Diet-induced weight loss alters hepatic glucocorticoid metabolism in type 2 diabetes mellitus

Context: Altered tissue-specific glucocorticoid metabolism has been described in uncomplicated obesity and type 2 diabetes. We hypothesized that weight loss induced by diet and exercise, which has previously been shown to reverse abnormal cortisol metabolism in uncomplicated obesity, also normalizes cortisol metabolism in patients with type 2 diabetes. Objective: Test the effects of a diet intervention with added exercise on glucocorticoid metabolism. Design: Two groups followed a Paleolithic diet (PD) for 12 weeks with added 180 min of structured aerobic and resistance exercise per week in one randomized group (PDEX). Setting: Umea University Hospital. Participants: Men and women with type 2 diabetes treated with lifestyle modification +/- metformin were included. Twenty-eight participants (PD, n = 15; PDEX, n = 13) completed measurements of glucocorticoid metabolism. Main outcome measures: Changes in glucocorticoid metabolite levels in 24-h urine samples, expression of HSD1181 mRNA in s.c. adipose tissue and conversion of orally administered cortisone to cortisol measured in plasma. Body composition and insulin sensitivity were measured using a hyperinsulinemic-euglycemic clamp, and liver fat was measured by magnetic resonance spectroscopy. Results: Both groups lost weight and improved insulin sensitivity. Conversion of orally taken cortisone to plasma cortisol and the ratio of 5 alpha-THF + 5 beta-THF/THE in urine increased in both groups. Conclusions: These interventions caused weight loss and improved insulin sensitivity with concomitant increases in the conversion of cortisone to cortisol, which is an estimate of hepatic HSD11B1 activity. This suggests that dysregulation of liver glucocorticoid metabolism in these patients is a consequence rather than a cause of metabolic dysfunction

Mining metadata from unidentified ITS sequences in GenBank: A case study in Inocybe (Basidiomycota)

<p>Abstract</p> <p>Background</p> <p>The lack of reference sequences from well-identified mycorrhizal fungi often poses a challenge to the inference of taxonomic affiliation of sequences from environmental samples, and many environmental sequences are thus left unidentified. Such unidentified sequences belonging to the widely distributed ectomycorrhizal fungal genus <it>Inocybe </it>(<it>Basidiomycota</it>) were retrieved from GenBank and divided into species that were identified in a phylogenetic context using a reference dataset from an ongoing study of the genus. The sequence metadata of the unidentified <it>Inocybe </it>sequences stored in GenBank, as well as data from the corresponding original papers, were compiled and used to explore the ecology and distribution of the genus. In addition, the relative occurrence of <it>Inocybe </it>was contrasted to that of other mycorrhizal genera.</p> <p>Results</p> <p>Most species of <it>Inocybe </it>were found to have less than 3% intraspecific variability in the ITS2 region of the nuclear ribosomal DNA. This cut-off value was used jointly with phylogenetic analysis to delimit and identify unidentified <it>Inocybe </it>sequences to species level. A total of 177 unidentified <it>Inocybe </it>ITS sequences corresponding to 98 species were recovered, 32% of which were successfully identified to species level in this study. These sequences account for an unexpectedly large proportion of the publicly available unidentified fungal ITS sequences when compared with other mycorrhizal genera. Eight <it>Inocybe </it>species were reported from multiple hosts and some even from hosts forming arbutoid or orchid mycorrhizae. Furthermore, <it>Inocybe </it>sequences have been reported from four continents and in climate zones ranging from cold temperate to equatorial climate. Out of the 19 species found in more than one study, six were found in both Europe and North America and one was found in both Europe and Japan, indicating that at least many north temperate species have a wide distribution.</p> <p>Conclusion</p> <p>Although DNA-based species identification and circumscription are associated with practical and conceptual difficulties, they also offer new possibilities and avenues for research. Metadata assembly holds great potential to synthesize valuable information from community studies for use in a species and taxonomy-oriented framework.</p

