Loss of vagal integrity disrupts immune components of the microbiota-gut-brain axis and inhibits the effect of Lactobacillus rhamnosus on behavior and the corticosterone stress response.

The vagus nerve is one of the major signalling components between the gut microbiota and brain. However, the exact relationship between gut-brain signaling along the vagus and the effects of gut microbes on brain function and behaviour is unclear. In particular, the relationship between the vagus nerve and immune signaling, that also appears to play a critical role in microbiota-gut-brain communication, has not been delineated. The aim of the present study was to determine the effect of subdiaphragmatic vagotomy on peripheral and central immune changes associated with the anxiolytic actions of L.rhamnosus. Male mice underwent vagotomy or sham surgery, followed by administration of L.rhamnosus for 14 days. L.rhamnosus administration following sham surgery resulted in reduced anxiety-like behaviour, and an attenuation of the hypothalamic-pituitary-adrenal axis (HPA axis), as indicated by reduced plasma corticosterone after acute restraint stress. These effects were associated with an increase in splenic T regulatory cells and a decrease in activated microglia in the hippocampus. The anxiolytic effects, HPA modulation and increase in T regulatory cells were prevented by vagotomy, whereas vagotomy alone led to a significant increase in activated microglia in the hippocampus that was not altered with L.rhamnosus treatment. Thus, both microbe induced and constitutive vagal signaling influences critical immune components of the microbiota-gut-brain axis. These findings suggest that, rather than acting as a direct neural link to the central nervous system, the role of the vagus nerve in gut-microbe to brain signalling is as an integral component of a bi-directional neuroimmunoendocrine pathway.

Minipuberty in Klinefelter syndrome: Current status and future directions.

Klinefelter syndrome is highly underdiagnosed and diagnosis is often delayed. With the introduction of non-invasive prenatal screening, the diagnostic pattern will require an updated description of the clinical and biochemical presentation of infants with Klinefelter syndrome. In the first months of life, the hypothalamic-pituitary-gonadal (HPG)-axis is transiently activated in healthy males during the so-called minipuberty. This period represents a "window of opportunity" for evaluation of the HPG-axis before puberty and without stimulation tests. Infants with Klinefelter syndrome present with a hormonal surge during the minipuberty. However, only a limited number of studies exist, and the results are contradictory. Further studies are needed to clarify whether infants with Klinefelter syndrome present with impaired testosterone production during the minipuberty. The aim of this review is to describe the clinical and biochemical characteristics of the neonate and infant with Klinefelter syndrome with special focus on the minipuberty and to update the clinical recommendations for Klinefelter syndrome during infancy.

The influence of hypertensive environment on adipose tissue remodeling measured by fluorescence lifetime imaging in spontaneously hypertensive rats.

There is a lack of information correlating low adiposity with hypertension experienced by Spontaneous Hypertensive Rats (SHR) or overweight and normotension in Wistar-Kyoto (WKY). We aimed to investigate this lipodystrophy phenomenon by measuring fluorescence lifetime (FLIM), optical redox ratio (ORR), serum levels of hypothalamic-pituitary-adrenal (HPA) and/or hypothalamic-pituitary-thyroid (HPT) hormones axes between Wistar, WKY and SHR before and after establishment of hypertension. Under high blood pressure, we evaluated serum adipokines. Brown adipose tissue was characterized as lower ORR and shorter FLIM compared to white adipose tissue. HPT axis showed a crucial role in the SHR adipose tissue configuration by attenuating whitening. The increased adiposity in WKY may act as a preventive agent for hypertension, since SHR, with low adiposity, establishes the disease. The hypertensive environment can highlight key adipokines that may result in new therapeutic approaches to the treatment of adiposity dysfunctions and hypertension.

Adrenal gland size in obstructive sleep apnea: Morphological assessment of hypothalamic pituitary adrenal axis activity.

OBJECTIVES: The association of obstructive sleep apnea (OSA) with hypothalamic pituitary adrenal (HPA) axis activation has not been fully understood from results of previous studies using hormonal assessments. We aimed to investigate the relationship between adrenal size, a potential marker reflecting HPA axis activity, and sleep parameters related to OSA. METHODS: We retrospectively reviewed data on 284 consecutive adult patients aged 20 to 80 y who had undergone polysomnography and abdominal computed tomography (CT). OSA was defined as none/mild (apnea-hypopnea index [AHI] <15, n = 75), moderate (AHI 15 to 30, n = 80), and severe OSA (AHI ≥30, n = 129). Widths of adrenal body and limbs were measured by abdominal CT. RESULTS: Adrenal size was greater in participants with severe OSA than in those with none/mild or moderate OSA (adrenal body width: 6.03 mm, none/mild OSA; 6.09 mm, moderate OSA; 6.78 mm, severe OSA; p <0.001; adrenal limb width: 3.75 mm, none/mild OSA; 3.95 mm, moderate OSA; 4.26 mm, severe OSA, p <0.001). Multivariate regression analysis showed that not the 3% oxygen desaturation index and time of SpO2 <90% but a higher arousal index was the only determinant factor for increased adrenal limb width (ß = 0.27, p <0.001) after adjusting for other variables that could affect adrenal size. Neither the arousal index nor hypoxic parameters were associated with adrenal body width. CONCLUSIONS: Results indicated that adrenal glands may enlarge in response to longstanding sleep fragmentation, suggesting the involvement of OSA in HPA axis augmentation.

