Echoes of shame: a comparison of the characteristics and psychological sequelae of recalled shame experiences across the voice hearing continuum.

BACKGROUND: Voice hearing occurs across a number of psychiatric diagnoses and appears to be present on a continuum within the general population. Previous research has highlighted the potential role of past experiences of shame in proneness to voice hearing in the general population. AIMS: This study aimed to extend this past research and compare people with distressing voices, people with voices but no distress, and a non-voice hearing control group, on various dimensions of shame and shame memory characteristics. METHOD: In a cross-sectional, online study 39 distressed voice hearers, 31 non-distressed voice hearers and 50 non-voice hearers undertook a shame memory priming task in which they were prompted to recall a memory of a shaming experience from their past. They then completed questionnaires assessing the characteristics of the recalled shame event and the psychological sequalae of this event (i.e. intrusions, hyperarousal, avoidance, the centrality of shame memories, external shame, and self-criticism). RESULTS: The majority of recalled shame memories involved experiences such as interpersonal criticism or experiences of being devalued. Univariate analyses found no significant differences between the three groups with regard to the shame events that were recalled, but the distressed voice hearer group reported significantly more hyperarousal, intrusions, self-criticism, and external shame in relation to their experience. CONCLUSIONS: The findings suggest that voice hearers recall similar types of shame experiences to non-voice hearers, but that problematic psychological sequelae of these shame experiences (in the form of intrusive memories, hyperarousal, external shame, and self-criticism) may specifically contribute to distressing voice hearing.

Alternative academic approaches for testing homologous recombination deficiency in ovarian cancer in the MITO16A/MaNGO-OV2 trial.

BACKGROUND: The detection of homologous recombination deficiency (HRD) can identify patients who are more responsive to platinum and poly ADP ribose polymerase inhibitors (PARPi). MyChoice CDx (Myriad) is the most used HRD test in ovarian cancer (OC). However, some limitations of commercial tests exist, because of the high rate of inconclusive results, costs, and the impossibility of evaluating functional resistance mechanisms. PATIENTS AND METHODS: Two academic genomic tests and a functional assay, the RAD51 foci, were evaluated to detect HRD. One hundred patients with high-grade OC enrolled in the MITO16A/MaNGO-OV2 trial and treated with first-line therapy with carboplatin, paclitaxel, and bevacizumab were analyzed. RESULTS: The failure rate of the two genomic assays was 2%. The sensitivity in detecting HRD when compared with Myriad was 98.1% and 90.6%, respectively. The agreement rate with Myriad was 0.92 and 0.87, with a Cohen's κ coefficient corresponding to 0.84 and 0.74, respectively. For the RAD51 foci assay, the failure rate was 30%. When the test was successful, discordant results for deficient and proficient tumors were observed, and additional HRD patients were identified compared to Myriad; sensitivity was 82.9%, agreement rate was 0.65, and Cohen's κ coefficient was 0.18. The HRD detected by genomic assays and residual tumor at primary surgery and stage was correlated with progression-free survival at multivariate analysis. CONCLUSIONS: Results suggest the feasibility of academic tests for assessing HRD status that show robust concordance with Myriad and correlation with clinical outcome. The contribution of the functional information related to the RAD51 foci test to the genomic data needs further investigation.

Association between follicular fluid leptin and serum insulin levels in nonoverweight women with polycystic ovary syndrome.

AIMS: We evaluated the links between leptin and visfatin levels and fertilization rates in nonoverweight (NOW) women with PCOS (NOW-PCOS) from Apulia undergoing in vitro fertilization/embryo transfer (IVF). MATERIALS AND METHODOLOGY: We recruited 16 NOW women with PCOS (NOW-PCOS) and 10 normally ovulating NOW women (control-NOW). All women underwent IVF. Androgens, 17- ß -estradiol (17 ß -E2), and insulin levels were measured in plasma and/or serum and leptin and visfatin levels were assayed in both serum and follicular fluid (FF-leptin, FF-visfatin). RESULTS: In NOW-PCOS, both serum and FF-leptin were significantly lower than in control-NOW. In NOW-PCOS, significant correlations were found between BMI and serum leptin and insulinemia and FF-leptin. By contrast, in control-NOW, FF-leptin levels were not correlated with insulinemia. Serum visfatin levels were not significantly different in NOW-PCOS and control-NOW, but FF-visfatin levels were 1.6-fold higher, although not significantly, in NOW-PCOS than in control-NOW. CONCLUSIONS: Both serum leptin levels and FF-leptin are BMI- and insulin-related in Southern Italian NOW-PCOS from Apulia. In line with other reports showing that FF-leptin levels are predictive of fertilization rates, lower than normal FF-leptin levels in NOW-PCOS may explain their lower fertilization rate and this may be related to the level of insulin and/or insulin resistance.

