Validated assays for the quantification of C9orf72 human pathology.

A repeat expansion mutation in the C9orf72 gene is the leading known genetic cause of FTD and ALS. The C9orf72-ALS/FTD field has been plagued by a lack of reliable tools to monitor this genomic locus and its RNA and protein products. We have validated assays that quantify C9orf72 pathobiology at the DNA, RNA and protein levels using knock-out human iPSC lines as controls. Here we show that single-molecule sequencing can accurately measure the repeat expansion and faithfully report on changes to the C9orf72 locus in what has been a traditionally hard to sequence genomic region. This is of particular value to sizing and phasing the repeat expansion and determining changes to the gene locus after gene editing. We developed ddPCR assays to quantify two major C9orf72 transcript variants, which we validated by selective excision of their distinct transcriptional start sites. Using validated knock-out human iPSC lines, we validated 4 commercially available antibodies (of 9 tested) that were specific for C9orf72 protein quantification by Western blot, but none were specific for immunocytochemistry. We tested 15 combinations of antibodies against dipeptide repeat proteins (DPRs) across 66 concentrations using MSD immunoassay, and found two (against poly-GA and poly-GP) that yielded a 1.5-fold or greater signal increase in patient iPSC-motor neurons compared to knock-out control, and validated them in human postmortem and transgenic mouse brain tissue. Our validated DNA, RNA and protein assays are applicable to discovery research as well as clinical trials.

Culture, diversity and inclusion: a survey of British Hip Society members.

AIM: To explore the perceptions and experiences of members of the British Hip Society (BHS) as they relate to culture, diversity and inclusion in the professional sphere. METHOD: BHS members participated in an anonymised online survey in 2021. Quantitative and qualitative data were collected on demographics, professional experiences and perceptions of workplace culture. Members provided suggestions for improving working culture and supporting inclusivity. RESULTS: A 45% response rate (n=217) was achieved. Most respondents were male consultant surgeons, of white ethnicity. Almost a quarter of respondents reported experiencing barriers to career progression within the hip subspecialty. Experience of barriers was more common among women and those of non-white ethnicity. Several members experienced an elitist, exclusive culture in the BHS which is closed to outsiders. Thematic analysis of textual data revealed narratives which portray the perception of the society as a closed-door society, and described a clique culture in orthopaedics, and the pervasiveness of discrimination and banter. CONCLUSION: We found that barriers to inclusion and diversity exist within the professional society. Exploring the narratives around these has informed strategies to overcome them and has shaped future BHS initiatives. To ensure our patients receive the best possible surgical care, it is vital that those with the skills and expertise to deliver it, are supported by the Society and feel a sense of belonging and representation.

Acceptability, feasibility and cost of point of care testing for sexually transmitted infections among South African adolescents where syndromic management is standard of care.

BACKGROUND: Young people (YP) in southern Africa are at substantial risk of HIV and sexually transmitted infections (STIs). Despite the epidemiological and biological link between STIs and HIV transmission and acquisition, infections such as Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) remain widely undiagnosed. Syndromic STI management is the standard of care in low- and middle-income countries (LMICs) despite a high prevalence of asymptomatic infections. We conducted an observational study to explore the acceptability, feasibility, and cost of a STI test-and-treat service for YP in Cape Town. METHODS: YP attending a mobile clinic (MC) and a youth centre clinic (YC) were offered STI screening. Urine testing for CT and NG using a 90-min molecular point-of-care (POC) test on the GeneXpert platform was conducted and treatment provided. Data were collated on demographics, sexual behaviour, presence of symptoms, uptake of same-day treatment, prevalence of CT/NG, and service acceptability. RESULTS: Three hundred sixty six participants were enrolled (median age 20, 83% female).57% (209/366) of participants tested positive for either CT (126/366, 34%) or NG (57/366, 16%) or co-infection (26/366, 7%). Clinical symptoms were a poor predictor of GeneXpert diagnosed CT or NG, with a sensitivity of 46.8% and 54.0% for CT and NG respectively. Although half of participants initially chose to receive same day results and treatment, only a third waited for results on the day. The majority of participants (91%) rated the service highly via a post-visit acceptability questionnaire. CONCLUSION: Curable STIs are highly prevalent in this population. STI screening using POC testing was feasible and acceptability was high. The study provides further impetus for moving policy beyond syndromic management of STIs in South Africa.

