Social capital of families of children with neurodevelopmental disabilities in South India.

AIM: To investigate the social capital of families with children with neurodevelopmental disabilities in South India receiving a community-based early intervention (Enabling Inclusion®) program and to explore determinants and associations between social capital and program duration, socio-demographic factors, family empowerment, and caregiver burden. METHOD: Using purposive sampling in a cross-sectional study design, 217 families (n = 71 received short Enabling Inclusion [<5 months]; n = 146 received long Enabling Inclusion [>9 months]) were recruited and completed the Short Adapted Social Capital Tool (SASCAT: cognitive, structural), measures of family empowerment, and caregiver strain. Descriptive statistics, regression, and correlations were used for analyses. RESULTS: In 52.1% of participants, low cognitive and structural social capital was observed. Higher odds of low structural social capital were observed for mothers with primary versus secondary education (adjusted odds ratio [OR] = 0.35; 95% confidence interval [CI] 0.13-0.90; p = 0.029); and caregivers of children with cerebral palsy versus autism (OR = 4.66; 95% CI 1.02-21.21; p = 0.046). Significant associations were found between structural social capital, the child's age, and support group membership (χ2 = 6.29; 4.70; degrees of freedom [df] = 2; 1; p = 0.04; p = 0.02 respectively), as well as between cognitive social capital and other disability in the family (χ2 = 4.62, df = 1, p = 0.03). INTERPRETATION: While program duration was not found to mediate social capital, mother's education and child's diagnosis emerged as key influential factors, warranting their consideration in interventions supporting families of children with neurodevelopmental disabilities in low- and-middle-income countries and elsewhere.

Proinflammatory changes in the maternal circulation, maternal-fetal interface, and placental transcriptome in preterm birth.

BACKGROUND: Preterm birth remains a leading obstetrical complication because of the incomplete understanding of its multifaceted etiology. It is known that immune alterations toward a proinflammatory profile are observed in women with preterm birth, but therapeutic interventions are still lacking because of scarcity of evidence in the integration of maternal and placental interrelated compartments. OBJECTIVE: This study aimed to obtain an integrated view of the maternal and placental contribution to preterm birth compared with normal term pregnancies for an in-depth understanding of the immune/inflammatory involvement, intending to identify novel strategies to mitigate the negative impact of inflammation. STUDY DESIGN: We prospectively recruited 79 women with preterm or term deliveries and collected placentas for RNA sequencing, histologic analyses, and to assess levels of inflammatory mediators. Blood samples were also collected to determine the circulating immune profiles by flow cytometry and to evaluate the circulating levels of inflammatory mediators. RESULTS: Placental transcriptomic analyses revealed 102 differentially expressed genes upregulated in preterm birth, including known and novel targets, which were highly enriched for inflammatory biological processes according to gene ontology analyses. Analysis of maternal immune cells revealed distinct profiles in preterm births vs term births, including an increased percentage of CD3- cells and monocyte subsets and decreased CD3+ cells along with Th17 subsets of CD4+ lymphocytes. Supporting our bioinformatic findings, we found increases in proinflammatory mediators in the plasma, placenta, and fetal membranes (primarily the amnion) of women with preterm birth, such as interleukin-6 and tumor necrosis factor-α. These findings were not distinct between spontaneous and iatrogenic preterm births except at a molecular level where spontaneous preterm birth presented with an elevated inflammatory profile compared with iatrogenic preterm birth. Analysis of placental histology revealed increased structural and inflammatory lesions in preterm vs term births. We found that genes upregulated in placentas with inflammatory lesions have enrichment of proinflammatory pathways. CONCLUSION: This work sheds light on changes within the immune system in preterm birth on multiple levels and compartments to help identify pregnancies at high risk of preterm birth and to discover novel therapeutic targets for preterm birth.

Pain coping skills training un-locks patient-centered pain care during the COVID- 19 lockdown.

