Author Correction: Discovery of a selective catalytic p300/CBP inhibitor that targets lineage-specific tumours.

In the originally published version of this Letter, the authors Arthur F. Kluge, Michael A. Patane and Ce Wang were inadvertently omitted from the author list. Their affiliations are: I-to-D, Inc., PO Box 6177, Lincoln, Massachusetts 01773, USA (A.F.K.); Mitobridge, Inc. 1030 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA (M.A.P.); and China Novartis Institutes for BioMedical Research, No. 4218 Jinke Road, Zhangjiang Hi-Tech Park, Pudong District, Shanghai 201203, China (C.W.). These authors contributed to the interpretation of results and design of compounds. In addition, author 'Edward A. Kesicki' was misspelled as 'Ed Kesicki'. These errors have been corrected online.

The Frequency and Severity of Gastrointestinal Symptoms in Rugby Players.

This study aimed to assess the self-reported frequency and severity of gastrointestinal symptoms (GIS) at rest and around rugby training and match play in male and female rugby union players. An online questionnaire was sent to registered rugby union players (sevens or fifteens). Thirteen GIS were assessed alongside perceptions of appetite around rugby and rest using Likert and visual analog scales. Questions investigating a range of medical and dietary factors were included. Three hundred and twenty-five players (male n=271, female n=54) participated in the study. More frequent GIS (at least one GIS experienced weekly/more often) was reported by players at rest (n=203; 62%) compared to around rugby (n=154; 47%). The overall severity of GIS was low (mild discomfort), but a portion of players (33%) did report symptoms of moderate severity around rugby. Female players reported more frequent and severe symptoms compared to male counterparts (p<0.001). Self-reported appetite was significantly lower after matches compared to training. There were no dietary or medical factors associated with GIS severity scores. This study describes GIS characteristics in male and female rugby union players. Half of the players assessed experienced some form of GIS that may affect nutrition, training, or performance, and should thus be a consideration for practitioners supporting this cohort.

Discovery of a selective catalytic p300/CBP inhibitor that targets lineage-specific tumours.

The dynamic and reversible acetylation of proteins, catalysed by histone acetyltransferases (HATs) and histone deacetylases (HDACs), is a major epigenetic regulatory mechanism of gene transcription and is associated with multiple diseases. Histone deacetylase inhibitors are currently approved to treat certain cancers, but progress on the development of drug-like histone actyltransferase inhibitors has lagged behind. The histone acetyltransferase paralogues p300 and CREB-binding protein (CBP) are key transcriptional co-activators that are essential for a multitude of cellular processes, and have also been implicated in human pathological conditions (including cancer). Current inhibitors of the p300 and CBP histone acetyltransferase domains, including natural products, bi-substrate analogues and the widely used small molecule C646, lack potency or selectivity. Here, we describe A-485, a potent, selective and drug-like catalytic inhibitor of p300 and CBP. We present a high resolution (1.95 Å) co-crystal structure of a small molecule bound to the catalytic active site of p300 and demonstrate that A-485 competes with acetyl coenzyme A (acetyl-CoA). A-485 selectively inhibited proliferation in lineage-specific tumour types, including several haematological malignancies and androgen receptor-positive prostate cancer. A-485 inhibited the androgen receptor transcriptional program in both androgen-sensitive and castration-resistant prostate cancer and inhibited tumour growth in a castration-resistant xenograft model. These results demonstrate the feasibility of using small molecule inhibitors to selectively target the catalytic activity of histone acetyltransferases, which may provide effective treatments for transcriptional activator-driven malignancies and diseases.

Vitiligo: Pathogenesis and New and Emerging Treatments.

