The overall survival of pediatric gliomas varies over a wide spectrum depending on the tumor grade. Low-grade gliomas have an excellent long-term survival, with a possible burden of surgery, irradiation, and chemotherapy; in contrast, high-grade gliomas generally have a short-term, devastating lethal outcome. Recent advances in understanding their molecular background will transform the classification and therapeutic approaches of pediatric gliomas. Molecularly targeted treatments may acquire a leading role in the primary treatment of low-grade gliomas and may provide alternative therapeutic strategies for high-grade glioma cases in the attempt to avoid the highly unsuccessful conventional therapeutic approaches. This review aims to overview this progress.Any painful or medical experience that we face is viewed from the lens with which we understand and view the experience […].

Studies show that social anxiety in adolescence have negative impact on quality of life. The study evaluates social anxiety links with mental and physical health factors in adolescents aged 15-19 years.

The research was performed in 2018 in secondary schools in Lithuania and included 1722 participants (46.1% males and 53.9% females). The social anxiety was assessed using Social Anxiety and Avoidance Scale for Adolescents. The main results were obtained using univariate and multivariate logistic regression analysis.

Total of 58.5% of adolescents were characterized by high social anxiety and 14.7% by high avoidance. Females more often were characterized by high anxiety compared to males. Multivariate logistic regression revealed that good mental health was a significant protective factor against high SA in adolescents. For females, high anxiety and avoidance were associated with living with both parents, for males, high anxiety was linked with mother’s university education. Very common stomach and abdominal pain in females as well as severe and very common stomach or abdominal pain in males, increase the risk of major social anxiety.

High social anxiety were more prevalent between females than males and was linked with various well-being and health aspects in adolescents.

High social anxiety were more prevalent between females than males and was linked with various well-being and health aspects in adolescents.

the purpose of this study was to evaluate the effects of training caregivers to use intervention strategies from the Enhanced Milieu Teaching with Phonological Emphasis (EMT + PE) program, delivered via telepractice, and to examine the effects on child speech and language outcomes for children with repaired cleft lip +/- palate (CL/P).

A multiple baseline within subject design across parent behaviors was replicated across three participating dyads. A pre-post intervention comparison was provided with a non-cleft twin.

Three mother-child dyads participated in this study. Children ranged in age from 21 to 27 months at the beginning of the study and all had a diagnosis of CL/P. A noncleft twin without CL/P was assessed pre- and post-intervention to provide a normative comparison.

Parents demonstrated a positive intervention effect by substantially increasing their use of EMT + PE intervention strategies during telepractice intervention sessions (Tau 0.675 to 1.1333). Following the conclusion of intervention, parents were able to maintain their use of strategies once direct coaching had been discontinued. Children demonstrated increased talking rate, improved speech production and expanded expressive vocabulary measures over the course of intervention. Speech and language development of a child without cleft palate was provided as a comparison.

Parents were trained through telepractice to effectively deliver EMT + PE speech and language facilitation strategies that resulted in increased language and speech outcomes for their children with CL/P.

Parents were trained through telepractice to effectively deliver EMT + PE speech and language facilitation strategies that resulted in increased language and speech outcomes for their children with CL/P.It has been reported that congenital muscular torticollis (CMT) may result in secondary scoliosis over long-term follow-ups. However, there are few reports on whether CMT causes pelvic malalignment syndrome (PMS). This study aimed to investigate the relationship between CMT and PMS and to determine the factors associated with the development of PMS in children with longstanding CMT. Medical records of 130 children with CMT who had long-term follow-up were reviewed retrospectively. The chi-squared test and logistic regression analysis were used to determine which initial clinical parameters contributed to the development of PMS. Among 130 children with CMT, 51 (39.2%) developed PMS with or without compensatory scoliosis during long-term follow-up, indicating a high prevalence of PMS in children with a CMT history. Initial clinical symptoms such as a limited range of motion of the neck or the presence of a neck mass could not predict the development of PMS. Even if the clinical symptoms are mild, long-term follow-up of children with CMT is essential to screen for PMS.

To compare cardiovascular risk and cardiorespiratory capacity in schoolchildren from a region in the extreme south of Chile according to nutritional status and muscular strength.

An analytical cross-sectional study was performed on a sample of 594 schoolchildren from 5th to 8th grade in the extreme south of Chile. Based on body mass index and lower limb muscle strength, participants were divided into four groups high strength-normal weight, high strength-overweight/obese, low strength-normal weight, and low strength-overweight/obese. Then, waist-to-height ratio and cardiorespiratory capacity, measured with the 20 m shuttle run test, were assessed to determine their cardiovascular risk, comparing the four groups.