BACKGROUND: In 2020, the COVID-19 virus sparked a crisis constituting a nationwide public health emergency that rapidly altered the provision of healthcare services for all Americans. Infectious disease mitigation led to widespread lockdowns of perceived nonessential services, programs, and non-emergent healthcare interventions. This lockdown exacerbated the public health dyad of uncontrolled pain and the opioid epidemic, which was already in a crisis state. Current literature supports the management of uncontrolled pain with a biopsychosocial approach, empowering patients to explore self-care to enhance activities of daily living. Pain Coping Skills Training (PCST) delivers real-life strategies that improve quality of life and strengthen self-efficacy. Self-efficacy has been identified as a patient outcome measure that demonstrates improved patient-perceived function and quality of life despite pain intensity. Studies have shown that nurse practitioners (APRN) are well-positioned to provide PCST to chronic pain sufferers. METHODS: A pretest-posttest design was utilized for this project to enhance pain self- efficacy through an APRN-led community-based intervention. INTERVENTION: Community-dwelling adults treated in a specialty pain management practice were self-selected to participate in a 6-week telehealth delivered PCST Program. This APRN delivered program presented basic pain education and a broad range of evidence-based nonpharmacologic pain management self-care tools. The primary outcome was improved Pain Self-efficacy measured with the pain self-efficacy questionnaire (PSEQ), with secondary outcomes of improved perceived pain intensity and function measured with the pain, enjoyment, and general activity (PEG) scale tracked weekly. RESULTS: Baseline PSEQ and weekly PEG scores were obtained and compared to scores after the program. Collateral data points included confidence in using complementary and alternative nonpharmacologic interventions, satisfaction with the program, and a qualitative patient statement regarding pre-and post-intervention participation. CONCLUSIONS: This project concluded that a Nurse Practitioner delivered PCST program via telehealth technology could provide community-dwelling adults with an intervention that improves pain self-efficacy, enhances self-reported PEG measures, and meets the social distancing requirements that continue to impact patients during the COVID-19 pandemic.

Perceptions of family-centred care among caregivers of children with cerebral palsy in South India: An exploratory study.

BACKGROUND: Parental views and expectations about family-centred care (FCC) need to be understood for its successful implementation. Knowledge of caregiver's perceptions and needs, within their social and cultural context, forms the basis for effective health care partnerships with families. The purpose of this study was to explore perceptions about FCC among caregivers of children with cerebral palsy (CP) in South India. METHOD: Fourteen caregivers of children with CP (aged 4-12 years) living in rural areas of the coastal region of Karnataka, India, participated in this qualitative study. Face-to-face semi-structured interviews were recorded and transcribed for analysis using the framework and hybrid approaches. Thematic mapping of the categories and themes was done to explore relationships about perceptions of FCC. RESULTS: Caregiver's life emerged inductively as a new theme highlighting caregiver's own physical and mental health, family roles and well-being, integrating the onus of care with household responsibilities, limited participation in personal activities and social isolation. The qualitative findings revealed the ubiquity of respectful and trusting relationships with health professionals while expressing paucity of coordinated comprehensive care, sporadic partnerships and opportunities for shared decision-making; desire for receiving specific information related to child's progress and prognosis; and general information on community resources and the need of empowerment and support groups. CONCLUSION: Our study has practical implications for the implementation of FCC within the South Indian context, by recognizing unique caregiver needs and expectations in sync with cultural perspectives towards childhood disability such as societal stigma, values and traditional beliefs; attitudes towards medical professionals; and life stressors and gender responsibilities.

Expanding access to nurse-managed medication for opioid use disorder.

BACKGROUND: Advanced practice registered nurses (APRNs) are increasingly caring for individuals with opioid use disorder. Advances have been made to increase APRN education, outreach, and prescribing privileges, but as demand for medication for opioid use disorder (MOUD) grows, evidence suggests that policy and care barriers inhibit the ability of APRNs to support MOUD. PURPOSE: This paper highlights the significant challenges of expanding access to buprenorphine prescribing by APRNs. FINDINGS: Barriers and recommendations were derived from the culmination of literature review, expert consensus discussions among a diverse stakeholder panel including patient representatives, and feedback from community webinars with care providers. DISCUSSION: We provide an overview of existing care barriers, promising practices, and proposed recommendations to enhance the care of individuals and communities with opioid use disorder.

Barrett's Registry Collaboration of academic centers in Ireland reveals high progression rate of low-grade dysplasia and low risk from nondysplastic Barrett's esophagus: report of the RIBBON network.

