Stroke Induces Prolonged Changes in Lipid Metabolism, the Liver and Body Composition in Mice

Acknowledgements We would like to thank the Biological Services Facility at the University of Manchester for expert animal husbandry and Karen Davies who helped with the MRI. The Histology Facility equipment that was used in this study was purchased by the University of Manchester Strategic Fund. Special thanks goes to Peter Walker for their help with the histology. Funding information This work was supported by the Kohn Foundation, an Edward Bonham Carter Doctoral Scholarship, an EPSRC/MRC Centre for Doctoral Training in Regenerative Medicine studentship grant (EP/L014904/1), and the Medical Research Council (MR/K501311/1).Peer reviewedPublisher PD

Potential role of miR-9 and miR-223 in recurrent ovarian cancer

<p>Abstract</p> <p>Background</p> <p>MicroRNAs (miRNAs) are small, noncoding RNAs that negatively regulate gene expression by binding to target mRNAs. miRNAs have not been comprehensively studied in recurrent ovarian cancer, yet an incurable disease.</p> <p>Results</p> <p>Using real-time RT-PCR, we obtained distinct miRNA expression profiles between primary and recurrent serous papillary ovarian adenocarcinomas (n = 6) in a subset of samples previously used in a transcriptome approach. Expression levels of top dysregulated miRNA genes, miR-223 and miR-9, were examined using TaqMan PCR in independent cohorts of fresh frozen (n = 18) and FFPE serous ovarian tumours (n = 22). Concordance was observed on TaqMan analysis for miR-223 and miR-9 between the training cohort and the independent test cohorts. Target prediction analysis for the above miRNA "recurrent metastatic signature" identified genes previously validated in our transcriptome study. Common biological pathways well characterised in ovarian cancer were shared by miR-9 and miR-223 lists of predicted target genes. We provide strong evidence that miR-9 acts as a putative tumour suppressor gene in recurrent ovarian cancer. Components of the miRNA processing machinery, such as Dicer and Drosha are not responsible for miRNA deregulation in recurrent ovarian cancer, as deluded by TaqMan and immunohistochemistry.</p> <p>Conclusion</p> <p>We propose a miRNA model for the molecular pathogenesis of recurrent ovarian cancer. Some of the differentially deregulated miRNAs identified correlate with our previous transcriptome findings. Based on integrated transcriptome and miRNA analysis, miR-9 and miR-223 can be of potential importance as biomarkers in recurrent ovarian cancer.</p

The Impact of the Pandemic on Mental Health in Ethnically Diverse Mothers : Findings from the Born in Bradford, Tower Hamlets and Newham COVID-19 Research Programmes

YesRestrictions implemented by the UK Government during the COVID-19 pandemic have served to worsen mental health outcomes, particularly amongst younger adults, women, those living with chronic health conditions, and parents of young children. Studies looking at the impact for ethnic minorities have reported inconsistent findings. This paper describes the mental health experiences of mothers from a large and highly ethnically diverse population during the pandemic, using secondary analysis of existing data from three COVID-19 research studies completed in Bradford and London (Tower Hamlets and Newham). A total of 2807 mothers participated in this study with 44% White British, 23% Asian/Asian British Pakistani, 8% Other White and 7% Asian/Asian British Bangladeshi backgrounds. We found that 28% of mothers experienced clinically important depressive symptoms and 21% anxiety symptoms during the pandemic. In unadjusted analyses, mothers from White Other, and Asian/Asian British Bangladeshi backgrounds had higher odds of experiencing symptoms, whilst mothers from Asian/Asian British Indian backgrounds were the least likely to experience symptoms. Once loneliness, social support and financial insecurity were controlled for, there were no statistically significant differences in depression and anxiety by ethnicity. Mental health problems experienced during the pandemic may have longer term consequences for public health. Policy and decision makers must have an understanding of the high risk of financial insecurity, loneliness and a lack of social support on mother’s mental health, and also recognise that some ethnic groups are far more likely to experience these issues and are, therefore, more vulnerable to poor mental health as a consequence.This study was funded by The Health Foundation COVID-19 Award (2301201), with further contributions from a Wellcome Trust infrastructure grant (WT101597MA); a joint grant from the UK Medical Research Council (MRC) and UK Economic and Social Science Research Council (ESRC) (MR/N024391/1); the National Institute for Health Research under its Applied Research Collaboration Yorkshire and Humber (NIHR200166); ActEarly UK Prevention Research Partnership Consortium (MR/S037527/1); Better Start Bradford through The National Lottery Community Fund; and the British Heart Foundation (CS/16/4/32482). The research conducted in London was funded by UKRI-ESRC ES/V004891/1 (Tower Hamlets), and by London Borough of Newham Public Health. Heys was supported by the NIHR Great Ormond Street Hospital Biomedical Research Centre

One-electron oxidation of [M(PtBu3)2] (M=Pd, Pt) : isolation of monomeric [Pd(PtBu3)2]+and redox-promoted C−H bond cyclometalation

Oxidation of zero-valent phosphine complexes [M(PtBu3)2] (M=Pd, Pt) has been investigated in 1,2-difluorobenzene solution using cyclic voltammetry and subsequently using the ferrocenium cation as a chemical redox agent. In the case of palladium, a mononuclear paramagnetic PdI derivative was readily isolated from solution and fully characterized (EPR, X-ray crystallography). While in situ electrochemical measurements are consistent with initial one-electron oxidation, the heavier congener undergoes C−H bond cyclometalation and ultimately affords the 14 valence-electron PtII complex [Pt(κ2PC-PtBu2CMe2CH2)(PtBu3)]+ with concomitant formation of [Pt(PtBu3)2H]+

