The complex circumstellar environment of supernova 2023ixf.

The early evolution of a supernova (SN) can reveal information about the environment and the progenitor star. When a star explodes in vacuum, the first photons to escape from its surface appear as a brief, hours-long shock-breakout flare1,2, followed by a cooling phase of emission. However, for stars exploding within a distribution of dense, optically thick circumstellar material (CSM), the first photons escape from the material beyond the stellar edge and the duration of the initial flare can extend to several days, during which the escaping emission indicates photospheric heating3. Early serendipitous observations2,4 that lacked ultraviolet (UV) data were unable to determine whether the early emission is heating or cooling and hence the nature of the early explosion event. Here we report UV spectra of the nearby SN 2023ixf in the galaxy Messier 101 (M101). Using the UV data as well as a comprehensive set of further multiwavelength observations, we temporally resolve the emergence of the explosion shock from a thick medium heated by the SN emission. We derive a reliable bolometric light curve that indicates that the shock breaks out from a dense layer with a radius substantially larger than typical supergiants.

Prevalence of type 2 diabetes mellitus in a representative sample of Greek adults and its association with modifiable risk factors: results from the Hellenic National Nutrition and Health Survey.

OBJECTIVE: Diabetes mellitus is a disease associated with many complications leading to premature death. The aim of this study was to estimate prevalence of type 2 diabetes (T2D), and the proportion of the population unaware of the condition, in association with modifiable risk factors. STUDY DESIGN: Data from the Hellenic National Nutrition and Health Survey were used (n = 3773 adults, 40.8% men) and were obtained by trained personnel. METHODS: Diabetes mellitus disease status was categorized as per the International Classification of Diseases codes (10th version). A subsample from the two main metropolitan areas was used to assess T2D and impaired fasting glucose (IFG) (n = 990; 38.2% men) from plasma analysis. RESULTS: The prevalence of T2D in the population was 5.2% in total, reaching 13.7% in adults aged >60 years (no sex differences). IFG was observed in 27.3% of adults in the two metropolitan areas, and 40% were unaware of having T2D in this subsample. The likelihood of having T2D significantly increased with age and body weight, whereas it decreased with higher educational level and physical activity (P for all <0.001). CONCLUSION: The high T2D prevalence in adults, especially among the older age-groups, suggests a major public health problem in Greece.

Insufficient glucocorticoid receptor signaling and flattened salivary cortisol profile are associated with metabolic and inflammatory indices in type 2 diabetes.

PURPOSE: Impaired negative feedback and hyperactivation of the hypothalamic-pituitary-adrenal (HPA) axis characterizes type 2 diabetes mellitus (T2DM). The glucocorticoid receptor (GR) is a key mediator of HPA axis negative feedback; however, its role in linking hypercortisolemia and T2DM-associated hyperglycemia, hyperlipidemia and inflammation is not yet known. METHODS: In peripheral mononuclear cells (PBMC) from 31 T2DM patients and 24 healthy controls, we measured various GR-signaling parameters such as phosphorylated GR (pGR-S211), GRα/GRß gene expression and GC-sensitivity [using the basal and dexamethasone (DEX)-induced leucine zipper (GILZ) and FK506 binding-protein (FKBP5) mRNA levels as well as the basal interleukin (IL)-1ß protein levels]. Diurnal salivary cortisol curve parameters such as the cortisol awaking response (CAR) and area under the curve (AUCtotal and AUCi) as well as inflammatory and metabolic indices were also determined. RESULTS: T2DM patients exhibited diminished pGR-S211 protein content, increased GRß, decreased basal GILZ and FKBP5 mRNA levels and increased IL-1ß levels. Flattened DEX-induced GILZ and FKBP5 response curves and a flattened salivary cortisol profile characterized T2DM patients. Significant associations of GR measures and saliva cortisol curve parameters with biochemical and clinical characteristics were found. CONCLUSION: Our novel data implicate an insufficient GR signaling in PBMCs in T2DM patients and HPA axis dysfunction. The significant associations of GR-signaling parameters with inflammatory and metabolic indices implicate that GR may be the critical link between HPA axis dysfunction, hypercortisolemia and diabetes-associated metabolic disturbances. Our findings provide significant insights into the contribution of GR-mediated mechanisms in T2DM aetiopathology and therapy.

Effects of 6 vs 3 eucaloric meal patterns on glycaemic control and satiety in people with impaired glucose tolerance or overt type 2 diabetes: A randomized trial.