Vitiligo is a complex disease with a multifactorial nature and a high impact on the quality of life of patients. Although there are multiple therapeutic alternatives, there is currently no fully effective treatment for this disease. In the current era, multiple drugs are being developed for the treatment of autoimmune diseases. This review assesses the available evidence on the pathogenesis of vitiligo, and a comprehensive review of treatments available for vitiligo now and in the near future is provided. This qualitative analysis spans 116 articles. We reviewed the mechanism of action, efficacy and safety data of phototherapy, afamelanotide, cyclosporine, phosphodiesterase 4 inhibitors, trichloroacetic acid, basic fibroblast growth factor, tumor necrosis factor (TNF) inhibitors, secukinumab, pseudocatalase and janus kinase (JAK) inhibitors. At the moment, there is no clearly outstanding option or fully satisfactory treatment for vitiligo, so it is necessary to keep up the development of new drugs as well as the publication of long-term effectiveness and safety data for existing treatments.

Human papillomavirus-based screening at extended intervals missed fewer cervical precancers than cytology in the HPV For Cervical Cancer (HPV FOCAL) trial.

While cervix screening using cytology is recommended at 2- to 3-year intervals, given the increased sensitivity of human papillomavirus (HPV)-based screening to detect precancer, HPV-based screening is recommended every 4- to 5-years. As organized cervix screening programs transition from cytology to HPV-based screening with extended intervals, there is some concern that cancers will be missed between screens. Participants in HPV FOr CervicAL Cancer (HPV FOCAL) trial received cytology (Cytology Arm) at 24-month intervals or HPV-based screening (HPV Arm) at 48-month intervals; both arms received co-testing (cytology and HPV testing) at exit. We investigated the results of the co-test to identify participants with cervical intraepithelial neoplasia grade 2 or higher (CIN2+) who would not have had their precancer detected if they had only their arm's respective primary screen. In the Cytology Arm, 25/62 (40.3%) identified CIN2+s were missed by primary screen (ie, normal cytology/positive HPV test) and all 25 had normal cytology at the prior 24-month screen. In the HPV arm, three CIN2+s (3/49, 6.1%) were missed by primary screen (ie, negative HPV test/abnormal cytology). One of these three misses had low-grade cytology findings and would also not have been referred to colposcopy outside of the trial. Multiple rounds of cytology did not detect some precancerous lesions detected with one round of HPV-based screening. In our population, cytology missed more CIN2+, even at shorter screening intervals, than HPV-based screening. This assuages concerns about missed detection postimplementation of an extended interval HPV-based screening program. We recommend that policymakers consider a shift from cytology to HPV-based cervix screening.

Improving Post-Release Care Engagement for People Living with HIV Involved in the Criminal Justice System: A Systematic Review.

Given sub-optimal HIV care outcomes for people living with HIV (PLWH) post-release from incarceration, we systematically searched peer-reviewed literature (2010-2021) describing controlled trial interventions aimed at improving Antiretroviral Therapy (ART) adherence and care linkage following release from correctional facilities for PLWH. Of 392 studies, 16 (4%) met the inclusion criteria. All studies were conducted in the United States and involved some form of intensive case management. Trials that scored highest in terms of study quality provided cell phones for engagement, reported sustained viral load suppression as a measurable outcome to infer ART adherence, and measured longitudinal data collected for at least 3-to-6 months following release. The two trials that demonstrated improved HIV viral load suppression involved Peer Navigators, and incentivized undetectable viral load, respectively. Facilitating support for addictions and addressing other social and structural barriers to achieving optimal health is also of vital importance in bridging care gaps for PLWH.

RESUMEN: Debido a los resultados suboptimos en los cuidados de las personas que viven con VIH después de su liberación del encarcelamiento, nosotros realizamos una revisión sistemática de la literatura (2010­2021) que describe ensayos control de intervenciones para mejorar la adherencia a la terapia antiretrovirales (TAR) y el vinculo con la atención medica después de la liberación del encarcelamiento de las personas que viven con VIH. De los 392 estudios, 16 (4%) cumplieron con los criterios de inclusión. Todos los estudios fueron realizados en los Estados Unidos e incluyen alguna forma de cuidados con manejo intensivo. Los ensayos que tenían los puntajes mas altos en términos de calidad proveían teléfonos celulares para la vinculación, reportaban supresión de la carga viral sostenida como medida indirecta de adherencia al TAR, y han medido datos longitudinales por lo menos de tres a seis meses después de la liberación carcelaria. Los dos ensayos que demostraron mejora en la supresión de la carga viral del VIH involucraban a los pares navegadores e incentivaban la carga viral no detectable, respectivamente. Facilitando el soporte para la adicción y el entendimiento de otras barreras sociales y estructurales para alcanzar una salud optima, es de vital importancia para superar las brechas en la atención de las personas que viven con VIH.