Трансоральная тиреоид- и паратиреоидэктомия: серия наблюдений

ЩИТОВИДНОЙ ЖЕЛЕЗЫ БОЛЕЗНИПАРАЩИТОВИДНЫХ ЖЕЛЕЗ БОЛЕЗНИОКОЛОЩИТОВИДНЫХ ЖЕЛЕЗ БОЛЕЗНИЭНДОКРИННЫЕ ХИРУРГИЧЕСКИЕ ОПЕРАЦИИХИРУРГИЯ ЭНДОКРИННЫХ ЖЕЛЕЗТИРЕОИДЭКТОМИЯЭНДОСКОПИЧЕСКАЯ ТЕХНИКАПАРАТИРЕОИДЭКТОМИЯОКОЛОЩИТОВИДНОЙ ЖЕЛЕЗЫ УДАЛЕНИЕТРАНСОРАЛЬНЫЙ ДОСТУПТРАНСОРАЛЬНАЯ ХИРУРГИЯ ШЕИДЕРМАТОЛОГИЧЕСКИЙ ИНДЕКСКАЧЕСТВО ЖИЗНИЦель. Представить результаты собственной серии трансоральных операций у пациентов с заболеваниями щитовидной и околощитовидных желез. Материал и методы. Трансоральная операция выполнена 20 женщинам и 1 мужчине. Все пациенты оперированы по поводу первичного заболевания и соответствовали критериям отбора на основании ультразвукового и цитологического исследований, гормонального фона, соматического статуса. Показаниями к операции в 17 случаях явился узловой зоб, в 2 случаях – диффузный токсический зоб, в 2 случаях – первичный гиперпаратиреоз, аденома околощитовидной железы. Хирургическая техника включала в себя трехпортовый доступ в нижнем своде преддверия рта и газовый способ поддержания рабочей полости. Для операции использовались стандартные лапароскопические инструменты и ультразвуковое энергетическое устройство. В послеоперационном периоде пациенты прошли тест по субъективной оценке эстетического результата операции с использованием опросника дерматологического индекса качества жизни. Результаты. Тиреоидэктомия выполнена 4 пациентам, 15 пациентам – гемитиреоидэктомия и 2 пациентам – паратиреоидэктомия. У одной пациентки трансоральная паратиреоидэктомия выполнена в составе симультанной операции по поводу синдрома множественной эндокринной неоплазии 1 типа. У двух пациентов после операции верифицирован папиллярный рак T1N0M0. Среднее время операции составило 196,1 мин (диапазон 110 – 300 мин). Средняя кровопотеря 39,5 мл (диапазон 10 – 300 мл). На девятой по счету операции потребовалась конверсия вследствие неконтролируемого кровотечения. В одном случае отмечен преходящий парез возвратного гортанного нерва, в одном случае гематома. После операции медиана и среднее значение дерматологического индекса качества жизни составили 1 (0; 4) и 2,05 соответственно, что свидетельствует о незначительном влиянии на качество жизни. Заключение. Трансоральная эндоскопическая операция на щитовидной и околощитовидных железах перспективна в отношении оптимального выбора у пациентов, желающих избежать рубца на шее.Objective. To present the results of the author’s own series of transoral operations in patients with pathology of the thyroid and parathyroid glands. Methods. Transoral surgery was performed in women (n=20) and man (n=1). All patients were operated on for the primary disease and met the selection criteria based on ultrasound and cytological examinations, hormonal levels, and somatic status. Indications for surgery were: nodular goiter in 17 cases, diffuse toxic goiter – in 2 cases, parathyroid adenoma – in 2 cases. The surgical technique included a three-port approach in the lower fornix of the vestibule of the mouth and a gas technique for maintaining the working cavity. Standard laparoscopic instruments and an energy based ultrasonic device were used for the operation. In the postoperative period, patients underwent a test for subjective assessment of the aesthetic result of the operation using the survey of the dermatology life quality index. Results. Thyroidectomy was performed in 4 patients, hemithyroidectomy – in 15 patients and parathyroidectomy – in 2 patients. In one patient, transoralparathyroidectomy was performed as a part of a simultaneous operation for multiple endocrine neoplasia type 1 syndrome. Papillary cancer T1N0M0 was verified in two patients after surgery. The mean operation time was 196.1 min (range 110 – 300 min). Average blood loss – 39.5 ml (range 10 – 300 ml). The nineth operation required the conversion due to severe bleeding. In one case, the temporary recurrent laryngeal nerve (RLN) injury was reported, in one case – hematoma. After surgery, the median and average values of the dermatology life quality index were 1 (IQR 0-4) and 2.05, respectively, which indicates an insignificant effect on the quality of life. Conclusion. Transoral endoscopic surgery on the thyroid and parathyroid glands would be the promising optimal choice in patients to avoid scarring on the neck

