Prepubertal Age Research Articles

Targeting against the activity of the NLRP3 inflammasome is a potential therapy for rat testicular tissue cryopreservation and transplantation.

The objective of the present experiment was to explore the role of NLRP3 inflammasome in the testicular tissue freezing, thawing and grafting; furthermore, the potential effect of a NLRP3 inhibitor on the function of testis transplant was explored. Tissues from male Wistar rats in pre-pubertal age were cryopreserved, thawed and auto-transplanted into the scrotum treated or not treated with the MCC950 (a NLRP3 inhibitor). After grafting, cryopreserved tissue was removed and analysed. Quantitative morphometric, immunohistochemical techniques and Western blotting were used to evaluate the survival of spermatogonia and the activation of the NLRP3 inflammasome after freezing/thawing/grafting. Moreover, serum IL-1β level was assessed with ELISA kits. The testicular transplants exhibited upregulated expression of the NLRP3 pathway meditors (NLRP3, IL-1β). In NLRP3 inhibition group, the rate of recovered grafts, the percentage of intact tubules and spermatogonial number were significantly higher than that in cryopreserved graft group. Moreover, serum concentration of IL-1β in NLRP3 inhibition group was significantly lower than that in cryopreserved graft group. Testicular tissue cryopreservation and transplantation exhibited upregulated expression of NLRP3 pathway and NLRP3 inflammasome blockade improves testicular graft function. These finding suggest that NLRP3 inflammasome is a therapeutic target for testicular tissue cryopreservation and transplantation.

Prenatal exposure to propionic acid induces altered locomotion and reactive astrogliosis in male rats

Autism spectrum disorder (ASD) is a range of neurodevelopmental disorders characterized by movement and social deficits with rapidly increasing incidence worldwide. Propionic acid (PPA) is a histone deacetylase inhibitor that regulates neuronal plasticity in the brain. Evaluation of the behavioral and cellular consequences of PPA exposure during a critical neurodevelopmental window is required. Therefore, in the present study we aimed to evaluate the effects of prenatal PPA exposure on locomotor behavior and astrocyte number, as well as on levels of nitric oxide (NO), synaptophysin (SYP; a marker of synaptic plasticity), and metallothionein 3 (MT-III; a marker of reactive oxygen species and zinc metabolism), in the prefrontal cortex (PFC) of male rats. All parameters were evaluated at three critical ages of development: postnatal days (PD) 21 (weaning age), PD35 (pre-pubertal age) and PD70 (post-pubertal age). Prenatal PPA exposure induced hypolocomotion and decreased rearing events at weaning age. Moreover, astrogliosis in the PFC was observed in PPA-treated rats at pre- and post-pubertal age. SYP levels were dramatically decreased in PPA-treated rats with simultaneous astrogliosis, suggesting reduced synaptic plasticity. MT-III expression was deregulated in PPA-treated rats. Finally, the expression of NO in the PFC remained unaltered in PPA-treated rats. These results mimic behavioral, neuronal and astrocytic characteristics observed in ASD patients.

P–624 Doxorubicin exposure detrimentally effects establishment of early ovarian reserve, ex-vivo mouse model

Abstract Study question Does exposure to chemotherapy agents used to treat cancer during pregnancy cause significant decrease in early establishment of the ovarian reserve? Summary answer Significant oocyte loss is noted following exposure of early mouse ovaries to doxorubicin. This apoptotic decline is not seen with cisplatin, docetaxel or paclitaxel exposure. What is known already Chemotherapy has been shown to adversely affect the ovarian reserve of pre-pubertal and reproductive age females. However, little is known regarding the effects in the next generation following treatment in pregnancy beyond observational population studies that examined rates of birth defects and developmental delays. Reproductive function in offspring develops over time and would be difficult to quantify in these short-term studies. An ex-vivo mouse ovary culture offers the ability to closely mimic maternal treatment level serum concentrations and directly evaluate the impact on oocyte number and cell death markers. Study design, size, duration In mice, the ovarian reserve is matured postnatally, mimicking the biologic second trimester activity of the human ovary. Wild-type C57bl/6 pups were collected on postnatal day 0. Ovaries were cultured in hanging well organ culture media with addition of DMSO or a chemotherapy agent. Immunofluorescence was used to quantify oocyte number and density. Power calculation showed a N of 11 per drug would be needed to demonstrate a decrease of ⅔ or more. Participants/materials, setting, methods: 83 ovaries were cultured, sectioned and analyzed in duplicate. Planned analysis at serum max and mid concentrations was performed at 48 hours and 5 days. Given clinically variation in concentrations of cisplatin, additional concentration samples were added. After noting the degradation following exposure to doxorubicin, additional samples at earlier time points of 12 and 24 hours of exposure were added for dynamic evaluation. Means were calculated and then compared using a 2-way ANOVA. Main results and the role of chance Doxorubicin exposure during establishment of the ovarian reserve resulted in a significant loss of oocyte number and density. At 12 hours a 22% decrease was noted; this increased to a loss of 91% of oocytes by 48 hours of exposure. The oocyte density fell from 693 oocytes/ mm² in the control to only 63 oocytes/ mm² in the serum max concentration (p = 0.003). Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) revealed early impact within the stroma by 12 hours with widespread apoptotic changes by 24 hours. Treatment with cisplatin resulted in a phenotypic change in the oocyte population with preservation of smaller, more peripheral cells. The average oocyte density remained similar to control even at the highest clinical concentrations, 536 oocytes/ mm² compared to 570 oocytes/ mm² (p = 0.772). Docetaxel and paclitaxel demonstrated an increase in oocyte number and density, though not enough to reach significance. The oocyte density 5 days following docetaxel exposure was 802 oocytes/ mm², a 41% increase (p = 0.12). The oocyte density 5 days following paclitaxel exposure was 780 oocytes/ mm², a 37% increase (p = 0.817). The drug exposure did impact stromal cells, as noted in TUNEL images. Limitations, reasons for caution This ex-vivo mouse model offers tight control of chemotherapy concentration, it does not account for filtration and modification by the placenta. Longer term cultures may also demonstrate that temporary arrest in small oocytes, such as those exposed to cisplatin, do not thrive and later progress to apoptosis. Wider implications of the findings: Doxorubicin is employed as the most common chemotherapy during pregnancy. Utilization may be to the serious detriment of the younger generation. If other alternatives are clinically effective they should be considered. No other models have explored the effect of fetal ovary exposure to chemotherapy on the establishment of ovarian reserve. Trial registration number Not applicable

