First principles of modelling the stabilization of microturbulence by fast ions

The observation that fast ions stabilize ion-temperature-gradient-driven microturbulence has profound implications for future fusion reactors. It is also important in optimizing the performance of present-day devices. In this work, we examine in detail the phenomenology of fast ion stabilization and present a reduced model which describes this effect. This model is derived from the high-energy limit of the gyrokinetic equation and extends the existing "dilution" model to account for nontrivial fast ion kinetics. Our model provides a physically-transparent explanation for the observed stabilization and makes several key qualitative predictions. Firstly, that different classes of fast ions, depending on their radial density or temperature variation, have different stabilizing properties. Secondly, that zonal flows are an important ingredient in this effect precisely because the fast ion zonal response is negligible. Finally, that in the limit of highly-energetic fast ions, their response approaches that of the "dilution" model; in particular, alpha particles are expected to have little, if any, stabilizing effect on plasma turbulence. We support these conclusions through detailed linear and nonlinear gyrokinetic simulations.Comment: 29 pages, 10 figures, 3 table

Laparoscopic adjustable gastric banding – should a second chance be given?

Background: Obesity is a chronic relapsing-remitting disease and a global pandemic, being associated with multiple comorbidities. Laparoscopic adjustable gastric banding (LAGB) is one of the safest surgical procedures used for the treatment of obesity, and even though its popularity has been decreasing over time, it still remains an option for a certain group of patients, producing considerable weight loss and improvement in obesity-associated comorbidities. Methods: The aim of this study was to evaluate the impact of weight loss following LAGB on obesity-associated comorbidities, and to identify factors that could predict better response to surgery, and patient sub-groups exhibiting greatest benefit. A total of 99 severely obese patients (81.2% women, mean age 44.19 ± 10.94 years, mean body mass index (BMI) 51.84 ± 8.77 kg/m2) underwent LAGB in a single institution. Results obtained 1, 2, and 5 years postoperatively were compared with the pre-operative values using SPPS software version 20. Results: A significant drop in BMI was recorded throughout the follow-up period, as well as in A1c and triglycerides, with greatest improvement seen 2 years after surgery (51.8 ± 8.7 kg/m2 vs 42.3 ± 9.2 kg/m2, p < 0.05, 55.5 ± 19.1 mmol/mol vs 45.8 ± 13.7 mmol/mol, p < 0.05, and 2.2 ± 1.7 mmol/l vs 1.5 ± 0.6 mmol/l). Better outcomes were seen in younger patients, with lower duration of diabetes before surgery, and lower pre-operative systolic blood pressure. Conclusions: Younger age, lower degree of obesity, and lower severity of comorbidities at the time of surgery can be important predictors of successful weight loss, making this group of patients the ideal candidates for LAGB

Ectopic hyperprolactinaemia due to a malignant Uterine Tumor Resembling Ovarian Sex Cord Tumors (UTROCST)

Purpose Moderate hyperprolactinaemia (2–5 times upper limit of normal) occurring in a patient with a normal pituitary MRI is generally considered to be due to a lesion below the level of detection of the MRI scanner assuming macroprolactin and stress have been excluded. Most patients with mild-to-moderate hyperprolactinaemia and a normal MRI respond to dopamine agonist therapy. We present the rare case of a patient who had prolactin elevation typical of a prolactin-secreting pituitary macroadenoma,with a normal cranial MRI, and in whom the prolactin rose further with dopamine agonist treatment. Subsequent investigations revealed ectopic hyperprolactinaemia to a uterine tumor resembling ovarian sex cord tumor (UTROSCT) which resolved following tumor resection. Although mostly considered to be benign, the UTROSCT recurred with recurrent hyperprolactinaemia and intraabdominal metastases. Methods We have systematically and critically reviewed existing literature relating to ectopic hyperprolactinaemia in general and UTROCST specifically. Results Fewer than 80 cases of UTROSCTs have been reported globally of which about 23% have shown malignant behaviour. There are fewer than 10 cases of paraneoplastic hyperprolactinaemia originating from uterine neoplasms including one other case of ectopic hyperprolactinaemia to a UTROSCT. Conclusions Our case demonstrates the importance of screening for extracranial hyperprolactinaemia in the context of: (1) substantially raised prolactin (10× ULN) and (2) normal cranial MRI assuming macroprolactin has been excluded. The majority of extracranial ectopic prolactin-secreting tumors occur in the reproductive organs.Methods: We have systematically and critically reviewed existing literature relating to ectopic hyperprolactinaemia in general and UTROCST specifically. Results: Fewer than 80 cases of UTROSCTs have been reported globally of which about 23% have shown malignant behaviour. There are fewer than 10 cases of paraneoplastic hyperprolactinaemia originating from uterine neoplasms including one other case of ectopic hyperprolactinaemia to a UTROSCT. Conclusions: Our case demonstrates the importance of screening for extracranial hyperprolactinaemia in the context of: (1) substantially raised prolactin (10xULN) and (2) normal cranial MRI assuming macroprolactin has been excluded. The majority of extracranial ectopic prolactin-secreting tumors occur in the reproductive organs

Antibiotic susceptibility of Streptococcus agalactiae isolated from Tilapia pond sediment in Lubao, Pampanga, Philippines

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Diagnosis and management of parathyroid carcinoma: a state-of-the-art review