The overweight/obese group with high muscular strength presented better indicators in anthropometric variables (waist circumference and waist-to-height ratio) than their peers with low muscular strength. Additionally, the overweight/obese group with low muscular strength presented a lower cardionality. These results encourage the scientific community to continue studying the role that muscle strength plays in modulating the effects of overweight and obesity on respiratory and cardiovascular conditions in childhood.Previous research indicate that socioeconomic status positively corresponds with adults’ and adolescents’ physical activity levels. This study investigated the relationship between parents’ education and income, and preschool children’s physical activity level. A total of 244 Norwegian preschool children aged four to six and their parents were enrolled in the study. The children wore an Actigraph GT1M accelerometer for seven consecutive days to measure their physical activity level. Parents completed a questionnaire that provided information about their education level and income level. To examine the relationship between the parents’ education and income and their children’s physical activity level at leisure, the Kruskal-Wallis H test was conducted. The results revealed that neither mothers’ nor fathers’ education level or income, were associated with their children’s minutes in moderate to vigorous physical activity (MVPA) at leisure. The preschool curriculum of Norway may be one explanation why socioeconomic status was not linked to physical activity in this study. Another possibility is that this study was limited to full-time students with two parents. More research is needed to determine whether parent income or education is linked to physical activity among more diverse or older children in Norway.Advanced neonatal care has increased the survival of neonates born prematurely, and prematurity is a well-known risk factor for asthma/wheezing disorders. Thus, this prospective study aimed to determine the early life factors associated with preschool wheezing in premature neonates. Preterm neonates born between 2012 and 2017 were recruited, excluding those with bacterial infection within 7 days of life, maternal sepsis, and maternal chorioamnionitis. Birth and admission history, comorbidities, and maternal history were documented. Respiratory problems were followed-up at the neonatal outpatient department. Patients were divided into wheezing and non-wheezing groups. Data were analyzed using the Mann-Whitney test and Fisher’s exact test, and multivariable logistic regression was used to define the risk factors of preschool wheezing/asthma. A total of 125 preterm infants were enrolled, including 19 in the wheezing group and 106 in the non-wheezing group. Patients in the wheezing group had longer duration of intubation (p = 0.025), higher rates for exclusive breast milk feeding (p = 0.012), and higher re-hospitalization rates for respiratory tract infections (p less then 0.001), especially for respiratory syncytial virus (RSV) bronchiolitis (p = 0.045). The incidence of allergic rhinitis was also higher in the wheezing group (p = 0.005). After multivariable logistic regression, allergic rhinitis and re-hospitalization for respiratory tract infections were two significant risk factors for preschool wheezing/asthma in premature neonates. Close follow-up of premature infants at high risk for asthma susceptibility is recommended.Our primary objective for this follow-up study was to compare the neurodevelopmental outcomes of a surviving cohort of infants using a split-week gestational model (early versus late) gestational age (GA) and the standard completed GA categorization. Neurodevelopmental outcomes using a split-week GA model defined as early (X, 0-3) and late (X, 4-6), with X being 23-26 weeks GA, were compared to outcomes using completed weeks GA. In total, 1012 infants were included in the study. Statistically significant differences were noted in outcomes between the early and late split of the gestational week at 23 weeks (early vs. late), with 13.3% vs. 54.5% for no neurodevelopmental impairment, and 53.3% vs. 22.7% for significant impairment (p = 0.034), respectively. There were no differences seen in the split week model for 24, 25, and 26 weeks. A trend towards improved neurodevelopmental outcomes was seen with each increasing gestation week. The split-week model did not provide additional information for pregnancies and infants between 24 and 26 weeks gestation. It did, however, provide information for counsel for infants at 23 weeks gestation, showing benefits in the late versus early half of the week.

The main aim of this study was to describe and conduct a bibliometric analysis of the state of research on stress, anxiety, and postpartum depression in mothers of preterm infants in the Neonatal Intensive Care Unit.

Women affected by premature births are particularly exposed to mental health difficulties in the postpartum period. The desire to comprehend and the growing interest in research on stress, anxiety, and postpartum depression in mothers of preterm infants in neonatal intensive care have led to a substantial rise in the number of documents in this field over the last years. Thus, it makes it vital to regularly review the state of knowledge on this phenomenon in order to identify progress and constraints, to stimulate reflection, and to encourage progress in future research.

This study examined 366 articles published in the Scopus database (1976-2020). Keyword analysis was also used to identify hot research trends to be developed in future studies. This study complies with the PRISMA-Scr guidelines for quality improvement research in the EQUATOR network.

Our results reveal that research in this field is in a period of high production and allows this flourishing body of work to be organized into different periods, highlighting the most important themes. In such a way, our research enriches the lively field by presenting a comprehensive understanding of the field.

The key contribution of this study is the development of a conceptual map of research on stress, anxiety, and postpartum depression in mothers of preterm infants in neonatal intensive care units.

