Denaturing purifications demonstrate that PRC2 and other widely reported chromatin proteins do not appear to bind directly to RNA in vivo.

Polycomb repressive complex 2 (PRC2) is reported to bind to many RNAs and has become a central player in reports of how long non-coding RNAs (lncRNAs) regulate gene expression. Yet, there is a growing discrepancy between the biochemical evidence supporting specific lncRNA-PRC2 interactions and functional evidence demonstrating that PRC2 is often dispensable for lncRNA function. Here, we revisit the evidence supporting RNA binding by PRC2 and show that many reported interactions may not occur in vivo. Using denaturing purification of in vivo crosslinked RNA-protein complexes in human and mouse cell lines, we observe a loss of detectable RNA binding to PRC2 and chromatin-associated proteins previously reported to bind RNA (CTCF, YY1, and others), despite accurately mapping bona fide RNA-binding sites across others (SPEN, TET2, and others). Taken together, these results argue for a critical re-evaluation of the broad role of RNA binding to orchestrate various chromatin regulatory mechanisms.

De novo mapping of α-helix recognition sites on protein surfaces using unbiased libraries.

The α-helix is one of the most common protein surface recognition motifs found in nature, and its unique amide-cloaking properties also enable α-helical polypeptide motifs to exist in membranes. Together, these properties have inspired the development of α-helically constrained (Helicon) therapeutics that can enter cells and bind targets that have been considered "undruggable", such as protein-protein interactions. To date, no general method for discovering α-helical binders to proteins has been reported, limiting Helicon drug discovery to only those proteins with previously characterized α-helix recognition sites, and restricting the starting chemical matter to those known α-helical binders. Here, we report a general and rapid screening method to empirically map the α-helix binding sites on a broad range of target proteins in parallel using large, unbiased Helicon phage display libraries and next-generation sequencing. We apply this method to screen six structurally diverse protein domains, only one of which had been previously reported to bind isolated α-helical peptides, discovering 20 families that collectively comprise several hundred individual Helicons. Analysis of 14 X-ray cocrystal structures reveals at least nine distinct α-helix recognition sites across these six proteins, and biochemical and biophysical studies show that these Helicons can block protein-protein interactions, inhibit enzymatic activity, induce conformational rearrangements, and cause protein dimerization. We anticipate that this method will prove broadly useful for the study of protein recognition and for the development of both biochemical tools and therapeutics for traditionally challenging protein targets.

What Are the Experiences of People with COPD Using Activity Monitors?: A Qualitative Scoping Review.

Physical activity monitoring technology (e.g. smartphone apps or wearables) can objectively record physical activity levels, potentially support interventions to increase activity levels, and support the self-management of Chronic Obstructive Pulmonary Disease (COPD). Insight into patients' experiences of monitoring physical activity is needed to inform future healthcare practice and policy utilizing this technology to support long-term positive health behavior change. This scoping review aimed to explore the experiences of using technology for monitoring physical activity among people with COPD. The Joanna Briggs Institute scoping review methodological framework was used. Relevant scientific databases (CINAHL Complete, MEDLINE, PsycINFO, SPORTDiscus, Cochrane Library and Scopus) were searched from 1st January 2016 to 16th March 2021. Thematic synthesis was used to analyze the data. Twelve studies exploring the experiences of people with COPD using technology for monitoring physical activity were included in the synthesis. Seven themes were developed and summarize experiences: 1) Monitoring and keeping track of their activity and health, 2) Supporting motivation to be active, 3) Acceptability of the device, 4) Experiencing technical issues with the device, 5) Setting appropriate and achievable goals for their health condition, 6) Integrating the device into their life and daily routine, and 7) Perceived physical and psychological benefits of using the device. Further high-quality research is needed to understand the experiences of people with COPD using technology to monitor physical activity in everyday life and better self-manage their health condition. Supporting people with COPD to monitor their physical activity could enable them to better self-manage their health condition.

Impact of type 2 diabetes on hospitalization and mortality in people with malignancy.

