Modeling Edar expression reveals the hidden dynamics of tooth signaling center patterning.

When patterns are set during embryogenesis, it is expected that they are straightly established rather than subsequently modified. The patterning of the three mouse molars is, however, far from straight, likely as a result of mouse evolutionary history. The first-formed tooth signaling centers, called MS and R2, disappear before driving tooth formation and are thought to be vestiges of the premolars found in mouse ancestors. Moreover, the mature signaling center of the first molar (M1) is formed from the fusion of two signaling centers (R2 and early M1). Here, we report that broad activation of Edar expression precedes its spatial restriction to tooth signaling centers. This reveals a hidden two-step patterning process for tooth signaling centers, which was modeled with a single activator-inhibitor pair subject to reaction-diffusion (RD). The study of Edar expression also unveiled successive phases of signaling center formation, erasing, recovering, and fusion. Our model, in which R2 signaling center is not intrinsically defective but erased by the broad activation preceding M1 signaling center formation, predicted the surprising rescue of R2 in Edar mutant mice, where activation is reduced. The importance of this R2-M1 interaction was confirmed by ex vivo cultures showing that R2 is capable of forming a tooth. Finally, by introducing chemotaxis as a secondary process to RD, we recapitulated in silico different conditions in which R2 and M1 centers fuse or not. In conclusion, pattern formation in the mouse molar field relies on basic mechanisms whose dynamics produce embryonic patterns that are plastic objects rather than fixed end points.

Staging and normal table of postembryonic development of the clownfish (Amphiprion ocellaris).

BACKGROUND: The clownfish Amphiprion ocellaris is one of the rare coral reef fish species that can be reared in aquaria. With relatively short embryonic and larval development, it could be used as a model species to study the impact of global changes such as temperature rise or anthropogenic threats (eg, pollution) on the postembryonic development at molecular and endocrinological levels. Establishing a developmental table allows us to standardize sampling for the scientific community willing to conduct experiments on this species on different areas: ecology, evolution, and developmental biology. RESULTS: Here, we describe the postembryonic developmental stages for the clownfish A. ocellaris from hatching to juvenile stages (30 days posthatching). We quantitatively followed the postembryonic growth and described qualitative traits: head, paired and unpaired fins, notochord flexion, and pigmentation changes. The occurrence of these changes over time allowed us to define seven stages, for which we provide precise descriptions. CONCLUSIONS: Our work gives an easy system to determine A. ocellaris postembryonic stages allowing, thus, to develop this species as a model species for coral reef fishes. In light of global warming, the access to the full postembryonic development stages of coral reef fish is important to determine stressors that can affect such processes.

A new look at population health through the lenses of cognitive, functional and social disability clustering in eastern DR Congo: a community-based cross-sectional study.

BACKGROUND: The importance of viewing health from a broader perspective than the mere presence or absence of disease is critical at primary healthcare level. However, there is scanty evidence-based stratification of population health using other criteria than morbidity-related indicators in developing countries. We propose a novel stratification of population health based on cognitive, functional and social disability and its covariates at primary healthcare level in DR Congo. METHOD: We conducted a community-based cross-sectional study in adults with diabetes or hypertension, mother-infant pairs with child malnutrition, their informal caregivers and randomly selected neighbours in rural and sub-urban health zones in South-Kivu Province, DR Congo. We used the WHO Disability Assessment Schedule 2.0 (WHODAS) to measure functional, cognitive and social disability. The study outcome was health status clustering derived from a principal component analysis with hierarchical clustering around the WHODAS domains scores. We calculated adjusted odds ratios (AOR) using mixed-effects ordinal logistic regression. RESULTS: Of the 1609 respondents, 1266 had WHODAS data and an average age of 48.3 (SD: 18.7) years. Three hierarchical clusters were identified: 9.2% of the respondents were in cluster 3 of high dependency, 21.1% in cluster 2 of moderate dependency and 69.7% in cluster 1 of minor dependency. Associated factors with higher disability clustering were being a patient compared to being a neighbour (AOR: 3.44; 95% CI: 1.93-6.15), residency in rural Walungu health zone compared to semi-urban Bagira health zone (4.67; 2.07-10.58), female (2.1; 1.25-2.94), older (1.05; 1.04-1.07), poorest (2.60; 1.22-5.56), having had an acute illness 30 days prior to the interview (2.11; 1.24-3.58), and presenting with either diabetes or hypertension (2.73; 1.64-4.53) or both (6.37; 2.67-15.17). Factors associated with lower disability clustering were being informally employed (0.36; 0.17-0.78) or a petty trader/farmer (0.44; 0.22-0.85). CONCLUSION: Health clustering derived from WHODAS domains has the potential to suitably classify individuals based on the level of health needs and dependency. It may be a powerful lever for targeting appropriate healthcare service provision and setting priorities based on vulnerability rather than solely presence of disease.