The Relationship Between Salivary Dehydroepiandrosterone Sulphate (DHEAS) Levels and Skeletal Maturation Parameters Before and During Pubertal Growth Spurt in Children

Objectives: This study aimed to assess the skeletal maturation by using salivary DHEAS levels and its correlation with existing skeletal maturity parameters represented by cervical vertebrae and MP3 region radiographs in adolescents in pre-pubertal and pubertal age groups. Methods: In this study, 80 children in the age range of 8 - 14 years were divided into two equal groups based on their chronological age as group I (pre-pubertal group) and group II (pubertal group). Pre-existing lateral cephalograms and medial phalanx of third finger (MP3) radiographs of their left hands were assessed. The levels of the DHEAS of each individual were analysed by ELISA kit. ANOVA with post-hoc Tukey’s test and student t-test were used for statistical analysis. P-value < 0.05 was considered significant. Results: The mean level of DHEAS values shown in the present study was 4.36 +/- 0.32 ng/mL in group I and 5.73+/-0.39 ng/mL in group II. This study showed that in group I, more subjects were in stage 1 of cervical vertebral maturation than stage 2 and there were significant differences between the two stages (P-value = 0.011); also, in group II, more subjects were in stage 3 than 4 and there were significant differences between the two stages (P-value = 0.017). This study revealed the highest salivary DHEAS levels to be in the F stage of pre-pubertal MP3 development in addition to the H stage of MP3 development in pubertal children. This study noted that there were significant differences for salivary DHEAS levels between males and females not only in pre-pubertal (P-value = 0.031), but also in pubertal stages (P-value < 0.001). Conclusions: Salivary DHEAS, like cervical vertebra and MP3 radiographs, can be used for growth assessment in young adolescents.

A REVIEW OF AYURVEDIC MANAGEMENT FOR DANDRUFF (DARUNAKA)

Dandruff is a common scalp disorder affecting almost half of the population. According to ayurveda, dandruff may be correlated to darunaka which is the most common cause of hair loss. Ayurveda classics dealt the different procedures and medications to treat the disease darunaka (dandruff). As a person with dandruff is more likely to feel down on the social ring, it is more of social concern and affects aesthetic value. Under kshudraroga, acharya sushruta referred to darunaka with symptoms such as rukshata, kandu, sphutana twak, etc. Dandruff may occur due to air pollution, water pollution, altered lifestyle, erratic daily routine, poor hygiene, and immune system, sweating, mental stress, etc., which can lead to many infections of bacteria and fungi. It is a common scalp condition that affects approximately half of the pre-pubertal age population and any gender and ethnicity. At some point in their lives, no population in any geographical area would have openly gone by without being affected by dandruff. The line of care for darunaka in the classics is shiroabhyanga, nasya, shirodhara, shirobasti, shirolepa and siravyadha. A review of ayurvedic management for dandruff (darunaka). Ancient acharyas have stated a multidimensional approach towards the management of darunaka. The multidimensional approach of ayurveda towards management of darunaka in the form of shodhana chikitsa, shamana aushadhis, and sthanika chikitsa along with nidana parivarjana gives satisfactory results to the patient.