The key contribution of this study is the development of a conceptual map of research on stress, anxiety, and postpartum depression in mothers of preterm infants in neonatal intensive care units.Pulmonary vein stenosis is a serious condition characterized by restriction or blockage due to fibrotic tissue ingrowth that develops in the pulmonary veins of infants or children. It is often progressive and can lead to severe pulmonary hypertension and death. Efforts to halt or reverse disease progression include surgery and catheter-based balloon dilation and stent implantation. Its cause and mechanism of progression are unknown. In this pilot study, we propose and explore the hypothesis that elevated wall shear stress at discrete pulmonary venous sites triggers stenosis. To assess this theory, we retrospectively analyzed cardiac catheterization, lung scan, and X-ray computed tomography data to estimate wall shear stress in the pulmonary veins at multiple time points during disease progression in two patients. Results are consistent with the existence of a level of elevated wall shear stress above which the disease is progressive and below which progression is halted. The analysis also suggests the possibility of predicting the target lumen size necessary in a given vein to reduce wall shear stress to normal levels and remove the trigger for stenosis progression.Children have a low risk for severe COVID-19 infections, but indirect consequences of the pandemic may affect their health. We evaluated nationwide data on children’s outpatient visits before and during the first wave of the COVID-19 pandemic in Germany. Data from the National Association of Statutory Health Insurance Physicians for all children with statutory health insurance and at least one physician’s office visit between January 2019 and June 2020 were evaluated for total visits and selected diagnoses for the 2nd quarter of 2019 (8.29 million children, controls) and the 2nd quarter of 2020 (8.5 million, pandemic). Outpatient visits per child fell by 18% during the first wave of the pandemic. Outpatient visits associated with diagnosed infections fell markedly by 51%, particularly for children up to age 5 years for gastroenteritis (73%), otitis media (71%), and streptococcal angina (78%). Outpatient visits for diagnosed chronic physical disorders (diabetes, celiac disease, and hay fever) and mental and behavioral disorders showed little change. Reduced contact between children appears to markedly reduce infection transmission. Infection risks in educational settings should be attenuated after the pandemic through targeted education and counseling and appropriate relationship prevention measures to improve quality of life and opportunities for children and to reduce stress and lost work time for parents.Craniosynostosis, the premature closure of cranial sutures, is one of the principal causes of pediatric skull deformities. It can cause aesthetic, neurological, acoustic, ophthalmological complications up to real emergencies. Craniosynostosis are primarily diagnosed with accurate physical examination, skull measurement and observation of the deformity, but the radiological support currently plays an increasingly important role in confirming a more precise diagnosis and better planning for therapeutic interventions. The clinician must know how to diagnose in the earliest and least invasive way for the child. In the past, technological limitations reduced the choices; today, however, there are plenty of choices and it is necessary to use the various types of available imaging correctly. In the future, imaging techniques will probably rewrite the common classifications we use today. We provide an updated review of the role of imaging in this condition, through the ages, to outline the correct choice for the clinician for an early and non-invasive diagnosis.

To evaluate extravascular findings on thoracic MDCT angiography in secondary pulmonary vein stenosis (PVS) due to total anomalous pulmonary venous connection (TAPVC) repair in children.

All patients aged ≤18 years with a known diagnosis of secondary PVS after TAPVC repair, confirmed by echocardiography, conventional angiography, and/or surgery, who underwent thoracic MDCT angiography studies between July 2008 and April 2021 were included. Two pediatric radiologists independently examined MDCT angiography studies for the presence of extravascular thoracic abnormalities in the lung, pleura, and mediastinum. The location and distribution of each abnormality (in relation to the location of PVS) were also evaluated. Interobserver agreement between the two independent pediatric radiology reviewers was studied using kappa statistics.

The study group consisted of 20 consecutive pediatric patients (17 males, 3 females) with secondary PVS due to TAPVC repair. Age ranged from 2 months to 8 years (mean, 16.1 months seen in pediatric secondary PVS due to TAPVC repair.

Our study characterizes the extravascular thoracic MDCT angiography findings in secondary pediatric PVS due to TAPVC repair. In the lungs and pleura, ground-glass opacity, interlobular septal thickening, and pleural thickening are common findings. Importantly, the presence of a mildly heterogeneously enhancing, non-calcified mediastinal soft tissue mass in the distribution of the PVS is a novel characteristic thoracic MDCT angiography finding seen in pediatric secondary PVS due to TAPVC repair.The complicated crown-root fracture of young permanent teeth is an uncommon traumatic dental injury that is usually treated in a complex way and is demanding not only for the dentist but even for the treated child. In this case report, we present the conservative treatment of a maxillary central incisor in a 10-year-old boy after a traumatic dental injury. Treatment included partial pulpotomy and adhesive fragment reattachment after reflection of the mucoperiosteal flap. The patient was fully asymptomatic at 24-month follow-up, with an aesthetically acceptable outcome. Vital pulp therapy and adhesive fragment reattachment can be a viable treatment option for complicated crown-root fractures, especially when treating immature permanent teeth.

Child abuse and neglect (CAN) is considered a serious problem worldwide. Dentists have a significant role in recognizing and reporting CAN cases.

The aim of this study was to assess the CAN-related knowledge and educational experiences among Saudi dental graduates.

Self-administered questionnaires were distributed to dental graduates from all dental schools in Saudi Arabia (

= 1552). Bivariate and multivariate logistic regression analyses were performed to assess the associations between knowledge level and different predictors.

A total of 988 dental graduates completed the questionnaire. The majority of them were dissatisfied with the amount of education they had received in their school (56.4%). Around 60% of the participants had inadequate knowledge regarding CAN. Graduates from government schools who received dental education about CAN and female participants had significantly higher odds of having adequate knowledge scores than others (odds ratio = 2.0, 3.1, and 1.7, respectively). Only 39.5% of the participants felt confident in their ability to identify CAN cases, and only 9.7% knew how to report such cases.

Graduate dental students have insufficient knowledge about CAN. More time should be dedicated to educating students about this important topic in dental curricula.

