AIM: To investigate efficacy and safety for granulocyte, monocyte apheresis in a population of pediatric patients with ulcerative colitis.METHODS: The ADAPT study was a prospective, openlabel, multicenter study in ped...AIM: To investigate efficacy and safety for granulocyte, monocyte apheresis in a population of pediatric patients with ulcerative colitis.METHODS: The ADAPT study was a prospective, openlabel, multicenter study in pediatric patients with moderate, active ulcerative colitis with pediatric ulcerative colitis activity index(PUCAI) of 35-64. Patients received one weekly apheresis with Adacolumn granulocyte, monocyte/macrophage adsorptive(GMA) apheresis over 5 consecutive weeks, optionally followed by up to 3 additional apheresis treatments over 3 consecutive weeks. The primary endpoint was the change in mean PUCAI between baseline and week 12; the secondary endpoint was improvement in PUCAI categorized as(Significant Improvement, PUCAI decrease of ≥ 35), Moderate Improvement(PUCAI decrease of 20 < 35), Small Improvement(PUCAI decrease of 10 < 20) or No change(PUCAI decrease of < 10). RESULTS: Twenty-five patients(mean age 13.5 years; mean weight 47.7 kg) were enrolled. In the intention-to-treat set(ITT), the mean value for PUCAI improvement was 22.3 [95%CI: 12.9-31.6; n = 21]. In the per-protocol(PP) set, the mean improvement was 36.3 [95%CI: 31.4-41.1; n = 8]. Significant Improvement was recorded for 9 out of 20 patients(45%); 5 out of 20 patients(25%) had Moderate Improvement and one patient(5%) had No Change in PUCAI score at week 12. In the PP set, six out of eight patients(75%) showed Significant Improvement; and in two out of eight patients(25%) Moderate Improvement was recorded. The endoscopic activity index(EAI) decreased by 3 points on average. Seven(7) out of 21(33%) patients in ITT and 4 out of 8(50%) patients in PP have used steroids during the clinical investigation. The mean steroid dosage for these patients in the ITT set decreased from a mean 12.4 mg to 10 mg daily on average from Baseline to week 12.CONCLUSION: Adacolumn; GMA apheresis treatment was effective in pediatric patients with moderate active Ulcerative Colitis. No new safety signals were reported. The present data contribute to considering GMA apheresis as a therapeutic option in pediatric patients having failed first line therapy.展开更多
AIM To assess the burden of norovirus(No V) and to determine the diversity of circulating strains among hospitalized children in Lebanon. METHODS Stool samples were collected from children presenting with acute gastro...AIM To assess the burden of norovirus(No V) and to determine the diversity of circulating strains among hospitalized children in Lebanon. METHODS Stool samples were collected from children presenting with acute gastroenteritis to six major hospitals in Lebanon. A total of 739 eligible stool samples, testing negative for diarrhea caused by rotavirus as a possible viral pathogen, were collected between January 2011 and June 2013. A standardized questionnaire including demographic, epidemiological and clinical observations was used at the time of hospitalization of children presenting with diarrhea. Viral RNA was extracted from stool samples followed by reverse transcription polymerase chain reaction and nucleotide sequencing of a fragment of the viral protein 1 capsid gene. Multiple sequence alignments were carried out and phylogenetic trees were constructed using the MEGA 6 software.RESULTS Overall, 11.2% of stool samples collected from children aged < 5 years tested positive for No V genogroups Ⅰ(GⅠ) and Ⅱ(GⅡ). GⅡ accounted for 10.6% of the gastroenteritis cases with only five samples being positive for GⅠ(0.7%). The majority of hospitalized children showed symptoms of diarrhea, dehydration, vomiting and fever. Upon sequencing of positive samples and based on their clustering in the phylogenetic tree, 4/5 of GⅠ gastroenteritis cases were designated GⅠ.3 and one case as GⅠ.4. GⅡ.4 was predominantly detected in stool of our study participants(68%). We report a JB-15/KOR/2008 GⅡ.4 Apeldoorn 2008-like variant strain circulating in 2011; this strain was replaced between 2012 and 2013 by a variant sharing homology with the Sydney/NSW0514/2012/AUS GⅡ.4 Sydney 2012 and Sydney 2012/FRA GⅡ.4 strains. We also report the co-circulation of non-GⅡ.4 genotypes among hospitalized children. Our data show that No V gastroenteritis can occur throughout the year with the highest number of cases detected during the hot months.CONCLUSION The majority of No V-associated viral gastroenteritis cases among our participants are attributable to GⅡ.4, which is compatible with results reported worldwide.展开更多
BACKGROUND The indirect methods of reference intervals(RI)establishment based on data mining are utilized to overcome the ethical,practical challenges and the cost associated with the conventional direct approach.AIM ...BACKGROUND The indirect methods of reference intervals(RI)establishment based on data mining are utilized to overcome the ethical,practical challenges and the cost associated with the conventional direct approach.AIM To generate RIs for serum creatinine in children and adolescents using an indirect statistical tool.METHODS Data mining of the laboratory information system was performed for serum creatinine analyzed from birth to 17 years for both genders.The timeline was set at six years from January 2013 to December 2018.Microsoft Excel 2010 and an indirect algorithm developed by the German Society of Clinical Chemistry and Laboratory Medicine’s Working Group on Guide Limits were used for the data analysis.RESULTS Data were extracted from 96104 samples and after excluding multiple samples for the same individual,we calculated RIs for 21920 males and 14846 females,with stratification into six discrete age groups.CONCLUSION Serum creatinine dynamics varied significantly across gender and age groups.展开更多
Genetic analyses of patients with transposition of the great arteries have identified rare copy number variations,suggesting that they may be significant to the aetiology of the disease.This paper reports the identifi...Genetic analyses of patients with transposition of the great arteries have identified rare copy number variations,suggesting that they may be significant to the aetiology of the disease.This paper reports the identification of a 16 p11.2 microduplication,a variation that has yet to be reported in association with transposition of the great arteries.The 16 p11.2 microduplication is associated with autism spectrum disorder and developmental delay,but with highly variable phenotypic effects.Autism and attention deficit disorders are observed more frequently in children with congenital heart disease than in the general population.Neonatal surgery is proposed as a risk factor,but as yet unidentified genetic abnormalities should also be taken into account.Thus,congenital heart abnormalities may constitute a part of the phenotypic spectrum associated with duplications at 16 p11.2.We suggest chromosomal microarray be considered part of the diagnostic work-up in patients with transposition of the great arteries.展开更多
Athletes are commonly advised not to compete or train during major symptoms of a viral acute respiratory illness(ARI),which most commonly is a common cold.It has been traditionally thought that heavy physical stress c...Athletes are commonly advised not to compete or train during major symptoms of a viral acute respiratory illness(ARI),which most commonly is a common cold.It has been traditionally thought that heavy physical stress could induce the worsening of symptoms of ARI and possibly cause potentially severe complications like myocarditis or sudden cardiac death(SCD).In addition,viral ARI may decrease athlete's performance.1 These concerns have been recently stressed during the coronavirus disease 2019(COVID-19)pandemic.2 However,it is anecdotally well-known that athletes commonly compete while experiencing common colds,most commonly due to picornaviral ARIs.In this perspective,we discuss what is known or not known regarding the risks of exercising during the viral ARI.展开更多
