Structural connectivity associated with familial risk for mental illness: A meta-analysis of diffusion tensor imaging studies in relatives of patients with severe mental disorders.

Schizophrenia (SCZ), bipolar disorder (BD), and major depressive disorder (MDD) are heritable conditions with overlapping genetic liability. Transdiagnostic and disorder-specific brain changes associated with familial risk for developing these disorders remain poorly understood. We carried out a meta-analysis of diffusion tensor imaging (DTI) studies to investigate white matter microstructure abnormalities in relatives that might correspond to shared and discrete biomarkers of familial risk for psychotic or mood disorders. A systematic search of PubMed and Embase was performed to identify DTI studies in relatives of SCZ, BD, and MDD patients. Seed-based d Mapping software was used to investigate global differences in fractional anisotropy (FA) between overall and disorder-specific relatives and healthy controls (HC). Our search identified 25 studies that met full inclusion criteria. A total of 1,144 relatives and 1,238 HC were included in the meta-analysis. The overall relatives exhibited decreased FA in the genu and splenium of corpus callosum (CC) compared with HC. This finding was found highly replicable in jack-knife analysis and subgroup analyses. In disorder-specific analysis, compared to HC, relatives of SCZ patients exhibited the same changes while those of BD showed reduced FA in the left inferior longitudinal fasciculus (ILF). The present study showed decreased FA in the genu and splenium of CC in relatives of SCZ, BD, and MDD patients, which might represent a shared familial vulnerability marker of severe mental illness. The white matter abnormalities in the left ILF might represent a specific familial risk for bipolar disorder.

N-acetylcysteine as an adjunctive treatment for bipolar depression: A systematic review and meta-analysis of randomized controlled trials.

OBJECTIVES: Previous studies and meta-analyses suggested that N-acetylcysteine (NAC) was superior to placebo in improving depression in bipolar disorder. However, more recent data, including two larger trials, found that NAC was no more effective than placebo. We conducted a meta-analysis to appraise the possible efficacy of NAC in treating bipolar depression. METHODS: A systematic review and meta-analysis of double-blind, placebo-controlled trials of NAC as a treatment augmentation strategy for bipolar depression was carried out in PubMed (1966-2020). We utilized random-effect analysis to evaluate improvement in depressive symptoms from baseline to endpoint as the primary efficacy measure. RESULTS: Six trials including 248 patients were included. Treatment augmentation with NAC showed a moderate effect size favoring NAC over placebo (d = 0.45, 95% C.I.: 0.06-0.84). There was substantial heterogeneity (I2  = 49%). Meta-regression analyses did not identify any moderator that might explain variation in heterogeneity, including baseline depressive symptom scores, mean NAC dose, or duration of study. CONCLUSIONS: Results from six clinical trials suggest that treatment augmentation with NAC for bipolar depression appears to be superior to placebo, with a moderate effect size, but a large confidence interval. Larger clinical trials, investigating possible moderating factors, such as NAC dose, treatment duration, baseline depression severity, or chronicity of illness, are warranted.

Individual prediction of symptomatic converters in youth offspring of bipolar parents using proton magnetic resonance spectroscopy.

Children of individuals with bipolar disorder (bipolar offspring) are at increased risk for developing mood disorders, but strategies to predict mood episodes are unavailable. In this study, we used support vector machine (SVM) to characterize the potential of proton magnetic resonance spectroscopy (1H-MRS) in predicting the first mood episode in youth bipolar offspring. From a longitudinal neuroimaging study, 19 at-risk youth who developed their first mood episode (converters), and 19 without mood episodes during follow-up (non-converters) were selected and matched for age, sex and follow-up time. Baseline 1H-MRS data were obtained from anterior cingulate cortex (ACC) and bilateral ventrolateral prefrontal cortex (VLPFC). Glutamate (Glu), myo-inositol (mI), choline (Cho), N-acetyl aspartate (NAA), and phosphocreatine plus creatine (PCr + Cr) levels were calculated. SVM with a linear kernel was adopted to classify converters and non-converters based on their baseline metabolites. SVM allowed the significant classification of converters and non-converters across all regions for Cho (accuracy = 76.0%), but not for other metabolites. Considering all metabolites within each region, SVM allowed the significant classification of converters and non-converters for left VLPFC (accuracy = 76.5%), but not for right VLPFC or ACC. The combined mI, PCr + Cr, and Cho from left VLPFC achieved the highest accuracy differentiating converters from non-converters (79.0%). Our findings from this exploratory study suggested that 1H-MRS levels of mI, Cho, and PCr + Cr from left VLPFC might be useful to predict the development of first mood episode in youth bipolar offspring using machine learning. Future studies that prospectively examine and validate these metabolites as predictors of mood episodes in high-risk individuals are necessary.

