The relations of circulating agouti-related peptide and leptin with altered sleep architecture in patients with active Cushing's disease: a pilot study.

AIM: To evaluate sleep architecture of patients with Cushing's disease (CD) and to explore whether agouti-related peptide (AgRP) and/or leptin play a permissive role in sleep alterations in patients with active CD. METHODS: We performed polysomnography on 26 patients with active CD and age 26 age- and sex-matched control subjects. Blood samples were obtained from all participants for the analyzes of AgRP and leptin. The laboratory and sleep-related parameters were compared. RESULTS: The groups were similar in age, gender, and body mass index. The CD group had reduced sleep efficiency (71.6 ± 12.1% vs. 78.8 ± 12.6%, p = 0.042) and increased wake after sleep onset (WASO%) (24.7 ± 13.1% vs. 17.4 ± 11.6%, p = 0.040) as compared to control group. Seventeen patients with CD (65.4%) and 18 control subjects (69.2%) had obstructive sleep apnea. Serum AgRP (13.2 ± 7.4 pg/ml vs. 9 ± 3.1, p = 0.029), leptin (59.5 mcg/l, [IQR] 32.6-94.6 vs. 25.3 mcg/l, [IQR] 12.9-57.5, p = 0.007) were higher in CD group. AgRP and leptin correlated negatively with total sleep time, sleep efficiency, stage N2 sleep (%), and positively with WASO%. In multiple regression analyses, serum cortisol (ß = - 0.359, p = 0.042) and AgRP (ß = - 0.481, p = 0.01) were significant predictor of sleep efficiency. AgRP was also significant predictor of WASO% (ß = 0.452 and p < 0.05). CONCLUSIONS: Active CD carries an increased risk of impaired sleep efficiency and continuity which may worsen health-related quality of life. Elevated circulating AgRP and, to a lesser extent, leptin may be associated with decreased sleep efficiency and continuity in patients with CD. Patients with CD who have subjective sleep symptoms should be screened with polysomnography.

Evaluation of sex hormone profile and semen parameters in acromegalic male patients.

OBJECTIVE: To investigate the changes in semen quality and bioavailable testosterone concentrations in acromegalic male patients according to their disease activity and compare them with patients with non-functional pituitary adenoma (NFA) and healthy controls (HC). METHODS: Twenty-four acromegalic patients with active disease, 22 acromegalic patients in remission, 10 HCs, and 10 patients with NFA were included. RESULTS: Total and calculated bioavailable testosterone concentrations were lower in patients with pituitary disease. Patients with acromegaly had more severely impaired total testosterone levels and semen parameters in comparison to HCs and patients with NFA. The degree of impairment was more prominent in acromegalic patients with active disease than acromegalic patients in remission. Acromegalic patients in remission had residual impairments in both semen quality and testosterone concentrations. Patients with NFA had the lowest concentrations of calculated bioavailable testosterone, followed by acromegalic patients with active disease and acromegalic patients in remission. Increasing growth hormone (GH) levels were found to be associated with both more severely impaired semen quality and androgen concentrations. CONCLUSION: Growth hormone hypersecretion can disturb reproductive biology and thereof semen quality. The reduction in semen quality and androgen levels may not fully recover upon disease control. Clinicians should be aware of the increased risk of impaired semen parameters and reduced total/bioavailable levels in acromegalic patients, especially in the setting of active disease.

A novel id-iri score: development and internal validation of the multivariable community acquired sepsis clinical risk prediction model.

We aimed to develop a scoring system for predicting in-hospital mortality of community-acquired (CA) sepsis patients. This was a prospective, observational multicenter study performed to analyze CA sepsis among adult patients through ID-IRI (Infectious Diseases International Research Initiative) at 32 centers in 10 countries between December 1, 2015, and May 15, 2016. After baseline evaluation, we used univariate analysis at the second and logistic regression analysis at the third phase. In this prospective observational study, data of 373 cases with CA sepsis or septic shock were submitted from 32 referral centers in 10 countries. The median age was 68 (51-77) years, and 174 (46,6%) of the patients were females. The median hospitalization time of the patients was 15 (10-21) days. Overall mortality rate due to CA sepsis was 17.7% (n = 66). The possible predictors which have strong correlation and the variables that cause collinearity are acute oliguria, altered consciousness, persistent hypotension, fever, serum creatinine, age, and serum total protein. CAS (%) is a new scoring system and works in accordance with the parameters in third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). The system has yielded successful results in terms of predicting mortality in CA sepsis patients.

