Impaired GABAergic regulation and developmental immaturity in interneurons derived from the medial ganglionic eminence in the tuberous sclerosis complex.

GABAergic interneurons play a critical role in maintaining neural circuit balance, excitation-inhibition regulation, and cognitive function modulation. In tuberous sclerosis complex (TSC), GABAergic neuron dysfunction contributes to disrupted network activity and associated neurological symptoms, assumingly in a cell type-specific manner. This GABAergic centric study focuses on identifying specific interneuron subpopulations within TSC, emphasizing the unique characteristics of medial ganglionic eminence (MGE)- and caudal ganglionic eminence (CGE)-derived interneurons. Using single-nuclei RNA sequencing in TSC patient material, we identify somatostatin-expressing (SST+) interneurons as a unique and immature subpopulation in TSC. The disrupted maturation of SST+ interneurons may undergo an incomplete switch from excitatory to inhibitory GABAergic signaling during development, resulting in reduced inhibitory properties. Notably, this study reveals markers of immaturity specifically in SST+ interneurons, including an abnormal NKCC1/KCC2 ratio, indicating an imbalance in chloride homeostasis crucial for the postsynaptic consequences of GABAergic signaling as well as the downregulation of GABAA receptor subunits, GABRA1, and upregulation of GABRA2. Further exploration of SST+ interneurons revealed altered localization patterns of SST+ interneurons in TSC brain tissue, concentrated in deeper cortical layers, possibly linked to cortical dyslamination. In the epilepsy context, our research underscores the diverse cell type-specific roles of GABAergic interneurons in shaping seizures, advocating for precise therapeutic considerations. Moreover, this study illuminates the potential contribution of SST+ interneurons to TSC pathophysiology, offering insights for targeted therapeutic interventions.

Menstrual pattern in polycystic ovary syndrome and hypothalamic-pituitary-ovarian axis immaturity in adolescents: a systematic review and meta-analysis.

OBJECTIVE: To analyze differences in the menstrual pattern, age at menarche, and body mass index (BMI) in adolescents with Hypothalamic-Pituitary-Ovarian (HPO) axis immaturity and Polycystic Ovary Syndrome (PCOS) through a systematic review and meta-analysis. METHODS: The PubMed, EMBASE, Web of Science, Virtual Health Library, Scopus databases were searched using combinations of descriptors. Study quality was assessed using the Newcastle-Ottawa Scale. For data analysis, the results were grouped into PCOS group and NPCOS group (HPO axis immaturity). We performed a meta-analysis of raw data and the inverse variance method, employing the standardized mean difference, of the age at menarche and BMI of adolescents. RESULTS: Participants totaled 1,718 from nine selected studies. The meta-analysis showed that the PCOS group had a higher BMI than the NPCOS group (SMD 0.334; CI95% 0.073 - 0.595; p = .012). The degree of heterogeneity of the studies was approximately 40%. No significant difference in age at menarche (SMD - 0.027; CI95% -0.227 - 0.172; p = 0.790) and menstrual patterns was found, but amenorrhea was described only in adolescents with PCOS. CONCLUSIONS: The main characteristic in menstrual pattern that differentiated PCOS patients from girls with HPO axis immaturity was amenorrhea. Also, the BMI of PCOS patients was nearly one third higher than that of adolescents with HPO axis immaturity.

T-Cell Acute Lymphoblastic Leukemia/Lymphoma (T-ALL) With Negative Screening Immaturity Markers and Gamma-Delta Receptor Expression.

T-cell acute lymphoblastic leukemia/lymphoma (T-ALL) is characterized by the combination of T-cell lineage and the presence of immaturity marker(s). Sometimes, the most common immaturity markers for initial flow cytometry screening in T-ALL may be negative, which can be a diagnostic pitfall. When a lack of common first-line immaturity markers is encountered in combination with gamma/delta T-cell receptor expression, a misdiagnosis of mature gamma-delta T-cell leukemia/lymphoma could be rendered. Here, we discuss two T-ALL cases with the absence of common flow cytometry immaturity markers and positive gamma/delta receptor expression.

Incidence and management of secondary deformities after megaendoprosthetic proximal femur replacement in skeletally immature bone sarcoma patients.