BACKGROUND/OBJECTIVES: The study aimed to compare the effects of two eucaloric meal patterns (3 vs 6 meals/day) on glycaemic control and satiety in subjects with impaired glucose tolerance and plasma glucose (PG) levels 140-199mg/dL at 120min (IGT-A) or PG levels 140-199mg/dL at 120min and >200mg/dL at 30/60/90min post-oral glucose load on 75-g OGTT (IGT-B), or overt treatment-naïve type 2 diabetes (T2D). SUBJECTS/METHODS: In this randomized crossover study, subjects with IGT-A (n=15, BMI: 32.4±5.2kg/m2), IGT-B (n=20, BMI: 32.5±5kg/m2) or T2D (n=12, BMI: 32.2±5.2kg/m2) followed a weight-maintenance diet (45% carbohydrates, 20% proteins, 35% fats) in 3 or 6 meals/day (each intervention lasting 12 weeks). Anthropometrics, diet compliance and subjective appetite were assessed every 2 weeks. OGTT and measurements of HbA1c and plasma lipids were performed at the beginning and end of each intervention period. RESULTS: Body weight and physical activity levels remained stable throughout the study. In T2D, HbA1c and PG at 120min post-OGTT decreased with 6 vs 3 meals (P<0.001 vs P=0.02, respectively). The 6-meal intervention also improved post-OGTT hyperinsulinaemia in IGT-A subjects and hyperglycaemia in IGT-B subjects. In all three groups, subjective hunger and desire to eat were reduced with 6 vs 3 meals/day (P<0.05). There were no differences in HOMA-IR or plasma lipids between interventions. CONCLUSION: Although weight loss remains the key strategy in hyperglycaemia management, dietary measures such as more frequent and smaller meals may be helpful for those not sufficiently motivated to adhere to calorie-restricted diets. Our study shows that 6 vs 3 meals a day can increase glycaemic control in obese patients with early-stage T2D, and may perhaps improve and/or stabilize postprandial glucose regulation in prediabetes subjects.

A kilonova as the electromagnetic counterpart to a gravitational-wave source.

Gravitational waves were discovered with the detection of binary black-hole mergers and they should also be detectable from lower-mass neutron-star mergers. These are predicted to eject material rich in heavy radioactive isotopes that can power an electromagnetic signal. This signal is luminous at optical and infrared wavelengths and is called a kilonova. The gravitational-wave source GW170817 arose from a binary neutron-star merger in the nearby Universe with a relatively well confined sky position and distance estimate. Here we report observations and physical modelling of a rapidly fading electromagnetic transient in the galaxy NGC 4993, which is spatially coincident with GW170817 and with a weak, short γ-ray burst. The transient has physical parameters that broadly match the theoretical predictions of blue kilonovae from neutron-star mergers. The emitted electromagnetic radiation can be explained with an ejected mass of 0.04 ± 0.01 solar masses, with an opacity of less than 0.5 square centimetres per gram, at a velocity of 0.2 ± 0.1 times light speed. The power source is constrained to have a power-law slope of -1.2 ± 0.3, consistent with radioactive powering from r-process nuclides. (The r-process is a series of neutron capture reactions that synthesise many of the elements heavier than iron.) We identify line features in the spectra that are consistent with light r-process elements (atomic masses of 90-140). As it fades, the transient rapidly becomes red, and a higher-opacity, lanthanide-rich ejecta component may contribute to the emission. This indicates that neutron-star mergers produce gravitational waves and radioactively powered kilonovae, and are a nucleosynthetic source of the r-process elements.

No association of psoriasis with autoimmune thyroiditis.

