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Background: With the introduction of new therapy modalities and the resulting increase in survival rates, childhood brain cancers have become a focal point of research in pediatric oncology. In current protocols, besides surgical resection and chemotherapy, radiotherapy is required to ensure optimal survival. Our aim was to determine which of the two major irradiation options, proton (PT) or photon (XRT), was the least harmful yet effective for children with brain tumors. Methods: The protocol was registered on PROSPERO in advance (CRD42022374443). A systematic search was performed in four databases (MEDLINE via (PubMed), Embase, Cochrane Library, and Scopus) on 23 April 2024. Odd ratios (OR) and mean differences (MD) with 95% confidence intervals (CI) were calculated using a random-effects model. Survival and six major types of side effects were assessed based on data in the articles and reported using the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Heterogeneity was assessed using Higgins and Thompson's I2 statistics. Results: Altogether, 5848 articles were screened, of which 33 were eligible for data extraction. The 5-year overall survival results showed statistically no significant difference between the two radiotherapy modalities (OR = 0.80, 95% CI: 0.51–1.23, p = 0.22, I2 = 0%). In terms of toxicity rates, an advantage was found for PT, particularly in terms of chronic endocrine side effects (hypothyroidism OR: 0.22, 95% CI: 0.10–0428, p = 0.002, I2 = 68%), neurocognitive decline (global IQ level MD: 13.06, 95% CI: 4.97–21.15, p = 0.009, I2 = 68%). As for hematological, acute side effects, neurological changes and ophthalmologic disorders PT can be beneficial for survivors in terms of reducing them. Conclusions: In comparison with XRT, PT can reduce most side effects, without significantly decreasing the survival rate. There is considerable clinical relevance in the findings, even not all of them are statistically significant, which may facilitate the development of protocols regarding the usage of radiotherapy methods, and may encourage the establishment of more proton centers, where more studies can be done. [ABSTRACT FROM AUTHOR]

The paired box 6 (Pax6) gene encodes a highly conserved transcription factor, involved in the development of eyes, brain, and endocrine glands. Homozygous loss of Pax6 resulted in neonatal death in mice, plus loss of eyes and malformation of cerebral cortex. In patients with heterozygous Pax6 mutations, a reduction in thickness of the frontoparietal cortex was detected, which was also observed in small eye mice. In this study, we found that Pax6 overexpression increased the cortical thickness, especially in the intermediate zone of the cortex, which conflicts with the report of Manuel et al. Pax6 overexpression appears to detain neurons in the intermediate zone while promoting cell proliferation. It is worth noting that the impact of Pax6 overexpression on cortical thickness and neuronal migration was temporal, explaining the differences with other reports. We postulated that the alteration of Pax6 isoform ratio by autoregulation might be responsible for this. JASPAR analysis together with the results of qPCR, Western blot, CUT&Tag, and rescue experiments revealed that Pax6 regulates neuronal migration and cell proliferation by indirectly mediating Wnt3a expression. Therefore, we propose that Pax6 participates in corticogenesis via interaction with Wnt3a in regulating neuronal migration and cell proliferation. [ABSTRACT FROM AUTHOR]

This article from the Journal of Neurological Surgery explores the impact of socioeconomic status (SES) on the presentation, management, and outcomes of patients with Rathke's cleft cysts (RCCs). The study, based on a retrospective review of 484 RCC patients, found that patients with public insurance and larger cysts were more likely to undergo surgery. English proficiency was associated with smaller cyst size, and uninsured patients had lower rates of resolution of visual symptoms postoperatively. Follow-up duration was correlated with income, PCP status, surgery, and insurance type, highlighting the need for further research to ensure equitable access to timely diagnosis, treatment, and follow-up for RCC patients. [Extracted from the article]

Background: Poly (ADP-ribose) polymerase inhibitors (PARPi) serve as crucial therapeutic agents in solid tumor treatment. Preclinical investigations suggest a potential protective function of PARPi against endocrine and metabolic impairments. Nevertheless, the existing body of evidence remains inconclusive on this aspect. Purpose: Our aim was to evaluate the potential impact of PARPi on endocrine and metabolic disruptions in clinical trials. Data sources: We conducted a comprehensive search across the Medline, EMBASE, PubMed, and Web of Science databases, along with the ClinicalTrials.gov registry. Study selection: Phase II/III randomized controlled trials (RCTs) investigating the effects of PARPi in metabolic and endocrine processes were selected for inclusion in patients with solid tumors. Data extraction: The primary outcomes of interest encompassed metabolic and endocrine dysfunctions. Data synthesis: A total of 26 trials (n = 9,590 patients) were included in our meta-analysis. Niraparib demonstrated an increased risk of any-grade hyperglycemia (OR = 2.15, 95% CI 1.28–3.62), with patients receiving PARPi for metastatic pancreatic cancer showing a higher susceptibility to any-grade hyperglycemia (OR = 1.78, 95% CI 1.04–3.04). Conversely, rucaparib exhibited a potential ameliorative effect on hyperglycemia (OR = 0.54, 95% CI 0.30–0.97). No statistically significant disparities were observed for other outcomes associated with PARPi utilization. Limitations: Among these RCTs included, 50% were assessed as low qualities due to high risk of bias. Conclusions: Our meta-analysis demonstrated that PARPi may exert adverse effects on endocrine and metabolic pathways. Close monitoring of hyperglycemia is recommended for patients undergoing niraparib therapy, especially those with pancreatic cancer. Trial registration: This meta-Analysis was prospectively registered in the PROSPERO database with ID CRD42023457959. Highlights: Preclinical studies indicate that PARPi may provide protection against endocrine and metabolic abnormalities. This systematic review and meta-analysis aimed to assess the association between PARPi and the incidence of endocrine and metabolic abnormalities in patients with solid tumors. Our findings revealed that PARPi adversely affect both endocrine and metabolic processes in patients with solid tumors. Special attention is warranted regarding hyperglycemia in patients treated with niraparib, particularly those with pancreatic cancer. The underlying mechanisms of PARPi's effects on endocrine and metabolic functions remain unclear, highlighting the need for further comprehensive research. [ABSTRACT FROM AUTHOR]

Current dissociation methods for solid tissues in scRNA-seq studies do not guarantee intact single-cell isolation, especially for sensitive and complex human endocrine tissues. Most studies rely on enzymatic dissociation of fresh samples or nuclei isolation from frozen samples. Dissociating whole intact cells from fresh-frozen samples, commonly collected by biobanks, remains a challenge. Here, we utilized the acetic-methanol dissociation approach (ACME) to capture transcriptional profiles of individual cells from fresh-frozen tissue samples. This method combines acetic acid-based dissociation and methanol-based fixation. In our study, we optimized this approach for human endocrine tissue samples for the first time. We incorporated a high-salt washing buffer instead of the standard PBS to stabilize RNA and prevent RNases reactivation during rehydration. We have designated this optimized protocol as ACME HS (ACetic acid-MEthanol High Salt). This technique aims to preserve cell morphology and RNA integrity, minimizing transcriptome changes and providing a more accurate representation of mature mRNA. We compared the ability of enzymatic, ACME HS, and nuclei isolation methods to preserve major cell types, gene expression, and standard quality parameters across 41 tissue samples. Our results demonstrated that ACME HS effectively dissociates and fixes cells, preserving cell morphology and high RNA integrity. This makes ACME HS a valuable alternative for scRNA-seq protocols involving challenging tissues where obtaining a live cell suspension is difficult or disruptive. [ABSTRACT FROM AUTHOR]

Dinotefuran, a chiral neonicotinoid pesticide, is known to cause endocrine disruption, but the specific impact of its enantiomers remains unclear. Xenopus laevis tadpoles were exposed to varying concentrations of R- and S-dinotefuran (0, 5, and 50 μg/L) for 21 days. Body length and developmental stages were measured, and hormone levels and HPT axis gene expression were analyzed. Molecular docking was performed to evaluate the activation of the thyroid hormone receptor (TRα) by the enantiomers. Dinotefuran exposure significantly decreased body length and delayed developmental stages, indicating developmental toxicity. It reduced T3, T4, and TSH levels, suggesting thyroid endocrine disruption. Dinotefuran increased the mRNA expression of TSH synthesis and receptor genes, likely compensating for lower T4. Changes in iodide uptake and deiodinase gene expression may explain reduced thyroid hormone levels. Molecular docking showed that both R- and S-dinotefuran can directly activate TRα. Additionally, enantioselective differences were observed at the gene expression level, indicating that the developmental toxicity and endocrine disruption effects of the dinotefuran enantiomers differ in their impact on HPT axis regulation. Dinotefuran altered HPT axis gene expression and thyroid hormone levels, causing thyroid endocrine disorders and delayed tadpole metamorphosis, posing a threat to frog populations. [ABSTRACT FROM AUTHOR]