Baseline clinical, hormonal and molecular markers associated with clinical response to IL-23 antagonism in hidradenitis suppurativa: A prospective cohort study.

Hidradenitis suppurativa is a complex inflammatory disease in which predicting therapeutic response remains challenging. IL-23 interacts with sex hormones but the relationships between the two in HS remains uninvestigated. To assess whether baseline clinical, hormonal or molecular markers are associated with clinical response to IL-23 antagonism with risankizumab in hidradenitis suppurativa. Twenty six individuals with Hurley stage 2/3 disease were administered risankizumab 150 mg Week 0, 4, 12. Baseline sex hormones and skin biopsies were taken. Clinical response at Week 16 assessed by the HiSCR, and differences between responders and non-responders assessed. Eighteen of 26 participants achieved HiSCR50 at week 16 (69.2%). Clinical response to IL-23 antagonism was associated with male gender, elevated total serum testosterone and decreased levels of FSH. Stratification by clinical responders/nonresponders identified differentially expressed genes including PLPP4 and MAPK10. Immunohistochemistry identified elevated numbers of CD11c, IL-17A and IL-17F positive cells compared to nonresponders. CD11c + cells significantly correlated with serum levels of total testosterone and inversely correlated with serum FSH. Clinical response to IL-23 antagonism in HS is associated with serum sex hormones, Th17 polarized inflammation in lesional tissue and CD11c + cells. These potential therapeutic biomarkers require further validation in larger cohorts but may suggest potential targeted HS therapy.

Research needs, environmental concerns, and logistical considerations for incorporating livestock grazing into coastal upland habitat management.

Along the Gulf of Mexico (GoM) coast, natural resource managers continually struggle with managing coastal uplands due to front-end costs, prolonged maintenance, and habitat-specific ecological needs. Prescribed fire, mechanical removal, and chemical treatments are common habitat management techniques used to remove invasive species, clear understory, and achieve other management goals. However, rapid development and changing climate exacerbate the difficulty in using these techniques. A potential alternative or complementary technique is using livestock for habitat management (i.e., targeted or controlled grazing). In other regions of the world, using livestock for conservation or restoration of managed lands has shown to be a less intrusive and more financially viable alternative. To better understand the research needs, logistical, and environmental concerns related to using livestock for habitat management in the coastal uplands of the GoM, we developed and distributed a survey to three groups of land users, including natural resource managers, researchers, and livestock producers in the region. Survey results show that over 96% of respondents are interested in using livestock for habitat management, but less than 10% of respondents were aware of any information that could be used to inform grazing practices for coastal upland habitat management along the Gulf of Mexico coast. There were differences among surveyed groups, but generally small-sized cattle breeds and goats were identified as the livestock with the most potential for environmental benefit and ease of containment. General concerns and areas for further investigation were implementation (e.g., which livestock type to use and grazing intensity), logistical considerations (e.g., fencing and rotational frequency), impacts of grazing on water quality, wildlife, vegetation, and livestock nutrition. Survey respondents overwhelmingly (at least 75% of each group) indicated that livestock grazing ideally would not be a standalone management practice and should be used in conjunction with other habitat management techniques such as prescribed burns, mechanical clearing, or chemical treatments. The results of the survey could be used to develop applied research projects and guidance documents that directly address informational needs related to using livestock for habitat management of coastal uplands along the Gulf of Mexico coast.

The impact of mentoring in trauma and orthopaedic training: a systematic review.