Discovery of (R)-(3-fluoropyrrolidin-1-yl)(6-((5-(trifluoromethyl)pyridin-2-yl)oxy)quinolin-2-yl)methanone (ABBV-318) and analogs as small molecule Nav1.7/ Nav1.8 blockers for the treatment of pain.

The voltage-gated sodium channel Nav1.7 is an attractive target for the treatment of pain based on the high level of target validation with genetic evidence linking Nav1.7 to pain in humans. Our effort to identify selective, CNS-penetrant Nav1.7 blockers with oral activity, improved selectivity, good drug-like properties, and safety led to the discovery of 2-substituted quinolines and quinolones as potent small molecule Nav1.7 blockers. The design of these molecules focused on maintaining potency at Nav1.7, improving selectivity over the hERG channel, and overcoming phospholipidosis observed with the initial leads. The structure-activity relationship (SAR) studies leading to the discovery of (R)-(3-fluoropyrrolidin-1-yl)(6-((5-(trifluoromethyl)pyridin-2-yl)oxy)quinolin-2-yl)methanone (ABBV-318) are described herein. ABBV-318 displayed robust in vivo efficacy in both inflammatory and neuropathic rodent models of pain. ABBV-318 also inhibited Nav1.8, another sodium channel isoform that is an active target for the development of new pain treatments.

Healthcare providers' experiences with advance care planning and goals of patient care medical treatment orders in residential aged care facilities: an explanatory descriptive study.

BACKGROUND: Advance care planning (ACP) is a process by which people communicate their healthcare preferences and values, planning for a time when they are unable to voice them. Within residential aged care facilities (RACF), both the completion and the clarity of ACP documents are varied and, internationally, medical treatment orders have been used to address these issues. AIMS: In this study, goals of patient care (GOPC) medical treatment orders were introduced alongside usual ACP in three RACF to improve healthcare decision-making for residents. This study explored the experiences of RACF healthcare providers with ACP and GOPC medical treatment orders. METHODS: The study used an explanatory descriptive approach. Within three RACF where the GOPC medical treatment orders had been introduced, focus groups and interviews with healthcare providers were performed. The transcribed interviews were analysed thematically. RESULTS: Healthcare providers not only reported support for ACP and GOPC but also discussed many problematic issues. Analysis of the data identified four main themes: enablers, barriers, resident autonomy and advance documentation (ACP and GOPC). CONCLUSION: Healthcare providers identified ACP and GOPC as positive tools for assisting with medical decision-making for residents. Although barriers exist in completion and activation of plans, healthcare providers described them as progressing resident-centred care. Willingness to follow ACP instructions was reported to be reduced by lack of trust by clinicians. Families were also reported to change their views from those documented in family-completed ACP, attributed to poor understanding of their purpose. Participants reported that GOPC led to clearer documentation of residents' medical treatment plans rather than relying on ACP documents alone.

Discovery of spirohydantoins as selective, orally bioavailable inhibitors of p300/CBP histone acetyltransferases.

p300 and CREB-binding protein (CBP) are essential for a multitude of cellular processes. Dysregulation of p300/CBP histone acetyltransferase activity is linked to a broad spectrum of human diseases including cancers. A novel drug-like spirohydantoin (21) has been discovered as a selective orally bioavailable inhibitor of p300/CBP histone acetyltransferase. Lead compound 21 is more potent than the first-in-class lead A-485 in both enzymatic and cellular assays and lacks the off-target inhibition of dopamine and serotonin transporters, that was observed with A-485.

