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Objective: This study assesses change in caregiver practices after integrating responsive care and early learning (RCEL) in nutrition and health services and community platforms in northern Ghana., Design: We trained health facility workers and community health volunteers to deliver RCEL counselling to caregivers of children under 2 years of age through existing health facilities and community groups. We assessed changes in caregivers' RCEL practices before and after the intervention with a household questionnaire and caregiver-child observations., Setting: The study took place in Sagnarigu, Gushegu, Wa East and Mamprugu-Moagduri districts from April 2022 to March 2023. Study sites included seventy-nine child welfare clinics (CWC) at Ghana Health Service facilities and eighty village savings and loan association (VSLA) groups., Participants: We enrolled 211 adult caregivers in the study sites who had children 0-23 months at baseline and were enrolled in a CWC or a VSLA., Results: We observed improvements in RCEL and infant and young child feeding practices, opportunities for early learning (e.g. access to books and playthings) in the home environment and reductions in parental stress., Conclusions: This study demonstrates the effectiveness of integrating RCEL content into existing nutrition and health services. The findings can be used to develop, enhance and advocate for policies integrating RCEL into existing services and platforms in Ghana. Future research may explore the relationship between positive changes in caregiver behaviour and improvements in child development outcomes as well as strategies for enhancing paternal engagement in care practices, improving child supervision and ensuring an enabling environment.

Purpose: Poverty amongst families with a child with disability adversely impacts child and family quality of life. We aimed to identify existing approaches to livelihood support for caregivers of children with developmental disabilities in low- and middle-income countries., Methods: This mixed-method study incorporated a scoping literature review and online stakeholder survey. We utilised the World Health Organization community-based rehabilitation (CBR) matrix as a guiding framework for knowledge synthesis and descriptively analysed the included articles and survey responses., Results: We included 11 peer-reviewed publications, 6 grey literature articles, and 49 survey responses from stakeholders working in 22 countries. Identified programmes reported direct and indirect strategies for livelihood support targeting multiple elements of the CBR matrix; particularly skills development, access to social protection measures, and self-employment; frequently in collaboration with specialist partners, and as one component of a wider intervention. Self-help groups were also common. No publications examined effectiveness of livelihood support approaches in mitigating poverty, with most describing observational studies at small scale., Conclusion: Whilst stakeholders describe a variety of direct and indirect approaches to livelihood support for caregivers of children with disabilities, there is a lack of published literature on content, process, and impact to inform future programme development and delivery.

The application of hydrogels for anti-cancer drug delivery has garnered considerable interest in the medical field. Current cancer treatment approaches, such as chemotherapy and radiation therapy, often induce severe side effects, causing significant distress and substantial health complications to patients. Hydrogels present an appealing solution as they can be precisely injected into specific sites within the body, facilitating the sustainable release of encapsulated drugs. This localized treatment approach holds great potential for reducing toxicity levels and improving drug delivery efficacy. In this study we developed a hydrogel delivery system containing polyamidoamine (PAMAM) dendrimer and polyethylene glycol (PEG) for solubility enhancement and sustained delivery of hydrophobic anti-cancer drugs. The three selected model drugs, e.g. silibinin, camptothecin, and methotrexate, possess limited aqueous solubility and thus face restricted application. In the presence of vinyl sulfone functionalized PAMAM dendrimer at 45 mg/mL concentration, drug solubility is increased by 37-fold, 4-fold, and 10-fold for silibinin, camptothecin, and methotrexate, respectively. By further crosslinking of the functionalized PAMAM dendrimer and thiolated PEG, we successfully developed a fast-crosslinking hydrogel capable of encapsulating a significant payload of solubilized cancer drugs for sustained release. In water, the drug encapsulated hydrogels release 30%-80% of their loads in 1-4 days. MTT assays of J82 and MCF7 cells with various doses of drug encapsulated hydrogels reveal that cytotoxicity is observed for all three drugs on both J82 and MCF7 cell lines after 48 h. Notably, camptothecin exhibits higher cytotoxicity to both cell lines than silibinin and methotrexate, achieving up to 95% cell death at experimental conditions, despite its lower solubility. Our experiments provide evidence that the PAMAM dendrimer-mediated hydrogel system significantly improves the solubility of hydrophobic drugs and facilitates their sustained release. These findings position the system as a promising platform for controlled delivery of hydrophobic drugs for intratumoral cancer treatment., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Introduction: Stunting (low height/length-for-age) in early life is associated with poor long-term health and developmental outcomes. Nutrition interventions provided during the first 1,000 days of life can result in improved catch-up growth and development outcomes. We assessed factors associated with stunting recovery at 24 months of age among infants and young Children enrolled in Pediatric Development Clinics (PDC) who were stunted at 11 months of age., Methods: This retrospective cohort study included infants and young children who enrolled in PDCs in two rural districts in Rwanda between April 2014 and December 2018. Children were included in the study if their PDC enrollment happened within 2 months after birth, were stunted at 11 months of age (considered as baseline) and had a stunting status measured and analyzed at 24 months of age. We defined moderate stunting as length-for-age z-score (LAZ) < -2 and ≥-3 and severe stunting as LAZ <-3 based on the 2006 WHO child growth standards. Stunting recovery at 24 months of age was defined as the child's LAZ changing from <-2 to > -2. We used logistic regression analysis to investigate factors associated with stunting recovery. The factors analyzed included child and mother's socio-demographic and clinical characteristics., Results: Of the 179 children who were eligible for this study, 100 (55.9%) were severely stunted at age 11 months. At 24 months of age, 37 (20.7%) children recovered from stunting, while 21 (21.0%) severely stunted children improved to moderate stunting and 20 (25.3%) moderately-stunted children worsened to severe stunting. Early stunting at 6 months of age was associated with lower odds of stunting recovery, with the odds of stunting recovery being reduced by 80% (aOR: 0.2; 95%CI: 0.07-0.81) for severely stunted children and by 60% (aOR: 0.4; 95% CI: 0.16-0.97) for moderately stunted children (p = 0.035). Lower odds of stunting recovery were also observed among children who were severely stunted at 11 months of age (aOR: 0.3; 95% CI: 0.1-0.6, p = 0.004). No other maternal or child factors were statistically significantly associated with recovery from stunting at 24 months in our final adjusted model., Conclusion: A substantial proportion of children who were enrolled in PDC within 2 months after birth and were stunted at 11 months of age recovered from stunting at 24 months of age. Children who were severely stunted at 11 months of age (baseline) and those who were stunted at 6 months of age were less likely to recover from stunting at 24 months of age compared to those with moderate stunting at 11 months and no stunting at 6 months of age, respectively. More focus on prevention and early identification of stunting during pregnancy and early life is important to the healthy growth of a child., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Nemerimana et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

