Abstract Serotonin (5-HT) action via the 5-HT2C receptor (5-HT2C R) provides an important modulatory influence over neurons of the prefrontal cortex (PFC), which is critically involved in disorders ...of executive function including substance use disorders. In the present study, we investigated the distribution of the 5-HT2C R in the rat prelimbic prefrontal cortex (PrL), a subregion of the medial prefrontal cortex (mPFC), using a polyclonal antibody raised against the 5-HT2C R. The expression of 5-HT2C R immunoreactivity (IR) was highest in the deep layers (layers V/VI) of the mPFC. The 5-HT2C R-IR was typically most intense at the periphery of cell bodies and the initial segment of cell processes. Approximately 50% of the 5-HT2C R-IR detected was found in glutamate decarboxylase, isoform 67 (GAD 67)-positive neurons. Of the subtypes of GABA interneurons identified by expression of several calcium-binding proteins, a significantly higher percentage of neurons expressing IR for parvalbumin also expressed 5-HT2C R-IR than did the percentage of neurons expressing calbindin-IR or calretinin-IR that also expressed 5-HT2C R-IR. Since parvalbumin is located in basket and chandelier GABA interneurons which project to cell body and initial axon segments of pyramidal cells, respectively, these results raise the possibility that the 5-HT2C R in the mPFC acts via the parvalbumin-positive GABAergic interneurons to regulate the output of pyramidal cells in the rat mPFC.
Serum uric acid (SUA) levels discriminating across the different strata of cardiovascular risk is still unknown. By utilizing a large population-based database, we assessed the threshold of SUA that ...increases the risk of total mortality and cardiovascular mortality (CVM). The URRAH study (Uric Acid Right for Heart Health) is a multicentre retrospective, observational study, which collected data from several large population-based longitudinal studies in Italy and subjects recruited in the hypertension clinics of the Italian Society of Hypertension. Total mortality was defined as mortality for any cause, CVM as death due to fatal myocardial infarction, stroke, sudden cardiac death, or heart failure. A total of 22 714 subjects were included in the analysis. Multivariate Cox regression analyses identified an independent association between SUA and total mortality (hazard ratio, 1.53 95% CI, 1.21–1.93) or CVM (hazard ratio, 2.08 95% CI, 1.146–2.97; P<0.001). Cutoff values of SUA able to discriminate total mortality (4.7 mg/dL 95% CI, 4.3–5.1 mg/dL) and CVM status (5.6 mg/dL 95% CI, 4.99–6.21 mg/dL) were identified. The information on SUA levels provided a significant net reclassification improvement of 0.26 and of 0.27 over the Heart Score risk chart for total mortality and CVM, respectively (P<0.001). Sex-specific cutoff values for total mortality and CVM were also identified and validated. In conclusion, SUA levels increasing the risk of total mortality and CVM are significantly lower than those used for the definition of hyperuricemia in clinical practice. Our data provide evidence of a cardiovascular SUA threshold that might contribute in clinical practice to improve identification of patients at higher risk of CVM.
OBJECTIVE:The Working Group on Uric Acid and Cardiovascular Risk of the Italian Society of Hypertension conceived and designed an ad-hoc study aimed at searching for prognostic cut-off values of ...serum uric acid (SUA) in predicting fatal myocardial infaction (MI) in women and men.
METHODS:The URic acid Right for heArt Health study is a nationwide, multicentre, observational cohort study involving data on individuals aged 18–95 years recruited on a regional community basis from all the territory of Italy under the patronage of the Italian Society of Hypertension with a mean follow-up period of 122.3 ± 66.9 months.
RESULTS:A total of 23 467 individuals were included in the analysis. Cut-off values of SUA able to discriminate MI status were identified by mean of receiver operating characteristic curves in the whole database (>5.70 mg/dl), in women (>5.26 mg/dl) and in men (>5.49 mg/dl). Multivariate Cox regression analyses adjusted for confounders (age, arterial hypertension, diabetes, chronic kidney disease, smoking habit, ethanol intake, BMI, haematocrit, LDL cholesterol and use of diuretics) identified an independent association between SUA and fatal MI in the whole database (hazard ratio 1.381, 95% confidence intervals, 1.096–1.758, P = 0.006) and in women (hazard ratio 1.514, confidence intervals 1.105–2.075, P < 0.01), but not in men.
CONCLUSION:The results of the current study confirm that SUA is an independent risk factor for fatal MI after adjusting for potential confounding variables, and demonstrate that a prognostic cut-off value associated to fatal MI can be identified at least in women.
Purpose
To provide the evidence-based recommendations on the role of testosterone (T) on age-related symptoms and signs remains.
Methods
The Italian Society of Andrology and Sexual Medicine (SIAMS) ...and the and the Italian Society of Endocrinology (SIE) commissioned an expert task force to provide an updated guideline on adult-onset male hypogonadism. Derived recommendations were based on Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system.
