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Delaware Contraceptive Access Now was a statewide contraceptive access program implemented in Delaware between 2015 and 2020. We evaluated the association of the program with contraceptive initiation in Delaware’s Medicaid program using a difference-in-differences design that compared changes in Delaware to changes in Maryland. Results suggest that program implementation was associated with increased initiation of long-acting reversible methods, particularly among adolescent patients aged 15 to 18 years. We found less-consistent evidence for changes to any contraceptive method. (Am J Public Health. 2022;112(S5):S537–S540. https://doi.org/10.2105/AJPH.2022.306938 )

Delaware Contraceptive Access Now was a statewide contraceptive access program implemented in Delaware between 2015 and 2020. We evaluated the association of the program with contraceptive initiation in Delaware's Medicaid program using a difference-in-differences design that compared changes in Delaware to changes in Maryland. Results suggest that program implementation was associated with increased initiation of long-acting reversible methods, particularly among adolescent patients aged 15 to 18 years. We found less-consistent evidence for changes to any contraceptive method. (Am J Public Health. 2022;112(S5):S537-S540. https://doi.org/10.2105/AJPH.2022.306938)

Myelin is required for the function of neuronal axons in the central nervous system, but the mechanisms that support myelin health are unclear. Although macrophages in the central nervous system have been implicated in myelin health 1 , it is unknown which macrophage populations are involved and which aspects they influence. Here we show that resident microglia are crucial for the maintenance of myelin health in adulthood in both mice and humans. We demonstrate that microglia are dispensable for developmental myelin ensheathment. However, they are required for subsequent regulation of myelin growth and associated cognitive function, and for preservation of myelin integrity by preventing its degeneration. We show that loss of myelin health due to the absence of microglia is associated with the appearance of a myelinating oligodendrocyte state with altered lipid metabolism. Moreover, this mechanism is regulated through disruption of the TGFβ1–TGFβR1 axis. Our findings highlight microglia as promising therapeutic targets for conditions in which myelin growth and integrity are dysregulated, such as in ageing and neurodegenerative disease 2 , 3 . Resident microglia in the central nervous system are identified as the specific macrophage population that regulates myelin growth and integrity.

ObjectiveAn international meeting was organised to develop consensus on (1) the landmarks to define the gastro-oesophageal junction (GOJ), (2) the occurrence and pathophysiological significance of the cardiac gland, (3) the definition of the gastro-oesophageal junctional zone (GOJZ) and (4) the causes of inflammation, metaplasia and neoplasia occurring in the GOJZ.DesignClinical questions relevant to the afore-mentioned major issues were drafted for which expert panels formulated relevant statements and textural explanations.A Delphi method using an anonymous system was employed to develop the consensus, the level of which was predefined as ≥80% of agreement. Two rounds of voting and amendments were completed before the meeting at which clinical questions and consensus were finalised.ResultsTwenty eight clinical questions and statements were finalised after extensive amendments. Critical consensus was achieved: (1) definition for the GOJ, (2) definition of the GOJZ spanning 1 cm proximal and distal to the GOJ as defined by the end of palisade vessels was accepted based on the anatomical distribution of cardiac type gland, (3) chemical and bacterial (Helicobacter pylori) factors as the primary causes of inflammation, metaplasia and neoplasia occurring in the GOJZ, (4) a new definition of Barrett’s oesophagus (BO).ConclusionsThis international consensus on the new definitions of BO, GOJ and the GOJZ will be instrumental in future studies aiming to resolve many issues on this important anatomic area and hopefully will lead to better classification and management of the diseases surrounding the GOJ.

Progesterone (P4) is essential for embryo implantation, but the extent to which the pro-gestational effects of P4 depend on the maternal immune compartment is unknown. Here, we investigate whether regulatory T cells (Treg cells) act to mediate luteal phase P4 effects on uterine receptivity in mice. P4 antagonist RU486 administered to mice on days 1.5 and 3.5 postcoitum to model luteal phase P4 deficiency caused fewer CD4 + Foxp3 + Treg cells and impaired Treg functional competence, along with dysfunctional uterine vascular remodeling and perturbed placental development in midgestation. These effects were linked with fetal loss and fetal growth restriction, accompanied by a Th1/CD8-skewed T cell profile. Adoptive transfer at implantation of Treg cells — but not conventional T cells — alleviated fetal loss and fetal growth restriction by mitigating adverse effects of reduced P4 signaling on uterine blood vessel remodeling and placental structure and by restoring maternal T cell imbalance. These findings demonstrate an essential role for Treg cells in mediating P4 effects at implantation and indicate that Treg cells are a sensitive and critical effector mechanism through which P4 drives uterine receptivity to support robust placental development and fetal growth.