One billion people worldwide have a disability, and 80 percent of them live in low- and middle-income countries (LMICs). The prevalence of feeding difficulties globally ranges from 25-45 percent to 33-80 percent in children without and with disabilities, respectively. The U.S. Agency for International Development's (USAID) flagship multi-sectoral nutrition project, USAID Advancing Nutrition, conducted a scoping review of programs supporting nutritional care of children with disability and non-disability related feeding difficulties. The non-systematic scoping review included a desk review of peer-reviewed and non-peer-reviewed literature and key informant interviews. In all, 127 documents with publication dates ranging from 2003 to 2022 were identified through keyword searches and snowballing and met the inclusion criteria, and 42 experts in nutrition and disability were interviewed. Findings were organized using structured matrices of challenges and opportunities across the universal progressive model of care framework in the identification and management of feeding difficulties and disabilities and support for children with feeding difficulties and disabilities and their families. The review found insufficient policies, programs, and evidence to support children with feeding difficulties and disabilities and their families. While some resources and promising approaches exist, they are not standardized or universally used, staff are not trained to use them, and there is insufficient funding to implement them. The combination of challenges in identifying feeding difficulties and disabilities, a lack of understanding of the link between disabilities and feeding, and weak or nonexistent referral or specialized services puts these children at risk of malnutrition. Additionally, their families face challenges providing the care they need, including coping with high care demands, accessing support, obtaining appropriate foods, and managing stigma. Four areas of recommendations emerged to support children with feeding difficulties and disabilities: (1) Strengthen systems to improve identification and service provision; (2) Provide direct support to families to address determinants that affect nutrition outcomes; (3) Conduct advocacy to raise awareness of the needs and opportunities; and (4) Build the evidence base on effective interventions to identify and support these children and their families., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: CMK has been involved in the implementation and evaluation of the Multi-Agency International Training and Support (MAITS) Working with Infants with Feeding Difficulties and Baby Ubuntu programmatic approaches in Rwanda. The authors have no other conflicts of interest to report., (Copyright: © 2023 Klein et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Early initiation of breastfeeding after birth and exclusive breastfeeding for the first six months improves child survival, nutrition and health outcomes. However, only 42% of newborns worldwide are breastfed within the first hour of life. Small and sick newborns are at greater risk of not receiving breastmilk and often require additional support for feeding. This study compares breastfeeding practices in Rwandan neonatal care units (NCUs) before and after the implementation of a package of interventions aimed to improve breastfeeding., Methods: This pre-post intervention study was conducted at two district hospital NCUs in rural Rwanda from October-December 2017 (pre-intervention) and September 2018-March 2019 (post-intervention). Only newborns admitted before their second day of life (DOL) were included. Data were extracted from patient charts for clinical and demographic characteristics, feeding, and patient outcomes. Exclusive breastfeeding at discharge was based on last recorded infant feeding on the day of discharge. Logistic regression analysis was used to evaluate factors associated with exclusive breastfeeding at discharge., Results: Pre-intervention, 255 newborns were admitted in the NCUs and 793 were admitted in post-intervention. Exclusive breastfeeding on the day of birth (DOL0) increased from 5.4% (12/255) to 35.9% (249/793). At discharge, exclusive breastfeeding increased from 69.6% (149/214) to 87.0% (618/710). The mortality rate decreased from 16.1% (41/255) to 10.5% (83/793). Factors associated with greater odds of exclusive breastfeeding at discharge included admission during the post-intervention period (aOR 4.91; 95% CI 1.99, 12.11), and admission for infection (aOR 2.99; 95% CI 1.13, 7.93). Home deliveries (aOR 0.15; 95% CI 0.05, 0.47), preterm delivery (aOR 0.36; 95% CI 0.15, 0.87) and delayed first breastmilk feed (aOR 0.04 for DOL3 vs. DOL0; 95% CI 0.01, 0.35) reduced odds of exclusive breastfeeding at discharge., Conclusions: Expansion and adoption of evidenced-based guidelines, using innovative approaches, aimed at the unique needs of small and sick newborns may help to improve earlier initiation of breastfeeding, decrease mortality, and improve exclusive breastfeeding on discharge from hospital among small and sick newborns. These interventions should be replicated in similar settings to determine their effectiveness., (© 2022. The Author(s).)

Infants born preterm, low birthweight or with other perinatal complications require frequent and accurate growth monitoring for optimal nutrition and growth. We implemented an mHealth tool to improve growth monitoring and nutritional status assessment of high risk infants. We conducted a pre-post quasi-experimental study with a concurrent control group among infants enrolled in paediatric development clinics in two rural Rwandan districts. During the pre-intervention period (August 2017-January 2018), all clinics used standard paper-based World Health Organization (WHO) growth charts. During the intervention period (August 2018-January 2019), Kirehe district adopted an mHealth tool for child growth monitoring and nutritional status assessment. Data on length/height; weight; length/height-for-age (L/HFA), weight-for-length/height (WFL/H) and weight-for-age (WFA) z-scores; and interval growth were tracked at each visit. We conducted a 'difference-in-difference' analysis to assess whether the mHealth tool was associated with greater improvements in completion and accuracy of nutritional assessments and nutritional status at 2 and 6 months of age. We observed 3529 visits. mHealth intervention clinics showed significantly greater improvements on completeness for corrected age (endline: 65% vs. 55%; p = 0.036), L/HFA (endline: 82% vs. 57%; p ≤ 0.001), WFA (endline: 93% vs. 67%; p ≤ 0.001) and WFL/H (endline: 90% vs. 59%; p ≤ 0.001) z-scores compared with control sites. Accuracy of growth monitoring did not improve. Prevalence of stunting, underweight and inadequate interval growth at 6-months corrected age decreased significantly more in the intervention clinics than in control clinics. Results suggest that integrating mHealth nutrition interventions is feasible and can improve child nutrition outcomes. Improved tool design may better promote accuracy., (© 2021 The Authors. Maternal & Child Nutrition published by John Wiley & Sons Ltd.)

Background: Neonatal Care Units (NCUs) provide special care to sick and small newborns and help reduce neonatal mortality. For parents, having a hospitalized newborn can be a traumatic experience. In sub-Saharan Africa, there is limited literature about the parents' experience in NCUs., Objective: Our study aimed to explore the experience of parents in the NCU of a rural district hospital in Rwanda., Methods: A qualitative study was conducted with parents whose newborns were hospitalized in the Ruli District Hospital NCU from September 2018 to January 2019. Interviews were conducted using a semi-structured guide in the participants' homes by trained data collectors. Data were transcribed, translated, and then coded using a structured code book. All data were organized using Dedoose software for analysis., Results: Twenty-one interviews were conducted primarily with mothers (90.5%, n = 19) among newborns who were most often discharged home alive (90.5%, n = 19). Four themes emerged from the interviews. These were the parental adaptation to having a sick neonate in NCU, adaptation to the NCU environment, interaction with people (healthcare providers and fellow parents) in the NCU, and financial stressors., Conclusion: The admission of a newborn to the NCU is a source of stress for parents and caregivers in rural Rwanda, however, there were several positive aspects which helped mothers adapt to the NCU. The experience in the NCU can be improved when healthcare providers communicate and explain the newborn's status to the parents and actively involve them in the care of their newborn. Expanding the NCU access for families, encouraging peer support, and ensuring financial accessibility for neonatal care services could contribute to improved experiences for parents and families in general., Competing Interests: The authors have declared that no competing interests exist.