INTRODUCTION: Trauma and orthopaedics is renowned for being a challenging yet rewarding career. The value of mentorship in medical and surgical training is known to be beneficial; however, the prevalence and quality of mentorship opportunities in orthopaedics are less well studied. Identifying the strengths and weaknesses of mentoring programmes in orthopaedic training and recognising barriers to effective mentorship are key to unlocking the full potential of future orthopaedic surgeons. METHODS: A comprehensive search of PubMed, Medline, EMBASE and the Cochrane Library was performed. All studies published in the English language that reported data on mentorship programmes in orthopaedic training were included. FINDINGS: A total of 23 studies met the inclusion criteria. These studies demonstrated that formal mentorship programmes in orthopaedics are lacking but are sought after, with a positive influence on satisfaction and future career choice/subspecialty selection identified. Several barriers to mentoring in the field were recognised including the difficulty faced by female trainees, the availability of mentors and time constraints. The opportunity to choose a mentor, a mentor with the same interests, regular meetings and the option of gender congruent mentorship were all identified as crucial requirements for effective mentorship. CONCLUSION: Mentorship opportunities must be more accessible to all orthopaedic trainees alike and should aim to incorporate the attributes identified to provide the highest calibre of training to prospective orthopaedic surgeons.

Inadvertent irreversible closure of arterial duct following therapeutic use of transplacental indomethacin in a fetus with severe Ebstein's anomaly and circular shunt.

We report on a fetal case of Ebstein's anomaly with severe tricuspid regurgitation, functional pulmonary atresia and progressive circular shunting (CS) across a widely patent ductus arteriosus (DA) and regurgitant pulmonary valve, contributing to significant systemic hypoperfusion. To mitigate the extent of CS and allow the pregnancy to continue, maternal non-steroidal anti-inflammatory drug (NSAID) therapy with indomethacin was started at 33 + 5 weeks to induce DA constriction. Rather than achieving the desired narrowing of the DA, the treatment led to its complete closure and only minimal antegrade flow across the pulmonary valve. While closure of the DA resulted in the anticipated improvement in fetal hemodynamics, at birth, the child was at risk of severe hypoxemia and its consequences due to the lack of adequate pulmonary perfusion. Reduction and eventual discontinuation of the NSAID treatment did not result in DA reopening. Our experience illustrates the risk of unintended irreversible DA closure when NSAIDs are used to treat CS. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Narrow pH tolerance found for a microbial fuel cell treating winery wastewater.

AIMS: The use of microbial fuel cells (MFC) to treat winery wastewater is promising; however, an initial acidic pH, fluctuating chemical oxygen demand (COD) levels and a lack of natural buffering in these wastewaters make providing a suitable buffer system at an ideal buffer to COD ratio. METHODS AND RESULTS: A lab scale MFC was designed, inoculated with anaerobic winery sludge and fed with synthetic winery wastewater. It was observed that at pH 6·5, the MFC performed best, the maximum output voltage was 0·63 ± 0·01 V for 60 ± 3 h, and the COD removal efficiency reached 77 ± 7%. The electrogens were affected by pH much more than the bulk COD degrading organisms. Fluorescent in situ hybridization suggested Betaproteobacteria played a significant role in electron transfer. CONCLUSIONS: A ratio of 1 mmol l-1 phosphate buffer to 100 mg l-1 COD was ideal to maintain a stable pH for MFCs treating synthetic winery wastewater. SIGNIFICANCE AND IMPACT OF THE STUDY: The results find the narrow pH tolerance for MFCs treating winery wastewater and demonstrate the significance of pH and buffer to COD ratio for steady performance of MFCs.

Uptake and acceptability of medical male circumcision among young males in two culturally distinct settings in South Africa: A longitudinal, community-based study (the MACHO study).