Urogenital tuberculosis in children 0 - 14 years old in the structure of other localizations of tuberculosis

Introduction. Extrapulmonary tuberculosis (EPTB) still has many features: there is a different approach to its definition in different countries, there is no screening, diagnosis is extremely difficult and requires financial costs, and bacteriological verification does not exceed 46%, complex restorative and reconstructive operations are used in treatment. the proportion of patients with isolated extrapulmonary localizations among tuberculosis patients is low.Purpose of the study. To study the structure of tuberculosis (TB) in children with the accentuation of EPTB in the current conditions to determine the development areas of preventive and diagnostic measures.Materials and methods. A retrospective two-stage study was carried out in the period from 1989 to 2018 among in-patient children aged 0 - 14 yrs. At the first stage, the structure of clinical forms of TB was assessed in 2306 children. Three comparison groups were formed following ten-year periods. At the second stage, 4 groups were identified according to age: early age, preschool age, primary school age, prepubertal age. The data obtained in the course of the study were statistically processed using the Microsoft Office 2007 (Microsoft Corp., USA) and Biostat 2009 (AnalystSoft Inc., USA) software package. The differences between the groups were determined using the χ2 test, and significant differences were considered when the value of the p < 0.05 criterion.Results. It was found that throughout the entire observation period in the region, the predominant localization of the specific process was respiratory TB. The proportion of isolated extrapulmonary lesions in children decreased from 11.1% in the period from 1999 to 2008 to 3.4% in the period from 2009 to 2018 (p = 0.000). At the same time, the most frequent localization (60.4 - 77.8% of cases) among EPTB remains urinary TB. In the dynamics from 1989 to 2018, the number of cases of the disease with combined forms of tuberculosis increased (from 3.1% to 7.2%; p = 0.000), mainly due to the establishment of several localizations of the lesion. The frequency of bacteriological confirmation of the diagnosis was significantly different at various localizations of the specific process. In children of the compared periods of childhood, the predominant localization of the specific process was isolated respiratory TB. The isolated extrapulmonary process localizations were more common in the age groups 7 - 11 and 12 - 14 yo, where it accounted for 10.8 - 12.4% of TB cases (p = 0.000). The localization of the EPTB also depended on the children's age. So, young children often developed damage to the osteoarticular system, in preschool children - the genitourinary and lymphatic (peripheral lymphadenopathy) systems, in younger schoolchildren and preschoolers - the genitourinary system. The frequency of bacteriological confirmation of the EPTB increased with the age. The combined forms of a specific process were more often observed in the age group of 7 - 11 yo, in the other groups their share was 77.4%, 87.1%, and 95.0% of cases. Respiratory TB and TB of other organs was confirmed bacteriologically more often in the age group 7 - 11 yo (19.4%), and in the group 12 - 14 yo in 12.9%, 4 - 6 yo in 10.0%, early age in 9.7%, which is much more frequent than confirmation of isolated respiratory TB.Conclusions. EPTB in children has not lost its position and due to the widespread introduction of the recombinant TB allergen and CT into clinical practice. It has become more often detected in combination with respiratory TB. Among the EPTB, genitourinary tuberculosis prevailed, which can be verified in contrast to damage to other organs. Raising the level of awareness of paediatricians and phthisiatrician-paediatricians about the frequency of EPTB occurrence makes it possible to form alertness in terms of the possibility of their development and to timely detect the disease at an early stage.

Взаємозв’язок показників обміну заліза і тиреоїдного гомеостазу у дітей із сидеропенією та йододефіцитом

Relationships between the iron metabolism indexes and thyroid homeostasis in children were investigated. For that purpose, 68 healthy children aged 6 to 11 years were examined (35 boys and 33 girls) with adequate iron and iodine supply (n =16), latent sideropenia (n = 16), mild iodine deficiency (n = 18) and combination of latent iron deficiency and mild iodine deficiency (n = 18). We found that in 13% of boys with latent sideropenia, 78% of boys and as many girls with mild iodine deficiency, 90% of boys and 88% of girls with combined iodine and iron deficiency, the thyroid-stimulating hormone (TSH) level in blood serum ranged from 2.5 to 4.2 mIU/l under the reference data of free triiodothyronine (fT3) and thyroxine (fT4). This observation points for development of minimal thyroid insufficiency (MTI). According to the TSH/fT4 index, MTI was found in 30% of boys and 38% of girls with combined iodine and iron deficiency. These children form the group of risk for development of subclinical hypothyroidism and require mandatory individual correction of MTI by administration of potassium iodide. We found direct moderate correlations between the contents of fT3 and fT4 in serum and the hemoglobin level (Hb) in blood, between the contents of the serum iron and ferritin (r from 0.42 to 0.64). We found also an inverse moderate correlation between the serum TSH content and indexes of iron metabolism (r from –0.56 to –0.61), and a direct moderate correlation between the TSH and total serum iron-binding capacity (r = 0.54). Therefore, iron deficiency can be considered a risk factor for the development of thyroid insufficiency, which requires control of functional capacity of thyroid gland in case of iron depot depletion. The most vulnerable period for the formation of thyroid dysfunction is a prepubertal age regardless of gender. The advisability of determining the indicators of iron metabolism and its correction under conditions of latent sideropenia, mild iodine deficiency and their combination for the prevention of MTI development was justified.