BACKGROUND: Common autoimmune diseases tend to coexist in the same patients. Few studies have examined the possible association between autoimmune thyroiditis and psoriasis or psoriatic arthritis (PsA), with inconsistent results. OBJECTIVE: To investigate the prevalence of autoimmune thyroiditis in psoriatic patients with or without PsA, living in an iodine-sufficient area. METHODS: We studied prospectively, 114 psoriatic patients with disease duration of 5-38 years, 30 of them with PsA, and 286 age- and body mass index (BMI)-matched subjects without psoriasis or known thyroid disease or autoimmune disease. A detailed medical history was obtained from all participants and clinical examination and laboratory evaluation was performed. Psoriasis severity was assessed with Psoriasis Area and Severity Index (PASI). Autoimmune thyroiditis was defined by the presence of positive autoantibodies to thyroid peroxidase and/or thyroglobulin. RESULTS: There was no difference in the prevalence of autoimmune thyroiditis between psoriatic patients and controls (20.2% vs. 19.6%). The prevalence of autoimmune thyroiditis in male and female psoriatic patients was similar (9.6% and 10.5% respectively), in contrast to the increased, as expected, prevalence in female vs. male controls (14.7% vs. 4.9%, P < 0.01). Detected cases with hypothyroidism due to autoimmune thyroiditis were similar in psoriatic patients and controls (7.9% and 7.0% respectively). Autoimmune thyroiditis in psoriatic patients was not related with age of psoriasis onset, psoriasis duration, PASI score, PsA and obesity. CONCLUSION: These data support that psoriatic patients with or without PsA do not have an increased risk for autoimmune thyroiditis.

Functional dyspepsia susceptibility is related to CD14, GNB3, MIF, and TRPV1 gene polymorphisms in the Greek population.

BACKGROUND: Functional dyspepsia (FD) susceptibility might be influenced by polymorphisms of genes related to inflammation (CD14, macrophage migration inhibitory factor [MIF]), motor (GNB3), and sensory dysfunction (GNB3, TRPV1). We examined the association between CD14 rs2569190, GNB3 rs5443, MIF rs222747, and TRPV1 rs755622 gene polymorphisms with FD (Rome III criteria) in the Greek population. METHODS: We genotyped 174 dyspeptics (115 with epigastric pain syndrome; 41% Helicobacter pylori positive) and 181 controls using polymerase chain reaction-based methods and we measured disease symptoms' burden with a modified Gastrointestinal Symptoms Related Scale. KEY RESULTS: Homozygous for the TT genotype and the T allele of the CD14 gene were significantly associated (OR [95% CI]) with FD (2.65 [1.42-4.94] and 1.67 [1.23-2.26], respectively). The CT, TT genotypes, and T allele frequencies of GNB3 showed also significant association with FD (2.18 [1.35-3.54], 3.46 [1.30-9.23], and 2.18 [1.48-3.19]). While heterozygous GC MIF genotype was more common in dyspeptics (1.67 [1.07-2.60]), homozygous CC genotype and the C allele of TRPV1 gene were more prevalent in controls (0.47 [0.25-0.87] and 0.69 [0.51-0.92], respectively). None of the gene polymorphism was related either to dyspepsia clinical syndrome type or to the H. pylori infection. Among dyspeptics, CD14 TT genotype was related to lower epigastric pain burden score (p<.011); CD14 CT genotype was related to higher epigastric burning and nausea burden scores (p<.04) while belching score was lower (p=.027) in MIF CG dyspeptics. CONCLUSION & INFERENCES: Functional dyspepsia susceptibility is related to CD14, GNB3, MIF, and TRPV1 gene polymorphisms, while CD14 and MIF gene variants are also associated with dyspepsia symptoms burden.

Effect of meal frequency on glucose and insulin levels in women with polycystic ovary syndrome: a randomised trial.

BACKGROUND/OBJECTIVES: The aim of the study was to compare the effect of two-meal patterns (three vs six meals per day) on glucose and insulin levels in women with polycystic ovary syndrome (PCOS). SUBJECTS/METHODS: In a randomised, crossover, 24-week study, 40 women with PCOS, aged 27±6 years, body mass index 27±6 kg/m(2), followed a weight maintenance diet (% carbohydrates:protein:fat, 40:25:35), consumed either as a three- or a six-meal pattern, with each intervention lasting for 12 weeks. Anthropometric measurements, diet compliance and subjective hunger, satiety and desire to eat were assessed biweekly. All women underwent an oral glucose tolerance test (OGTT) with 75 g glucose for measurement of plasma glucose and insulin at the beginning and end of each intervention. HaemoglobinA1c (HbA1c), blood lipids and hepatic enzymes were measured at the beginning and end of each intervention. RESULTS: Body weight remained stable throughout the study. Six meals decreased significantly fasting insulin (P=0.014) and post-OGTT insulin sensitivity (Matsuda index, P=0.039) vs three meals. After incorporation of individual changes over time, with adjustment for potential confounders, the only variable that remained significant was the Matsuda index, which was then used in multivariate analysis and general linear models. Six meals improved post-OGTT insulin sensitivity independently of age and body weight vs three meals (P=0.012). No significant differences were found between six and three meals for glucose, HbA1c, blood lipids, hepatic enzymes, subjective desire to eat and satiety. CONCLUSIONS: Six meals had a more favourable effect on post-OGTT insulin sensitivity in women with PCOS compared with isocaloric three meals.