Barrett's esophagus (BE) is the main pathological precursor of esophageal adenocarcinoma (EAC). Progression to high-grade dysplasia (HGD) or EAC from nondysplastic BE (NDBE), low-grade dysplasia (LGD) and indefinite for dysplasia (IND) varies widely between population-based studies and specialized centers for many reasons, principally the rigor of the biopsy protocol and the accuracy of pathologic definition. In the Republic of Ireland, a multicenter prospective registry and bioresource (RIBBON) was established in 2011 involving six academic medical centers, and this paper represents the first report from this network. A detailed clinical, endoscopic and pathologic database registered 3,557 patients. BE was defined strictly by both endoscopic evidence of Barrett's epithelium and the presence of specialized intestinal metaplasia (SIM). A prospective web-based database was used to gather information with initial and follow-up data abstracted by a data manager at each site. A total of 2,244 patients, 1,925 with no dysplasia, were included with complete follow-up. The median age at diagnosis was 60.5 with a 2.1:1 male to female ratio and a median follow-up time of 2.7 years (IQR 1.19-4.04), and 6609.25 person years. In this time period, 125 (5.57%) progressed to HGD/EAC, with 74 (3.3%) after 1 year of follow-up and 38 (1.69%) developed EAC, with 20 (0.89%) beyond 1 year. The overall incidence of HGD/EAC was 1.89% per year; 1.16% if the first year is excluded. The risk of progression to EAC alone overall was 0.57% per year, 0.31% excluding the first year, and 0.21% in the 1,925 patients who had SIM alone at diagnosis. Low-grade dysplasia (LGD) progressed to HGD/EAC in 31% of patients, a progression rate of 12.96% per year, 6.71% with the first year excluded. In a national collaboration of academic centers in Ireland, the progression rate for NDBE was similar to recent population studies. Almost one in two who progressed was evident within 1 year. Crucially, LGD diagnosed and confirmed by specialist gastrointestinal pathologists represents truly high-risk disease, highlighting the importance of expertise in diagnosis and management, and providing indirect support for ablative therapies in this context.

Distinct inflammatory profile in preeclampsia and postpartum preeclampsia reveal unique mechanisms.

Preeclampsia (PE) is a poorly understood pregnancy complication. It has been suggested that changes in the maternal immune system may contribute to PE, but evidence of this remains scarce. Whilst PE is commonly experienced prepartum, it can also occur in the postpartum period (postpartum PE-PPPE), and the mechanisms involved are unknown. Our goal was to determine whether changes occur in the maternal immune system and placenta in pregnancies complicated with PE and PPPE, compared to normal term pregnancies. We prospectively recruited women and collected blood samples to determine the circulating immune profile, by flow cytometry, and assess the circulating levels of inflammatory mediators and angiogenic factors. Placentas were collected for histological analysis. Levels of alarmins in the maternal circulation showed increased uric acid in PE and elevated high-mobility group box 1 in PPPE. Analysis of maternal immune cells revealed distinct profiles in PE vs PPPE. PE had increased percentage of lymphocytes and monocytes whilst PPPE had elevated NK and NK-T cells as well. Elevated numbers of immune cells (CD45+) were detected in placentas from women that developed PPPE, and those were macrophages (CD163+). This work reveals changes within the maternal immune system in both PE and PPPE, and indicate a striking contrast in how this occurs. Importantly, elevated immune cells in the placenta of women with PPPE strongly suggest a prenatal initiation of the pathology. A better understanding of these changes will be beneficial to identify women at high risk of PPPE and to develop novel therapeutic targets.

Uric Acid Crystals Induce Placental Inflammation and Alter Trophoblast Function via an IL-1-Dependent Pathway: Implications for Fetal Growth Restriction.