Results
Clinical diagnosis of adult-onset hypogonadism should be based on a combination of clinical and biochemical parameters. Testosterone replacement therapy (TRT) should be offered to all symptomatic subjects with hypogonadism after the exclusion of possible contraindications. T gels and the long-acting injectable T are currently available preparations showing the best efficacy/safety profile. TRT can improve all aspects of sexual function, although its effect is limited in more complicated patients. Body composition (reducing fat mass and increasing lean mass) is improved after TRT, either in subjects with or without metabolic syndrome or type 2 diabetes. Conversely, the role of TRT in improving glycometabolic control is more conflicting. TRT can result in increasing bone mineral density, particularly at lumbar site, but no information on fracture risk is available. Limited data support the use of TRT for improving other outcomes, including mood frailty and mobility.
Conclusions
TRT can improve sexual function and body composition particularly in less complicated adult and in aging subjects with hypogonadism. When hypogonadism is adequately diagnosed, T appropriately prescribed and subjects correctly followed up, no short-term increased risk of adverse events is observed. Longer and larger studies are advisable to better clarify TRT long-term efficacy/safety profile.
A high-efficiency wideband code-division multiple-access (W-CDMA) base-station amplifier is presented using high-performance GaN heterostructure field-effect transistors to achieve high gain and ...efficiency with good linearity. For high efficiency, class J/E operation was employed, which can attain up to 80% efficiency over a wide range of input powers and power supply voltages. For nonconstant envelope input, the average efficiency is further increased by employing the envelope-tracking architecture using a wide-bandwidth high-efficiency envelope amplifier. The linearity of overall system is enhanced by digital pre-distortion. The measured average power-added efficiency of the amplifier is as high as 50.7% for a W-CDMA modulated signal with peak-to-average power ratio of 7.67 dB at an average output power of 37.2 W and gain of 10.0 dB. We believe that this corresponds to the best efficiency performance among reported base-station power amplifiers for W-CDMA. The measured error vector magnitude is as low as 1.74% with adjacent channel leakage ratio of -51.0 dBc at an offset frequency of 5 MHz
Klinefelter's syndrome Lanfranco, Fabio; Kamischke, Axel; Zitzmann, Michael ...
The Lancet (British edition),
07/2004, Letnik:
364, Številka:
9430
Journal Article
Recenzirano
Klinefelter's syndrome is the most common genetic cause of human male infertility, but many cases remain undiagnosed because of substantial variation in clinical presentation and insufficient ...professional awareness of the syndrome itself. Early recognition and hormonal treatment of the disorder can substantially improve quality of life and prevent serious consequences. Testosterone replacement corrects symptoms of androgen deficiency but has no positive effect on infertility. However, nowadays patients with Klinefelter's syndrome, including the non-mosaic type, need no longer be considered irrevocably infertile, because intracytoplasmic sperm injection offers an opportunity for procreation even when there are no spermatozoa in the ejaculate. In a substantial number of azoospermic patients, spermatozoa can be extracted from testicular biopsy samples, and pregnancies and livebirths have been achieved. The frequency of sex chromosomal hyperploidy and autosomal aneuploidies is higher in spermatozoa from patients with Klinefelter's syndrome than in those from normal men. Thus, chromosomal errors might in some cases be transmitted to the offspring of men with this syndrome. The genetic implications of the fertilisation procedures, including pretransfer or prenatal genetic assessment, must be explained to patients and their partners.
Important efforts have been made to describe the neural and cognitive features of healthy and clinical populations. However, the neural and cognitive features of socially vulnerable individuals ...remain largely unexplored, despite their proneness to developing neurocognitive disorders. Socially vulnerable individuals can be characterised as socially deprived, having a low socioeconomic status, suffering from chronic social stress, and exhibiting poor social adaptation. While it is known that such individuals are likely to perform worse than their peers on executive function tasks, studies on healthy but socially vulnerable groups are lacking. In the current study, we explore whether neural power and connectivity signatures can characterise executive function performance in healthy but socially vulnerable individuals, shedding light on the impairing effects that chronic stress and social disadvantages have on cognition. We measured resting-state electroencephalography and executive functioning in 38 socially vulnerable participants and 38 matched control participants. Our findings indicate that while neural power was uninformative, lower delta and theta phase synchrony are associated with worse executive function performance in all participants, whereas delta phase synchrony is higher in the socially vulnerable group compared to the control group. Finally, we found that delta phase synchrony and years of schooling are the best predictors for belonging to the socially vulnerable group. Overall, these findings suggest that exposure to chronic stress due to socioeconomic factors and a lack of education are associated with changes in slow-wave neural connectivity and executive functioning.
In the frame of the Uric Acid Right for Heart Health (URRAH) study, a nationwide multicenter study involving adult participants recruited on a regional community basis from all the territory of Italy ...under the patronage of the Working Group on Uric Acid and Cardiovascular Risk of the Italian Society of Hypertension, we searched for the cut-off values of the ratio between serum uric acid (SUA) and serum creatinine (sCr) able to predict cardiovascular (CV) events.
Among 20 724 participants followed-up for 126 ± 64 months, after detecting cut-off by the receiver operating characteristic curves, we calculated by Cox models adjusted for confounders having CV events as dependent variable the hazard ratio (HR) of SUA/sCr > cut-off. We also verified if the role of cut-off varied with increasing SUA/sCr.