Evaluation of bottom-up interventions targeting community-dwelling frail older people in Belgium: methodological challenges and lessons for future comparative effectiveness studies.

BACKGROUND: Optimizing the organization of care for community-dwelling frail older people is an important issue in many Western countries. In Belgium, a series of complex, innovative, bottom-up interventions was recently designed and implemented to help frail older people live at home longer. As the effectiveness of these interventions may vary between different population groups according to their long-term care needs, they must be evaluated by comparison with a control group that has similar needs. METHODS: The goal was to identify target groups for these interventions and to establish control groups with similar needs and to explore, per group, the extent to which the utilization of long-term care is matched to needs. We merged two databases: a clinical prospective database and the routine administrative database for healthcare reimbursements. Through Principal Component Analysis followed by Clustering, the intervention group was first stratified into disability profiles. Per profile, comparable control groups for clinical variables were established, based on propensity scores. Using chi-squared tests and logistic regression analysis, long-term care utilization at baseline was then compared per profile and group studied. RESULTS: Stratification highlighted five disability profiles: people with low-level limitations; people with limitations in instrumental activities of daily life and low-level of cognitive impairment; people with functional limitations; people with functional and cognitive impairments; and people with functional, cognitive, and behavioral problems. These profiles made it possible to identify long-term care needs. For instance, at baseline, those who needed more assistance with hygiene tasks also received more personal nursing care (P < 0.05). However, there were some important discrepancies between the need for long-term care and its utilization: while 21% of patients who were totally dependent for hygiene tasks received no personal nursing care, personal nursing care was received by 33% of patients who could perform hygiene tasks. CONCLUSIONS: The disability profiles provide information on long-term care needs but not on the extent to which those needs are met. To assess the effectiveness of interventions, controls at baseline should have similar disability profiles and comparable long-term care utilization. To allow for large comparative effectiveness studies, these dimensions should ideally be available in routine databases.

Serum calcium normal range in 1000 term newborns.

INTRODUCTION: Serum calcium rapidly declines at birth because of the sudden interruption of the maternal-fetal calcium influx. Several factors are known to influence serum calcium in the first days of life, including circulating concentrations of maternal vitamin D. Objective was to establish the normal range variations of neonatal serum calcium according to the French current vitamin D supplementation during pregnancy, i.e. 100,000 IU of cholecalciferol during the third trimester. METHODS: We included in our prospective cohort study 1002 mother-newborn dyads from, with recruitments from April 2012 to July 2014 in France, in two recruiting centers located in Paris neighborhoods. RESULTS: Total serum calcium at 3 days of life in neonates varied from 2.06 to 2.73 mmol/L [2.5 and 97.5 percentiles], with a mean of 2.45 mmol/L. Serum calcium was similar between babies born from vitamin D supplemented mothers and those born from the non-supplemented ones. Univariate and multivariable analyses demonstrated the importance of maternal and cord blood 25(OH)D concentrations for newborn serum calcium maintenance. CONCLUSION: We established that the expected serum calcium in neonates ranges between 2.06 and 2.73 mmol/L which is significantly wider than the adult range. This finding should help physicians in the diagnosis of hypo- or hypercalcemia. In addition, our study supports the importance of vitamin D supplementation and 25(OH)D status for neonatal serum calcium maintenance.

Patterning by heritage in mouse molar row development.