Excessive placental inflammation is associated with several pathological conditions, including stillbirth and fetal growth restriction. Although infection is a known cause of inflammation, a significant proportion of pregnancies have evidence of inflammation without any detectable infection. Inflammation can also be triggered by endogenous mediators, called damage associated molecular patterns or alarmins. One of these damage-associated molecular patterns, uric acid, is increased in the maternal circulation in pathological pregnancies and is a known agonist of the Nlrp3 inflammasome and inducer of inflammation. However, its effects within the placenta and on pregnancy outcomes remain largely unknown. We found that uric acid (monosodium urate [MSU]) crystals induce a proinflammatory profile in isolated human term cytotrophoblast cells, with a predominant secretion of IL-1ß and IL-6, a result confirmed in human term placental explants. The proinflammatory effects of MSU crystals were shown to be IL-1-dependent using a caspase-1 inhibitor (inhibits IL-1 maturation) and IL-1Ra (inhibits IL-1 signaling). The proinflammatory effect of MSU crystals was accompanied by trophoblast apoptosis and decreased syncytialization. Correspondingly, administration of MSU crystals to rats during late gestation induced placental inflammation and was associated with fetal growth restriction. These results make a strong case for an active proinflammatory role of MSU crystals at the maternal-fetal interface in pathological pregnancies, and highlight a key mediating role of IL-1. Furthermore, our study describes a novel in vivo animal model of noninfectious inflammation during pregnancy, which is triggered by MSU crystals and leads to reduced fetal growth.

Antenatal Suppression of IL-1 Protects against Inflammation-Induced Fetal Injury and Improves Neonatal and Developmental Outcomes in Mice.

Preterm birth (PTB) is commonly accompanied by in utero fetal inflammation, and existing tocolytic drugs do not target fetal inflammatory injury. Of the candidate proinflammatory mediators, IL-1 appears central and is sufficient to trigger fetal loss. Therefore, we elucidated the effects of antenatal IL-1 exposure on postnatal development and investigated two IL-1 receptor antagonists, the competitive inhibitor anakinra (Kineret) and a potent noncompetitive inhibitor 101.10, for efficacy in blocking IL-1 actions. Antenatal exposure to IL-1ß induced Tnfa, Il6, Ccl2, Pghs2, and Mpges1 expression in placenta and fetal membranes, and it elevated amniotic fluid IL-1ß, IL-6, IL-8, and PGF2α, resulting in PTB and marked neonatal mortality. Surviving neonates had increased Il1b, Il6, Il8, Il10, Pghs2, Tnfa, and Crp expression in WBCs, elevated plasma levels of IL-1ß, IL-6, and IL-8, increased IL-1ß, IL-6, and IL-8 in fetal lung, intestine, and brain, and morphological abnormalities: e.g., disrupted lung alveolarization, atrophy of intestinal villus and colon-resident lymphoid follicle, and degeneration and atrophy of brain microvasculature with visual evoked potential anomalies. Late gestation treatment with 101.10 abolished these adverse outcomes, whereas Kineret exerted only modest effects and no benefit for gestation length, neonatal mortality, or placental inflammation. In a LPS-induced model of infection-associated PTB, 101.10 prevented PTB, neonatal mortality, and fetal brain inflammation. There was no substantive deviation in postnatal growth trajectory or adult body morphometry after antenatal 101.10 treatment. The results implicate IL-1 as an important driver of neonatal morbidity in PTB and identify 101.10 as a safe and effective candidate therapeutic.

Alarmins at the maternal-fetal interface: involvement of inflammation in placental dysfunction and pregnancy complications 1.

Inflammation is known to be associated with placental dysfunction and pregnancy complications. Infections are well known to be a cause of inflammation but they are frequently undetectable in pregnancy complications. More recently, the focus has been extended to inflammation of noninfectious origin, namely caused by endogenous mediators known as "damage-associated molecular patterns (DAMPs)" or alarmins. In this manuscript, we review the mechanism by which inflammation, sterile or infectious, can alter the placenta and its function. We discuss some classical DAMPs, such as uric acid, high mobility group box 1 (HMGB1), cell-free fetal deoxyribonucleic acid (DNA) (cffDNA), S100 proteins, heat shock protein 70 (HSP70), and adenosine triphosphate (ATP) and their impact on the placenta. We focus on the main placental cells (i.e., trophoblast and Hofbauer cells) and describe the placental response to, and release of, DAMPs. We also covered the current state of knowledge about the role of DAMPs in pregnancy complications including preeclampsia, fetal growth restriction, preterm birth, and stillbirth and possible therapeutic strategies to preserve placental function.

Machine Learning EEG to Predict Cognitive Functioning and Processing Speed Over a 2-Year Period in Multiple Sclerosis Patients and Controls.