INTRODUCTION: Megaendoprosthetic reconstruction of bone defects in skeletally immature patients has led to the development of unique complications and secondary deformities not observed in adult patient cohorts. With an increasing number of megaendoprosthetic replacements performed, orthopedic oncologists still gain experience in the incidence and type of secondary deformities caused. In this study, we report the incidence, probable cause and management outcome of two secondary deformities after megaendoprosthetic reconstruction of the proximal femur: hip dysplasia and genu valgum. MATERIALS AND METHODS: Retrospective analysis of 14 patients who underwent primary and/or repeat reconstruction/surgery with a megaendoprosthetic proximal femur replacement between 2018 and 2022. RESULTS: Mean patient age was 9.1 years (range 4-17 years). Stress shielding was observed in 71.4%. Hip dislocation was the most frequent complication (50%). While four dislocations occurred without an underlying deformity, secondary hip dysplasia was identified in 58.3% (n = 7/12) of intraarticular resections and reconstructions, leading to dislocation in 71.4% (n = 5/7). A genu valgum deformity was observed in 41.6% (n = 5/12). The incidence of secondary hip dysplasia and concomitant genu valgum was 42.9% (n = 3/7). Triple pelvic osteotomy led to rebound hip dysplasia in two cases (patients aged < 10 years), whereas acetabular socket replacement led to stable hip joints over the course of follow-up. Temporary hemiepiphyseodesis was applied to address secondary genu valgum. CONCLUSIONS: Patients aged < 10 years were prone to develop secondary hip dysplasia and genu valgum following proximal femur replacement in this study. Management of secondary deformities should depend on remaining skeletal growth. Stress shielding was observed in almost all skeletally immature patients.

Outcomes of "Over the Top" Anterior Cruciate Ligament Reconstruction Associated with a Lateral Extra-Articular Tenodesis in Children.

(1) Purpose: The incidence of anterior cruciate ligament (ACL) ruptures in children and adolescents has considerably increased during the last decades due to higher levels of competitive athletic activity, and early sport specialization and professionalization. Contemporary ACL reconstruction techniques have recently been subject to renewed interest in this population. The objective of this study is to report the short- and mid-term results of our physis-sparing ACL reconstruction technique using an "over the top" technique associated with a modified Lemaire procedure. (2) Methods: A retrospective series of 12 junior soccer players who presented to our clinic with a torn ACL between January 2019 and September 2021 was reviewed. The inclusion criteria were patients under 15 years with open tibial and femoral physes, with a stable contralateral knee, a minimum follow-up of 6 months, and a time frame from injury to surgery of <3 months. Patients with previous knee surgery, structural concomitant injuries, muscular, neurological, or vascular abnormalities, or hypersensitivity to metal alloys were excluded. The functional evaluation was performed using the International Knee Documentation Committee (IKDC) rating, Lysholm score, and Tegner activity level. Moreover, clinical and radiological assessments were also performed, including KT-1000 and knee X-rays. (3) Results: We identified 1 female and 11 male patients with ACL tears, with a mean age of 13.17 ± 0.9 months. Concomitant injuries include isolated vertical and bucket-handle tears of the medial meniscus, lateral meniscus tears, bilateral tear of both menisci. The mean follow-up time was 26 ± 12.6 months. The average IKDC, Lysholm and Tegner scores were 93.29 ± 11.04, 95.08 ± 13.2 and 9 ± 0.0 points, respectively. The average KT-1000 score of the participants was 0.96 ± 1.6 points. None of the included patients reported post-surgical complications or required additional surgeries. (4) Conclusions: Our novel ACL reconstruction with LET technique is a safe procedure that resulted in good clinical outcomes, lower failure rate and return to sports in skeletally immature patients.

Risk factors for poor oocyte yield and oocyte immaturity after GnRH agonist triggering.