Growth Disturbances in Pediatric Patients Receiving Long-Term Tyrosine Kinase Inhibitor Therapy

Background:Since their approval in 2003, Tyrosine Kinase Inhibitors (TKIs) targeting bcr-abl1 kinase activity have changed the treatment paradigm for children with chronic myeloid leukemia (CML) and Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL). However, off-target inhibition of kinases, such as src and c-kit, can result in impaired osteoblast function, cause an imbalance in calcium and phosphate metabolism, and result in growth impairment in children. The aim of our study was to examine growth over time in pediatric patients receiving TKIs for CML or Ph+ ALL.Description: This is a single institutional retrospective longitudinal cohort study of patients (≤ 21 years of age) diagnosed with CML or Ph+ ALL between January 2000 and December 2015 who received a TKI and had ≥ 1 year of growth data available as of May 31, 2016. Patient demographics, treatment details including the type and duration of TKI therapy and details of concomitant conventional therapy (chemotherapy and radiation) were abstracted. Growth data was abstracted from the start of TKI at yearly intervals up to a maximum of five years or age 20 and from their last available appointment. Specific variables for growth included height, height percentile, height-SDS (height - standard deviation score or z score) and BMI-SDS (body mass index - standard deviation score). Height-SDS and BMI-SDS were determined using the CDC growth chart by age and gender. Age at diagnosis was used as a surrogate for expected pubertal status: pre-pubertal (3 - 8.9 years), pubertal/peri-pubertal (9 - 15.9 years), post-pubertal (16+ years). Overall change in height-SDS / BMI-SDS from baseline to 1-year and last follow-up were compared by diagnosis, gender, and pubertal age using ANOVA. Statistical analysis was performed using SAS® v9.3 (Cary, NC). For all analyses, a p-value of <0.05 was considered to be statistically significant.Results: Our cohort included 48 patients who received a TKI (n=29 CML, n=19 Ph+ ALL) - 46% were male and 38% were non-Hispanic white. The mean age at diagnosis was 12.1 ± 3.7 years for CML and 9.0 ± 4.6 years for Ph+ ALL patients (p=0.01). As expected, mean duration of TKI treatment was longer in CML (4.3 ± 2.8 years) versus Ph+ ALL (2.7 ± 1.7 years). The average duration of follow-up was similar in both groups (CML 4.6 ± 3.54 years vs Ph+ ALL 4.1 ± 2.9 years, p=0.60). At time of diagnosis, the mean Height-SDS for the entire cohort was 0.13 ± 1.28 with no difference between patients by diagnosis (p=0.92). At one year following treatment with TKI a decrease in mean height-SDS was noted, with a more significant difference in Ph+ ALL patients (-0.54 ± 0.21) compared to CML patients (-0.18 ± 0.39) (p=0.002). This difference remained significant at last follow-up (Ph+ ALL -0.96 ± 0.70, CML -0.52 ± 0.74, p=0.05) (Figure 1). There was no significant difference in mean change in height-SDS at 1 year or last follow-up by gender. Overall, the decrease in height-SDS at 1 year was most significant in the pre-pubertal age group (-0.51 ± 0.27) as compared to pubertal/peri-pubertal and post-pubertal groups (-0.26 ± 0.46 and -0.10 ± 0.24 respectively; p=0.04). BMI-SDS at baseline did not differ by diagnosis but did show a significant decrease at one year in Ph+ ALL versus CML patients (-0.18 ± 0.65 and 0.39 ± 0.54 respectively, p=0.003); this stabilized at the time of last follow up (-0.01 ± 0.75 and 0.38 ± 0.80 respectively, p=0.11).Conclusions: Our data underscores the concern of growth disturbances following prolonged TKI exposure in children, the role of exposure relative to pubertal change in bone growth, and the need for understanding off-target mechanisms in childhood survivors. Stabilization of BMI-SDS at the end of follow up with accompanying drop in mean height-SDS points to a mechanism of growth disturbance beyond nutritional deficiencies. This large pediatric cohort treated with TKIs is the first to include Ph+ ALL patients who were younger at onset of TKI treatment, and more likely to be pre/peripubertal at the start TKI exposure. Future directions will focus on a prospective study of musculoskeletal and other organ toxicities in patients treated with TKIs in childhood. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

An Association of Pediatric Psoriasis with Metabolic Syndrome in Thai Children: 20 Years Retrospective Study.

