The evolution of the field of assisted reproduction technology (ART) in the last 40 years has significantly contributed to the management of global infertility. Despite the great numbers of live ...births that have been achieved through ART, there is still potential for increasing the success rates. As a result, there is a need to create optimum conditions in order to increase ART efficacy. The selection of the best sperm, oocyte, and embryo, as well as the achievement of optimal endometrial receptivity, through the contribution of new diagnostic and treatment methods, based on a personalized proteomic approach, may assist in the attainment of this goal. Proteomics represent a powerful new technological development, which seeks for protein biomarkers in human tissues. These biomarkers may aid to predict the outcome, prevent failure, and monitor in a personalized manner in vitro fertilization (IVF) cycles. In this review, we will present data from studies that have been conducted in the search for such biomarkers in order to identify proteins related to good sperm, oocyte, and embryo quality, as well as optimal endometrial receptivity, which may later lead to greater results and the desirable ART outcome.
Female fertility has been a field of interest for the scientific community throughout the years. The contribution of proteomics in the study of female fertility as well as female infertility and in ...vitro fertilization (IVF) has been significant. Proteomics is a recently developed field, extensively applied to the identification and quantification of proteins, which could be used as potential biomarkers in a diagnostic, prognostic, or predictive manner in a variety of medical conditions.
The present review focuses on proteomic studies of the oocyte and endometrial environment as well as on conditions related to infertility, such as polycystic ovarian syndrome, endometriosis, obesity, and unexplained infertility. Moreover, this review presents studies that have been done in an effort to search for fertility biomarkers in individuals following the IVF procedure.
The comprehension of the molecular pathways behind female fertility and infertility could contribute to the diagnosis, prognosis, and prediction of infertility. Moreover, the identification of proteomic biomarkers for IVF cycles could predict the possible outcome of an IVF cycle, prevent an unsuccessful IVF, and monitor the IVF cycle in a personalized manner, leading to increased success rates. Figure: see text.
Limited recent molecular epidemiology data are available for pediatric Central Nervous System (CNS) infections in Europe. The aim of this study was to investigate the molecular epidemiology of ...enterovirus (EV) involved in CNS infections in children. Cerebrospinal fluid (CSF) from children (0-16 years) with suspected meningitis-encephalitis (ME) who were hospitalized in the largest pediatric hospital of Greece from October 2017 to September 2020 was initially tested for 14 common pathogens using the multiplex PCR FilmArray
ME Panel (FA-ME). CSF samples positive for EV, as well as pharyngeal swabs and stools of the same children, were further genotyped employing Sanger sequencing. Of the 330 children tested with FA-ME, 75 (22.7%) were positive for EV and 50 different CSF samples were available for genotyping. The median age of children with EV CNS infection was 2 months (IQR: 1-60) and 44/75 (58.7%) of them were male. There was a seasonal distribution of EV CNS infections, with most cases detected between June and September (38/75, 50.7%). EV genotyping was successfully processed in 84/104 samples: CSF (
= 45/50), pharyngeal swabs (
= 15/29) and stools (
= 24/25). Predominant EV genotypes were CV-B5 (16/45, 35.6%), E30 (10/45, 22.2%), E16 (6/45, 13.3%) and E11 (5/45, 11.1%). However, significant phylogenetic differences from previous described isolates were detected. No unusual neurologic manifestations were observed, and all children recovered without obvious acute sequelae. Specific EV circulating genotypes are causing a significant number of pediatric CNS infections. Phylogenetic analysis of these predominant genotypes found genetic differences from already described EV isolates.
Pediatric cancer and its treatment may have an impact on the neurocognitive functions of childhood cancer survivors (CCS). The aim of the present meta-analysis was to compare the intelligence ...quotient (IQ) scores between CCS of acute lymphoblastic leukemia (ALL) and controls. A comprehensive electronic search identified original research articles that reported scores of the Wechsler Intelligence Scale (WISC; WISC-III, WISC-IV and WISC-R) for children and adolescents, aged 6-16 years at evaluation, survivors of ALL and healthy controls. The included CCS had completed anticancer treatment and were in remission at the time of assessment. A total of 16 studies were included in the meta-analysis, out of 128 extracted studies, and involved a total of 1,676 children and adolescents: 991 CCS (ALL) and 685 healthy controls. Among the studies, a random effects model revealed a moderate estimate of effect size standardized mean difference (SMD), -0.78; 95% CI, -1.05 to -0.50, indicating that the WISC scores for total IQ were significantly lower in the CCS than in the controls. The mean total IQ range was 85.2-107.2 in the CCS and 88.4-114.1 in the controls. The difference in the mean total IQ between controls and CCS ranged from -13.8 to 20.6. As regards the WISC scores for verbal IQ, 11 studies were included. A random effects model revealed a moderate estimate of effect size (SMD, -0.71; 95% CI, -1.05 to -0.38), indicating that the WISC scores for verbal IQ were significantly lower in the CCS than in the controls. Among the 9 studies that had available data for performance IQ scores, a fixed effect model revealed a moderate estimate of effect size (SMD, -0.80; 95% CI, -1.09 to -0.52), indicating that the WISC scores for performance IQ were significantly lower in the CCS than in the controls. As the survival rates of children and adolescents with ALL are steadily increasing, regular, lifelong follow-up for neurocognitive late effects is imperative in order to improve their education and employment prospects and overall, their quality of life.