Background: Little is known about father's involvement in the care of children born with perinatal risk factors. This study aimed to understand father's involvement in the care of children born preterm, low birth weight (LBW) and/or with hypoxic ischemic encephalopathy (HIE) in rural Rwanda and assess child and home environment factors associated with father involvement., Methods: A cross-sectional study of children born preterm, LBW or with HIE who were discharged from Kirehe District Hospital neonatal unit from May 2015 to April 2016 and those enrolled in a neonatal unit follow-up programme from May 2016 to November 2017. Interviews were conducted when the children were ages 24-47 months in the child's home. Primary caregivers reported on father involvement in parenting, home environment, child disability, and child development outcomes. Children's nutritional status were directly measured. Only children whose fathers were living in the home were included in the sample. Bivariate analyses were conducted using Fisher's exact test and Wilcoxon Rank Sum test., Results: A total of 236 children aged 24-47 months were included in this study, 66.4% were born preterm or LBW with a mean age of 33.3 months. 73.5% of children were at risk of disability and 77.7% had potential delay in overall child development. 15.5% of fathers reported engaging in four or more activities with their child in the last 3 days. Factors associated with father involvement included smaller household size (p = 0.004), mother engaged in decision-making (p = 0.027), being on-track in developmental milestones for problem solving (p = 0.042) and mother's involvement in learning activities (p = 0.043); the number of activities a father engaged in was significantly associated with the child's overall development (p = 0.032)., Conclusion: We found that father involvement in activities to support learning was low amongst children born preterm/LBW and/or with HIE. Programme interventions should encourage fathers to engage with their children given the benefits for children's development., (© 2021 John Wiley & Sons, Ltd.)

Background: Neonatal mortality contributes to nearly half of child deaths globally and the majority of these deaths are preventable. Poor quality of care is a major driver of neonatal mortality in low- and middle-income countries. The All Babies Count (ABC) intervention was designed to reduce neonatal mortality through provision of equipment and supplies, training, mentorship, and data-driven quality improvement (QI) with peer-to-peer learning through learning collaborative sessions (LCS). We aim to describe the ABC scale-up in seven rural district hospitals from 2017 to 2019 focusing on the QI strategies implemented in hospital neonatal care units (NCUs) and the resultant neonatal care outcomes., Methods: A pre-post quasi experimental study was conducted in 7 rural hospitals in Rwanda in two phases. The baseline periods were April-June 2017 for Phase I and July-September 2017 for Phase II; with end-line data collected during the same periods in 2019. Data included facility audits of supplies and staffing, LCS surveys of QI skills, and reports of implemented QI change ideas. Data on NCU admissions and deaths were extracted from Health Management Information System (HMIS). Facility-reported change ideas were coded into common themes. Changes in post-post neonatal mortality were measured using Chi-squared tests., Results: NCUs were run by a median of 1 nurse [interquartile range (IQR):1-2] at baseline and endline. Median NCU admissions increased from 121 [IQR: 77-155] to 137 [IQR: 79-184]. Availability of advanced equipment improved (syringe pumps: 57-100 %, vital sign monitors: 51-100 % and CPAP machine: 14-100 %). There were significant improvements in QI skills among NCU staff. All 7 NCUs (100 %) addressed non-adherence to protocol as a priority gap, 5 NCUs (86 %) also improved communication with families. NCU case fatality rate declined from 12.4 to 7.8 % (p = 0.001)., Conclusions: The ABC package of interventions combining the provision of essential equipment to NCU, clinical training and strong mentorship, QI coaching, and the LCS approach for peer-to-peer learning was associated with significant neonatal mortality reduction and services utilization in the intervention hospitals.

Background: Global investments in neonatal survival have resulted in a growing number of children with morbidities surviving and requiring ongoing care. Little is known about the caregivers of these children in low- and middle-income countries, including maternal mental health which can further negatively impact child health and development outcomes. We aimed to assess the prevalence and factors associated with poor maternal mental health in mothers of children born preterm, low birthweight (LBW), and with hypoxic ischemic encephalopathy (HIE) at 24-47 months of age in rural Rwanda., Methods: Cross-sectional study of children 24-47 months born preterm, LBW, or with HIE, and their mothers discharged from the Neonatal Care Unit (NCU) at Kirehe Hospital between May 2015-April 2016 or discharged and enrolled in a NCU follow-up program from May 2016-November 2017. Households were interviewed between October 2018 and June 2019. Mothers reported on their mental health and their child's development; children's anthropometrics were measured directly. Backwards stepwise procedures were used to assess factors associated with poor maternal mental health using logistic regression., Results: Of 287 total children, 189 (65.9%) were born preterm/LBW and 34.1% had HIE and 213 (74.2%) screened positive for potential caregiver-reported disability. Half (n = 148, 51.6%) of mothers reported poor mental health. In the final model, poor maternal mental health was significantly associated with use of violent discipline (Odds Ratio [OR] 2.29, 95% Confidence Interval [CI] 1.17,4.45) and having a child with caregiver-reported disability (OR 2.96, 95% CI 1.55, 5.67). Greater household food security (OR 0.80, 95% CI 0.70-0.92) and being married (OR = 0.12, 95% CI 0.04-0.36) or living together as if married (OR = 0.13, 95% CI 0.05, 0.37) reduced the odds of poor mental health., Conclusions: Half of mothers of children born preterm, LBW and with HIE had poor mental health indicating a need for interventions to identify and address maternal mental health in this population. Mother's poor mental health was also associated with negative parenting practices. Specific interventions targeting mothers of children with disabilities, single mothers, and food insecure households could be additionally beneficial given their strong association with poor maternal mental health.

Background: Sufficient knowledge of the disproportionate burden of undernutrition among vulnerable children is required for accelerating undernutrition reduction in low-income countries., Objectives: We aimed to assess the prevalence of stunting, underweight and wasting and associated factors among high-risk children born preterm, with low birth weight or other birth and neurodevelopmental injuries, who received nutritional support and clinical care follow-up in a Pediatric Development Clinic (PDC) in rural Rwanda., Methods: This cross-sectional study included all children from rural areas enrolled in PDC between April 2014-September 2017 aged 6-59 months at their last visit during this period. Anthropometric measurements, socioeconomic and clinical characteristics were extracted from an electronic medical records system. We used the World Health Organization child growth standards to classify stunting, underweight and wasting. Factors associated with undernutrition were identified using logistic regression analysis., Results: Of 641 children, 58.8% were stunted, 47.5% were underweight and 25.8% were wasted. Small for gestational age was associated with increased odds of stunting [OR 2.63; 95% CI 1.58-4.36] and underweight (OR 2.33; 95% CI 1.46-3.71), while history of feeding difficulties was significantly associated with wasting (OR: 3.36; 95% CI: 2.20-5.13) and underweight (OR: 2.68; 95% CI: 1.78-4.04). Later age at PDC enrollment was associated with increased odds of stunting (OR: 1.06; 95% CI: 1.01-1.11), underweight (OR: 1.09; 95% CI: 1.05-1.14) and wasting (OR: 1.07; 95% CI: 1.04-1.10)., Conclusions: The prevalence of stunting, underweight and wasting are high in this at-risk population, highlighting the need for specific interventions to address undernutrition among children with similar characteristics. Early PDC enrollment of high-risk infants may reduce undernutrition risk., Competing Interests: The authors have no competing interests to declare., (Copyright: © 2020 The Author(s).)