Asymptomatic carriage rates and case fatality of SARS-CoV-2 infection in residents and staff in Irish nursing homes.

BACKGROUND: SARS-CoV-2 has disproportionately affected nursing homes (NH). In Ireland, the first NH case COVID-19 occurred on 16 March 2020. A national point-prevalence testing programme of all NH residents and staff took place (18 April 2020 to 5 May 2020). AIMS: to examine characteristics of NHs across three Irish Community Health Organisations, proportions with COVID-19 outbreaks, staff and resident infection rates symptom profile and resident case fatality. METHODS: in total, 45 NHs surveyed, requesting details on occupancy, size, COVID-19 outbreak, outbreak timing, total symptomatic/asymptomatic cases and outcomes for residents from 29 February 2020 to 22 May 2020. RESULTS: surveys were returned from 62.2% (28/45) of NHs (2,043 residents, 2,303 beds). Three-quarters (21/28) had COVID-19 outbreaks (1,741 residents, 1,972 beds). Median time from first COVID-19 case in Ireland to first case in these NHs was 27.0 days. Resident incidence was 43.9% (764/1,741)-40.8% (710/1,741) laboratory confirmed, with 27.2% (193/710) asymptomatic and 3.1% (54/1,741) clinically suspected. Resident case fatality was 27.6% (211/764) for combined laboratory-confirmed/clinically suspected COVID-19. Similar proportions of residents in NHs with 'early-stage' (<28 days) versus 'later-stage' outbreaks developed COVID-19. Lower proportions of residents in 'early' outbreak NHs had recovered compared with those with 'late' outbreaks (37.4 versus 61.7%; χ2 = 56.9, P < 0.001). Of 395 NH staff across 12 sites with confirmed COVID-19, 24.7% (99/398) were asymptomatic. There was a significant correlation between the proportion of staff with symptomatic COVID-19 and resident numbers with confirmed/suspected COVID-19 (Spearman's rho = 0.81, P < 0.001). CONCLUSION: this study demonstrates the significant impact of COVID-19 on the NH sector. Systematic point-prevalence testing is necessary to reduce risk of transmission from asymptomatic carriers and manage outbreaks in this setting.

Remote screening of retinal and optic disc diseases using handheld nonmydriatic cameras in programmed routine occupational health checkups onsite at work centers.

PURPOSE: To evaluate the first year outcomes of a remote screening program for detection of retinal diseases using handheld nonmydriatic cameras in occupational routine checkups performed onsite at work centers. METHODS: Cross-sectional, first year screening program outcomes audit. Participants were volunteers recruited from staff within work centers. Retinal fundus images were captured by technicians, and images and data were anonymized and sent securely to a remote server. A team of ophthalmologists, all retinal specialists, remotely read the images using a custom-made software and sent telematic reports of findings within 24-48 h. The main items evaluated were the detection of retinal abnormalities and the relationship between retinal findings and demographic data such as age and sex. RESULTS: A total of 19,881 workers were evaluated in 52 centers. Mean age was 41.1 years old, 43.9% men and 56.1% women. Mean duration of the test was around 2 min. Of the workers, 7.8% presented abnormalities in retinal fundus images, being the main findings choroidal nevus (2.4%), macular pigment abnormalities (1.5%), glaucomatous optic disc (1.2%), and macular signs of high myopia (1.1%). The presence of abnormalities was associated with greater age, being 5%, 7.9%, 12.6%, and 19.7% in workers less than 40 years, from 40 to 49, 50-59, and ≥ 60 years (p < 0.05), respectively. Men had more abnormalities in retinal fundus images than women (8.6 vs. 7.2; p < 0.05 RR: 1.2; CI 1092-1322). CONCLUSIONS: Mass screening of retinal and optic disc abnormalities during occupational health routine checkups is a feasible, quick, and efficient tool for early detection of potential vision-threatening disease markers.

