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Marcus Ground,1 Thijmen Veenendaal,1 Daniel Rexie Chiluzi,1 Geoffrey Nkhonjera,2 Arie C Glas,1 Lisanne Glas-van Dijk1 1Mulanje Mission Hospital, Mulanje, Malawi; 2Oncology Department, Queen Elizabeth Central Hospital, Blantyre, MalawiCorrespondence: Marcus Ground, Email marcus.ground@gmail.comAbstract: We present the case of an HIV-positive man diagnosed with multicentric Castleman disease (MCD) associated with human herpesvirus 8 (HHV8) infection, complicated by renal failure. This subtype of an otherwise rare disease is a complication of HIV and HHV8 infection. The diagnosis and management of HHV8-MCD in the developing world is challenging—in part due to its rarity, but largely due to the limited access to histology and other laboratory services. Our case presented with a confusing constellation of symptoms and was diagnosed with MCD on histology. Here we discuss the epidemiology, pathogenesis, diagnosis, and treatment of HHV8-MCD in the context of HIV infection in a resource-limited setting, in the hope that greater awareness will lead to more prompt recognition.Keywords: Castleman disease, HIV, lymphoproliferative disorders, case report, human herpesvirus 8

Abstract Commander is a multiprotein complex that orchestrates endosomal recycling of integral cargo proteins and is essential for normal development. While the structure of this complex has recently been described, how cargo proteins are selected for Commander-mediated recycling remains unclear. Here we identify the mechanism through which the unstructured carboxy-terminal tail of the cargo adaptor sorting nexin-17 (SNX17) directly binds to the Retriever sub-complex of Commander. SNX17 adopts an autoinhibited conformation where its carboxy-terminal tail occupies the cargo binding groove. Competitive cargo binding overcomes this autoinhibition, promoting SNX17 endosomal residency and the release of the tail for Retriever association. Furthermore, our study establishes the central importance of SNX17-Retriever association in the handover of integrin and lipoprotein receptor cargoes into pre-existing endosomal retrieval sub-domains. In describing the principal mechanism of cargo entry into the Commander recycling pathway we provide key insight into the function and regulation of this evolutionary conserved sorting pathway.

Objective: Providing medical care to preterm infants can be rewarding yet also stressful for healthcare providers in the neonatal care unit (NICU). While the impact of provider-parent communication on parent-related stress and satisfaction is widely accepted, little is known about the provider perspective. Therefore, this study explores the relationships between neonatal care providers' communicative competence and their professional quality of life and job satisfaction. Methods: Using the NICU Communication Framework, we conducted a cross-sectional survey among N = 300 Dutch pediatricians‑neonatologists, nurses, and ancillary staff. Results: Communication performance and providers' job satisfaction were correlated, particularly in terms of perceived quality of care, professional relationships, and personal rewards. When providers deemed communication important and perceived themselves as skilled communicators, job satisfaction increased. Experiencing sufficient time for conversations with parents was inversely correlated with provider fatigue and burn-out. Yet, providers reported insufficient opportunity for communication. Conclusion: These results warrant reflection on the importance of communication in neonatal care, for the wellbeing of parents and providers alike. Innovation: Focusing on the provider perspective, this study provides novel insights into the relationships between communication and outcomes of care. Our findings uniquely emphasize the power of communication to foster staff satisfaction and reduce burn-out in the NICU.

Summary: Human leukocyte antigen (HLA) class-I molecules present fragments of the cellular proteome to the T cell receptor (TCR) of cytotoxic T cells to control infectious diseases and cancer. The large number of combinations of HLA class-I allotypes and peptides allows for highly specific and dedicated low-affinity interactions to a diverse array of TCRs and natural killer (NK) cell receptors. Whether the divergent HLA class-I peptide complex is exclusive for interactions with these proteins is unknown. Using genome-wide CRISPR-Cas9 activation and knockout screens, we identified peptide-specific HLA-C∗07 combinations that can interact with the surface molecules CD55 and heparan sulfate. These interactions closely resemble the HLA class-I interaction with the TCR regarding both the affinity range and the specificity of the peptide and HLA allele. These findings indicate that various proteins can specifically bind HLA class-I peptide complexes due to their polymorphic nature, which suggests there are more interactions like the ones we describe here.