AIM: To compare the characteristics of and outcomes for people with malignancies with and without a co-diagnosis of diabetes. METHODS: Emergency department and hospital discharge data from a single centre for the period between 1 January 2015 and 31 December 2017 were used to identify people with a diagnosis of a malignancy and diabetes. Multivariate Cox regression models were used to estimate the effect of diabetes on all-cause mortality. A truncated negative binomial regression model was used to assess the impact of diabetes on length of hospital inpatient stay. Prentice-Williams-Peterson total time models were used to assess the effect of diabetes on number of emergency department re-presentations and inpatient re-admissions. RESULTS: Of 7004 people identified with malignancies, 1195 (17.1%) were also diagnosed with diabetes. A diagnosis of diabetes was associated with a greater number of inpatient re-admissions [adjusted hazard ratio 1.13 (95% CI 1.03, 1.24)], a greater number of emergency department re-presentations [adjusted hazard ratio 1.13 (95% CI 1.05, 1.22)] and longer length of stay [adjusted incidence rate ratio 1.14 (95% CI 1.04, 1.25)]. A co-diagnosis of diabetes was also associated with a 48% increased risk of all-cause mortality [adjusted hazard ratio 1.48 (95% CI 1.22-1.76)]. CONCLUSIONS: People with malignancies and diabetes had significantly more emergency department presentations, more inpatient admissions, longer length of hospital stay and higher rates of all-cause mortality compared to people with a malignancy without diabetes.

Exosomes derived from induced vascular progenitor cells promote angiogenesis in vitro and in an in vivo rat hindlimb ischemia model.

Induced vascular progenitor cells (iVPCs) were created as an ideal cell type for regenerative medicine and have been reported to positively promote collateral blood flow and improve cardiac function in a rat model of myocardial ischemia. Exosomes have emerged as a novel biomedicine that mimics the function of the donor cells. We investigated the angiogenic activity of exosomes from iPVCs (iVPC-Exo) as a cell-free therapeutic approach for ischemia. Exosomes from iVPCs and rat aortic endothelial cells (RAECs) were isolated using a combination of ultrafiltration and size-exclusion chromatography. Nanoparticle tracking analysis revealed that exosome isolates fell within the exosomal diameter (<150 nm). These exosomes contained known markers Alix and TSG101, and their morphology was validated using transmission electron microscopy. When compared with RAECs, iVPCs significantly increased the secretion of exosomes. Cardiac microvascular endothelial cells and aortic ring explants were pretreated with RAEC-Exo or iVPC-Exo, and basal medium was used as a control. iVPC-Exo exerted an in vitro angiogenic effect on the proliferation, tube formation, and migration of endothelial cells and stimulated microvessel sprouting in an ex vivo aortic ring assay. Additionally, iVPC-Exo increased blood perfusion in a hindlimb ischemia model. Proangiogenic proteins (pentraxin-3 and insulin-like growth factor-binding protein-3) and microRNAs (-143-3p, -291b, and -20b-5p) were found to be enriched in iVPC-Exo, which may mediate iVPC-Exo induced vascular growth. Our findings demonstrate that treatment with iVPC-Exo promotes angiogenesis in vitro, ex vivo, and in vivo. Collectively, these findings indicate a novel cell-free approach for therapeutic angiogenesis.NEW & NOTEWORTHY The results of this work demonstrate exosomes as a novel physiological mechanism by which induced vascular progenitor cells exert their angiogenic effect. Moreover, angiogenic cargo of proteins and microRNAs may define the biological contributors in activating endothelial cells to form a new capillary plexus for ischemic vascular diseases.

Phosphorylation of synaptic GTPase-activating protein (synGAP) by polo-like kinase (Plk2) alters the ratio of its GAP activity toward HRas, Rap1 and Rap2 GTPases.