Graduate dental students have insufficient knowledge about CAN. More time should be dedicated to educating students about this important topic in dental curricula.Social well-being is an intrinsic part of the current concept of health. In the context of chronic disease, there are many challenges we face in order to provide social well-being to patients and their families, even more if we talk about rare diseases. TransplantChild, a European Reference Network (ERN) in paediatric transplantation, works to improve the quality of life of transplanted children. It is not possible to improve the quality of life if the human and material resources are not available. With this study, we want to identify the economic aids, facilities, services, and financed products that are offered to families in different European centres. We also want to find out who provides these resources and the accessibility to them. We designed an ad hoc survey using the EU Survey software tool. The survey was sent to representatives of the 26 ERN members. In this article we present the results obtained in relation to two of the aspects analysed long-term financial assistance and drugs, pharmaceuticals and medical devices. Some resources are equally available in all participating centres but there are significant differences in others, such as education aids or parapharmacy product financing. A local analysis of these differences is necessary to find feasible solutions for equal opportunities for all transplanted children in Europe. The experience of centres that already provide certain solutions successfully may facilitate the implementation of these solutions in other hospitals.(1) Background The assessment of postural segment control in premature infants seems to be critical during the onset of upright gross motor development, especially sitting. Identifying correlations between postural segment control and the development of sitting milestones could help with promoting optimal gross motor movement. However, data on this topic in home-raised premature infants via longitudinal design are still limited. The purpose of this study was to examine relationships between postural segment control and sitting development through series assessments from the corrected age of 4 months until the early onset of independent sitting attainment. (2) Methods 33 moderate-to-late premature infants were recruited. Their trunk segment control was assessed using the Segmental Assessment of Trunk Control (SATCo), and sitting development was examined by the Alberta Infant Motor Scale (AIMS). Relationships between SATCo and sitting scores were analysed using Spearman’s rank correlation (rs). (3) Results significant fair-to-good correlations between segmental trunk control and sitting scales were found from 4 months (rs = 0.370-0.420, p less then 0.05) to the age of independent sitting attainment (rs = 0.561-0.602, p less then 0.01). (4) Conclusion relationships between the trunk segment control and sitting ability of moderate-to-late preterm infants were increased in accordance with age.(1) Background Immune-mediated necrotizing myopathy (IMNM) is a rare form of inflammatory muscle disease which is even more rare in pediatric patients. To increase the knowledge of juvenile IMNM, we here present the clinical findings on long-term follow-up, myopathological changes, and therapeutic strategies in two juvenile patients. (2) Methods Investigations included phenotyping, determination of antibody status, microscopy on muscle biopsies, MRI, and response to therapeutic interventions. (3) Results Anti-signal recognition particle (anti-SRP54) and anti- 3-hydroxy-3-methylglutarly coenzyme A reductase (anti-HMGCR) antibodies (Ab) were detected in the patients. Limb girdle presentation, very high CK-levels, and a lack of skin rash at disease-manifestation and an absence of prominent inflammatory signs accompanied by an abnormal distribution of α-dystroglycan in muscle biopsies initially hinted toward a genetically caused muscle dystrophy. Further immunostaining studies revealed an increase of proteins involved in chaperone-assisted autophagy (CASA), a finding already described in adult IMNM-patients. Asymmetrical muscular weakness was present in the anti-SRP54 positive Ab patient. After initial stabilization under therapy with intravenous immunoglobulins and methotrexate, both patients experienced a worsening of their symptoms and despite further therapy escalation, developed a permanent reduction of their muscle strength and muscular atrophy. (4) Conclusions Diagnosis of juvenile IMNM might be complicated by asymmetric muscle weakness, lack of cutaneous features, absence of prominent inflammatory changes in the biopsy, and altered α-dystroglycan.

Pediatric dentistry shares many skills with pediatrics. This review evaluates the amount of literature on pediatric dentistry in the first 30 pediatric journals classified by the Web of Science in 2019. The aim was to perform a quantitative analysis of the main dental topics addressed.

A scoping review with the PRISMA-ScR criteria was performed. The Clarivate Analytics Journal Citation Report was consulted for journals ranked in the category „Pediatrics” in 2019. Papers were searched in PubMed using an ad hoc prepared string.

A total of 504 papers were included. Papers on dental hard tissues were the most prevalent (45.6%), followed by dental public health (23.2%), orofacial development (15.3%), soft tissues related conditions (12.3%), and orofacial trauma (3.6%). Increasing trends have been observed for total papers published (R

= 0.9822) and total dental papers (R

= 0.8862), with no statistically significant differences (χ

(6) = 0.051

> 0.05). The majority of papers (

= 292, 57.9%) were cited between 1 and 10 times, whilst less than 7% of papers received more than 40 citations.

It is desirable that papers on pediatric dentistry increase in the pediatric scenario, allowing the two related disciplines to intertwine more in the future.