It is known from paleontology studies that two premolars have been lost during mouse evolution. During mouse mandible development, two bud-like structures transiently form that may represent rudimentary precursors of the lost premolars. However, the interpretation of these structures and their significance for mouse molar development are highly controversial because of a lack of molecular data. Here, we searched for typical tooth signaling centers in these two bud-like structures, and followed their fate using molecular markers, 3D reconstructions, and lineage tracing in vitro. Transient signaling centers were indeed found to be located at the tips of both the anterior and posterior rudimentary buds. These centers expressed a similar set of molecular markers as the "primary enamel knot" (pEK), the signaling center of the first molar (M1). These two transient signaling centers were sequentially patterned before and anterior to the M1 pEK. We also determined the dynamics of the M1 pEK, which, slightly later during development, spread up to the field formerly occupied by the posterior transient signaling center. It can be concluded that two rudimentary tooth buds initiate the sequential development of the mouse molars and these have previously been mistaken for early stages of M1 development. Although neither rudiment progresses to form an adult tooth, the posterior one merges with the adjacent M1, which may explain the anterior enlargement of the M1 during mouse family evolution. This study highlights how rudiments of lost structures can stay integrated and participate in morphogenesis of functional organs and help in understanding their evolution, as Darwin suspected long ago.

The effect of temperature and a herbicide mixture on freshwater periphytic algae.

Temperature is a strong driver of biofilm formation and of the dynamics of microalgae in freshwater. Moreover, exposure to herbicides is a well-known stressor of periphytic communities in anthropized aquatic environments. We tested these two environmental factors on periphytic communities that had been sampled from the littoral zone of Lake Geneva and acclimatized in the lab for 3 weeks at 18, 21, 24 and 28 °C. After this acclimation period, differences in the composition of the diatom community and decreases in cell density were observed corresponding to the temperature gradient. These acclimated communities were then exposed to 23 and 140 nM of a mixture composed of equitoxic quantities of atrazine, terbutryn, diuron and isoproturon. The periphytic community was more sensitive to the herbicide mixture at 18 °C than at higher temperatures, suggesting that higher temperature reduced its toxicity. Small and pioneer diatom species known to be promoted by contamination also appeared to benefit from higher temperatures. Temperature therefore appears to condition the herbicide sensitivity of periphytic communities.

Microdeletion of exon 3 in the HBA2 gene associated with mild α-thalassemia trait.

A mother and son presented with mild symptoms of thalassemia trait. Polymerase chain reaction (PCR) amplification of their globin genes revealed a previously unreported 203 bp microdeletion in the HBA2 gene (NG_000006.1:g.34305_34507del; HBA2:c301-30_*44del). Both mother and son were heterozygous for the deletion which included DNA coding for all of exon 3. DNA sequence analysis revealed a six nucleotide repeat (5'-CGGGCC-3') flanking the breakpoint, suggesting that the microdeletion may have arisen as a result of reciprocal recombination within the HBA2 alleles.

Gonadotropin administration to mimic mini-puberty in hypogonadotropic males: pump or injections?

Objective: Newborns with congenital hypogonadotropic hypogonadism (CHH) have an impaired postnatal activation of the gonadotropic axis. Substitutive therapy with recombinant gonadotropins can be proposed to mimic physiological male mini-puberty during the first months of life. The aim of this study was to compare the clinical and biological efficacy of two treatment modalities of gonadotropins administration during mini-puberty in CHH neonates. Design: Multicenter retrospective analytical epidemiological study comparing two treatments, pump vs injection, between 2004 and 2019. Methods: Clinical (penile size, testis size, testicular descent) and biological parameters (serum concentrations of testosterone, anti-Müllerian hormone (AMH) and Inhibin B) were compared between the two groups by multivariate analyses. Results: Thirty-five patients were included. A significantly higher increase in penile length and testosterone level was observed in the injection group compared to the pump group (+0.16 ± 0.02 mm vs +0.10 ± 0.02 mm per day, P = 0.002; and +0.04 ± 0.007 ng/mL vs +0.01 ± 0.008 ng/mL per day, P = 0.001). In both groups, significant increases in penile length and width, testosterone, AMH, and Inhibin B levels were observed, as well as improved testicular descent (odds ratio of not being in a scrotal position at the end of treatment = 0.97 (0.96; 0.99)). Conclusions: Early postnatal administration of recombinant gonadotropins in CHH boys is effective in stimulating penile growth, Sertoli cell proliferation, and testicular descent, with both treatment modalities.

Medical child abuse: Medical history and red flags in French adolescents.