Background and Objectives: Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy, but their use is associated with a spectrum of immune-related adverse events (irAEs), including endocrine disorders. This study aims to investigate the incidence, timing, treatment modalities, and impact of ICI-related endocrine side effects in cancer patients. Materials and Methods: This retrospective study analyzed 139 cancer patients treated with ICIs between 2016 and 2022. Data regarding endocrine irAEs, including hypothyroidism, hyperthyroidism, hypophysitis, and diabetes mellitus, were collected. The study examined the timing of irAE onset, management approaches, and the association between irAEs and treatment outcomes. Results: The most common endocrine irAE was hypothyroidism (65.5%), followed by hyperthyroidism (2.3%), hypophysitis (8.6%), and diabetes mellitus (0.7%). These disorders typically emerged within the first six months of ICI therapy. Most cases were managed conservatively or with hormone replacement therapy. Patients who developed endocrine irAEs exhibited a higher objective response rate (ORR) and clinical benefit rate (CBR) compared to those without irAEs. Conclusions: Endocrine dysfunction is a significant toxicity of ICI therapy. Early recognition, prompt diagnosis, and appropriate management are crucial to minimize their impact on patient health and quality of life. This study highlights the potential association between irAEs and improved clinical outcomes. Further research is needed to elucidate the underlying mechanisms and identify predictive biomarkers for irAE development. [ABSTRACT FROM AUTHOR]

The pathogenesis of long COVID (LC) still presents many areas of uncertainty. This leads to difficulties in finding an effective specific therapy. We hypothesize that the key to LC pathogenesis lies in the presence of chronic functional damage to the main anti-inflammatory mechanisms of our body: the three reflexes mediated by the vagus nerve, the hypothalamic-pituitary-adrenal (HPA) hormonal axis, and the mitochondrial redox status. We will illustrate that this neuro-endocrine-metabolic axis is closely interconnected and how the SARS-CoV-2 can damage it at all stages through direct, immune-inflammatory, epigenetic damage mechanisms, as well as through the reactivation of neurotropic viruses. According to our theory, the direct mitochondrial damage carried out by the virus, which replicates within these organelles, and the cellular oxidative imbalance, cannot be countered in patients who develop LC. This is because their anti-inflammatory mechanisms are inconsistent due to reduced vagal tone and direct damage to the endocrine glands of the HPA axis. We will illustrate how acetylcholine (ACh) and cortisol, with its cytoplasmatic and cellular receptors respectively, are fundamental players in the LC process. Both Ach and cortisol play multifaceted and synergistic roles in reducing inflammation. They achieve this by modulating the activity of innate and cell-mediated immunity, attenuating endothelial and platelet activation, and modulating mitochondrial function, which is crucial for cellular energy production and anti-inflammatory mechanisms. In our opinion, it is essential to study the sensitivity of the glucocorticoids receptor in people who develop LC and whether SARS-CoV-2 can cause long-term epigenetic variations in its expression and function. [ABSTRACT FROM AUTHOR]

Aging affects the structure and functions of all organs and systems in the organism. In the elderly, significant changes in hormonal levels are observed. These translate to a predisposition for chronic diseases, including cardiovascular, neurodegenerative, and metabolic disorders. Therefore, tremendous scientific effort is focused on investigating molecular mechanisms and drugs with the potential to reduce hormonal changes in old age and their impact. Sirtuin 1 (SIRT1), a member of the sirtuin family of deacetylases, has been extensively studied as a regulator of multiple pathways related to antioxidant properties, optimal immune response, and metabolism. SIRT1 plays a key role in regulating various hormonal pathways and maintaining homeostasis. In the present study, we review the interplay between SIRT1 and hormonal regulations, including the endocrine role of the hypothalamic–pituitary–thyroid, –adrenal, –gonadal, and –liver axes, of other endocrine glands, and of non-endocrine tissues in the aging organism. The application of natural SIRT1 activators, such as resveratrol, curcumin, paeonol, and Buyang Huanwu Decoction, for the treatment of aging and senescence is discussed. SIRT1 activators improve mitochondrial function, reduce oxidative stress, and promote longevity, but their clinical application is limited by low bioavailability and poor permeability across biological barriers. For this reason, advanced delivery strategies are being considered, including nose-to-brain drug delivery and nanotechnology-based formulations. [ABSTRACT FROM AUTHOR]

The aim of the study was to present a review of the literature and research on the carotid body (CB) over the past years and update the latest findings. The purpose of this article is to present a general overview and comparative analysis of CB between species, from the microanatomy to the pathology of CB. This study gives information about the embryological development and physiological aspects of anatomical findings and their differences. The second part of the article gives a comparative analysis of the pathology of CB. Neoplasia of the CB in humans, namely, paraganglioma, in most cases, is part of a genetic MEN syndrome (multiple endocrine neoplasia). In dogs, paraganglioma is also involved with multiple neoplasia formations throughout the body, including endocrine and neuroendocrine glands. From this perspective, dogs are the most suitable specimens for studying carotid body tumors and their involvement in a MEN-like syndrome. [ABSTRACT FROM AUTHOR]

Background: The novel coronavirus strain SARS-CoV-2 triggered the COVID-19 pandemic with severe economic and social ramifications. As the pathophysiology of SARS-CoV-2 infection in the respiratory system becomes more understood, growing evidence suggests that the virus also impacts the homeostasis-regulating neuroendocrine system, potentially affecting other organ systems. Summary: This review explores the interactions between SARS-CoV-2 and the neuroendocrine system, highlighting the effect of this virus on various endocrine glands, including the brain, hypothalamus, pituitary, pineal, thyroid, parathyroid, adrenal glands, pancreatic islets, gonads, and adipose tissue. The viral invasion disrupts normal hormonal pathways, leading to a range of endocrine disorders, immune dysregulation, and metabolic disturbances. Key Messages: There is potential for SARS-CoV-2 to induce autoimmune responses, exacerbate existing endocrine conditions, and trigger new-onset disorders. Understanding these interactions is crucial for developing treatment strategies that address not only the respiratory symptoms of COVID-19 but also its endocrine complications. The review emphasizes the need for further research to elucidate the long-term effects of SARS-CoV-2 on endocrine health. [ABSTRACT FROM AUTHOR]

Introduction: The parathyroid gland is a small endocrine gland that appears as small oval-shaped bodies with a brown color. It is called the parathyroid gland due to its location closely with the thyroid gland. Materials and Methods: The study used six adult males of Felis catus from the local markets in Baghdad. Formalin (10%) was used to fix the samples for preparing all specimens to conduct histological study. They were passed in an alcohol ascending series 70, 80, 90 and 100% and cleared by xylene. Masson's Trichrome stain (MTc), Haris hematoxlin and Eosin stain (H&E), Periodic Acid Schiff stain (PAS), were used to stain the gained sections. Results: The current study observed the presence of two pairs of parathyroid glands in Felis catus animal, which are in contact with the thyroid gland, occupying an apical peripheral site and a lateral peripheral site, and located within the thyroid gland tissue embedded in its substance. Moreover, the gland appears as lobes consist of 2-4 with oval or irregular in shape and surrounded with a thin capsule. A capsule of connective tissue surrounds the parathyroid gland in F. catus is an extension of the capsule of the thyroid gland consisting of collagen, elastic and reticular fibers, nuclei of smooth muscle fibers, blood vessels, and nerves. The septa are extended from the capsule which divides the gland into lobules, the parathyroid gland tissue has three types of cells represented by chief cells, which are the most common cells, while the other two types are Oxiphyl cells and water-clear cells. Conclusion: The current study Felis catus, observed the presence of two pairs of parathyroid glands in Felis catus animal, which are in contact with the thyroid gland. Moreover, the gland appears as lobes consist of 2-4 with oval or irregular in shape and surrounded with a thin capsule, and their internal histological structure consists of three cell kinds: chief, Oxphill, and water clear cells. [ABSTRACT FROM AUTHOR]

The current work attempted to examine the histological and immunohistochemical features of the pancreas in the southern white-breasted hedgehog (Erinaceus concolor). Five adult male individuals were used in this study. Utilizing hematoxylin and eosin as well as Masson's trichrome, staining was performed on paraffin sections of the pancreas. Immunofluorescent staining investigated the expression pattern of glucagon, insulin, somatostatin, neuropeptide Y (NY), and pancreatic polypeptide (PP). The exocrine pancreas comprised pyramidal and oval-shaped acini, exhibiting the clustering of zymogen droplets in the apical cytoplasm of acinar cells. The endocrine pancreas was distinguished as a large α islet of Langerhans and small β islets. Alpha cells were localized on the periphery of islets with an intensity of 20.6% ± 12.56. In comparison, Beta cells with 25.14% ± 5.89 intensity were gathered in the middle of the pancreatic islets. Delta cells exhibited 25.69% ± 5.13 intensity and were distributed through the islets. NY and PP cells were detected with 22.74% ± 3.25 and 16.80% ± 4.77 intensity, respectively. These cells showed prevalent distribution in the islets. In conclusion, it appears that although the pancreas of the southern white-breasted hedgehog is generally like other mammalian species, there are some species-specific features in density and dispersal of endocrine cells which can be attributed to the physiological purpose of the pancreas in this species. Future histophysiological investigations are still needed to explore the exact relationship between the histological organization of the pancreas and its function in that animal. [ABSTRACT FROM AUTHOR]