BACKGROUND: Young South Africans experience high rates of HIV infection. While nationally scaled medical male circumcision (MMC) can help to curb HIV infection rates in countries such as South Africa (SA), MMC uptake has not been consistent or universal, suggesting variable acceptability among men. Both MMC and traditional male circumcision (TMC) are practised in SA. For male circumcision to be most effective for HIV prevention, it should be performed prior to sexual debut with complete removal of the foreskin. OBJECTIVES: The MACHO (Male Adolescent Choices for HIV Prevention Options) study investigated uptake of and preference for MMC v. TMC in two culturally distinct settings in SA. METHODS: This observational, longitudinal, cohort study investigated circumcision preferences and uptake in 100 males (aged 14 - 17 years) and their legal guardians in Cape Town (Western Cape Province) and Soweto (Gauteng Province). Data were collected via surveys administered every 4 months over a 24-month period. RESULTS: A total of 100 uncircumcised adolescent boys (Cape Town n=50, Soweto n=50; mean (interquartile range) age 15 (14 - 16) years) and their guardians were enrolled. At baseline, 42 boys from Soweto (84%) and none from Cape Town expressed a preference for MMC over TMC. Sowetan participants were more likely to elect circumcision (MMC n=11 (22%), TMC n=1 (2%)) than those from Cape Town (TMC n=1 (2%), MMC n=0) over 13.6 months of follow-up (hazard ratio 18.9; 95% confidence interval 2.37 - 150.71; p=0.006). CONCLUSIONS: MMC was the preferred option for young men in Soweto compared with those in Cape Town, and this translated into practice. Despite knowledge of the benefits of early MMC, many participants delayed uptake, potentially reducing the MMC benefits before sexual debut. Programmes promoting circumcision should consider the influence of local practices. To realise full HIV prevention benefits, efforts should be made to ensure that circumcision is promoted, and that all circumcision is safe, performed prior to sexual debut, and contextually responsive.

Training in oral and maxillofacial surgery: a medicine-first perspective.

Specialist registration in oral and maxillofacial surgery (OMFS) requires dual medical and dental qualification involving at least eight years of undergraduate study. Training has continued to evolve since dual qualification was introduced and has often resulted in unwarranted repetition. If a time-based curriculum is necessary, second degree trainees should be allowed to pursue research and audit, and gain relevant clinical experience in lieu of repeating previously covered material. Junior surgical training could be integrated into the second degree. A programme that records competencies during the second degree may demonstrate equivalent to other aspects of junior training. One barrier is timetabling, which often restricts the integration of second degree trainees with OMFS units. Junior training in OMFS could be streamlined if the content was agreed nationally. This would also offer the opportunity for those key institutions that implement these changes to take on a prominent role in OMFS training.

Combining trauma severity indices to create a unified craniofacial disruption index: addition of the frontobasal unit to the ZS model.

Craniomaxillofacial injuries account for a large number of emergency attendances and a substantial proportion of the workload of acute clinicians. Although data exist on frequency of involvement of the craniofacial bones, assessments of severity are lacking, and scoring systems for fractures of individual bones and complex craniomaxillofacial trauma often fail to include the frontobasal unit. To rectify this, we have devised a validated scoring system to evaluate the severity of trauma to this region and have merged it with a pre-existing model to create a cohesive craniofacial disruption index. Published papers were reviewed and the frontobasal unit defined. Clinically important anatomical regions were assigned a graduated score that depended on the severity of disruption, and this was applied in the cases of 13 patients with known craniofacial fractures of varying severity. Correlation with existing models was calculated and used as a marker of validity. Our frontobasal system showed strong positive correlation with a consensus of OMFS clinicians (r=0.783, p<0.01). When amalgamated with the pre-existing ZS score to create the Craniofacial Disruption Index, it correlated strongly with all previous scoring systems (r≥0.729, p<0.001). The index is a user-friendly, validated model that enables comparison of the severity of complex craniofacial injuries. It has many potential uses because of its digital, automated method of calculation.

Association between Smoking Exposure, Neoadjuvant Chemotherapy Response and Survival Outcomes following Radical Cystectomy: Systematic Review and Meta-Analysis.