Children born preterm, low birth weight (LBW) or with other perinatal risk factors are at high-risk of malnutrition. Regular growth monitoring and early intervention are essential to promote optimal feeding and growth; however, monitoring growth in preterm infants can be complex. This study evaluated growth monitoring of infants under 6 months enrolled in Paediatric Development Clinics (PDCs) in rural Rwanda. We reviewed electronic medical records (EMR) of infants enrolled in PDCs before age 2 months with their first visit between January 2015 and December 2016 and followed them until age 6 months. Nurse classification of anthropometric measures and nutritional status were extracted from the EMR. Interval growth and length-for-age, weight-for-length, and weight-for-age z-scores were calculated using World Health Organization anthropometry software as a 'gold standard' comparison to nurse classifications. Two hundred and ninety-four patients enrolled and had 2,033 visits during the study period. Referral reasons included prematurity/LBW (73.8%) and hypoxic ischemic encephalopathy (28.2%). Nurses assessed interval growth at 58.7% of visits, length-for-age at 66.4%, weight-for-length at 65.6% and weight-for-age at 66.4%. Nurses and gold standard assessment agreed on interval growth at 53.3% of visits and length-for-age at 63.7%, weight-for-length at 78.2% and weight-for-age at 66.3%. At 6 months, 46.5% were stunted, 19.9% were wasted and 44.2% were underweight. There were significant challenges to optimizing growth and growth monitoring among high-risk infants served by PDCs, including incomplete and inaccurate assessments. Developing tools for clinician decision support in assessing growth and providing specialized nutritional counselling are essential to supporting optimal outcomes in this population., (© 2020 The Authors. Maternal & Child Nutrition published by John Wiley & Sons Ltd.)

Introduction: Reliable Health Management and Information System (HMIS) data can be used with minimal cost to identify areas for improvement and to measure impact of healthcare delivery. However, variable HMIS data quality in low- and middle-income countries limits its value in monitoring, evaluation and research. We aimed to review the quality of Rwandan HMIS data for maternal and newborn health (MNH) based on consistency of HMIS reports with facility source documents., Methods: We conducted a cross-sectional study in 76 health facilities (HFs) in four Rwandan districts. For 14 MNH data elements, we compared HMIS data to facility register data recounted by study staff for a three-month period in 2017. A HF was excluded from a specific comparison if the service was not offered, source documents were unavailable or at least one HMIS report was missing for the study period. World Health Organization guidelines on HMIS data verification were used: a verification factor (VF) was defined as the ratio of register over HMIS data. A VF<0.90 or VF>1.10 indicated over- and under-reporting in HMIS, respectively., Results: High proportions of HFs achieved acceptable VFs for data on the number of deliveries (98.7%;75/76), antenatal care (ANC1) new registrants (95.7%;66/69), live births (94.7%;72/76), and newborns who received first postnatal care within 24 hours (81.5%;53/65). This was slightly lower for the number of women who received iron/folic acid (78.3%;47/60) and tested for syphilis in ANC1 (67.6%;45/68) and was the lowest for the number of women with ANC1 standard visit (25.0%;17/68) and fourth standard visit (ANC4) (17.4%;12/69). The majority of HFs over-reported on ANC4 (76.8%;53/69) and ANC1 (64.7%;44/68) standard visits., Conclusion: There was variable HMIS data quality by data element, with some indicators with high quality and also consistency in reporting trends across districts. Over-reporting was observed for ANC-related data requiring more complex calculations, i.e., knowledge of gestational age, scheduling to determine ANC standard visits, as well as quality indicators in ANC. Ongoing data quality assessments and training to address gaps could help improve HMIS data quality., Competing Interests: The authors have declared that no competing interests exist.

Background: As neonatal care improves in low-resource settings, more preterm or low birth weight (LBW) babies are surviving, but little is known about their long-term outcomes. Globally, preterm and/or LBW babies are at increased risk of mortality, malnutrition, and developmental delay., Objectives: We aim to describe the differences in development in rural Rwandan children at 24-36 months of age born preterm and/or LBW compared to their peers born term or normal birth weight (term/NBW), and to assess factors associated with poor development., Methods: We conducted a cross-sectional study using secondary data analysis from two combined datasets from 2014, using Ages and Stages Questionnaire (ASQ-3) for developmental assessment and anthropometrics for nutritional status (stunting and wasting). Demographic and clinical factors associated with poor developmental outcomes in univariate regression at α = 0.20 were included in a full model; we used backward stepwise penalized multivariable logistic regression to identify a final model at α = 0.05., Findings: In total, 445 children were included; 405 term/NBW, and 40 preterm and/or LBW. Half of them (n = 234; 52.6%) had developmental delay, including 207 (51.1%) among term/NBW and 27 (67.5%) among preterm and/or LBW (p = 0.048). In the final model, term/NBW children with stunting alone had a significant increase in the odds of developmental delay (OR 2.05, 95% CI 1.37-3.07), and children with wasting had a borderline statistically significant increased odds of developmental delay (OR 5.79, 95% CI 0.98-34.39). Being preterm and/or LBW and not stunted completely predicted delay., Conclusion: Half of the children had developmental delay in our sample from rural Rwanda. Preterm and/or LBW infants were more likely to have developmental delay, and the main predictor of developmental delay was stunting, with high rates of stunting observed also in term/NBW infants. Interventions to reduce undernutrition and prevent prematurity and LBW, alongside investments to promote early stimulation for optimal development, are needed if gains in addressing developmental delay are to be made., Competing Interests: The authors have no competing interests to declare., (Copyright: © 2019 The Author(s).)

Background: Child growth stunting remains a challenge in sub-Saharan Africa, where 34% of children under 5 years are stunted, and causing detrimental impact at individual and societal levels. Identifying risk factors to stunting is key to developing proper interventions. This study aimed at identifying risk factors of stunting in Rwanda., Methods: We used data from the Rwanda Demographic and Health Survey (DHS) 2014-2015. Association between children's characteristics and stunting was assessed using logistic regression analysis., Results: A total of 3594 under 5 years were included; where 51% of them were boys. The prevalence of stunting was 38% (95% CI: 35.92-39.52) for all children. In adjusted analysis, the following factors were significant: boys (OR 1.51; 95% CI 1.25-1.82), children ages 6-23 months (OR 4.91; 95% CI 3.16-7.62) and children ages 24-59 months (OR 6.34; 95% CI 4.07-9.89) compared to ages 0-6 months, low birth weight (OR 2.12; 95% CI 1.39-3.23), low maternal height (OR 3.27; 95% CI 1.89-5.64), primary education for mothers (OR 1.71; 95% CI 1.25-2.34), illiterate mothers (OR 2.00; 95% CI 1.37-2.92), history of not taking deworming medicine during pregnancy (OR 1.29; 95%CI 1.09-1.53), poorest households (OR 1.45; 95% CI 1.12-1.86; and OR 1.82; 95%CI 1.45-2.29 respectively)., Conclusion: Family-level factors are major drivers of children's growth stunting in Rwanda. Interventions to improve the nutrition of pregnant and lactating women so as to prevent low birth weight babies, reduce poverty, promote girls' education and intervene early in cases of malnutrition are needed.