A plausible prognostic cut-off of SUA/sCr was found and was the same in the whole database, in men and in women (>5.35). The HR of SUA/sCr > cut-off was 1.159 (95% confidence interval CI 1.092-1.131, P < 0.03) in all, 1.161 (95% CI 1.021-1.335, P < 0.02) in men, and 1.444 (95% CI 1.012-1.113, P < 0.03) in women. In increasing quintiles of SUA/sCr the cut-offs were >3.08, >4.87, >5.35, >6.22 and >7.58, respectively. The HRs significantly increased from the 3rd to the 5th quintile (1.21, 95% CI 1.032-1.467, P = 0.018; 1.294, 95% CI 1.101-1.521, P = 0.002; and 1.642, 95% CI 1.405-1.919, P < 0.0001; respectively), that is, over 5.35, whereas the 2nd quintile was not significantly different from the 1st (reference).
Having SUA/sCr >5.35 is an independent CV risk indicator both in men and women. The cut-off is dynamic and significantly increases with increasing SUA/sCr.
OBJECTIVE:To assess the prognostic cut-off values of serum uric acid (SUA) in predicting fatal and morbid heart failure in a large Italian cohort in the frame of the Working Group on Uric Acid and ...Cardiovascular Risk of the Italian Society of Hypertension.
METHODS:The URic acid Right for heArt Health (URRAH) study is a nationwide, multicentre, cohort study involving data on individuals aged 18–95 years, recruited on a community basis from all regions of Italy under the patronage of the Italian Society of Hypertension with a mean follow-up period of 128 ± 65 months. Incident heart failure was defined on the basis of International Classification of Diseases Tenth Revision codes and double-checked with general practitioners and hospital files. Multivariate Cox regression models having fatal and morbid heart failure as dependent variables, adjusted for sex, age, SBP, diabetes, estimated glomerular filtration rate, smoking habit, ethanol intake, BMI, haematocrit, LDL cholesterol, previous diagnosis of heart failure and use of diuretics as possible confounders, were used to search for an association between SUA as a continuous variable and heart failure. By means of receiver operating characteristic curves, two prognostic cut-off values (one for all heart failure and one for fatal heart failure) were identified as able to discriminate between individuals doomed to develop the event. These cut-off values were used as independent predictors to divide individuals according to prognostic cut-off values in a multivariate Cox models, adjusted for confounders.
RESULTS:A total of 21 386 individuals were included in the analysis. In Cox analyses, SUA as a continuous variable was a significant predictor of all hazard ratio 1.29 (1.23–1.359), P < 0.0001 and fatal hazard ratio 1.268 (1.121–1.35), P < 0.0001 incident heart failure. Cut-off values of SUA able to discriminate all and fatal heart failure status were identified by mean of receiver operating characteristic curves in the whole databaseSUA more than 5.34 mg/dl (confidence interval 4.37–5.6, sensitivity 52.32, specificity 63.96, P < 0.0001) was the univariate prognostic cut-off value for all heart failure, whereas SUA more than 4.89 mg/dl (confidence interval 4.78–5.78, sensitivity 68.29, specificity 49.11, P < 0.0001) for fatal heart failure. The cut-off for all heart failure and the cut-off value for fatal heart failure were accepted as independent predictors in the Cox analysis models, the hazard ratios being 1.645 (1.284–2.109, P < 0.0001) for all heart failure and 1.645 (1.284–2.109, P < 0.0001) for fatal heart failure, respectively.
CONCLUSION:The results of the current study confirm that SUA is an independent risk factor for all heart failure and fatal heart failure, after adjusting for potential confounding variables and demonstrate that a prognostic cut-off value can be identified for all heart failure (>5.34 mg/dl) and for fatal heart failure (>4.89 mg/dl).
The Working Group on Uric Acid and Cardiovascular Risk of the Italian Society of Hypertension conceived and designed an ad hoc study aimed at searching for prognostic cut-off values of serum uric ...acid (SUA) in predicting combined (fatal and non-fatal) cerebrovascular (CBV) events in the whole database. The URic acid Right for heArt Health study is a nationwide, multicenter, observational cohort study involving data on subjects aged 18-95 years recruited on a regional community basis from all the territory of Italy under the patronage of the Italian Society of Hypertension with a mean follow-up period of 120.7 ± 61.8 months. A total of 14,588 subjects were included in the analysis. A prognostic cut-off value of SUA able to discriminate combined CBV events (>4.79 mg/dL or >284.91 µmol/L) was identified by means of receiver operating characteristic curve in the whole database. Multivariate Cox regression analysis adjusted for confounders (age, sex, arterial hypertension, diabetes, chronic kidney disease, smoking habit, ethanol intake, body mass index, low-density lipoprotein cholesterol, and use of diuretics) identified an independent association between SUA and combined CBV events in the whole database (HR 1.249, 95% confidence interval, 1.041-1.497, p = 0.016). The results of the present study confirm that SUA is an independent risk marker for CBV events after adjusting for potential confounding variables, including arterial hypertension, and demonstrate that >4.79 mg/dL is a valid prognostic cut-off value.
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