STUDY QUESTION: What are the potential risk factors for poor oocyte recuperation rate (ORR) and oocyte immaturity after GnRH agonist (GnRHa) ovulation triggering? SUMMARY ANSWER: Lower ovarian reserve and LH levels after GnRHa triggering are risk factors of poor ORR. Higher BMI and anti-Müllerian hormone (AMH) levels are risk factors of poor oocyte maturation rate (OMR). WHAT IS KNOWN ALREADY: The use of GnRHa to trigger ovulation is increasing. However, some patients may have a suboptimal response after GnRHa triggering. This suboptimal response can refer to any negative endpoint, such as suboptimal oocyte recovery, oocyte immaturity, or empty follicle syndrome. For some authors, a suboptimal response to GnRHa triggering refers to a suboptimal LH and/or progesterone level following triggering. Several studies have investigated a combination of demographic, clinical, and endocrine characteristics at different stages of the treatment process that may affect the efficacy of the GnRHa trigger and thus be involved in a poor endocrine response or efficiency but no consensus exists. STUDY DESIGN, SIZE, DURATION: Bicentric retrospective cohort study between 2015 and 2021 (N = 1747). PARTICIPANTS/MATERIALS, SETTING, METHODS: All patients aged 18-43 years who underwent controlled ovarian hyperstimulation and ovulation triggering by GnRHa alone (triptorelin 0.2 mg) for ICSI or oocyte cryopreservation were included. The ORR was defined as the ratio of the total number of retrieved oocytes to the number of follicles >12 mm on the day of triggering. The OMR was defined as the ratio of the number of mature oocytes to the number of retrieved oocytes. A logistic regression model with a backward selection method was used for the analysis of risk factors. Odds ratios (OR) are displayed with their two-sided 95% confidence interval. MAIN RESULTS AND THE ROLE OF CHANCE: In the multivariate analysis, initial antral follicular count and LH level 12-h post-triggering were negatively associated with poor ORR (i.e. below the 10th percentile) (OR: 0.61 [95% CI: 0.42-0.88]; P = 0.008 and OR: 0.86 [95% CI: 0.76-0.97]; P = 0.02, respectively). A nonlinear relationship was found between LH level 12-h post-triggering and poor ORR, but no LH threshold was found. A total of 25.3% of patients suffered from oocyte immaturity (i.e. OMR < 75%). In the multivariate analysis, BMI and AMH levels were negatively associated with an OMR < 75% (OR: 4.34 [95% CI: 1.96-9.6]; P < 0.001 and OR: 1.22 [95% CI: 1.03-1.12]; P = 0.015, respectively). Antigonadotrophic pretreatment decreased the risk of OMR < 75% compared to no pretreatment (OR: 0.72 [95% CI: 0.57-0.91]; P = 0.02). LIMITATIONS, REASONS FOR CAUTION: Our study is limited by its retrospective design and by the exclusion of patients who had hCG retriggers. However, this occurred in only six cycles. We were also not able to collect information on the duration of pretreatment and the duration of wash out period. WIDER IMPLICATIONS OF THE FINDINGS: In clinical practice, to avoid poor ORR, GnRHa trigger alone should not be considered in patients with higher BMI and/or low ovarian reserve, balanced by the risk of ovarian hyperstimulation syndrome. In the case of a low 12-h post-triggering LH level, practicians must be aware of the risk of poor ORR, and hCG retriggering could be considered. STUDY FUNDING/COMPETING INTEREST(S): None. TRIAL REGISTRATION NUMBER: N/A.

Effect of hip dysplasia on the development of the femoral head growth plate.

Purpose: The purpose of this study was to observe whether developmental dysplasia of the hip (DDH) affects the development of the femoral head growth plate and to analyze the risk factors. Methods: We selected female patients aged between 11 and 20 years with unilateral DDH and unclosed femoral head growth plate (s). The selected patients underwent anteroposterior radiography of the hip joint to compare the degree of development of the femoral head growth plate on both sides and to identify risk factors that affect the development of the growth plate in the femoral head. Results: We included 48 female patients with unilateral DDH, with an average age of 14 years (range: 11.1-18.5 years) and an average BMI of 20.4 kg/m² (range: 15.5 kg/m²-27.9 kg/m²). Among them, 23 patients had earlier development of the femoral head growth plate on the affected side than on the healthy side, while the degree of development of the femoral head growth plate in 25 patients was the same as that on the contralateral side. When the Tönnis angle was greater than 29.5°C and/or the Reimers migration index was greater than 48.5%, there was a statistically significant difference in the acceleration of femoral head growth plate development. Conclusion: An abnormal relative position of the acetabulum-femoral head caused by DDH can accelerate closure of the femoral head growth plate in immature female patients. The risk factors are a Tönnis angle greater than 29.5°C and/or Reimers migration index greater than 48.5%.