Prader-Willi Syndrome in children: Quality of life and caregiver burden.

Prader-Willi syndrome is a complex condition requiring constant care and supervision of the affected child. AIM: To evaluate quality of life and caregiver burden in children with Prader-Willi syndrome. METHODS: All children with Prader-Willi syndrome, attending a tertiary referral centre, were invited to participate (n = 44). Quality of life was evaluated using the PedsQL questionnaire. Family impact modules and parent proxy reports evaluated the impact on the quality of life of the child and family. Additional challenges were captured using a burden questionnaire. RESULTS: Nineteen children participated. Median age was 7.9 years (0.6-18.1 years). Majority were female (n = 14, 74%). Median age at diagnosis was 2.5 weeks (range birth-2 years 8 months). Growth hormone treatment was in place for the majority (n = 14, 74%). Increased weight and age were identified as significantly impacting on family functioning and relationships. Parents perceived increased weight and age to have a significant negative impact on their child's psychosocial health and social functioning. Caregivers of children >12 years reported an increased burden of care. Disruption to routines, restriction of social activities and psychological difficulties were reported as increasing caregiver burden. CONCLUSION: Prader-Willi syndrome impacts significantly on quality of life for both the affected child and the family.

Dietary intake and growth in children with Prader-Willi syndrome.

BACKGROUND: The management of Prader-Willi Syndrome (PWS) requires strict dietary supervision to prevent obesity, avoid micronutrient deficiencies and ensure optimal growth. The present study aimed to examine the growth and dietary intake of children with PWS. METHODS: All children with genetically confirmed PWS attending Children's Health Ireland (CHI) at Tallaght (n = 44) were invited to participate. Anthropometry was performed and body composition measured using bioelectrical impedance analysis. Three-day food diaries were used to evaluate dietary intake and the presence of early feeding issues was assessed. Serum haemoglobin, ferritin and vitamin D levels were measured. RESULTS: Nineteen children participated, with a mean (range) age of 7.6 (0.6-18.1) years. Most were female (n = 14, 74%). Twenty-percent (n = 3) were underweight, 60% (n = 9) were healthy weight, n = 1 was overweight and n = 2 were obese. Mean (range) percentage body fat was 25.7% (10%-40%). Eigthy-three percent reported early feeding issues. Ninety-four percent (n = 16) achieved ≤ 100% of estimated average requirement (EAR) for energy. Mean daily energy intake for ≤ 5 years old was 722 kcal (9 kcal cm-1 /72-112% EAR); for those ≥ 12 years, it was 1203 kcal (8.3 kcal cm-1 /41%-82% EAR). Suboptimal calcium, vitamin D, iron, zinc and fibre intake was evident. Iron deficiency anaemia and vitamin D insufficiency occurred in two children. CONCLUSIONS: The present study provides the first Irish data for PWS and shows that energy intake does not appear to be excessive, with four in five patients being underweight or of a normal BMI. Suboptimal dietary intake of several micronutrients was evident and biochemical nutrient deficiencies were present.

Disease detection at the 48-month exit round of the HPV FOCAL cervical cancer screening trial in women per-protocol eligible for routine screening.