Chronic myeloid leukemia(CML)in minors is a rare disease which can be effectively treated by tyrosine kinase inhibitors(TKIs)since the year 2000.A majority of pediatricians will encounter one or two CML patients in th...Chronic myeloid leukemia(CML)in minors is a rare disease which can be effectively treated by tyrosine kinase inhibitors(TKIs)since the year 2000.A majority of pediatricians will encounter one or two CML patients in the course of their careers and will typically have to rely on written information along with their own intuition to provide care.Knowledge of response to TKIs and of agespecific side effects has an impact on the design of pediatric CML trials in many ways aiming to contribute toward greater predictability of clinical improvements.Information from a registry on a rare disease like CML offers the enormous benefit of enabling treating physicians to interact and share their collective experience.The International Registry on Pediatric CML(IR-PCML)was founded at Poitiers/France almost 10 years ago.Since then,the number of collaboration centers and in parallel of registered patients continuously increased(>550 patients as of December 2019).Ideally,from a given treatment center in a country data are transferred to a national coordinator who interacts with the IR-PCML.In the sense of quality assurance,the registry can offer dissemination of knowledge on state-of-the-art diagnostics(including reference appraisal),optimal treatment approaches,and follow-up procedures within a network that is exerting its strength via participation.With continuous growth during the recent years,very rare subgroups of patients could be identified(e.g.,CML diagnosed at age<3 years,children presenting with specific problems at diagnosis or during course of treatment)which had not been described before.Publications coming from the IR-PCML disseminated this useful information derived from patients who robustly participate and share information about their disease,among themselves and with their caregivers and clinicians.Patient input driving the collection of data on this rare leukemia is the basis for the considerable success of bringing new therapeutics into clinical use.展开更多
Survivors of pediatric central nervous system (CNS) cancer are at risk for long term sequelae concerning school participation. Therefore, the purpose of the study was to develop and evaluate a school-participation que...Survivors of pediatric central nervous system (CNS) cancer are at risk for long term sequelae concerning school participation. Therefore, the purpose of the study was to develop and evaluate a school-participation questionnaire for patients and parents based on the International Classification of Functioning, Disability and Health (ICF). The items of the School Participation Scales-24/7 (S-PS-24/7) meet different functions, activities and participation aspects, as well as environmental factors listed in the ICF, using everyday language. The study sample consisted of 48 pediatric brain tumor patients and their parents. Reliability scores for the S-PS-24/7 components were acceptable or high. For investigating validity, items were correlated with data from a neurocognitive assessment battery with promising results. This approach enables a description of educational outcome on a functional level instead of using global measures. This facilitates counseling of patients, parents and teachers with respect to academic achievement and specific intervention programs.展开更多
Objectives Assessing physical activity and cardiometabolic risk in masters athletes as an example of very high physical activity at old age.Methods Forty-three men were studied in full factorial design,either as sprin...Objectives Assessing physical activity and cardiometabolic risk in masters athletes as an example of very high physical activity at old age.Methods Forty-three men were studied in full factorial design,either as sprint or jump-trained masters athletes(MA,n=10,age 60–75 years),as young sprint or jump-trained athletes(YA,n=10,age 20–35 years),older control participants(OC,n=11,age 60–75 years)or as young control participants(AC,n=12,age 20–35 years).We performed bio-electrical impedance analysis and assessed serum markers of lipids and glucose metabolism and C-reactive protein,structured training hours,and habitual activity via mobile actimetry.Results Body fat was greater in OC than in MA(23.9[SD 4.2]%vs.14.0[SD 5.7]%,p<0.001),and also greater than in YA and YC(both p<0.001).Weekly training hours were comparable between MA and YA(7.9[SD3.3]hours vs.11.1[SD 4.8]hours,p=0.69).Habitual walking distance was greater in MA than in OC(7,387[SD 4,923]m/day vs.4,110[SD 1,772]m/day,p=0.039),and so was habitual running distance(667[SD690]m/day vs.132[427]m/day,p<0.001).HOMA-index was greater in OC than in MA(2.07[SD 1.39]vs.0.80[SD 0.41],p=0.0039),and so was C-reactive protein(1.35[SD 1.74]mg/l vs.0.58[SD 0.27]mg/ml,p=0.018),whereas serum lipids showed only moderate or no effect(all p between 0.036 and 0.07).Conclusions Improved body composition and physical activity levels in MA are associated with lower cardiometabolic risk,which seems more pronounced for insulin sensitivity and inflammaging than for lipid metabolism.展开更多
Dear Editor,We are much obliged that Hadziselimovic1 has used our data2 to highlight the substantial proportion of boys with cryptorchidism where gonadotropin insufficiency is an important factor related to the pathog...Dear Editor,We are much obliged that Hadziselimovic1 has used our data2 to highlight the substantial proportion of boys with cryptorchidism where gonadotropin insufficiency is an important factor related to the pathogenesis.We have recently presented a study on a series of 453 consecutive boys with bilateral nonsyndromic cryptorchidism,in which we conducted hormonal evaluations and assessed germ cell numbers in testicular biopsies.3 In this series,45%of the boys were classified as having gonadotropin insufficiency.3 Identifying these patients at the time of surgery is important.A recent follow-up study of 208 boys with nonsyndromic bilateral cryptorchidism from our department showed that the boys with gonadotropin insufficiency had an impaired fertility potential after surgery compared to boys with an intact hypothalamus–pituitary–gonadal feedback mechanism.4 In a review from 2022,Hadziselimovic5 suggested that infertility in patients diagnosed with cryptorchid testes is a consequence of a hormonal deficiency rather than temperature-induced cellular damage.展开更多
Background:The role of systemic tumor immune environment(STIE)is unclear in hepatocellular carcinoma(HCC).This study aimed to exam the cells in the STIE,their changes after transarterial chemoembolisation(TACE),stereo...Background:The role of systemic tumor immune environment(STIE)is unclear in hepatocellular carcinoma(HCC).This study aimed to exam the cells in the STIE,their changes after transarterial chemoembolisation(TACE),stereotactic body radiotherapy(SBRT),and immunotherapy(IO)and explore their significance in the treatment response of patients with unresectable HCC.Methods:This is a prospective biomarker study of patients with unresectable HCC.The treatment was sequential TACE,SBRT(27.5-40 Gy/5 fractions),and IO.The treatment response was assessed according to modified Re-sponse Evaluation Criteria in Solid Tumors(mRECIST)by magnetic resonance imaging(MRI)after 6 months of treatment.Longitudinal data of STIE cells was extracted from laboratory results of complete blood cell counts,in-cluding leukocytes,lymphocytes,neutrophils,monocytes,eosinophils,basophils,and platelets.Peripheral blood samples were collected at baseline and after TACE,SBRT,and IO for T-lymphocyte subtyping by flow cytometry.Generalized estimation equation was employed for longitudinal analyses.Results:A total of 35 patients with unresectable HCC were enrolled:23 patients in the exploratory cohort and 12 in