Limited prospective severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) data in children regarding the impact of Omicron variant in seropositivity have been reported. We investigated ...SARS-CoV-2 seropositivity in children between 1 September 2021 and 30 April 2022, representing Delta and Omicron predominance periods. Serum samples from children admitted to the major tertiary Greek paediatric hospital for any cause, except for COVID-19, were randomly collected and tested for SARS-CoV-2 natural infection antibodies against nucleocapsid antigen (Elecsys® Anti-SARS-CoV-2 reagent). A total of 506/1312 (38.6%) seropositive children (0–16 years) were detected (males: 261/506(51.6%); median age (IQR): 95.2 months(24–144)). Seropositivity rates (%) increased from Delta to Omicron period from 29.7% to 48.5% (P-value<0.0001). Seropositivity increased for all age groups, except for the age group of 0–1 year (P-value:0.914). The highest seropositivity rate was detected in April 2022 (52.6%) and reached 73.9% specifically for the age group 12–16 years. No significant differences were detected in seropositivity with respect to gender, origin, or hospitalisation status. Median (IQR) antibody titres were higher in the Omicron vs. Delta period in all age groups, especially in 12–16 years 32.2 COI (7–77.1) vs. 11.4 COI(2.8–50.2), P-value:0.009). During Omicron variant period increased SARS-CoV-2 seropositivity was detected in paediatric population, especially in adolescents, implicating either increased transmissibility or reinfection rates.
Several recent studies have documented an increased incidence of newly diagnosed type 1 Diabetes (T1D) cases in children and adolescents during the COVID-19 pandemic and a more severe presentation at ...diabetes onset. In this descriptive study, we present the experience of the Diabetes Centre of the Division of Endocrinology, Diabetes, and Metabolism of the First Department of Pediatrics of the National and Kapodistrian University of Athens Medical School at "Aghia Sophia" Children's Hospital in Athens, Greece, concerning new cases of T1D diagnosis during the COVID-19 pandemic (March 2020- December 2021). Patients who had already been diagnosed with T1D and needed hospitalization due to poor control during the pandemic have been excluded from this study. Eighty- three children and adolescents with a mean age of 8,5 ± 4.02 years were admitted to the hospital due to newly diagnosed T1D during this 22 months' period in comparison to 34 new cases in the previous year. All patients admitted during the pandemic with a new diagnosis of T1D, presented in their majority with DKA (Ph: 7.2) representing an increase of new severe cases in comparison to previous years (Ph 7.2 versus 7.3, p value: 0.021, in the previous year), p-value: 0.027. 49 cases presented with DKA, of which 24 were characterized moderate and 14 severe DKA (28.9% and 16,9%, respectively), while 5 patients newly diagnosed, needed to be admitted to the ICU to recover from severe acidosis. Whether a previous COVID- 19 infection could have been the triggering factor is not supported by the SARS-Cov2 specific antibodies analysis in our cohort of patients. As far as HbA1c is concerned there was no statistically significant difference between the pre COVID-19 year and the years of the pandemic (11.6% versus 11.9%, p- value: 0.461). Triglycerides values were significantly higher in patients with new onset T1D during COVID-19 years compared to those before the pandemic (p value= 0.032). Additionally, there is a statistically significant correlation between Ph and Triglycerides for the whole period 2020-2021 (p-value<0.001), while this correlation is not significant for the year 2019. More large- scale studies are required to confirm these observations.
