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BMJ Case Reports Jun 2024This case report describes a man in his 20s presenting with bilateral crypto-orchidism, micropenis and underdeveloped secondary sexual characteristics. The patient also...
This case report describes a man in his 20s presenting with bilateral crypto-orchidism, micropenis and underdeveloped secondary sexual characteristics. The patient also exhibited hyposmia, eunuchoid stature and gynecomastia. Biochemical investigations revealed low levels of testosterone, luteinising hormone and follicle-stimulating hormone. Hence, he was diagnosed with Kallmann syndrome. Imaging studies showed an absent right kidney and cystic dilatation of the distal ureteric bud, seminal vesicle and absent/hypoplastic ejaculatory duct. The association of hypogonadotropic hypogonadism with Zinner syndrome, a rare condition characterised by renal agenesis, seminal vesicle cyst and ejaculatory duct obstruction, was noted.
Topics: Humans; Male; Hypogonadism; Kallmann Syndrome; Seminal Vesicles; Kidney; Ejaculatory Ducts; Adult; Penis
PubMed: 38901851
DOI: 10.1136/bcr-2023-259363 -
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 -
Biotechnology Journal Jun 2024Follicle-stimulating hormone (FSH) is an important protein used for bovine ovarian hyperstimulation in multiple ovulation and embryo transfer technology (MOET). Several...
Follicle-stimulating hormone (FSH) is an important protein used for bovine ovarian hyperstimulation in multiple ovulation and embryo transfer technology (MOET). Several attempts to produce bovine FSH (bFSH) in recombinant systems have been reported, nonetheless, up to date, the most commonly used products are partially purified preparations derived from porcine or ovine (pFSH or oFSH) pituitaries. Here we describe the development of a biotechnology process to produce a novel, hyperglycosylated, long-acting recombinant bFSH (LA-rbFSH) by fusing copies of a highly O-glycosylated peptide. LA-rbFSH and a nonmodified version (rbFSH) were produced in suspension CHO cell cultures and purified by IMAC with high purity levels (>99%). LA-rbFSH presented a higher glycosylation degree and sialic acid content than rbFSH. It also demonstrated a notable improvement in pharmacokinetic properties after administration to rats, including a higher concentration in plasma and a significant (seven-fold) reduction in apparent clearance (CL). In addition, the in vivo specific bioactivity of LA-rbFSH in rats was 2.4-fold higher compared to rbFSH. These results postulate this new molecule as an attractive substitute for commercially available porcine pituitary-derived products.
Topics: Animals; Follicle Stimulating Hormone; CHO Cells; Glycosylation; Cattle; Cricetulus; Recombinant Proteins; Rats; Female; Biotechnology
PubMed: 38900054
DOI: 10.1002/biot.202400260 -
Pediatric Transplantation Aug 2024Growth retardation and short final height is a common complication of chronic kidney disease (CKD) beginning in childhood, with profound deleterious effects on quality... (Review)
Review
BACKGROUND
Growth retardation and short final height is a common complication of chronic kidney disease (CKD) beginning in childhood, with profound deleterious effects on quality of life, mental health, and social achievement. Despite optimal treatments of causative factors for growth retardation in children with CKD, more than 50% of patients reach end-stage renal failure with a height >2 SD below the mean, and most do not demonstrate "catch-up" growth after receiving a kidney transplant. Four decades ago, recombinant human growth hormone (rhGH) treatment was introduced after studies showed increased growth velocity and improved height SDS in uremic subjects. Since then, an abundance of published data showed significant improvements in health-related quality of life, and most studies revealed no significant adverse effects. Clinical practice guidelines recommended rhGH treatment in CKD Stages 3-5D and after transplantation. Despite these guidelines, this therapy remained underutilized. Most commonly cited barriers to the implementation of rhGH treatment were the need for daily injections, financial challenges, physicians' unfamiliarity with guidelines, and fear of adverse events.
CONCLUSIONS
rhGH has been shown to improve growth and final height in short children with CKD, with minimal adverse effects. Despite data of its successful use generated over 3 decades, this treatment is underutilized. More judicious utilization of the treatment should emphasize educating patients, their care givers, and members of the multidisciplinary treating team. Additional studies are needed to assess the longer-term rhGH treatment in larger cohorts of patients, leading to additional supportive data and clearer recommendations.