Event-related potentials (ERPs) show promise to be objective indicators of cognitive functioning. The aim of the study was to examine if ERPs recorded during an oddball task would predict cognitive functioning and information processing speed in Multiple Sclerosis (MS) patients and controls at the individual level. Seventy-eight participants (35 MS patients, 43 healthy age-matched controls) completed visual and auditory 2- and 3-stimulus oddball tasks with 128-channel EEG, and a neuropsychological battery, at baseline (month 0) and at Months 13 and 26. ERPs from 0 to 700 ms and across the whole scalp were transformed into 1728 individual spatio-temporal datapoints per participant. A machine learning method that included penalized linear regression used the entire spatio-temporal ERP to predict composite scores of both cognitive functioning and processing speed at baseline (month 0), and months 13 and 26. The results showed ERPs during the visual oddball tasks could predict cognitive functioning and information processing speed at baseline and a year later in a sample of MS patients and healthy controls. In contrast, ERPs during auditory tasks were not predictive of cognitive performance. These objective neurophysiological indicators of cognitive functioning and processing speed, and machine learning methods that can interrogate high-dimensional data, show promise in outcome prediction.

Active Video Gaming for Children with Cerebral Palsy: Does a Clinic-Based Virtual Reality Component Offer an Additive Benefit? A Pilot Study.

AIMS: To compare changes in gross motor skills and functional mobility between ambulatory children with cerebral palsy who underwent a 1-week clinic-based virtual reality intervention (VR) followed by a 6-week, therapist-monitored home active video gaming (AVG) program and children who completed only the 6-week home AVG program. METHODS: Pilot non-randomized controlled trial. Five children received 1 hour of VR training for 5 days followed by a 6-week home AVG program, supervised online by a physical therapist. Six children completed only the 6-week home AVG program. The Gross Motor Function Measure Challenge Module (GMFM-CM) and Six Minute Walk Test (6MWT) evaluated change. RESULTS: There were no significant differences between groups. The home AVG-only group demonstrated a statistically and clinically significant improvement in GMFM-CM scores following the 6-week AVG intervention (median difference 4.5 points, interquartile range [IQR] 4.75, p = 0.042). The VR + AVG group demonstrated a statistically and clinically significant decrease in 6MWT distance following the intervention (median decrease 68.2 m, IQR 39.7 m, p = 0.043). All 6MWT scores returned to baseline at 2 months post-intervention. CONCLUSION: Neither intervention improved outcomes in this small sample. Online mechanisms to support therapist-child communication for exercise progression were insufficient to individualize exercise challenge.

Uterotonic Neuromedin U Receptor 2 and Its Ligands Are Upregulated by Inflammation in Mice and Humans, and Elicit Preterm Birth.

Uterine labor requires the conversion of a quiescent (propregnancy) uterus into an activated (prolabor) uterus, with increased sensitivity to endogenous uterotonic molecules. This activation is induced by stressors, particularly inflammation in term and preterm labor. Neuromedin U (NmU) is a neuropeptide known for its uterocontractile effects in rodents. The objective of the study was to assess the expression and function of neuromedin U receptor 2 (NmU-R2) and its ligands NmU and the more potent neuromedin S (NmS) in gestational tissues, and the possible implication of inflammatory stressors in triggering this system. Our data show that NmU and NmS are uterotonic ex vivo in murine tissue, and they dose-dependently trigger labor by acting specifically via NmU-R2. Expression of NmU-R2, NmU, and NmS is detected in murine and human gestational tissues by immunoblot, and the expression of NmS in placenta and of NmU-R2 in uterus increases considerably with gestation age and labor, which is associated with amplified NmU-induced uterocontractile response in mice. NmU- and NmS-induced contraction is associated with increased NmU-R2-coupled Ca++ transients, and Akt and Erk activation in murine primary myometrial smooth muscle cells (mSMCs), which are potentiated with gestational age. NmU-R2 is upregulated in vitro in mSMCs and in vivo in uterus in response to proinflammatory interleukin 1beta (IL1beta), which is associated with increased NmU-induced uterocontractile response and Ca++ transients in murine and human mSMCs; additionally, placental NmS is markedly upregulated in vivo in response to IL1beta. In human placenta at term, immunohistological analysis revealed NmS expression primarily in cytotrophoblasts; furthermore, stimulation with lipopolysaccharide (LPS; Gram-negative endotoxin) markedly upregulates NmS expression in primary human cytotrophoblasts isolated from term placentas. Correspondingly, decidua of women with clinical signs of infection who delivered preterm display significantly higher expression of NmS compared with those without infection. Importantly, in vivo knockdown of NmU-R2 prevents LPS-triggered preterm birth in mice and the associated neonatal mortality. Altogether, our data suggest a critical role for NmU-R2 and its ligands NmU and NmS in preterm labor triggered by infection. We hereby identify NmU-R2 as a relevant target for preterm birth.