PURPOSE: Studies exploring the association of cigarette smoking and long-term survival outcomes following radical cystectomy have yielded mixed results. We performed a systematic review and meta-analysis to investigate the impact of tobacco smoking exposure, duration, intensity and cessation on response to neoadjuvant chemotherapy and long-term survival outcomes in patients undergoing radical cystectomy for bladder cancer. MATERIALS AND METHODS: We systematically searched PubMed®, MEDLINE®, Embase® and Cochrane® Library databases for original articles published before April 2019. Primary end points were neoadjuvant chemotherapy response, overall and cancer specific mortality, and recurrence-free survival after radical cystectomy. Observational studies reporting Cox proportional hazards regression or logistic regression analysis were independently screened. Available multivariable hazard ratios and corresponding 95% CIs were included in the quantitative analysis. Sensitivity analyses were performed as appropriate. A risk of bias assessment was completed for nonrandomized studies. RESULTS: Our electronic search identified a total of 649 articles. After a detailed review we selected 17 studies that addressed the impact of smoking status on survival outcomes in 13,777 patients after radical cystectomy for bladder cancer. Pooled meta-analysis revealed that active smokers have an increased risk of overall mortality (HR 1.21, 95% CI 1.08-1.36; p=0.001, I2=0%), cancer specific mortality (HR 1.24, 95% CI 1.13-1.36; p <0.00001, I2=0%) and bladder cancer recurrence (HR 1.24, 95% CI 1.12-1.38; p <0.0001, I2=3%). Sensitivity analyses evaluating only patients who underwent neoadjuvant chemotherapy followed by radical cystectomy showed an advantage of non/never smokers in terms of neoadjuvant chemotherapy complete response rate (HR 0.47, 95% CI 0.29-0.75; p=0.001, I2=0%). CONCLUSIONS: Smoking status is associated with lower neoadjuvant chemotherapy response rates and higher overall and cancer specific mortality as well as bladder cancer recurrence after radical cystectomy. Appropriate preoperative counseling, together with tightened followup, may have a pivotal role in improving the smoking-related long-term survival outcomes in patients with bladder cancer.

Best practices in near-infrared fluorescence imaging with indocyanine green (NIRF/ICG)-guided robotic urologic surgery: a systematic review-based expert consensus.

PURPOSE: The aim of the present study is to investigate the impact of the near-infrared (NIRF) technology with indocyanine green (ICG) in robotic urologic surgery by performing a systematic literature review and to provide evidence-based expert recommendations on best practices in this field. METHODS: All English language publications on NIRF/ICG-guided robotic urologic procedures were evaluated. We followed the PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analyses) statement to evaluate PubMed®, Scopus® and Web of Science™ databases (up to April 2019). Experts in the field provided detailed pictures and intraoperative video-clips of different NIRF/ICG-guided robotic surgeries with recommendations for each procedure. A unique QRcode was generated and linked to each underlying video-clip. This new exclusive feature makes the present the first "dynamic paper" that merges text and figure description with their own video providing readers an innovative, immersive, high-quality and user-friendly experience. RESULTS: Our electronic search identified a total of 576 papers. Of these, 36 studies included in the present systematic review reporting the use of NIRF/ICG in robotic partial nephrectomy (n = 13), robotic radical prostatectomy and lymphadenectomy (n = 7), robotic ureteral re-implantation and reconstruction (n = 5), robotic adrenalectomy (n = 4), robotic radical cystectomy (n = 3), penectomy and robotic inguinal lymphadenectomy (n = 2), robotic simple prostatectomy (n = 1), robotic kidney transplantation (n = 1) and robotic sacrocolpopexy (n = 1). CONCLUSION: NIRF/ICG technology has now emerged as a safe, feasible and useful tool that may facilitate urologic robotic surgery. It has been shown to improve the identification of key anatomical landmarks and pathological structures for oncological and non-oncological procedures. Level of evidence is predominantly low. Larger series with longer follow-up are needed, especially in assessing the quality of the nodal dissection and the feasibility of the identification of sentinel nodes and the impact of these novel technologies on long-term oncological and functional outcomes.

Baseline demographics, clinical features and predictors of conversion among 200 individuals in a longitudinal prospective psychosis-risk cohort.