Abstract Background Guidelines and regulations in response to the COVID-19 pandemic have significantly impacted the health care sector. We explore these impacts in the gender-based violence (GBV) services sector and, more specifically, in the context of women’s shelters. Methods Using an interpretive description and integrated knowledge mobilization approach, we interviewed 8 women’s shelter clients, 26 staff, and conducted focus groups with 24 Executive Directors. Results We found that pandemic responses challenged longstanding values that guide work in women’s shelters, specifically feminist and anti-oppressive practices. Physical distancing, masking, and closure of communal spaces intended to slow or stop the spread of the novel coronavirus created barriers to the provision of care, made it difficult to maintain or create positive connections with and among women and children, and re-traumatized some women and children. Despite these challenges, staff and leaders were creative in their attempts to provide quality care, though these efforts, including workarounds, were not without their own challenges. Conclusions This research highlights the need to tailor crisis response to sector-specific realities that support service values and standards of care.

Analyses of the Caribbean continue to divide the region based on colonial heritage, which is largely a result of the fact that it primarily consists of small islands. In this article, we demonstrate the inaccuracy of such categorizations on the basis of two sets of arguments. Based on historical as well as contemporary evidence from the Dutch Caribbean, we show that different islands that were artificially united into a single jurisdiction by colonial powers commonly experience intense inter-island rivalries and separatist tendencies. In addition, however, we show evidence pointing to frequent contacts and shared regional identities between neighboring islands belonging to different (post)colonial spheres of influence, both in the past and in the present. In sum, therefore, our interdisciplinary analysis -- combining insights from history and political science -- shows that small islands experience seemingly contradictory tendencies towards both island nationalism and inter-island cooperation, but that cooperation can only work if it is initiated on the terms of islands themselves, and not determined by colonial rulers or metropolitan states.

AimTo review the evidence on safety of maintaining family integrated care practices and the effects of restricting parental participation in neonatal care during the SARS-CoV-2 pandemic.MethodsMEDLINE, EMBASE, PsycINFO and CINAHL databases were searched from inception to the 14th of October 2020. Records were included if they reported scientific, empirical research (qualitative, quantitative or mixed methods) on the effects of restricting or promoting family integrated care practices for parents of hospitalised neonates during the SARS-CoV-2 pandemic. Two authors independently screened abstracts, appraised study quality and extracted study and outcome data.ResultsWe retrieved 803 publications and assessed 75 full-text articles. Seven studies were included, reporting data on 854 healthcare professionals, 442 parents, 364 neonates and 26 other family members, within 286 neonatal units globally. The pandemic response resulted in significant changes in neonatal unit policies and restricting parents' access and participation in neonatal care. Breastfeeding, parental bonding, participation in caregiving, parental mental health and staff stress were negatively impacted.ConclusionThis review highlights that SARS-CoV-2 pandemic-related hospital restrictions had adverse effects on care delivery and outcomes for neonates, families and staff. Recommendations for restoring essential family integrated care practices are discussed.

Aim: Tree crowns determine light interception, carbon and water exchange. Thus, understanding the factors causing tree crown allometry to vary at the tree and stand level matters greatly for the development of future vegetation modelling and for the calibration of remote sensing products. Nevertheless, we know little about large-scale variation and determinants in tropical tree crown allometry. In this study, we explored the continental variation in scaling exponents of site-specific crown allometry and assessed their relationships with environmental and stand-level variables in the tropics. Location: Global tropics. Time period: Early 21st century. Major taxa studied: Woody plants. Methods: Using a dataset of 87,737 trees distributed among 245 forest and savanna sites across the tropics, we fitted site-specific allometric relationships between crown dimensions (crown depth, diameter and volume) and stem diameter using power-law models. Stand-level and environmental drivers of crown allometric relationships were assessed at pantropical and continental scales. Results: The scaling exponents of allometric relationships between stem diameter and crown dimensions were higher in savannas than in forests. We identified that continental crown models were better than pantropical crown models and that continental differences in crown allometric relationships were driven by both stand-level (wood density) and environmental (precipitation, cation exchange capacity and soil texture) variables for both tropical biomes. For a given diameter, forest trees from Asia and savanna trees from Australia had smaller crown dimensions than trees in Africa and America, with crown volumes for some Asian forest trees being smaller than those of trees in African forests. Main conclusions: Our results provide new insight into geographical variability, with large continental differences in tropical tree crown allometry that were driven by stand-level and environmental variables. They have implications for the assessment of ecosystem function and for the monitoring of woody biomass by remote sensing techniques in the global tropics.

