Neonatal Stage Research Articles

Investigating the Transient Regenerative Potential of Cardiac Muscle Using a Neonatal Pig Partial Apical Resection Model.

Researchers have shown that adult zebrafish have the potential to regenerate 20% of the ventricular muscle within two months of apex resection, and neonatal mice have the capacity to regenerate their heart after apex resection up until day 7 after birth. The goal of this study was to determine if large mammals (porcine heart model) have the capability to fully regenerate a resected portion of the left ventricular apex during the neonatal stage, and if so, how long the regenerative potential persists. A total of 36 piglets were divided into the following groups: 0-day control and surgical groups and seven-day control and surgical groups. For the apex removal groups, each piglet was subjected to a partial wall thickness resection (~30% of the ventricular wall thickness). Heart muscle function was assessed via transthoracic echocardiograms; the seven-day surgery group experienced a decrease in ejection fraction and fractional shortening. Upon gross necropsy, for piglets euthanized four weeks post-surgery, all 0-day-old hearts showed no signs of scarring or any indication of the induced injury. Histological analysis confirmed that piglets in the 0-day surgery group exhibited various degrees of regeneration, with half of the piglets showing full regeneration and the other half showing partial regeneration. However, each piglet in the seven-day surgery group demonstrated epicardial fibrosis along with moderate to severe dissecting interstitial fibrosis, which was accompanied by an abundant collagenous extracellular matrix as the result of a scar formation in the resection site. Histology of one 0-day apex resection piglet (briefly lain on and accidentally killed by the mother sow three days post-surgery) revealed dense, proliferative mesenchymal cells bordering the fibrin and hemorrhage zone and differentiating toward immature cardiomyocytes. We further examined the heart explants at 5-days post-surgery (5D PO) and 1-week post-surgery (1W PO) to assess the repair progression. For the 0-day surgery piglets euthanized at 5D PO and 1W PO, half had abundant proliferating mesenchymal cells, suggesting active regeneration, while the other half showed increased extracellular collagen. The seven-day surgery piglets euthanized at 5D PO, and 1W PO showed evidence of greatly increased extracellular collagen, while some piglets had proliferating mesenchymal cells, suggesting a regenerative effort is ongoing while scar formation seems to predominate. In short, our qualitative findings suggest that the piglets lose the full myocardial regenerative potential by 7 days after birth, but greatly preserve the regenerative potential within 1 day post-partum.

Shared and Distinct Functional Effects of Patient-Specific Tbr1 Mutations on Cortical Development.

T-Box Brain Transcription Factor 1 (TBR1) plays essential roles in brain development, mediating neuronal migration, fate specification, and axon tract formation. While heterozygous loss-of-function and missense TBR1 mutations are associated with neurodevelopmental conditions, the effects of these heterogeneous mutations on brain development have yet to be fully explored. We characterized multiple mouse lines carrying Tbr1 mutations differing by type and exonic location, including the previously generated Tbr1 exon 2-3 knock-out (KO) line, and we analyzed male and female mice at neonatal and adult stages. The frameshift patient mutation A136PfsX80 (A136fs) caused reduced TBR1 protein in cortex similar to Tbr1 KO, while the missense patient mutation K228E caused significant TBR1 upregulation. Analysis of cortical layer formation found similar defects between KO and A136fs homozygotes in their CUX1+ and CTIP2+ layer positions, while K228E homozygosity produced layering defects distinct from these mutants. Meanwhile, the examination of cortical apoptosis found extensive cell death in KO homozygotes but limited cell death in A136fs or K228E homozygotes. Despite their discordant cortical phenotypes, these Tbr1 mutations produced several congruent phenotypes, including anterior commissure reduction in heterozygotes, which was previously observed in humans with TBR1 mutations. These results indicate that patient-specific Tbr1 mutant mice will be valuable translational models for pinpointing shared and distinct etiologies among patients with TBR1-related developmental conditions.SIGNIFICANCE STATEMENT Mutations of the TBR1 gene increase the likelihood of neurodevelopmental conditions such as intellectual disability and autism. Therefore, the study of TBR1 can offer insights into the biological mechanisms underlying these conditions, which affect millions worldwide. To improve the modeling of TBR1-related conditions over current Tbr1 knock-out mice, we created mouse lines carrying Tbr1 mutations identical to those found in human patients. Mice with one mutant Tbr1 copy show reduced amygdalar connections regardless of mutation type, suggesting a core biomarker for TBR1-related disorders. In mice with two mutant Tbr1 copies, brain phenotypes diverge by mutation type, suggesting differences in Tbr1 gene functionality in different patients. These mouse models will serve as valuable tools for understanding genotype-phenotype relationships among patients with neurodevelopmental conditions.