[Changes in neonatal care : Implications for ophthalmological care]. / Wandel der neonatologischen Versorgung : Implikationen für die augenärztliche Versorgung.

BACKGROUND: Preterm infants are at risk of characteristic, sometimes life-threatening diseases and development of deficits related to immaturity. In the field of ophthalmology, retinopathy of prematurity (ROP) and vision impairment reflect structural and functional disturbances in this large group of patients. In high income countries, more and more very immature preterm infants survive into adolescence and adulthood. OBJECTIVE: To characterize the impact of an increasing number of surviving individuals born preterm on the provision of ophthalmological care in Germany. MATERIAL AND METHODS: A literature search and analysis of key figures and quality indicators published in national health registers were carried out. RESULTS: Currently, about 60,000 preterm infants are born in Germany every year. Of these, approximately 3600 extremely immature preterm infants with a gestational age < 28 weeks are treated with a curative approach on neonatal units. The survival rate is around 80%. A rise in the proportion of infants suffering from severe ROP has not been observed in recent years in Germany. The incidences of other structural and functional visual impairments vary between 3% and 25% in high income countries. CONCLUSION: The incidence of ROP apparently has not increased in Germany. However, specific peculiarities of the structure and function of the visual system of individuals born preterm have to be taken into account. Approximately 70,000 outpatient check-ups of infants and toddlers, who require both, ophthalmological and developmental neurological expertise, are estimated for Germany each year.

Internal Fixation of Unstable Osteochondritis Dissecans of the Knee: Long-term Outcomes in Skeletally Immature and Mature Patients.

BACKGROUND: Osteochondritis dissecans (OCD) is a disorder originating in the subchondral bone, leading to focal lesions with risk of fragmentation and secondary damage of the articular cartilage. It remains controversial if surgical treatment of such lesions is equally successful in skeletally immature and mature patients. PURPOSE: To determine (1) the long-term clinical success rate after internal fixation of unstable OCD in skeletally immature and mature patients based on physeal status, (2) if patient-specific and procedural variables influence the risk of failure, and (3) patient-reported outcome measures over time. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: A multicenter retrospective cohort study was conducted investigating skeletally immature and mature patients treated for unstable OCD lesions of the knee between 2000 and 2015. The healing rate was assessed by radiological imaging and clinical follow-up. Failure was defined as any definitive reoperation for the initially treated OCD lesion. RESULTS: A total of 81 patients met inclusion criteria, including 25 skeletally immature patients and 56 patients with closed physes at the time of surgery. After a mean follow-up time of 11.3 ± 4 years, 58 (71.6%) patients had healed lesions, whereas the lesions failed to heal in 23 (28.4%) patients. No significant difference in risk of failure was observed based on physeal maturation status (hazard ratio, 0.78; 95% CI, 0.33-1.84; P = .56). Lateral versus medial condylar lesion location conferred an increased risk of failure (P < .05) for both skeletally immature and mature patients. Multivariate analysis of skeletal maturity status showed that a lateral femoral condylar location was an independent risk factor for failure (hazard ratio, 0.22; 95% CI, 0.1-0.5; P < .05). The mean patient-reported outcome scores (International Knee Documentation Committee [IKDC] score and Knee injury and Osteoarthritis Outcome Score [KOOS]) increased significantly after surgery and remained high at the final follow-up (P < .05). The final scores (mean ± SD) at a mean follow-up of 135.8 months (range, 80-249 months) were IKDC, 86.6 ± 16.7; KOOS Pain, 88.7 ± 18.1; KOOS Symptoms, 89.3 ± 12.6; KOOS Activities of Daily Living, 89.3 ± 21.6; KOOS Sport and Recreation, 79.8 ± 26.3; and KOOS Quality of Life, 76.7 ± 26.3. CONCLUSION: The long-term results after internal fixation of OCD fragments show high rates of healing and sustainable subjective improvement of knee function and quality of life. A healing rate of 72% was noted at a mean follow-up of 11.3 years. The stage of skeletal maturity had no significant influence on the rate of failure. Lateral femoral condylar lesion location is an independent risk factor for failure in skeletally mature and immature patients.