SynGAP is a Ras and Rap GTPase-activating protein (GAP) found in high concentration in the postsynaptic density (PSD) fraction from mammalian forebrain where it binds to PDZ domains of PSD-95. Phosphorylation of pure recombinant synGAP by Ca2+/calmodulin-dependent protein kinase II (CaMKII) shifts the balance of synGAP's GAP activity toward inactivation of Rap1; whereas phosphorylation by cyclin-dependent kinase 5 (CDK5) has the opposite effect, shifting the balance toward inactivation of HRas. These shifts in balance contribute to regulation of the numbers of surface AMPA receptors, which rise during synaptic potentiation (CaMKII) and fall during synaptic scaling (CDK5). Polo-like kinase 2 (Plk2/SNK), like CDK5, contributes to synaptic scaling. These two kinases act in concert to reduce the number of surface AMPA receptors following elevated neuronal activity by tagging spine-associated RapGAP protein (SPAR) for degradation, thus raising the level of activated Rap. Here we show that Plk2 also phosphorylates and regulates synGAP. Phosphorylation of synGAP by Plk2 stimulates its GAP activity toward HRas by 65%, and toward Rap1 by 16%. Simultaneous phosphorylation of synGAP by Plk2 and CDK5 at distinct sites produces an additive increase in GAP activity toward HRas (∼230%) and a smaller, non-additive increase in activity toward Rap1 (∼15%). Dual phosphorylation also produces an increase in GAP activity toward Rap2 (∼40-50%), an effect not produced by either kinase alone. As we previously observed for CDK5, addition of Ca2+/CaM causes a substrate-directed doubling of the rate and stoichiometry of phosphorylation of synGAP by Plk2, targeting residues also phosphorylated by CaMKII. In summary, phosphorylation by Plk2, like CDK5, shifts the ratio of GAP activity of synGAP to produce a greater decrease in active Ras than in active Rap, which would produce a shift toward a decrease in the number of surface AMPA receptors in neuronal dendrites.

Marteilia refringens and Marteilia pararefringens sp. nov. are distinct parasites of bivalves and have different European distributions.

Marteilia refringens causes marteiliosis in oysters, mussels and other bivalve molluscs. This parasite previously comprised two species, M. refringens and Marteilia maurini, which were synonymized in 2007 and subsequently referred to as M. refringens 'O-type' and 'M-type'. O-type has caused mass mortalities of the flat oyster Ostrea edulis. We used high throughput sequencing and histology to intensively screen flat oysters and mussels (Mytilus edulis) from the UK, Sweden and Norway for infection by both types and to generate multi-gene datasets to clarify their genetic distinctiveness. Mussels from the UK, Norway and Sweden were more frequently polymerase chain reaction (PCR)-positive for M-type (75/849) than oysters (11/542). We did not detect O-type in any northern European samples, and no histology-confirmed Marteilia-infected oysters were found in the UK, Norway and Sweden, even where co-habiting mussels were infected by the M-type. The two genetic lineages within 'M. refringens' are robustly distinguishable at species level. We therefore formally define them as separate species: M. refringens (previously O-type) and Marteilia pararefringens sp. nov. (M-type). We designed and tested new Marteilia-specific PCR primers amplifying from the 3' end of the 18S rRNA gene through to the 5.8S gene, which specifically amplified the target region from both tissue and environmental samples.

Asymmetric changes in circulating insulin levels after an increase compared with a reduction in insulin pump basal rate in people with Type 1 diabetes.

AIMS: To investigate circulating insulin profiles after a clinically relevant insulin pump basal rate increase vs a reduction, and the associated glucose responses. METHODS: A cohort of 12 adults with Type 1 diabetes undertook this two-stage university hospital study using Accu-Chek pumps (Roche Diagnostics, Mannheim, Germany) and insulin aspart. An insulin basal rate change of 0.2 unit/h (increase in first stage, reduction in second stage) was implemented at ~09:30 h, after a single overnight basal rate (without bolus insulin), while fasting participants rested. Frequent venous samples for the assessment of plasma free insulin, glucose and cortisol were collected from 60 min before until 300 min after rate change. The primary outcome was time to steady-state insulin. RESULTS: The 0.2-unit/h rate change represented a mean ± sd alteration of 23 ± 6%. After the rate increase, the median (interquartile range) times to 80% and 90% steady-state insulin were 170 (45) min and 197 (87) min, respectively. By contrast, after rate reduction, 80% steady-state insulin was not achieved. After the rate increase, mean ± se insulin levels increased by 4.3 ± 3.1%, 12.0 ± 2.9% and 25.6 ± 2.6% at 60, 120 and 300 min, respectively (with no significant difference until 180 min). After the rate reduction, insulin decreased by 8.3 ± 3.0% at 300 min (with no significant difference until 300 min). After rate reduction, glucose levels paradoxically declined by 17.4 ± 3.7% after 300 min; cortisol levels also fell during observation (P = 0.0003). CONCLUSIONS: The time to circulating insulin change after a 0.2-unit/h basal rate change was substantial, and was greater after a reduction than after an increase. Counter-regulatory hormone circadian variation may affect glycaemia when implementing minor changes at low basal rates. Both direction of basal rate change, and time of day, warrant consideration when anticipating the clinical effects of basal rate changes.