Characterization and predicted role of the microRNA expression profile in amnion from obese pregnant women.

Maternal obesity and nutrient excess in utero increase the risk of future metabolic diseases. The mechanisms underlying this process are poorly understood, but probably include genetic, epigenetic alterations and changes in fetal nutrient supply. We have studied the microRNA (miRNA) expression profile in amnion from obese and control women at delivery to investigate if a specific miRNA signature is associated with obesity. The expression profile of 365 human miRNAs was evaluated with the TaqMan Array in amnion from 10 obese and 5 control (prepregnancy body mass index (BMI) >30 and <25 kg m(-2), respectively) women at delivery. Target genes and miRNA-regulated pathways were predicted by bioinformatics. Anthropometric and biochemical parameters were also measured in mothers and newborns. Seven miRNAs were expressed only in obese women (miR-422b, miR-219, miR-575, miR-523, miR-579, miR-618 and miR-659), whereas 13 miRNAs were expressed at a higher level and 12 miRNAs at a lower level in obese women than in controls. MicroRNAs significantly downregulated the neurotrophin, cancer/ErbB, mammalian target of rapamycin, insulin, adipocytokine, actin cytoskeleton and mitogen-activated protein kinase signaling pathways. In conclusion, we show that the miRNA profile is altered in amnion during obesity and hypothesize that this could affect pathways important for placental growth and function, thereby contributing to an increase in the newborn's risk of future metabolic diseases.

UCP1 -3826 AG+GG genotypes, adiponectin, and leptin/adiponectin ratio in severe obesity.

BACKGROUND AND AIMS: Non-alcoholic fatty liver disease (NAFLD) and metabolic syndrome (MS) are well-recognized complications of obesity. This study was designed to evaluate the role of the UCP1 -3826 A>G polymorphism, adiponectin levels, leptin/adiponectin ratio (L/A), and main biochemical parameters in 102 unrelated severely obese adults [61 females and 41 males, median body mass index (BMI) = 47.8 kg/m2] with NAFLD, with (MS+) or without MS (MS-) from Southern Italy. SUBJECT AND METHODS: The UCP1 polymorphism was tested by the TaqMan method, main biochemical parameters by routinary methods, adiponectin, and leptin serum levels by enzyme-linked immunosorbent assay. MS was diagnosed according to the American Heart Association criteria, liver steatosis was detected by ultrasound. RESULTS: MS was present in 53% male and 66% female obese patients. Only total cholesterol (p=0.04 males and p=0.002 females) and L/A ratio (p=0.03 males) differed between MS+ and MS- obese patients. At multivariate analysis, severe liver steatosis was significantly associated with: UCP1 (AG+GG) genotypes [odds ratio-confidence interval (OR-CI): 4.25; 1.12-16.13], MS (OR-CI: 8.47; 1.78-40.25), low adiponectin levels (OR-CI: 0.92; 0.87-0.98), high alanine aminotransferase levels (OR-CI: 1.03; 1.00-1.06), age (ORCI: 1.08; 1.00-1.15), and male gender (OR-CI: 10.78; 1.61- 71.96). CONCLUSION: In addition to traditional factors, total cholesterol and L/A ratio appear to contribute to MS characterization in severe obesity. Furthermore, the UCP1 (AG+GG) genotypes and low adiponectin levels could predispose to a more severe liver steatosis independently of MS presence. Based on our data, polymorphic UCP1 (AG+GG) obese patients with low adiponectin levels appear to be high-risk subjects for worsening of liver steatosis, a NAFLD, possibly requiring a second-step evaluation by liver biopsy.

Molecular analysis of the adiponectin gene in severely obese patients from southern Italy.