P673Improvement of arterial stiffness and myocardial deformation in patients with poorly controlled diabetes mellitus type 2 after optimization of antidiabetic medication.

BACKGROUND: Arterial stiffness is associated with increased risk for cardiovascular disease. The purpose of this study is to investigate the arterial stiffness and myocardial deformation in patients with poorly controlled diabetes mellitus type 2 before and after glycemic control by optimal medication. METHODS: In 50 patients with uncontrolled type 2 diabetes(age:52±10years)and 25 controls of similar age and sex and no atherosclerotic risk factors we measured at baseline and 6 months after glycemic control a) carotid-femoral pulse wave velocity(PWVc m/sec-Complior SP ALAM),central systolic blood pressure(cSBP -mmHg),augmentation index(AI%), of the aortic pulse wave(ArteriographTensioMed) b)S',E'(m/sec)andE'/A'of mitral annulus by Tissue Doppler c)LV longitudinal strain(GLS-%),systolic(LongSr-l/sec)and diastolic(LongSrE-l/sec)strain rate, twisting(Tw-deg),peak twisting(Tw)and untwisting(unTw-deg/sec)velocity using speckle tracking echocardiography.The degree of LV untwisting was calculated as the percentage difference between peak twisting and untwisting at MVO(%dp PeakTw-UntwMVO)and between peak twisting and untwisting at peak and end of the mitral inflow E wave d)perfusion boundary region(PBR- micrometers)of the sublingual arterial microvessels(ranged from 5-25 micrometers)using Sideview,Darkfield imaging(Microscan,Glycocheck).Increased PBR is considered an accurate index of reduced endothelial glucocalyx thickness because of a deeper RBC penetration in the glucocalyx e) Flow mediated dilatation(FMD) of the brachial artery and percentage difference of FMD (FMD%). RESULTS: Compared to controls,diabetics had higher PWVa(10.3±2.2 vs. 8.1±1.9), AI(27.9±15 vs. 19.4±14.7), PWVc(11.8±3.2 vs. 8.8±1.3),cSBP(136±20 vs. 119±18),PBR (2.1±0.2 vs 1.89±0.1)and lower GLS(-15±3 vs. -18±3),LongSr(-0.78±0.1 vs. -0.96±0.2),LongSrE(0.77±0.29 vs. 1.2±0.3),S',E' and E/A(p<0.05 for all comparisons). Baseline FMD was related with Untw at peak E%(r=0,65, p<0.05). Six months after the modification of antidiabetic medication all patients achieved glycaemic control and there was a reduction of PWVc(12.3±2.9 vs. 11.3±3.2,p<0.05) in parallel with a increase of Untw velocity (-73±27 vs. -98±43,p<0.05),Untw MVO%(20±9 vs. 30±2),Untw peak E% (40±14 vs. 50±16)and FMD%(7.8±3 vs. 13.6±11,p<0.01).Reduced PWVc was related with reduced SBP(r=0.62),cSBP(r=0.55)and increased LongsrE(r=-0.50), Untw at end E(r=-0.56)respectively(p<0.05 for all associations). CONCLUSION: Glycaemic control after optimizing medical treatment improves arterial stiffness, LV myocardial strain, twisting and untwisting velocity in diabetics.

Severe paraneoplastic hypoglycemia secondary to a gastrointestinal stromal tumour masquerading as a stroke.

