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Microglia are specialized brain-resident macrophages that arise from primitive macrophages colonizing the embryonic brain 1 . Microglia contribute to multiple aspects of brain development, but their precise roles in the early human brain remain poorly understood owing to limited access to relevant tissues 2-6 . The generation of brain organoids from human induced pluripotent stem cells recapitulates some key features of human embryonic brain development 7-10 . However, current approaches do not incorporate microglia or address their role in organoid maturation 11-21 . Here we generated microglia-sufficient brain organoids by coculturing brain organoids with primitive-like macrophages generated from the same human induced pluripotent stem cells (iMac) 22 . In organoid cocultures, iMac differentiated into cells with microglia-like phenotypes and functions (iMicro) and modulated neuronal progenitor cell (NPC) differentiation, limiting NPC proliferation and promoting axonogenesis. Mechanistically, iMicro contained high levels of PLIN2 + lipid droplets that exported cholesterol and its esters, which were taken up by NPCs in the organoids. We also detected PLIN2 + lipid droplet-loaded microglia in mouse and human embryonic brains. Overall, our approach substantially advances current human brain organoid approaches by incorporating microglial cells, as illustrated by the discovery of a key pathway of lipid-mediated crosstalk between microglia and NPCs that leads to improved neurogenesis., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Human ageing is accompanied by poor responses to infection and decreased vaccine efficacy. While the causes of this can be attributed to defects in the immune system that increase with age, it is unknown whether mitochondrial dysfunction may also contribute to these phenomena. This study aims to assess mitochondrial dysfunction in CD4+ terminal effector memory T cells re-expressing CD45RA (TEMRA) cells and other CD4+ memory T cell subtypes, which are increased in number in the elderly population, with respect to how their metabolic responses to stimulation are altered compared to CD4+ naïve T cells. In this study, we show that CD4+ TEMRA cells exhibit altered mitochondrial dynamics compared to CD4+ naïve cells and CD4+ central and effector memory cells, with a 25% reduction in OPA1 expression. CD4+ TEMRA and memory cells show increased upregulation of Glucose transporter 1 following stimulation and higher levels of mitochondrial mass compared to CD4+ naïve T cells. Additionally, TEMRA cells exhibit a decrease in mitochondrial membrane potential compared to other CD4+ memory cell subsets by up to 50%. By comparing young to aged individuals, more significant mitochondria mass and lower membrane potential were observed in CD4+ TEMRA of young individuals. In conclusion, we suggest that CD4+ TEMRA cells may be impaired with respect to their metabolic response to stimulation, possibly contributing to impaired responses to infection and vaccination.

Unlabelled: We report a case of extrapulmonary tuberculosis with oligoarthritis and synovitis in a 6-year-old girl with undiagnosed disseminated tuberculosis., Clinical Case: The child, adopted from Ethiopia, was admitted to the pediatric rheumatology unit for suspected idiopathic juvenile arthritis. She presented with clinical signs of subacute arthritis of the right knee. Joint symptoms began insidiously and followed a short period of fever and pain in the right hip. Clinical examination showed voluminous cervical lymphadenitis, night sweats, and a moderate alteration of the child's general condition. The medical history revealed that since her arrival in France, 2 years before, she had had febrile subacute pneumonia. A review of the chest x-ray diagnosed primary pulmonary tuberculosis. An intradermal tuberculin test confirmed the diagnosis with a phlyctenular response and a diameter exceeding 20mm. Additional evaluation showed cervical lymphadenitis and intense synovitis of the right hip and knee joints. With an appropriate antitubercular regimen, her condition improved within a few months. After 1 year of treatment, magnetic resonance imaging (MRI) showed normalization of the impaired joints with no functional sequelae., Discussion: Although the spine is a common target for osteoarticular tuberculosis (OAT), peripheral involvement in this case underlines the polymorphism of OAT in children. It illustrates a case of OAT strictly located to the synovial membranes, which usually occurs in one-third of OAT cases. In addition, MRI showed tenosynovitis of the quadriceps. The child presented with unilateral oligoarthritis instead of chronic insidious monoarthritis or symmetrical oligoarthritis as usually described in pediatric OAT. When available, MRI is the best way to evaluate OAT lesions. Mycobacterium tuberculosis can be isolated from sputum, gastric aspiration, and joint fluid or synovial biopsy. Histological lesions can reveal advanced tuberculosis with the presence of caseous follicular lesions. Rapid bacterial detection using polymerase chain reaction remains insufficiently useful in those situations. The recommended therapeutic regimen consists of 3 months with four antitubercular agents (rifampicin, isoniazid, pyrazinamide, and ethambutol) followed by 9 months of a dual therapy (isoniazid, rifampicin)., (Copyright © 2010 Elsevier Masson SAS. All rights reserved.)