PurposeTo explore epidemiological data of pediatric psoriasis age under 18 years old regarding, types of psoriasis, the correlation with metabolic syndrome (MetS), treatments, and treatment outcomes of at least one year follow-up.Patients and MethodsThis was a 20-year-retrospective study of pediatric psoriasis patients in a single tertiary pediatric referral center, Faculty of Medicine, Khon Kaen University, Thailand, between January 2001 and December 2020. The diagnosis of psoriasis was based on recorded diagnosis from ICD-10, and medical record was evaluated by certified pediatricians.ResultsThere were 177 pediatric psoriasis in the study population. The mean age was 10.50, SD 4.80. The mean body mass index (BMI) was 19.10 (SD 5.44). There were 52 cases (29.37%) with MetS. Pediatric psoriasis patients over the age of 12 years old developed MetS 27 out of 70 cases (0.38) compared to the patients younger than 12 years old (25 out of 107 cases, 0.23), absolute risk reduction = 0.15, 95% CI 0.01–0.29, P = 0.029. The overall outcomes of pediatric psoriasis were good even though traditional topical and systemic treatments were provided in the study population.ConclusionThe present study revealed that there was 15% increased MetS in the pediatric psoriasis patients over the age of 12 years old as compared to the patients of prepubertal age (≤12 years old). Increased attention to the early detection of MetS in pediatric psoriasis is recommended. Biologic therapy would be an alternative option in severe recalcitrant pediatric psoriasis cases in the future.

Síndrome de pseudotumor cerebri en la población pediátrica: características clínicas, tratamiento y pronóstico

IntroductionPseudotumor cerebri (PC) in prepubertal patients displays certain characteristics that differentiate it from its presentation at the postpubertal stage. The aim of this study is to describe the characteristics of paediatric patients diagnosed with PC at our centre and to compare them according to their pubertal status. Patients and methodsWe included patients aged between 1 and 18 years who were diagnosed with PC in a tertiary-level hospital between 2006 and 2019 and who met the updated diagnostic criteria for PC. They were classified according to body weight and pubertal status. Subsequently, we analysed results from lumbar punctures, neuroimaging studies, ophthalmological assessments, and treatments received during follow-up. ResultsWe included 28 patients, of whom 22 were of prepubertal age and 6 were of postpubertal age. The mean age (standard deviation) was 9.04 (2.86) years. Among the postpubertal patients, 83.3% were boys, 66.7% of whom presented overweight/obesity. In the group of prepubertal patients, 27% were boys, 31.8% of whom were overweight. The most frequent symptoms were headache (89.9%) and blurred vision (42.9%). All patients presented papilloedema, and 21.4% manifested sixth nerve palsy. Possible triggers were identified in 28.6% of cases. Nineteen percent of patients presented clinical recurrence, all of whom were prepubertal patients. Complete clinical resolution was achieved in 55.6% of patients. ConclusionPrepubertal patients with PC show lower prevalence of obesity, higher prevalence of secondary aetiologies, and higher recurrence rates than postpubertal patients.

Analysis of the scoliosis onset mechanisms for children and optimal rehabilitation interventions through aquatic activities

It is known, certainly, that it is much easier to form a correct attitude than to correct the vicious one, a reason that must determine the approach of prophylactic means of physical therapy and therapeutic swimming. The identification, at an early stage, of the etiological factors responsible for the installation of postural deficiencies, is a determining factor in the management of programs for their maintenance or recovery in children of prepubertal age. The study took place at the Constantinescu Mihai Physiotherapy Office of Suceava and at the Cornișa Botoșani Swimming Complex. It is known that the correct position is formed from childhood, and movement and exercise are the main factors of its construction. In this sense, the paper proposes kinetic recovery and therapeutic swimming programs in order to strengthen the postural status in children during growth and development. In this regard, we have set the following objectives: identification of children with vicious postural attitudes because of the overloads in the prepubertal period and analysis of the scoliosis mechanisms in children of prepubertal age on a vulnerable somato-functional status. Keywords: therapeutic swimming, evaluation, scoliosis, children, analysis,

Maternal overweight induced by reduced litter size impairs the behavioral neurodevelopment of offspring

AimsWe assessed the influence of maternal overweight on the behavioral neurodevelopment of male and female offspring in prepubertal age by reducing the litter size. Main methodsTo reduce litter size in Wistar rats, the offspring of generation 0 (G0) were culled for 12 pups (6 males and 6 females: normal litter, NL-G1) or 4 pups (2 males and 2 females: small litter, SL-G1). In G1 dams, overweight was characterized, maternal behavior and locomotor activity were assessed. At G2, we quantified the ultrasonic vocalizations in post-natal day 5 (PND5); we evaluated olfactory discrimination in the homing behavior test on PND13; and in PND28–32 (prepubertal age), we performed the following tests: social play behavior, hole board, object recognition, and open field. At the end of the experiments, hippocampus and prefrontal cortex were dissected to quantify the synaptophysin by western blotting. Key findingsOur data demonstrated that a reduction in litter size was able to induce maternal overweight without altering the parameters related to overweight in the offspring. The SL-G2 offspring showed deficits in early social communication, olfactory discrimination, social play behavior, and the exploration of objects, in addition to increasing repetitive and stereotyped movements. There were also changes in the synaptophysin levels in the hippocampus and prefrontal cortex of the offspring from reduced litter dams. In conclusion, maternal overweight caused by litter reduction impairs behavioral neurodevelopment, inducing autism-like symptoms in the offspring. SignificanceThis study alerts the public about the negative consequences of maternal overweight in the descendants.

The Effect of Information Placebo on Physical Activity in Overweight and Obese Children.