Many endocrine glands exhibit circadian rhythmicity, but the interplay between the central circadian clock in the suprachiasmatic nucleus (SCN), the peripheral endocrine clock, and hormones is sparsely understood. We therefore studied the cellular localizations of the clock protein PER1, parathyroid hormone (PTH) and calcitonin (CT) in the parathyroid and thyroid glands, respectively. Thyroid glands, including the parathyroids, were dissected at different time-points from rats housed in 12 h:12 h light–darkness cycles, and were double-immunostained for PER1 and PTH or CT. Sera were analyzed for PTH, CT, phosphate, and calcium. In both glands, PER1 expression peaked late at night, while limited staining was seen during the daytime. High-resolution microscopy revealed cytosolic PER1 at zeitgeber time (ZT)12, and nucleic staining at ZT24 in both PTH and CT cells. PTH peaked at Z12–ZT16, while neither CT staining nor serum CT oscillated during the daily cycle. Serum PTH was significantly higher at ZT12 than ZT24, but only phosphate was found to exhibit significant diurnal oscillation. The staining of the calcium-sensitive receptor (CSR) did not demonstrate circadian oscillation. In conclusion, PER1 expression peaked late at night/early in the morning in hormone-producing cells of both the thyroid and parathyroid glands. In the parathyroids, this was preceded by a PTH peak, while neither CT nor CRS were found to oscillate. [ABSTRACT FROM AUTHOR]

Psychosocial stress has been proposed to induce a redistribution of immune cells, but a comparison with an active placebo-psychosocial stress control condition is lacking so far. We investigated immune cell redistribution due to psychosocial stress compared to that resulting from an active placebo-psychosocial stress but otherwise identical control condition. Moreover, we tested for mediating effects of endocrine parameters and blood volume changes. The final study sample comprised 64 healthy young men who underwent either a psychosocial stress condition (Trier Social Stress Test; TSST; n = 38) or an active placebo-psychosocial stress control condition (PlacTSST; n = 26). Immune cell counts and hemoglobin, epinephrine, norepinephrine, ACTH, renin, and aldosterone levels, as well as those of saliva cortisol, were determined before and up to 30 min after the TSST/PlacTSST. The TSST induced greater increases in total leukocyte, monocyte, and lymphocyte levels as compared to the PlacTSST (p's ≤ 0.001), but in not granulocyte counts. Neutrophil granulocyte counts increased in reaction to both the TSST and PlacTSST (p's ≤ 0.001), while eosinophil and basophil granulocyte counts did not. The psychosocial stress-induced increases in immune cell counts from baseline to peak (i.e., +1 min after TSST cessation) were independently mediated by parallel increases in epinephrine (ab's ≤ −0.43; 95% CIs [LLs ≤ −0.66; ULs ≤ −0.09]). Subsequent decreases in immune cell counts from +1 min to +10 min after psychosocial stress cessation were mediated by parallel epinephrine, renin, and blood volume decreases (ab's ≥ 0.17; 95% CIs [LLs ≥ 0.02; ULs ≥ 0.35]). Our findings indicate that psychosocial stress specifically induces immune cell count increases in most leukocyte subpopulations that are not secondary to the physical or cognitive demands of the stress task. Increases in the number of circulating neutrophil granulocytes, however, are not psychosocial stress-specific and even occur in situations with a low probability of threat or harm. Our findings point to a major role of epinephrine in mediating stress-induced immune cell count increases and of epinephrine, renin, and blood volume changes in mediating subsequent immune cell count decreases from +1 min to +10 min after psychosocial stress cessation. [ABSTRACT FROM AUTHOR]

Hypothalamic obesity (HO) is defined as abnormal weight gain resulting in severe persistent obesity due to physical, tumor‐ and/or treatment‐related damage to the hypothalamus. HO epidemiology is poorly understood. We developed a database algorithm supporting the standardized identification of tumor/treatment‐related HO (TTR‐HO) patients. The algorithm is used to estimate incidence rates of TTR‐HO patients in the German healthcare context from a representative claims database (n = 5.42 million) covering 2010–2020. Patients were identified based on surgery/radiotherapy procedures and HO‐associated tumor diagnoses (n = 3976). HO was defined by incident obesity and validated based on incident diabetes insipidus diagnoses and desmopressin prescription within a 12‐month period after surgery/radiotherapy. Uncertainty due to algorithm definitions is explored in sensitivity analyses. Estimated annual incidence of TTR‐HO in Germany is between 0.7 and 1.7 cases per 1,000,000 persons (2019 prevalence: n = 1262 patients). With observed cases in all age groups, two HO‐incidence peaks are identified: children/young adults aged 10–24 years and adults aged 40–44 years. Most frequent HO‐validated tumor diagnoses are benign sellar/suprasellar tumors (6.1/1,000,000 persons over 9 years), including tumors of the craniopharyngeal duct (1.3/1,000,000), neoplasms of the pituitary gland (4.1/1,000,000), and nonspecific brain tumors of endocrine glands (2.4/1,000,000). This is the first real‐world database analysis of TTR‐HO epidemiology, refining current estimates of HO epidemiology and early patient identification. A more comprehensive characterization of patients with HO as well as a better understanding of clinical implications will be crucial in developing optimal treatment strategies to improve patient outcomes. [ABSTRACT FROM AUTHOR]

The use of organochlorine pesticides (OCPs) in specific regions is still prevalent. Moreover, the impact of past utilization can be observed in the present environmental matrices. The present study monitored the extent of contamination of OCPs in the soil and vegetable samples of Gaya, Bihar, India. For this, 63 soil and vegetable samples were collected from the vegetable cultivated area of Gaya. The collected samples were extracted using a Soxhlet extraction unit and OCPs were analysed with a gas chromatography–mass spectrometry detector. The concentration data generated from the analysis were interpreted using statistical tools and software. Mean concentration (μg/g) of Σ19OCPs in soil from residential, agricultural, commercial, and polyhouse sites were 0.69, 2.21, 0.17, and 0.72, respectively. Similarly, in vegetable samples, mean concentration (μg/g) of Σ19OCPs were 0.91, 0.96, 1.00, and 0.67, respectively. Among the monitored vegetable types, the concentration of OCPs increased in the order: pods > tubers > leaves > fruits > roots > stem. The bioconcentration factor of 19 OCPs showed that 61.90% of vegetable samples were hyperaccumulators. The results of molecular diagnostic ratio and positive matrix factorization reported the recent inputs of heptachlor, aldrin, endrin and methoxychlor; the past application of dichlorodimethyltrichloroethane (DDT), endosulfan, and chlordane; and the degradation of DDT to its metabolites and aldrin to dieldrin, which make up an overall source profile of OCPs in study area. The study found that incremental lifetime cancer risks and hazard quotients ranged from 6.98 × 10–8 to 1.31 × 10–5 and 4.25 × 10–2 to 4.63 × 10–1, respectively in vegetable samples which indicate low to high ILCR and low non-carcinogenic risk to populations exposed to OCPs. The study indicates the long lasting impact of past pesticide use by studying the contamination in soil and vegetables, and raises serious concerns about food safety. The contamination poses direct health risk to consumers related to potential carcinogenic and endocrine disrupting effects. Thus monitoring on the ground level could be a force to modify region specific policies, health, and remediation measures related to exposure to OCPs. [ABSTRACT FROM AUTHOR]

Background: Aldosterone is the principal mineralocorticoid hormone and the final effector of the renin-angiotensin-aldosterone system. This hormone is primarily synthesized by the CYP11B2 enzyme and produced by the adrenal zona glomerulosa. Through genomic and non-genomic effects, it plays an important role in cardiovascular and renal disease. To counteract aldosterone-mediated damage, steroidal mineralocorticoid receptor antagonists are recommended by international guidelines, but endocrine side effects often limit their use in a substantial proportion of patients. Conversely, nonsteroidal mineralocorticoid receptor antagonists, with an improved selectivity and safety profile, are gaining a prominent position among therapeutic pillars. However, blocking the mineralocorticoid receptors does not completely inhibit aldosterone effects because of escape mechanisms and non-genomic activity. Thus, inhibiting aldosterone synthesis could be a promising strategy to prevent aldosterone-mediated cardiorenal damage. The limited specificity for CYP11B2 and side effects due to off-target activity hampered the development of first-generation aldosterone synthase inhibitors (ASIs). Summary: The development of highly specific ASIs led to successful clinical trials in patients with resistant and uncontrolled hypertension. Additionally, a recent randomized clinical trial showed a significant benefit of ASIs in patients with chronic kidney disease and albuminuria. Key Messages: The strength of the clinical evidence collected so far is still limited, and larger outcome-based clinical trials are needed to confirm the promising role of ASIs in cardiorenal damage. [ABSTRACT FROM AUTHOR]