Case report: Bilateral damage to the immature optic radiation and secondary massive loss of retinal ganglion cells causing tunnel vision.

We describe the case of a 30-year-old woman, who needed a formal report on her visual impairment to seek support from society. She was born preterm, and during her neonatal period, she suffered from bilateral intraventricular hemorrhage (IVH) grade 3, a condition that can cause cerebral visual impairment (CVI) due to damage to the retro-geniculate visual pathways. Individuals with such brain damage of this severity are often restricted by cerebral palsy (CP) and intellectual disability, and thus have a limited ability to cooperate in the assessment of visual function. However, our patient was capable of providing reliable test results, and she manifested only a small island of central vision in each eye, with additional reduced visual acuities. She cooperated well in examinations involving MRI of the brain, optical coherence tomography (OCT) of retinal ganglion cells, and multi-focal visual evoked potentials, with each test providing information about potential limitations in the structural prerequisites for visual function. What distinguishes our case is the severity of the damage to the optic radiations and the massive secondary loss of most of her retinal ganglion cells (GCs). However, there is some measurable visual function, which may be due to developmental neuroplasticity during early development, when surviving GCs prioritize the central visual field. Despite her visual difficulties, she is a keen portrait painter. Our patient may be representative of, and a spokesperson for, other individuals with extensive brain damage of the same etiology, who are unable to perform perimetric tests and therefore run the risk of not being recognized as severely visually impaired, and consequently, not being given the best conditions for habilitation. OCT may serve as a helpful diagnostic tool. Aim: This study aims to describe visual behavior and practical applications of visual function in relation to structural prerequisites for visual function.

Overcoming chemoresistance in non-angiogenic colorectal cancer by metformin via inhibiting endothelial apoptosis and vascular immaturity.

The development of chemoresistance which results in a poor prognosis often renders current treatments for colorectal cancer (CRC). In this study, we identified reduced microvessel density (MVD) and vascular immaturity resulting from endothelial apoptosis as therapeutic targets for overcoming chemoresistance. We focused on the effect of metformin on MVD, vascular maturity, and endothelial apoptosis of CRCs with a non-angiogenic phenotype, and further investigated its effect in overcoming chemoresistance. In situ transplanted cancer models were established to compare MVD, endothelial apoptosis and vascular maturity, and function in tumors from metformin- and vehicle-treated mice. An in vitro co-culture system was used to observe the effects of metformin on tumor cell-induced endothelial apoptosis. Transcriptome sequencing was performed for genetic screening. Non-angiogenic CRC developed independently of angiogenesis and was characterized by vascular leakage, immaturity, reduced MVD, and non-hypoxia. This phenomenon had also been observed in human CRC. Furthermore, non-angiogenic CRCs showed a worse response to chemotherapeutic drugs in vivo than in vitro. By suppressing endothelial apoptosis, metformin sensitized non-angiogenic CRCs to chemo-drugs via elevation of MVD and improvement of vascular maturity. Further results showed that endothelial apoptosis was induced by tumor cells via activation of caspase signaling, which was abrogated by metformin administration. These findings provide pre-clinical evidence for the involvement of endothelial apoptosis and subsequent vascular immaturity in the chemoresistance of non-angiogenic CRC. By suppressing endothelial apoptosis, metformin restores vascular maturity and function and sensitizes CRC to chemotherapeutic drugs via a vascular mechanism.

Familial association and epidemilogical factors as risk factors for developing first time and recurrent patella dislocation: a systematic review and best knowledge synthesis of present literature.