It is desirable that papers on pediatric dentistry increase in the pediatric scenario, allowing the two related disciplines to intertwine more in the future.Non-alcoholic fatty liver disease (NAFLD) is a major health issue worldwide, being frequently associated with obesity, unbalanced dietary regimens, and reduced physical activity. Despite their greater adiposity and reduced physical activity, women show a lower risk of developing NAFLD in comparison to men, likely a consequence of a sex-specific regulation of liver metabolism. In the liver, sex differences in the uptake, synthesis, oxidation, deposition, and mobilization of lipids, as well as in the regulation of inflammation, are associated with differences in NAFLD prevalence and progression between men and women. Given the major role of sex hormones in driving hepatic sexual dimorphism, this review will focus on the role of sex hormones and their signaling in the regulation of hepatic metabolism and in the molecular mechanisms triggering NAFLD development and progression.Atrial fibrillation is very common among the elderly and/or obese. While myocardial fibrosis is associated with atrial fibrillation, the exact mechanisms within atrial myocytes and surrounding non-myocytes are not fully understood. This review considers the potential roles of myocardial fibroblasts and myofibroblasts in fibrosis and modulating myocyte electrophysiology through electrotonic interactions. Coupling with (myo)fibroblasts in vitro and in silico prolonged myocyte action potential duration and caused resting depolarization; an optogenetic study has verified in vivo that fibroblasts depolarized when coupled myocytes produced action potentials. This review also introduces another non-myocyte which may modulate both myocardial (myo)fibroblasts and myocytes epicardial adipose tissue. Epicardial adipocytes are in intimate contact with myocytes and (myo)fibroblasts and may infiltrate the myocardium. Adipocytes secrete numerous adipokines which modulate (myo)fibroblast and myocyte physiology. These adipokines are protective in healthy hearts, preventing inflammation and fibrosis. However, adipokines secreted from adipocytes may switch to pro-inflammatory and pro-fibrotic, associated with reactive oxygen species generation. Pro-fibrotic adipokines stimulate myofibroblast differentiation, causing pronounced fibrosis in the epicardial adipose tissue and the myocardium. Adipose tissue also influences myocyte electrophysiology, via the adipokines and/or through electrotonic interactions. Deeper understanding of the interactions between myocytes and non-myocytes is important to understand and manage atrial fibrillation.The inflammatory cytokine interleukin-26 (IL-26) is highly expressed in the serum and synovial fluid of patients with inflammatory arthritis. The effect of IL-26 on human articular chondrocytes (HACs) remains unclear. Obesity is associated with disability of patients with rheumatoid arthritis and disease activity in those with ankylosing spondylitis. The saturated free fatty acid palmitate with IL-1β can synergistically induce catabolic effects in HACs. The aim of this study was to evaluate the effects of IL-26 and palmitate in HACs. In this study, palmitate markedly synergizes the IL-26-induced proinflammatory effects and matrix protease, including COX-2, IL-6, and MMP-1, in HACs via the toll-like receptor 4 (TLR4)-ERK1/2-c-Jun signal transduction pathway. The synergistic catabolic effects of palmitate and IL-26 were attenuated by inhibitors of TLR4 (TAK242), ERK1/2 (U0126), or c-Jun (SP600125) in HACs and cartilage matrix. In addition, metformin, a potential inhibitor of TLR4, also decreased expression of COX-2 and IL-6 induced by co-incubation with IL-26 and palmitate. IL-26 and palmitate synergistically induced expression of inflammatory and catabolic mediators, resulting in articular cartilage matrix breakdown. The present study also revealed a possible mechanism and therapeutic targets against articular cartilage degradation by increased saturated fatty acids in patients with inflammatory arthritis.Diabetic kidney disease (DKD) is a frequent, potentially devastating complication of diabetes mellitus. Several factors are involved in its pathophysiology. At a cellular level, diabetic kidney disease is associated with many structural and functional alterations. Autophagy is a cellular mechanism that transports intracytoplasmic components to lysosomes to preserve cellular function and homeostasis. Autophagy integrity is essential for cell homeostasis, its alteration can drive to cell damage or death. Diabetic kidney disease is associated with profound autophagy dysregulation. Autophagy rate and flux alterations were described in several models of diabetic kidney disease. Some of them are closely linked with disease progression and severity. Some antidiabetic agents have shown significant effects on autophagy. A few of them have also demonstrated to modify disease progression and improved outcomes in affected patients. Other drugs also target autophagy and are being explored for clinical use in patients with diabetic kidney disease. The modulation of autophagy could be relevant for the pharmacological treatment and prevention of this disease in the future. Therefore, this is an evolving area that requires further experimental and clinical research. Here we discuss the relationship between autophagy and Diabetic kidney disease and the potential value of autophagy modulation as a target for pharmacological intervention.The current process of meat production using livestock has significant effects on the global environment, including high emissions of greenhouse gases. In recent years, cultured meat has attracted attention as a way to acquire animal proteins. However, the lack of markers that isolate proliferating cells from bovine tissues and the complex structure of the meat make it difficult to culture meat in a dish. In this study, we screened 246 cell-surface antibodies by fluorescence-activated cell sorting for their capacity to form colonies and their suitability to construct spheroid „meat buds”. CD29+ cells (Ha2/5 clone) have a high potency to form colonies and efficiently proliferate on fibronectin-coated dishes. Furthermore, the meat buds created from CD29+ cells could differentiate into muscle and adipose cells in a three-dimensional structure. The meat buds embedded in the collagen gel proliferated in the matrix and formed large aggregates. Approximately 10 trillion cells can theoretically