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Medicine Jun 2024Treatment outcomes for different causes of childhood dwarfism vary widely, and there are no studies on the economic burden of treatment in relation to outcomes. This...
Treatment outcomes for different causes of childhood dwarfism vary widely, and there are no studies on the economic burden of treatment in relation to outcomes. This paper compared the efficacy and healthcare costs per unit height of recombinant human growth hormone (rhGH) for the treatment of growth hormone deficiency (GHD) and idiopathic short stature (ISS) with a view to providing a more cost-effective treatment option for children. We retrospectively analyzed 117 cases (66 cases of GHD and 51 cases of ISS) of short-stature children who first visited Weifang People's Hospital between 2019.1 and 2022.1 and were treated with rhGH for 1 to 3 years to track the treatment effect and statistically analyzed by using paired t tests, non-parametric tests, and chi-square tests, to evaluate the efficacy of rhGH treatment for GHD and ISS children and the medicinal cost. The annual growth velocity (GV) of children with GHD and ISS increased the fastest during 3 to 6 months after treatment and then gradually slowed down. The GV of the GHD group was higher than that of the ISS group from 0 to 36 months after treatment (P < .05 at 3, 6, 9, and 12 months); the height standard deviation scores (HtSDS) of the children in the GHD and ISS groups increased gradually with the increase of the treatment time, and the changes in the height standard deviation scores (ΔHtSDS) of the GHD group were more significant than those of the ISS group (P < .05 at 3, 6, 9, and 12 months). (2) The medical costs in the pubertal group for a 1-cm increase in height were higher than those of children in the pre-pubertal group at the same stage (3 to 24 months P < .05). The longer the treatment time within the same group, the higher the medical cost of increasing 1cm height. RhGH is effective in treating children with dwarfism to promote height growth, and the effect on children with GHD is better than that of children with ISS; the earlier the treatment time, the lower the medical cost and the higher the comprehensive benefit.
Topics: Humans; Human Growth Hormone; Child; Retrospective Studies; Male; Female; Dwarfism; Recombinant Proteins; Body Height; Treatment Outcome; Child, Preschool; Growth Disorders; Economics, Pharmaceutical; Cost-Benefit Analysis; Health Care Costs; Adolescent
PubMed: 38905369
DOI: 10.1097/MD.0000000000038350 -
Medicine Jun 2024The link between celiac disease (CeD) and thyroid dysfunction has been investigated. However, it is uncertain if CeD is causally linked to thyroid dysfunction. A...
The link between celiac disease (CeD) and thyroid dysfunction has been investigated. However, it is uncertain if CeD is causally linked to thyroid dysfunction. A 2-sample Mendelian randomization study was conducted to ascertain the causal connection between CeD and thyroid dysfunction. Using data from the FinnGen Consortium, a 2-sample Mendelian randomization study was conducted to look at the connection between thyroid dysfunction and CeD. Another replication of the data from the UK Biobank was subsequently performed to confirm our findings. Furthermore, a sequence of sensitivity analyses was performed. The inverse variance weighting technique demonstrates that genetically determined CeD is substantially linked with hypothyroidism, thyrotoxicosis, Graves' disease, and free thyroxine. However, no significant associations were found between CeD and thyroid-stimulating hormone or thyroiditis. Moreover, we achieve the same results in duplicate datasets, which increases the reliability of our findings. This study suggests that CeD and thyroid dysfunction are linked, and it gives theoretical support and new ways of thinking about how to diagnose and treat both conditions.
Topics: Humans; Mendelian Randomization Analysis; Celiac Disease; Thyroid Diseases; Hypothyroidism; Thyrotropin
PubMed: 38905357
DOI: 10.1097/MD.0000000000038474 -
Science Advances Jun 2024The suprachiasmatic nucleus (SCN) sets the phase of oscillation throughout the brain and body. Anatomical evidence reveals a portal system linking the SCN and the...
The suprachiasmatic nucleus (SCN) sets the phase of oscillation throughout the brain and body. Anatomical evidence reveals a portal system linking the SCN and the organum vasculosum of the lamina terminalis (OVLT), begging the question of the direction of blood flow and the nature of diffusible signals that flow in this specialized vasculature. Using a combination of anatomical and in vivo two-photon imaging approaches, we unequivocally show that blood flows unidirectionally from the SCN to the OVLT, that blood flow rate displays daily oscillations with a higher rate at night than in the day, and that circulating vasopressin can access portal vessels. These findings highlight a previously unknown central nervous system communication pathway, which, like that of the pituitary portal system, could allow neurosecretions to reach nearby target sites in OVLT, avoiding dilution in the systemic blood. In both of these brain portal pathways, the target sites relay signals broadly to both the brain and the rest of the body.