Phosphorylation of synaptic GTPase-activating protein (synGAP) by Ca2+/calmodulin-dependent protein kinase II (CaMKII) and cyclin-dependent kinase 5 (CDK5) alters the ratio of its GAP activity toward Ras and Rap GTPases.

synGAP is a neuron-specific Ras and Rap GTPase-activating protein (GAP) found in high concentrations in the postsynaptic density (PSD) fraction from the mammalian forebrain. We have previously shown that, in situ in the PSD fraction or in recombinant form in Sf9 cell membranes, synGAP is phosphorylated by Ca(2+)/calmodulin-dependent protein kinase II (CaMKII), another prominent component of the PSD. Here, we show that recombinant synGAP (r-synGAP), lacking 102 residues at the N terminus, can be purified in soluble form and is phosphorylated by cyclin-dependent kinase 5 (CDK5) as well as by CaMKII. Phosphorylation of r-synGAP by CaMKII increases its HRas GAP activity by 25% and its Rap1 GAP activity by 76%. Conversely, phosphorylation by CDK5 increases r-synGAP's HRas GAP activity by 98% and its Rap1 GAP activity by 20%. Thus, phosphorylation by both kinases increases synGAP activity; CaMKII shifts the relative GAP activity toward inactivation of Rap1, and CDK5 shifts the relative activity toward inactivation of HRas. GAP activity toward Rap2 is not altered by phosphorylation by either kinase. CDK5 phosphorylates synGAP primarily at two sites, Ser-773 and Ser-802. Phosphorylation at Ser-773 inhibits r-synGAP activity, and phosphorylation at Ser-802 increases it. However, the net effect of concurrent phosphorylation of both sites, Ser-773 and Ser-802, is an increase in GAP activity. synGAP is phosphorylated at Ser-773 and Ser-802 in the PSD fraction, and its phosphorylation by CDK5 and CaMKII is differentially regulated by activation of NMDA-type glutamate receptors in cultured neurons.

Boundary-Layer Effects on Acoustic Transmission Through Narrow Slit Cavities.

We explore the slit-width dependence of the resonant transmission of sound in air through both a slit array formed of aluminum slats and a single open-ended slit cavity in an aluminum plate. Our experimental results accord well with Lord Rayleigh's theory concerning how thin viscous and thermal boundary layers at a slit's walls affect the acoustic wave across the whole slit cavity. By measuring accurately the frequencies of the Fabry-Perot-like cavity resonances, we find a significant 5% reduction in the effective speed of sound through the slits when an individual viscous boundary layer occupies only 5% of the total slit width. Importantly, this effect is true for any airborne slit cavity, with the reduction being achieved despite the slit width being on a far larger scale than an individual boundary layer's thickness. This work demonstrates that the recent prevalent loss-free treatment of narrow slit cavities within acoustic metamaterials is unrealistic.

Non-tuberculous mycobacterial infection in hospitalized children: a case series.