Background: COVID-19, caused by SARS-CoV-2, has impacted over 264 million people and caused over 5 million deaths worldwide. Symptoms often include viral pneumonia, with complications like acute respiratory distress or sepsis, as well as myocarditis and kidney damage. The purpose of the study is to investigate the impact of COVID-19 on endocrine glands, as well as to develop a classification of stages of the course of COVID-19 to improve and simplify morphological diagnosis. Methods: The studies conducted include systemic analysis of the para-clinical data of patients who died of COVID-19 (according to medical documentation); a macroscopic study assessing the size and weight of external manifestations of endocrine organ lesions in COVID-19 cases with statistical evaluation of the detected signs. Archive analysis covers para-clinical data and data on significant concomitant and background pathologies based on the medical histories of 780 deaths from COVID-19 in infectious diseases hospitals of the city of Kostanay (Kazakhstan) during the period from 2019 to 2022. Result: Using pathomorphologic data from COVID-19 autopsies, we developed a scale for semi-quantitative analysis of each case. Medical data analysis suggests that the most notable endocrine changes are elevated blood glucose and low catecholamine levels due to adrenal hemosiderosis. No significant changes in sex or thyroid hormones were observed. Conclusion: The obtained findings require further consideration, given that the studied patients make up a rather diverse group. Nevertheless, the study can serve as an additional source of information in the struggle against COVID-19. [ABSTRACT FROM AUTHOR]

Climate change is increasing both seasonal temperatures and the frequency and severity of heat extremes. As the endocrine system facilitates physiological adaptations to temperature changes, diseases with an endocrinological basis have the potential to affect thermoregulation and increase the risk of heat injury. The effect of climate change and associated high temperature exposure on endocrine axis development and function, and on the prevalence and severity of diseases associated with hormone deficiency or excess, is unclear. This Perspective summarizes current knowledge relating to the hormonal effects of heat exposure in species ranging from rodents to humans. We also describe the potential effect of high temperature exposures on patients with endocrine diseases. Finally, we highlight the need for more basic science, clinical and epidemiological research into the effects of heat on endocrine function and health; this research could enable the development of interventions for people most at risk, in the context of rising environmental temperatures. Climate change is causing human populations to be exposed to increasingly higher ambient temperatures and more frequent and extreme heatwaves than previously observed. This Perspective considers the available evidence on the endocrine effects of heat exposure, and maps out a path for future research into this field. [ABSTRACT FROM AUTHOR]

Bluetongue virus (BTV), a major peril to the sheep industry, infects a wide range of the cells in the infected animals including mononuclear, dendritic and epithelial cells. However, little is known about its tropism for the secretory epithelial cells of endocrine glands and the pathogenesis it induces. The aim of the study was to assess the BTV load, antigen distribution in the tissue of the pituitary, thyroid as well as adrenal glands and associated histopathological consequences. BTV antigens were localized using immunohistochemistry in the thyroid's epithelial cells, zona fasciculata and zona reticularis cells and the anterior pituitary epithelial cells. The real-time PCR portrayed the high viral load in adrenals at 7th days postinoculation (DPI) and in thyroid and pituitary glands at 15th DPI. Serum examination revealed variation in the T-3 and T-4 of infected animals in comparison to the control group. Caspase-3 immunolocalization revealed BTV-1 induces apoptosis in the affected cells of endocrine gland of infected animals. Further, this study signifies the tropism of BTV in the novel sites (endocrine glands) of the host that might be one of the reasons for the poor performance of infected animals. [ABSTRACT FROM AUTHOR]

Owing to their endocrine disruption effect, the hormone levels in animal-source food and medicines need to be efficiently and accurately quantified by a reliable analytical method. In the current study, by using a homonuclear decoupling and heteronuclear single quantum correlation (HSQC) experiment, coupled with non-uniform sampling (NUS) that was used to shorten the experimental time, we developed a method to quantify 10 hormone residues in animal-source products. This method was validated following the guidelines of USP–NF 2022. The application of the homonuclear decoupling (HD) technique to conventional HSQC yielded 2D spectra that exhibited excellent signal separation and specificity. For all the tested hormones, good linearity with correlation coefficients of more than 0.99 was observed in the linear range of 0.2–6 mg/0.6 mL. Satisfactory precision and recoveries of spiked animal samples were also obtained. Finally, the method was applied in residue determination of 10 hormones in real animal-source samples at the ug/g level. [ABSTRACT FROM AUTHOR]

Simple Summary: With global warming, heat stress has become an increasingly serious problem for poultry because of their abundant feathers, limited sweat glands, and fast metabolism. To alleviate the losses caused by poultry heat stress, it is important to investigate the mechanisms and control strategies for poultry heat stress. When heat stress occurs, the neuroendocrine system in poultry will be disrupted, while several organs in the body will be damaged, affecting the poultry's production performance and health. Adding nutrients to feed is a mild and effective means of heat stress management and holds significant implications for the poultry farming industry. Heat stress (HS) due to high temperatures has adverse effects on poultry, including decreased feed intake, lower feed efficiency, decreased body weight, and higher mortality. There are complex mechanisms behind heat stress in poultry involving the neuroendocrine system, organ damage, and other physiological systems. HS activates endocrine glands, such as the pituitary, adrenal, thyroid, and gonadal, by the action of the hypothalamus and sympathetic nerves, ultimately causing changes in hormone levels: HS leads to increased corticosterone levels, changes in triiodothyronine and thyroxine levels, decreased gonadotropin levels, reduced ovarian function, and the promotion of catecholamine release, which ultimately affects the normal productive performance of poultry. Meanwhile, heat stress also causes damage to the liver, lungs, intestines, and various immune organs, severely impairing organ function in poultry. Nutrient additives to feed are important measures of prevention and treatment, including natural plants and extracts, probiotics, amino acids, and other nutrients, which are effective in alleviating heat stress in poultry. Future studies need to explore the specific mechanisms through which heat stress impacts the neuroendocrine system in poultry and the interrelationships between the axes and organ damage so as to provide an effective theoretical basis for the development of preventive and treatment measures. [ABSTRACT FROM AUTHOR]

Simple Summary: Multiple Endocrine Neoplasia (MEN) is a rare genetic disorder of humans and animals, characterized by developing tumors in multiple endocrine glands. Paraganglioma (PGL) is often linked with MEN, and its occurrence is commonly associated with metabolism-related mutation genes, which currently include SDHA, SDHB, SDHC, SDHD, and SDHAF2. While sporadic cases of concurrent endocrine neoplasia have been documented in veterinary medicine, particularly in dogs, genetic investigations in this domain are lacking and still limited. This study aimed to describe the gross and histological features of multiple endocrine and non-endocrine neoplasia, including multiple PGLs found in two Boxer dogs. Additionally, the identified PGLs were immunohistochemically evaluated, and the subunits 2, 3, and 4 of the SDHD gene were screened for possible mutations. The tumors identified include aortic and carotid body PGLs, thyroid follicular-compact carcinoma, and subcutaneous lipomas. One case also had a Leydig cell tumor and adrenal cortex hyperplasia, while the other had H-type pancreatic carcinoma. Three out of 4 PGLs appeared benign, but one aortic body tumor showed malignant features with neoplastic emboli at its edge. Immunohistochemical analysis confirmed the neuroendocrine origin of all PGLs, with positive staining for Chromogranin A, NSE, and variable positivity for S100. No somatic mutations were found in exons 2, 3, and 4 of the SDHD gene in any of the evaluated PGLs. The absence of mutations in the evaluated SDHD gene subunits suggests the involvement of other genetic factors or pathways in the development of these tumors, warranting further investigation in this field. [ABSTRACT FROM AUTHOR]