UNLABELLED: We report the case of a 70-year-old previously healthy female who presented acutely to the Accident and Emergency department with left-sided vasomotor symptoms including reduced muscle tone, weakness upon walking and slurred speech. Physical examination confirmed hemiparesis with VIIth nerve palsy and profound hepatomegaly. A random glucose was low at 1.7 mmol/l, which upon correction resolved her symptoms. In hindsight, the patient recalled having had similar episodes periodically over the past 3 months to which she did not give much attention. While hospitalized, she continued having episodes of symptomatic hypoglycaemia during most nights, requiring treatment with i.v. dextrose and/or glucagon. Blood tests including insulin and C-peptide were invariably suppressed, in correlation with low glucose. A Synacthen stimulation test was normal (Cort (0') 390 nmol/l, Cort (30') 773 nmol/l). A computed tomography scan showed multiple lobulated masses in the abdomen, liver and pelvis. An ultrasound guided biopsy of one of the pelvic masses was performed. Immunohistochemistry supported the diagnosis of a gastrointestinal stromal tumour (GIST) positive for CD34 and CD117. A diagnosis of a non islet cell tumour hypoglycaemia (NICTH) secondary to an IGF2 secreting GIST was confirmed with further biochemical investigations (IGF2=96.5 nmol/l; IGF2:IGF1 ratio 18.9, ULN <10). Treatment with growth hormone resolved the patient's hypoglycaemic symptoms and subsequent targeted therapy with Imatinib was successful in controlling disease progression over an 8-year observation period. LEARNING POINTS: NICTH can be a rare complication of GISTs that may manifest with severe hypoglycaemia and neuroglucopenic symptoms.NICTH can masquerade as other pathologies thus causing diagnostic confusion.Histological confirmation of GIST induced NICTH and exclusion of other conditions causing hypoglycaemia is essential.Mutational analysis of GISTs should be carried out in all cases as it guides treatment decision.Tailored management of hypoglycaemia, in this case using growth hormone and targeted cyto-reductive therapy, minimizes the risk of possible life-threatening complications.

Increased prevalence of polycystic ovary syndrome in premenopausal women with nonalcoholic fatty liver disease.

OBJECTIVE: Limited data exist concerning the presence of polycystic ovary syndrome (PCOS) in premenopausal women with nonalcoholic fatty liver disease (NAFLD). We aimed to investigate the prevalence of PCOS in overweight and obese premenopausal women with NAFLD. DESIGN: Prospective, observational, and cross-sectional study. METHODS: We studied 110 apparently healthy, overweight, and obese (BMI: 25.1-49.1 kg/m(2)) premenopausal women (age: 18-45 years) reporting no or minimal alcohol consumption for NAFLD with abdominal ultrasonography after excluding causes of secondary liver disease and for PCOS (Rotterdam criteria) with clinical examination, biochemical evaluation, and pelvic ultrasonography. Insulin resistance (IR) was assessed by homeostasis model assessment of IR (HOMA-IR), and free androgen index was calculated. RESULTS: NAFLD was detected in 71/110 women (64.5%). Women with NAFLD compared to women without NAFLD were more commonly diagnosed with PCOS (43.7% vs 23.1%, respectively, P=0.04), metabolic syndrome (30.2% vs 5.3%, respectively, P=0.003), and abnormal lipid profile (81.1% vs 51.3%, P=0.002). All women with abnormal glucose metabolism had NAFLD (P=0.01). Although PCOS was associated with NAFLD (OR 2.6, 95% CI: 1.1-6.2, P=0.04), in a multivariate analysis higher HOMA-IR values (OR 2.2, 95% CI: 1.1-4.4, P=0.02) and triglyceride levels (OR 1.01, 95% CI: 1.00-1.02, P=0.04) independently predicted NAFLD, after adjusting for age, BMI, and waist-to-hip ratio. CONCLUSIONS: These findings indicate an increased prevalence of PCOS in overweight and obese premenopausal women with NAFLD, although it is not supported that the syndrome is primarily involved in NAFLD. Evaluation for PCOS may be considered in these women.

Treatment of Experimental Candida Sepsis with a Janus Kinase Inhibitor Controls Inflammation and Prolongs Survival.

Janus kinases (JAK) are intracellular tyrosine kinases that transduce cytokine-mediated signals to the nucleus, promoting gene expression. Cytokines play a major role in microbial sepsis, which is often associated with uncontrolled inflammation leading to death. JAK inhibitors have been used for the treatment of several autoimmune diseases by modulating immune response, but they have never been tested against microbial sepsis. Ruxolitinib is a small-molecule inhibitor of JAK1/2 proteins, which are involved in the downstream signaling pathway of the vast majority of proinflammatory and anti-inflammatory cytokines. We therefore studied the effect of ruxolitinib in a mouse model of sepsis due to Candida albicans. When ruxolitinib therapy (50 mg/kg [of body weight]/day) was started 1 day before infection, the median survival time was reduced by 3 days, the fungal loads in all organs were higher, the inflammation was significantly less, and serum tumor necrosis factor alpha (TNF-α) and interleukin 10 (IL-10) levels and IL-10/TNF-α ratios were higher than in controls. When ruxolitinib therapy (50 to 1.5 mg/kg/day) was started 1 day after infection, an inverted-U relationship was found, with 6.25 mg/kg/day prolonging median survival time by 6 days, resulting in similar fungal loads, less inflammation, and similar cytokine levels but higher IL-10/TNF-α ratios than the controls. The optimal dose of ruxolitinib controlled infection and prolonged survival with less inflammation than in control animals. Administration of JAK inhibitors may be a promising therapeutic adjunct that needs further investigation.