the validation cohort.STIE circulating cells,especially lymphocytes,were heterogenous at baseline and changed differentially after TACE,SBRT,and IO in both cohorts.SBRT caused the greatest reduction of 0.7×10^(9)/L(95%CI:0.3×10^(9)/L-1.0×10^(9)/L,P<0.001)in lymphocytes;less reduction was associated with significantly better treatment response.The analysis of T-lymphocyte lineage revealed that the baseline levels of CD4+T cells(P=0.010),type 1 T helper(Th1)cells(P=0.007),and Th1/Th17 ratios(P=0.001)were significantly higher in responders,while regulatory T(Treg)cells(P=0.002),Th17 cells(P=0.047),and Th2/Th1 ratios(P=0.028)were significantly higher in non-responders.After treatment with TACE,SBRT and IO,T-lymphocyte lineage also changed differentially.More reductions were observed in CD25^(+)CD8^(+)T cells and CD127^(+)CD8^(+)T cells after SBRT in non-responders,while increases in natural killer T(NKT)cells after SBRT(10.4%vs.3.4%,P=0.001)and increases in the lymphocyte counts were noted during IO in responders.Conclusions:STIE cells are significant for treatment response,can be reshaped differentially after TACE,SBRT,and IO.The most significant changes of T-lymphocyte lineage are SBRT associated modulations in CD25^(+)CD8^(+)T cells,CD127^(+)CD8^(+)T cells,and NKT cells,which also have significant effects on the ultimate treatment response after TACE-SBRT-IO(ClinicalTrails.gov identifier:GCOG0001/NCT05061342).展开更多
The one-bead-one-compound （OBOC） combinatorial peptide library is a powerful tool to identify ligand and receptor interactions. Here, we applied the OBOC library technology to identify mimotopes specific to the immu...The one-bead-one-compound （OBOC） combinatorial peptide library is a powerful tool to identify ligand and receptor interactions. Here, we applied the OBOC library technology to identify mimotopes specific to the immunoglobulin E （IgE） epitopes of the major shellfish allergen tropomyosin. OBOC peptide libraries with 8-12 amino acid residues were screened with serum samples from patients with shellfish allergy for IgE mimotopes of tropomyosin. Twenty-five mimotopes were identified from the screening and their binding reactivity to tropomyosin-specific IgE was confirmed by peptide ELISA. These mimotopes could be divided into seven clusters based on sequence homology, and epitope mapping by EpiSearch of the clustered mimotopes was performed to characterize and confirm the validity of mimotopes. Five out of six of the predicted epitopes were found to overlap with previously identified epitopes of tropomyosin. To further confirm the mimicry potential of mimotopes, BALB/c mice were immunized with mimotopes conjugated to keyhole limpet hemocyanin and assayed for their capacity to induce tropomyosin-specific antibodies. BALB/c mice that received mimotope immunization were found to have an elevated level of tropomyosin-specific immunoglobulin G, but not mice that received an irrelevant mimotope. This study pioneers the successful application of the OBOC libraries using whole sera to screen and identify multiple shrimp allergen mimotopes and validates their mimicry potential using in vitro, in vivo, and in silico methods.展开更多
Background Peer victimization has been recognized as a common social problem affecting children and adolescents in all parts of the world. This study aims to examine the prevalence of different types of peer victimiza...Background Peer victimization has been recognized as a common social problem affecting children and adolescents in all parts of the world. This study aims to examine the prevalence of different types of peer victimization and to evaluate the associations between peer victimization and health correlates. Methods Using a large population sample of 18,341 adolescents aged 15–17 years from 6 cities in China, this study esti-mated the prevalence of different types of peer victimization, addictive behaviors, and health-related variables with self-administrated questionnaires. A three-phase logistical regression analysis was conducted to investigate the associations between peer victimization and addictive behaviors as well as health-related factors among adolescents. Results A total of 42.9% of the surveyed Chinese adolescents have been bullied by peers, with boys reporting higher rate on overt victimization (36.9%) and girls on relational forms (33.9%). School environment (34.7%) was the most frequent scene of peer violence, followed by neighborhood, family, and internet. Addictive behaviors except substance abuse were found related to higher possibility of peer victimization (aOR 1.21–1.73, P<0.001). Peer victimization was significantly associated with more depressive symptoms, post-traumatic stress disorder symptoms, and suicide ideation and deliberate self-harm (aOR 1.05–2.27, P<0.001), and poorer self-esteem and health-related quality of life (aOR 0.95–0.97, P<0.001). Conclusion Possible explanations of the associations found in this study are discussed and implications for future services are raised.展开更多
Background:Respiratory morbidity of former preterm infants and especially those with bronchopulmonary dysplasia(BPD)is high during infancy and early childhood.Data sources:We performed a review based on a literature s...Background:Respiratory morbidity of former preterm infants and especially those with bronchopulmonary dysplasia(BPD)is high during infancy and early childhood.Data sources:We performed a review based on a literature search including EMBASE,MEDLINE,and CINAHL databases to identify all relevant papers published in the English and German literature on influenza and respiratory syncytial virus infection associated with preterm infant,prematurity,and BPD between 1980 and 2014.Results:Recurrent respiratory symptoms remain common at preschool age,school age and even into young adulthood.Acute viral respiratory tract infections due to different pathogens cause significant morbidity and necessitate rehospitalizations during the fi rst years of life.Infl uenza virus infection plays a minor role compared to respiratory syncytial virus(RSV)associated respiratory tract infection during infancy and early childhood.Nevertheless,particular morbidity to both viruses is high.Conclusions:The particular burden of both viral diseases in preterm infants is dominated by RSV and its associated rehospitalizations during the fi rst two years of life.Prophylactic measures include vaccination against influenza virus of family members and caregivers and active immunization starting at the age of 6 months,and monthly injections of palivizumab during the cold season to avoid severe RSV disease and its sequelae.展开更多
Aberrant right subclavian artery(arteria lusoria) is the most common congenital root anomaly, remaining asymptomatic in most cases. Nevertheless, some of the 20%-40% of those affected present tracheo-esophageal sympto...Aberrant right subclavian artery(arteria lusoria) is the most common congenital root anomaly, remaining asymptomatic in most cases. Nevertheless, some of the 20%-40% of those affected present tracheo-esophageal symptoms. We report on a 6-year-old previously healthy girl presenting with progressive dysphagia over 4 wk. Diagnostics including barium swallow, echocardiography and magnetic resonance angiography(MRA) revealed a retro-esophageal compression by an aberrant right subclavian artery. Despite the successful, uneventful transposition of this arteria lusoria to the right common carotid via right-sided thoracotomy, the girl was suffering from persisting dysphagia. Another barium swallow showed the persistent compression of the esophagus on the level where the arteria lusoria had originated. As MRA showed no evidence of a significant re-obstruction by the transected vascular stump, we suspected a persisting ligamentum arteriosum. After a second surgical intervention via left-sided thoracotomy consisting of transecting the obviously persisting ligamentum and shortening the remaining arterial stump of the aberrant right subclavian artery, the patient recovered fully. In this case report we discuss the potential relevance of a persisting ligamentum arteriosum for patients with leftaortic arch suffering from dysphagia lusoria and rational means of diagnosing, as well as the surgical options to prevent re-do surgery.展开更多