Objective: Describe the epidemiology of tourniquet syndromes and a cohort of such children admitted to the pediatric emergency department (PED), analyze the family's social situation to detect neglect behaviors, and analyze subsequent hospital admissions., Patient and Methods: From 1st January 2003 to 31st May 2009 in the PED, all patients admitted for tourniquet syndrome were included in the study. The data collected were day and time of admission, age, sex, length of stay, medical coverage, type and location of the constrictive agent, therapeutic management, progression, and complications. PED social workers in relation with child protective services (CPS) recovered information on the family's social situation., Results: During the study period, 57 children were registered. The mean number of admissions per year was 8 (range: 2-15). The mean age was 5.5+/-4 months. The toe was the most frequent location (95%). The penis was injured in 2 cases and labia majora in 1 case. The constrictive agent was often a hair (95%). One case of abuse was detected. The analysis of family social situations showed that 53% had no or incomplete medical coverage, 67% were already followed by CPS with extreme poverty or lived in dilapidated housing. Insufficient hygiene or neglect was found in 67% of the families with incomplete or no social coverage. The analysis of 2003-2007 period for later admissions identified that 15 accidents in the home occurred in 12 children. Among these families, 58% were already known by CPS for neglect behavior., Conclusion: Although most tourniquet syndromes seem accidental, this entity is often associated with a lack of hygiene. Several and distant locations (e.g., toes and genitals), multiple and/or separated knots, constrictive agents inconsistent with a safe environment for the child, and penile location in an infant require meticulous investigation because of a higher incidence of child neglect., (Copyright 2010 Elsevier Masson SAS. All rights reserved.)

Aim: Analysis of domestic low-voltage (220-240 V) electrical injury in children admitted to a pediatric emergency department to illustrate the low risk of initial or delayed risk of arrhythmia., Material and Methods: Retrospective study between 2001 and 2008 analyzing all children aged less than 15 years admitted for a low-voltage electrical injury. The data collected were age, sex, time and circumstances of the accident, time and day of admission, transport modalities, presence of risk factors for arrhythmia (transthoracic current, wet skin, tetany, loss of consciousness or neurological symptoms, and initial EKG abnormalities), injuries, EKG, muscular and/or cardiac enzyme values, progression and complications. For statistical analysis, data were entered in Microsoft Excel tables. Analysis was done with StatView5.1 (SAS Institute) and Epi Info 6.04fr (VF, ENSP epiconcept). In the descriptive analysis, the data are presented as mean values with SD, median and range., Results: Forty-eight children were included. The mean annual number of admissions was equal to 6 (range, 3-12). The mean age was 6.2 + or - 4.3 years (median, 4.6 years). There was a male predominance: the overall sex ratio was 1.5, i.e., 3 before the age of 2 and 2.6 before the age of 10. The electrical injury occurred after contact with a wire or a connected cord or after the introduction of a metallic object in a wall socket. Ten children had risk factors of arrhythmia (mainly wet skin or thoracic pain). Twenty-nine children suffered from burns to the extremities (digits and hands, 70 %). At admission, 45 children had an EKG performed. The initial EKG was considered abnormal in 8 cases showing: sinusal tachycardia (n=4), incomplete right bundle branch block (n=4), and V(1) negative T waves (n=1). The EKG normalized within the first 12h. Hospitalization for cardiac monitoring was required for 18 children. No delayed arrhythmia occurred. In a mean time of 3.5h after the accident, a troponin dosage was given to 15 children and was normal in all cases. One child developed rhabdomyolysis and evolved without needing dialysis., Conclusion: After a low-voltage electrical injury, initial arrhythmia is not frequent, with often a nonspecific and transitory EKG expression; delayed arrhythmia is very rare. Children presenting to the emergency department after such an electrical accident, who are asymptomatic, without any risk factors for arrhythmia (wet skin, tetany, vertical pathway of the current, preexistent cardiological conditions, loss of consciousness) and with a normal initial EKG do not require cardiac monitoring., (Copyright 2010 Elsevier Masson SAS. All rights reserved.)