Abstract P1023: Single-Cell Metabolic Reconstruction Predicts Regenerative Capacity In Cardiomyocytes

Background: Adult mammalian hearts have limited regenerative capacity following ischemic injury, whereas neonatal hearts can fully regenerate. Uncovering the mechanisms underlying this ability could identify potential avenues for treatment following cardiac injuries. There has been evidence that changes in the tricarboxylic acid (TCA) cycle are involved in transition of cells out of a pluripotent state. Our hypothesis is that a specific metabolic profile will be associated with regenerative capacity in cardiomyocytes (CMs), and our subsequent goal is to characterize its activity. Methods: Previously published single-cell RNA-Seq data (GSE130699, GSE153481) from mouse hearts subjected to ischemic or sham injury at neonatal (P1) or adult (P8) stages (10987 CMs) were used to calculate metabolic reaction activity scores (RAS), which assign activity to each reaction based on gene expression (Damiani et al, 2020). We then used enrichment analysis to compare metabolic changes between experimental conditions. CMs were clustered into metabolic clusters based on RAS and compared to clusters based on total gene expression. We identified the metabolic reactions that are the best predictors of regenerative ability using LASSO regularization logistic regression. Results: Significant (p ≤ .05) differences in metabolism were identified between neonatal and adult CMs. Clustering based on RAS revealed four distinct metabolic profiles in neonatal CMs, but only two (regenerative and non-regenerative) in adult CMs. Compared to other CM clusters, regenerative CMs exhibited significantly upregulated TCA, nucleic acid, and folate metabolism. This subpopulation was enriched in the neonatal condition, resulting in the significant differences seen in overall CM metabolism between conditions. Further, regression using metabolic activity allowed us to predict the regenerative subpopulation of CMs with greater than 85% accuracy. Conclusion: In conclusion, we characterize the unique metabolic profiles of CMs that can be used to identify the regenerative subpopulation of CMs. This suggests that the different metabolic profile seen in regenerative CMs may play a significant role in their regenerative capacity and their differentiation to non-regenerative CMs.

Mouse Cyp2c expression and zonation structure in the liver begins in the early neonatal stage.

In the adult liver, drug-metabolizing enzymes such as cytochrome P450 (CYP) efficiently metabolize drugs by forming an expression pattern called "zonation" structure around the central veins (CV). However, most previous studies on CYPs have focused on the expression levels of CYP mRNA and proteins in the whole liver. In this study, we analyzed not only the expression levels of Cyp2c family mRNAs and proteins in mice during fetal liver development, but also the relationship with their localization. In the whole fetal liver, Cyp2c mRNA and protein were hardly expressed. On the other hand, zonation analysis results showed that only some cells around the CV of the fetal liver expressed Cyp2c. In addition, the protein expression level of Cyp2c in the whole liver during the neonatal period started from postnatal day (P) 7 in both males and females, while the zonation was weakly formed from P5. This study suggested that fetal liver cannot metabolize Cyp2c substrate drugs transferred from mother to fetus due to the low expression of Cyp2c and unformed zonation. The expression level of Cyp2c protein in neonates was lower than that in adult liver, and the zonation structure was not clear, suggesting that drug metabolism was not sufficient. Furthermore, this study revealed that the expression level of Cyp2c does not correlate with the formation of zonation structures, because Cyp2c expression is found in hepatocytes near the CV even in the fetal and neonatal stages, when Cyp2c protein expression is hardly detectable in the whole liver.