The prognosis for children with recurrent or refractory neuroblastoma remains a significant clinical challenge,and currently there are no known curative salvage regimens.In this paper we investigated the effect of ima...The prognosis for children with recurrent or refractory neuroblastoma remains a significant clinical challenge,and currently there are no known curative salvage regimens.In this paper we investigated the effect of imatinib with rapamycin and the chemotherapeutic agents temozolomide and irinotecan.We treated two children with recurrent neuroblastoma with this so called RIST protocol.Both patients,off therapy for 15 and 31 months,respectively are well,and developing normally,without any complications.These findings suggest that a combination regimen of RIST may provide a therapeutic benefit with a favorable toxicity profile to a unfortunate subset of patients with neuroblastoma.展开更多
Although the incidence of pediatric heart failure is low, the mortality is relatively high, with severe clinical symptoms requiring repeated hospitalization or intensive care treatment in the surviving patients. Cardi...Although the incidence of pediatric heart failure is low, the mortality is relatively high, with severe clinical symptoms requiring repeated hospitalization or intensive care treatment in the surviving patients. Cardiac biopsy specimens have revealed a higher number of resident human cardiac progenitor cells, with greater proliferation and differentiation capacity, in the neonatal period as compared with adults, demonstrating the regeneration potential of the young heart, with rising interest in cardiac regeneration therapy in critically ill pediatric patients. We review here the available literature data, searching the MEDLINE, Google Scholar and EMBASE database for completed, and www.clinicaltrials.gov homepage for ongoing studies involving pediatric cardiac regeneration reports. Because of difficulties conducting randomized blinded clinical trials in pediatric patients, mostly case reports or cohort studies with a limited number of individuals have been published in the field of pediatric regenerative cardiology. The majority of pediatric autologous cell transplantations into the cardiac tissue have been performed in critically ill children with severe or terminal heart failure. Congenital heart disease, myocarditis, and idiopathic hypertrophic or dilated cardiomyopathy leading to congestive heart failure are some possible areas of interest for pediatric cardiac regeneration therapy. Autologous bone marrow mononuclear cells, progenitor cells, or cardiospheres have been applied either intracoronary or percutaneously intramyocardially in severely ill children, leading to a reported clinical benefit of cell-based cardiac therapies. In conclusion, compassionate use of autologous stem cell administration has led to at least short-term improvement in heart function and clinical stability in the majority of the critically ill pediatric patients.展开更多
This study assessed the feasibility of testis tissue cryopreservation (TTC) for fertility preservation in prepubescent boys with cryptorchidism. From January 2014 to December 2022, the University Hospital of Copenhage...This study assessed the feasibility of testis tissue cryopreservation (TTC) for fertility preservation in prepubescent boys with cryptorchidism. From January 2014 to December 2022, the University Hospital of Copenhagen (Rigshospitalet, Copenhagen, Denmark) implemented TTC for 56 boys with cryptorchidism to preserve their reproductive potential. Testis tissue samples were collected during orchiopexy (32 cases) or at subsequent follow-up procedures (24 cases), necessitated by an increased risk of infertility as indicated by hormonal assessments and/or findings from initial surgical biopsies. Testis samples were procured for TTC and pathological analysis. The cohort had an average age of 1.3 (range: 0.3–3.8) years at the time of orchiopexy, with 91.1% presenting bilateral cryptorchidism. The study revealed a median germ cell count of 0.39 (range: 0–2.88) per seminiferous tubule, with germ cells detected in 98.0% of the bilateral biopsies and 100% of the unilateral, indicating a substantial potential for fertility in these immature tissues. A dark spermatogonia (Ad) was detected in 37 out of 56 patients evaluated, with a median Ad spermatogonia count of 0.027 (range: 0.002–0.158) per seminiferous tubule. A total of 30.2% of the samples lacked Ad spermatogonia, indicative of potential gonadotrophin insufficiency. The median hormone levels measured were as follows: follicle-stimulating hormone (FSH) at 0.69 (range: 0.16–2.5) U l−1, luteinizing hormone (LH) at 0.21 (range: 0.05–3.86) U l−1, and inhibin B at 126 (range: 17–300) pg ml−1. Despite early orchiopexy, 20%–25% of boys with cryptorchidism remain at risk for future infertility, substantiating the necessity of TTC as a precaution. The study highlights the need for refined predictive techniques to identify boys at higher risk of future infertility.展开更多
In late 2019,heavy restrictions were enforced on public activities worldwide to diminish the spread of the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)virus[1].These restrictions,which included school c...In late 2019,heavy restrictions were enforced on public activities worldwide to diminish the spread of the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)virus[1].These restrictions,which included school closures and strictly limited sports and leisure opportunities,particularly impacted children and adolescents[2].Lifestyle changes in children and adolescents led to reduced physical activity levels[2,3],increased sedentary behavior[3,4],changes in eating habits,and changes in sleep habits[3].展开更多
Objective: To investigate the relationship between child care by domestic helper and specific language impairment (SLI). Design: Retrospective case-control study. Setting: A Child Assessment Center in Hong Kong that r...Objective: To investigate the relationship between child care by domestic helper and specific language impairment (SLI). Design: Retrospective case-control study. Setting: A Child Assessment Center in Hong Kong that receives referrals from primary and secondary care settings. Participants: We reviewed medical records of all new referrals younger than 5 years during a 4-year period (1999-2003) and compared children with SLI (cases) with those referred with other behavioral problems and assessed to have normal language and overall development (controls) using the Griffiths Mental Developmental Scale. Specific language impairment was defined as a language quotient more than 1 SD below the mean and below the general dev-elopmental quotient in children with normal general developmental quotient but without neurological or other organic diseases. Results: Four hundred ninety-six children were included (237 cases and 259 controls). The mean ages of cases and controls were 2.51 and 2.89 years, respectively. Boys predominated (cases=73.4% , controls= 60.2% ). The odds ratio (OR) of SLI for children cared for by a full-time domestic helper was 1.71 (95% confidence interval CI , 1.06-2.77; P=.03), after adjusting for confounding sociodemographic variables. Male gender (OR=1.91; 95% CI, 1.25-2.90), positive family history (OR=2.70; 95% CI, 1.55-4.73), fewer siblings (P=.01), and lower paternal occupational status (P=.01) were also risk factors for an SLI. Child care by a domestic helper was associated with a higher severity of an SLI in ordinal regression analysis (P=.048). Conclusions: Child care by a domestic helper is associated with increasing risk and severity of an SLI. Further studies are required to confirm the association and to evaluate whether avoidance of child care by a domestic helper could be recommended for children with an SLI or prone to develop an SLI.展开更多