BACKGROUND: Medical child abuse (MCA; or Munchausen syndrome by proxy) is a severe form of adult and medical maltreatment of children. Currently, few data on MCA in adolescents exist. OBJECTIVE: To describe the clinical characteristics and medical history of children and adolescents aged 10 to 18 years with suspected or confirmed MCA in the pediatric hospital setting. METHODS: We included patients aged 10 to 18 years who were seen in five tertiary care hospitals in the Paris area and identified by physician recall such as suspected MCA between 2015 and 2021. RESULTS: We included 29 adolescents; the mean (SD) age was 12.9 (10.8-15.0) years at suspected diagnosis. Medical wandering was common, with a mean of 23 (12.8-33.2) alleged symptoms and 33 (9.2-56.8) specialized consultations in a mean of six different hospitals. The mean number of emergency visits was 11.8 (0-25.9) and radiologic exams 24.3 (5-43.6). Overall, 62 % (18/29) of the adolescents had an underlying organic pathology. The impact of MCA on quality of life was major, with a high rate of school dropout (96 %). The mean delay to the suspected diagnosis was 5.8 (2.6-9) years, and even when recognized, it was rarely the subject of a social or judiciary report (only 42 % of adolescents). In total, 50 % of the adolescents subsequently exhibited Munchausen syndrome. CONCLUSION: Adolescent MCA is poorly known among the medical profession. Increasing awareness, education and knowledge of risk factors could contribute to better care.

Microbe-mediated intestinal NOD2 stimulation improves linear growth of undernourished infant mice.

The intestinal microbiota is known to influence postnatal growth. We previously found that a strain of Lactiplantibacillus plantarum (strain LpWJL) buffers the adverse effects of chronic undernutrition on the growth of juvenile germ-free mice. Here, we report that LpWJL sustains the postnatal growth of malnourished conventional animals and supports both insulin-like growth factor-1 (IGF-1) and insulin production and activity. We have identified cell walls isolated from LpWJL, as well as muramyl dipeptide and mifamurtide, as sufficient cues to stimulate animal growth despite undernutrition. Further, we found that NOD2 is necessary in intestinal epithelial cells for LpWJL-mediated IGF-1 production and for postnatal growth promotion in malnourished conventional animals. These findings indicate that, coupled with renutrition, bacteria cell walls or purified NOD2 ligands have the potential to alleviate stunting.

The Severity of Congenital Hypothyroidism With Gland-In-Situ Predicts Molecular Yield by Targeted Next-Generation Sequencing.

INTRODUCTION: Congenital hypothyroidism with gland-in-situ (CH-GIS) is usually attributed to mutations in the genes involved in thyroid hormone production. The diagnostic yield of targeted next-generation sequencing (NGS) varied widely between studies. We hypothesized that the molecular yield of targeted NGS would depend on the severity of CH. METHODS: Targeted NGS was performed in 103 CH-GIS patients from the French national screening program referred to the Reference Center for Rare Thyroid Diseases of Angers University Hospital. The custom targeted NGS panel contained 48 genes. Cases were classified as solved or probably solved depending on the known inheritance of the gene, the classification of the variants according to the American College of Medical Genetics and Genomics, the familial segregation, and published functional studies. Thyroid-stimulating hormone at CH screening and at diagnosis (TSHsc and TSHdg) and free T4 at diagnosis (FT4dg) were recorded. RESULTS: NGS identified 95 variants in 10 genes in 73 of the 103 patients, resulting in 25 solved cases and 18 probably solved cases. They were mainly due to mutations in the TG (n = 20) and TPO (n = 15) genes. The molecular yield was, respectively, 73% and 25% if TSHsc was ≥ and < 80 mUI/L, 60% and 30% if TSHdg was ≥ and < 100 mUI/L, and 69% and 29% if FT4dg was ≤ and > 5 pmol/L. CONCLUSION: NGS in patients with CH-GIS in France found a molecular explanation in 42% of the cases, increasing to 70% when TSHsc was ≥ 80 mUI/L or FT4dg was ≤ 5 pmol/L.

Puberty induction with recombinant gonadotropin: What impact on future fertility?