Objective: To establish a rat model of pharmacological ovariectomy by GnRH-a injection and to preliminarily investigate the reproductive endocrine effects of Xiangshao granules on pharmacologically ovariectomized rats. Methods: A rat model of pharmacological ovariectomy was established by injecting female rats with Gonadotropin-releasing hormone agonist(GnRH-a).The rats were randomly divided into four groups: GnRH-a injected saline group (GnRH-a + NS); GnRH-a injected oestradiol group (GnRH-a + E2); GnRH-a injected Xiangshao granule group (GnRH-a + Xiangshao), and the control group of saline-injected rats (NS + NS). The number of rats per group was 6.According to observations of the rats' vaginal smears, modelling was determined as successful. Then corresponding drug gavage intervention was administered for 28 days, and rat body weight and anal temperature were measured every other day to adjust the drug intervention amount according to body weight changes. Plasma sex hormone levels (E2, FSH, LH), uterine weight, uterine index and endometrial histomorphological changes, ovarian weight, and ovarian index and ovarian histomorphological changes were measured in each group after the gavage. Results: (1) Plasma sex hormone levels (E2, FSH, LH) of the GnRH-a + NS, GnRH-a + E2, and GnRH-a + Xiangshao granule groups were significantly lower than the NS + NS group (P < 0.001), while the E2 level of the GnRH-a + E2 group was higher than that of the GnRH-a + Xiangshao granule group (P < 0.05). The FSH level of the GnRH-a + E2 group was significantly lower than that of the GnRH-a + Xiangshao granule group (P < 0.05). The LH level of the GnRH-a + E2 group was significantly lower than those in the GnRH-a + NS and GnRH-a + Xiangshao granule groups (P < 0.001, P = 0.001). The LH and FSH levels of the GnRH-a + NS and GnRH-a + Xiangshao granule groups were not significantly different (P > 0.05). (2) Compared with the NS + NS group, the uterine weight and uterine index, and ovarian weight and ovarian index of GnRH-a injected rats in each model all significantly decreased (P < 0.001). Between the groups, the uterine weight and uterine index, and ovarian weight and ovarian index of GnRH-a + E2 and GnRH-a + Xiangshao granule groups were all significantly higher than those of the GnRH-a + NS group (P < 0.001, P < 0.05). The uterine weight and uterine index, and ovarian weight and ovarian index of the GnRH-a + E2 group increased compared with the GnRH-a + Xiangshao granule group (P < 0.05). (3) Compared with the NS + NS group, the number of primordial follicles of the GnRH-a + NS, GnRH-a + E2, and GnRH-a + Xiangshao granule groups increased significantly and the number of growing follicles and mature follicles significantly decreased. (4) Rats' uterine wall of the NS + NS and various GnRH-a groups was significantly thinner, with the endothelial layer atrophied, while the uterine wall of the GnRH-a + E2 and GnRH-a + Xiangshao granule groups was thicker obviously, with the number of vaginal folds and blood vessels also increasing. Specifically, the uterus and vagina improvements in the GnRH-a + E2 group were more obvious than in GnRH-a + NS and GnRH-a + Xiangshao granule groups. Conclusion: GnRH-a injection can reduce the levels of sex hormones E2, FSH, and LH in rats, causing perimenopausal symptoms such as hot flashes, while Xiangshao and E2 granules could significantly improve such symptoms and exert a slight oestrogenic effect, to a lesser extent than E2 does. Trial registration: Not applicable. [ABSTRACT FROM AUTHOR]

Glyphosate is a chemical compound derived from glycine, marketed as a broadspectrum herbicide, and represents one of the most widely used pesticides in the world. For a long time, it was assumed that glyphosate was harmless, either due to its selective enzymatic acting method on plants, and because commercial formulations were believed to contain only inert chemicals. Glyphosate is widely spread in the environment, the general population is daily exposed to it via different routes, including the consumption of both plant, and non-plant based foods. Glyphosate has been detected in high amounts in workers' urine, but has been detected likewise in bodily fluids, such as blood and maternal milk, and also in 60%-80% of general population, including children. Considering its massive presence, daily exposure to glyphosate could be considered a health risk for humans. Indeed, in 2015, the IARC (International Agency for Research on Cancer) classified glyphosate and its derivatives in Group 2A, as probable human carcinogens. In 2022, nevertheless, EFSA (European Food Safety Authority) stated that the available data did not provide sufficient evidence to prove the mutagenic/carcinogenic effects of glyphosate. Therefore, the European Commission (EC) decided to renew the approval of glyphosate for another 10 years. The purpose of this review is to examine the scientific literature, focusing on potential risks to human health arising from exposure to glyphosate, its metabolites and its commercial products (e.g., Roundup®), with particular regard to its mutagenic and carcinogenic potential and its effects as endocrine disrupter (ED) especially in the human reproductive system. [ABSTRACT FROM AUTHOR]

Vertebrates exhibit a left–right asymmetry from the central structures to the peripheral paired endocrine organs. However, the asymmetries in paired endocrine glands and the pathological consequences of such asymmetries remain largely unknown. The adrenal gland constitutes a pair of peripheral end organs in the neuroendocrine system, responsible for producing steroid hormones under stimuli. In the present study, the lateralized asymmetry of left and right adrenal glands in leptin receptor-deficit db/db mice was investigated. First, a morphological and histological examination showed that adrenal mass and adrenal cortex volume in db/db mice were significantly higher than in non-diabetic control mice. Then, adrenal transcriptomic and serum metabolomic analyses were performed. Adrenal steroid profiling showed that the levels of corticosterone and aldosterone in the right adrenal gland of db/db mice were two times higher than in the left one. The expression of multiple genes related to adrenal regeneration and innervation in db/db mice was reduced in contrast to the increased steroid hormone secretion. Furthermore, an examination of morphogens in asymmetric adrenal development revealed a significant differential expression of Shh and its receptor gene Ptch1. In conclusion, the present study has provided evidence that a superior steroidogenesis exists in the right adrenal gland of db/db mice and suggested that Shh signaling may play an important role in asymmetric adrenal responses in type 2 diabetes and its complications. [ABSTRACT FROM AUTHOR]

This article analyzes the results from 112 Extended One-Generation Reproductive Toxicity studies. The objective was to determine if test animals show consistent endocrine and reproductive effects within the same and across different generations and life stages. The analysis, grounded in a comprehensive Binary Matrix, included 530 observed effects and 193 unique, statistically significant associations. Associations' strength was quantified using Jaccard (J) coefficients to measure effect co-occurrence in the same study. Associated effects co-occur infrequently across the whole dataset (median J = 0.231). However, specific patterns emerged: associations of same effects across generations exhibited a higher strength (median J = 0.400) compared to associations of different effects (median J = 0.222). Notably, associations with effects observed in both the parental animals of the adult first filial generation (P1) and developing second filial generations (dF2) demonstrated J coefficients (with medians ranging from 0.300 to 0.430) that were approximately twofold higher than those of other associations. Consistently, equivalent life stage associations across generations revealed statistically significant higher association strengths for the P1 and dF2 generations (medians of 0.375 and 0.333, respectively) compared to other generations (medians of 0.200 and 0.174), possibly due to longer exposure duration and altered cross-talk between pregnant P1 dam and its conceptus. Overall, it is concluded that co-occurrence of associated effects in the same study is rather infrequent and that associations with effects in P1 and dF2 are stronger than all other associations. In general, the findings underscore the importance of independently analyzing each effect per generation due to the generally low co-occurrence rates of associated effects, challenging traditional expectations of generational continuity in toxic effects. Highlights: Identifying endocrine and reproductive toxicants is crucial for safeguarding the ability for humans to reproduce, as well as for protecting human embryos, fetuses, and children. This objective requires that the intrinsic toxic properties related to endocrine and reproductive health are thoroughly investigated. 112 recently conducted Extended One-Generation Reproductive Toxicity studies were evaluated and analyzed for endocrine and reproductive toxicity. The results show that it is much more common to observe endocrine/reproductive effects in only one generation, but not in another, within the same study (degrees of co-occurrence as low as approximately 9%). Associations with effects in the parental animals of the adult first filial generation and/or developing second filial generation are significantly stronger than all other associations (degrees of co-occurrence as high as approximately 49%). The necessity of independently analyzing each endocrine and reproductive effect within each generation is highlighted. Observed endocrine and reproductive effects should not be disregarded simply because they occur in one generation but not in another. [ABSTRACT FROM AUTHOR]

Over three decades ago, two independent groups of investigators identified free D‐aspartic and later D‐serine in specific brain nuclei and endocrine glands. This finding revealed a novel, non‐proteinogenic role of these molecules. Moreover, the finding that aged proteins from the human eye crystallin, teeth, bone, blood vessels or the brain incorporate D‐aspartic acids to specific primary protein sequences fostered the hypothesis that aging might be related to D‐amino acid isomerization of body proteins. The experimental confirmation that schizophrenia and neurodegenerative diseases modify plasma free D‐amino acids or tissue levelsnurtured the opportunity of using D‐amino acids as therapeutic agents for several disease treatments, a strategy that prompted the successful current application of D‐amino acids to human medicine. [ABSTRACT FROM AUTHOR]