To assess the effect of 1 week of consuming a placebo "energy drink" compared with a week of drinking regular water on daily physical activity in obese children participating in a weight reduction multidisciplinary program. Seventeen prepubertal (age = 128.7 [26.6]m) overweight and obese children (7 females and 10 males) participated in the study. Participants received 7 bottles of mineral water per week for 2 weeks. Different types of information were randomly provided regarding the drink consumed in each week: standard (water) versus deliberate positive information (presumed energy drink and placebo). Daily step count was measured using pedometers and compared using paired t test. After consuming the placebo drink, children demonstrated a significantly higher average daily step number (10,452 [4107]) compared with the days they drank water (8168 [2928], P < .005). This difference was attributed mainly to male participants. The use of placebo in the form of deliberate positive information was associated with a significant increase in real-life physical activity in overweight and obese children, especially in boys. Positive information may be used to encourage children with obesity to enhance daily physical activity and energy expenditure.

Expression of Kisspeptin, Neurokinin B, and Dynorphin During Pubertal Development in Female Sheep

Puberty onset depends upon an increase in pulsatile GnRH/LH secretion, which in sheep is the result of reduced sensitivity to estrogen negative feedback. Neurons within the arcuate nucleus of the hypothalamus (ARC) expressing kisspeptin, neurokinin B (NKB), and dynorphin (i.e. KNDy neurons) express estrogen receptors and are believed to play a key role in mediating the effects of estrogen on GnRH/LH secretion. Therefore, the purpose of this study was to assess changes in kisspeptin, NKB, and dynorphin within the ARC across pubertal development in female sheep. Blood samples were collected at 12-minute intervals for 4 hours and assessed for LH secretion in five age groups of ewes: 5 months (n=6), 6 months (n=6), 7 months (n=5), 8 months (n=5), and 10 months (n=6) of age. Following each bleed, ewes were sacrificed, hypothalamic tissue containing the ARC was collected, and then processed for use in dual immunofluorescence and RNAscope. Mean LH and LH pulse frequencies followed the expected patterns: concentrations and frequencies were low during the prepubertal ages (5-7 months of age), intermediate during the peripubertal age (8 months of age), and elevated in the postpubertal age group (10 months of age). Using immunofluorescence, kisspeptin and NKB immuno-positive cell numbers did not change significantly (P > 0.50) over time with cell numbers averaging 235.3±16.8 and 231.3±16.8, respectively. Colocalization of kisspeptin and NKB was greater than 90% for all age groups. Using RNAscope, the total number of cells expressing mRNA for kisspeptin and dynorphin did not change significantly (P > 0.05) over time with cell numbers averaging 46.7±12.0 and 28.3±10.0 cells/hemisection, respectively. Taken together, our data suggest that the increase in LH secretion that drives puberty onset is not limited by changes in kisspeptin, NKB, or dynorphin expression, but may instead depend on other factors such as changes in receptor expression or changes in KNDy neuron activity via a reduction in inhibitory and/or an increase in stimulatory afferent inputs.

Pituitary Volume Cutoffs as Another Tool for Determining Growth Hormone Treatment Eligibility

Abstract Background: The GH stimulation test (GHST) is the gold standard for the diagnosis of GH deficiency (GHD), yet a significant number of short children fail to be diagnosed as GHD. We have speculated that pituitary volume (PV) could be used in conjunction with results from the GHST to diagnose GHD; however, cutoff values for low PVs need to be further explored. Objective: To define a diagnostic cutoff value of PV for determining GH treatment eligibility for patients (PTs) with short stature. Patients and Methods: The database of GHST results at a Pediatric Endocrinology center was queried for PTs aged 6-18 yrs who underwent a GHST, MRI, and blood work between 1/2018 - 6/2019. PTs with relevant comorbidities were excluded. Clonidine and L-dopa were used to induce GH secretion during the GHST. GHD was defined as a peak GH ≤ 10 ng/mL. MRIs were acquired on a Philips 1.5 or 3.0 T scanner (1mm slices) and PV was calculated using the ellipsoid formula (LxWxH/2). 144 PTs were the subjects of this study. ROC curve analysis was utilized to generate cutoff values. PV was used to predict GHD in prepubertal (age &amp;lt; 11 yrs) and pubertal (age &amp;gt; 11 yrs) children. The value with the greatest Youden index (J) was selected as the definitive cutoff. Results: The mean (MN) and median (MD) ages of PTs were 12.2 ± 2.2 and 12.3, respectively. The MN and MD ages of prepubertal PTs (n=43) were 9.4 ± 1.1 and 9.7, respectively. The MN and MD ages of pubertal PTs (n=103) were 13.4 ± 1.4 and 13.2, respectively. Initially, 10 ng/mL was utilized as the cutoff for GHD. For predicting GHD from PV in prepubertal PTs, sensitivity was 89.47% and specificity was 66.67%. The distance to corner was 0.3488, and the highest J was 0.5641, corresponding to a PV of 240.00 mm3. The Area Under the Curve (AUC) was 0.6581 with a standard error (SE) of 0.2429 (p&amp;gt;0.05). For predicting GHD from PV in pubertal PTs, sensitivity was 72.94% and specificity was 81.25%. The distance to corner was 0.3292, and the highest J was 0.5419, corresponding to a PV of 275.00 mm3. The AUC was 0.7901 with a SE of 0.0687 (p&amp;lt;0.05). Further analysis was done to explore the use of 7 ng/mL as the cutoff for GHD. For predicting GHD from PV in prepubertal PTs, sensitivity was 25.00% and specificity was 90.91%. The distance to corner was 0.7555, and the highest J was 0.1591, corresponding to a PV of 133.66 mm3. The AUC was 0.4989 with a SE of 0.0931 (p&amp;gt;0.05). For predicting GHD from PV in pubertal PTs, sensitivity was 57.89% and specificity was 63.64%. The distance to corner was 0.5563, and the highest J was 0.2153, corresponding to a PV of 240.00 mm3. The AUC was 0.6112 with a SE of 0.0584 (p&amp;lt;0.05). Conclusion: PVs ≤ 275.00 mm3 in pubertal PTs should be considered low; however, cutoffs for prepubertal PVs were not significant in this study. To our knowledge, we present the first study to generate a PV cutoff based on the GHST. Future studies including more PTs and tanner staging will further improve the accuracy of PV cutoffs for GHT eligibility.