Spontaneous pneumothorax associated with Staphylococcus aureus

Pneumothorax is a condition in which there is free air between the parietal and visceral pleural sheets. The neonatal stage is the most common period when it develops during childhood. It is a problem that requires urgent intervention. We presented the case of a spontaneous pneumothorax in a newborn with positive culture of S. aureus.

Expression of voltage-gated Ca2+ channels, Insp3Rs, and RyRs in the immature mouse ovary

BackgroundThe postnatal mammalian ovary undergoes a series of changes to ensure the maturation of sufficient follicles to support ovulation and fecundation over the reproductive life. It is well known that intracellular [Ca2+]i signals are necessary for ovulation, fertilization, and egg activation. However, we lack detailed knowledge of the molecular identity, cellular distribution, and functional role of Ca2+ channels expressed during folliculogenesis. In the neonatal period, ovarian maturation is controlled by protein growth factors released from the oocyte and granulosa cells. Conversely, during the early infantile period, maturation becomes gonadotropin-dependent and is controlled by granulosa and theca cells. The significance of intracellular Ca2+ signaling in folliculogenesis is supported by the observation that mice lacking the expression of Ca2+/calmodulin-dependent kinase IV in granulosa cells suffer abnormal follicular development and impaired fertility.ResultsUsing immunofluorescence in frozen ovarian sections and confocal microscopy, we assessed the expression of high-voltage activated Ca2+ channel alpha subunits and InsP3 and ryanodine receptors in the postnatal period from 3 to 16 days. During the neonatal stage, oocytes from primordial and primary follicles show high expression of various Ca2+-selective channels, with granulosa and stroma cells expressing significantly less. These channels are likely involved in supporting Ca2+-dependent secretion of peptide growth factors. In contrast, during the early and late infantile periods, Ca2+ channel expression in the oocyte diminishes, increasing significantly in the granulosa and particularly in immature theca cells surrounding secondary follicles.ConclusionsThe developmental switch of Ca2+ channel expression from the oocytes to the perifollicular cells likely reflects the vanishing role of the oocytes once granulosa and theca cells take control of folliculogenesis in response to gonadotropins acting on their receptors.

Assessing Individual- and Community-Level Variability in Predictors of Neonatal, Infant, and Under-Five Child Mortality in Ethiopia Using a Multilevel Modeling Approach.

Background: In low-and middle-income countries, child mortality rates are basic indicators of a country’s socio-economic situation and quality of life. The Ethiopian government is currently working to reduce child mortality to accomplish its long-term development goals. Using data from the Ethiopian Mini Demographic and Health Survey, 2019, this study analyzed the determinants of child mortality in Ethiopia. Methods: A total of 4806 children were considered in the final analyses. Multivariate analysis was used to estimate the effects of the predictors simultaneously on each child mortality outcome. Results: The findings revealed that 31.6% of children died during the neonatal stage, 39.1% during the infant stage, and 48.5% during the under-five stage. Variation in child mortality was discovered between Ethiopian community clusters, with the result of heterogeneity between clusters on newborn mortality (χ2 = 202.4, p-value < 0.0001), (χ2 = 777.35, p-value < 0.0001), and (χ2 = 112.92, p-value < 0.0001). Children’s neonatal, infant, and under-five mortality intracluster correlation coefficient (ICC) were 0.35, 0.33, and 0.36, respectively, across communities. Conclusions: In Ethiopia, under-five mortality remains a serious public health issue, with wide variations and high rates among community clusters. Intervention measures focusing on lowering rates of household poverty, increasing education opportunities, and improving access to health care could assist in reducing child mortality in Ethiopia.

Meis1 Regulates Nociceptor Development and Behavioral Response to Tactile Stimuli.