Vinegar from Anacardium othonianum Rizzini using submerged fermentation.

BACKGROUND: Anacardium othonianum Rizzini is a native Cerrado fruit, recently described in the literature. Its use is restricted to its native region and there is a lack of studies regarding production of vinegar from the pulp. This work aims to investigate the production of A. othonianum Rizzini vinegar using submerged fermentation. RESULTS: The density, alcohol content, proximal composition, pH, color coordinates, and chromatographic profile of the volatile compounds were analyzed in the slurry, fermented juice, and vinegar produced from the corpulent parts of A. othonianum Rizz. Sensory acceptance and willingness to pay were also assessed with vinegar at 4% and 6% of total acidity. The results indicated compliance with European legislation and the presence of volatile compounds such as carbon dioxide, acetic acid, ethanol, and acetaldehyde in the analyzed vinegars. Our results indicate the potential of vinegar production from A. othonianum, with 74% and 86% willingness to pay. CONCLUSIONS: The process of transformation of the fruit pulp into new products can contribute to fruit valorization and consequent preservation of the plant in the Cerrado biome. To the best of our knowledge, this is the first report of volatile compounds and minerals in A. othonianum Rizz. slurry. Our observations can be used as a basis for future studies regarding the preparation of vinegars from this species and for investigating their application in cooking and guiding consumer perception. © 2020 Society of Chemical Industry.

Molecular characterization of different preproGnRHs in Astyanax altiparanae (Characiformes): Effects of GnRH on female reproduction.

Gonadotropin-releasing hormone (GnRH) is a key molecule in the initiation of the hypothalamic-pituitary-gonadal axis. Thus, knowledge about GnRH may contribute to the effectiveness of species reproduction. Using a Neotropical tetra Astyanax altiparanae as a fish model species, the GnRH forms were characterized at the molecular level and the role of injected GnRHs in vivo was evaluated. The full-length complementary DNA (cDNA) sequences of preproGnRH2 (612 bp) and preproGnRH3 (407 bp) of A. altiparanae were obtained, and the GnRH1 form was not detected. The cDNA sequences of preproGnRH2 and preproGnRH3 were found to be conserved, but a change in the amino acid at position 8 of the GnRH3 decapeptide of A. altiparanae was observed. All the injected GnRHs stimulated lhß messenger RNA (mRNA) expression but not fshß mRNA expression, and only GnRH2 was able to increase maturation-inducing steroid (MIS) levels and possibly stimulate oocyte release. Furthermore, only GnRH2 was able to start the entire reproductive hormonal cascade and induce spawning.

Improving water use efficiency by changing hydraulic and stomatal characteristics in soybean exposed to drought: the involvement of nitric oxide.

A variety of cellular responses is needed to ensure the plants survival during drought, but little is known about the signaling mechanisms involved in this process. Soybean cultivars (EMBRAPA 48 and BR 16, tolerant and sensitive to drought, respectively) were exposed to the following treatments: control conditions (plants in field capacity), drought (20% of available water in the soil), sodium nitroprusside (SNP) treatment (plants irrigated and treated with 100-µM SNP [SNP-nitric oxide (NO) donor molecule], and Drought + SNP (plants subjected to drought and SNP treatment). Plants remained in these conditions until the reproductive stage and were evaluated for physiological (photosynthetic pigments, chlorophyll a fluorescence and gas exchange rates), hydraulic (water potential, osmotic potential and leaf hydraulic conductivity) and morpho-anatomical traits (biomass, venation density and stomatal characterization). Exposure to water deficit considerably reduced water potential in both cultivars and resulted in decrease in photosynthesis and biomass accumulation. The addition of the NO donor attenuated these damaging effects of water deficit and increased the tolerance index of both cultivars. The results showed that NO was able to reduce plant's water loss, while maintaining their biomass production through alteration in stomatal characteristics, hydraulic conductivity and the biomass distribution pattern. These hydraulic and morpho-anatomical alterations allowed the plants to obtain, transport and lose less water to the atmosphere, even in water deficit conditions.