Climate change is being intensified by anthropogenic emission of greenhouse gasses, highlighting the value of forests for carbon dioxide storing carbon in their biomass. Seasonally dry tropical forests are a neglected, threatened, but potentially critical biome for helping mitigate climate change. In South America, knowing the amount and distribution of carbon in Caatinga seasonally dry vegetation is essential to understand its contribution to the global carbon cycle and subsequently design a strategic plan for its conservation. The present study aimed to model and map the spatial distribution of the potential forest biomass stock across 32 forest fragments of Caatinga, in the state of Bahia, Brazil, using regression kriging and Inverse Square of Distance techniques, building from point measurements of vegetation biomass made on-the-ground in ecological plots. First, a model for estimating biomass was fitted as a function of environmental variables to apply regression kriging, and then applied to the maps of the selected components. Elevation, temperature, and precipitation explained 46% of the biomass variations in the Caatinga. The model residuals showed strong spatial dependence and were mapped based on geostatistical criteria, selecting the spherical semivariogram model for interpolation by ordinary kriging. Biomass was also mapped by the Inverse Square of Distance approach. The quality of the regression model suggests that there is good potential for estimating biomass here from environmental variables. The regression kriging showed greater detail in the spatial distribution and revealed a spatial trend of increasing biomass from the north to south of the domain. Additional studies with greater sampling intensity and the use of other explanatory variables are suggested to improve the model, as well as to maximize the technique’s ability to capture the actual biomass behavior in this newly studied seasonally dry ecosystem.

Abstract Background The development of second generation sequencing methods has enabled large scale DNA variation studies at moderate cost. For the high throughput discovery of single nucleotide polymorphisms (SNPs) in species lacking a sequenced reference genome, we set-up an analysis pipeline based on a short read de novo sequence assembler and a program designed to identify variation within short reads. To illustrate the potential of this technique, we present the results obtained with a randomly sheared, enzymatically generated, 2-3 kbp genome fraction of six pooled Meleagris gallopavo (turkey) individuals. Results A total of 100 million 36 bp reads were generated, representing approximately 5-6% (~62 Mbp) of the turkey genome, with an estimated sequence depth of 58. Reads consisting of bases called with less than 1% error probability were selected and assembled into contigs. Subsequently, high throughput discovery of nucleotide variation was performed using sequences with more than 90% reliability by using the assembled contigs that were 50 bp or longer as the reference sequence. We identified more than 7,500 SNPs with a high probability of representing true nucleotide variation in turkeys. Increasing the reference genome by adding publicly available turkey BAC-end sequences increased the number of SNPs to over 11,000. A comparison with the sequenced chicken genome indicated that the assembled turkey contigs were distributed uniformly across the turkey genome. Genotyping of a representative sample of 340 SNPs resulted in a SNP conversion rate of 95%. The correlation of the minor allele count (MAC) and observed minor allele frequency (MAF) for the validated SNPs was 0.69. Conclusion We provide an efficient and cost-effective approach for the identification of thousands of high quality SNPs in species currently lacking a sequenced genome and applied this to turkey. The methodology addresses a random fraction of the genome, resulting in an even distribution of SNPs across the targeted genome.

BackgroundActive parent participation in neonatal care and collaboration between parents and professionals during infant hospitalization in the neonatal intensive care unit (NICU) is beneficial for infants and their parents. A tool is needed to support parents and to study the effects and implementation of parent-partnered models of neonatal care.MethodsWe developed and psychometrically evaluated a tool measuring active parent participation and collaboration in neonatal care within six domains: Daily Care, Medical Care, Acquiring Information, Parent Advocacy, Time Spent with Infant and Closeness and Comforting the Infant. Items were generated in focus group discussions and in-depth interviews with professionals and parents. The tool was completed at NICU-discharge by 306 parents (174 mothers and 132 fathers) of preterm infants. Subsequently, we studied structural validity with confirmatory factor analysis (CFA), construct validity, using the Average Variance Extracted and Heterotrait-Monotrait ratio of correlations, and hypothesis testing with correlations and univariate linear regression. For internal consistency we calculated composite reliability (CR). We performed multiple imputations by chained equations for missing data.ResultsA 31 item tool for parent participation and collaboration in neonatal care was developed. CFA revealed high factor loadings of items within each domain. Internal consistency was 0.558 to 0.938. Convergent validity and discriminant validity were strong. Higher scores correlated with less parent depressive symptoms (r = -0.141, 95%CI -0.240; -0.029, p = 0.0141), less impaired parent-infant bonding (r = -0.196, 95%CI -0.302; -0.056, p