Background: In Africa, a high proportion of children are at risk for developmental delay. Early interventions are known to improve outcomes, but they are not routinely available. The Rwandan Ministry of Health with Partners In Health/Inshuti Mu Buzima created the Pediatric Development Clinic (PDC) model for providing interdisciplinary developmental care for high-risk infants in rural settings. As retention for chronic care has proven challenging in many settings, this study assesses factors related to retention to care after 12 months of clinic enrollment., Methods: This study describes a retrospective cohort of children enrolled for 12 months in the PDC program in Southern Kayonza district between April 2014-March 2015. We reviewed routinely collected data from electronic medical records and patient charts. We described patient characteristics and the proportion of patients retained, died, transferred out or lost to follow up (LTFU) at 12 months. We used Fisher's exact test and multivariable logistic regression to identify factors associated with retention in care., Results: 228 children enrolled in PDC from 1 April 2014-31 March 2015, with prematurity/low birth weight (62.2%) and hypoxic ischemic encephalopathy (34.5%) as the most frequent referral diagnoses. 64.5% of children were retained in care and 32.5% were LTFU after 12 months. In the unadjusted analysis, we found male sex (p = 0.189), having more children at home (p = 0.027), health facility of first visit (p = 0.006), having a PDC in the nearest health facility (p = 0.136), referral in second six months of PDC operation (p = 0.006), and social support to be associated (100%, p < 0.001) with retention after 12 months. In adjusted analysis, referral in second six months of PDC operation (Odds Ratio (OR) 2.56, 95% CI 1.36, 4.80) was associated with increased retention, and being diagnosed with more complex conditions (trisomy 21, cleft lip/palate, hydrocephalus, other developmental delay) was associated with LTFU (OR 0.34, 95% CI 0.15, 0.76). As 100% of those receiving social support were retained in care, this was not able to be assessed in adjusted analysis., Conclusions: PDC retention in care is encouraging. Provision of social assistance and decentralization of the program are major components of the delivery of services related to retention in care.

Background: Nearly a quarter of a million children have acquired HIV, prompting the implementation of new protocols-Option B and B+-for treating HIV+ pregnant women. While efficacy has been demonstrated in randomized trials, there is limited real-world evidence on the impact of these changes. Using longitudinal, routinely collected data we assessed the impact of the adoption of WHO Option B in Rwanda on mother to infant transmission., Methods: We used interrupted time series analysis to evaluate the impact of Option B on mother-to-child HIV transmission in Rwanda. Our primary outcome was the proportion of HIV tests in infants with positive results at six weeks of age. We included data for 20 months before and 22 months after the 2010 policy change., Results: Of the 15,830 HIV tests conducted during our study period, 392 tested positive. We found a significant decrease in both the level (-2.08 positive tests per 100 tests conducted, 95% CI: -2.71 to -1.45, p < 0.001) and trend (-0.11 positive tests per 100 tests conducted per month, 95% CI: -0.16 to -0.07, p < 0.001) of test positivity. This represents an estimated 297 fewer children born without HIV in the post-policy period or a 46% reduction in HIV transmission from mother to child., Conclusions: The adoption of Option B in Rwanda contributed to an immediate decrease in the rate of HIV transmission from mother to child. This suggests other countries may benefit from adopting these WHO guidelines.

Background: Over half of under-five deaths occur in sub-Saharan Africa and appropriate, timely, quality care is critical for saving children's lives. This study describes the context surrounding children's deaths from the time the illness was first noticed, through the care-seeking patterns leading up to the child's death, and identifies factors associated with care-seeking for these children in rural Rwanda., Methods: Secondary analysis of a verbal and social autopsy study of caregivers who reported the death of a child between March 2013 to February 2014 that occurred after discharge from the child's birth facility in southern Kayonza and Kirehe districts in Rwanda. Bivariate analyses using Fisher's exact tests were conducted to identify child, caregiver, and household factors associated with care-seeking from the formal health system (i.e., community health worker or health facility). Factors significant at α = 0.10 significance level were considered for backwards stepwise multivariate logistic regression, stopping when remaining factors were significantly associated with care-seeking at α = 0.05 significance level., Results: Among the 516 eligible deaths among children under-five, 22.7% (n = 117) did not seek care from the health system. For those who did, the most common first point of contact was community health workers (45.8%). In multivariate logistic regression, higher maternal education (OR = 3.36, 95% CI: 1.89, 5.98), having diarrhea (OR = 4.21, 95%CI: 1.95, 9.07) or fever (OR = 2.03, 95%CI: 1.11, 3.72), full household insurance coverage (3.48, 95%CI: 1.79, 6.76), and longer duration of illness (OR = 22.19, 95%CI: 8.88, 55.48) were significantly associated with formal care-seeking., Conclusion: Interventions such as community health workers and insurance promote access to care, however a gap remains as many children had no contact with the health system prior to death and those who sought formal care still died. Further efforts are needed to respond to urgent cases in communities and further understand remaining barriers to accessing appropriate, quality care.

Background: As care for preterm and low birth weight (LBW) infants improves in resource-limited settings, more infants are surviving the neonatal period. Preterm and (LBW) infants are at high-risk of nutritional and medical comorbidities, yet little is known about their developmental outcomes in low-income countries. This study evaluated the health, nutritional, and developmental status of preterm/LBW children at ages 1-3 years in Rwanda., Methods: Cross-sectional study of preterm/LBW infants discharged between October 2011 and October 2013 from a hospital neonatal unit in rural Rwanda. Gestational age and birth weight were gathered from hospital records to classify small for gestational age (SGA) at birth and prematurity. Children were located in the community for household assessments in November-December 2014. Caregivers reported demographics, health status, and child development using locally-adapted Ages and Stages Questionnaires (ASQ-3). Anthropometrics were measured. Bivariate associations with continuous ASQ-3 scores were conducted using Wilcoxon Rank Sum and Kruskal Wallis tests., Results: Of 158 eligible preterm/LBW children discharged from the neonatal unit, 86 (54.4%) were alive and located for follow-up. Median birth weight was 1650 grams, median gestational age was 33 weeks, and 50.5% were SGA at birth. At the time of household interviews, median age was 22.5 months, 46.5% of children had feeding difficulties and 39.5% reported signs of anemia. 78.3% of children were stunted and 8.8% wasted. 67.4% had abnormal developmental screening. Feeding difficulties (p = 0.008), anemia symptoms (p = 0.040), microcephaly (p = 0.004), stunting (p = 0.034), SGA (p = 0.023), very LBW (p = 0.043), lower caregiver education (p = 0.001), and more children in the household (p = 0.016) were associated with lower ASQ-3 scores., Conclusions: High levels of health, growth, and developmental abnormalities were seen in preterm/LBW children at age 1-3 years. As we achieve necessary gains in newborn survival in resource-limited settings, follow-up and early intervention services are critical for ensuring high-risk children reach their developmental potential.