PURPOSE: The aim of our study was to perform a systematic review and best knowledge synthesis of the present literature concerning the familial association and epidemiological factors as risk factors for developing first-time and recurrent patella dislocation. METHODS: The study was conducted according to the PRISMA guidelines and registered in PROSPERO. EMBASE and PubMed were systematically searched on the 5th of May 2022. Studies investigating participants with genetic and epidemiological risk factors for the first time as well as recurrent patella dislocation were included. The records were screened, and data were extracted independently by two researchers supervised by a third independent assessor. RESULTS: A total of 6,649 records were screened, and 67 studies were included. Familial association was described as a risk factor for patella dislocation in 17 studies. One study found that participants with a family history of patella dislocation had a 3.7 higher risk for patella dislocation in the contralateral asymptomatic knee, and another study found a family history of PD in 9% of 74 participants. Eleven studies found an accumulation of patella dislocation across generations in specific families. Additionally, a range of genetic syndromes was associated with patella dislocation. Young age is a well-investigated risk factor for patella dislocation, but the results are inconsistent. Only five and eight studies investigated skeletal immaturity and gender as risk factors for patella dislocation, respectively. CONCLUSION: There may be a familial association with patella dislocation, but further investigation is necessary to determine the strength and etiology of the association. There is weak evidence that epidemiological risk factors, such as age, skeletal immaturity, gender, and BMI are risk factors for patella dislocation. LEVEL OF EVIDENCE: IV.

Intestinal atresia and necrotizing enterocolitis: Embryology and anatomy.

The primitive gut originates at week 3 of gestation from the endoderm, with posterior incorporation of the remaining embryo layers. Wnt, Notch and TLR4 pathways have been shown to play central roles in the correct development of the intestine. The classical hypothesis for intestinal atresia development consists of failure in bowel recanalization or a vascular accident with secondary bowel reabsorption. These have been challenged due to the high frequency of associated malformations, and furthermore, with the discovery of molecular pathways and genes involved in bowel formation and correlated defects producing atresia. Necrotizing enterocolitis (NEC) has a multifactorial pathogenesis with prematurity being the most important risk factor; therefore, bowel immaturity plays a central role in NEC. Some of the same molecular pathways involved in gut maturation have been found to correlate with the predisposition of the immature bowel to develop the pathological findings seen in NEC.

Outcome of Santulli enterostomy in patients with immaturity of ganglia: single institutional experience from a case series.

BACKGROUND: Immaturity of ganglia (IG) is an extremely rare disease and always requires surgical intervention in the neonatal period, but without guidelines to choose the ideal enterostomy procedure, the timing of stoma closure remains controversial. The aim of this study was to report our experience using Santulli enterostomy for the treatment of nine infants diagnosed with IG. METHODS: Patients who underwent Santulli enterostomy and were diagnosed with IG in our center between 2016 and 2021 were retrospectively studied. Temporary stoma occlusion and a 24-h delayed film of barium enema (BE) were performed to evaluate intestinal peristalsis function to determine the timing of stoma closure. The demographic data, clinical and radiological findings, stoma occlusion and stoma closure results were explored. RESULTS: A total of 9 infants underwent Santulli enterostomy and were diagnosed with IG postoperatively. Their median gestational age at birth was 36 weeks (range 31-42), and their median birth weight was 2765 g (range 1300-3400). All patients had symptom onset in the neonatal period, including abdominal distension and biliary vomiting. Eight patients showed obvious small bowel dilatation in the plain films, except for one patient's films that suggested gastrointestinal perforation with free gas downstream of the diaphragm. BE was performed in 6 patients, all of which had microcolons. The median age at operation was 3 days (range 1-23). Seven patients had an obvious transitional zone (TZ) during laparotomy, and the position of the TZ was 25-100 cm proximal above the ileocecal (IC) valve. Immature ganglion cells were present in the colon in 7 patients and the terminal ileum in 6 patients. The median age of successful stoma occlusion was 5 M (range 2-17) and 8 M (range 4-22) at ostomy closure. There was little or no barium residue in the 24-h delayed film of BE before stoma closure, and all patients were free of constipation symptoms during the follow-up. CONCLUSION: Santulli enterostomy appears to be a suitable and efficient procedure for IG, combined with temporary stoma occlusion and 24-h delayed film of BE to evaluate the recovery of intestinal peristalsis function.

Palisading-like arrangement of immature ganglion cell in myenteric ganglia is a unique pathological feature of immaturity of ganglia.