A Novel Method Using Confocal Laser Scanning Microscopy for Three-Dimensional Analysis of Human Dental Enamel Subjected to Ceramic Bracket Debonding.

The aim of this in vitro study was to present a method using confocal laser scanning microscopy for three-dimensional analysis of human dental enamel subjected to ceramic bracket debonding. The labial enamel surfaces of three upper central incisors were prepared and mounted in the form of standardized specimens. A sample repositioning protocol was established to enable surface measurement and analysis before and after bracket debonding. Observations were made of representative areas measuring 1,280 × 1,280 µm2, in the center of the enamel samples, as well as of the total topography (2,500 × 3,500 µm) of the bonding areas provided by the equipment software. Noncontact three-dimensional high-resolution image analyses revealed the capabilities of the employed technique and methodology to permit the examination of specific characteristics and alterations on the surfaces, before and after the debonding and finishing procedures. The new protocol was effective to provide qualitative and quantitative assessments of changes on the same dental surfaces at different trial times. The methodology constitutes a feasible tool for revealing the effects of debonding of ceramic brackets on sound and previously injured dental enamel surfaces.

Longitudinal proton spectroscopy study of the prefrontal cortex in youth at risk for bipolar disorder before and after their first mood episode.

OBJECTIVES: To investigate neurochemical abnormalities in the left and right ventrolateral prefrontal cortex (VLPFC) and anterior cingulate cortex (ACC) of youth at risk for bipolar disorder using proton magnetic resonance spectroscopy before and after their first mood episode. METHODS: Children and adolescents offspring of parents with bipolar I disorder (at-risk group, n = 117) and matched healthy controls (HC group, n = 61) were recruited at the University of Cincinnati. At-risk subjects had no lifetime major mood and psychotic disorders at baseline, and were followed up every 4 months to monitor for development of a major depressive, manic, hypomanic, or mixed mood episode. Levels of N-acetyl-aspartate (NAA), phosphocreatine plus creatine (PCr + Cr), choline-containing compounds, myo-inositol, and glutamate were determined using LCModel and corrected for partial volume effects. RESULTS: There were no baseline differences in metabolite levels for any of the brain regions between at-risk and HC youth. Nineteen at-risk subjects developed a first mood episode during follow-up. Survival analyses showed that baseline PCr + Cr levels in the left VLPFC significantly predicted a mood episode during follow-up in the at-risk group (HR: 0.47, 95% CI: 0.27-0.82, P = 0.008). There were no longitudinal changes in metabolites levels in the VLPFC and ACC before and after a mood episode in at-risk subjects. CONCLUSIONS: We found no evidence for abnormal proton spectroscopy metabolite levels in the VLPFC and ACC of at-risk youth, prior and after the development of their first mood episode. Preliminary findings of association between baseline PCr + Cr levels in the left VLPFC and risk to develop a mood episode warrant further investigation.

Physicochemical characterization of 'Cerrado' cashew (Anacardium othonianum Rizzini) fruits and pseudofruits.

BACKGROUND: The Cerrado occupies 23% of Brazil. A. othonianum is a native Cerrado species that presents differently colored pseudofruits. This report describes the morphometric properties, physicochemical characterization, and phenolic and flavonoid compound compositions of 30 accessions of A. othonianum. RESULTS: The morphometric properties show that an average fruit had 21.97 mm length, 18.61 mm width, and 11.13 mm thickness, with 2.52 g mass. The pseudofruits had 28.84 mm apex width with 12.83 g of mass. The hue parameters of the pseudofruits were 18.67 ± 2.00 and 83.32 ± 1.97° (P < 0.05), reflecting their red to yellow color. The titratable acidity of the accessions was 0.91 ± 0.09 to 3.02 ± 0.02% (P < 0.05), soluble solid content was 9.60 ± 0.17 to 13.47 ± 0.38 °Brix (P < 0.05), and pH ranged from 2.83 ± 0.06 to 3.83 ± 0.06 (P < 0.05). Fourteen flavonoid compounds were identified. The most common compounds in the accessions were vitexin (93% of the accessions), hesperidin (57% of the accessions), epicatechin (34% of the accessions), and kaempferol-3-O-glucoside (30% of the accessions). Cluster analysis generated four groups with the traits ΔE, °h, C, soluble solid content, titratable acidity, pH, total flavonoids, and their identified compounds. CONCLUSIONS: Although all accessions are A. othonianum, there the chemical composition and the physical characteristics of these fruits vary. This is the first report in the literature using wild accessions. Greater disclosure of the species characteristic is interesting because it can increase income for the local population. © 2019 Society of Chemical Industry.