Association of Multigenerational Family History of Depression With Lifetime Depressive and Other Psychiatric Disorders in Children

Three-generation family studies of depression have established added risk of psychopathology for offspring with 2 previous generations affected with depression compared with 1 or none. Because of their rigorous methodology, there are few of these studies, and existing studies are limited by sample sizes. Consequently, the 3-generation family risk paradigm established in family studies can be a critical neuropsychiatric tool if similar transmission patterns are reliably demonstrated with the family history method. To examine the association of multigenerational family history of depression with lifetime depressive disorders and other psychopathology in children. In this analysis of the Adolescent Brain Cognitive Development (ABCD) study data, retrospective, cross-sectional reports on psychiatric functioning among 11 200 children (generation 3 [G3]) and parent reports on parents' (G2) and grandparents' (G1) depression histories were analyzed. The ABCD study sampling weights were used for generalized estimating equation models and descriptive analyses. Data were collected from September 2016 to November 2018, and data were analyzed from July to November 2020. Four risk categories were created, reflecting how many prior generations had history of depression: (1) neither G1 nor G2 (G1-/G2-), (2) only G1 (G1+/G2-), (3) only G2 (G1-/G2+), and (4) both G1 and G2 (G1+/G2+). Child lifetime prevalence and relative risks of psychiatric disorders were based on child and caregiver reports and grouped according to familial risk category derived from G1 and G2 depression history. Among 11 200 included children, 5355 (47.8%) were female, and the mean (SD) age was 9.9 (0.6) years. By parent reports, the weighted prevalence of depressive disorder among children was 3.8% (95% CI, 3.2-4.3) for G1-/G2- children, 5.5% (95% CI, 4.3-7.1) for G1+/G2- children, 10.4% (95% CI, 8.6-12.6) for G1-/G2+ children, and 13.3% (95% CI, 11.6-15.2) for G1+/G2+ children (Cochran-Armitage trend = 243.77; P < .001). The weighted suicidal behavior prevalence among children was 5.0% (95% CI, 4.5-5.6) for G1-/G2- children, 7.2% (95% CI, 5.8-8.9) for G1+/G2- children, 12.1% (95% CI, 10.1-14.4) for G1-/G2+ children, and 15.0% (95% CI, 13.2-17.0) for G1+/G2+ children (Cochran-Armitage trend = 188.66; P < .001). By child reports, the weighted prevalence of depressive disorder was 4.8% (95% CI, 4.3-5.5) for G1-/G2- children, 4.3% (95% CI, 3.2-5.7) for G1+/G2- children, 6.3% (95% CI, 4.9-8.1) for G1-/G2+ children, and 7.0% (95% CI, 5.8-8.5) for G1+/G2+ children (Cochran-Armitage trend = 9.01; P = .002), and the weighted prevalence of suicidal behaviors was 7.4% (95% CI, 6.7-8.2) for G1-/G2- children, 7.0% (95% CI, 5.6-8.6) for G1+/G2- children, 9.8% (95% CI, 8.1-12.0) for G1-/G2+ children, and 13.8% (95% CI, 12.1-15.8) for G1+/G2+ children (Cochran-Armitage trend = 46.69; P < .001). Similar patterns were observed for other disorders for both parent and child reports and across sex, socioeconomic status, and race/ethnicity. In this study, having multiple prior affected generations was associated with increased risk of childhood psychopathology. Furthermore, these findings were detectable even at prepubertal ages and existed in diverse racial/ethnic and socioeconomic groups. Clinically, they underscore the need for screening for family history in pediatric settings and highlight implications for biological research with homogenous subgroups using magnetic resonance imaging or genetic analyses.