BACKGROUND: Immaturity of ganglia (IG), an allied disorder of Hirschsprung disease (AD-HSCR), develops as neonatal ileus, but the dysmotility spontaneously resolves after several months. The diagnosis of IG using HE staining is often difficult. We herein report a new pathological finding of IG called the 'palisading-like pattern', which may be helpful for improving the diagnostic accuracy. METHODS: Cases of IG that were managed over the past 28 years were retrospectively reviewed. We investigated the clinical course and pathological findings for Hematoxylin-Eosin (HE) staining. The conventional diagnostic criteria for IG were (1) a normal or slightly increased number of ganglion cells and (2) ganglion cells with small nuclei. RESULTS: Among the 155 cases, 28 were diagnosed with IG, and 10 were retrospectively confirmed by HE staining. A palisading-like pattern was confirmed at the time of the initial ileostomy (median age, 2.5 days), and the palisading-like pattern had completely disappeared by the time of stoma closure (median age, 215 days) in all 10 cases. A palisading-like pattern is not present in other diseases. CONCLUSIONS: Even if immunostaining data are not available for a further analysis, the detection of a palisading-like pattern on HE staining makes an accurate diagnosis possible. LEVEL OF EVIDENCE: LEVEL IV.

Immunophenotypic characteristics of T lineage acute lymphoblastic leukemia: absence of immaturity markers-TdT, CD34 and HLADR is not uncommon.

INTRODUCTION: T ALL may show variable morphological features and immunophenotypic analysis for characterisation of immature nature of these cells is needed to establish a diagnosis and distinguish from reactive conditions and mature T cell leukemias. Sometimes immaturity markers-CD34, TdT and HLA DR may not be expressed by blasts. The aim of the present study was to analyse immunophenotype of T ALLs especially with respect to absence of immaturity markers. METHODS: Thirty-eight cases of T ALL diagnosed over a period of two and half years were analysed retrospectively with respect to clinical features, haematological features and flow cytometric immunophenotyping for T, B, Myeloid and immaturity markers. Student's T-test was used for comparing quantitative data and Chi-square test/Fishers exact T-test for qualitative variables. P value less than 0.05 was considered significant. RESULTS: The most common T-lineage marker expressed was cCD3 and CD7 which were expressed in 100% cases followed by CD5 in 86.8% cases. The most common immaturity marker expressed was TdT (39.5% cases) followed by CD34 (34.2% cases). Thirteen cases (34.2%) were negative for all three of the immaturity markers i.e. TdT-/CD34-/HLADR. Absence of CD34 was associated with absence of expression of HLA DR (P<0.05) and aberrant expression of B lineage markers (P<0.05). CONCLUSION: T-ALL is a rare and aggressive disease. Many cases lack immaturity markers viz, TdT, CD34 and HLADR. In such cases a comprehensive approach taking into account the clinical presentation, cytomorphology and immunophenotyping is diagnostic in experienced hands. Further, molecular studies may be needed to aid diagnosis.

Diaphyseal giant cell tumor with multiple relapses in a skeletally immature patient: a case report.

Giant cell tumor (GCT) is an aggressive osteolytic lesion mostly affecting the meta-epiphyses of long bones at skeletal maturity. Occurrence of the GCT in diaphysis is a rare entity in adult and exceptionally rare in pediatric population. This is the only third diaphyseal case reported in pediatric population. We report a case of recurrent diaphyseal GCT in a skeletally immature patient of 15-year-old male at the right radius after previous resection with plate and screw fixation. Upon optimal investigations, en-bloc resection of the tumor with radial resection and ulna centralization with wrist arthrodesis was done for a campanacci stage III GCT. The patient had an uneventful recovery without recurrence for 2 years and 2 months following surgery. The main challenge relies on accurate diagnosis due to uncommon location that hinders adequate treatment plan, therefore diagnosis should be solely based on histopathology findings.

[Influence of age, growth potential and functionality in the management of bone tumours in children : example of the rotationplasty]. / Cas clinique. Influence de l'âge, du potentiel de croissance et de la fonctionnalité dans la prise en charge des tumeurs osseuses de l'enfant : exemple de la plastie de rotation.