Nociceptors in the dorsal root ganglia (DRG) and trigeminal ganglia (TG) are necessary for transmitting pain and itch signals. However, the molecular mechanism regulating nociceptor development remains largely unknown. This study identifies that the transcription factor Meis1 is generally expressed in two groups of sensory neurons in the developing DRG. During prenatal and neonatal stages, approximately 2/3 of Meis1+ neurons are Runx1+ nociceptors, while 1/3 of Meis1+ neurons are NF200+ myelinated neurons. At postnatal stages, Meis1 expression in nociceptors is gradually reduced. Here, we constructed a Meis1 conditional knockout mouse line to selectively delete Meis1 in Nav1.8 lineage nociceptors. Microarray analyses showed that differentially expressed genes in the Meis1 mutant DRG were enriched in pathways related to sensory perception of pain and nervous system development. In addition, Meis1 regulates the expression of some marker genes of Nppb+ neurons and C-LTMRs. Furthermore, Meis1 mutant mice exhibit behavioral deficits in response to light mechanical pain, static touch and chemical itch. Therefore, this study reveals that Meis1 is required to regulate the development of nociceptors.

Oral language difficulties in patients aged 4 to 7 years at the chone type C health center

The latest research shows the importance of early care in children who have difficulties in oral language, this condition has consequences, their socio-emotional development is also affected. of them, causing a negative impact on their relationship with society. The objective is to determine the causes that generate disorders in the use of oral language in patients 4 to 7 years of the Chone Type ¨C¨ Health Center. A sample of 25 patients was taken, 18 boys and 7 girls, who attend this medical unit in search of treatment for their language problem, different factors were analyzed, from the mother's gestation phase, neonatal stage and early childhood correlating them with the development of cognitive ability according to their age. The research has a qualitative approach, in addition the inductive and descriptive method was used. The applied technique was a test that contains a series of oral questions, visual and playful activities to verify the skills and abilities that the patient possesses, according to the evolutionary stage. It was found that children with language disorders also experience social, emotional and interaction problems with other people.

Perinatal Exposure to Bisphenol A and Developmental Programming of the Cardiovascular Changes in the Offspring.

Bisphenol A (BPA) is an industrial ubiquitous compound, frequently used to produce synthetic polymers and epoxy resins. BPA is a well-recognized endocrine disruptor and xenoestrogen compound. Evidence from epidemiological and experimental studies suggests that perinatal BPA exposure (gestation and/or lactation) increases the risk of developing various diseases, including the cardiovascular system. Developmental programming refers to environmental insults during the critical window of development that affect the structure and physiology of body systems, causing permanent changes in later stages. BPA influences the developmental programming of non-communicable diseases in the offspring. In the present review, we discuss the developmental programming of cardiovascular diseases related to perinatal exposure to BPA, supported by epidemiological and experimental evidence from published literature. The majority of the reported studies found a positive association between perinatal BPA exposure and adverse cardiovascular repercussions in the fetal, neonatal, and adulthood stages. The possible underlying mechanisms include epigenetic modifications of genes involved in cardiac muscle development, autonomic tone, collagenous and non-collagenous extracellular matrix, cardiac remodeling and calcium homeostasis, and mitochondrial energy metabolism. Epigenetics can modify the outcome of any disease. Hence, in the present review, we also discuss the role of epigenetics in preventing cardiovascular diseases following perinatal exposure to BPA. We also highlight how future treatment and drug delivery related to cardiovascular involvement could be based on epigenetic markers.