Congenital hypogonadotropic hypogonadism (CHH) is a group of rare diseases characterized by inadequate secretion of the gonadotropins LH (luteinizing hormone) and FSH (follicle stimulating hormone) during the physiological activation periods of the gonadotropic axis. The disease? (anomaly) is present from fetal life and usually persists throughout life. Clinically, hypogonadotropic hypogonadism is associated with neonatal clinical signs (micropenis, cryptorchidism in boys in about half of the cases). The diagnosis is sometimes only evoked in the presence of an absence or arrest of pubertal maturation in the adolescent, which is often poorly tolerated physically and psychologically. Different therapeutic options for pubertal induction have been described, but we lack the necessary larger randomized trials to define the best approaches for both sexes. Historically, congenital hypogonadotropic hypogonadism diagnosed at puberty is treated with testosterone injections. These injections allow the development of secondary sexual characteristics, without an increase in testicular volume in severe forms (FSH deficiency), and a pubertal statural peak. During the last twenty years, studies have underlined the beneficial role of recombinant gonadotropins to induce puberty in this population for future fertility. This is what we will develop.

People with chronic wounds cared for at home in Belgium: Prevalence and exploration of care integration needs using health care trajectory analysis.

BACKGROUND: Little is known about the prevalence of people with chronic wounds cared for at home and their care integration needs in Belgium. In high-income countries, chronic wounds are associated with ageing processes, chronic diseases and social and financial vulnerability, resulting in multiple needs. To meet these needs, many health care providers (with nurses figuring prominently) are involved. This can lead to fragmented health care trajectories and the need to strengthen care coordination. OBJECTIVES: This study aims to estimate the prevalence of people with chronic wounds cared for at home in Belgium. It also seeks to explore their health care trajectories and the risk of fragmentation of care to inform policy makers, care providers and research. DESIGN: Cross-sectional. SETTING(S): Home care. PARTICIPANTS: Routinely collected data of reimbursed care of 3467 people with a chronic wound cared for at home in 2018. METHODS: We applied a stratification method to our sample based on health care trajectories. First, we constructed individual sequences of care received during the year. Then we summarised the health care events using a K-mers approach. Finally, a multinomial mixture model was used on the previously obtained summary to cluster individuals according to their health care trajectories. Afterwards, other epidemiological, socioeconomic and health care use indicators were calculated for each health care trajectory group. We also estimated the prevalence of people with chronic wounds treated at home. RESULTS: We constructed six health care trajectory groups for two age categories (<65 and ≥65 years) showing different intensity of care use and type of care. In some health care trajectory groups, generalist care was found to be predominant. In others, specialist care appeared more prevalent. Depending on the health care trajectory group, a significant proportion of people had multiple care providers involved (mainly nurses, medical specialists and GPs), and many of them also had multiple transitions between care settings. The prevalence of people with chronic wounds treated at home rises significantly with age: 0.3%, 95%CI (0.2%-0.4%) for people aged under 65, 2.5%, 95%CI (2.3%-2.8%) for people aged 65 and over. CONCLUSION: A significant proportion of people with chronic wounds experienced multiple transitions and met many health care providers. This can lead to complex trajectories and risk of fragmentation. Nurses, who are intensively involved in wound care at home, with the appropriate skills, could play a 'reference' role to promote continuity of care and better coordination. REGISTRATION: Not registered.

Growth hormone treatment improves final height in children with X-linked hypophosphatemia.

BACKGROUND/AIM: Despite optimal conventional treatment (oral phosphate supplements and active vitamin D analogs), about 40-50% of children with well-controlled X-linked hypophosphatemia (XLH) show linear growth failure, making them less likely to achieve an acceptable final height. Here, we studied the hypothesis that rhGH treatment improves final height in children with XLH and growth failure. METHODS: Two cohorts of children with XLH were included in this retrospective longitudinal analysis: (1) a cohort treated with rhGH for short stature (n = 34) and (2) a cohort not treated with rhGH (n = 29). The mean duration of rhGH treatment was 4.4 ± 2.9 years. We collected the auxological parameters at various time points during follow-up until final height. RESULTS: In rhGH-treated children, 2 years of rhGH therapy was associated with a significant increase in height from - 2.4 ± 0.9 to - 1.5 ± 0.7 SDS (p < 0.001). Their mean height at rhGH discontinuation was - 1.2 ± 0.9 SDS and at final height was - 1.3 ± 0.9 SDS corresponding to 165.5 ± 6.4 cm in boys and 155.5 ± 6.3 cm in girls. Notably, the two groups had similar final heights; i.e., the final height in children not treated with rhGH being - 1.2 ± 1.1 SDS (165.4 ± 6.8 cm in boys and 153.7 ± 7.8 cm in girls), p = 0.7. CONCLUSION: Treatment with rhGH permits to improve final height in children with XLH and growth failure, despite optimal conventional treatment. We propose therefore that rhGH therapy could be considered as an option for short stature in the context of XLH.