HPV FOCAL is a randomized control trial of cervical cancer screening. The intervention arm received baseline screening for high-risk human papillomavirus (HPV) and the control arm received liquid-based cytology (LBC) at baseline and 24 months. Both arms received 48-month exit HPV and LBC cotesting. Exit results are presented for per-protocol eligible (PPE) screened women. Participants were PPE at exit if they had completed all screening and recommended follow-up and had not been diagnosed with cervical intraepithelial neoplasia Grade 2 or worse (CIN2+) earlier in the trial. Subgroups were identified based upon results at earlier trial screening. There were 9,457 and 9,552 and women aged 25-65 randomized to control and intervention and 7,448 (77.8%) and 8,281 (86.7%), respectively, were PPE and screened. Exit cotest results were similar (p = 0.11) by arm for PPE and the relative rate (RR) of CIN2+ for intervention vs. control was RR = 0.83 (95% CI: 0.56-1.23). The RR for CIN2+ comparing intervention women baseline HPV negative to control women with negative cytology at baseline and at 24 months, was 0.68 (95% CI: 0.43-1.06). PPE women who had a negative or CIN1 colposcopy in earlier rounds had elevated rates (per 1,000) of CIN2+ at exit, control 31 (95% CI: 14-65) and intervention 43 (95% CI: 25-73). Among PPE women HPV negative at exit LBC cotesting identified little CIN2+, Rate = 0.3 (95% CI: 0.1-0.7). This per-protocol analysis found that screening with HPV using a 4-year interval is as safe as LBC with a 2-year screening interval. LBC screening in HPV negative women at exit identified few additional lesions.

Transcriptome analysis of responses in Brachypodium distachyon overexpressing the BdbZIP26 transcription factor.

BACKGROUND: Biotic and abiotic stresses are the major cause of reduced growth, persistence, and yield in agriculture. Over the past decade, RNA-Sequencing and the use of transgenics with altered expression of stress related genes have been utilized to gain a better understanding of the molecular mechanisms leading to salt tolerance in a variety of species. Identification of transcription factors that, when overexpressed in plants, improve multiple stress tolerance may be valuable for crop improvement, but sometimes overexpression leads to deleterious effects during normal plant growth. RESULTS: Brachypodium constitutively expressing the BdbZIP26:GFP gene showed reduced stature compared to wild type plants (WT). RNA-Seq analysis comparing WT and bZIP26 transgenic plants revealed 7772 differentially expressed genes (DEGs). Of these DEGs, 987 of the DEGs were differentially expressed in all three transgenic lines. Many of these DEGs are similar to those often observed in response to abiotic and biotic stress, including signaling proteins such as kinases/phosphatases, calcium/calmodulin related proteins, oxidases/reductases, hormone production and signaling, transcription factors, as well as disease responsive proteins. Interestingly, there were many DEGs associated with protein turnover including ubiquitin-related proteins, F-Box and U-box related proteins, membrane proteins, and ribosomal synthesis proteins. Transgenic and control plants were exposed to salinity stress. Many of the DEGs between the WT and transgenic lines under control conditions were also found to be differentially expressed in WT in response to salinity stress. This suggests that the over-expression of the transcription factor is placing the plant in a state of stress, which may contribute to the plants diminished stature. CONCLUSION: The constitutive expression of BdbZIP26:GFP had an overall negative effect on plant growth and resulted in stunted plants compared to WT plants under control conditions, and a similar response to WT plants under salt stress conditions. The results of gene expression analysis suggest that the transgenic plants are in a constant state of stress, and that they are trying to allocate resources to survive.

Global Prison Health Care Governance and Health Equity: A Critical Lack of Evidence.

The large and growing population of people who experience incarceration makes prison health an essential component of public health and a critical setting for reducing health inequities. People who experience incarceration have a high burden of physical and mental health care needs and have poor health outcomes. Addressing these health disparities requires effective governance and accountability for prison health care services, including delivery of quality care in custody and effective integration with community health services.Despite the importance of prison health care governance, little is known about how prison health services are structured and funded or the methods and processes by which they are held accountable. A number of national and subnational jurisdictions have moved prison health care services under their ministry of health, in alignment with recommendations by the World Health Organization and the United Nations Office on Drugs and Crime. However, there is a critical lack of evidence on current governance models and an urgent need for evaluation and research, particularly in low- and middle-income countries.Here we discuss why understanding and implementing effective prison health governance models is a critical component of addressing health inequities at the global level.

Social Determinants of Health and Retention in HIV Care Among Recently Incarcerated Women Living with HIV in Canada.