Intestinal Epithelial Stem/Progenitor Cells Are Controlled by Mucosal Afferent Nerves

Background: The maintenance of the intestinal epithelium is of great importance for the survival of the organism. A possible nervous control of epithelial cell renewal was studied in rats and mice. Methods: Mucosal afferent nerves were stimulated by exposing the intestinal mucosa to capsaicin (1.6 mM), which stimulates intestinal external axons. Epithelial cell renewal was investigated in the jejunum by measuring intestinal thymidine kinase (TK) activity, intestinal H-3-thymidine incorporation into DNA, and the number of crypt cells labeled with BrdU. The influence of the external gut innervation was minimized by severing the periarterial nerves. Principal Findings: Luminal capsaicin increased all the studied variables, an effect nervously mediated to judge from inhibitory effects on TK activity or H-3-thymidine incorporation into DNA by exposing the mucosa to lidocaine (a local anesthetic) or by giving four different neurotransmitter receptor antagonists i.v. (muscarinic, nicotinic, neurokinin1 (NK1) or calcitonin gene related peptide (CGRP) receptors). After degeneration of the intestinal external nerves capsaicin did not increase TK activity, suggesting the involvement of an axon reflex. Intra-arterial infusion of Substance P (SP) or CGRP increased intestinal TK activity, a response abolished by muscarinic receptor blockade. Immunohistochemistry suggested presence of M3 and M5 muscarinic receptors on the intestinal stem/progenitor cells. We propose that the stem/progenitor cells are controlled by cholinergic nerves, which, in turn, are influenced by mucosal afferent neuron(s) releasing acetylcholine and/or SP and/or CGRP. In mice lacking the capsaicin receptor, thymidine incorporation into DNA and number of crypt cells labeled with BrdU was lower than in wild type animals suggesting that nerves are important also in the absence of luminal capsaicin, a conclusion also supported by the observation that atropine lowered thymidine incorporation into DNA by 60% in control rat segments. Conclusion: Enteric nerves are of importance in maintaining the intestinal epithelial barrier.Original Publication:Ove Lundgren, Mats Jodal, Madeleine Jansson, Anders T Ryberg and Lennart Svensson, Intestinal Epithelial Stem/Progenitor Cells Are Controlled by Mucosal Afferent Nerves, 2011, PLOS ONE, (6), 2, 16295.http://dx.doi.org/10.1371/journal.pone.0016295Copyright: Public Library of Science (PLoS)http://www.plos.org

Fit and fat from enlarged badges: a field experiment on male sand lizards.

To investigate the impact of nuptial coloration (the badge) on male fitness in the Swedish sand lizard (Lacerta agilis), we conducted a manipulation experiment in a natural population. Males in one group had their badges enlarged by being painted as cheaters and were compared to a control group with respect to mate acquisition, body condition and survival. Badge enlargement did not affect survival, but elevated mate acquisition by almost 400%, and body condition in small males. This increase in condition is likely to stem from greater access to female-associated sites with high food availability

Intestinal Epithelial Stem/Progenitor Cells Are Controlled by Mucosal Afferent Nerves