BACKGROUND: Severe obesity is a major worldwide public health concern affecting 0.5-5% of the adult population. Adiponectin (Acpr30), an adipokine secreted from adipocytes, shows pleiotropic beneficial effects on obesity and related disorders. In this study, sequence analysis of Acpr30 gene (ACDC) was performed in a highly selected population of severely obese young adult patients from Southern Italy to investigate the associations between polymorphisms in the ACDC gene and the development of severe obesity concomitantly with other features of the metabolic syndrome. METHODS: The ACDC gene was analyzed by direct sequencing in the severely obese patients (n=220) and compared to healthy controls (n=116). The associations between the ACDC gene single-nucleotide polymorphisms (SNPs) and the levels of serum Acpr30 as well as the correlation with the presence of severe obesity jointly associated with other features of the metabolic syndrome were also investigated. Total serum Acpr30 concentrations were measured by the ELISA method. RESULTS: ACDC gene molecular screening revealed the presence of previously described SNPs and a new nucleotide alteration, c.355T>G, leading to a protein variant, p.L119V. Measurement of serum concentration of Acpr30 demonstrated lower levels of Acpr30 in the obese population compared to controls (30.5+/-28.3 vs. 43.9+/-35.7 microg/ml, p<0.01); in particular, significantly lower Acpr30 concentrations were observed in obese patients bearing c.-11377C>G SNP CG+GG genotypes than in those with CC genotype (22.9+/-20.5 vs. 33.1+/-29.4 microg/ml, p<0.05). CONCLUSIONS: Our results confirmed that low serum levels of Acpr30 are related to severe obesity and a difference in protein expression is associated with variants in ACDC gene promoter region.

Perinatal risk factors and mode of delivery correlated to survival and psychomotor disability in extremely low birth weight infants.

BACKGROUND/AIMS: Extreme preterm birth, <28 weeks of gestation, represents a public health concern with major economic implications, being the leading cause of neonatal mortality and morbidity. METHODS: A single-centre retrospective cohort study was carried out to assess the role of caesarean section and to identify perinatal factors affecting neonatal survival and psychomotor development in these infants. 57 cases with complete maternal, obstetrical and neonatological information were selected for this study and neurological development was assessed for at least 18 months of life. RESULTS: Infant survival and neurological morbidity rates were directly and inversely correlated to birth weights and gestational age at birth, respectively. In multivariate analysis only extreme prematurity (

Estimation of fetal weight by measurement of fetal thigh soft-tissue thickness in the late third trimester.

OBJECTIVE: The accuracy of current formulae for the sonographic estimation of fetal weight (EFW) is compromised by significant intra- and interobserver variability of biometrical measurements, particularly circumferences. The aim of this study was to assess the reliability of the linear measurement of mid-thigh soft-tissue thickness (STT) and to derive a novel formula for EFW. METHODS: This was a prospective study involving 388 singleton uncomplicated pregnancies. There were three consecutive phases: (1) to verify the relationship between STT and birth weight, (2) to derive a novel formula for EFW using femur length and STT only, and (3) to test the accuracy of the new equation. Only the 290 patients who delivered within 48 h of measurement were considered for the analysis. A comparison with other formulae was performed. RESULTS: STT was significantly correlated with both abdominal circumference and birth weight (r(2) = 0.36 and 0.46, respectively; P < 0.001). Both intra- and interobserver variability were satisfactory (0.44 +/- 0.27 and 0.57 +/- 0.35 mm, respectively). The equation for EFW was developed using multiple stepwise regression analysis (EFW = - 1687.47 + (54.1 x femur length) + (76.68 x STT)) and tested prospectively on 69 patients. The new formula yielded results (r = 0.79) that were slightly better in accuracy than two other published equations, and had an absolute mean error of < 15% in 97% of cases. CONCLUSIONS: Our findings confirm the potential of the linear measurement of mid-thigh STT as a valuable parameter for the sonographic assessment of fetal growth and EFW. Our new equation is apparently at least as reliable as the most widely used formulae for EFW.

Metabolic syndrome and ADRB3 gene polymorphism in severely obese patients from South Italy.