Women living with HIV (WLWH) are over-represented in corrections in Canada, yet little is known about women's experiences post-release. We used CHIWOS cross-sectional data from WLWH to estimate associations between social determinants of health and HIV-related care outcomes among WLWH with recent (within past year) or ever (before past year) incarceration experience. Lifetime incarceration prevalence was 36.9% (6.5% recent; 30.4% ever), with significant differences by province of residence (British Columbia: 10% recent; 52% ever; Ontario: 5%; 24%; Quebec: 6%; 22%; p < 0.001). In adjusted multinomial logistic regression analyses, compared with never incarcerated, recent incarceration was associated with Indigenous ancestry, lower annual income (< $20,000 CAD), unstable housing, current sex work, injection drug use (IDU), and sub-optimal antiretroviral therapy (ART) adherence, while ever incarceration was associated with current sex work, IDU, and experiencing adulthood violence. Our findings have implications regarding supports needed by WLWH in the post-release period, including ART adherence and achieving health and social goals.

Violence and other social structural factors linked to incarceration for women living with HIV in Metro Vancouver: need for trauma-informed HIV care in prisons and post-Release.

Despite women living with HIV (WLWH) being disproportionately criminalized and overrepresented within correctional facilities, there remains limited longitudinal research with WLWH examining factors that make WLWH vulnerable to incarceration. Data are drawn from SHAWNA (Sexual health and HIV/AIDS: Women's Longitudinal Needs Assessment), a community-based research cohort with cisgender and transgender WLWH in Metro Vancouver, Canada. Multivariable logistic regression using generalized estimating equations (GEE) and an exchangeable working correlation matrix was used to prospectively model correlates of recent incarceration exposure over a seven-year period. Amongst 289 WLWH, 76% had been incarcerated in their lifetime, and 17% had experienced recent incarceration. In multivariable GEE analysis, younger age (AOR: 0.92 per year older, 95% CI: 0.89-0.96), recent homelessness (AOR: 2.81, 95% CI: 1.46-5.41), recent gender-based (physical and/or sexual) violence (AOR: 2.26, 95% CI: 1.20-4.22) and recent opioid use (AOR: 1.83, 95% CI: 1.00-3.36), were significantly associated with recent incarceration. Lifetime exposure to gender-based violence by police (AOR: 1.97, CI: 0.97-4.02) was marginally associated with increased odds of recent incarceration. This research suggests a critical need for trauma-informed interventions for WLWH during and following incarceration. Interventions must be gender specific, include housing and substance use supports, and address the impact of gender-based violence.

Protein Phosphatases in G1 Regulation.

Eukaryotic cells make the decision to proliferate, to differentiate or to cease dividing during G1, before passage through the restriction point or Start. Keeping cyclin-dependent kinase (CDK) activity low during this period restricts commitment to a new cell cycle and is essential to provide the adequate timeframe for the sensing of environmental signals. Here, we review the role of protein phosphatases in the modulation of CDK activity and as the counteracting force for CDK-dependent substrate phosphorylation, in budding and fission yeast. Moreover, we discuss recent findings that place protein phosphatases in the interface between nutritional signalling pathways and the cell cycle machinery.

Public views and attitudes about municipal waste management: Empirical evidence from Athens, Greece.

One of the major problems of modern cities is waste management. Cooperation and active public participation are key elements in the effective implementation of waste management programs. The purpose of this work is to investigate the views and attitudes of Athens residents towards recycling, composting and the operation of green centers, which are the key elements of solid waste management as it follows from the recently updated National Waste Management Plan. A structured questionnaire was designed and addressed to the residents of Athens. According to the main findings, half of the respondents are involved in recycling, and the majority of the respondents are willing to participate in future composting programs and have a positive opinion about the operation of green centers. The main obstacle for their further participation is their hesitation regarding the proper operation of the programs (recycling, composting, green centers). There is a need to build up the trust between citizens and the state. Active public involvement is required to successfully implement municipal solid waste strategies during all the phases (planning, siting and operation) in order to ensure public acceptance. In addition, targeted information and awareness campaigns can also contribute to this aim.