Septins,components of the fourth cytoskeleton,play an indispensable role in establishing and maintaining epithelial cell polarity.However,the molecular mechanisms underlying the dynamic assembly of higher-order septin...Septins,components of the fourth cytoskeleton,play an indispensable role in establishing and maintaining epithelial cell polarity.However,the molecular mechanisms underlying the dynamic assembly of higher-order septin structures and the establishment of epithelial cell polarity remain elusive.Here,weshow that septinsform a previouslyunrecognized dynamic structure with liquid-like properties in polarized Madin-Darby canine kidney cells.We identified Septin 6(SEPT6)as the key human septin that undergoes liquid-liquid phase separation(LLPS)both in vitro and in vivo through weak,multivalent interactions mediated by its C-terminal tail.SEPT6 mutants defective in LLPS in vitro also fail to support adherens junction integrity and cell polarity establishment in 2D and 3D cell cultures.Our findings indicate that weak,multivalent interactions are essential forthe assembly of higher-order septin structures in cells.We propose that these interactions,in conjunction with conventional interactions between folded domains,generate partially ordered septin assemblies that support the apical-basal axis and lumen formation in metazoans.展开更多
基金Supported by Otsuka Frankfurt Research Institute, the legal and financial sponsor for this clinical trial, Otsuka Pharmaceutical Europe Ltd. supported the realization of this paper
文摘AIM: To investigate efficacy and safety for granulocyte, monocyte apheresis in a population of pediatric patients with ulcerative colitis.METHODS: The ADAPT study was a prospective, openlabel, multicenter study in pediatric patients with moderate, active ulcerative colitis with pediatric ulcerative colitis activity index(PUCAI) of 35-64. Patients received one weekly apheresis with Adacolumn granulocyte, monocyte/macrophage adsorptive(GMA) apheresis over 5 consecutive weeks, optionally followed by up to 3 additional apheresis treatments over 3 consecutive weeks. The primary endpoint was the change in mean PUCAI between baseline and week 12; the secondary endpoint was improvement in PUCAI categorized as(Significant Improvement, PUCAI decrease of ≥ 35), Moderate Improvement(PUCAI decrease of 20 < 35), Small Improvement(PUCAI decrease of 10 < 20) or No change(PUCAI decrease of < 10). RESULTS: Twenty-five patients(mean age 13.5 years; mean weight 47.7 kg) were enrolled. In the intention-to-treat set(ITT), the mean value for PUCAI improvement was 22.3 [95%CI: 12.9-31.6; n = 21]. In the per-protocol(PP) set, the mean improvement was 36.3 [95%CI: 31.4-41.1; n = 8]. Significant Improvement was recorded for 9 out of 20 patients(45%); 5 out of 20 patients(25%) had Moderate Improvement and one patient(5%) had No Change in PUCAI score at week 12. In the PP set, six out of eight patients(75%) showed Significant Improvement; and in two out of eight patients(25%) Moderate Improvement was recorded. The endoscopic activity index(EAI) decreased by 3 points on average. Seven(7) out of 21(33%) patients in ITT and 4 out of 8(50%) patients in PP have used steroids during the clinical investigation. The mean steroid dosage for these patients in the ITT set decreased from a mean 12.4 mg to 10 mg daily on average from Baseline to week 12.CONCLUSION: Adacolumn; GMA apheresis treatment was effective in pediatric patients with moderate active Ulcerative Colitis. No new safety signals were reported. The present data contribute to considering GMA apheresis as a therapeutic option in pediatric patients having failed first line therapy.
基金Supported by an investigator-initiated research grant from Merck Sharpe and Dohme(MSD)University Review Board Grant,American University of Beirut
文摘AIM To assess the burden of norovirus(No V) and to determine the diversity of circulating strains among hospitalized children in Lebanon. METHODS Stool samples were collected from children presenting with acute gastroenteritis to six major hospitals in Lebanon. A total of 739 eligible stool samples, testing negative for diarrhea caused by rotavirus as a possible viral pathogen, were collected between January 2011 and June 2013. A standardized questionnaire including demographic, epidemiological and clinical observations was used at the time of hospitalization of children presenting with diarrhea. Viral RNA was extracted from stool samples followed by reverse transcription polymerase chain reaction and nucleotide sequencing of a fragment of the viral protein 1 capsid gene. Multiple sequence alignments were carried out and phylogenetic trees were constructed using the MEGA 6 software.RESULTS Overall, 11.2% of stool samples collected from children aged < 5 years tested positive for No V genogroups Ⅰ(GⅠ) and Ⅱ(GⅡ). GⅡ accounted for 10.6% of the gastroenteritis cases with only five samples being positive for GⅠ(0.7%). The majority of hospitalized children showed symptoms of diarrhea, dehydration, vomiting and fever. Upon sequencing of positive samples and based on their clustering in the phylogenetic tree, 4/5 of GⅠ gastroenteritis cases were designated GⅠ.3 and one case as GⅠ.4. GⅡ.4 was predominantly detected in stool of our study participants(68%). We report a JB-15/KOR/2008 GⅡ.4 Apeldoorn 2008-like variant strain circulating in 2011; this strain was replaced between 2012 and 2013 by a variant sharing homology with the Sydney/NSW0514/2012/AUS GⅡ.4 Sydney 2012 and Sydney 2012/FRA GⅡ.4 strains. We also report the co-circulation of non-GⅡ.4 genotypes among hospitalized children. Our data show that No V gastroenteritis can occur throughout the year with the highest number of cases detected during the hot months.CONCLUSION The majority of No V-associated viral gastroenteritis cases among our participants are attributable to GⅡ.4, which is compatible with results reported worldwide.
文摘BACKGROUND The indirect methods of reference intervals(RI)establishment based on data mining are utilized to overcome the ethical,practical challenges and the cost associated with the conventional direct approach.AIM To generate RIs for serum creatinine in children and adolescents using an indirect statistical tool.METHODS Data mining of the laboratory information system was performed for serum creatinine analyzed from birth to 17 years for both genders.The timeline was set at six years from January 2013 to December 2018.Microsoft Excel 2010 and an indirect algorithm developed by the German Society of Clinical Chemistry and Laboratory Medicine’s Working Group on Guide Limits were used for the data analysis.RESULTS Data were extracted from 96104 samples and after excluding multiple samples for the same individual,we calculated RIs for 21920 males and 14846 females,with stratification into six discrete age groups.CONCLUSION Serum creatinine dynamics varied significantly across gender and age groups.
文摘Genetic analyses of patients with transposition of the great arteries have identified rare copy number variations,suggesting that they may be significant to the aetiology of the disease.This paper reports the identification of a 16 p11.2 microduplication,a variation that has yet to be reported in association with transposition of the great arteries.The 16 p11.2 microduplication is associated with autism spectrum disorder and developmental delay,but with highly variable phenotypic effects.Autism and attention deficit disorders are observed more frequently in children with congenital heart disease than in the general population.Neonatal surgery is proposed as a risk factor,but as yet unidentified genetic abnormalities should also be taken into account.Thus,congenital heart abnormalities may constitute a part of the phenotypic spectrum associated with duplications at 16 p11.2.We suggest chromosomal microarray be considered part of the diagnostic work-up in patients with transposition of the great arteries.