BACKGROUND: DSM-5 proposes an Attenuated Psychosis Syndrome (APS) for further investigation, based upon the Attenuated Positive Symptom Syndrome (APSS) in the Structured Interview for Psychosis-Risk Syndromes (SIPS). SIPS Unusual Thought Content, Disorganized Communication and Total Disorganization scores predicted progression to psychosis in a 2015 NAPLS-2 Consortium report. We sought to independently replicate this in a large single-site high-risk cohort, and identify baseline demographic and clinical predictors beyond current APS/APSS criteria. METHOD: We prospectively studied 200 participants meeting criteria for both the SIPS APSS and DSM-5 APS. SIPS scores, demographics, family history of psychosis, DSM Axis-I diagnoses, schizotypy, and social and role functioning were assessed at baseline, with follow-up every 3 months for 2 years. RESULTS: The conversion rate was 30% (n = 60), or 37.7% excluding participants who were followed under 2 years. This rate was stable across time. Conversion time averaged 7.97 months for 60% who developed schizophrenia and 15.68 for other psychoses. Mean conversion age was 20.3 for males and 23.5 for females. Attenuated odd ideas and thought disorder appear to be the positive symptoms which best predict psychosis in a logistic regression. Total negative symptom score, Asian/Pacific Islander and Black/African-American race were also predictive. As no Axis-I diagnosis or schizotypy predicted conversion, the APS is supported as a distinct syndrome. In addition, cannabis use disorder did not increase risk of conversion to psychosis. CONCLUSIONS: NAPLS SIPS findings were replicated while controlling for clinical and demographic factors, strongly supporting the validity of the SIPS APSS and DSM-5 APS diagnosis.

Oxidative stress-driven parvalbumin interneuron impairment as a common mechanism in models of schizophrenia.

Parvalbumin inhibitory interneurons (PVIs) are crucial for maintaining proper excitatory/inhibitory balance and high-frequency neuronal synchronization. Their activity supports critical developmental trajectories, sensory and cognitive processing, and social behavior. Despite heterogeneity in the etiology across schizophrenia and autism spectrum disorder, PVI circuits are altered in these psychiatric disorders. Identifying mechanism(s) underlying PVI deficits is essential to establish treatments targeting in particular cognition. On the basis of published and new data, we propose oxidative stress as a common pathological mechanism leading to PVI impairment in schizophrenia and some forms of autism. A series of animal models carrying genetic and/or environmental risks relevant to diverse etiological aspects of these disorders show PVI deficits to be all accompanied by oxidative stress in the anterior cingulate cortex. Specifically, oxidative stress is negatively correlated with the integrity of PVIs and the extracellular perineuronal net enwrapping these interneurons. Oxidative stress may result from dysregulation of systems typically affected in schizophrenia, including glutamatergic, dopaminergic, immune and antioxidant signaling. As convergent end point, redox dysregulation has successfully been targeted to protect PVIs with antioxidants/redox regulators across several animal models. This opens up new perspectives for the use of antioxidant treatments to be applied to at-risk individuals, in close temporal proximity to environmental impacts known to induce oxidative stress.

An expert consensus definition of failure of a treatment to provide adequate relief (F-PAR) for chronic constipation - an international Delphi survey.

BACKGROUND: As treatments for constipation become increasingly available, it is important to know when to progress along the treatment algorithm if the patient is not better. AIM: To establish the definition of failure of a treatment to provide adequate relief (F-PAR) to support this management and referral process in patients with chronic constipation. METHODS: We conducted an international Delphi Survey among gastroenterologists and general practitioners with a special interest in chronic constipation. An initial questionnaire based on recognised rating scales was developed following a focus group. Data were collected from two subsequent rounds of questionnaires completed by all authors. Likert scales were used to establish a consensus on a shorter list of more severe symptoms. RESULTS: The initial focus group yielded a first round questionnaire with 84 statements. There was good consensus on symptom severity and a clear severity response curve, allowing 67 of the symptom-severity pairings to be eliminated. Subsequently, a clear consensus was established on further reduction to eight symptom statements in the final definition, condensed by the steering committee into five diagnostic statements (after replicate statements had been removed). CONCLUSIONS: We present an international consensus on chronic constipation, of five symptoms and their severities, any of which would be sufficient to provide clinical evidence of treatment failure. We also provide data representing an expert calibration of commonly used rating scales, thus allowing results of clinical trials expressed in terms of those scales to be converted into estimates of rates of provision of adequate relief.