Homocysteine, cortisol, diabetes mellitus, and psychopathology.

OBJECTIVE: This study investigates the association of homocysteine and cortisol with psychological factors in type 2 diabetic patients. METHOD: Homocysteine, cortisol, and psychological variables were analyzed from 131 diabetic patients. Psychological factors were assessed with the Eysenck Personality Questionnaire (EPQ), Hostility and Direction of Hostility Questionnaire (HDHQ), the Symptom Checklist 90-R (SCL 90-R), the Zung Self-Rating Depression Scale (ZDRS), and the Maudsley O-C Inventory Questionnaire (MOCI). Blood samples were taken by measuring homocysteine and cortisol in both subgroups during the initial phase of the study (T0). One year later (T1), the uncontrolled diabetic patients were reevaluated with the use of the same psychometric instruments and with an identical blood analysis. RESULTS: The relation of psychoticism and homocysteine is positive among controlled diabetic patients (P value = 0.006 < 0.05) and negative among uncontrolled ones (P value = 0.137). Higher values of cortisol correspond to lower scores on extraversion subscale (r(p) = -0.223, P value = 0.010). Controlled diabetic patients showed a statistically significant negative relationship between homocysteine and the act-out hostility subscale (r(sp) = -0.247, P = 0.023). There is a statistically significant relationship between homocysteine and somatization (r(sp) = -0.220, P = 0.043). CONCLUSIONS: These findings support the notion that homocysteine and cortisol are related to trait and state psychological factors in patients with diabetes mellitus type 2.

The role of acetic acid on glucose uptake and blood flow rates in the skeletal muscle in humans with impaired glucose tolerance.

BACKGROUND/OBJECTIVES: Previous studies support the glucose-lowering effect of vinegar. However, the effect of vinegar on muscle glucose metabolism and endothelial function has not been studied in humans. This open, randomized, crossover, placebo-controlled study aims to investigate the effects of vinegar on muscle glucose metabolism, endothelial function and circulating lipid levels in subjects with impaired glucose tolerance (IGT) using the arteriovenous difference technique. SUBJECTS/METHODS: Eight subjects with IGT (4 males, age 46±10 years, body mass index 30±5) were randomised to consume 0.50 mmol vinegar (6% acetic acid) or placebo before a mixed meal. Plasma samples were taken for 300 min from the radial artery and the forearm vein for measurements of glucose, insulin, triglycerides, non-esterified fatty acids (NEFAs) and glycerol. Muscle blood flow was measured with strain gauge plethysmography. Glucose flux was calculated as the arteriovenous difference of glucose multiplied by the blood flow rates. RESULTS: Vinegar compared with placebo: (1) decreased arterial plasma insulin (Poverall<0.001; P75 min=0.014, ß=-42), (2) increased forearm blood flow (Poverall<0.001; P240 min=0.011, ß=1.53; P300 min=0.023, ß=1.37), (3) increased muscle glucose uptake (Poverall<0.001; P60 min=0.029, ß=2.78) and (4) decreased arterial plasma triglycerides (Poverall=0.005; P240 min<0.001, ß=-344; P300 min<0.001, ß=-373), without changing NEFA and glycerol. CONCLUSIONS: In individuals with IGT, vinegar ingestion before a mixed meal results in an enhancement of muscle blood flow, an improvement of glucose uptake by the forearm muscle and a reduction of postprandial hyperinsulinaemia and hypertriglyceridaemia. From this point of view, vinegar may be considered beneficial for improving insulin resistance and metabolic abnormalities in the atherogenic prediabetic state.

Beyond BRCA: new hereditary breast cancer susceptibility genes.