Squamous carcinoma in pilonidalis sinus: case report and review of literature.

AIM: We report a case of squamous carcinoma arising from a pilonidal sinus. CASE REPORT: Patient of 83 years old, that after 30 years had a recurrence of pilonidal sinus revealed by a sacral abscess studied with pelvic CT scan and MRI. After clinical investigation, traditional open surgical technique was performed and pathologic studies revealed a squamous carcinoma. The patient performed a new CT scan with persistence of disease, and a second surgical look with mass excision until the presacral fascia and V-Y flap was performed. Histological exami-nation was found to be positive for squamous carcinoma on the margin and the patient underwent adjuvant radiotherapy cycles with a close follow-up with evidence of free disease survival. He died after 5 years for old age. DISCUSSION: The incidence of carcinoma arising from a pilonidalis sinus is about 0.1% and the most important risk factor is represented by a chronic abscess from 20-30 years. In literature there are about 100 cases. Gold standard treatment is surgery with complete excision of the presacral fascia, while radiotherapy decrease the risk of recurrence. CONCLUSION: All cases reported in literature are submitted as case report. Sacro-coccyxal fistula should be treated early because chronic inflammation can determine neoplastic degeneration. Histological examination should be performed routinely. Gold standard is surgery with wide excision. There is no evidence about the gold standard for the reconstructive time.

The International Society for Bipolar Disorders Task Force report on pediatric bipolar disorder: Knowledge to date and directions for future research.

OBJECTIVES: Over the past two decades, there has been tremendous growth in research regarding bipolar disorder (BD) among children and adolescents (ie, pediatric BD [PBD]). The primary purpose of this article is to distill the extant literature, dispel myths or exaggerated assertions in the field, and disseminate clinically relevant findings. METHODS: An international group of experts completed a selective review of the literature, emphasizing areas of consensus, identifying limitations and gaps in the literature, and highlighting future directions to mitigate these gaps. RESULTS: Substantial, and increasingly international, research has accumulated regarding the phenomenology, differential diagnosis, course, treatment, and neurobiology of PBD. Prior division around the role of irritability and of screening tools in diagnosis has largely abated. Gold-standard pharmacologic trials inform treatment of manic/mixed episodes, whereas fewer data address bipolar depression and maintenance/continuation treatment. Adjunctive psychosocial treatment provides a forum for psychoeducation and targets primarily depressive symptoms. Numerous neurocognitive and neuroimaging studies, and increasing peripheral biomarker studies, largely converge with prior findings from adults with BD. CONCLUSIONS: As data have accumulated and controversy has dissipated, the field has moved past existential questions about PBD toward defining and pursuing pressing clinical and scientific priorities that remain. The overall body of evidence supports the position that perceptions about marked international (US vs elsewhere) and developmental (pediatric vs adult) differences have been overstated, although additional research on these topics is warranted. Traction toward improved outcomes will be supported by continued emphasis on pathophysiology and novel therapeutics.

Study of the role of telomerase in colorectal cancer: preliminary report and literature review.

AIM: The aim of our study is to focus on hTERT (human Telomerase Reverse Transcriptase) expression to identify tumoral tissue after a comparison to TP53 and KRAS. More than 85% of cancer cells contain genetic aberrations and also overexpression of hTERT, and, in fact, the promoter of hTERT characterizes all malignant cells. PATIENTS AND METHODS: Our sample is composed of 18 patients, including 10 with CRC that underwent surgical procedure and 8 patients without CRC, which represent the control group. The hTERT gene expression, KRAS and p53 were evaluated by methodical Real Time - PCR on RNA extracted from tumor tissues, peritumoral tissue and control cases. RESULTS: Within the CRC group the evaluation of the tumor tissue showed an increase of hTERT expression with a statistical significance (> 0.1) in 5 of these, also associated with substantial increase of KRAS (> 0.2). The peritumoral tissue assessment showed important increase in KRAS in 4 patients (> 0.2), while hTERT is not found to be particularly increased. The value of p53 did not show any particular significance (<0.1). DISCUSSION: The analysis of our data leads us to consider that the increase of hTERT is evident in patients suffering from CRC and that some of them will become significant in relation to the increase of KRAS and independent of p53. In peritumoral tissues, however, KRAS increases considerably, instead hTERT maintains a low concentration and this is compatible with the cellular evolution of the neoplastic tissue adjacent to the tumor. CONCLUSIONS: hTERT could be used for diagnosis and prognosis in the future, to be able to identify the risk of tumor progression and to set up an adequate therapy.