Topics: Suprachiasmatic Nucleus; Animals; Mice; Hypothalamus; Brain; Portal System; Male; Vasopressins; Cerebrovascular Circulation; Circadian Rhythm
PubMed: 38905332
DOI: 10.1126/sciadv.adn8350 -
Animal Reproduction 2024Reviewing the current state of knowledge on reproductive performance and productive traits in rams has many advantages. First, the compilation of this information will... (Review)
Review
Reviewing the current state of knowledge on reproductive performance and productive traits in rams has many advantages. First, the compilation of this information will serve as a literature resource for scientists conducting research around the world and will contribute to the understanding of the data collected and interpreted by researchers on the different hormonal strategies used to improve reproductive performance in rams. Second, it will allow scientists to identify current knowledge gaps and set future research priorities in ram reproduction. Rams play an important role in the global flock economy, but their reproductive analysis has been limited in the use of hormonal technologies to increase the productivity of sheep flocks. In this review, we cite the most important works on six hormones that, in one way or another, modify the hypothalamus-pituitary-gonadal axis, at different doses, in and out of the reproductive season, breeds, application methods, among other factors. The overall aim is to increase the reproductive efficiency of rams in different scenarios and, in some cases, of other species due to the lack of limited information on rams.
PubMed: 38903866
DOI: 10.1590/1984-3143-AR2024-0007 -
BMC Endocrine Disorders Jun 2024An increase of IGF-1 has been reported during therapy with dopamine agonists (DA) for prolactinomas; in such cases a correct diagnosis is pivotal to avoid an unnecessary...
PURPOSE
An increase of IGF-1 has been reported during therapy with dopamine agonists (DA) for prolactinomas; in such cases a correct diagnosis is pivotal to avoid an unnecessary reduction or withdrawal of DA, which are needed to maintain normal prolactin levels. This study was aimed to measure IGF-1 levels, at baseline and during follow-up, in a cohort of patients with prolactinoma, treated with cabergoline, stratified by body mass index.
METHODS
We retrospectively enrolled 35 patients (15 F/20 M; age m ± SD, years: 43.4 ± 13.7) with prolactinoma (21 microadenomas and 14 macroadenomas) who were followed-up at the Endocrinology Unit, in Siena, and with available pituitary hormone assessment at baseline and during follow-up (m ± SD, years: 2.74 ± 0.55).
RESULTS
IGF-1 increased in the whole cohort, but remaining within normal range, except two patients, in whom acromegaly was ruled out with oral glucose tolerance test. After dividing patients by weight, this trend was confirmed only in subjects with overweight and obesity (OV/OB) (p = 0.04). Interestingly, the reduction of prolactin levels was significantly greater in the OV/OB compared to normal-weight patients (median decrease of 97.5% versus 88.2%, p = 0.04).
CONCLUSIONS
Since DA and normalization of prolactin are known to improve insulin sensitivity, we speculated they have favored the increase of IGF-1 in OV/OB. Our results should be confirmed and the hypothesis proven by further studies.
Topics: Humans; Prolactinoma; Insulin-Like Growth Factor I; Female; Male; Adult; Retrospective Studies; Dopamine Agonists; Pituitary Neoplasms; Middle Aged; Cabergoline; Body Weight; Follow-Up Studies; Prolactin; Body Mass Index; Prognosis
PubMed: 38902646
DOI: 10.1186/s12902-024-01622-4 -
Clinical Genitourinary Cancer May 2024The number of cancer patients undergoing chronic treatment with target therapy is increasing. Although much is known about the toxicity of conventional anticancer... (Review)
Review
The number of cancer patients undergoing chronic treatment with target therapy is increasing. Although much is known about the toxicity of conventional anticancer therapies, evidence on the effects of tyrosine kinase inhibitors (TKIs) on fertility is still lacking. Therefore, this review was undertaken to evaluate the effects of TKIs on male gonadal function. A comprehensive search of PubMed and Scopus databases was conducted, focusing on the effects of TKIs on spermatogenesis and testicular endocrine function. We included animal studies, observational studies, and case reports published up to December 31, 2023. Identified articles were reviewed and analyzed to evaluate the impact of TKIs on the male gonad. Their long-term effects, the reversibility of the observed changes, and the underlying molecular mechanisms involved were recorded. The findings emerging on the effects of TKIs on male gonadal function are conflicting. Although specific TKIs (imatinib, gefitinib, sorafenib, sunitinib, quizartinib, dasatinib, and nilotinib) have been identified as potentially as potential interfering with spermatogenesis and hormone production, the extent and severity of these effects may vary from patient to patient and between different drugs within this drug class. Experimental studies on mouse models have suggested a potential interference with spermatogenesis. Evidence also suggests that TKIs affects the hypothalamic-pituitary-testicular axis, decreasing serum testosterone and gonadotropin levels. The effects of TKIs on male gonadal function highlight the need for personalized treatment choices. Potential fertility concerns can help minimize adverse effects and improve patient outcomes. Addressing the potential impact of TKIs on male fertility helps optimize cancer treatment and survival outcomes.