Phthalate compounds that are commonly found in everyday life are diethyl phthalate (DEP). This compound is dangerous because it is carcinogenic, xenoestrogenic and has endocrine disrupting effects. The accumulation of plastic in landfill causes this compound to be identified in leachate with an existing concentration of 1,277 mg/L. Biological treatment is one of the appropriate technologies in DEP removal. The treatment involves the degradation of DEP using fungi isolated from leacheate samples. Degradation tests were carried out at varying concentrations of 2 mg/l, 4 mg/l, 6 mg/l, 8 mg/l and 10 mg/l in a test time span of 15 days and analyzed every 3 days. Concentration testing was perfomed using High Performance Liquid Chromatography (HPLC). DEP removal efficiency reached 98-99% in each concentration variation on day 9 with a specific fungal growth rate of 0.0002-0.068/day. [ABSTRACT FROM AUTHOR]

Background Neoadjuvant endocrine therapy presents an important downstaging option with lower toxicity than neoadjuvant chemotherapy in oestrogen receptor (ER)-positive early breast cancer. Meta-analysis of the effects of neoadjuvant endocrine therapy on surgical outcomes across randomized clinical trials (RCTs) and cohort studies has not previously been performed. Methods A systematic review and meta-analysis was performed to evaluate the effect of neoadjuvant endocrine therapy on surgical outcomes (PROSPERO (international prospective register of systematic reviews, 2020)) compared with surgery followed by adjuvant endocrine therapy. PubMed and EMBASE were searched to identify RCT and cohort studies between 1946 and 27 March 2024. Two independent reviewers manually screened the identified records and extracted the data. Risk of bias was assessed using the Cochrane Collaboration tools and random-effects meta-analysis was done with ReviewManager. Results The search identified 2390 articles eligible for screening. The review included 20 studies (12 cohort and 8 RCTs); 19 were included in the meta-analysis with a total of 6382 patients. Overall, neoadjuvant endocrine therapy was associated with a lower mastectomy rate compared with surgery first (risk ratio (RR) 0.53, 95% c.i. 0.44 to 0.64). Subgroup analysis showed similar improvement in the mastectomy rate in the neoadjuvant endocrine therapy group versus control group irrespective of study type (RCT: RR 0.58, 95% c.i. 0.50 to 0.66; cohorts: RR 0.48, 95% c.i. 0.33 to 0.70). There was no difference in the mastectomy rate by duration of neoadjuvant endocrine therapy (more than 4 months: RR 0.57, 95% c.i. 0.42 to 0.78; 4 months or less than 4 months: RR 0.52, 95% c.i. 0.43 to 0.64). Most of the studies were characterized by moderate-quality evidence with significant heterogeneity. Conclusion Neoadjuvant endocrine therapy is associated with a reduction in mastectomy rate. Given the moderate methodological quality of previous studies, further RCTs are required. Registration ID CRD42020209257 [ABSTRACT FROM AUTHOR]

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Background: Water bodies are affected by chemical contamination, including micropollutants, which is not fully captured by conventional chemical monitoring methods. The inclusion of integrative, effect-based in vivo and in vitro methods in standardized assessment procedures offers the possibility of bridging discrepancies between chemical and biological assessments and has already been proposed in several studies. However, there is a need to develop a comparable ecotoxicological assessment system for surface waters as for chemical and ecological status. This study aims to contribute to this discourse by investigating the temporal and spatial variation of ecotoxicological effects by assessing water grab samples of 15 different sites in central Germany over the course of 1 year using different in vitro assays. Results: The level of measured estrogenicity and anti-estrogenicity varied between the four measurement campaigns, while baseline toxicity, dioxin-like effects and mutagenicity showed relatively constant detectable effects over the study period. The impact of conventionally treated wastewater appeared to be one of the strongest influencing stressors, as direct comparisons of ecotoxicity upstream and downstream of wastewater treatment plant dischargers showed a significant increase for most of the conducted bioassays. Comparison of the measured estrogenicity with proposed threshold values showed effects within ecotoxicologically relevant ranges. Conclusions: Bioassays record ecotoxicological effects on the basis of specific modes of action, allowing whole groups of substances to be identified as pollutants. Recording ecotoxicological status in this way is a useful complement to water assessment tools and can contribute to successful water management. Although most of the assays in this study were very consistent in detecting strong anthropogenic influences, possible temporal variations of individual assays should be taken into account when planning sampling strategies to improve the comparability of results. [ABSTRACT FROM AUTHOR]

Background: Hot flashes are a common side effect of endocrine therapy (ET) that contribute to poor quality of life and decreased treatment adherence. Methods: Patients with breast cancer wo were receiving ET and experiencing hot flashes were enrolled through three parallel, randomized trials conducted in the United States, China, and South Korea. Participants were randomized to either immediate acupuncture (IA) or delayed acupuncture control (DAC). IA participants received 20 acupuncture sessions over 10 weeks, whereas DAC participants received usual care, then crossed over to acupuncture with a reduced intensity. The primary end point was a change in score on the endocrine symptom subscale of the Functional Assessment of Cancer Therapy (FACT)‐Endocrine Symptoms between baseline and week 10. Secondary end points included the hot flash score and the FACT‐Breast score. A planned pooled analysis of individual patient data was performed using longitudinal mixed models. Results: In total, 158 women with stage 0–III breast cancer were randomized (United States, n = 78; China, n = 40; South Korea, n = 40). At week 10, IA participants reported statistically significant improvements in the endocrine symptom subscale score (mean change ± standard error: 5.1 ± 0.9 vs. 0.2 ± 1.0; p =.0003), the hot flash score (−5.3 ± 0.9 vs. −1.4 ± 0.9; p <.003), and the FACT‐Breast total score (8.0 ± 1.6 vs. −0.01 ± 1.6; p =.0005) compared with DAC participants. The effect of the acupuncture intervention differed by site (p =.005). Conclusions: Acupuncture led to statistically and clinically meaningful improvements in hot flashes, endocrine symptoms, and breast cancer‐specific quality of life in women undergoing ET for breast cancer in the United States, China, and South Korea. In a pooled analysis of three parallel trials, acupuncture significantly reduced hot flashes and other endocrine symptoms in women with stage 0–III breast cancer undergoing endocrine therapy in the United States, China, and South Korea. In the women studied, acupuncture led to statistically and clinically meaningful improvements in hot flashes, endocrine symptoms, and breast cancer‐specific quality of life. [ABSTRACT FROM AUTHOR]

Introduction: The thyroid gland is one of the most important endocrine glands in the body. Goitre is an abnormal thyroid enlargement, and it is considered one of the most common endocrinal conditions encountered in the Iraqi population. Numerous pathological conditions, such as thyroid cancers, are associated with LGR5 expression. The LGR5 receptor is similar in its structure to the TSH receptor, this may explain the role of LGR5 in thyroidal pathophysiology. Objectives: Our study will attempt to explore the expression of LGR5 factor in goitrous patients and try to make a comparison between goitrous and non-goitrous (normal thyroid) ones. Materials and Methods: Participants were assigned into three groups: toxic goitre cases, non-toxic goitre cases, and controls. Histologic specimens were collected from the patients and studied by immunohistochemical staining for the LGR5 factor. These were quantitated and tested statistically against other indices such as age, gender, and the presence of thyroid toxicity. Results: Goitrous patients have been shown to express a substantially higher level of LGR5 factors as compared to controls. Patients with toxic goitre had noticeably higher LGR5 levels than patients with non-toxic goitre. Clinically-toxic patients had prominently higher LGR5 levels and in particular when they get older as compared to patients with nontoxic goitre. Conclusion: Nevertheless, the present study has a high evidence level, but it might possess some limitations. Interestingly, the study denotes the first original retrospective hospital-based case-control research in connection with the examination of LGR5 expression in thyroid tissues of patients from the Iraqi population. [ABSTRACT FROM AUTHOR]

Aims Peripheral cortisol represents one biological measure of the hypothalamic–pituitary–adrenal (HPA) axis, a significant component of the stress system, which is altered by chronic alcohol consumption. However, whether heavy alcohol use affects the HPA axis differentially between the sexes and whether basal cortisol levels are a biomarker of prospective alcohol intake is unknown. Methods We recruited light moderate (LM) and binge-heavy (BH) drinkers of alcohol (n  = 118). Repeated fasting morning cortisol levels were studied over a 2-hour period to assess basal levels while participants underwent a neuroimaging scan. Results Significantly higher average cortisol levels in BH compared to LM groups across four timepoints were observed (P  < .018). Overall sex differences were observed with women showing higher initial cortisol levels at the first timepoint with a blunted decrease over the morning relative to men (P  < .003). Average morning cortisol differentially predicted prospective future 30-day daily reports of alcohol consumption by sex and group, such that LM males had a positive significant relationship and BH males had a negative non-significant relationship between cortisol and drinking. Conclusions Findings indicate that morning plasma cortisol is upregulated in the BH vs. LM group. Although females had higher initial morning cortisol levels, BH males showed a dysregulated negative relationship between stress and binge drinking in contrast to the LM group. Future work should further investigate the role of cortisol and other stress hormones as biomarkers of problematic drinking behaviors in men and women. [ABSTRACT FROM AUTHOR]