FACILITY BASED NEWBORN CARE &amp; HOMOEOPATHY

A newborn struggle in the rst month of his or her life as is evident from mythology that Lord Krishna too had a turbulent neonatal stage. The struggle of newborns continues in India even today and that too in the state of UP even today. The current Neonatal Mortality Rate in India is 22 per 1000 live births (UNIGME, 2019), 24.9 as per NFHS 5 (2019-2021) &amp; for the state of UP, it is 35.7 (NFHS 5, 2019-2021). The high neonatal mortality both in India and UP stand as a testimony to this fact as reducing this indicator is a priority. The current article focuses on the initiatives of the role of homoeopathy in public health system to address neonatal mortality. Basically, there are two approaches to reduce neonatal mortality. These are Home Based Neonatal Care (HBNC) practices and the Facility Based Neonatal Care (FBNC) practices. The article focuses exclusively on the second approach which is FBNC .There are three objectives of the article. The rst is to nd out the current status of Homoeopathy in the FBNC practices, the second is to nd out the details of the current &amp; past implementation strategies and the third is to nd out the link between Homoeopathy &amp; HBNC/FBNC practices. The study uses secondary data. The gap that the article worked on is to explore a link between Homoeopathy &amp; HBNC/FBNC &amp; its modalities. It deciphers whether there is a functional link or not &amp; suggests future strategies based on the functionality of the link.The article also proposes a 2 year plan to introduce homoeopathy in the eld of newborn care where all the related stake holders of the state &amp; national level will be involved. It will be a step in the right direction to fulll the plans to achieve the SDG by 2030 especially for neonatal &amp; infant mortality related goals. For the benet of the readers, the article includes its expected outcome, relevance to society &amp; policy making through the context of the identied issues &amp; the research gap. Through all these sections, the current article puts an effort to fulll the three cited objectives of the current study related to incorporation of homoeopathy in newborn care.

Role of Homoeopathy in Home Based Newborn Care (HBNC) practices in UP and India

A newborn struggle in the first month of his or her life as is evident from mythology that Lord Krishna too had a turbulent neonatal stage. The struggle of newborns continues in India even today and that too in the state of UP even today. The current Neonatal Mortality Rate in India is 22 per 1000 live births (UNIGME, 2019), 24.9 as per NFHS 5 (2019-2021) &amp; for the state of UP, it is 35.7 (NFHS 5, 2019-2021). The high neonatal mortality both in India and UP stand as a testimony to this fact as reducing this indicator is a priority. The current article focuses on the initiatives of the role of homoeopathy in public health system to address neonatal mortality. Basically, there are two approaches to reduce neonatal mortality. These are Home Based Neonatal Care (HBNC) practices and the Facility Based Neonatal Care (FBNC) practices. The article focuses exclusively on the first approach which is HBNC .There are three objectives of the article. The first is to find out the current status of Homoeopathy in the HBNC practices, the second is to find out the details of the current &amp; past implementation strategies and the third is to find out the link between Homoeopathy &amp; HBNC practices. The study uses secondary data. The gap that the article worked on is to explore a link between Homoeopathy &amp; HBNC &amp; its modalities. It deciphers whether there is a functional link or not &amp; suggests future strategies based on the functionality of the link. The article also proposes a 2 year plan to introduce homoeopathy in the field of newborn care where all the related stake holders of the state &amp; national level will be involved. It will be a step in the right direction to fulfill the plans to achieve the SDG by 2030 especially for neonatal &amp; infant mortality related goals. For the benefit of the readers, the article includes its expected outcome, relevance to society &amp; policy making through the context of the identified issues &amp; the research gap. Through all these sections, the current ......

Vitamin A supplementation downregulates ADH1C and ALDH1A1 mRNA expression in weaned beef calves.