基金funded by the Jenny and Antti Wihuri Foundation(OR)。
文摘Athletes are commonly advised not to compete or train during major symptoms of a viral acute respiratory illness(ARI),which most commonly is a common cold.It has been traditionally thought that heavy physical stress could induce the worsening of symptoms of ARI and possibly cause potentially severe complications like myocarditis or sudden cardiac death(SCD).In addition,viral ARI may decrease athlete's performance.1 These concerns have been recently stressed during the coronavirus disease 2019(COVID-19)pandemic.2 However,it is anecdotally well-known that athletes commonly compete while experiencing common colds,most commonly due to picornaviral ARIs.In this perspective,we discuss what is known or not known regarding the risks of exercising during the viral ARI.
文摘Chronic myeloid leukemia(CML)in minors is a rare disease which can be effectively treated by tyrosine kinase inhibitors(TKIs)since the year 2000.A majority of pediatricians will encounter one or two CML patients in the course of their careers and will typically have to rely on written information along with their own intuition to provide care.Knowledge of response to TKIs and of agespecific side effects has an impact on the design of pediatric CML trials in many ways aiming to contribute toward greater predictability of clinical improvements.Information from a registry on a rare disease like CML offers the enormous benefit of enabling treating physicians to interact and share their collective experience.The International Registry on Pediatric CML(IR-PCML)was founded at Poitiers/France almost 10 years ago.Since then,the number of collaboration centers and in parallel of registered patients continuously increased(>550 patients as of December 2019).Ideally,from a given treatment center in a country data are transferred to a national coordinator who interacts with the IR-PCML.In the sense of quality assurance,the registry can offer dissemination of knowledge on state-of-the-art diagnostics(including reference appraisal),optimal treatment approaches,and follow-up procedures within a network that is exerting its strength via participation.With continuous growth during the recent years,very rare subgroups of patients could be identified(e.g.,CML diagnosed at age<3 years,children presenting with specific problems at diagnosis or during course of treatment)which had not been described before.Publications coming from the IR-PCML disseminated this useful information derived from patients who robustly participate and share information about their disease,among themselves and with their caregivers and clinicians.Patient input driving the collection of data on this rare leukemia is the basis for the considerable success of bringing new therapeutics into clinical use.
文摘Survivors of pediatric central nervous system (CNS) cancer are at risk for long term sequelae concerning school participation. Therefore, the purpose of the study was to develop and evaluate a school-participation questionnaire for patients and parents based on the International Classification of Functioning, Disability and Health (ICF). The items of the School Participation Scales-24/7 (S-PS-24/7) meet different functions, activities and participation aspects, as well as environmental factors listed in the ICF, using everyday language. The study sample consisted of 48 pediatric brain tumor patients and their parents. Reliability scores for the S-PS-24/7 components were acceptable or high. For investigating validity, items were correlated with data from a neurocognitive assessment battery with promising results. This approach enables a description of educational outcome on a functional level instead of using global measures. This facilitates counseling of patients, parents and teachers with respect to academic achievement and specific intervention programs.
文摘Objectives Assessing physical activity and cardiometabolic risk in masters athletes as an example of very high physical activity at old age.Methods Forty-three men were studied in full factorial design,either as sprint or jump-trained masters athletes(MA,n=10,age 60–75 years),as young sprint or jump-trained athletes(YA,n=10,age 20–35 years),older control participants(OC,n=11,age 60–75 years)or as young control participants(AC,n=12,age 20–35 years).We performed bio-electrical impedance analysis and assessed serum markers of lipids and glucose metabolism and C-reactive protein,structured training hours,and habitual activity via mobile actimetry.Results Body fat was greater in OC than in MA(23.9[SD 4.2]%vs.14.0[SD 5.7]%,p<0.001),and also greater than in YA and YC(both p<0.001).Weekly training hours were comparable between MA and YA(7.9[SD3.3]hours vs.11.1[SD 4.8]hours,p=0.69).Habitual walking distance was greater in MA than in OC(7,387[SD 4,923]m/day vs.4,110[SD 1,772]m/day,p=0.039),and so was habitual running distance(667[SD690]m/day vs.132[427]m/day,p<0.001).HOMA-index was greater in OC than in MA(2.07[SD 1.39]vs.0.80[SD 0.41],p=0.0039),and so was C-reactive protein(1.35[SD 1.74]mg/l vs.0.58[SD 0.27]mg/ml,p=0.018),whereas serum lipids showed only moderate or no effect(all p between 0.036 and 0.07).Conclusions Improved body composition and physical activity levels in MA are associated with lower cardiometabolic risk,which seems more pronounced for insulin sensitivity and inflammaging than for lipid metabolism.
文摘Dear Editor,We are much obliged that Hadziselimovic1 has used our data2 to highlight the substantial proportion of boys with cryptorchidism where gonadotropin insufficiency is an important factor related to the pathogenesis.We have recently presented a study on a series of 453 consecutive boys with bilateral nonsyndromic cryptorchidism,in which we conducted hormonal evaluations and assessed germ cell numbers in testicular biopsies.3 In this series,45%of the boys were classified as having gonadotropin insufficiency.3 Identifying these patients at the time of surgery is important.A recent follow-up study of 208 boys with nonsyndromic bilateral cryptorchidism from our department showed that the boys with gonadotropin insufficiency had an impaired fertility potential after surgery compared to boys with an intact hypothalamus–pituitary–gonadal feedback mechanism.4 In a review from 2022,Hadziselimovic5 suggested that infertility in patients diagnosed with cryptorchid testes is a consequence of a hormonal deficiency rather than temperature-induced cellular damage.
基金supported by the Shenzhen Science and Technology Program(grant number:KQTD20180411185028798).