be obtained from 100 g of bovine tissue by culturing and amplifying them using these methods. The CD29+ cell characteristics of bovine tissue provide insights into the production of meat alternatives in vitro.Bone complications of cystinosis have been recently described. The main objectives of this paper were to determine in vitro the impact of CTNS mutations and cysteamine therapy on human osteoclasts and to carry out a genotype-phenotype analysis related to osteoclastic differentiation. Human osteoclasts were differentiated from peripheral blood mononuclear cells (PBMCs) and were treated with increasing doses of cysteamine (0, 50, 200 µM) and then assessed for osteoclastic differentiation. Results are presented as median (min-max). A total of 17 patients (mainly pediatric) were included, at a median age of 14 (2-61) years, and a eGFR of 64 (23-149) mL/min/1.73 m2. Most patients (71%) were under conservative kidney management (CKM). The others were kidney transplant recipients. Three functional groups were distinguished for CTNS mutations cystinosin variant with residual cystin efflux activity (RA, residual activity), inactive cystinosin variant (IP, inactive protein), and absent protein (AP). PBMCs from patients with residual cystinosin activity generate significantly less osteoclasts than those obtained from patients of the other groups. In all groups, cysteamine exerts an inhibitory effect on osteoclastic differentiation at high doses. This study highlights a link between genotype and osteoclastic differentiation, as well as a significant impact of cysteamine therapy on this process in humans.Cell-based therapy represents a promising treatment strategy for cartilage defects. Alone or in combination with scaffolds/biological signals, these strategies open many new avenues for cartilage tissue engineering. However, the choice of the optimal cell source is not that straightforward. Currently, various types of differentiated cells (articular and nasal chondrocytes) and stem cells (mesenchymal stem cells, induced pluripotent stem cells) are being researched to objectively assess their merits and disadvantages with respect to the ability to repair damaged articular cartilage. In this paper, we focus on the different cell types used in cartilage treatment, first from a biological scientist’s perspective and then from a clinician’s standpoint. We compare and analyze the advantages and disadvantages of these cell types and offer a potential outlook for future research and clinical application.Incretin-potentiated glucose-stimulated insulin secretion (GSIS) is critical to maintaining euglycemia, of which GLP-1 receptor (GLP-1R) on β-cells plays an indispensable role. Recently, α-cell-derived glucagon but not intestine-derived GLP-1 has been proposed as the critical hormone that potentiates GSIS via GLP-1R. However, the function of glucagon receptors (GCGR) on β-cells remains elusive. Here, using GCGR or GLP-1R antagonists, in combination with glucagon, to treat single β-cells, α-β cell clusters and isolated islets, we found that glucagon potentiates insulin secretion via β-cell GCGR at physiological but not high concentrations of glucose. Furthermore, we transfected primary mouse β-cells with RAB-ICUE (a genetically encoded cAMP fluorescence indicator) to monitor cAMP level after glucose stimulation and GCGR activation. Using specific inhibitors of different adenylyl cyclase (AC) family members, we revealed that high glucose concentration or GCGR activation independently evoked cAMP elevation via AC5 in β-cells, thus high glucose stimulation bypassed GCGR in promoting insulin secretion. Additionally, we generated β-cell-specific GCGR knockout mice which glucose intolerance was more severe when fed a high-fat diet (HFD). We further found that β-cell GCGR activation promoted GSIS more than GLP-1R in HFD, indicating the critical role of GCGR in maintaining glucose homeostasis during nutrient overload.Using unsupervised metabolomics, we defined the complex metabolic conditions in the cortex of a mouse model of Rett syndrome (RTT). RTT, which represents a cause of mental and cognitive disabilities in females, results in profound cognitive impairment with autistic features, motor disabilities, seizures, gastrointestinal problems, and cardiorespiratory irregularities. Typical RTT originates from mutations in the X-chromosomal methyl-CpG-binding-protein-2 (Mecp2) gene, which encodes a transcriptional modulator. It then causes a deregulation of several target genes and metabolic alterations in the nervous system and peripheral organs. We identified 101 significantly deregulated metabolites in the Mecp2-deficient cortex of adult male mice; 68 were increased and 33 were decreased compared to wildtypes. Pathway analysis identified 31 mostly upregulated metabolic pathways, in particular carbohydrate and amino acid metabolism, key metabolic mitochondrial/extramitochondrial pathways, and lipid metabolism. In contrast, neurotransmitter-signaling is dampened. This metabolic fingerprint of the Mecp2-deficient cortex of severely symptomatic mice provides further mechanistic insights into the complex RTT pathogenesis. The deregulated pathways that were identified-in particular the markedly affected amino acid and carbohydrate metabolism-confirm a complex and multifaceted metabolic component in RTT, which in turn signifies putative therapeutic targets. Furthermore, the deregulated key metabolites provide a choice of potential biomarkers for a more detailed rating of disease severity and disease progression.Cellular stress induces the formation of membraneless protein condensates in both the nucleus and cytoplasm. The nucleocytoplasmic transport of proteins mainly occurs through nuclear pore complexes (NPCs), whose efficiency is affected by various stress conditions. Here, we report that hyperosmotic stress compartmentalizes nuclear 26S proteasomes into dense nuclear foci, independent of signaling cascades. Most of the proteasome foci were detected between the condensed chromatin mass and inner nuclear membrane. The proteasome-positive puncta were not colocalized with other types of nuclear bodies and were reversibly dispersed when cells were returned to the isotonic medium. The structural integrity of 26S proteasomes in the nucleus was slightly affected under the hyperosmotic condition. We also found that these insulator-body-like proteasome foci were possibly formed through disrupted nucleus-to-cytosol transport, which was mediated by the sequestration