Our previous studies demonstrated that oral vitamin A supplementation during late-stage pregnancy and the neonatal stage enhances birth weight, growth performance, and mRNA expression related to muscle and preadipocyte development in beef cattle. The alcohol dehydrogenase 1C (ADH1C) c.-64T > C genotype also correlated with vitamin A concentration in beef production. This study aimed to investigate the effects of vitamin A supplementation on the muscle development and vitamin A metabolism in weaned beef calves with different ADH1C genotypes. Twenty male calves (90 d of age; initial BW: 89.03 kg [SD 8.60]) were stratified according to ADH1C genotype and vitamin A treatment (duration: 3 months) and randomly assigned to 4 groups with a 2 × 2 factorial arrangement. Vitamin A treatments included the following: control (10,000 IU/kg of as-fed, a. TT type; b. TC type); treatment (40,000 IU/kg of as-fed, c. TT type; and d. TC type). Parameters including BW, FI, blood, longissimus dorsi muscle, and liver status during the experimental period were analyzed using the generalized linear model (GLM) procedure and Tukey's test by SAS 9.4 program. Serum vitamin A was significantly increased (P < 0.05) in the vitamin A treatment group at 4 and 6 months of age. TT type calves showed higher serum vitamin A concentration (P < 0.05) than the TC type calves. Serum triglyceride and non-esterified fatty acid (NEFA) levels increased (P < 0.05) in the treatment group compared with the control at 6 months of age. However, BW, ADG and FI showed no differences between the groups. In addition, mRNA expression in longissimus dorsi muscle revealed upregulation of paired box 7 (PAX7) (P < 0.05) after the vitamin A treatment period based on biopsy results. Both ADH1C and aldehyde dehydrogenase (ALDH) 1A1 mRNA expression was downregulated (P < 0.01) by vitamin A supplementation. The TC type of ADH1C showed higher mRNA expression than the TT type. However, no effect was observed on adipogenic mRNA expression (preadipocyte factor-1 [PREF-1], peroxisome proliferator-activated receptor gamma [PPARγ], fatty acid binding protein 4 [FABP4]) in all groups. Our findings suggest that weaned calves treated with vitamin A may promote the storage of satellite cells by elevating PAX7 gene expression in the muscle. The TC type calves may show increased capacity for vitamin A metabolism, which can be used in genetically customizing feed management to maximize beef production in the calves.

Cumulative residual symbolic dispersion entropy and its multiscale version: Methodology, verification, and application

In quantifying the complexity characteristics of neurophysiological signals, the most advanced entropy methods still have some inevitable limitations of poor accuracy, robustness, and reliability. To solve these limits, this study proposes a novel entropy estimator, termed cumulative residual symbolic dispersion entropy (CRSDE). Meanwhile, a corresponding multiscale variant, time-shift cumulative residual symbolic dispersion entropy (TCRSDE), is introduced to quantify the time series's irregularity on multiple time scales. The CRSDE starts with an improved symbolic dynamics filter (ISDF) based on the equal probability dividing criterion, mapping a raw time series to symbolic series. Next, embedding theory is applied to derive the dispersion patterns. Finally, the cumulative residual probabilities of all dispersion patterns are counted, and corresponding CRSDE results are calculated. A series of performance validations are executed using synthetic and real-world datasets. The simulation results confirm CRSDE's optimal estimation accuracy and robustness to noise and data length. The findings of EEG dataset demonstrate that CRSDE could realize the best reliability with the lowest root mean square deviation (RMSD; <0.05). In the multiscale version, TCRSDE, a time-shift coarse-graining is introduced. The verification findings confirm that the TCRSDE can avoid incorrect estimates and achieve the best-estimated stability on all scales with the smallest coefficient of variation (CV; <0.01) and shortest running time. Finally, CRSDE method is applied to neonatal sleep EEG. Compared to other methods, CRSDE shows the most significant differences, with all p-values less than 0.01 via a nonparametric Mann-Whitney U test. Meanwhile, CRSDE obtains the highest Hedges' g effect size values and least outliers at three sleep stages. Therefore, CRSDE performs best in quantifying neurodynamics of neonatal sleep stages.

Valproic Acid and Propionic Acid Modulated Mechanical Pathways Associated with Autism Spectrum Disorder at Prenatal and Neonatal Exposure.

Autism spectrum disorder (ASD) is a composite disorder of brain development with uncertain etiology and pathophysiology. Genetic factors are important in ASD causation, although environmental factors are also involved in ASD pathophysiology. Environmental factors might affect the genetic processes of brain development through the modulation of molecular pathways that might be involved with ASD. Valproic acid and propionic acid are the major environmental factors that serve as medicine and food preservative. VPA is used as an anti-epileptic medicine, but it has adverse effects on pregnant women and alters the developmental patterns of the embryo. It is a multi- targeting agent and affects 5-HT, GABA, etc. PPA is a secondary metabolite of gut microbiota that is commonly used as a food preservative. PPA plays a significant role in ASD causation by altering the several developmental molecular pathways like PTEN/Akt, mTOR/Gskβ, Cytokines activated pathways, etc., at the prenatal and neonatal stage. Moreover, ASD complexity might be increased by other important factors like vitamin A deficiency. Vitamin A is important for cortical brain development and neuronal cell differentiation. Additionally, several important genes such as RELN, Lhx2, CREB, IL-6, NMDA, BDNF, etc., are also altered in ASD and involved in brain development, central nervous system, and enteric nervous system. These genes affect neuronal differentiation, hyperactivity, oxidative stress, oxytocin, and GABA imbalance lead to improper behavior in autistic individuals. These genes are also studied in VPA and PPA ASD-like animal models. In this review, we explored the mechanical pathways that might be altered with VPA and PPA exposures at the embryonic developmental stage or neonatal developmental stage.