Epididymal cyst in children.

The terms "epididymal cyst" and "spermatocele" are commonly used to describe the same entity, but, conversely, they are slightly different. Epididymal cyst is a benign mass, and it is more common than previously thought in prepubertal age. Pathogenic mechanisms for epididymal cyst have not been fully clarified yet, even if epididymal cysts have been reported in association with other malformations of the urinary tract or complex syndromes. Epididymal cyst is easily characterized and differentiated from spermatocele using ultrasound imaging. Conservative management constitutes the treatment of choice in the majority of cases, and surgery is recommended only in selected cases. Conclusion:To date, a review on epididymal cyst in childhood is lacking in the literature. Herein, an overview of knowledge about epididymal cyst in children has been carried out with particular attention to differential diagnosis, proper management, and practice guidelines for caregivers of children who may present with an epididymal cyst. What is Known: • Epididymal cyst is a benign sac in the testicles which is usually asymptomatic. • Epididymal cyst is easily diagnosed by ultrasound scans, and it is considered a self-limiting disease in the majority of cases. What is New: • Insight on differential diagnosis between epididymal cyst and spermatocele. • Valuable knowledge on the best management strategy for epididymal cyst and on practice guidelines for parents of children presenting with epididymal cyst.

Histological study of normal human suprarenal gland of different age groups

Background: Adrenal gland is a lifesaving endocrine gland of the human body. Knowledge of normal microscopic anatomy of the Adrenal gland facilitates Pathologists to correlate and make the differential diagnosis of various adrenal glands associated clinical conditions on histopathological examination.&#x0D; Aims and Objective: To study histological features of human adrenal gland in the post-natal period at different ages.&#x0D; Materials and Methods: Present study is conducted with 98 human adrenal glands from 49 unclaimed dead bodies during an autopsy and 22 human adrenal glands from 11 cadavers during routine dissection in S.V Medical College, Tirupati, which were utilized after obtaining consent from the close kith and kin. During the autopsy/dissection, the samples collected were from 2 Years to 64 years of age individuals of both sex with typical external features and divided into three groups. The first group consisted of less than 25 years of age. The second group consists of ages between 26 years to 50 years. The third group included 51 years and above, and all the specimens are processed for histological staining and observed under the microscope.&#x0D; Results: At 2 years well-developed capsule with large vessels and well-differentiated zones of definitive cortex and medulla were identified. The thick muscular coat of the central vein was identified at 20 years. At 36 years &amp; 45 years, cellular architecture in various zones is very well differentiated. At 65 years, the cortico-medullary demarcation was irregular, and vascularity decreased.&#x0D; Conclusion: Histological features of pre-pubertal, adult, and old age group sections helps in the understanding of post-natal changes in the growth of the Suprarenal gland and its functions.

Allometric Scaling of Force-velocity Test Output Among Pre-pubertal Basketball Players.

Basketball is characterized by high-intensity episodes predominantly reliant on anaerobic metabolism. The force-velocity test enables individual determination of an optimal braking force and emerged as appropriate to estimate optimal peak power. It has rarely been used in youth basketball. This study aimed to examine the contribution of body size, composition, and biological maturation to interindividual variation in force-velocity test output among pre-pubertal basketball players. The sample consisted of 64 male participants (8.4-12.3 years). Stature, sitting height, body mass and two skinfolds were measured, and leg length estimated. Fat-free mass and lower limb volume were estimated from anthropometry. Age at peak height velocity was predicted from maturity offset. Optimal peak power was correlated with all body size descriptors (correlation: 0.541-0.700). Simple allometric models explained 30-47% of inter-individual variance, with fat-free mass being the best predictor of performance. Whole-body fat-free mass (as a surrogate for active muscle mass) plus the indicator of maturation emerged as the best proportional allometric model (53% explained variance). Even at pre-pubertal ages, the interpretation of the force-velocity test requires assessing the metabolically active component of body mass.

Hyperglycaemic hyperosmolar state in an obese prepubertal girl with type 2 diabetes: case report and critical approach to diagnosis and therapy

IntroductionIsolated Hyperosmolar Hyperglycaemic Syndrome (HHS) is a life-threatening condition characterized by elevated serum glucose concentrations and hyperosmolality without significant ketosis. It is often described in obese adults with unknown Type 2 Diabetes (T2D), rarely in youth. In childhood the most common cause of metabolic glucose related derangement is Diabetic Ketoacidosis (DKA) in Type 1 Diabetes (T1D). Interestingly, both components can be combined with each other, thus the prevalent condition needs to be recognised implying a different therapeutic approach.Case presentationIn this case, we report a prepubertal Caucasian obese girl admitted for two episodes of combined HHS/DKA in order to elucidate her clinical course taking into account the current pediatric recommendations based on adult guidelines for HHS.ConclusionsThe treatment of HHS and even more of HHS/DKA in youth is still controversial as no specific guidelines for children are available especially during the prepubertal age. The description of our case might be helpful and offer relevant points for future consensus.