Socio-Economic Impacts of COVID-19 on Working Mothers in France.

Beyond its devastating consequences for public health, the COVID-19 pandemic had a major impact on gender inequalities, labour markets and families. Compared to many European countries, the French approach to lockdown was among the more stringent, although the measures taken by the French government to support employment, to some extent, mitigated the worst effects of the crisis on families. This article analyses the implications of COVID lockdown restrictions on gender equality and well-being for couples with children in France. The study adopted a multidimensional approach to gender inequalities associated with paid work and various dimensions of living conditions, involving gender-differentiated access to personal work spaces in the home, personal leisure time outside the home, and local support networks during the first phase of lockdown (March-June 2020). Drawing on data from the COCONEL survey, carried out by the Institut national d'études démographiques on a quota sample of the French adult population in April/May 2020, the authors controlled for variables including socio-economic status, age, family structure and place of residence. The survey data were complemented by a longitudinal set of in-depth interviews enabling the research team to capture the differential effects of the pandemic within couples. The main findings indicate that, despite the frequency of dual-employment arrangements for heterosexual couple households with dependent children, French mothers were nevertheless more likely to reduce their working time and/or withdraw from the labour market. Within the households surveyed, mothers were less likely than fathers to leave the home during the day, particularly for personal leisure activities. The presence of children in households increased gender inequality in both employment and living conditions across all socio-economic categories. In conclusion, the authors consider whether the pandemic might have a long-term impact on gender norms and inequalities within families, and how the findings about changes in gender inequalities could be used to inform public policy development.

Determinants of Final Height in Patients Born Small for Gestational Age Treated with Recombinant Growth Hormone.

INTRODUCTION: About 8% of children born small for gestational age (SGA) do not reach a final height within the normal range. Recombinant human growth hormone (rhGH) has been shown to be effective in increasing the final height in children born SGA. Our objective was to identify predictive factors of final height in children born SGA treated with rhGH. MATERIALS AND METHODS: In this retrospective study, conducted in a tertiary pediatric endocrinology referral center, we recruited all patients born SGA (defined as birth length or weight <10th percentile) treated with rhGH for more than 12 months for whom final height data were available. Some patients had received gonadotropin-releasing hormone (GnRH) analog therapy. RESULTS: We included 252 patients with an average birth length of -2.0 ± 0.7 SD and birth weight of -1.7 ± 1.0 SD. After 4.6 ± 2.8 years of rhGH treatment, their height increased from -2.2 ± 0.9 SD to -1.5 ± 0.9 SD. In multivariate analysis, we identified 8 factors that predict 46% of the final height, namely, cause of SGA (p < 0.0001), GnRH analog therapy >2 years (p = 0.006), birth length (p < 0.02), height at the start of rhGH (p < 0.0001), IGF-1 level at the start of rhGH (p = 0.0002), growth velocity during the 1st year of treatment (p = 0.0002), and age and height at the onset of puberty (p < 0.0001, p = 0.0007, respectively). CONCLUSION: In this large cohort of SGA patients who had reached their final height, we were able to confirm that growth hormone increases final height in short SGA children. In addition, we identified several factors associated with a better response to growth hormone treatment.

Comparative analysis of the health status of the population in six health zones in South Kivu: a cross-sectional population study using the WHODAS.