OBJECTIVE: To evaluate the prevalence of beta(3)-adrenergic receptor (ADRB3) Trp64Arg polymorphism and its relationship with the metabolic syndrome in severe obesity. DESIGN: Cross-sectional outpatients study. PATIENTS AND METHODS: In 265 (100 men) severely obese non-diabetic subjects and 78 (25 men) healthy volunteers, genomic DNA was isolated from peripheral leukocytes. In obese patients, plasma concentrations of leptin, lipids, glucose and insulin, the homeostasis model assessment index and blood pressure have been measured. The Trp64Arg mutation was identified with the real-time TaqMan method. RESULTS: Neither genotype distribution nor allele frequency differed between the two groups. The metabolic syndrome prevalence was 59% in obese subjects, and was higher in men than in women (65 vs 55%: P=0.03). The body mass index (BMI) was related to age tertiles (beta=0.08; P<0.001; multiple linear regression) in Trp64Arg-positive obese subjects. CONCLUSION: We confirm the high prevalence of the metabolic syndrome among severely obese subjects. ADRB3 polymorphism was significantly related to insulin resistance only in obese male subjects. Moreover, increased BMI was related to age in obese subjects with the ADRB3 polymorphism.

Neoadjuvant chemotherapy in cervical cancer: a 67 patients experience.

The purpose of this study was to evaluate the efficacy and toxicity of neoadjuvant chemotherapy in patients with locally advanced cervical cancer. Between 1992 and 2003, all consecutive women with locally advanced cervical cancer receiving neoadjuvant chemotherapy were identified. Sixty-seven patients received neoadjuvant chemotherapy: 34 had stage I disease, 28 had stage II disease, and 5 had stage III disease. Clinical response to neoadjuvant chemotherapy occurred in 61 patients, including six with complete and 55 with partial response; five women showed stable disease and one progressed. After neoadjuvant chemotherapy, 58 women underwent surgery, whereas the remaining nine received radiation. Hematologic toxicity was seen in 14 patients, with most of them consisting in severe anemia. The 5-year survival rate and median survival were 63% and 93 months. In univariate analysis, response to neoadjuvant chemotherapy, treatment after neoadjuvant chemotherapy, cervical stromal invasion >50%, and lymph node involvement were important prognostic factor responsible for survival. Neoadjuvant chemotherapy followed by surgery seems to be tolerated and active in the treatment of locally advanced cervical cancer and might be an alternative choice of therapy to chemoradiation. A prospective randomized trial with a larger number of cases is needed.

Remodeling of mouse milk glycoconjugates by transgenic expression of a human glycosyltransferase.

The mammary gland is a unique biosynthetic tissue that produces a variety of species-specific glycoconjugates, but the factors regulating the production of specific glycoconjugates are not well understood. To explore the underlying regulation, a fusion gene containing a cDNA encoding the human alpha 1,2-fucosyltransferase (alpha 1,2FT), which generates the H-blood group antigen, flanked by the murine whey acidic protein promoter and a polyadenylation signal, was introduced into mice. Milk samples from transgenic animals contained soluble forms of the alpha 1,2FT, as revealed by Western blots of milk samples using an anti-alpha 1,2FT antiserum and by the demonstration of alpha 1,2FT enzyme activity. Milk from transgenic animals also contained large quantities of 2'-fucosyllactose (Fuc alpha 1-2Gal beta 1-4Glc) and modified glycoproteins containing the H-antigen, whereas milk from control animals lacked these glycoconjugates. Expression levels of 2'-fucosyllactose were high in most animals and represented 1/3 to nearly 1/2 of the total milk oligosaccharides. These results demonstrate that heterologous transgenic expression of a glycosyltransferase can result in the expression of both the transgene and its secondary gene products and that the structures of milk oligosaccharides can be remodeled depending on expression of the appropriate enzyme. Furthermore, these results suggest that the lactating mammary gland may be a unique biosynthetic reactor for the production of biologically active oligosaccharides and glycoconjugates.

Determination of copper in infant formula by graphite furnace atomic absorption spectroscopy with a L'vov platform.

A rapid method for the determination of sub-part-per-million levels of copper in infant formula, which does not require decomposition of the sample matrix before analysis, has been developed. The method uses L'vov platform graphite furnace atomic absorption spectroscopy (GFAAS), a technique that greatly reduces matrix interferences limiting the applicability of normal GFAAS. The sample preparation consists of dilution of a weighed sample of infant formula to a known volume with a 0.5% solution of Triton X-100 in deionized water. The accuracy of the method, as assessed from the results of overspike recovery studies (96.5-101.3% recovery) for different matrix types and comparison to results generated with alternative methodologies, can be considered excellent. The overall precision of the method ranges from 2.5 to 4.3% RSD for different matrix types.