Approximately 5-10% of breast cancer cases might be inheritable, up to 30% of which are due to BRCA1/2 mutations. During the past few years and thanks to technology evolution, we have been witnesses of an intensive search of additional genes with similar characteristics, under the premise that successful gene discovery will provide substantial opportunities for primary and secondary prevention of breast cancer. Consequently, new genes have emerged as breast cancer susceptibility genes, including rare germline mutations in high penetrant genes, such as TP53 and PTEN, and more frequent mutations in moderate penetrant genes, such as CHEK2, ATM and PALB2. This review will summarize current data on new findings in breast cancer susceptibility genes.

The impact of metformin treatment on adiponectin and resistin levels in women with polycystic ovary syndrome: a prospective clinical study.

Women with polycystic ovary syndrome (PCOS) are often characterized by adiposity and insulin resistance (IR). Recent studies in patients with obesity and diabetes mellitus type 2 (DMt2) indicate that adiponectin and resistin may play a role in the pathophysiology of IR. The aim of this study was to identify a possible correlation between the plasma levels of adiponectin and resistin and IR in patients with PCOS. Thirty-one women of reproductive age were enrolled in this prospective study after being diagnosed with PCOS and IR according to Rotterdam and American Diabetes Association (ADA) criteria, respectively. Every patient was treated with a daily dose of 1275 mg metformin for 6 months. Adiponectin, resistin, and the primary hormonal and metabolic parameters of the syndrome were evaluated at entry and endpoint of treatment. Adiponectin plasma levels were reduced after metformin treatment, but resistin levels were not significantly affected. Our study suggests that circulating levels of adiponectin should be evaluated with skepticism in patients with PCOS. The adipokine's role in the manifestation of IR in PCOS remains unclear and needs further investigation.

Adipose tissue lipolysis and circulating lipids in acute and subacute critical illness: effects of shock and treatment.

PURPOSE: The purpose of this study is to assess lipid metabolism at the tissue level in critically ill subjects. MATERIALS AND METHODS: We studied 182 patients with systemic inflammatory response syndrome/severe sepsis or shock during the acute (day 1) and subacute phase of critical illness (day 6). All subjects had a tissue microdialysis (MD) catheter placed in femoral adipose tissue upon admission to the intensive care unit (ICU). Plasma cholesterol, high-density lipoprotein, low-density lipoprotein, free fatty acids (FFAs), triglyceride, and MD glycerol (GLYC) were measured on days 1 and 6 in the ICU. RESULTS: On admission, 56% of the patients had increased levels (>200 µmol/L) of MD GLYC. Patients with shock displayed more pronounced subcutaneous tissue lipolysis and more profound derangements of circulating lipids vs patients without shock (but no appreciable differences in FFA levels). Furthermore, in patients with shock during the acute period, there were positive, albeit weak, correlations of subcutaneous tissue lipolysis (MD GLYC), plasma FFAs (r=0.260; P=.01), and norepinephrine's dose (r=0.230; P=.01), whereas during the subacute phase, MD GLY levels were higher in patients receiving glucocorticoids (344.7±276.0 µmol/L vs 252.2±158.4 µmol/L; P=.03). CONCLUSIONS: Subcutaneous tissue lipolysis is only one of the many determinants of plasma FFAs. Routinely applied therapeutic modalities in the ICU interfere with adipose tissue metabolism.

Hexaminolevulinate-guided transurethral resection of non-muscle-invasive bladder cancer does not reduce the recurrence rates after a 2-year follow-up: a prospective randomized trial.

PURPOSE: To assess the impact of hexaminolevulinate (HAL) on the long-term recurrence rate of NMIBC. METHODS: A total of 130 patients with bladder tumour were randomized into two groups. The patients in one group had a HAL instillation before surgery, and they first had a white-light and after that a blue-light cystoscopy (BL group) and resection. The second group had only white-light cystoscopy (WL group) and resection. They have been followed up with cystoscopy every 3 months for a period of up to 40 months. RESULTS: The recurrence-free period was not significantly different between the two groups (BL and WL groups) (long-rank test p = 0.202). The use of HAL helped detect four flat lesions and 28 papillary lesions with cancer that would have been missed under WL only, on 16 out of the 54 patients (29.6 % CI 95 % 11.1-33.3). The use of HAL changed the proposed postoperative treatment and follow-up for one out of the five patients. CONCLUSIONS: Although the use of HAL cystoscopy identified at least one cancer lesion more than WL cystoscopy on one out of the three patients, the recurrence-free period was not significantly different.