islets taken from young db/db mice showed similar disruptions in [Ca(2+)](i) dynamics as cytokine-treated islets. Additional studies of control islets showed that the cytokine-induced elevation in basal [Ca(2+)](i) was due to both greater calcium influx through L-type-calcium-channels and reduced endoplasmic reticulum (ER) calcium storage. Many of these cytokine-induced disruptions could be reproduced by SERCA blockade. Our data suggest that chronic low-grade inflammation produces circulating cytokine levels that are sufficient to induce beta-cell dysfunction and may play a contributing role in beta-cell failure in early T2D., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Activation of adenosine A(2A) receptors inhibits inflammation in ischemia/reperfusion injury, and protects against cell damage at the injury site. Following transplantation 50% of islets die due to inflammation and apoptosis. This study investigated the effects of adenosine A(2A) receptor agonists (ATL146e and ATL313) on glucose-stimulated insulin secretion (GSIS) in vitro and transplanted murine syngeneic islet function in vivo. Compared to vehicle controls, ATL146e (100 nM) decreased insulin stimulation index [SI, (insulin)(high glucose)/(insulin)(low glucose)] (2.36 +/- 0.22 vs. 3.75 +/- 0.45; n = 9; p < 0.05). Coculture of islets with syngeneic leukocytes reduced SI (1.41 +/- 0.17; p < 0.05), and this was restored by ATL treatment (2.57 +/- 0.18; NS). Addition of a selective A(2A)AR antagonist abrogated ATL's protective effect, reducing SI (1.11 +/- 0.42). ATL treatment of A(2A)AR(+/+) islet/A(2A)AR(-/-) leukocyte cocultures failed to protect islet function (SI), implicating leukocytes as likely targets of A(2A)AR agonists. Diabetic recipient C57BL/6 mice (streptozotocin; 250 mg/kg, IP) received islet transplants to either the renal subcapsular or hepatic-intraportal site. Recipient mice receiving ATL therapy (ATL 146e or ATL313, 60 ng/kg/min, IP) achieved normoglycemia more rapidly than untreated recipients. Histological examination of grafts suggested reduced cellular necrosis, fibrosis, and lymphocyte infiltration in agonist-treated animals. Administration of adenosine A(2A) receptor agonists (ATL146e or ATL313) improves in vitro GSIS by an effect on leukocytes, and improves survival and functional engraftment of transplanted islets by inhibiting inflammatory islet damage in the peritransplant period, suggesting a potentially significant new strategy for reducing inflammatory islet loss in clinical transplantation.