Background: Children affected by HIV are at risk for poor mental health. We conducted a pilot randomized controlled trial (RCT) of the Family Strengthening Intervention (FSI-HIV), a family home-visiting intervention to promote mental health and improve parent-child relationships in families with caregivers living with HIV, hypothesizing that child and family outcomes would be superior to usual care social work services., Methods: Eighty two families (N = 170 children, 48.24% female; N = 123 caregivers, 68.29% female) with at least one HIV-positive caregiver (n = 103, 83.74%) and school-aged child (ages 7-17) (HIV+ n = 21, 12.35%) were randomized to receive FSI-HIV or treatment-as-usual (TAU). Local research assistants blind to treatment conducted assessments of child mental health, parenting practices, and family functioning at baseline, post-intervention, and 3-month follow-up. Multilevel modeling assessed effects of FSI-HIV on outcomes across three time points., Trial Registration: NCT01509573, 'Pilot Feasibility Trial of the Family Strengthening Intervention in Rwanda (FSI-HIV-R).' https://clinicaltrials.gov/ct2/show/;NCT01509573?term=Pilot+Feasibility+Trial+of+the+Family+Strengthening+Intervention+in+Rwanda+%28FSI-HIV-R%29&rank=1., Results: At 3-month follow-up, children in FSI-HIV showed fewer symptoms of depression compared to TAU by both self-report (β = -.246; p = .009) and parent report (β = -.174; p = .035) but there were no significant differences by group on conduct problems, functional impairment, family connectedness, or parenting., Conclusions: Family-based prevention has promise for reducing depression symptoms in children affected by HIV. Future trials should examine the effects of FSI-HIV over time in trials powered to examine treatment mediators., (© 2017 Association for Child and Adolescent Mental Health.)

Background: As more high-risk newborns survive the neonatal period, they remain at significant medical, nutritional, and developmental risk. However, no follow-up system for early intervention exists in most developing countries. In 2014, a novel Pediatric Development Clinic (PDC) was implemented to provide comprehensive follow-up to at-risk under-five children, led by nurses and social workers in a district hospital and surrounding health centers in rural Rwanda., Methods: At each PDC visit, children undergo clinical/nutritional assessment and caregivers participate in counseling sessions. Social assessments identify families needing additional social support. Developmental assessment is completed using Ages and Stages Questionnaires. A retrospective medical record review was conducted to evaluate the first 24 months of PDC implementation for patients enrolled between April 2014-December 2015 in rural Rwanda. Demographic and clinical characteristics of patients and their caregivers were described using frequencies and proportions. Completion of different core components of PDC visits were compared overtime using Fisher's Exact test and p -values calculated using trend analysis., Results: 426 patients enrolled at 5 PDC sites. 54% were female, 44% were neonates and 35% were under 6 months at enrollment. Most frequent referral reasons were prematurity/low birth weight (63%) and hypoxic-ischemic encephalopathy (34%). In 24 months, 2787 PDC visits were conducted. Nurses consistently completed anthropometric measurements (age, weight, height) at all visits. Some visit components were inconsistently recorded, including adjusted age ( p  = 0.003), interval growth, danger sign assessment, and feeding difficulties ( p  < 0.001). Completion of other visit components, such as child development counseling and play/stimulation activities, were low but improved with time ( p  < 0.001)., Conclusions: It is feasible to implement PDCs with non-specialized providers in rural settings as we were able to enroll a diverse group of high-risk infants. We are seeing an improvement in services offered at PDCs over time and continuous quality improvement efforts are underway to strengthen current gaps. Future studies looking at the outcomes of the children benefiting from the PDC program are underway.

Fostering children is common in sub-Saharan Africa, but few studies examine these children's mental health needs. This study investigated the impact of living in a foster family on the mental health of HIV-positive, HIV-affected and HIV-unaffected children (n = 681 aged 10-17) in rural Rwanda. Regression analyses assessed the impact of living in a foster family on mental health, parenting, and daily hardships; multiple mediation analyses assessed whether family factors mediated the association between foster status and mental health. HIV-positive children were eight times more likely to live in foster families than HIV-unaffected children. Being HIV-affected was predictive of depression and irritability symptoms after controlling for family factors. Controlling for HIV-status, foster children had more symptoms of depression, anxiety, and irritability than non-fostered children. Positive parenting fully mediated the association between foster status and mental health. Mental health and parenting interventions for foster children and HIV-affected children may improve child outcomes.

Introduction: The prevalence of diabetes mellitus is rapidly rising in SSA. Interventions are needed to support the decentralization of services to improve and expand access to care. We describe a clinical mentorship and quality improvement program that connected nurse mentors with nurse mentees to support the decentralization of type 2 diabetes care in rural Rwanda., Methods: This is a descriptive study. Routinely collected data from patients with type 2 diabetes cared for at rural health center NCD clinics between January 1, 2013 and December 31, 2015, were extracted from EMR system. Data collected as part of the clinical mentorship program were extracted from an electronic database. Summary statistics are reported., Results: The patient population reflects the rural settings, with low rates of traditional NCD risk factors: 5.6% of patients were current smokers, 11.0% were current consumers of alcohol, and 11.9% were obese. Of 263 observed nurse mentee-patient encounters, mentor and mentee agreed on diagnosis 94.4% of the time. Similarly, agreement levels were high for medication, laboratory exam, and follow-up plans, at 86.3%, 87.1%, and 92.4%, respectively., Conclusion: Nurses that receive mentorship can adhere to a type 2 diabetes treatment protocol in rural Rwanda primary health care settings.

The Problem: The community health needs assessment (CHNA) mandate of the Patient Protection and Affordable Care Act (ACA) has the potential to make significant and sustainable change in the health of communities. However, to date many hospital-led assessments have used traditional, top-down data collection approaches that overemphasize individualized community member deficits and underutilize collaboration across sectors., Purpose: The purpose of this paper is to present the principles of community-based participatory research (CBPR) as a framework for conducting CHNAs in a way that mitigates the potential for harm, waste, and misrepresentation of community assets and needs that characterizes many existing CHNA processes, illustrating the power of applying CBPR partnerships to this process., Key Points: CBPR is a framework to engage community members directly in research design, the collection and analysis of data, and the creation of action plans that address research findings. Key principles include collaborative involvement, establishment of empowering processes, and long-term commitment. A case example of an innovative community partnership demonstrates the power and challenges of taking a CBPR approach to the CHNA process., Conclusions: CBPR has incredible potential to be incorporated into ACA-mandated hospital CHNAs, leading to increased impact and shared power with community members.

Introduction: Few evidence-based interventions exist to support parenting and child mental health during the process of caregiver HIV status disclosure in sub-Saharan Africa. A secondary analysis of a randomized-controlled trial was conducted to examine the role of family-based intervention versus usual social work care (care as usual) in supporting HIV status disclosure within families in Rwanda., Method: Approximately 40 households were randomized to family-based intervention and 40 households to care as usual. Parenting, family unity, and child mental health during the process of disclosure were studied using quantitative and qualitative research methods., Results: Many of the families had at least one caregiver who had not disclosed their HIV status at baseline. Immediately post-intervention, children reported lower parenting and family unity scores compared with those in the usual-care group. These changes resolved at 3-month follow-up. Qualitative reports from clinical counselor intervention sessions described supported parenting during disclosure. Overall findings suggest adjustments in parenting, family unity, and trust surrounding the disclosure process., Conclusion: Family-based intervention may support parenting and promote child mental health during adjustment to caregiver HIV status disclosure. Further investigation is required to examine the role of family-based intervention in supporting parenting and promoting child mental health in HIV status disclosure.