Sterile inflammation and pregnancy complications: a review.

Inflammation is essential for successful embryo implantation, pregnancy maintenance and delivery. In the last decade, important advances have been made in regard to endogenous, and therefore non-infectious, initiators of inflammation, which can act through the same receptors as pathogens. These molecules are referred to as damage-associated molecular patterns (DAMPs), and their involvement in reproduction has only recently been unraveled. Even though inflammation is necessary for successful reproduction, untimely activation of inflammatory processes can have devastating effect on pregnancy outcomes. Many DAMPs, such as uric acid, high-mobility group box 1 (HMGB1), interleukin (IL)-1 and cell-free fetal DNA, have been associated with pregnancy complications, such as miscarriages, preeclampsia and preterm birth in preclinical models and in humans. However, the specific contribution of alarmins to these conditions is still under debate, as currently there is lack of information on their mechanism of action. In this review, we discuss the role of sterile inflammation in reproduction, including early implantation and pregnancy complications. Particularly, we focus on major alarmins vastly implicated in numerous sterile inflammatory processes, such as uric acid, HMGB1, IL-1α and cell-free DNA (especially that of fetal origin) while giving an overview of the potential role of other candidate alarmins.

Pregnant individuals with uncomplicated pregnancies display pro-inflammatory immune changes when exposed to the COVID-19 pandemic.

PROBLEM: The COVID-19 pandemic has been shown to have a detrimental impact on the mental health of pregnant individuals, and chronic stress can alter the immune profile. However, the effects of the COVID-19 pandemic on the immune system in pregnancy are still poorly understood. We aimed to evaluate the impact of pandemic exposure on the maternal immune profile in uncomplicated pregnancies. METHOD OF STUDY: We collected blood and placenta samples from pregnant individuals exposed and unexposed to the pandemic to compare their immune and inflammatory profiles. We performed co-culture with circulating maternal immune cells and endothelial cells to assess endothelial activation. Statistical analysis was performed using unpaired t-test, Mann-Whitney, or Fisher's exact test as appropriate. RESULTS: In exposed individuals, we observed a decreased proportion of Th2 cells (p < .0001) and Treg/Th17 ratio (p < .05), as well as an increased Th1/Th2 ratio (p < .0001). Levels of IL-1ß (p < .01) and IL-18 (p < .01) were increased in the circulation of exposed participants, whilst other mediators were significantly decreased (IFNγ, IL-8, MCP-1, amongst others). Furthermore, we observed increased production of ICAM, hallmark of endothelial activation, when we co-cultured endothelial cells with immune cells from exposed individuals. Vaccination status impacted the cellular profile with increased proportions of Th1 and B cells in vaccinated participants. CONCLUSION: Overall, we observed a pro-inflammatory bias in the circulation of pregnant individuals exposed to the COVID-19 pandemic, with otherwise uncomplicated pregnancies. Our work also supports an association between the increased risk of endothelial activation/hypertension and SARS-CoV2 infection, which might be driven in part by exposure to the pandemic and associated stressors.

A capacity-building intervention for parents of children with disabilities in rural South India.