PubMed: 38901138
DOI: 10.1016/j.clgc.2024.102131 -
PloS One 2024Numerous organs, including the thyroid gland, depend on vitamin D to function normally. Insufficient levels of serum 25-hydroxyvitamin D [25(OH)D] are seen as a...
BACKGROUND
Numerous organs, including the thyroid gland, depend on vitamin D to function normally. Insufficient levels of serum 25-hydroxyvitamin D [25(OH)D] are seen as a potential factor contributing to the emergence of several thyroid disorders, however, the causal relationship remains unclear. Here we use a Mendelian randomization (MR) approach to investigate the causal effect of serum 25(OH)D concentration on the indicators of thyroid function.
METHODS
We conducted a two-sample MR analysis utilizing summary data from the most extensive genome-wide association studies (GWAS) of serum 25(OH)D concentration (n = 443,734 and 417,580), thyroid-stimulating hormone (TSH, n = 271,040), free thyroxine (fT4, n = 119,120), free triiodothyronine (fT3, n = 59,061), total triiodothyronine (TT3, n = 15,829), as well as thyroid peroxidase antibody levels and positivity (TPOAb, n = 12,353 and n = 18,297), low TSH (n = 153,241), high TSH (n = 141,549), autoimmune hypothyroidism (n = 287,247) and autoimmune hyperthyroidism (n = 257,552). The primary analysis was conducted using the multiplicative random-effects inverse variance weighted (IVW) method. The weighted mode, weighted median, MR-Egger, MR-PRESSO, and Causal Analysis Using Summary Effect estimates (CAUSE) were used in the sensitivity analysis.
RESULTS
The IVW, as well as MR Egger and CAUSE analysis, showed a suggestive causal effect of 25(OH)D concentration on high TSH. Each 1 SD increase in serum 25(OH)D concentration was associated with a 12% decrease in the risk of high TSH (p = 0.02). Additionally, in the MR Egger and CAUSE analysis, we found a suggestive causal effect of 25(OH)D concentration on autoimmune hypothyroidism. Specifically, each 1 SD increase in serum 25(OH)D concentration was associated with a 16.34% decrease in the risk of autoimmune hypothyroidism (p = 0.02).
CONCLUSIONS
Our results support a suggestive causal effect which was negative in direction across all methods used, meaning that higher genetically predicted vitamin D concentration possibly lowers the odds of having high TSH or autoimmune hypothyroidism. Other thyroid parameters were not causally influenced by vitamin D serum concentration.
Topics: Humans; Mendelian Randomization Analysis; Vitamin D; Thyroid Gland; Genome-Wide Association Study; Thyrotropin; Thyroid Function Tests; Hypothyroidism; Triiodothyronine; Thyroxine; Hyperthyroidism
PubMed: 38900813
DOI: 10.1371/journal.pone.0304253 -
PloS One 2024Arginine vasopressin (AVP) and oxytocin (OT) are well-known as neuropeptides that regulate various social behaviors in mammals. However, little is known about their role...
Arginine vasopressin (AVP) and oxytocin (OT) are well-known as neuropeptides that regulate various social behaviors in mammals. However, little is known about their role in mouse female sexual behavior. Thus, we investigated the role of AVP (v1a and v1b) and OT receptors on female sexual behavior. First, we devised a new apparatus, the bilevel chamber, to accurately observe female mouse sexual behavior. This apparatus allowed for a more precisely measurement of lordosis as receptivity and rejection-like behavior (newly defined in this study), a reversed expression of proceptivity. To address our research question, we evaluated female sexual behavior in mice lacking v1a (aKO), v1b (bKO), both v1a and v1b (dKO), and OT (OTRKO) receptors. aKO females showed decreased rejection-like behavior but a normal level of lordosis, whereas bKO females showed almost no lordosis and no change in rejection-like behavior. In addition, dKO females showed normal lordosis levels, suggesting that the v1b receptor promotes lordosis, but not necessarily, while the v1a receptor latently suppresses it. In contrast, although OTRKO did not influence lordosis, it significantly increased rejection-like behavior. In summary, the present results demonstrated that the v1a receptor inhibits proceptivity and receptivity, whereas the v1b and OT receptors facilitate receptivity and proceptivity, respectively.