HIV-affected families report higher rates of harmful alcohol use, intimate partner violence (IPV) and family conflict, which can have detrimental effects on children. Few evidence-based interventions exist to address these complex issues in Sub-Saharan Africa. This mixed methods study explores the potential of a family-based intervention to reduce IPV, family conflict and problems related to alcohol use to promote child mental health and family functioning within HIV-affected families in post-genocide Rwanda. A family home-visiting, evidence-based intervention designed to identify and enhance resilience and communication in families to promote mental health in children was adapted and developed for use in this context for families affected by caregiver HIV in Rwanda. The intervention was adapted and developed through a series of pilot study phases prior to being tested in open and randomized controlled trials (RCTs) in Rwanda for families affected by caregiver HIV. Quantitative and qualitative data from the RCT are explored here using a mixed methods approach to integrate findings. Reductions in alcohol use and IPV among caregivers are supported by qualitative reports of improved family functioning, lower levels of violence and problem drinking as well as improved child mental health, among the intervention group. This mixed methods analysis supports the potential of family-based interventions to reduce adverse caregiver behaviors as a major mechanism for improving child well-being. Further studies to examine these mechanisms in well-powered trials are needed to extend the evidence-base on the promise of family-based intervention for use in low- and middle-income countries.

Implementation lessons: (1) implementation of an effective quality improvement and patient safety program in a rural hospital setting requires collaboration between hospital leadership, Ministry of Health and other stakeholders. (2) Building Quality Improvement (QI) capacity to develop engaged QI teams supported by mentoring can improve quality and patient safety., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Suicide is a leading cause of death for young people. Children living in sub-Saharan Africa, where HIV rates are disproportionately high, may be at increased risk., Aims: To identify predictors, including HIV status, of suicidal ideation and behaviour in Rwandan children aged 10-17., Method: Matched case-control study of 683 HIV-positive, HIV-affected (seronegative children with an HIV-positive caregiver), and unaffected children and their caregivers., Results: Over 20% of HIV-positive and affected children engaged in suicidal behaviour in the previous 6 months, compared with 13% of unaffected children. Children were at increased risk if they met criteria for depression, were at high-risk for conduct disorder, reported poor parenting or had caregivers with mental health problems., Conclusions: Policies and programmes that address mental health concerns and support positive parenting may prevent suicidal ideation and behaviour in children at increased risk related to HIV., (© The Royal College of Psychiatrists 2015.)

Objective: The objective of this study is to assess the feasibility and acceptability of an intervention to reduce mental health problems and bolster resilience among children living in households affected by caregiver HIV in Rwanda., Design: Pre-post design, including 6-month follow-up., Methods: The Family Strengthening Intervention (FSI) aims to reduce mental health problems among HIV-affected children through improved child-caregiver relationships, family communication and parenting skills, HIV psychoeducation and connections to resources. Twenty families (N = 39 children) with at least one HIV-positive caregiver and one child 7-17 years old were enrolled in the FSI. Children and caregivers were administered locally adapted and validated measures of child mental health problems, as well as measures of protective processes and parenting. Assessments were administered at pre and postintervention, and 6-month follow-up. Multilevel models accounting for clustering by family tested changes in outcomes of interest. Qualitative interviews were completed to understand acceptability, feasibility and satisfaction with the FSI., Results: Families reported high satisfaction with the FSI. Caregiver-reported improvements in family connectedness, good parenting, social support and children's pro-social behaviour (P < 0.05) were sustained and strengthened from postintervention to 6-month follow-up. Additional improvements in caregiver-reported child perseverance/self-esteem, depression, anxiety and irritability were seen at follow-up (P < .05). Significant decreases in child-reported harsh punishment were observed at postintervention and follow-up, and decreases in caregiver reported harsh punishment were also recorded on follow-up (P < 0.05)., Conclusion: The FSI is a feasible and acceptable intervention that shows promise for improving mental health symptoms and strengthening protective factors among children and families affected by HIV in low-resource settings.

Universities have traditionally had a vested interest in the civic preparation of students. In order to understand the unique situation of this population of students in a university serving non-traditional community students, qualitative data was used to identify pathways and barriers associated with their civic engagement. Results suggest themes associated with time, knowledge, and access.

The purpose of this article is to examine the attitudes and substance use behaviors of African American adolescents living in the Midwest. A baseline survey was administered to 463 African American teens between the ages of 11-19. The article examines the relationship between attitudes toward drugs and drug-using behavior in this African American sample. Drug use will be compared to national drug use norms established by the Youth Risk Behavior Surveillance Survey. Overall participants had fairly negative attitudes toward drugs. Sixty percent of the sample reported that they were committed to a drug-free life, 74% had made a decision to stay away from marijuana, 79% reported making a decision not to smoke cigarettes, and 71% reported they would not get drunk in the next year. Females were more likely to stay away from marijuana than males. In this current study there is cause for alarm; participants reported higher percentages of ever smoking cigarettes and marijuana than the Youth Risk Behavior Surveillance Survey. This study shows there is a need to provide substance abuse prevention programs for African American adolescents. Limitations and future directions are also discussed.

Numerous studies and interventions have been designed to either reduce the prevalence of risky behaviors (substance use, sexual activity, etc.) or increase the level of educational activity for adolescents. Research suggests that these two constructs may be related yet little is known about this relationship among African American youth. Archival data from the Risk Reduction Project was used to explore the connection between the protective factors of educational aspirations/expectations and recent participation in risky behavior. Results suggest that recent use of marijuana, alcohol to the point of intoxication, and sexual activity predicted lower aspirations and expectations among African American youth. From a positive youth development perspective, this study suggests the development of holistic interventions that build educational assets in youth, in addition to working to minimize risk behaviors. Limitations and suggestions for future research are also discussed.

The purpose of this article is to examine the self-reported sexual attitudes and behaviors of adolescents living in the Midwest. A survey was administered to 463 African American youths ages 11-19. The results indicate that intent to have sexual intercourse, reported likelihood toward having sexual intercourse, and whether participants felt that they would have sex in the next 3 months were predictors of whether they had sexual intercourse at the 3-month follow-up. The results also revealed that the opinions of referent others did not predict sexual intercourse at 3 months. Negative attitudes toward condoms did predict condom use at 3 months and the opinions of referent others also predicted condom use at 3 months. Limitations as well as future research are also discussed.

The purpose of this article was to assess the overall health behaviors of African American emerging adults who live in a Midwestern city. Two hundred participants, ages 18-25, completed a 129-item survey. Results indicate that African American emerging adults are engaged in relatively healthy behaviors (i.e., physical activity, low substance use). The results also showed that within the emerging adult developmental period, there are differences in behavior for those who are in the younger (18-20) versus those that are older (21-25) in the developmental period. Limitations, future research, and implications for practice will also be discussed.

Arctic temperatures are increasing in response to greenhouse gas forcing and polar bears have already responded to changing conditions. Declines in body stature and vital rates have been linked to warming-induced loss of sea-ice. As food webs change and human activities respond to a milder Arctic, exposure of polar bears and other arctic marine organisms to infectious agents may increase. Because of the polar bear's status as arctic ecosystem sentinel, polar bear health could provide an index of changing pathogen occurrence throughout the Arctic, however, exposure and monitoring protocols have yet to be established. We examine prevalence of antibodies to Toxoplasma gondii, and four morbilliviruses (canine distemper [CDV], phocine distemper [PDV], dolphin morbillivirus [DMV], porpoise morbillivirus [PMV]) including risk factors for exposure. We also examine the relationships between antibody levels and hematologic values established in the previous companion article. Antibodies to Toxoplasma gondii and morbilliviruses were found in both sample years. We found a significant inverse relationship between CDV titer and total leukocytes, neutrophils, monocytes, and eosinophils, and a significant positive relationship between eosinophils and Toxoplasma gondii antibodies. Morbilliviral prevalence varied significantly among age cohorts, with 1-2 year olds least likely to be seropositive and bears aged 5-7 most likely. Data suggest that the presence of CDV and Toxoplasma gondii antibodies is associated with polar bear hematologic values. We conclude that exposure to CDV-like antigen is not randomly distributed among age classes and suggest that differing behaviors among life history stages may drive probability of specific antibody presence.