Preoperative Somatostatin Analogue Treatment Might Trigger Apoptosis and Autophagy in Tumor Tissues of Patients with Acromegaly: A Pilot Study.

OBJECTIVE: To evaluate the effect of preoperative somatostatin analog (SRL) treatment on proteins associated with apoptosis and autophagy in patients with acromegaly and to determine factors correlating with these parameters. METHODS: Ex-vivo tumor samples of 11 SRL-treated and 9 SRL-untreated patients were retrospectively included in the study. Apoptotic and autophagic proteins were determined via immunohistochemical staining and apoptosis was evaluated via in situ DNA end labeling (TUNEL). RESULTS: TUNEL, caspase-3, and ATG-5 immunopositivity was significantly increased (p<0.01, p=0.01, p=0.01, respectively), survivin and beclin-1 immunopositivity was significantly decreased (p=0.03, p=0.02, respectively) in SRL-treated patients as compared with SRL-untreated controls. Ki-67 index was decreased significantly in the SRL-treated group (p=0.01). Significant positive correlations were detected between TUNEL and caspase-3 immunopositivity (r=0.577, p<0.01), and between survivin and beclin-1 immunopositivity (r=0.503, p=0.03). Age at diagnosis, preoperative GH, IGF-1 levels, tumor size, and invasion status were not found to affect TUNEL positivity nor did they correlate with caspase-3, survivin, beclin-1, ATG-5 immunopositivity (p>0.05 for all). Preoperative SRL treatment was the only factor that had a significant effect on TUNEL positivity (adjusted R2=0.39, p=0.02). Preoperative treatment duration was positively correlated with TUNEL and caspase-3 immunopositivity (r=0.526, p=0.02; r=0.475, p=0.04, respectively) and negatively correlated with survivin immunopositivity (r=-0.533, p=0.01). CONCLUSIONS: Somatostatin analog treatment might induce apoptosis, increase autophagy, and decrease cell proliferation in GH-secreting adenomas. Also, proteins related to cross-talk between autophagy and apoptosis are upregulated after SRL treatment.

Effect of Dephytinization by Fermentation and Hydrothermal Autoclaving Treatments on the Antioxidant Activity, Dietary Fiber, and Phenolic Content of Oat Bran.

Fermentation and hydrothermal methods were tested to reduce the phytic acid (PA) content of oat bran, and the effects of these methods on the dietary fiber (DF) and total phenolic (TP) contents as well as the antioxidant activity (AA) were also investigated. Fermentation with 6% yeast and for 6 h resulted in 88.2% reduction in PA content, while it only resulted in 32.5% reduction in the sample incubated for 6 h without yeast addition. The PA loss in autoclaved oat bran sample (1.5 h, pH 4.0) was 95.2% while it was 41.8% at most in the sample autoclaved without pH adjustment. In both methods, soluble, insoluble, and total DF contents of samples were remarkably higher than the control samples. Also for TP in the oat bran samples, both processes led to 17% and 39% increases, respectively, while AA values were 8% and 15%, respectively. Among all samples, the autoclaving process resulted in the lowest PA and the greatest amount of bioactive compounds.

Daily life reflections of acromegaly guidelines.