Growth and reproduction of the mangrove crab Goniopsis cruentata (Latreille, 1803) (Crustacea: Decapoda: Grapsidae) in southeastern Brazil.

Goniopsis cruentata is a common semi-terrestrial crab in Brazilian mangroves and an important fishery resource for traditional communities in the northeastern Brazilian coast. Aiming to contribute to the knowledge about the species, this study evaluated the carapace width and weight growth curves, the relative growth of weight versus carapace width, and the temporal variation of gonadosomatic and hepatosomatic indices for the species. A total of 524 crabs were collected in a mangrove area of Ubatuba municipality, state of São Paulo. The growth-curves parameters and longevity (tmax) were estimated for males (CW∞=50.6 mm, WE=56.4 g, k=2.24, t0=0.003631502 year-1, tmax=1.3 years) and females (CW∞=50.7 mm, WE∞=58.8 g, k=2.50, t0=0.003247209 year-1, tmax=1.2 years). The age at onset of sexual maturity was 0.23 years for both genders. The weight-growth model was isometric for the immature developmental stages and allometric negative for adults. The species exhibited a continuous reproduction, with breeding peaks in spring and summer months. The weight dynamics of gonads and hepatopancreas were not clearly related. The growth and reproductive patterns indicated that Goniopsis cruentata has a life-history that prioritizes reproduction instead of survival. The species exhibited some of the highest growth rates and lowest longevity estimates reported for brachyuran species in Brazil.

Prevalence and clinical correlates of alcohol use disorders among bipolar disorder patients: results from the Brazilian Bipolar Research Network.

OBJECTIVES: To investigate prevalence rates and clinical correlates of alcohol use disorders (AUD) among bipolar disorder (BD) patients in a large sample from the Brazilian Bipolar Research Network. METHODS: Four hundred and eighty-three DSM-IV BD patients, divided according to the presence or absence of a lifetime AUD diagnosis (BD-AUD vs. BD-nonAUD), were included. Demographic and clinical characteristics of these two groups were compared. Logistic regression was performed to identify which characteristics were most strongly associated with a lifetime AUD diagnosis. RESULTS: Nearly 23% presented a lifetime AUD diagnosis. BD-AUD patients were more likely to be male, to present rapid cycling, post-traumatic stress disorder (PTSD), anorexia, other substance use disorders (SUD), family history of SUD, any substance misuse during the first mood episode, history of psychosis, suicide attempts, and younger age at onset of illness than BD-nonAUD patients. Logistic regression showed that the variables most strongly associated with a lifetime AUD diagnosis were SUD (non-alcohol), any substance misuse during the first mood episode, PTSD, male gender, suicide attempt, family history of SUD, and younger age at onset of BD. CONCLUSIONS: BD-AUD patients begin their mood disorder earlier and present more suicidal behaviors than BD-nonAUD patients. Personal and family history of SUD may be good predictors of comorbid AUD among BD patients. These variables are easily assessed in the clinical setting and may help to identify a particularly severe subgroup of BD patients.

Qualitative and quantitative evaluation of human dental enamel after bracket debonding: a noncontact three-dimensional optical profilometry analysis.