Non-tuberculous mycobacteria (NTM) illness is an emerging life-threatening infection, and paediatric features have not been well studied. The objective of our study was to review the NTM isolates of hospitalized paediatric patients identified at our institution and to describe the characteristics of these cases. Our retrospective chart review from 2010 to 2013 identified 45 patients with 46 positive NTM cultures. Fifteen (33%) patients had received haematopoietic cell transplant, 13 (29%) had cystic fibrosis, and six (13%) were previously healthy. Twenty-seven (59%) NTM isolates were Mycobacterium chelonae/abscessus, 14 (30%) were M. avium intracellulare, and four (9%) were M. immunogenum. The majority (65%) of cases were community-acquired, and 20 (43%) patients were treated as infection. This case series identified a predominance of M. chelonae/abscessus, and includes a substantial number of haematopoietic cell transplant patients, which reflects the changing spectrum of NTM disease as molecular diagnostics improve and quaternary care facilities provide for a larger immunocompromised population.

Herbage intake and milk production of late-lactation dairy cows offered a second-year chicory crop during summer.

Chicory (Cichorum intybus L.) is a summer-active forage herb which has been proposed as an option to increase summer feed supply, increase dry matter intake, nutrient intake, and milk yield from nonirrigated dairy production systems in southern Australia. Dry matter intake, nutrient intake, milk yield, and yield of milk fat and protein of predominantly Holstein-Friesian dairy cows in late lactation consuming 3 herbage-based diets (4 replicates per treatment) were measured. The 3 grazed herbages were second-year chicory (CHIC) and perennial ryegrass (Lolium perenne L.; PRG) monocultures and a mixed sward (~50:50) of chicory and perennial ryegrass (MIX). All diets (CHIC, PRG, and MIX) were supplemented with alfalfa (Medicago sativa L.) hay (5.5kg of DM/cow per day) and an energy-based concentrate pellet (4.0kg of DM/cow per day). There were no significant differences in milk yield (12.0 to 12.6kg/d across the treatments) or the yield of milk fat (539 to 585g/d) and milk protein (433 to 447g/d) between the 3 herbage-based diets. No differences in DMI (17.9 to 19.2kg/d) or estimated metabolizable energy intake (173 to 185MJ/d) were noted between treatments. Estimated metabolizable energy concentrations in the forages on offer were lower in CHIC than PRG (7.6 vs. 8.2MJ/kg of dry matter), but the concentration in consumed herbage was not different (9.1 vs. 9.2MJ/kg of dry matter); as such, potential for increased milk yield in cows offered CHIC was limited. Increased concentration of polyunsaturated fatty acids was observed in chicory herbage compared with perennial ryegrass. This was associated with increased milk conjugated linoleic acid and milk polyunsaturated fatty acids when chicory formed part of the diet (CHIC compared to PRG and MIX). Chicory could be used as an alternative to perennial ryegrass in summer; however, the developmental stage of chicory will influence concentrations of metabolizable energy and neutral detergent fiber and, therefore, intake and milk production responses compared with perennial ryegrass.

PDZ affinity chromatography: a general method for affinity purification of proteins based on PDZ domains and their ligands.

PDZ (PSD-95, DiscsLarge, ZO1) domains function in nature as protein binding domains within scaffold and membrane-associated proteins. They comprise ∼90 residues and make specific, high affinity interactions with complementary C-terminal peptide sequences, with other PDZ domains, and with phospholipids. We hypothesized that the specific, strong interactions of PDZ domains with their ligands would make them well suited for use in affinity chromatography. Here we describe a novel affinity chromatography method applicable for the purification of proteins that contain PDZ domain-binding ligands, either naturally or introduced by genetic engineering. We created a series of affinity resins comprised of PDZ domains from the scaffold protein PSD-95, or from neuronal nitric oxide synthase (nNOS), coupled to solid supports. We used them to purify heterologously expressed neuronal proteins or protein domains containing endogenous PDZ domain ligands, eluting the proteins with free PDZ domain peptide ligands. We show that Proteins of Interest (POIs) lacking endogenous PDZ domain ligands can be engineered as fusion products containing C-terminal PDZ domain ligand peptides or internal, N- or C-terminal PDZ domains and then can be purified by the same method. Using this method, we recovered recombinant GFP fused to a PDZ domain ligand in active form as verified by fluorescence yield. Similarly, chloramphenicol acetyltransferase (CAT) and ß-Galactosidase (LacZ) fused to a C-terminal PDZ domain ligand or an N-terminal PDZ domain were purified in active form as assessed by enzymatic assay. In general, PDZ domains and ligands derived from PSD-95 were superior to those from nNOS for this method. PDZ Domain Affinity Chromatography promises to be a versatile and effective method for purification of a wide variety of natural and recombinant proteins.