Declines in sea-ice habitats have resulted in declining stature, productivity, and survival of polar bears in some regions. With continuing sea-ice declines, negative population effects are projected to expand throughout the polar bear's range. Precise causes of diminished polar bear life history performance are unknown, however, climate and sea-ice condition change are expected to adversely impact polar bear (Ursus maritimus) health and population dynamics. As apex predators in the Arctic, polar bears integrate the status of lower trophic levels and are therefore sentinels of ecosystem health. Arctic residents feed at the apex of the ecosystem, thus polar bears can serve as indicators of human health in the Arctic. Despite their value as indicators of ecosystem welfare, population-level health data for U.S. polar bears are lacking. We present hematological reference ranges for southern Beaufort Sea polar bears. Hematological parameters in southern Beaufort Sea polar bears varied by age, geographic location, and reproductive status. Total leukocytes, lymphocytes, monocytes, eosinophils, and serum immunoglobulin G were significantly greater in males than females. These measures were greater in nonlactating females ages ≥5, than lactating adult females ages ≥5, suggesting that females encumbered by young may be less resilient to new immune system challenges that may accompany ongoing climate change. Hematological values established here provide a necessary baseline for anticipated changes in health as arctic temperatures warm and sea-ice declines accelerate. Data suggest that females with dependent young may be most vulnerable to these changes and should therefore be a targeted cohort for monitoring in this sentinel.

Neonatal Borna disease (NBD) virus infection in the Lewis rat results in life-long viral persistence and causes behavioral and neurodevelopmental abnormalities. A hallmark of the disorder is progressive loss of cerebellar Purkinje and dentate gyrus granule cells. Findings of increased brain metallothionein-I and -II (MT-I/-II) mRNA expression in cDNA microarray experiments led us to investigate MT isoforms and their relationship to brain zinc metabolism, cellular toxicity, and neurodevelopmental abnormalities in this model. Real-time PCR confirmed marked induction of MT-I/-II mRNA expression in the brains of NBD rats (40.5-fold increase in cerebellum, p<0.0001; 6.8-fold increase in hippocampus, p=0.003; and 9.5-fold increase in striatum, p=0.0012), whereas a trend toward decreased MT-III mRNA was found in hippocampus (1.25-fold decrease, p=0.0841). Double label immunofluorescence revealed prominent MT-I/-II expression in astrocytes throughout the brain; MT-III protein was decreased in granule cell neurons and increased in astrocytes, with differential subcellular distribution from cytoplasmic to nuclear compartments in NBD rat hippocampus. Modified Timm staining of hippocampus revealed reduced zinc in mossy fiber projections to the hilus and CA3, accumulation of zinc in glial cells and degenerating granule cell somata, and robust mossy fiber sprouting into the inner molecular layer of the dentate gyrus. Zinc Transporter 3 (ZnT-3) mRNA expression was decreased in hippocampus (2.3-fold decrease, p= 0.0065); staining for its correlate protein was reduced in hippocampal mossy fibers. Furthermore, 2 molecules implicated in axonal pathfinding and mossy fiber sprouting, the extracellular matrix glycoprotein, tenascin-R (TN-R), and the hyaluronan receptor CD44, were increased in NBD hippocampal neuropil. Abnormal zinc metabolism and mechanisms of neuroplasticity may contribute to the pathogenesis of disease in this model, raising more general implications for neurodevelopmental damage following viral infections in early life.

Primary lymphomas of the female genital tract are rare. Most involve the cervix rather than the uterine corpus. All of those previously reported have been B-cell lymphomas, with the exception of 1 case report of an endometrial T-cell lymphoma in a Japanese woman. We report the case of a white woman from the United States with a diffuse large cell lymphoma of the endometrium, characterized as a peripheral T-cell type on the basis of immunophenotypic and molecular probe studies. Staging evaluation revealed tumor limited to the endometrium (stage IE). The patient underwent a total abdominal hysterectomy, bilateral salpingo-oophorectomy, and lymph node dissection and received 6 cycles of combination chemotherapy, after which she remained free of disease at last follow-up of 36 months. Unusual features of this lymphoma case are discussed, with emphasis on differential diagnosis and speculation on histogenesis. This case illustrates that, while most peripheral T-cell lymphomas are widely disseminated at presentation, those limited to a single extranodal site may have a favorable outcome akin to that associated with high-grade extranodal B-cell lymphomas of early stage.

This article describes the laboratory investigation of an unusual hemoglobinopathy involving hemoglobin (Hb) S, HbSG(Philadelphia), and alpha-thalassemia-2 in a patient whose phenotype was HbSC by alkaline electrophoresis. Findings of a mean corpuscular volume of 62 fL and microcytes on the blood smear were inconsistent with HbSC disease. The patient's clinical course over several years had been mildly symptomatic. Testing in our hospital laboratory using isoelectric focusing and cation-exchange high-performance liquid chromatography to separate hemoglobins showed an unknown variant. Additional studies, including globin chain electrophoresis, reverse-phase high-performance liquid chromatography, and polymerase chain reaction-based DNA analysis were performed at reference laboratories, which reported the following findings: HbG(Philadelphia) associated with alpha-thalassemia-2, HbS and HbG(Philadelphia), and the alpha-globin deletions defining the -alpha3.7/-alpha3.7 genotype. The hemoglobin molecular defects, alpha-thalassemia-2, and the pattern of inheritance are discussed.

Mucosa-associated lymphoid tissue (MALT) lymphomas are low-grade B-cell lymphomas that occur in a variety of extranodal sites but rarely as a primary hepatic lymphoma. We describe the histological findings, immunophenotype, and immunohistochemistry of one such lymphoma found incidentally in a 69-year-old woman. The lymphoid infiltrate invaded the liver in a serpiginous configuration with entrapment of nodules of normal liver. Reactive follicles were surrounded by intermediate-sized lymphoid cells with slightly irregular nuclei and pale cytoplasm. Only a few scattered lymphoepithelial lesions were identified since most of the bile ducts were destroyed. The immunophenotype determined by flow cytometry identified the lymphoid cells as being CD19, CD20 positive and exhibiting lambda light chain restriction. CD5, CD10, and CD23 were negative. Immunohistochemistry showed the neoplastic cells to be positive for CD20 (L-26) and bcl-2. The reactive follicles were negative for bcl-2. CD3 showed only a few scattered T cells. Cyclin D1 did not stain the neoplastic cells. Cytokeratin (AE1/AE3) highlighted the lymphoepithelial lesions and residual bile ducts. MALT lymphomas need to be recognized and distinguished from other B-cell lymphomas, particularly mantle cell lymphomas, because of the difference in behavior and treatment.