OBJECTIVES: The aim of this study was to undertake a qualitative and quantitative evaluation of changes on enamel surfaces after debonding of brackets followed by finishing procedures, using a high-resolution three-dimensional optical profiler and to investigate the accuracy of the technique. MATERIALS AND METHODS: The labial surfaces of 36 extracted upper central incisors were examined. Before bonding, the enamel surfaces were subjected to profilometry, recording four amplitude parameters. Brackets were then bonded using two types of light-cured orthodontic adhesive: composite resin and resin-modified glass ionomer cement. Finishing was performed by three different methods: pumice on a rubber cup, fine and ultrafine aluminum oxide discs, and microfine diamond cups followed by silicon carbide brushes. The samples were subsequently re-analyzed by profilometry. RESULTS: Wilcoxon signed-rank test, Kruskal-Wallis test (p < 0.05) and a posteriori Mann-Whitney U test with Bonferroni correction (p < 0.0167) revealed a significant reduction of enamel roughness when diamond cups followed by silicon carbide brushes were used to finish surfaces that had remnants of resin-modified glass ionomer adhesive and when pumice was used to finish surfaces that had traces of composite resin. Enamel loss was minimal. CONCLUSIONS: The 3D optical profilometry technique was able to provide accurate qualitative and quantitative assessment of changes on the enamel surface after debonding. CLINICAL RELEVANCE: Morphological changes in the topography of dental surfaces, especially if related to enamel loss and roughness, are of considerable clinical importance. The quantitative evaluation method used herein enables a more comprehensive understanding of the effects of orthodontic bonding on teeth.

Editorial: A Roadmap for Advancing the Field in Early-Onset Psychosis.

The number of umbrella reviews, the systematic reviews of all systematic reviews and meta-analyses in a specified subject, have increased exponentially in recent years. In February 2024, a PubMed search with the term "umbrella review" yielded 840 publications in 2023, compared with 77 in 2013, and 16 in 2003. As the number of scientific publications grows, also does the need to synthesize the current state of knowledge to guide research efforts, clinical practice, and health policies.1,2.

Gray matter abnormalities as brain structural vulnerability factors for bipolar disorder: A review of neuroimaging studies of individuals at high genetic risk for bipolar disorder.

OBJECTIVE: Cortical and subcortical gray matter abnormalities have been reported in individuals at high genetic risk for bipolar disorder, but the findings are inconsistent. The aim of this study was to review the available literature to identify common findings that could represent brain structural vulnerability factors for bipolar disorder and to discuss challenges for the advancement of the field. METHOD: A systematic search was conducted using the PubMed database to identify all original articles investigating cortical or subcortical gray matter abnormalities in first-degree relatives of bipolar disorder patients. RESULTS: Very few findings were replicated, with the exception of larger insular cortex volumes in adult first-degree relatives and larger right inferior frontal gyrus in offspring of probands with bipolar disorder, both when compared with healthy controls. Isolated findings included decreased gray matter density in the left thalamus, decreased gray matter volumes in the left hippocampus and parahippocampal gyrus, and thicker right hippocampus in unaffected first-degree relatives. Genetic liability for bipolar disorder was associated with gray matter volumes in regions of the anterior cingulate cortex, ventral striatum, medial frontal gyrus, right precentral gyrus, right insular cortex, and medial orbital gyrus. Some studies found no evidence for gray matter abnormalities in first-degree relatives of bipolar disorder patients. CONCLUSIONS: Possible reasons for the discrepancies of findings across studies include small samples sizes, small effect size of susceptibility genes, the phenotypic heterogeneity of bipolar disorder, and the possible confounding effect of other Axis I psychopathologies among the relatives of patients. Future multisite, prospective, large studies with more homogeneous samples would be a key strategy to advance the field. The ultimate benefit would be an understanding of how to use brain imaging tools to identify individuals at increased risk for bipolar disorder and develop preventive strategies for that population.

Trait impulsivity is increased in bipolar disorder patients with comorbid alcohol use disorders.