Milk production and composition of mid-lactation cows consuming perennial ryegrass-and chicory-based diets.

Dry matter intakes (DMI), nutrient selection, and milk production responses of dairy cows grazing 3 herbage-based diets offered at 2 allowances were measured. The 2 allowances were 20 (low) and 30 (high) kg of dry matter (DM)/cow per day and these were applied to 3 herbage types: perennial ryegrass (PRG) and chicory (CHIC+) monocultures and a mixed sward of chicory and perennial ryegrass (MIX). The CHIC+ diet was supplemented with alfalfa hay (approximately 2 kg of DM/cow per day) to maintain dietary neutral detergent fiber (NDF) concentration and all diets were supplemented with energy-based pellets (6 kg of DM/cow per day). Holstein-Friesian dairy cows averaging 136 ± 30 d in milk were allocated to 4 replicates of the 6 treatments using stratified randomization procedures. Cows were adapted to their experimental diets over a 14-d period, with measurements of DMI, milk yield, and composition conducted over the following 10 d. Herbage DMI was lowest (12.8 vs. 14.0 kg of DM/d) for CHIC+ compared with the MIX and PRG, although total forage intake (grazed herbage plus hay) was similar (14.0 to 15.0 kg of DM/d) across the 3 treatments. Milk production, milk protein, and milk fat concentrations were not different between herbage types. Grazed herbage DMI increased with increasing herbage allowance and this was associated with increased milk protein concentration (3.23 to 3.34%) and total casein production (41.7 to 43.6 mg/g). Concentrations of polyunsaturated fatty acids in milk fat, particularly linoleic acid, were increased in milk from cows offered the CHIC+ or the MIX diets, indicating potential benefits of chicory herbage on milk fatty acid concentrations. Although feeding CHIC+ or MIX did not increase milk yield, these herbage types could be used as an alternative to perennial ryegrass pasture in spring.

Multicenter Australian trial of islet transplantation: improving accessibility and outcomes.

Whilst initial rates of insulin independence following islet transplantation are encouraging, long-term function using the Edmonton Protocol remains a concern. The aim of this single-arm, multicenter study was to evaluate an immunosuppressive protocol of initial antithymocyte globulin (ATG), tacrolimus and mycophenolate mofetil (MMF) followed by switching to sirolimus and MMF. Islets were cultured for 24 h prior to transplantation. The primary end-point was an HbA1c of <7% and cessation of severe hypoglycemia. Seventeen recipients were followed for ≥ 12 months. Nine islet preparations were transported interstate for transplantation. Similar outcomes were achieved at all three centers. Fourteen of the 17 (82%) recipients achieved the primary end-point. Nine (53%) recipients achieved insulin independence for a median of 26 months (range 7-39 months) and 6 (35%) remain insulin independent. All recipients were C-peptide positive for at least 3 months. All subjects with unstimulated C-peptide >0.2 nmol/L had cessation of severe hypoglycemia. Nine of the 17 recipients tolerated switching from tacrolimus to sirolimus with similar graft outcomes. There was a small but significant reduction in renal function in the first 12 months. The combination of islet culture, ATG, tacrolimus and MMF is a viable alternative for islet transplantation.

Views and experiences of healthcare practitioners supporting people with COPD who have used activity monitors: "More than just steps".

