Shade avoidance: phytochrome signalling and other aboveground neighbour detection cues

Plants compete with neighbouring vegetation for limited resources. In competition for light, plants adjust their architecture to bring the leaves higher in the vegetation where more light is available than in the lower strata. These architectural responses include accelerated elongation of the hypocotyl, internodes and petioles, upward leaf movement (hyponasty), and reduced shoot branching and are collectively referred to as the shade avoidance syndrome. This review discusses various cues that plants use to detect the presence and proximity of neighbouring competitors and respond to with the shade avoidance syndrome. These cues include light quality and quantity signals, mechanical stimulation, and plant-emitted volatile chemicals. We will outline current knowledge about each of these signals individually and discuss their possible interactions. In conclusion, we will make a case for a whole-plant, ecophysiology approach to identify the relative importance of the various neighbour detection cues and their possible interactions in determining plant performance during competitio

Synthesis of Porous Inorganic Hollow Fibers without Harmful Solvents

A route for the fabrication of porous inorganic hollow fibers with high surface-area-to-volume ratio that avoids harmful solvents is presented. The approach is based on bio-ionic gelation of an aqueous mixture of inorganic particles and sodium alginate during wet spinning. In a subsequent thermal treatment, the bio-organic material is removed and the inorganic particles are sintered. The method is applicable to the fabrication of various inorganic fibers, including metals and ceramics. The route completely avoids the use of organic solvents, such as N-methyl-2-pyrrolidone, and additives associated with the currently used fiber fabrication methods. In addition, it inherently avoids the manifestation of so-called macro voids and allows the facile incorporation of additional metal oxides in the inorganic hollow fibers

Self-report and parent-report of physical and psychosocial well-being in Dutch adolescents with type 1 diabetes in relation to glycemic control

BACKGROUND: To determine physical and psychosocial well-being of adolescents with type 1 diabetes by self-report and parent report and to explore associations with glycemic control and other clinical and socio-demographic characteristics. METHODS: Demographic, medical and psychosocial data were gathered from 4 participating outpatient pediatric diabetes clinics in the Netherlands. Ninety-one patients completed the Child Health Questionnaire-CF87 (CHQ-CF87), Centre for Epidemiological Studies scale for Depression (CES-D), and the DFCS (Diabetes-specific Family Conflict Scale). Parents completed the CHQ-PF50, CES-D and the DFCS. RESULTS: Mean age was 14.9 years (± 1.1), mean HbA(1c )8.8% (± 1.7; 6.2–15.0%). Compared to healthy controls, patients scored lower on CHQ subscales role functioning-physical and general health. Parents reported less favorable scores on the behavior subscale than adolescents. Fewer diabetes-specific family conflicts were associated with better psychosocial well-being and less depressive symptoms. Living in a one-parent family, being member of an ethnic minority and reporting lower well-being were all associated with higher HbA(1c )values. CONCLUSION: Overall, adolescents with type 1 diabetes report optimal well-being and parent report is in accordance with these findings. Poor glycemic control is common, with single-parent families and ethnic minorities particularly at risk. High HbA(1c )values are related to lower social and family functioning

Prevention and management of adverse events related to regorafenib

Regorafenib is an oral multikinase inhibitor that has shown antitumor activity in a range of solid tumors. Based on data from phase III clinical trials, regorafenib is indicated for the treatment of adult patients with metastatic colorectal cancer who have previously been treated with, or are not considered candidates for, other available therapies, and in patients with advanced gastrointestinal stromal tumors that cannot be surgically removed and no longer respond to other appropriate treatments. A panel of oncology nurses, research coordinators, and other medical oncology experts, experienced in the care of patients treated with regorafenib, met to discuss the best practice for the management of regorafenib-associated adverse events (AEs). The panel agreed that, in clinical trials and daily practice with regorafenib, AEs are common but mostly manageable. The most common and/or important AEs associated with regorafenib were considered to be hand-foot skin reaction, rash or desquamation, stomatitis, diarrhea, hypertension, liver abnormalities, and fatigue. This manuscript describes the experience and recommendations of the panel for managing these AEs in everyday clinical practice. Appropriate education, monitoring, and management are considered essential for reducing the incidence, duration, and severity of regorafenib-associated AEs. © 2013 The Author(s)

conceptual mapping of a complex adaptive system based on multi-disciplinary expert insights