BACKGROUND: Up to 60% of bipolar disorder (BD) patients develop alcohol use disorders (AUD) at some point in their lives. The causes of this highly prevalent comorbidity are unknown. High trait impulsivity characterizes both isolated BD and AUD and may be a link to explain the association between BD and AUD. In this study, our aims were to investigate whether BD patients with comorbid AUD would present higher trait impulsivity levels compared to BD patients without comorbid AUD, and whether trait impulsivity levels differ within subgroups of BD according to the subcategory of AUD (abuse vs. dependence, alcoholism alone vs. alcoholism plus drug use disorders). SAMPLING AND METHODS: Forty-seven outpatients with BD with comorbid AUD (alcoholic BD group) were compared to 66 outpatients with BD alone (nonalcoholic BD group) and to 90 healthy controls (HC). BD and AUD diagnoses were obtained using the Structured Clinical Interview for DSM-IV diagnoses. Impulsivity was assessed using the Barratt Impulsiveness Scale (BIS-11), a self-report instrument that measures trait impulsivity in three domains: nonplanning, attentional and motor. RESULTS: Alcoholic BD patients scored significantly higher than nonalcoholic BD and HC on the total and on each subscale BIS scores. Within the alcoholic BD patients, alcohol abusers and alcohol dependents did not statistically differ from each other on the BIS-11 scores. BD patients with AUD plus drug use disorders presented statistically higher nonplanning impulsivity than BD patients with AUD alone. CONCLUSIONS: This was a cross-sectional study and causal inferences about the relationship between impulsivity and the comorbidity phenomenon cannot be made. Increased impulsivity may be a trait marker for the co-occurrence between BD and AUD, and mediate some severe manifestations of this comorbidity.

Hospital resource utilisation from HPV-related diseases in England: a real-world cost analysis.

BACKGROUND AND OBJECTIVE: HPV (human papillomavirus) is the virus most often responsible for sexually transmitted infections. The burden of HPV-related diseases on hospital resources represents a major public health problem. The objective of this study was to quantify the lifetime economic burden of HPV-related diseases based on hospital resources from the perspective of National Health Service (NHS) in England. METHODS: Patients' data were extracted, anonymised and aggregated by NHS digital from Hospital Episode Statistics (HES) database of patients admitted in 2015 and followed for three years. Data on hospitalizations were identified according to the International Classification of Diseases (ICD-10 CM). Health Resource Group (HRG) tariffs and National Reference Costs were used to estimate the hospitalization costs of anal, cervical, genital, oropharyngeal cancers as well as anogenital warts and cervical dysplasia. RESULTS: A total of 19,296 hospitalized patients were included in the estimation model, (39% was male and 61% female. At admission, the average age was 60 and 50 years old, respectively). Life-time costs per patients diagnosed with oropharyngeal cancer were £16,911 (£17,142 for male and £16,334 for female), penile cancer £12,539, vaginal cancer £12,676, anal cancer £13.773 (£12,590 for male, £14,525 for female). Cervical cancer accounted for £12,721, whereas cervical dysplasia for £3932. Resource used for hospitalized patients with anogenital warts was equal to £872 (£884 and £856 for men and women, respectively). On average, outpatient accounted for 39% of the total lifetime costs. CONCLUSION: The results of this study highlight that a substantial amount of resources is utilized for the treatment of HPV-related diseases at hospital level in England. These measures have the potential to inform policy decisions to ensure an optimal use of the NHS resources.

Brain functional activation and first mood episode in youth at risk for bipolar disorder.

BACKGROUND: In order to identify biomarkers of prodromal mood disorders, we examined functional brain activation in children and adolescent at familial risk for bipolar disorder. METHODS: Offspring of parents with bipolar I disorder (at-risk youth; N = 115, mean ± SD age: 13.6 ± 2.7; 54 % girls) and group-matched offspring of healthy parents (healthy controls; N = 58, mean ± SD age: 14.2 ± 3.0; 53 % girls) underwent functional magnetic resonance imaging while performing a continuous performance task with emotional and neutral distracters. At baseline, at-risk youth had no history of mood episodes or psychotic disorders. Subjects were followed longitudinally until developing their first mood episode or being lost to follow-up. Standard event-related region-of-interest (ROI) analyses were performed to compare brain activation at baseline between groups and in survival analyses. RESULTS: At baseline, at-risk youth exhibited reduced activation to emotional distracters in the right ventrolateral prefrontal cortex (VLPFC) (p = 0.04). Activation was not significantly altered in additional ROIs, including left VLPFC, bilateral amygdala, caudate, or putamen. In those at-risk youth who developed their first mood episode during follow-up (n = 17), baseline increased activation in right VLPFC, right caudate, and right putamen activation predicted the development of a mood episode. LIMITATIONS: Sample size of converters, loss to follow-up, and number of statistical comparisons. CONCLUSIONS: We found preliminary evidence that a reduced activation in right VLPFC might be a marker of risk for or resilience to mood disorders in at-risk youth. Conversely, an increased activation in the right VLPFC, caudate, and putamen might indicate an increased risk for the later development of their first mood episode.