of NPC components into osmostress-responding stress granules. These data suggest that phase separation in both the nucleus and cytosol may be a major cell survival mechanism during hyperosmotic stress conditions.Transcorneal electrical stimulation (TES) has emerged as a non-invasive neuromodulation approach that exerts neuroprotection via diverse mechanisms, including neurotrophic, neuroplastic, anti-inflammatory, anti-apoptotic, anti-glutamatergic, and vasodilation mechanisms. Although current studies of TES have mainly focused on its applications in ophthalmology, several lines of evidence point towards its putative use in treating depression. Apart from stimulating visual-related structures and promoting visual restoration, TES has also been shown to activate brain regions that are involved in mood alterations and can induce antidepressant-like behaviour in animals. The beneficial effects of TES in depression were further supported by its shared mechanisms with FDA-approved antidepressant treatments, including its neuroprotective properties against apoptosis and inflammation, and its ability to enhance the neurotrophic expression. This article critically reviews the current findings on the neuroprotective effects of TES and provides evidence to support our hypothesis that TES possesses antidepressant effects.Direct pulp capping is an effective treatment for preserving dental pulp against carious or traumatic pulp exposure via the formation of protective reparative dentin by odontoblast-like cells. Reparative dentin formation can be stimulated by several signaling molecules; therefore, we investigated the effects of secreted frizzled-related protein (SFRP) 1 that was reported to be strongly expressed in odontoblasts of newborn molar tooth germs on odontoblastic differentiation and reparative dentin formation. In developing rat incisors, cells in the dental pulp, cervical loop, and inner enamel epithelium, as well as ameloblasts and preodontoblasts, weakly expressed Sfrp1; however, Sfrp1 was strongly expressed in mature odontoblasts. Human dental pulp cells (hDPCs) showed stronger expression of SFRP1 compared with periodontal ligament cells and gingival cells. SFRP1 knockdown in hDPCs abolished calcium chloride-induced mineralized nodule formation and odontoblast-related gene expression and decreased BMP-2 gene expression. Conversely, SFRP1 stimulation enhanced nodule formation and expression of BMP-2. Direct pulp capping treatment with SFRP1 induced the formation of a considerable amount of reparative dentin that has a structure similar to primary dentin. Our results indicate that SFRP1 is crucial for dentinogenesis and is important in promoting reparative dentin formation in response to injury.Eutrophication is a leading problem in water bodies all around the world in which nitrate is one of the major contributors. The present study was conducted to study the effects of various concentrations of nitrate on two eukaryotic green microalgae, Chlamydomonas sp. MACC-216 and Chlorella sp. MACC-360. For this purpose, both microalgae were grown in a modified tris-acetate-phosphate medium (TAP-M) with three different concentrations of sodium nitrate, i.e., 5 mM (TAP-M5), 10 mM (TAP-M10) and 15 mM (TAP-M15), for 6 days and it was observed that both microalgae were able to remove nitrate completely from the TAP-M5 medium. Total amount of pigments decreased with the increasing concentration of nitrate, whereas protein and carbohydrate contents remained unaffected. High nitrate concentration (15 mM) led to an increase in lipids in Chlamydomonas sp. MACC-216, but not in Chlorella sp. MACC-360. Furthermore, Chlamydomonas sp. MACC-216 and Chlorella sp. MACC-360 were cultivated for 6 days in synthetic wastewater (SWW) with varying concentrations of nitrate where both microalgae grew well and showed an adequate nitrate removal capacity.Neutrophils are the most abundant immune cell in the circulation of human and act as gatekeepers to discard foreign elements that have entered the body. They are essential in initiating immune responses for eliminating invaders, such as microorganisms and alien particles, as well as to act as immune surveyors of cancer cells, especially during the initial stages of carcinogenesis and for eliminating single metastatic cells in the circulation and in the premetastatic organs. Since neutrophils can secrete a whole range of factors stored in their many granules as well as produce reactive oxygen and nitrogen species upon stimulation, neutrophils may directly or indirectly affect carcinogenesis in both the positive and negative directions. An intricate crosstalk between tumor cells, neutrophils, other immune cells and stromal cells in the microenvironment modulates neutrophil function resulting in both anti- and pro-tumor activities. Both the anti-tumor and pro-tumor activities require chemoattraction towards the g tumor growth and homing at metastatic sites. Cathepsin G was found to be essential for neutrophil-supported lung colonization of cancer cells. These data level up the complexity of the dual role of neutrophils in cancer.Inherited retinal degenerations (IRD) affecting either photoreceptors or pigment epithelial cells cause progressive visual loss and severe disability, up to complete blindness. Retinal organoids (ROs) technologies opened up the development of human inducible pluripotent stem cells (hiPSC) for disease modeling and replacement therapies. However, hiPSC-derived ROs applications to IRD presently display limited maturation and functionality, with most photoreceptors lacking well-developed outer segments (OS) and light responsiveness comparable to their adult retinal counterparts. In this review, we address for the first time the microenvironment where OS mature, i.e., the subretinal space (SRS), and discuss SRS role in photoreceptors metabolic reprogramming required for OS generation. We also address bioengineering issues to improve culture systems proficiency to promote OS maturation in hiPSC-derived ROs. This issue is crucial, as satisfying the demanding metabolic needs of photoreceptors may unleash hiPSC-derived ROs full potential for disease modeling, drug development, and replacement therapies.Retrospective observational studies have reported that statins improve clinical outcomes in patients previously treated with programmed cell death protein 1 (PD-1)-targeting monoclonal antibodies for malignant pleural mesothelioma (MPM) and advanced non-small cell lung cancer (NSCLC). In multiple