Parathyroid carcinoma is one of the least common endocrine malignancies and accounts for approximately 1% of all patients with primary hyperparathyroidism. A systematic review of peer-reviewed literature published between January 2000 and March 2022 via Medline, Embase, Cochrane Central Register of Controlled Trials, EudraCT, ClinicalTrials.gov, CINAHL and SCOPUS was conducted. Manuscripts were eligible if they included data on adult non-pregnant populations with parathyroid carcinoma. No restrictions regarding interventions, comparators or duration of follow-up were imposed. Single case reports, reviews or meta-analyses were excluded. Outcomes of interest were molecular pathogenesis, clinical presentation, differential diagnosis, treatment, follow-up and overall survival. Study quality was evaluated using the Newcastle-Ottawa Scale for observational studies. This review included 75 studies from 17 countries, reporting on more than 3000 patients with parathyroid carcinoma. CDC73 mutation has been recognised as playing a pivotal role in molecular pathogenesis. Parathyroid carcinoma typically presents with markedly increased calcium and parathyroid hormone levels. The most frequently described symptoms were bone and muscle pain or weakness. En bloc resection remains the gold standard for the surgical approach. The 5-year overall survival ranged from 60 to 93%, with resistant hypercalcaemia a significant cause of mortality. Emerging evidence indicating that targeted therapy, based on molecular biomarkers, presents a novel treatment option. The rarity of PC and need for personalised treatment warrant multidisciplinary management in a 'centre of excellence' with a track record in PC management

Phenome-wide analysis of Taiwan Biobank reveals novel glycemia-related loci and genetic risks for diabetes

To explore the complex genetic architecture of common diseases and traits, we conducted comprehensive PheWAS of ten diseases and 34 quantitative traits in the community-based Taiwan Biobank (TWB). We identified 995 significantly associated loci with 135 novel loci specific to Taiwanese population. Further analyses highlighted the genetic pleiotropy of loci related to complex disease and associated quantitative traits. Extensive analysis on glycaemic phenotypes (T2D, fasting glucose and Hb

Mitochondrial and sarcoplasmic reticulum abnormalities in cancer cachexia: Altered energetic efficiency?

Background Cachexia is a wasting condition that manifests in several types of cancer, and the main characteristic is the profound loss of muscle mass. Methods The Yoshida AH-130 tumor model has been used and the samples have been analyzed using transmission electronic microscopy, real-time PCR and Western blot techniques. Results Using in vivo cancer cachectic model in rats, here we show that skeletal muscle loss is accompanied by fiber morphologic alterations such as mitochondrial disruption, dilatation of sarcoplasmic reticulum and apoptotic nuclei. Analyzing the expression of some factors related to proteolytic and thermogenic processes, we observed in tumor-bearing animals an increased expression of genes involved in proteolysis such as ubiquitin ligases Muscle Ring Finger 1 (MuRF-1) and Muscle Atrophy F-box protein (MAFBx). Moreover, an overexpression of both sarco/endoplasmic Ca2 +-ATPase (SERCA1) and adenine nucleotide translocator (ANT1), both factors related to cellular energetic efficiency, was observed. Tumor burden also leads to a marked decreased in muscle ATP content. Conclusions In addition to muscle proteolysis, other ATP-related pathways may have a key role in muscle wasting, both directly by increasing energetic inefficiency, and indirectly, by affecting the sarcoplasmic reticulum-mitochondrial assembly that is essential for muscle function and homeostasis. General significance The present study reports profound morphological changes in cancer cachectic muscle, which are visualized mainly in alterations in sarcoplasmic reticulum and mitochondria. These alterations are linked to pathways that can account for energy inefficiency associated with cancer cachexia. Highlights ► Skeletal muscle from cachectic animals showed fiber morphologic alterations. ► These alterations are mitochondrial disruption and dilatation of sarcoplasmic reticulum. ► An overexpression of both sarco/endoplasmic Ca2 +-ATPase (SERCA1) and adenine nucleotide translocator (ANT1) was reported. ► Tumor burden also leads to a marked decreased in muscle ATP content. Previous article in issu

TMEM258 Is a Component of the Oligosaccharyltransferase Complex Controlling ER Stress and Intestinal Inflammation

Summary - Significant insights into disease pathogenesis have been gleaned from population-level genetic studies; however, many loci associated with complex genetic disease contain numerous genes, and phenotypic associations cannot be assigned unequivocally. In particular, a gene-dense locus on chromosome 11 (61.5–61.65 Mb) has been associated with inflammatory bowel disease, rheumatoid arthritis, and coronary artery disease. Here, we identify TMEM258 within this locus as a central regulator of intestinal inflammation. Strikingly, Tmem258 haploinsufficient mice exhibit severe intestinal inflammation in a model of colitis. At the mechanistic level, we demonstrate that TMEM258 is a required component of the oligosaccharyltransferase complex and is essential for N-linked protein glycosylation. Consequently, homozygous deficiency of Tmem258 in colonic organoids results in unresolved endoplasmic reticulum (ER) stress culminating in apoptosis. Collectively, our results demonstrate that TMEM258 is a central mediator of ER quality control and intestinal homeostasis.Leona M. and Harry B. Helmsley Charitable Trust (2014PG-IBD016)Crohn's and Colitis Foundation of AmericaNational Institutes of Health (U.S.) (grant DK043351)National Institutes of Health (U.S.) (grant DK097485