Malignant bone tumours in children are rare diseases whose survival rate has progressively improved in recent years thanks to advances in pharmacology, surgery and radiotherapy. We present the particular case of a very young child with Ewing's sarcoma of the thigh. We discuss the influence of this young age on short and long term care. Limb skeletal immaturity and the residual growth potential need to be integrated to define the safest oncological and functional strategy. For this purpose, we summarize the different possible reconstructive options. We describe the Van Nes rotationplasty that was proposed in our patient's case and we will detail the issues in terms of functional well-being and self-image.

Les tumeurs malignes osseuses de l'enfant sont des pathologies rares dont la survie s'est progressivement améliorée au cours des dernières années grâce aux progrès médicamenteux, chirurgicaux et radiothérapeutiques. Nous présentons le cas particulier d'une très jeune enfant atteinte d'un sarcome d'Ewing de la cuisse. Nous discutons de l'influence de ce jeune âge sur la prise en charge à court et à long termes. L'immaturité squelettique et le potentiel de croissance résiduelle des membres doivent être intégrés pour définir l'attitude la plus sûre sur le plan oncologique et la plus fonctionnelle. à cette fin, nous résumons les différentes options reconstructives possibles. Nous décrivons la plastie de rotation de Van Nes qui a été proposée à notre patiente et nous détaillerons les enjeux relatifs au bien-être fonctionnel et à l'image de soi.

Low folate induces abnormal neuronal maturation and DNA hypomethylation of neuronal differentiation-related genes in cultured mouse neural stem and progenitor cells.

Folate deficiency in a fetus is well known to cause neurodevelopment defects and development disorders. A low level of folate is also thought to be a risk for depression in adults. We have previously shown that post-weaning low folate induces neuronal immaturity in the dentate gyrus in mice, which suggests that low folate causes neuropsychological disorders via inhibition of neuronal maturation. In this study, we examined the effects of low folate on expression and epigenetic modification of genes involved in neuronal differentiation and maturation in primary mouse neural stem/progenitor cells (NSPCs) in vitro. An increase in Nestin (NSPC marker)-positive cells was observed in cells differentiated in a low folate medium for 3 days. An increase in ßIII-tubulin (Tuj1: immature neuron marker)-positive cells and a decrease in microtubule-associated protein 2 (MAP2: mature neuron marker)-positive cells were observed in cells differentiated in a low folate medium for 7 days. In these cells, mRNA levels for genes involved in neuronal differentiation and maturation were altered. Hypomethylation of DNA, but not of histone proteins, was also observed at some promoters of these neuronal genes. The level of S-adenosylmethionine (SAM), a methyl donor, was decreased in these cells. The abnormalities in neural maturation and changes in gene expression in culture under low folate conditions were partially normalized by addition of SAM (5 µM). Based on these results, decreased SAM may induce DNA hypomethylation at genes involved in neuronal differentiation and maturation under low folate conditions, and this hypomethylation may be associated with low folate-induced neuronal immaturity.

Checkmate ao rei: como reinventar o pai / King checkmate: how to reinvent the father

Este artigo tem como objetivo abordar a questão da paternidade na psicoterapia familiar. Uma revisão crítica das teorias sistêmicas e especialmente do pós-modernismo é oferecida, dentro da qual a "revelação da verdade" não parece ter recebido atenção adequada. Ao contrário, este trabalho pretende demonstrar a sua importância, principalmente, no engajamento dos pais na terapia, a fim de passar de um aspecto protetor em relação aos filhos, que nunca têm idade para saber a verdade, ao seu pleno respeito. Em seguida, aborda o problema da parentificação dos filhos e da imaturidade de alguns pais e descreve como intervir na psicoterapia, de modo a restaurar o equilíbrio emocional e a aceitação de responsabilidades por parte do pai. Para atingir esse objetivo, é útil incluir a história do desenvolvimento da família e da terceira geração como uma ponte entre pais e filhos na terapia.

This paper describes how to engage fathers in family therapy. It starts from a critical review of systems theory and postmodernism around the topic of the truth and family secrets. The Author describes how to challenge fathers' resistances and to motivate them to reveal the truth to their children in therapy. The fundamental passage from being protective to being respectful of children is outlined too. The process of immaturity transmitted through generations can bring children to perform adult and responsible roles instead of their fathers. Then, the third older generation can be activated and considered as an emotional bridge in connecting fathers and children in order to transform inverted roles and responsibilities.