The impact of emotion awareness and regulation on social functioning in individuals at clinical high risk for psychosis.

BACKGROUND: Social functioning (SF) difficulties are ubiquitous among individuals at clinical high risk for psychosis (CHR), but it is not yet clear why. One possibility is suggested by the observation that effective SF requires adaptive emotion awareness and regulation. Previous reports have documented deficits in emotion awareness and regulation in individuals with schizophrenia, and have shown that such deficits predicted SF. However, it is unknown whether these deficits are present prior to the onset of psychosis or whether they are linked to SF in CHR individuals. METHOD: We conducted a cross-sectional comparison of emotion awareness and regulation in 54 individuals at CHR, 87 with schizophrenia and 50 healthy controls (HC). Then, within the CHR group, we examined links between emotion awareness, emotion regulation and SF as indexed by the Global Functioning Scale: Social (Cornblatt et al. 2007). RESULTS: Group comparisons indicated significant differences between HC and the two clinical groups in their ability to identify and describe feelings, as well as the use of suppression and reappraisal emotion-regulation strategies. Specifically, the CHR and schizophrenia groups displayed comparable deficits in all domains of emotion awareness and emotion regulation. A hierarchical multiple regression analysis indicated that difficulties describing feelings accounted for 23.2% of the SF variance. CONCLUSIONS: The results indicate that CHR individuals display substantial emotion awareness and emotion-regulation deficits, at severity comparable with those observed in individuals with schizophrenia. Such deficits, in particular difficulties describing feelings, predate the onset of psychosis and contribute significantly to poor SF in this population.

Quercetin attenuates neuronal death against aluminum-induced neurodegeneration in the rat hippocampus.

Aluminum is a light weight and toxic metal present ubiquitously on earth, which has gained considerable attention due to its neurotoxic effects. It also has been linked ecologically and epidemiologically to several neurological disorders, including Alzheimer's disease (AD), Parkinson's disease (PD), Guamanian-Parkinsonian complex and Amyotrophic lateral sclerosis (ALS). The mechanism of aluminum neurotoxicity is poorly understood, but it is well documented that aluminum generates reactive oxygen species (ROS). Enhanced ROS production leads to disruption of cellular antioxidant defense systems and release of cytochrome c (cyt-c) from mitochondria to cytosol resulting in apoptotic cell death. Quercetin (a natural flavonoid) protects it from oxidative damage and has been shown to decrease mitochondrial damage in various animal models of oxidative stress. We hypothesized that if oxidative damage to mitochondria does play a significant role in aluminum-induced neurodegeneration, and then quercetin should ameliorate neuronal apoptosis. Administration of quercetin (10 mg/kg body wt/day) reduced aluminum (10 mg/kg body wt/day)-induced oxidative stress (decreased ROS production, increased mitochondrial superoxide dismutase (MnSOD) activity). In addition, quercetin also prevents aluminum-induced translocation of cyt-c, and up-regulates Bcl-2, down-regulates Bax, p53, caspase-3 activation and reduces DNA fragmentation. Quercetin also obstructs aluminum-induced neurodegenerative changes in aluminum-treated rats as seen by Hematoxylin and Eosin (H&E) staining. Further electron microscopic studies revealed that quercetin attenuates aluminum-induced mitochondrial swelling, loss of cristae and chromatin condensation. These results indicate that treatment with quercetin may represent a therapeutic strategy to attenuate the neuronal death against aluminum-induced neurodegeneration.