Funding Information: This study was partially funded by VLIR-UOS. The study sponsors had no role in the study design, the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication. Publisher Copyright: © 2022, The Author(s).Background: HIV drug resistance (HIVDR) continues to threaten the effectiveness of worldwide antiretroviral therapy (ART). Emergence and transmission of HIVDR are driven by several interconnected factors. Though much has been done to uncover factors influencing HIVDR, overall interconnectedness between these factors remains unclear and African policy makers encounter difficulties setting priorities combating HIVDR. By viewing HIVDR as a complex adaptive system, through the eyes of multi-disciplinary HIVDR experts, we aimed to make a first attempt to linking different influencing factors and gaining a deeper understanding of the complexity of the system. Methods: We designed a detailed systems map of factors influencing HIVDR based on semi-structured interviews with 15 international HIVDR experts from or with experience in sub-Saharan Africa, from different disciplinary backgrounds and affiliated with different types of institutions. The resulting detailed system map was conceptualized into three main HIVDR feedback loops and further strengthened with literature evidence. Results: Factors influencing HIVDR in sub-Saharan Africa and their interactions were sorted in five categories: biology, individual, social context, healthcare system and ‘overarching’. We identified three causal loops cross-cutting these layers, which relate to three interconnected subsystems of mechanisms influencing HIVDR. The ‘adherence motivation’ subsystem concerns the interplay of factors influencing people living with HIV to alternate between adherence and non-adherence. The ‘healthcare burden’ subsystem is a reinforcing loop leading to an increase in HIVDR at local population level. The ‘ART overreliance’ subsystem is a balancing feedback loop leading to complacency among program managers when there is overreliance on ART with a perceived low risk to drug resistance. The three subsystems are interconnected at different levels. Conclusions: Interconnectedness of the three subsystems underlines the need to act on the entire system of factors surrounding HIVDR in sub-Saharan Africa in order to target interventions and to prevent unwanted effects on other parts of the system. The three theories that emerged while studying HIVDR as a complex adaptive system form a starting point for further qualitative and quantitative investigation.publishersversionpublishe

the interplay of two wicked problems

Funding Information: This work was funded by VLIR-UOS, grant numbers TZ2019SIN263 and TZ2020JOI032A101. Publisher Copyright: ©Concern is justified observing the link between the AIDS and COVID-19 pandemics. COVID-19 outcomes are significantly worse in many people living with HIV (PLHIV), even when vaccinated, because of their impaired immune system. Moreover, CD4 T-cells are affected by both HIV and SARS-CoV-2.1-3 SARS-CoV-2 variants can evolve in immunosuppressed patients due to prolonged viral replication in the context of an inadequate immune response.4 Accelerated intrahost evolution of SARS-CoV-2 was reported in a South African HIV patient with antiretroviral therapy (ART) failure.5 6 With 25 million HIV patients in sub-Saharan Africa (SSA) of whom an estimated 8 million are not virologically suppressed, this potentially creates a reservoir for future variants. Such variants, arising in PLHIV anywhere in the world, can spread to other continents, as has been reported for variants of concern (VoCs) (Beta, Omicron) and variants of interest (B.1.6.20, B.1.640.2) that arose in Africa.7-9 Conversely, the COVID-19 pandemic impacts HIV treatment programmes, due to supply chain issues, overburdening of healthcare systems, limiting access to testing, treatment and prevention programmes and further increasing inequalities.10 Modelled COVID-19 disruptions of HIV programmes in SSA included decreased functionality of HIV prevention programmes, HIV testing and treatment, healthcare services such as viral load testing, adherence counselling, drug regimen switches and ART interruptions, which may lead to selection of drug-resistant HIV.11 A 6-month interruption affecting 50% of the population would lead to a median number of excess deaths of 296 000, during 1 year. Scientists advocate for the AIDS and COVID-19 pandemics in Africa to be addressed simultaneously, by increasing African access to COVID-19 vaccines, prioritising research on the interaction between HIV care and COVID-19, maintaining high-quality HIV services and integrating health services for both viruses.7 Both the COVID-19 and the AIDS pandemic, more specifically the issue of HIV drug resistance (HIVDR), have previously been described as wicked problems which are best studied as complex adaptive systems (CASs).12-15Wicked problems consist of diverse interconnected factors and require complexity-informed and locally adapted solutions rather than one solution that fits all. We recently designed a qualitative model of all known factors influencing HIVDR in SSA and analysed its complexity.13 Our detailed systems map featured three main feedback loops driving HIVDR, representing (1) the alternation between adherence and non-adherence, (2) the impact of an overburdened healthcare system and (3) the importance of sustaining global efforts of tackling HIVDR even when new antiretroviral drugs with high genetic barriers become available. These HIV-related feedback loops are interconnected with COVID-19 pandemic impact (in yellow, figure 1). The loop starts from PLHIV with an unsuppressed viral load, which weakens the immune system and may in turn slow down immune clearance of SARS-CoV-2, allowing prolonged replication and mutation of the virus in the context of an inadequate immune response. Prolonged viral clearance facilitates the selection of immune escape SARS-CoV-2 variants. Variants may emerge that have a selective advantage and therefore may spread through populations due to increased transmissibility (with possibly increased virulence), thereby creating an additional burden on the healthcare system, putting the overall healthcare system and the HIV care at risk. These stressors on the healthcare system lead to a higher risk of unsuppressed viral load in PLHIV, increasing the risk of HIVDR. Figure 1 shows the need to address both wicked problems simultaneously and to do so in a complexity-informed manner as they are inevitably linked and influence each other. Evidently, the exact interconnections between both pandemics need to be locally assessed. For instance, a study in South Africa showed that while lockdown severely impacted HIV testing and ART initiation, ART provision was largely maintained, indicating that the strength of the connection between the virological suppression-related loop and the pandemic, indicated in figure 1, are context-dependent.16publishersversionpublishe