BACKGROUND: The eastern Democratic Republic of Congo (DRC) has experienced decades-long armed conflicts which have had a negative impact on population's health. Most research in public health explores measures that focus on a specific health problem rather than overall population health status. The aim of this study was to assess the health status of the population and its predictors in conflict settings of South Kivu province, using the World Health Organization Disability Assessment Schedule (WHODAS). METHODS: Between May and June 2019, we conducted a community-based cross-sectional survey among 1440 adults in six health zones (HZ), classified according to their level of armed conflict intensity and chronicity in four types (accessible and stable, remote and stable, intermediate and unstable). The data were collected by a questionnaire including socio-demographic data and the WHODAS 2.0 tool with 12 items. The main variable of the study was the WHODAS summary score measuring individual's health status and synthesize in six domains of disability (household, cognitive, mobility, self-care, social and society). Univariate analysis, correlation and comparison tests as well as hierarchical multiple linear regression were performed. RESULTS: The median WHODAS score in the accessible and stable (AS), remote and stable (RS), intermediate (I) and unstable (U) HZ was 6.3 (0-28.6); 25 (6.3-41.7); 22.9 (12.5-33.3) and 39.6 (22.9-54.2), respectively. Four of the six WHODAS domain scores (household, cognitive, mobility and society) were the most altered in the UHZs. The RSHZ and IHZ had statistically comparable global WHODAS scores. The stable HZs (accessible and remote) had statistically lower scores than the UHZ on all items. In regression analysis, the factors significantly associated with an overall poor health status (or higher WHODAS score) were advanced age, being woman, being membership of an association; being divorced, separated or widower and living in an unstable HZ. CONCLUSIONS: Armed conflicts have a significantly negative impact on people's perceived health, particularly in crisis health zones. In this area, we must accentuate actions aiming to strengthen people's psychosocial well-being.

Magnetic resonance imaging is a valuable tool to evaluate the therapeutic efficacy of burosumab in children with X-linked hypophosphatemia.

PURPOSE: To examine the MRI diagnostic performance in the assessment of therapeutic response to burosumab in children with X-linked hypophosphatemia (XLH). DESIGN: Prospective longitudinal open cohort. PATIENTS: Seventeen children with XLH, average age of 10.2 ± 2.7 years, had a knee MRI at baseline and after 1 year of burosumab. INTERVENTION: Children received burosumab at an average dose of 1.4 ± 0.5 mg/kg during 1 year for the treatment of severe rickets (the target serum phosphate ≥ 1.2 mmol/L (≥3.7 mg/dL). The primary endpoint was the change from baseline to 12 months in rachitic lesions on knee MRI. Secondary endpoints were changes in biochemical parameters of phosphate and alkaline phosphatase (ALP). RESULTS: One year of treatment with burosumab significantly reduced radiological disease activity on knee MRI (by 44 ± 29% in the transverse extent of widening) which was accompanied by a significant reduction in biochemical activity, namely in serum ALP activity, by 28 ± 17%. Additionally, MRI parameters after 1 year of treatment with burosumab (the maximum width of medial physis at 12 months and the change from baseline in the maximum width of lateral physis) were associated with ALP activity at 12 months. CONCLUSION: We suggest that MRI is a valuable and quantitative tool to evaluate the therapeutic response to burosumab. MRI could be an excellent alternative to standard bone radiographs for evaluation of the rachitic lesions in a clinical setting avoiding repeated exposition to ionizing radiation.

Effectiveness of a short functional restoration program for patients with chronic low back pain: A cohort study of 193 patients.

OBJECTIVE: Functional restoration programs (FRPs) are integrative programs to improve function in chronic low back pain (cLBP). They are costly and time-consuming. The aim was to assess the effectiveness of a condensed FRP (CFRP) for patients with cLBP in professional activity. METHODS: Longitudinal 3 months study of patients with cLBP in one tertiary care hospital, participating in a CFRP over 4 separate days. The primary outcome was the Oswestry Disability Index (ODI). Secondary outcomes included pain, quality of life (EQ5D), patient acceptable symptom state, presenteeism, absenteeism and psychological distress. Outcomes were compared using paired sample Student's t-test or Chi2 between baseline and last follow-up. Logistic regression was used to identify factors associated with better response (improvement of ODI higher than 12.8). RESULTS: In all, 193 patients were analysed, mean age 44.6 (standard deviation (SD) 10.4) years, mean cLBP duration 9.0 (SD 8.8) years. A small improvement was observed for ODI (mean difference -5.9, 95% confidence interval: -7.6, -4.1), as well as most other outcomes. Multivariate analysis showed an association between ODI improvement and higher duration of low back pain (odds ratio for 5 years: 1.41 (1.06,1.88)) and lower baseline back strength (Sorensen, odds ratio for 1min: 0.54 [0.29,0.99]). CONCLUSION: This CFRP showed small effect to improve function, pain and other quality of life, in cLBP. Four-day programs may be an interesting option in cLBP patients still in professional activity for whom a long 1-month FRP is difficultly manageable. Further studies with randomized controlled designs are needed to confirm the benefits.