INTRODUCTION: Activity monitors (apps and wearables) are increasingly used by the general population, including people with Chronic Obstructive Pulmonary Disease (COPD). There is potential for activity monitors to support increases in physical activity for people with COPD and healthcare practitioners (HCPs) are likely to be key in supporting their use, but little is currently known about HCPs' views or experiences. This qualitative research aimed to explore HCPs' views and experiences of supporting people with COPD who have used activity monitors. METHODS: Seventeen semi-structured telephone or online interviews were conducted with HCPs between September 2020 and May 2021. HCPs included two nurses, an occupational therapist, a physician, and 13 physiotherapists. Participants were recruited via social media advertisements. They all had experience of supporting people with COPD who had used activity monitors. Interviews were analysed using reflexive thematic analysis. FINDINGS: Four themes were developed highlighting the challenges and benefits of HCPs supporting patients with using activity monitors and utilising patient-collected activity data; 1) Skills and experience are needed to increase accessibility and engagement, 2) Objectively monitored physical activity can support exercise prescription, 3) Applications of activity monitors vary across different settings, and 4) Support is needed for future use of activity monitors. DISCUSSION: HCPs recognised the potential for activity monitors to impact patients' ability to self-manage their COPD. However, there is a lack of guidance and information to support integration within practice. Future research is needed to co-develop information and guidelines for people with COPD and HCPs.

A Systematic Review of Inequalities in the Mental Health Experiences of Black African, Black Caribbean and Black-mixed UK Populations: Implications for Action.

BACKGROUND: Measurable differences in the experience and treatment of mental health conditions have been found to exist between different racial categories of community groups. The objective of this research was to review the reported mental health of Black African-Caribbean communities in the UK, determinants of mental health, and interventions to enhance their experiences of mental health services. METHOD: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement was applied. To be included, papers must be published in a peer reviewed journal; report on adult populations (over 18) from any of Black African, Black Caribbean or Black mixed people in the UK; and assess (quantitative), or discuss (qualitative) mental health experiences, determinants of mental health, or interventions intended to enhance experiences of mental health services among the target population. The aims, inclusion criteria, data extraction, and data quality evaluation were specified in advance. Searches were conducted using EBSCO (PsychInfo; MEDLINE; CINAHL Plus; psychology and behavioural sciences collection). The search strategy included search terms relating to the aim. Risk of bias was assessed using a standard tool, records were organised using Endnote, and data were extracted and synthesised using Microsoft Excel. RESULTS: Thirty-six studies were included, of which 26 were quantitative and six reported exclusively on Black participants. Black populations were less likely to access mental health support via traditional pathways due to stigma and mistrust of mental health services. Black Africans especially, sought alternative help from community leaders, which increased the likelihood of accessing treatment at the point of crisis or breakdown, which in turn increased risk of being detained under the Mental Health Act and via the criminal justice system. DISCUSSION: Findings suggest a cycle of poor mental health, coercive treatment, stigma, and mistrust of services as experienced by Black communities. Evidence was limited by poorly defined ethnic categories, especially where Black populations were subsumed into one category. It is recommended that mental health services work collaboratively with cultural and faith communities in supporting Black people to cope with mental illness, navigate mental health pathways, and provide culturally appropriate advice. Protocol Registration Number PROSPERO CRD42021261510.

Conservative approach to the management of morbidly adherent placentae.

OBJECTIVE: To determine the effect of conservative management of morbidly adherent placentae on maternal morbidity and mortality and to review management options METHODS: All case notes of patients with placenta accreta and percreta between June 2008 and August 2010 were studied retrospectively. RESULTS: Eight placentae percretae and 4 placentae accretae were identified out of a total of 11,358 deliveries.All 12 patients underwent caesarean section. Placentae percretae were intentionally left in situ. Interventional radiology was used in these cases. There was one emergency hysterectomy for massive obstetric haemorrhage,one case of disseminated intravascular coagulation,one case of early sepsis and 3 cases of delayed sepsis.Average blood loss was 2490 ml with the mean volume transfused being 1425 ml. The mean hospital stay was 7 days and 2 patients were admitted to intensive care. One patient was readmitted with sepsis complicated by a utero-cutaneous fistula (complete placenta praevia).Another patient required re-embolisation 5 months post delivery for persistent haemorrhage. No ureteric or bladder injuries occurred. CONCLUSIONS: Conservative management of placenta percreta is an alternative to caesarean hysterectomy. It is associated with lower maternal morbidity rates.However, monitoring for sepsis and secondary postpartum haemorrhage is essential. Rare complications such as utero-cutanus fistulae may occur.