BACKGROUND: A disability service organization piloted a parent capacity-building intervention for parents of children with developmental disabilities in rural South India. AIMS: To examine the impact of this parent capacity-building group intervention on parent empowerment, peer support, social inclusion, advocacy skills, and the factors influencing these outcomes. METHODS AND PROCEDURES: A qualitative study recruited 37 participants from 17 parent groups through convenience sampling. Six focus groups occurred six months post the start of this intervention and explored these parents' experiences with the groups and their perceived impacts. OUTCOMES AND RESULTS: Qualitative analysis yielded four main themes and corresponding sub-themes: peer support (feeling peaceful and supported, building self-efficacy), social inclusion (space to share, acceptance and identity), knowledge sharing (increasing awareness, accepting advice), and advocacy (building confidence, making requests). Participation in parent groups provided participants with opportunities to find peer support, utilize knowledge sharing, feel socially included, and build advocacy skills. CONCLUSIONS AND IMPLICATIONS: This study provides a greater understanding of the impact and benefits of parent capacity-building interventions in low-resource settings. Results will improve this intervention and guide other organizations in creating similar programs. WHAT THIS PAPER ADDS: This paper adds perspectives of parents who are caregivers of children with developmental disabilities in rural South India. More specifically, this paper highlights the impact of a parent-focused intervention in group settings in both rural and urban areas. Parent support group interventions are not common in India and low- and middle-income countries and there is a paucity of literature describing these interventions and their impact. In this study, parents described a need for multifaceted interventions to support their child in the community. These parent groups provided space for caregivers of children with developmental disabilities to make connections, feel validated, and grow confidence to utilize new knowledge or advice shared by other parents to further enhance their lives. Further, parent-group settings provide opportunities to build advocacy skills through timely discussions. Parents reported an increase in feelings of acceptance within the group itself but not within the wider community. This highlights the need for involving the wider community in interventions to promote integration for families with children with disabilities.

Enabling local provision of assistive products in rural South India: an organisational survey of needs, barriers, and facilitators.

Objective: Access to assistive products (APs) is essential to maximising function, participation, and inclusion of persons with disabilities. Challenges to AP access in low- and middle-income countries include stigma, costs, supply, and rehabilitation capacity gaps. This study aimed to examine AT access in the context of a low-resource setting in rural South India. Objectives were to examine rehabilitation professionals' perceptions of AP needs, barriers and facilitators of AP provision, and AT knowledge.Methods: A descriptive study design with a 2-part online survey methodology was utilized. This study was conducted in April-September 2020 at a non-governmental organization (NGO) serving children and adults with disabilities in 3 districts of rural South India. Purposive sampling of NGO's multidisciplinary rehabilitation professionals (N=62) was used. The survey was developed based on WHO's Assistive Products List (APL). Barriers and facilitators were classified according to the principles of AT access. Analyses revealed acceptability, affordability, and availability as the top three barrier themes across disciplines, including poor acceptance by clients/families due to stigma, high AP costs, and a long waitlist for government-provided devices. Acceptability, affordability, and accessibility were the top three facilitator themes, including community awareness, availability of AP funding, client/family education, and AT service provision training.Impact: Our study identified key enabling strategies for AT access, aimed at reducing reported barriers. Enabling AP provision was determined to be multi-factorial, aimed at users/ families, service providers, organizations, communities, and policymakers. Local stakeholder groups are crucial to understanding challenges and opportunities to AP provision within a low-resource context.

Identified barriers to assistive product (AP) provision in rural South India include poor acceptance by clients/families due to stigma, high AP costs, limited AP availability, and rehabilitation capacity gaps.Suggested facilitators to AP provision in rural South India include improving AP acceptability, affordability, and accessibility through community awareness, client/family education, AP funding and supply, and assistive technology (AT) service provision capacity building.An organisational-level survey based on the WHO's Priority Assistive Products List and the Principles of AT Access can identify local needs, barriers and facilitators.An AT access strategies in resource-limited areas may be developed based on barriers and facilitators identified by local/regional rehabilitation professionals.

Exploring rehabilitation providers' perspectives of assistive technology access after the implementation of a paediatric AT provision program in rural South India.

A paediatric Assistive Technology (AT) Provision Program was implemented by a non-governmental rehabilitation facility in rural South India to support rehabilitation providers in providing needed AT access for children with disabilities. Capacity-building measures for providers and other supports based on the AT needs, barriers, and facilitators to AT access were implemented that aligned with the AT global report for low-middle income countries (LMIC). This study explores how the initiatives from the AT Provision Program have influenced the perspectives of rehabilitation providers on AT access.Using a qualitative design eight paediatric rehabilitation providers were purposively sampled for virtual semi-structured interviews. Findings were analysed using thematic analysis.Six overarching themes were identified: (1) Stigma associated with AT use, (2) Organisational response to changing needs, (3) Financial factors related to family socioeconomic status and the organisation providing AT services, (4) Inequity of AT service access in rural areas, (5) Provider AT awareness and confidence and, (6) Quality assurance. Rehabilitation providers' experiences informed future AT capacity-building strategies within a low-resource context. Our findings provide valuable insights for the development of comprehensive AT Provision Program initiatives to provide AT access for children with disabilities in LMIC settings.