PURPOSE: To determine the differences in acromegaly diagnosis, treatment, and follow-up among Turkish endocrinologists, and to investigate how the published guidelines are applied in clinical practice. METHODS: The questionnaire was formatted as an electronic survey, conducted between November and December 2015, and sent weekly for 6 weeks via e-mail to 528 endocrinologists in Turkey. RESULTS: The questionnaire was answered by 37.4 % of endocrinologists. Insulin-like growth factor-1 and nadir growth hormone level after 75 g oral glucose tolerance test (nadir GH-OGTT) were the most commonly preferred methods for the initial diagnosis. A total of 49.5 % of the participants reported using preoperative medical therapy (MT) either routinely or on a case-to-case basis. Somatostatin analogs were the most commonly used drugs, both in pre- and postoperative MT. Disease activity following surgery was assessed in the 3rd postoperative month using IGF-1 levels. Similarly, IGF-1 monitoring was preferred in the follow-up period. Monitoring nadir GH-OGTT levels was the most commonly used method in the assessment of discordant test results. The dose titration was done at month 3 after the start of MT. Resistance to SRLs was considered after using the maximal dose for at least 6 months. Pegvisomant was generally used in second- and third-line therapy. Similarly, cabergoline was not preferred in monotherapy by the majority of participants. Radiotherapy was considered in patients with incomplete response to surgery and medical treatments. CONCLUSIONS: Although there were subtle differences, clinical practice guidelines were usually followed among Turkish endocrinologists.

Successful treatment of non-healing pressure ulcers with topical n-acetyl cysteine.

OBJECTIVE: N-acetyl cysteine (NAC) is a thiol compound with antioxidant and vasodilatory properties. It has multiple potential uses-including as an aid to wound healing-supported by varying levels of evidence. Pressure ulcers (PUs) are a major problem affecting older and bed-bound patients, and are associated with significant morbidity, mortality, and health-care costs. We aimed to study whether topical NAC treatment may be useful in non-healing PUs in a prospective case study in two debilitated nursing home residents suffering from a total of three treatment-resistant PUs. METHOD: PUs were staged as described by the National Pressure Ulcer Advisory Panel. The ulcers were measured at the beginning and weekly thereafter with a standard wound measuring paper ruler. RESULTS: The first patient had a category 3 pressure ulcer and the second patient had one category 3 and one category 4 ulcer. Topical NAC vial administration significantly improved healing in all three PUs without any side effects. CONCLUSION: Our data indicate that NAC may be used in treatment-resistant PUs successfully.

The problem of unrecognized acromegaly: surgeries patients undergo prior to diagnosis of acromegaly.

PURPOSE: To reveal the variety of symptoms experienced by patients before acromegaly diagnosis and to emphasize unneeded surgeries that patients undergo related to acromegaly prior to diagnosis of the disease. METHODS: In total, 490 consecutive adult patients with acromegaly who were treated at our institution between 1998 and 2014 were included in this cross-sectional study, of which 313 could be contacted. Participants were questioned about their complaints at initial consultation and at the time of diagnosis, the first medical professional who they consulted, interval between onset and diagnosis, and surgeries they had undergone. RESULTS: This study included 313 participants, of whom 181 were women. The mean age was 48.8 ± 12.0 years. Patients most frequently presented with acral growth of hands and feet (32.6%) and headache (26.2%). Internists were the medical specialists who were most frequently first consulted (29.4%) then neurosurgeons (11.8%). Acromegaly was generally diagnosed by endocrinologists (55%), followed by neurosurgeons (23%). The median elapsed period prior to diagnosis was 24 months, interquartile range 6.0-48.0 months. Some 45.7% had undergone surgery; 35.2% were related to acromegaly symptoms: head and throat surgery (12.8%), nose surgery (9.3%), thyroidectomy (6.4%), carpal tunnel surgery (4.8%). The delay period for patients who had an operation prior to acromegaly diagnosis was significantly longer than for those who had no operations (p < 0.001). CONCLUSIONS: Acromegaly patients mostly present to internal medicine professionals. Surgeries related to acromegaly complications and symptoms before diagnosis cause a long delay period before diagnosis. Medical staff must be more aware of the clinical aspects of acromegaly.

Intravitreal ranibizumab for neovascular age-related macular degeneration patients with good baseline visual acuity and the predictive factors for visual outcomes.