Admission to acute care hospitals for adolescent substance abuse: a national descriptive analysis

BACKGROUND: Use of alcohol and illicit drugs by adolescents remains a problem in the U.S. Case identification and early treatment can occur within a broad variety of healthcare and non-healthcare settings, including acute care hospitals. The objective of this study is to describe the extent and nature of adolescent admissions to the acute inpatient setting for substance abuse (SA). We use the Agency for Healthcare Research and Quality (AHRQ) 2000 Healthcare Cost and Utilization Project Kids Inpatient Database (HCUP-KID) which includes over 2.5 million admissions for youth age 20 and under to 2,784 hospitals in 27 states in the year 2000. Specifically, this analysis estimates national number of admissions, mean total charges, and mean lengths of stay for adolescents between the ages of 12 and 17 admitted to an acute care hospital for the following diagnostic categories from the AHRQ's Clinical Classifications Software categories: "alcohol-related mental disorders" and "substance-related mental disorders". Frequency and percentage of total admissions were calculated for demographic variables of age, gender and income and for hospital characteristic variables of urban/rural designation and children's hospital designation. RESULTS: SA admissions represented 1.25 percent of adolescent admissions to acute care hospitals. Nearly 90 percent of the admission occurred in non-Children's hospitals. Most were for drug dependence (38%) or non-dependent use of alcohol or drugs (35%). Costs were highest for drug dependence admissions. Nearly half of admissions had comorbid mental health diagnoses. Higher rates of admission were seen in boys, in older adolescents, and in "self-pay" patients. Alcohol and drug rehabilitation/detoxification, alone or in combination with psychological and psychiatric evaluation and therapy, was documented for 38 percent of admissions. Over 50 percent of cases had no documentation of treatment specific to substance use behavior. CONCLUSION: General acute care hospitals have a significant and important opportunity to recognize, treat, and refer adolescents with substance abuse problems. These results suggest that inpatient facilities should develop and implement policies and processes to ensure that adolescent substance abusers admitted to their institutions receive appropriate care during the admission and appropriate referral to community care resources

Innovative solutions to sticky situations: Antiadhesive strategies for treating bacterial infections

ABSTRACT Bacterial adherence to host tissue is an essential process in pathogenesis, necessary for invasion and colonization and often required for the efficient delivery of toxins and other bacterial effectors. As existing treatment options for common bacterial infections dwindle, we find ourselves rapidly approaching a tipping point in our confrontation with antibiotic-resistant strains and in desperate need of new treatment options. Bacterial strains defective in adherence are typically avirulent and unable to cause infection in animal models. The importance of this initial binding event in the pathogenic cascade highlights its potential as a novel therapeutic target. This article seeks to highlight a variety of strategies being employed to treat and prevent infection by targeting the mechanisms of bacterial adhesion. Advancements in this area include the development of novel antivirulence therapies using small molecules, vaccines, and peptides to target a variety of bacterial infections. These therapies target bacterial adhesion through a number of mechanisms, including inhibition of pathogen receptor biogenesis, competition-based strategies with receptor and adhesin analogs, and the inhibition of binding through neutralizing antibodies. While this article is not an exhaustive description of every advancement in the field, we hope it will highlight several promising examples of the therapeutic potential of antiadhesive strategies.</jats:p

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Prevalence of problem alcohol use among patients attending primary care for methadone treatment

<p>Abstract</p> <p>Background</p> <p>Problem alcohol use is associated with adverse health outcomes among current or former heroin users and primary care is providing methadone treatment for increasing numbers of this population. This study aimed todetermine the prevalence of problem alcohol use among current or former heroin users attending primary care for methadone treatment and to describe the socio-demographic characteristics and health service utilisation characteristics associated with problem alcohol uses.</p> <p>Methods</p> <p>We conducted a cross sectional survey of patients sampled from a national database of patients attending general practice for methadone treatment. Participants were recruited by their general practitioner and data was collected using an interviewer-administered questionnaire, which included the Alcohol Use Disorders Identification Test ('AUDIT'), with a score of >7 considered abnormal (ie 'AUDIT positive cases') and socio-demographic, medical and substance use characteristics.</p> <p>Results</p> <p>We interviewed 196 patients (71% of those invited, 31% of those sampled, 11% of the national database). The median age was 32 years, 55% were hepatitis C positive, 79% had used illicit drugs in the previous month and 68% were male. Sixty-eight 'AUDIT positive' cases were identified (prevalence of 35%, 95% CI = 28–41%) and these were more likely to have attended a local Emergency Department in the previous year (p < 0.05) and less likely to have attended a hospital clinic in the previous year (p < 0.05). Twenty-seven (14%) scored 20 or higher indicating possible alcohol dependence.</p> <p>Conclusion</p> <p>Problem alcohol use has a high prevalence among current or former heroin users attending primary care for methadone treatment and interventions that address this issue should be explored as a priority. Interventions that address problem alcohol use in this population should be considered as a priority, although the complex medical and psychological needs of this population may make this challenging.</p