Topics: Humans; Kidney Transplantation; Child; Human Growth Hormone; Growth Disorders; Quality of Life; Body Height; Kidney Failure, Chronic; Renal Insufficiency, Chronic; Treatment Outcome; Recombinant Proteins; Practice Guidelines as Topic; Adolescent
PubMed: 38899494
DOI: 10.1111/petr.14803 -
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 -
Journal of Animal Science Jun 2024The study objective was to investigate the effect of repeated hypothalamic-pituitary-adrenal (HPA) axis stimulation using synthetic adrenocorticotropic hormone (ACTH)...
The study objective was to investigate the effect of repeated hypothalamic-pituitary-adrenal (HPA) axis stimulation using synthetic adrenocorticotropic hormone (ACTH) intramuscular injections on hair cortisol concentration, growth, and behavior in preweaned dairy calves. Twenty-seven Holstein calves were assigned to nine triads (based on sex and birth order) and randomly assigned to 1 of 3 treatments: 1) control (CON; 2 mL saline weekly); 2) moderate (MOD; alternating Cosyntropin [2 mcg/kg body weight (BW)] and saline weekly); or 3) frequent (FREQ; Cosyntropin [2 mcg/kg BW] weekly). Calves received their first injection on study day 0 (7±1 d of age). Hair was collected from the tail switch between days -5 and -3 (baseline), 21, and 49 and analyzed for cortisol concentration. To verify the endogenous cortisol release by Cosyntropin during the treatment period, saliva was collected on days 0, 14, 28, and 42 before injection and every 15 min for 2 h after injection for analysis of salivary cortisol concentration. Calves were fitted with accelerometers to continuously monitor lying time, number of lying bouts, and lying bout duration throughout the study. Growth measures (BW, hip height, hip width) were recorded weekly. Data were analyzed using repeated measures ANOVA (SAS, Version 9.4), and models included the fixed effects of treatment, time (min or study day), and interaction between treatment and time. Temperature humidity index was included as a continuous covariate in all models. We observed a treatment × min interaction (P < 0.0001), whereby salivary cortisol concentration was lower in CON calves compared to MOD and FREQ calves 15 to 120 min post injection. While hair cortisol concentration was not influenced by treatment, concentration decreased from day 21 (1.28±0.03 ng/mL) to 49 (0.93±0.03 ng/mL). Average body weight was similar across treatments (CON [59.4±1.09 kg], MOD [58.6±0.98 kg], and FREQ [57.6±0.96 kg]; P=0.50). There was no evidence to suggest a difference in average daily lying time (CON [18.5±0.23 h/d], MOD [18.6±0.23 h/d], and FREQ [18.5±0.23 h/d]; P=0.99). These results suggest that repeated HPA axis stimulation through Cosyntropin administration increased salivary cortisol concentration, but did not influence hair cortisol concentration, growth, or behavior in preweaned dairy calves.
PubMed: 38898575
DOI: 10.1093/jas/skae171 -
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 -
World Neurosurgery Jun 2024To investigate the long-term clinical outcomes of staged surgical resection in giant Pituitary Neuroendocrine Tumors(pitNET).Method We performed a retrospective analysis...
To investigate the long-term clinical outcomes of staged surgical resection in giant Pituitary Neuroendocrine Tumors(pitNET).Method We performed a retrospective analysis of the clinical data of 16 patients who underwent surgery. The patients were diagnosed and underwent surgery at the Department of Neurosurgery of Shiyan Taihe Hospital from January 2013 to March 2021. Among the cases, 12 patients underwent primarily transsphenoidal surgery followed by secondary transcranial surgery, while 4 patients underwent primarily transsphenoidal surgery followed by secondary transsphenoidal surgery. Before the surgery, all patients underwent a pituitary MRI scan, pituitary hormone level examination, visual acuity, and visual field examination. A pituitary MRI was rechecked within 1 week after the operation. A tumor resection rate of 100% on MRI was considered as a total resection, between 90% to 100% as a subtotal resection, and lower than 90% as a partial resection. After the surgery, regular clinical visits and telephone or internet platform follow-ups were conducted. Outcome In our clinical investigation, after staged surgery 10 patients had a total resection, 5 had a subtotal resection, and 1 had a partial resection depending on the tumor size and invasion. The clinical outcomes showed that 1 case suffered from postoperative intracranial infection, 1 case had decreased visual acuity, and 6 cases experienced decreased pituitary function after surgery.Postoperative complications were cured after symptomatic treatment, except for 1 patient who experienced decreased vision and 1 patient sufferred hypopituitarism required long-term oral levothyroxine tablet treatment. No cases of intracranial hemorrhage or death were caused by intentionally staged resection surgery. Conclusion Staged surgery for giant pitNET is a safe and effective clinical surgery strategy.
PubMed: 38897401
DOI: 10.1016/j.wneu.2024.06.069