FGFR1 mutations have been identified in both Kallmann syndrome and normosmic HH (nIHH). To date, few mutations in the FGFR1 gene have been structurally or functionally characterized in vitro to ...identify molecular mechanisms that contribute to the disease pathogenesis. We attempted to define the in vitro functionality of two FGFR1 mutants (R254W and R254Q), resulting from two different amino acid substitutions of the same residue, and to correlate the in vitro findings to the patient phenotypes. Two unrelated GnRH deficient probands were found to harbor mutations in FGFR1 (R254W and R254Q). Mutant signaling activity and expression levels were evaluated in vitro and compared to a wild type (WT) receptor. Signaling activity was determined by a FGF2/FGFR1dependent transcription reporter assay. Receptor total expression levels were assessed by Western blot and cell surface expression was measured by a radiolabeled antibody binding assay. The R254W maximal receptor signaling capacity was reduced by 45% (p<0.01) while R254Q activity was not different from WT. However, both mutants displayed diminished total protein expression levels (40 and 30% reduction relative to WT, respectively), while protein maturation was unaffected. Accordingly, cell surface expression levels of the mutant receptors were also significantly reduced (35% p<0.01 and 15% p<0.05, respectively). The p.R254W and p.R254Q are both loss-of-function mutations as demonstrated by their reduced overall and cell surface expression levels suggesting a deleterious effect on receptor folding and stability. It appears that a tryptophan substitution at R254 is more disruptive to receptor structure than the more conserved glutamine substitution. No clear correlation between the severity of in vitro loss-of-function and phenotypic presentation could be assigned.
► Two mutations in FGFR1 (R254W and R254Q) were found in 2 GnRH deficient probands. ► The R254W maximal receptor signaling capacity was reduced by 45%. ► Both mutants displayed diminished total protein expression levels (40 and 30%). ► Cell surface expression levels of the mutants were reduced (35% and 15%). ► No correlation between the in vitro findings and the phenotype was assigned.
Pediatric cancer and its treatment may have an impact on the neurocognitive functions of childhood cancer survivors (CCS). The aim of the present meta-analysis was to compare the intelligence ...quotient (IQ) scores between CCS of acute lymphoblastic leukemia (ALL) and controls. A comprehensive electronic search identified original research articles that reported scores of the Wechsler Intelligence Scale (WISC; WISC-III, WISC-IV and WISC-R) for children and adolescents, aged 6-16 years at evaluation, survivors of ALL and healthy controls. The included CCS had completed anticancer treatment and were in remission at the time of assessment. A total of 16 studies were included in the meta-analysis, out of 128 extracted studies, and involved a total of 1,676 children and adolescents: 991 CCS (ALL) and 685 healthy controls. Among the studies, a random effects model revealed a moderate estimate of effect size standardized mean difference (SMD), -0.78; 95% CI, -1.05 to -0.50, indicating that the WISC scores for total IQ were significantly lower in the CCS than in the controls. The mean total IQ range was 85.2-107.2 in the CCS and 88.4-114.1 in the controls. The difference in the mean total IQ between controls and CCS ranged from -13.8 to 20.6. As regards the WISC scores for verbal IQ, 11 studies were included. A random effects model revealed a moderate estimate of effect size (SMD, -0.71; 95% CI, -1.05 to -0.38), indicating that the WISC scores for verbal IQ were significantly lower in the CCS than in the controls. Among the 9 studies that had available data for performance IQ scores, a fixed effect model revealed a moderate estimate of effect size (SMD, -0.80; 95% CI, -1.09 to -0.52), indicating that the WISC scores for performance IQ were significantly lower in the CCS than in the controls. As the survival rates of children and adolescents with ALL are steadily increasing, regular, lifelong follow-up for neurocognitive late effects is imperative in order to improve their education and employment prospects and overall, their quality of life. Key words: cancer, acute lymphoblastic leukemia, survivors, learning difficulties, cognitive, IQ, intelligence, children, adolescents, chemotherapy, radiotherapy, WISC, education
A rare disorder of sex development is 45,X/46,XY mosaicism, which is phenotypically very heterogenous, ranging from normal male (or female) to that of genital ambiguity of varying degrees.
We report ...a case of a neonate with 45,X/46,XY mosaicism and hydrocolpos, and we point out the dilemma and the difficulty in gender assignment.
Gender assignment of cases with frank genital ambiguity is often difficult to be determined, because several factors have to be taken into consideration, such as genital appearance, anticipated urological and sexual function, capacity for future fertility, gonadal malignancy risk, and psychosocial factors. A multidisciplinary approach is definitely needed in the management of such cases.
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