Low energy availability, particularly when problematic (i.e., prolonged and/or severe), has numerous negative consequences for health and sports performance as characterized in relative energy deficiency in sport. These consequences may be driven by disturbances in endocrine function, although scientific evidence clearly linking endocrine dysfunction to decreased sports performance and blunted or diminished training adaptations is limited. We describe how low energy availability-induced changes in sex hormones manifest as menstrual dysfunction and accompanying hormonal dysfunction in other endocrine axes that lead to adverse health outcomes, including negative bone health, impaired metabolic activity, undesired outcomes for body composition, altered immune response, problematic cardiovascular outcomes, iron deficiency, as well as impaired endurance performance and force production, all of which ultimately may influence athlete health and performance. Where identifiable menstrual dysfunction indicates hypothalamic-pituitary-ovarian axis dysfunction, concomitant disturbances in other hormonal axes and their impact on the athlete's health and sports performance must be recognized as well. Given that the margin between podium positions and "losing" in competitive sports can be very small, several important questions regarding low energy availability, endocrinology, and the mechanisms behind impaired training adaptations and sports performance have yet to be explored. [ABSTRACT FROM AUTHOR]

Immune checkpoint inhibitors (ICIs) are associated with multiple endocrine side effects, including thyroid disfunctions. In addition, the efficacy and safety profiles of ICIs in the pediatric population need clarification. Here, we discuss the main evidence regarding the efficacy and thyroid toxicities of ICIs in children. [ABSTRACT FROM AUTHOR]

ABSTRACT: Background: The thyroid gland is one of the largest endocrine glands in the body, secreting thyroxine (T4) and triiodothyronine (T3). Mild hypothyroidism can have negative consequences for a variety of tissues, even though clinically the patients are euthyroid. Many research studies were conducted to evaluate the serum creatinine levels of people with hypothyroidism; however, relatively little research was conducted to evaluate serum urea and serum creatinine levels in subclinical hypothyroidism. As a result, the current study was carried out to investigate urea, uric acid, and creatinine levels in hypothyroidism. Objectives: Our study aimed to determine and correlate the levels of urea, uric acid and creatinine in newly diagnosed primary hypothyroidism cases. Materials and Methods: In this cross-sectional study, 96 newly diagnosed cases of primary hypothyroidism were included. The findings were correlated with 20–60-year-old and sex-matched cases. Serum urea was determined by the kinetic method (Glutamate Dehydrogenase Method), serum uric acid by the uricase method and serum creatinine by Jaffe's method in Erba's Mannheim fully automated analyser. Result: This study showed a positive correlation between uric acid and thyroid stimulating hormone (TSH) and a negative correlation between urea and creatinine. There was no statistical significance in the mean values of urea, uric acid and creatinine but an increased level of urea, uric acid and creatinine was seen in the age group 20–30 years when compared with the other age groups. Conclusion: The study concludes that serum urea showed a positive correlation with TSH, whereas uric acid and creatinine showed a negative correlation with TSH, and there was no statistical significance in the mean values of urea, uric acid and creatinine in hypothyroid patients. [ABSTRACT FROM AUTHOR]

Objective: Species of the genus Achillea (from the family Compositae or Asteraceae) are widely used for their numerous pharmacological properties. The present paper reviews pharmacological actions and their possible underlying molecular mechanisms reported for various species of Achillea. Materials and Methods: Various databases including PubMed, Science Direct, and Scopus were used. Results: Immunosuppressive, anti-inflammatory and anti-oxidant effects were shown for these plants. In addition, it was shown that these plants pose wound-healing properties and antimicrobial effects on various bacteria as well as antitumor effects on different cell lines. Achillea species showed anti-arrhythmic, anti-thrombotic, vasorelaxant, anti-hyperlipidemic, anti-hypertensive, hepatoprotective and gastroprotective effects. In addition, the plants showed different endocrine effects such as anti-diabetic, estrogenic and antispermatogenic properties. Neurological effects of the plants also included anti-nociceptive and anti-anxiety actions. Clinical studies also indicated therapeutic effect of A. millefolium on multiple sclerosis, chemotherapy-induced oral mucositis in cancer patients, and dysmenorrhea but did not affect atopic dermatitis. Conclusion: Achillea species could be of therapeutic potential for treating of a wide range of diseases but further investigations are needed regarding the other properties of Achillea plants. [ABSTRACT FROM AUTHOR]

Redox homeostasis is a crucial phenomenon that is obligatory for maintaining the healthy status of cells. However, the loss of redox homeostasis may lead to numerous diseases that ultimately result in a compromised quality of life. Skeletal muscle is an endocrine organ that secretes hundreds of myokines. Myokines are peptides and cytokines produced and released by muscle fibers. Skeletal muscle secreted myokines act as a robust modulator for regulating cellular metabolism and redox homeostasis which play a prime role in managing and improving metabolic function in multiple organs. Further, the secretory myokines maintain redox homeostasis not only in muscles but also in other organs of the body via stabilizing oxidants and antioxidant levels. Myokines are also engaged in maintaining mitochondrial dynamics as mitochondria is a central point for the generation of reactive oxygen species (ROS). Ergo, myokines also act as a central player in communicating signals to other organs, including the pancreas, gut, liver, bone, adipose tissue, brain, and skin via their autocrine, paracrine, or endocrine effects. The present review provides a comprehensive overview of skeletal muscle‐secreted myokines in managing redox homeostasis and quality of life. Additionally, probable strategies will be discussed that provide a solution for a better quality of life. [ABSTRACT FROM AUTHOR]

Laser speckle coherence imaging (LSCI) is an emerging imaging modality that enables noninvasive visualization and assessment of tissue perfusion and microcirculation. In this article, we evaluated LSCI in imaging perfusion in clinical oncology through a systematic review of the literature. The inclusion criterion for the literature search in PubMed, Web of Science and Scopus electronic databases was the use of LSCI in clinical oncology, meaning that all animal, phantom, ex vivo, experimental, research and development, and purely methodological studies were excluded. Thirty-six articles met the inclusion criteria. The anatomic locations of the neoplasms in the selected articles were brain (5 articles), breasts (2 articles), endocrine glands (4 articles), skin (12 articles), and the gastrointestinal tract (13 articles). While LSCI is emerging as an appealing imaging modality, it is crucial for more clinical sites to initiate clinical trials. A lack of standardized protocols and interpretation guidelines are posing the most significant challenge. [ABSTRACT FROM AUTHOR]

Purpose: Maternal cortisol levels in pregnancy may support the growth of or adversely affect fetal organs, including the brain. While moderate cortisol levels are essential for fetal development, excessive or prolonged elevations may have negative health consequences for both the mother and the offspring. Little is known about predictors of altered hypothalamic–pituitary–adrenal (HPA) axis activity during pregnancy. This study examined maternal hair cortisol concentration (HCC) in the 3rd trimester of pregnancy in relation to severe psychopathology. Methods: Hair samples were collected from 69 women, 32 with a lifetime diagnosis of severe mental disorders (bipolar I or II disorder, moderate or severe depressive disorder, schizophrenic spectrum disorder), and 37 non-clinical controls. Hair samples were collected during the 3rd trimester, and liquid chromatography tandem mass spectrometry was used for cortisol assessment. Psychiatric diagnosis and current level of symptomatic functioning were assessed using the structured clinical interview from the DSM-5 and the global assessment of functioning scale. Results: Women with a lifetime diagnosis of severe mental illness had significantly elevated HCC compared to controls. Poorer current symptomatic functioning was also significantly associated with elevated HCC in pregnancy. Conclusions: The implications of alterations in HCC on both maternal and infant health need further study. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Primary hyperaldosteronism with type 3 autoimmune polyendocrine syndrome was a rare combination of both hyper‐ and hypoendocrine gland function. Comprehensive treatment including surgery and replacement therapy might be an effective strategy. Primary aldosteronism (PA) is a common cause of secondary hypertension originating from hormones. Type 3 autoimmune polyendocrine syndrome (APS‐3) is characterized by the simultaneous or subsequent occurrence of autoimmune‐mediated endocrine gland damage, except for Addison disease. Here we reported an extremely rare case of a 63‐year‐old woman with PA and APS‐3 who initially presented with hypertension (HT). The APS‐3 of this patient mainly exhibited type 1 diabetes mellitus (T1DM) and Hashimoto's thyroiditis. She underwent the adrenal adenoma resection with a histopathologic diagnosis of adrenal cortical adenoma. After surgery, the HT of this patient was immediately reversed, and the concentration of serum potassium went back to normal. Then, this patient was administered with replacement therapy of insulin and levothyroxine sodium tablets (L‐T4). [ABSTRACT FROM AUTHOR]