The perspectives of rehabilitation providers in low- and middle-income countries are important to expand the limited research in understanding Assistive Technology (AT) provision in these countries to advance program development and planning.Organized access to AT in rural communities, particularly in developing countries such as India, enables children with disabilities to improve their participation in social, recreational, and educational opportunities.Exploring rehabilitation providers' perspectives gives insight into barriers and opportunities surrounding AT access within their cultural context, and how it influences their clinical practice.Integrating the AT Access Principle framework from the 2022 WHO-UNICEF Global Report on AT, this study evaluates the current AT systems in rural south India and can further inform strategic planning in low-middle income countries to mitigate access barriers encountered along the AT access pathway.

Identification of divergent placental profiles in clinically distinct pregnancy complications revealed by the transcriptome.

INTRODUCTION: Pregnancy complications, including preeclampsia (PE), preterm birth (PTB), and intra-uterine growth restriction (IUGR) have individually been associated with inflammation but the combined comparative analysis of their placental profiles at the transcriptomic and histological levels is lacking. METHODS: Bulk RNA-sequencing of human placental biopsies from uncomplicated term pregnancies (CTL) and pregnancies complicated with early-onset (EO), and late-onset (LO) PE, as well as PTB and term IUGR were used to characterize individual molecular profiles. We also applied immune-cell-specific cellular deconvolution to address local immune cell compositions and analyzed placental lesions by histology to further characterize these complications. RESULTS: Transcriptome analysis revealed that clinically distinct complications differentiated themselves in unique ways compared to CTLs. Only TMEM136 was commonly modulated. Compared to CTLs, we found that PTB and IUGR were the most distinct, with LOPE being the least distinct. PTB and IUGR revealed differently enhanced inflammatory pathways, where PTB had general inflammatory responses and IUGR had immune cell activation. This inflammation was reflected in the histological profile for PTB only, whereas structural lesions were elevated in all complications. Placental lesions additionally had corresponding enhancement in inflammatory and structural biological processes. We observed that having co-complications, particularly for PTB with or without IUGR, impacted placental transcriptomes. Lastly, cellular deconvolution uncovered shared immune features among the complications. DISCUSSION: Overall, we provide evidence that these pregnancy complications are not only distinct in their clinical manifestations but also in their placental profiles, which could be leveraged to understand their underlying mechanisms and could offer therapeutic targets.

Predictive biomarkers and initial analysis of maternal immune alterations in postpartum preeclampsia reveal an immune-driven pathology.

Introduction: Postpartum preeclampsia (PPPE) is an under-diagnosed condition, developing within 48 hours to 6 weeks following an uncomplicated pregnancy. The etiology of PPPE is still unknown, leaving patients vulnerable and making the identification and treatment of patients requiring postpartum care an unmet need. We aimed to understand the immune contribution to PPPE at the time of diagnosis, as well as uncover the predictive potential of perinatal biomarkers for the early postnatal identification of high-risk patients. Methods: Placentas were collected at delivery from uncomplicated pregnancies (CTL) and PPPE patients for immunohistochemistry analysis. In this initial study, blood samples in PPPE patients were collected at the time of PPPE diagnosis (48h-25 days postpartum; mean 7.4 days) and compared to CTL blood samples taken 24h after delivery. Single-cell transcriptomics, flow cytometry, intracellular cytokine staining, and the circulating levels of inflammatory mediators were evaluated in the blood. Results: Placental CD163+ cells and 1st trimester blood pressures can be valuable non-invasive and predictive biomarkers of PPPE with strong clinical application prospects. Furthermore, changes in immune cell populations, as well as cytokine production by CD14+, CD4+, and CD8+ cells, suggested a dampened response with an exhausted phenotype including decreased IL1ß, IL12, and IFNγ as well as elevated IL10. Discussion: Understanding maternal immune changes at the time of diagnosis and prenatally within the placenta in our sizable cohort will serve as groundwork for pre-clinical and clinical research, as well as guiding clinical practice for example in the development of immune-targeted therapies, and early postnatal identification of patients who would benefit from more thorough follow-ups and risk education in the weeks following an uncomplicated pregnancy.