Topics: Animals; Female; Receptors, Vasopressin; Receptors, Oxytocin; Sexual Behavior, Animal; Mice; Mice, Knockout; Male; Oxytocin; Mice, Inbred C57BL; Arginine Vasopressin
PubMed: 38900750
DOI: 10.1371/journal.pone.0304703 -
Frontiers in Neuroanatomy 2024The amygdala is a noticeable bilateral structure in the medial temporal lobe and it is composed of at least 13 different nuclei and cortical areas, subdivided into the...
INTRODUCTION
The amygdala is a noticeable bilateral structure in the medial temporal lobe and it is composed of at least 13 different nuclei and cortical areas, subdivided into the deep nuclei, the superficial nuclei, and the remaining nuclei which contain the central nucleus (CeA). CeA mediates the behavioral and physiological responses associated with fear and anxiety through pituitary-adrenal responses by modulating the liberation of the hypothalamic Corticotropin Releasing Factor/Hormone.
METHODS
Five dolphins of three different species, belonging to the family Delphinidae (three striped dolphins, one common dolphin, and one Atlantic spotted dolphin), were used for this study. For a precise overview of the CeA's structure, thionine staining and the immunoperoxidase method using calbindin D-28k were employed.
RESULTS
CeA extended mainly dorsal to the lateral nucleus and ventral to the striatum. It was medial to the internal capsule and lateral to the optic tract and the medial nucleus of the amygdala.
DISCUSSION
The dolphin amygdaloid complex resembles that of primates, including the subdivision, volume, and location of the CeA.
PubMed: 38899230
DOI: 10.3389/fnana.2024.1382036 -
Behavioral and Brain Functions : BBF Jun 2024Autism Spectrum Disorder (ASD) is a group of neurodevelopmental disorders with higher incidence in males and is characterized by atypical verbal/nonverbal communication,...
BACKGROUND
Autism Spectrum Disorder (ASD) is a group of neurodevelopmental disorders with higher incidence in males and is characterized by atypical verbal/nonverbal communication, restricted interests that can be accompanied by repetitive behavior, and disturbances in social behavior. This study investigated brain mechanisms that contribute to sociability deficits and sex differences in an ASD animal model.
METHODS
Sociability was measured in C58/J and C57BL/6J mice using the 3-chamber social choice test. Bulk RNA-Seq and snRNA-Seq identified transcriptional changes in C58/J and C57BL/6J amygdala within which DMRseq was used to measure differentially methylated regions in amygdala.
RESULTS
C58/J mice displayed divergent social strata in the 3-chamber test. Transcriptional and pathway signatures revealed immune-related biological processes differ between C58/J and C57BL/6J amygdala. Hypermethylated and hypomethylated genes were identified in C58/J versus C57BL/6J amygdala. snRNA-Seq data in C58/J amygdala identified differential transcriptional signatures within oligodendrocytes and microglia characterized by increased ASD risk gene expression and predicted impaired myelination that was dependent on sex and sociability. RNA velocity, gene regulatory network, and cell communication analysis showed diminished oligodendrocyte/microglia differentiation. Findings were verified using Bulk RNA-Seq and demonstrated oxytocin's beneficial effects on myelin gene expression.
LIMITATIONS
Our findings are significant. However, limitations can be noted. The cellular mechanisms linking reduced oligodendrocyte differentiation and reduced myelination to an ASD phenotype in C58/J mice need further investigation. Additional snRNA-Seq and spatial studies would determine if effects in oligodendrocytes/microglia are unique to amygdala or if this occurs in other brain regions. Oxytocin's effects need further examination to understand its' potential as an ASD therapeutic.
CONCLUSIONS
Our work demonstrates the C58/J mouse model's utility in evaluating the influence of sex and sociability on the transcriptome in concomitant brain regions involved in ASD. Our single-nucleus transcriptome analysis elucidates potential pathological roles of oligodendrocytes and microglia in ASD. This investigation provides details regarding regulatory features disrupted in these cell types, including transcriptional gene dysregulation, aberrant cell differentiation, altered gene regulatory networks, and changes to key pathways that promote microglia/oligodendrocyte differentiation. Our studies provide insight into interactions between genetic risk and epigenetic processes associated with divergent affiliative behavior and lack of positive sociability.
Topics: Animals; Male; Microglia; Mice; Amygdala; Female; Oligodendroglia; Autism Spectrum Disorder; Mice, Inbred C57BL; Social Behavior; Gene Expression Profiling; Phenotype; Sex Characteristics; Transcriptome; Disease Models, Animal; Oxytocin
PubMed: 38898502
DOI: 10.1186/s12993-024-00240-3