016 Case report: Turner syndrome

This is the case report of a 16-year-old adolescent with Turner Syndrome and a family and personal background of migraines without auras. The diagnosis was at the neonatal stage with XO karyotype [ [1] Thayalan K, Chung K, Kothari A. Turner syndrome – The clinical spectrum and management dilemmas. AJUM November 2018 21 (4) 219. Google Scholar ]. Growth Hormone and steroid therapy to induce growth and puberty was prescribed [ [2] Irzyniec T. Jeż W. Lepska K. Maciejewska-Paszek I. Frelich J. Childhood growth hormone treatment in women with Turner syndrome - benefits and adverse effects. Sci Rep. 2019 Nov 4; 9: 15951 Crossref PubMed Scopus (11) Google Scholar ]. Sex hormone treatment consisted of transdermal estrogens in increasing doses. Over the last 6 months micronized progesterone was added and the patient had withdrawal bleeding [ [3] Viuff M.H. Berglund A. Juul S. Andersen N.H. Stochholm K. Gravholt C.H. Sex Hormone Replacement Therapy in Turner Syndrome: Impact on Morbidity and Mortality. J Clin Endocrinol Metab. 2020; (Feb 1;105(2):dgz039) Crossref PubMed Scopus (19) Google Scholar ]. Later on, the patient received contraceptives for a year as steroid substitution treatment [ [4] Mathez ALG, Monteagudo PT, do Nascimento Verreschi IT, Dias-da-Silva MR. Levonorgestrel correlates with less weight gain than other progestins during hormonal replacement therapy in Turner Syndrome patients. Sci Rep. 2020 May 19;10(1):8298. Google Scholar ]. The reason for consultation was a refusal to continue receiving contraceptives due to poor tolerance with permanent headaches and poor quality of life. An interdisciplinary approach was made and steroid treatment in Turner Syndrome patients was highlighted. The advised treatment was transdermal estrogens and cyclic micronized progesterone together with Topiramate to prevent migraines, and psychological support was recommended. Fertility counseling was performed [ [5] Oktay K. Bedoschi G. Berkowitz K. Bronson R. Kashani B. McGovern P. et al. Fertility Preservation in Women with Turner Syndrome: A Comprehensive Review and Practical Guidelines. J Pediatr Adolesc Gynecol. 2016 Oct; 29: 409-416 Abstract Full Text Full Text PDF PubMed Scopus (78) Google Scholar ].

CASK is a key organizer of the structural and electrical polarity of the cardiomyocyte