Young people in state care, often due to abuse or neglect, have a four-fold increased risk of drug and alcohol use compared to their peers. The SOLID study aimed to investigate the feasibility of a definitive randomised controlled trial, comparing two behaviour change interventions to reduce risky substance use (illicit drugs and alcohol), and improve mental health, in young people in care. We recruited young people in care aged 12-20 years, self-reporting substance use within the previous 12 months and residing in 1 of 6 participating local authority sites in the North East of England. Participants were randomised to either i. Motivational Enhancement Therapy (MET), ii. Social Behaviour and Network Therapy (SBNT) or iii. Control (usual care). All interventions were delivered by trained drug and alcohol workers. Follow-up data were collected 12 months post recruitment. Feasibility for trial progression was compared to pre-specified stop: go criteria (recruitment of 60% of eligible participants, 80% of participants attending 60% of offered sessions and retention of 70% of participants at 12 month follow up). Of 1450 eligible participants, 860 (59%) were screened for drug and alcohol use by social workers, 211 (24.5%) met inclusion criteria for the trial and 112 young people (7.7%) consented and were randomised. Sixty of these 112 participants (54%) completed 12-month follow-up questionnaires. Only 15 out of the 76 (20%) participants allocated to an intervention arm attended any of the offered MET or SBNT sessions. By reference to pre-specified stop: go criteria it is not feasible to conduct a definitive trial for SOLID in its current format. Despite co-designing procedures with staff and young people in care, the screening, referral and treatment pathway did not work here. Future work may require dedicated clinically embedded research resource to evaluate effectiveness of new interventions in services.

Background Important insight into the mechanisms through which gene-environmental interactions cause schizophrenia can be achieved through preclinical studies combining prenatal immune stimuli with disease-related genetic risk modifications. Accumulating evidence associates JNK signalling molecules, including MKK7/ MAP2K7 , with genetic risk. We tested the hypothesis that Map2k7 gene haploinsufficiency in mice would alter the prenatal immune response to the viral mimetic polyriboinosinic-polyribocytidylic acid (polyI:C), specifically investigating the impact of maternal versus foetal genetic variants. Methods PolyI:C was administered to dams (E12.5), and cytokine/chemokine levels were measured 6 h later, in maternal plasma, placenta and embryonic brain. Results PolyI:C dramatically elevated maternal plasma levels of most cytokines/chemokines. Induction of IL-1β, IL-2, IL-10, IL-12, TNF-α and CXCL3 was enhanced, while CCL5 was suppressed, in Map2k7 hemizygous (Hz) dams relative to controls. Maternal polyI:C administration also increased embryonic brain chemokines, influenced by both maternal and embryonic genotype: CCL5 and CXCL10 levels were higher in embryonic brains from Map2k7 dams versus control dams; for CCL5, this was more pronounced in Map2k7 Hz embryos. Placental CXCL10 and CXCL12 levels were also elevated by polyI:C, the former enhanced and the latter suppressed, in placentae from maternal Map2k7 Hzs relative to control dams receiving polyI:C. Conclusions The results demonstrate JNK signalling as a mediator of MIA effects on the foetus. Since both elevated CXCL10 and supressed CXCL12 compromise developing GABAergic interneurons, the results support maternal immune challenge contributing to schizophrenia-associated neurodevelopmental abnormalities. The influence of Map2k7 on cytokine/chemokine induction converges the genetic and environmental aspects of schizophrenia, and the overt influence of maternal genotype offers an intriguing new insight into modulation of embryonic neurodevelopment by genetic risk.

Acute kidney injury (AKI), a common complication in paediatric intensive care units (PICU), is associated with increased morbidity and mortality. In this single centre, prospective, observational cohort study, neutrophil gelatinase-associated lipocalin in urine (uNGAL) and plasma (pNGAL) and renal angina index (RAI), and combinations of these markers, were assessed for their ability to predict severe (stage 2 or 3) AKI in children and young people admitted to PICU. In PICU children and young people had initial and serial uNGAL and pNGAL measurements, RAI calculation on day 1, and collection of clinical data, including serum creatinine measurements. Primary outcomes were severe AKI and renal replacement therapy (RRT). Secondary outcomes were length of stay, hospital acquired infection and mortality. The area under the Receiver Operating Characteristic (ROC) curves and Youden index was used to determine biomarker performance and identify optimum cut-off values. Of 657 children recruited, 104 met criteria for severe AKI (15∙8%) and 47 (7∙2%) required RRT. Severe AKI was associated with increased length of stay, hospital acquired infection, and mortality. The area under the curve (AUC) for severe AKI prediction for Day 1 uNGAL, Day 1 pNGAL and RAI were 0.75 (95% Confidence Interval [CI] 0∙69, 0∙81), 0∙64 (95% CI 0∙56, 0∙72), and 0.73 (95% CI 0∙65, 0∙80) respectively. The optimal combination of measures was RAI and day 1 uNGAL, giving an AUC of 0∙80 for severe AKI prediction (95% CI 0∙71, 0∙88). In this heterogenous PICU cohort, urine or plasma NGAL in isolation had poorer prediction accuracy for severe AKI than in previously reported homogeneous populations. However, when combined together with RAI, they produced good prediction for severe AKI.