Aims: Analyze the epidemiology and the distribution of judo injuries in a pediatric population., Patients and Methods: A retrospective study was conducted from May 2006 to May 2008, including all patients aged less than 15 years admitted to a tertiary-level pediatric emergency unit. The data collected were age, sex, geographic origin, time and day of admission, duration in the pediatric emergency department, body weight, type and location of injuries, and progression. For statistical analysis, data were entered in Microsoft Excel tables. In the descriptive analysis, data are presented as mean values with SD. To compare qualitative variables, a chi(2) test was used and the two-tailed Fisher exact test if the expected value was lesser or equal to 5. Statistical significance was considered at P<0.05., Results: During the study period, 173 patients were included, with a male:female ratio of 2.46. The mean age was 10.6+/-2.4 years. Most children were admitted during the weekend (59 %). The distribution of lesions was contusions (44 %), fractures (31 %), sprains (19 %), dislocations (3 %), and wounds (3 %). The upper extremities were more frequently affected than the lower extremities (46 % vs. 25 %), with a significant male prevalence (78 %) (P<0.0001), dominated by fractures (54 %), especially clavicle fractures (72 %). Compared to the other injuries, the male population had a significantly higher risk of fractures (P=0.04). Thirteen children required hospitalization for surgical repair of fractures., Conclusion: Frequent and often benign, judo accidents in children are different from adult injuries in their mechanisms and injury distribution. There is also an additional risk of growth plate damage. Risk factors have been attributed to an increased injury incidence: body weight loss over 5 % or overweight, age and judo experience, and male gender. During competition and training sessions, the evaluation and prevention of these factors could decrease the occurrence of such injuries., (Copyright 2009 Elsevier Masson SAS. All rights reserved.)

Aims: Provide a descriptive analysis of children admitted to a tertiary care pediatric emergency department (PED) for a nasal foreign body (NFB) and describe the current knowledge and management of such accidents., Material and Methods: A retrospective study was conducted from January 2003 to May 2008, including all patients aged less than 15 years admitted for a NFB. The data collected were age, sex, geographic origin, time and day of admission, duration in PED, duration of NFB insertion, nostril location, symptoms and clinical signs, prehospital extraction attempts, facial x-ray, extraction mode, referral to an ENT specialist, progression, and complications. For statistical analysis, the data were entered in Microsoft Excel spreadsheets. The data were analyzed with StatView 5.1 (SAS Institute) and EpiInfo 6.04fr (VF, ENSP Epiconcept). In the descriptive analysis, the data are presented as mean values with standard deviation, median with extreme values or with 95% confidence intervals where appropriate, unless otherwise indicated. To compare qualitative variables, a chi(2) test (Mantel-Haenszel) was used and the two-tailed Fisher exact test if the expected value was 5 or less. Statistical significance was set at p<0.05., Results: A total of 388 patients were included (393 NFB). The annual mean number of cases was 68. The annual distribution showed a higher number in January, March, April, and October following Christmas, Easter and Halloween celebrations, totaling 40% of all NFB admissions. The sex-ratio was 0.95. Children aged less than 4 years accounted for 71% of the studied population. The mean age was 3.5+/-1.6 years (range, 1.4-13 years). The majority of accidents occurred at home (95%). The length of time spent in the PED was 78+/-57 min. The NFB duration of insertion was unknown in one-quarter of cases, present for less than 4 h in 65% of cases. No symptoms were described in most cases (88%). When symptoms were described, bleeding, pain or nasal discomfort, and foul nasal odor were the principal symptoms. The right nostril was the predominant location (60%). This difference tended to disappear in the group of children aged less than 4 years. Five children had bilateral NFB. Nonorganic compounds accounted for 80% of the NFB: plastic beads or balls (39%), plastic or toy parts (20%), stones or pebbles (11%), and paper (6%). The extraction was instrumental in 82% of cases, and 26% of patients were referred to an ENT specialist when PED attempts were unsuccessful. One child needed hospitalization for extraction under general anesthesia of two beads located deep in the same nostril. No complication occurred. Five children had repeated accidents within an average delay of 6 months., Conclusion: Often benign, this frequent accident can be serious in case of batteries or neodymium magnet insertion: the extraction becomes an emergency because of risks of nasal mucosa necrosis and/or nasal septum perforation. In other cases, positive pressure techniques (the parent's kiss or its variants) could be tried first in the emergency department or at home at the time of a call to emergency services before a medical visit.