文摘Background:The role of systemic tumor immune environment(STIE)is unclear in hepatocellular carcinoma(HCC).This study aimed to exam the cells in the STIE,their changes after transarterial chemoembolisation(TACE),stereotactic body radiotherapy(SBRT),and immunotherapy(IO)and explore their significance in the treatment response of patients with unresectable HCC.Methods:This is a prospective biomarker study of patients with unresectable HCC.The treatment was sequential TACE,SBRT(27.5-40 Gy/5 fractions),and IO.The treatment response was assessed according to modified Re-sponse Evaluation Criteria in Solid Tumors(mRECIST)by magnetic resonance imaging(MRI)after 6 months of treatment.Longitudinal data of STIE cells was extracted from laboratory results of complete blood cell counts,in-cluding leukocytes,lymphocytes,neutrophils,monocytes,eosinophils,basophils,and platelets.Peripheral blood samples were collected at baseline and after TACE,SBRT,and IO for T-lymphocyte subtyping by flow cytometry.Generalized estimation equation was employed for longitudinal analyses.Results:A total of 35 patients with unresectable HCC were enrolled:23 patients in the exploratory cohort and 12 in the validation cohort.STIE circulating cells,especially lymphocytes,were heterogenous at baseline and changed differentially after TACE,SBRT,and IO in both cohorts.SBRT caused the greatest reduction of 0.7×10^(9)/L(95%CI:0.3×10^(9)/L-1.0×10^(9)/L,P<0.001)in lymphocytes;less reduction was associated with significantly better treatment response.The analysis of T-lymphocyte lineage revealed that the baseline levels of CD4+T cells(P=0.010),type 1 T helper(Th1)cells(P=0.007),and Th1/Th17 ratios(P=0.001)were significantly higher in responders,while regulatory T(Treg)cells(P=0.002),Th17 cells(P=0.047),and Th2/Th1 ratios(P=0.028)were significantly higher in non-responders.After treatment with TACE,SBRT and IO,T-lymphocyte lineage also changed differentially.More reductions were observed in CD25^(+)CD8^(+)T cells and CD127^(+)CD8^(+)T cells after SBRT in non-responders,while increases in natural killer T(NKT)cells after SBRT(10.4%vs.3.4%,P=0.001)and increases in the lymphocyte counts were noted during IO in responders.Conclusions:STIE cells are significant for treatment response,can be reshaped differentially after TACE,SBRT,and IO.The most significant changes of T-lymphocyte lineage are SBRT associated modulations in CD25^(+)CD8^(+)T cells,CD127^(+)CD8^(+)T cells,and NKT cells,which also have significant effects on the ultimate treatment response after TACE-SBRT-IO(ClinicalTrails.gov identifier:GCOG0001/NCT05061342).
文摘The one-bead-one-compound （OBOC） combinatorial peptide library is a powerful tool to identify ligand and receptor interactions. Here, we applied the OBOC library technology to identify mimotopes specific to the immunoglobulin E （IgE） epitopes of the major shellfish allergen tropomyosin. OBOC peptide libraries with 8-12 amino acid residues were screened with serum samples from patients with shellfish allergy for IgE mimotopes of tropomyosin. Twenty-five mimotopes were identified from the screening and their binding reactivity to tropomyosin-specific IgE was confirmed by peptide ELISA. These mimotopes could be divided into seven clusters based on sequence homology, and epitope mapping by EpiSearch of the clustered mimotopes was performed to characterize and confirm the validity of mimotopes. Five out of six of the predicted epitopes were found to overlap with previously identified epitopes of tropomyosin. To further confirm the mimicry potential of mimotopes, BALB/c mice were immunized with mimotopes conjugated to keyhole limpet hemocyanin and assayed for their capacity to induce tropomyosin-specific antibodies. BALB/c mice that received mimotope immunization were found to have an elevated level of tropomyosin-specific immunoglobulin G, but not mice that received an irrelevant mimotope. This study pioneers the successful application of the OBOC libraries using whole sera to screen and identify multiple shrimp allergen mimotopes and validates their mimicry potential using in vitro, in vivo, and in silico methods.
文摘Background Peer victimization has been recognized as a common social problem affecting children and adolescents in all parts of the world. This study aims to examine the prevalence of different types of peer victimization and to evaluate the associations between peer victimization and health correlates. Methods Using a large population sample of 18,341 adolescents aged 15–17 years from 6 cities in China, this study esti-mated the prevalence of different types of peer victimization, addictive behaviors, and health-related variables with self-administrated questionnaires. A three-phase logistical regression analysis was conducted to investigate the associations between peer victimization and addictive behaviors as well as health-related factors among adolescents. Results A total of 42.9% of the surveyed Chinese adolescents have been bullied by peers, with boys reporting higher rate on overt victimization (36.9%) and girls on relational forms (33.9%). School environment (34.7%) was the most frequent scene of peer violence, followed by neighborhood, family, and internet. Addictive behaviors except substance abuse were found related to higher possibility of peer victimization (aOR 1.21–1.73, P<0.001). Peer victimization was significantly associated with more depressive symptoms, post-traumatic stress disorder symptoms, and suicide ideation and deliberate self-harm (aOR 1.05–2.27, P<0.001), and poorer self-esteem and health-related quality of life (aOR 0.95–0.97, P<0.001). Conclusion Possible explanations of the associations found in this study are discussed and implications for future services are raised.
文摘Background:Respiratory morbidity of former preterm infants and especially those with bronchopulmonary dysplasia(BPD)is high during infancy and early childhood.Data sources:We performed a review based on a literature search including EMBASE,MEDLINE,and CINAHL databases to identify all relevant papers published in the English and German literature on influenza and respiratory syncytial virus infection associated with preterm infant,prematurity,and BPD between 1980 and 2014.Results:Recurrent respiratory symptoms remain common at preschool age,school age and even into young adulthood.Acute viral respiratory tract infections due to different pathogens cause significant morbidity and necessitate rehospitalizations during the fi rst years of life.Infl uenza virus infection plays a minor role compared to respiratory syncytial virus(RSV)associated respiratory tract infection during infancy and early childhood.Nevertheless,particular morbidity to both viruses is high.Conclusions:The particular burden of both viral diseases in preterm infants is dominated by RSV and its associated rehospitalizations during the fi rst two years of life.Prophylactic measures include vaccination against influenza virus of family members and caregivers and active immunization starting at the age of 6 months,and monthly injections of palivizumab during the cold season to avoid severe RSV disease and its sequelae.
文摘Aberrant right subclavian artery(arteria lusoria) is the most common congenital root anomaly, remaining asymptomatic in most cases. Nevertheless, some of the 20%-40% of those affected present tracheo-esophageal symptoms. We report on a 6-year-old previously healthy girl presenting with progressive dysphagia over 4 wk. Diagnostics including barium swallow, echocardiography and magnetic resonance angiography(MRA) revealed a retro-esophageal compression by an aberrant right subclavian artery. Despite the successful, uneventful transposition of this arteria lusoria to the right common carotid via right-sided thoracotomy, the girl was suffering from persisting dysphagia. Another barium swallow showed the persistent compression of the esophagus on the level where the arteria lusoria had originated. As MRA showed no evidence of a significant re-obstruction by the transected vascular stump, we suspected a persisting ligamentum arteriosum. After a second surgical intervention via left-sided thoracotomy consisting of transecting the obviously persisting ligamentum and shortening the remaining arterial stump of the aberrant right subclavian artery, the patient recovered fully. In this case report we discuss the potential relevance of a persisting ligamentum arteriosum for patients with leftaortic arch suffering from dysphagia lusoria and rational means of diagnosing, as well as the surgical options to prevent re-do surgery.
文摘The prognosis for children with recurrent or refractory neuroblastoma remains a significant clinical challenge,and currently there are no known curative salvage regimens.In this paper we investigated the effect of imatinib with rapamycin and the chemotherapeutic agents temozolomide and irinotecan.We treated two children with recurrent neuroblastoma with this so called RIST protocol.Both patients,off therapy for 15 and 31 months,respectively are well,and developing normally,without any complications.These findings suggest that a combination regimen of RIST may provide a therapeutic benefit with a favorable toxicity profile to a unfortunate subset of patients with neuroblastoma.