PURPOSE: To evaluate the efficacy of intravitreal ranibizumab for the treatment of neovascular age-related macular degeneration (nAMD) patients with a visual acuity (VA) of ≥ 20/40 and to investigate the predictive factors for visual outcomes. METHODS: The present study is a retrospective analysis of patients with VA ≥ 20/40. Injections were given monthly for the first 3 months and thereafter as needed. The patients were divided into two groups; group 1, patients not receiving further injections beyond the 3 loading doses, and group 2, those who received further injections. Next, group 2 was divided into two subgroups; group 2A, patients who did not experience VA loss, and group 2B, those who experienced VA loss. Data collected for each patient included VA and central retinal thickness (CRT) measured at baseline, months 3, 6, 9, and 12. RESULTS: The study included 96 eyes of 96 patients. Change in VA showed a significant inverse correlation with total number of injections at month 12 (r=-0.34, P=0.001), and the presence of pigment epithelial detachment (PED) at baseline (r=-0.35, P<0.01). VA outcomes were better in group 1 than group 2 at all time points (P<0.001 for all). Change in VA at month 3 was not significantly different between groups 2A and 2B (P=0.26); however, change in VA at month 6, 9, and 12 were statistically different between the two groups (P<0.001 for all). CONCLUSION: Intravitreal ranibizumab is an effective treatment for nAMD patients with good VA. The presence of PED, need for reinjection, and VA loss were unfavorable prognostic factors.

Effect of storage and insect infestation on the mineral and vitamin contents of wheat grain and flour.

The objective of this study was to evaluate how storage and Sitophilus granarius L. infestation affects mineral and vitamin (thiamin and riboflavin) contents of wheat grain and flour obtained from the wheat. Wheat samples were infested with nonsexed S. granarius at a rate of two adults per kilogram, and stored for 6 mo at 30 +/- 1 degrees C and 70 +/- 5% relative humidity. Every 30 d, samples of wheat were collected and evaluated for insect population, mineral, thiamin, and riboflavin contents. Flour milled from these wheat samples was also evaluated for mineral, thiamin, and riboflavin contents. None of the analyses performed on the uninfested wheat and flour samples showed any noticeable change during the storage period. The insect population of the infested wheat samples increased during the storage period. The ratio of the mineral contents to dry matter significantly increased in the infested wheat and flour samples during the infestation period, whereas thiamin and riboflavin contents considerably decreased. The feeding habits of S. granarius and the distribution of minerals and vitamins in the wheat grain caused the changes observed in the levels of these compounds. The effects of infestation were greatest in the latter stages, during which the insect population increased greatly.

Vitamin B12, folate, homocysteine and urinary methylmalonic acid levels in infants.

Serum vitamin B12 and folate, and their functional markers, plasma homocysteine and urinary methylmalonate (uMMA) were measured in 204 healthy, term infants at birth, and at 2 and 6 months. Compared with infants receiving formula food, those fed mother's milk had lower vitamin B12 and folate at 2 and 6 months. In infants receiving mother's milk, vitamin B12 levels were similar at birth (238 pg/ml) and 2 months (243 pg/ml), whereas with formula milk the level was significantly higher at 2 months (558 pg/ml) than at birth (257 pg/ml). Vitamin B12 was negatively correlated with homocysteine at birth and 6 months. The level of uMMA (mmol/mol creatinine) was higher at 2 (mother's milk, 25.5; formula, 23.97) and 6 months (19.77; 15) than at birth (11.97; 10.88), and was not correlated with vitamin B12 levels. Homocysteine may be a reliable marker of vitamin B12 status in neonates and infants; however, uMMA is not suitable as a marker of vitamin B12 status.

Effects of wheat maturation stage and cooking method on dietary fiber and phytic acid contents of firik, a wheat-based local food.

Samples of two durum wheat cultivars (cvs. Duraking and Ege 88) at different maturation stages (13, 16, 19, 22, 25 days post anthesis) were processed into firik (a wheat-based specialty food) using two different cooking methods: roasting (scorching) on flames and boiling at atmospheric pressure. Both the acid detergent and neutral detergent fiber contents of the firiks produced from two durum wheat samples decreased significantly (p < 0.01) with maturation. Total P contents of the firiks of both cultivars produced by both methods showed a significant downward trend within the period of maturation while their phytic acid contents showed a significant upward trend (p < 0.01). It was possible to obtain a reduced phytic acid, high fiber product from the wheats harvested at early stages of maturation (13 and 16 days after anthesis).