Introduction: The size of the pituitary gland varies in normal subjects according to age, sex, and other conditions. The knowledge of normal range of pituitary gland size is important to enable radiologists to suggest what might be an abnormal pituitary gland. Measurements regarding the normal pituitary gland for various age ranges are helpful in diagnosing pathologies in the pituitary gland. Aim: To study the shape, size and mean normal volume of pituitary gland in different age groups of both genders of normal subjects with Magnetic Resonance Imaging (MRI) and to produce accurate data for the dimensions of the normal pituitary gland in 605 patients. Materials and Methods: The study was a cross sectional study carried out in the Department of Radio-diagnosis, SSG Hospital, Vadodara, Gujarat. MRI Brain studies of 605 patients were reviewed which includes 317 males and 288 females, ranging from one year to 80 years of age. Patients with pituitary gland or other endocrine abnormalities were excluded from the study. All MRI images were acquired on GE 1.5Tesla MRI machine using standard head coil. Mid-sagittal T2 weighted image were the pituitary stalk could be seen is selected to study the shape and to measure the Anteroposterior and craniocaudal dimensions and coronal T2 FLAIR image were the pituitary stalk could be identified is selected for measuring transverse dimension. The volume of the Pituitary gland was calculated using the formula volume = Anteroposterior (AP) diameter x Transverse (TR) diameter x craniocaudal (CC) diameter x 0.52. Statistical calculations were done by Software Open Epi Version 3 for epidemiological age groups. Results: The observation was divided into eight groups according to the age. Mean height of pituitary gland in female subjects of each age group was greater than that of male subjects in the same group except for age group 51 to 60 years. Height of pituitary gland reached a maximum in the 11 to 20 years of age group in both males and females, after which, there was a decline in the pituitary height in the subsequent age groups. The mean pituitary height in the age group 1-10 years was 4.41±0.80 mm. In the age group 11-20 years, mean pituitary height was 6.46±1.35 mm. In the age group 21-30 years it was 6.21±1.26 mm and in 31-40 years age group it was 6.11±1.10 mm whereas in 41-50 years age group it was 6.10±1.36 mm. In 51-60 years age group it was 5.76±1.25 mm, and in 61-70 years age group it was 5.70±1.22 mm, and in individuals above 70 years of age, mean pituitary height was 5.56±1.23 mm. In all the age groups and in both sexes, the commonest shape was flat which was seen in 56% of people followed by concave shape, seen in 33% and convex shape, seen in 11% people. The mean pituitary volume in the age group 1-10 years was 150±68.40 mm3 in males and 185±102.36 mm3 in females and in the age group 11-20 years the mean pituitary volume in males was 355±132 mm3 and in females was 398±145 mm3 . In the age group 21-30 years, the mean pituitary volume in males was 364±122 mm3 and in females was 370±105 mm3 . In the age group 31-40 years, the mean pituitary volume in males was 327±136 mm3 and in females was 377±121 mm3 . In 41-50 age groups mean pituitary volume in males was 324±156 mm3 and in females it was 408±147 mm3 . In the age group 51-60 years, mean pituitary volume in males was 393±173 mm3 and in females it was 361±138 mm3 . In the age group 61-70 years, mean pituitary volume in males was 347±149 mm3 and in females was 366±179 mm3 .In individuals above 70 years of age the mean pituitary volume in males was 326±162 mm3 and in females it was 396±136 mm3 . Conclusion: Normal variations in size and shape of the pituitary gland are necessary to identify the abnormal glands. The size of the pituitary gland needs to be compared with the normal range of height and volume of the pituitary gland in corresponding age and gender groups before labelling it as normal or abnormal. In cases with borderline abnormality in size and shape of the pituitary gland, further evaluation by dynamic contrast study should be carried out to look for pathological lesions. [ABSTRACT FROM AUTHOR]

The thyroid is an endocrine gland that produces and secretes triiodothyronine (T3), and thyroxine (T4) hormones. These hormones are essential for maintaining body homeostasis. Indian costus is a medicinal plant used in the treatment of thyroid disorders. The aim of the study is to use Indian costus in its particles and nanoparticles to treat the thyroid, which was infected with an overdose of melatonin. Nano Indian costus was prepared using microwave plasma and pulsed laser deposition (PLD). To determine the most effective technique for creating the Indian costus nanoparticles, the material was examined using an atomic force microscope (AFM) in its bulk and nanoparticle forms. It was found that the microwave plasma method gave better results than PLD, where the average nanoparticle diameter was 21.11nm for the microwave plasma method and 40.02nm for the PLD. Thyroid hormones regained their normal levels of T3 and T4 after receiving Indian costus nanoparticles prepared by microwave plasma, which proved more effective than Indian costus nanoparticles prepared by PLD. [ABSTRACT FROM AUTHOR]

Hypoxia is a common environmental stressor in aquatic ecosystems, and during the cultivation process, Megalobrama amblycephala is prone to death because it is hypoxia-intolerant, which brings huge economic losses to farmers. The pituitary gland is a crucial endocrine gland in fish, and it is mainly involved in the secretion, storage, and regulation of hormones. In the present study, we compared the transcriptional responses to serious hypoxia in the pituitary gland among hypoxia-sensitive (HS) and hypoxia-tolerant (HT) M. amblycephala and a control group that received a normal oxygen supply (C0). The fish were categorized according to the time required to lose balance during a hypoxia treatment. A total of 129,251,170 raw reads were obtained. After raw sequence filtering, 43,461,745, 42,609,567, and 42,730,282 clean reads were obtained for the HS, HT, and C0 groups, respectively. A transcriptomic comparison revealed 1234 genes that were differentially expressed in C0 vs. HS, while 1646 differentially expressed genes were obtained for C0 vs. HT. In addition, the results for HS vs. HT showed that 367 upregulated and 41 downregulated differentially expressed genes were obtained for a total of 408 differentially expressed genes. A KEGG analysis of C0 vs. HS, C0 vs. HT, and HS vs. HT identified 315, 322, and 219 enriched pathways, respectively. Similar hypoxia-induced transcription patterns suggested that the downregulated DEGs and enriched pathways were related to pathways of neurodegeneration in multiple diseases, pathways in cancer, thermogenesis, microRNAs in cancer, diabetic cardiomyopathy, and renin secretion. However, in the upregulated DEGs, the PI3K-Akt signaling pathway (C0 vs. HS), microRNAs in cancer (C0 vs. HT), and HIF-1 signaling pathway (HS vs. HT) were significantly enriched. There is a lack of clarity regarding the role of the pituitary gland in hypoxic stress. These results not only provide new insights into the mechanism by which pituitary tissue copes with hypoxia stress in M. amblycephala but also offer a basis for breeding M. amblycephala with hypoxia-resistant traits. [ABSTRACT FROM AUTHOR]

Nephrotic syndrome is a clinical syndrome characterized by massive proteinuria, called nephrotic range proteinuria (over 3.5 g per day in adults or 40 mg/m2 per hour in children), hypoalbuminemia, oncotic edema, and hyperlipidemia, with an increasing incidence over several years. Nephrotic syndrome carries severe morbidity and mortality risk. The main pathophysiological event in nephrotic syndrome is increased glomerular permeability due to immunological, paraneoplastic, genetic, or infective triggers. Because of the marked increase in the glomerular permeability to macromolecules and the associated urinary loss of albumins and hormone-binding proteins, many metabolic and endocrine abnormalities are present. Some of them are well known, such as overt or subclinical hypothyroidism, growth hormone depletion, lack of testosterone, vitamin D, and calcium deficiency. The exact prevalence of these disorders is unknown because of the complexity of the human endocrine system and the differences in their prevalence. This review aims to comprehensively analyze all potential endocrine and hormonal complications of nephrotic syndrome and, vice versa, possible kidney complications of endocrine diseases that might remain unrecognized in everyday clinical practice. [ABSTRACT FROM AUTHOR]

Extramammary Paget disease (EMPD) is a rare cutaneous intraepithelial adenocarcinoma, which is mostly distributed in areas with sweat gland cells and mainly occurs in the anogenital skin of women. The male genital tract involvement is extremely rare and often occurs with other malignant tumors. Paget's disease in the scrotum with sweat gland carcinoma is even rarer. In the first report of scrotal endocrine sweat gland carcinoma associated with Paget disease by Saidi et al. in 1997, no more than 50 cases have been reported in the relevant research worldwide. Early EMPD combined with sweat gland carcinoma is mainly surgical treatment, and there is no standard treatment plan for advanced EMPD with sweat gland carcinoma. Previous article has reported that chemotherapy such as paclitaxel, fluorouracil, platinum, and vinblastine and molecular targeted therapy based on the genetic test results of patients have certain efficacy. Here, we report a 79-year-old male case diagnosed with human epidermal growth factor receptor 2 (HER-2) overexpression, which was effectively controlled by chemotherapy and anti--HER-2 treatment such as pyrotinib. [ABSTRACT FROM AUTHOR]