Although the organization of the cardiomyocyte membrane into functional microdomains directly influences the anisotropic propagation of the action potential, the mechanisms underlying the rod-like structural organization of cardiomyocytes during postnatal development are poorly understood. We have previously shown in the adult cardiomyocyte that CASK regulates sodium channel expression at the lateral membrane in interaction with focal adhesion complexes. In addition, preliminary results have shown that the expression level of CASK evolves during postnatal development and is altered during post-infarction myocardial remodeling in rat. To unravel the implication of CASK in postnatal cardiomyocyte differentiation and in the acquisition of structural and electrical function. CASK viral constructs were designed to inhibit the expression of CASK in neonatal and adult cardiac myocytes, in vitro (Ad-shCASK) and in vivo (AAV-shCASK). Proteomic analysis shows that CASK invalidation differentially regulates the expression of different protein families between neonatal and adult myocytes, suggesting a different role for CASK during postnatal development. Immunostaining experiments on isolated neonatal cardiomyocytes showed that CASK is required for the correct organization of the cardiomyocyte cytoskeleton, and impact both mechanical and electrical junction formation. Neonatal cardiomyocytes invalidated for CASK display abnormal contractility, focal adhesion fragility, and anoikis. Echocardiography phenotyping of CASK-invalidated rats at the neonatal and adult stages reveals eccentric ventricular remodeling and decreased systolic performance. However, in neonatal CASK-invalidated rats, the contractile reserve is preserved and the cardiac output is increased. In addition, mild electrical remodeling is observed since only neonatal CASK-invalidated rats display QT prolongation and slowed heart rhythm. This study demonstrates that CASK confers the ability to orchestrate both cardiomyocyte molecular organization and tissue cohesion. CASK appears to be a key modulator in molecular arrangement of electrical and structural polarity of cardiomyocytes during postnatal development.

Thalamocortical axons regulate neurogenesis and laminar fates in the early sensory cortex

Area-specific axonal projections from the mammalian thalamus shape unique cellular organization in target areas in the adult neocortex. How these axons control neurogenesis and early neuronal fate specification is poorly understood. By using mutant mice lacking the majority of thalamocortical axons, we show that these axons are required for the production and specification of the proper number of layer 4 neurons in primary sensory areas by the neonatal stage. Part of these area-specific roles is played by the thalamus-derived molecule, VGF. Our work reveals that extrinsic cues from sensory thalamic projections have an early role in the formation of cortical cytoarchitecture by enhancing the production and specification of layer 4 neurons.

Newly repairing technique of deformed hand by a posterior interosseous flap in an infant: A case report.

IntroductionMany non-surgical methods were performed to repair the deformities in the skeletal system to avoid severe complications post-open surgery, especially within the childhood stage or below. We aim, in this case, to present a new technique for repairing bony deformities in the childhood stage, which fewer studies have to instigate its efficacy versus open surgery.Case presentationWe present a 14-months-old infant with wrist extravasation injury at the neonatal stage (day 1), end with a right wrist volar contraction and complete loss of brain homunculus of the right hand.DiscussionWe used a reverse posterior interosseous flap to reconstruct the soft tissue and release the flexor tendons of the hand. The flap was conducted entirely and was rapidly adapted to the recipient beds to achieve good color and texture harmonies. Within following up for 12 weeks, the patient restored hand function.ConclusionMore global cohort studies are required to compare precisely the efficacy between surgical options and the used technique in our case for salvaging deformities in childhood.

PP2A-associated tau hyperphosphorylation was involved in sevoflurane induced neonatal neurotoxicity.

The effects of sevoflurane anesthesia on childhood neurodevelopment and adult brain function have attracted increasing scientific attentions. However, the exact mechanisms underlying hyperphosphorylation of tau protein in sevoflurane induced abnormalities in central nervous system (CNS) development, particularly in the hippocampus, have not been fully determined. We utilized molecular biological and behavioral approaches to compare the changes in cognitive function in mice exposed to repeated sevoflurane during the neonatal stage, and to assess whether PP2A-associated tau hyperphosphorylation is involved in sevoflurane induced neonatal neurotoxicity. We reported that mice anesthetized with repeated sevoflurane during the neonatal period caused cognitive dysfunction during the adulthood. More importantly, we found that hyperphosphorylation of tau protein and decreased level of protein phosphatase 2A (PP2A) were detected in the hippocampus of mice after neonatal exposure of sevoflurane. Meanwhile, GSK-3β activity was found to be increased with repeated sevoflurane exposure, but not for more than 2weeks. Our results suggest that PP2A-associated hyperphosphorylation of tau protein might contribute to sevoflurane induced developmental neurotoxicity. These findings could provide a theoretical basis for the safely usage of sevoflurane in pediatric surgeries, and offer a valuable reference and potential therapeutic targets for the development of neuroprotective drugs.