mouse cancer models, de novo synthesis of mevalonate and cholesterol inhibitors was found to synergize with anti-PD-1 antibody therapy. In the present study, we investigated whether statins affect programmed death-ligand 1 (PD-L1) expression in cancer cells. Four statins, namely simvastatin, atorvastatin, lovastatin, and fluvastatin, decreased PD-L1 expression in melanoma and lung cancer cells. In addition, we found that AKT and β-catenin signaling involved PD-L1 suppression by statins. Our cellular and molecular studies provide inspiring evidence for extending the clinical evaluation of statins for use in combination with immune checkpoint inhibitor-based cancer therapy.Mitochondrial dysfunction plays a pivotal role in the Alzheimer’s Disease (AD) pathology. Disrupted mitochondrial dynamics (i.e., fusion/fission balance), which are essential for normal mitochondria structure and function, are documented in AD. Caveolin-1 (Cav-1), a membrane/lipid raft (MLR) scaffolding protein regulates metabolic pathways in several different cell types such as hepatocytes and cancer cells. Previously, we have shown decreased expression of Cav-1 in the hippocampus of 9-month (m) old PSAPP mice, while hippocampal overexpression of neuron-targeted Cav-1 using the synapsin promoter (i.e., SynCav1) preserved cognitive function, neuronal morphology, and synaptic ultrastructure in 9 and 12 m PSAPP mice. Considering the central role of energy production in maintaining normal neuronal and synaptic function and survival, the present study reveals that PSAPP mice exhibit disrupted mitochondrial distribution, morphometry, and respiration. In contrast, SynCav1 mitigates mitochondrial damage and loss and enhances mitochondrial respiration. Furthermore, by examining mitochondrial dynamics, we found that PSAPP mice showed a significant increase in the phosphorylation of mitochondrial dynamin-related GTPase protein (DRP1), resulting in excessive mitochondria fragmentation and dysfunction. In contrast, hippocampal delivery of SynCav1 significantly decreased p-DRP1 and augmented the level of the mitochondrial fusion protein, mitofusin1 (Mfn1) in PSAPP mice, a molecular event, which may mechanistically explain for the preserved balance of mitochondria fission/fusion and metabolic resilience in 12 m PSAPP-SynCav1 mice. Our data demonstrate the critical role for Cav-1 in maintaining normal mitochondrial morphology and function through affecting mitochondrial dynamics and explain a molecular and cellular mechanism underlying the previously reported neuroprotective and cognitive preservation induced by SynCav1 in PSAPP mouse model of AD.Glioblastoma (GBM) is the most aggressive malignant glioma. Therapeutic targeting of GBM is made more difficult due to its heterogeneity, resistance to treatment, and diffuse infiltration into the brain parenchyma. Better understanding of the tumor microenvironment should aid in finding more effective management of GBM. GBM-associated macrophages (GAM) comprise up to 30% of the GBM microenvironment. Therefore, exploration of GAM activity/function and their specific markers are important for developing new therapeutic agents. In this study, we identified and evaluated the expression of ALDH1A2 in the GBM microenvironment, and especially in M2 GAM, though it is also expressed in reactive astrocytes and multinucleated tumor cells. We demonstrated that M2 GAM highly express ALDH1A2 when compared to other ALDH1 family proteins. Additionally, GBM samples showed higher expression of ALDH1A2 when compared to low-grade gliomas (LGG), and this expression was increased upon tumor recurrence both at the gene and protein levels. We demonstrated that the enzymatic product of ALDH1A2, retinoic acid (RA), modulated the expression and activity of MMP-2 and MMP-9 in macrophages, but not in GBM tumor cells. Thus, the expression of ALDH1A2 may promote the progressive phenotype of GBM.With the nucleus as an exception, mitochondria are the only animal cell organelles containing their own genetic information, called mitochondrial DNA (mtDNA). During oocyte maturation, the mtDNA copy number dramatically increases and the distribution of mitochondria changes significantly. As oocyte maturation requires a large amount of ATP for continuous transcription and translation, the availability of the right number of functional mitochondria is crucial. There is a correlation between the quality of oocytes and both the amount of mtDNA and the amount of ATP. Suboptimal conditions of in vitro maturation (IVM) might lead to changes in the mitochondrial morphology as well as alternations in the expression of genes encoding proteins associated with mitochondrial function. Dysfunctional mitochondria have a lower ability to counteract reactive oxygen species (ROS) production which leads to oxidative stress. The mitochondrial function might be improved with the application of antioxidants and significant expectations are laid on the development of new IVM systems supplemented with mitochondria-targeted reagents. Different types of antioxidants have been tested already on animal models and human rescue IVM oocytes, showing promising results. This review focuses on the recent observations on oocytes’ intracellular mitochondrial distribution and on mitochondrial genomes during their maturation, both in vivo and in vitro. Recent mitochondrial supplementation studies, aiming to improve oocyte developmental potential, are summarized.Mitochondria are essential organelles that are not only responsible for energy production but are also involved in cell metabolism, calcium homeostasis, and apoptosis. Targeting mitochondria is a key strategy for bacteria to subvert host cells’ physiology and promote infection. Helicobacter (H.) pylori targets mitochondria directly. However, mitochondrial genome (mtDNA) polymorphism (haplogroup) is not yet considered an important factor for H. pylori infection. Here, we clarified the association of mitochondrial haplogroups with H. pylori prevalence and the ability to perform damage. Seven mtDNA haplogroups were identified among 28 H. pylori-positive subjects. Haplogroup B was present at a higher frequency and haplotype D at a lower one in the H. pylori population than in that of the H. pylori-negative one. The fibroblasts carrying high-frequency haplogroup displayed a higher apoptotic rate and diminished mitochondrial respiration following H. pylori infection. mtDNA mutations were accumulated more in the H. pylori-positive population than in that of the H.