BackgroundMany parents develop stress-related symptoms and depression when their preterm infant is hospitalised in the neonatal intensive care unit (NICU) after birth. We reviewed the evidence of parent well-being with preterm infants hospitalised in single family rooms (SFRs) or in open bay neonatal units (OBUs).MethodsFor this systematic review and meta-analysis, we searched MEDLINE, EMBASE, PsycINFO, Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, Clinicaltrials.gov, and International Clinical Trials Registry Platform (ICTRP) databases from inception through 22 November 2019 using controlled terms and text words related to prematurity and NICU-design. We included randomised and non-randomised studies comparing outcomes in parents with preterm infants admitted to SFRs or OBUs. Methodological quality was assessed using Cochrane Collaboration's Risk of Bias Tool for randomised controlled trials and the Risk of Bias Tool for Non-Randomised Studies of Interventions (ROBINS-I). Outcomes included: parental stress, satisfaction, participation (presence/involvement/skin-to-skin care), self-efficacy, parent-infant-bonding, depression, anxiety, post-traumatic stress, empowerment, and degree of family-centred care. Summary estimates were calculated using random effects models with standardised mean differences (SMDs). PROSPERO registration: CRD42016050643.FindingsWe identified 614 unique publications. Eleven study populations (1, 850 preterm infants, 1, 549 mothers and 379 fathers) were included. All but one study were at serious to critical risk of bias. SFRs were associated with higher levels of parental presence, involvement, and skin-to-skin care. Upon discharge, SFRs were associated with lower stress levels (n = 828 parents, SMD-0·30,95%CI -0·50;-0·09, p

Background: Enhancing the application of shared decision-making (SDM) is critical for integrating patient preferences in breast cancer treatment choices. We investigated the effect of an adapted multilevel SDM implementation program in breast cancer care. Methods: Breast cancer patients qualifying for (neo)adjuvant systemic treatment were included in a multicenter before–after study. Consultations were audio recorded between June 2018 and July 2019 and analyzed using the five-item Observing Patient Involvement in Decision-Making (OPTION-5) instrument to score SDM application by clinicians. The Shared Decision-Making Questionnaire (SDM-Q-9) was used to rate patients’ perceived SDM level. Consultation duration, decision types, number of options discussed and consultations per patient were monitored. Regression analysis was used to investigate the correlated variables and program components. Results: Mean OPTION-5 scores increased from 33.9 (n = 63) before implementation to 54.3 (n = 49) after implementation (p < 0.001). The SDM-Q-9 scores did not change: 91.1 (n = 51) at baseline versus 88.9 (n = 23) after implementation (p = 0.81). Without increasing consultation time, clinicians discussed more options after implementation. The regression analysis showed that exposure to the implementation program, redistribution of tasks and discussing feedback from consultations was associated with a higher level of SDM. Conclusion: The multilevel program helped clinicians achieve clinically relevant improvement in SDM, especially when it is tailored to (individuals in) teams and includes (e-)training, discussing feedback on consultations and redistribution of tasks.

IntroductionFall rates and fall-related injuries among community-dwelling older adults (≥65 years) are expected to increase rapidly, due to the aging population worldwide. Fall prevention programs (FPPs), consisting of strength and balance exercises, have been proven effective in reducing fall rates among older adults. However, these FPPs have not reached their full potential as most programs are under-enrolled. Therefore, this study aims to identify promising strategies that promote participation in FPPs among community-dwelling older adults.MethodsThis is an exploratory qualitative study. Previously, barriers and facilitators for participation in FPPs by older adults had been identified. Next, six strategies had been designed using the Intervention Mapping approach: (1) reframing; (2) informing about benefits; (3) raising awareness of risks; (4) involving social environment; (5) offering tailored intervention; (6) arranging practicalities. Strategies were validated during semi-structured interviews with community-dwelling older adults (n = 12) at risk of falling. Interviews were audio-recorded, transcribed, and analyzed following a qualitative thematic methodology, with a hybrid approach.ResultsAll strategies were considered important by at least some of the respondents. However, two strategies stood out: (1) reframing ‘aging’ and ‘fall prevention’: respondents preferred to be approached differently, taking a ‘life course’ perspective about falls, and avoiding confronting words; and (2) ‘informing about benefits’ (e.g., ‘living independently for longer’); which was mentioned to improve the understanding of the relevance of participating in FPPs. Other strategies were considered important to take into account too, but opinions varied more strongly.DiscussionThis study provides insight into potential strategies to stimulate older adults to participate in FPPs. Results suggest that reframing ‘aging’ and ‘fall prevention’ may facilitate the dialogue about fall prevention, by communicating differently about the topic, for example ‘staying fit and healthy’, while focusing on the benefits of participating in FPPs. Gaining insight into the strategies’ effectiveness and working mechanisms is an area for future research. This could lead to practical recommendations and help professionals to enhance older adults’ participation in FPPs. Currently, the strategies are further developed to be applied and evaluated for effectiveness in multiple field labs in a central Dutch region (Utrecht).