Novel Leptin Receptor Mutations Identified in Two Girls with Severe Obesity Are Associated with Increased Bone Mineral Density

Background: Recessive mutations in the leptin receptor (LEPR) are a rare cause of hyperphagia and severe early-onset obesity. To date, the phenotype has only been described in 25 obese children, some of whom also had altered immune function, hypogonadotropic hypogonadism, reduced growth hormone secretion, hypothalamic hypothyroidism or reduced adult height. We provide a detailed description of the phenotype of 2 affected girls to add to this knowledge. Methods: Whole-exome sequencing and targeted sequencing were used to detect the LEPR mutations. RNA analysis was performed to assess the effect of splice-site mutations. Results: In 2 unrelated girls with severe obesity, three novel LEPR mutations were detected. Longitudinal growth data show normal childhood growth, and in the older girl, a normal adult height despite hypogonadotropic hypogonadism and the lack of an obvious pubertal growth spurt. Bone age is remarkably advanced in the younger (prepubertal) girl, and bone mineral density (BMD) is high in both girls, which might be directly or indirectly related to leptin resistance. Conclusion: The spectrum of clinical features of LEPR deficiency may be expanded with increased BMD. Future observations in LEPR-deficient subjects should help further unravel the role of leptin in human bone biology

Dementia in Rare Genetic Neurodevelopmental Disorders:A Systematic Literature Review

BACKGROUND AND OBJECTIVES: Knowledge of young-onset Alzheimer disease in adults with Down syndrome has greatly improved clinical care. However, little is known about dementia in rare genetic neurodevelopmental disorders (RGNDs). In this review, a comprehensive overview is provided of reports on dementia and cognitive/adaptive trajectories in adults with RGNDs. METHODS: A systematic literature review was conducted in Embase, Medline ALL, and PsycINFO on December 6, 2022. The protocol was registered in PROSPERO (CRD42021223041). Search terms for dementia, cognitive and adaptive functioning, and RGNDs were combined using generic terms and the Orphanet database. Study characteristics and descriptive data on genetic diagnosis, clinical and neuropathologic features, comorbidities, and diagnostic methods were extracted using a modified version of the Cochrane Data Extraction Template. RESULTS: The literature search yielded 40 publications (17 cohorts, 23 case studies) describing dementia and/or cognitive or adaptive trajectories in adults with 14 different RGNDs. Dementia was reported in 49 individuals (5 cohorts, 20 cases) with a mean age at onset of 44.4 years. Diagnostics were not disclosed for half of the reported individuals (n = 25/49, 51.0%). A total of 44 different psychodiagnostic instruments were used. MRI was the most reported additional investigation (n = 12/49, 24.5%). Comorbid disorders most frequently associated with cognitive/adaptive decline were epilepsy, psychotic disorders, and movement disorders. DISCUSSION: Currently available literature shows limited information on aging in RGNDs, with relatively many reports of young-onset dementia. Longitudinal data may provide insights into converging neurodevelopmental degenerative pathways. We provide recommendations to optimize dementia screening, diagnosis, and research.</p

Dementia in Rare Genetic Neurodevelopmental Disorders:A Systematic Literature Review

BACKGROUND AND OBJECTIVES: Knowledge of young-onset Alzheimer disease in adults with Down syndrome has greatly improved clinical care. However, little is known about dementia in rare genetic neurodevelopmental disorders (RGNDs). In this review, a comprehensive overview is provided of reports on dementia and cognitive/adaptive trajectories in adults with RGNDs. METHODS: A systematic literature review was conducted in Embase, Medline ALL, and PsycINFO on December 6, 2022. The protocol was registered in PROSPERO (CRD42021223041). Search terms for dementia, cognitive and adaptive functioning, and RGNDs were combined using generic terms and the Orphanet database. Study characteristics and descriptive data on genetic diagnosis, clinical and neuropathologic features, comorbidities, and diagnostic methods were extracted using a modified version of the Cochrane Data Extraction Template. RESULTS: The literature search yielded 40 publications (17 cohorts, 23 case studies) describing dementia and/or cognitive or adaptive trajectories in adults with 14 different RGNDs. Dementia was reported in 49 individuals (5 cohorts, 20 cases) with a mean age at onset of 44.4 years. Diagnostics were not disclosed for half of the reported individuals (n = 25/49, 51.0%). A total of 44 different psychodiagnostic instruments were used. MRI was the most reported additional investigation (n = 12/49, 24.5%). Comorbid disorders most frequently associated with cognitive/adaptive decline were epilepsy, psychotic disorders, and movement disorders. DISCUSSION: Currently available literature shows limited information on aging in RGNDs, with relatively many reports of young-onset dementia. Longitudinal data may provide insights into converging neurodevelopmental degenerative pathways. We provide recommendations to optimize dementia screening, diagnosis, and research.</p