文摘Although the incidence of pediatric heart failure is low, the mortality is relatively high, with severe clinical symptoms requiring repeated hospitalization or intensive care treatment in the surviving patients. Cardiac biopsy specimens have revealed a higher number of resident human cardiac progenitor cells, with greater proliferation and differentiation capacity, in the neonatal period as compared with adults, demonstrating the regeneration potential of the young heart, with rising interest in cardiac regeneration therapy in critically ill pediatric patients. We review here the available literature data, searching the MEDLINE, Google Scholar and EMBASE database for completed, and www.clinicaltrials.gov homepage for ongoing studies involving pediatric cardiac regeneration reports. Because of difficulties conducting randomized blinded clinical trials in pediatric patients, mostly case reports or cohort studies with a limited number of individuals have been published in the field of pediatric regenerative cardiology. The majority of pediatric autologous cell transplantations into the cardiac tissue have been performed in critically ill children with severe or terminal heart failure. Congenital heart disease, myocarditis, and idiopathic hypertrophic or dilated cardiomyopathy leading to congestive heart failure are some possible areas of interest for pediatric cardiac regeneration therapy. Autologous bone marrow mononuclear cells, progenitor cells, or cardiospheres have been applied either intracoronary or percutaneously intramyocardially in severely ill children, leading to a reported clinical benefit of cell-based cardiac therapies. In conclusion, compassionate use of autologous stem cell administration has led to at least short-term improvement in heart function and clinical stability in the majority of the critically ill pediatric patients.
基金financially supported by the University Hospital of Copenhagen,Rigshospitalet,the Danish Child Cancer Foundation(2021-7395)Vissing Fonden(519140 AHO/PPT)the Research Fund between Rigshospitalet and Odense University Hospital(136-A5544).
文摘This study assessed the feasibility of testis tissue cryopreservation (TTC) for fertility preservation in prepubescent boys with cryptorchidism. From January 2014 to December 2022, the University Hospital of Copenhagen (Rigshospitalet, Copenhagen, Denmark) implemented TTC for 56 boys with cryptorchidism to preserve their reproductive potential. Testis tissue samples were collected during orchiopexy (32 cases) or at subsequent follow-up procedures (24 cases), necessitated by an increased risk of infertility as indicated by hormonal assessments and/or findings from initial surgical biopsies. Testis samples were procured for TTC and pathological analysis. The cohort had an average age of 1.3 (range: 0.3–3.8) years at the time of orchiopexy, with 91.1% presenting bilateral cryptorchidism. The study revealed a median germ cell count of 0.39 (range: 0–2.88) per seminiferous tubule, with germ cells detected in 98.0% of the bilateral biopsies and 100% of the unilateral, indicating a substantial potential for fertility in these immature tissues. A dark spermatogonia (Ad) was detected in 37 out of 56 patients evaluated, with a median Ad spermatogonia count of 0.027 (range: 0.002–0.158) per seminiferous tubule. A total of 30.2% of the samples lacked Ad spermatogonia, indicative of potential gonadotrophin insufficiency. The median hormone levels measured were as follows: follicle-stimulating hormone (FSH) at 0.69 (range: 0.16–2.5) U l−1, luteinizing hormone (LH) at 0.21 (range: 0.05–3.86) U l−1, and inhibin B at 126 (range: 17–300) pg ml−1. Despite early orchiopexy, 20%–25% of boys with cryptorchidism remain at risk for future infertility, substantiating the necessity of TTC as a precaution. The study highlights the need for refined predictive techniques to identify boys at higher risk of future infertility.
基金funded by the Austrian Federal Ministry for Arts,Culture,Civil Service,and Sport,Grant number GZ2021-0.361.671.
文摘In late 2019,heavy restrictions were enforced on public activities worldwide to diminish the spread of the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)virus[1].These restrictions,which included school closures and strictly limited sports and leisure opportunities,particularly impacted children and adolescents[2].Lifestyle changes in children and adolescents led to reduced physical activity levels[2,3],increased sedentary behavior[3,4],changes in eating habits,and changes in sleep habits[3].
文摘Objective: To investigate the relationship between child care by domestic helper and specific language impairment (SLI). Design: Retrospective case-control study. Setting: A Child Assessment Center in Hong Kong that receives referrals from primary and secondary care settings. Participants: We reviewed medical records of all new referrals younger than 5 years during a 4-year period (1999-2003) and compared children with SLI (cases) with those referred with other behavioral problems and assessed to have normal language and overall development (controls) using the Griffiths Mental Developmental Scale. Specific language impairment was defined as a language quotient more than 1 SD below the mean and below the general dev-elopmental quotient in children with normal general developmental quotient but without neurological or other organic diseases. Results: Four hundred ninety-six children were included (237 cases and 259 controls). The mean ages of cases and controls were 2.51 and 2.89 years, respectively. Boys predominated (cases=73.4% , controls= 60.2% ). The odds ratio (OR) of SLI for children cared for by a full-time domestic helper was 1.71 (95% confidence interval CI , 1.06-2.77; P=.03), after adjusting for confounding sociodemographic variables. Male gender (OR=1.91; 95% CI, 1.25-2.90), positive family history (OR=2.70; 95% CI, 1.55-4.73), fewer siblings (P=.01), and lower paternal occupational status (P=.01) were also risk factors for an SLI. Child care by a domestic helper was associated with a higher severity of an SLI in ordinal regression analysis (P=.048). Conclusions: Child care by a domestic helper is associated with increasing risk and severity of an SLI. Further studies are required to confirm the association and to evaluate whether avoidance of child care by a domestic helper could be recommended for children with an SLI or prone to develop an SLI.
基金the Ministry of Science and Technology of China and the National Natural Science Foundation of China(32090040,2022YFA1303100,92254302,W2411017,2022YFA0806800,92153302,91854203,31621002,2017YFA0503600,91953000,and 31970655)the Ministry of Education(RT_17R102)+1 种基金Plans for Major Provincial Science&Technology Projects of Anhui Province(202303a0702003)the Fundamental Research Funds for the Central Universities(KB9100000007,KB9100000006,and KB9100000013).
文摘Septins,components of the fourth cytoskeleton,play an indispensable role in establishing and maintaining epithelial cell polarity.However,the molecular mechanisms underlying the dynamic assembly of higher-order septin structures and the establishment of epithelial cell polarity remain elusive.Here,weshow that septinsform a previouslyunrecognized dynamic structure with liquid-like properties in polarized Madin-Darby canine kidney cells.We identified Septin 6(SEPT6)as the key human septin that undergoes liquid-liquid phase separation(LLPS)both in vitro and in vivo through weak,multivalent interactions mediated by its C-terminal tail.SEPT6 mutants defective in LLPS in vitro also fail to support adherens junction integrity and cell polarity establishment in 2D and 3D cell cultures.Our findings indicate that weak,multivalent interactions are essential forthe assembly of higher-order septin structures in cells.We propose that these interactions,in conjunction with conventional interactions between folded domains,generate partially ordered septin assemblies that support the apical-basal axis and lumen formation in metazoans.