Background: The maintenance of the intestinal epithelium is of great importance for the survival of the organism. A possible nervous control of epithelial cell renewal was studied in rats and mice. Methods: Mucosal afferent nerves were stimulated by exposing the intestinal mucosa to capsaicin (1.6 mM), which stimulates intestinal external axons. Epithelial cell renewal was investigated in the jejunum by measuring intestinal thymidine kinase (TK) activity, intestinal H-3-thymidine incorporation into DNA, and the number of crypt cells labeled with BrdU. The influence of the external gut innervation was minimized by severing the periarterial nerves. Principal Findings: Luminal capsaicin increased all the studied variables, an effect nervously mediated to judge from inhibitory effects on TK activity or H-3-thymidine incorporation into DNA by exposing the mucosa to lidocaine (a local anesthetic) or by giving four different neurotransmitter receptor antagonists i.v. (muscarinic, nicotinic, neurokinin1 (NK1) or calcitonin gene related peptide (CGRP) receptors). After degeneration of the intestinal external nerves capsaicin did not increase TK activity, suggesting the involvement of an axon reflex. Intra-arterial infusion of Substance P (SP) or CGRP increased intestinal TK activity, a response abolished by muscarinic receptor blockade. Immunohistochemistry suggested presence of M3 and M5 muscarinic receptors on the intestinal stem/progenitor cells. We propose that the stem/progenitor cells are controlled by cholinergic nerves, which, in turn, are influenced by mucosal afferent neuron(s) releasing acetylcholine and/or SP and/or CGRP. In mice lacking the capsaicin receptor, thymidine incorporation into DNA and number of crypt cells labeled with BrdU was lower than in wild type animals suggesting that nerves are important also in the absence of luminal capsaicin, a conclusion also supported by the observation that atropine lowered thymidine incorporation into DNA by 60% in control rat segments. Conclusion: Enteric nerves are of importance in maintaining the intestinal epithelial barrier.Original Publication:Ove Lundgren, Mats Jodal, Madeleine Jansson, Anders T Ryberg and Lennart Svensson, Intestinal Epithelial Stem/Progenitor Cells Are Controlled by Mucosal Afferent Nerves, 2011, PLOS ONE, (6), 2, 16295.http://dx.doi.org/10.1371/journal.pone.0016295Copyright: Public Library of Science (PLoS)http://www.plos.org

Using a paleo ratio to assess adherence to paleolithic dietary recommendations in a randomized controlled trial of individuals with type 2 diabetes

This study is a secondary analysis of a randomized controlled trial using Paleolithic diet and exercise in individuals with type 2 diabetes. We hypothesized that increased adherence to the Paleolithic diet was associated with greater effects on blood pressure, blood lipids and HbA1c independent of weight loss. Participants were asked to follow a Paleolithic diet for 12 weeks and were randomized to supervised exercise or general exercise recommendations. Four-day food records were analyzed, and food items characterized as “Paleolithic” or “not Paleolithic”. Foods considered Paleolithic were lean meat, poultry, fish, seafood, fruits, nuts, berries, seeds, vegetables, and water to drink; “not Paleolithic” were legumes, cereals, sugar, salt, processed foods, and dairy products. A Paleo ratio was calculated by dividing the Paleolithic calorie intake by total calorie intake. A mul-tiple regression model predicted the outcome at 12 weeks using the Paleo ratio, group affiliation, and outcome at baseline as predictors. The Paleo ratio increased from 28% at baseline to 94% after the intervention. A higher Paleo ratio was associated with lower fat mass, BMI, waist circumference, sys-tolic blood pressure, and serum triglycerides at 12 weeks, but not with lower HbA1c levels. The Paleo ratio predicted triglyceride levels independent of weight loss (p = 0.046). Moreover, an increased monounsaturated/saturated fatty acids ratio and an increased polyunsaturated/saturated fatty acids ratio was associated with lower triglyceride levels independent of weight loss. (p = 0.017 and p = 0.019 respectively). We conclude that a higher degree of adherence to the Paleolithic diet recommendations improved fat quality and was associated with improved triglyceride levels independent of weight loss among individuals with type 2 diabetes

Internet-delivered acceptance-based behavior therapy for generalized anxiety disorder: A pilot study

AbstractObjectiveInternet-delivered cognitive behavior therapy (ICBT) has been developed and tested for treating persons with generalized anxiety disorder (GAD). A new form of CBT focuses on acceptance (of internal experiences or difficult psychological content), mindfulness and valued actions. To date this form of CBT has not been delivered via the internet for persons with GAD. The aim of this study was to describe the functionality of a new internet-delivered acceptance-based behavior therapy for GAD, and to test the effect of the intervention in an open pilot trial.MethodsFollowing exclusion of two patients we included 14 patients diagnosed with GAD from two primary care clinics. At 2–3months follow-up after treatment 10 patients completed the outcome measures. The treatment lasted for an average of 15weeks and consisted of acceptance-based techniques, behavior therapy components and homework assignments.ResultsA majority of participants completed all modules during the treatment. Findings on the Penn State Worry Questionnaire showed a within-group improvement of Cohen's d=2.14 at posttreatment. At the follow-up results were maintained. Client satisfaction ratings were high.ConclusionsWe conclude that internet-delivered acceptance-based behavior therapy potentially can be a promising new treatment for GAD. A controlled trial of the program has already been completed