Partial Reconstitution of the Hypothalamo-Pituitary Axes After Pituitary Stalk Sectioning and Specific Magnetic Resonance Imaging Findings.

BACKGROUND: Pituitary stalk sectioning is only essential in cases of craniopharyngioma originating from the stalk or metastatic tumor to the stalk. Some patients can discontinue postoperative antidiuretic hormone (ADH) supplementation with special conditions. METHODS: Sixty-three patients with craniopharyngiomas who were treated by surgery with pituitary stalk sectioning were included in this study. Great care was taken to preserve the fine arteries running along the lateral walls of the third ventricle. Removal rates, change of endocrinologic status, and magnetic resonance imaging (MRI) findings were investigated. RESULTS: Total removal was achieved in 52 of 54 patients in initial surgery (96.3%), and in 5 of 9 patients in retreatment (55.6%). ADH supplementation was required in all patients from the day of surgery, but was discontinued in 29 of 54 patients among the initial surgery group (53.7%) and in 2 of 9 patients among the retreatment group (22.2%). Preservation of thyroid hormone secretion was observed in 24 of 31 patients who could discontinue ADH (77.4%), but only in 12 of 32 patients who could not discontinue ADH (37.5%). Recovery from diabetes insipidus (DI) was significantly associated with preservation of thyroid function (P < 0.01). Postoperative MRI showed that part of the hypothalamus was enhanced in patients with recovery from DI. CONCLUSIONS: Total removal was achieved in 91% of all cases. Half of the patients could discontinue ADH supplementation, which was associated with preservation of thyroid function. The findings of hypothalamic enhancement on postoperative MRI may be associated with recovery from DI.

Functional gastrointestinal disorders and gut-brain axis: What does the future hold?

Despite their high prevalence, lack of understanding of the exact pathophysiology of the functional gastrointestinal disorders has restricted us to symptomatic diagnostic tools and therapies. Complex mechanisms underlying the disturbances in the bidirectional communication between the gastrointestinal tract and the brain have a vital role in the pathogenesis and are key to our understanding of the disease phenomenon. Although we have come a long way in our understanding of these complex disorders with the help of studies on animals especially rodents, there need to be more studies in humans, especially to identify the therapeutic targets. This review study looks at the anatomical features of the gut-brain axis in order to discuss the different factors and underlying molecular mechanisms that may have a role in the pathogenesis of functional gastrointestinal disorders. These molecules and their receptors can be targeted in future for further studies and possible therapeutic interventions. The article also discusses the potential role of artificial intelligence and machine learning and its possible role in our understanding of these scientifically challenging disorders.

Clinical Consultation Guide on Imaging in Male Infertility and Sexual dysfunction.

Imaging can benefit clinicians in evaluating men with infertility or sexual dysfunction by giving an overview of a patient's overall clinical condition before undertaking an invasive procedure. An understanding of the limitations and advantages of image modalities used in clinical practice will ensure that clinicians can optimize patient care with imaging when necessary. PATIENT SUMMARY: The objective of this article was to review the current literature on imaging modalities used for the diagnosis and management of male infertility and sexual dysfunction. An understanding of the advantages and limitations of these imaging modalities will ensure that clinicians can optimize patient care with imaging when necessary.

Correlations between changes in the hypothalamic-pituitary-adrenal axis and neurochemistry of the anterior cingulate gyrus in postpartum depression.

BACKGROUND: This study aimed to investigate associations between indicators of hypothalamic-pituitary-adrenal axis (HPA) functioning and metabolite levels in the anterior cingulate gyrus (ACG) of women with postpartum depression (PPD). METHODS: The sample (mean age = 28.5 ±â€¯4.6 years) consisted of 20 women with PPD and 19 postpartum euthymic (PPE) women. Brain metabolites were quantified by proton magnetic resonance spectroscopy (1H-MRS). Salivary cortisol samples were collected upon awakening and 30 min and 12 h later, at 20.6 ±â€¯6.6 (PPD) and 23.0 ±â€¯7.4 (PPE) weeks after childbirth. RESULTS: There were no significant differences between groups in respect to metabolite levels in the ACG. Compared with PPE, PPD women had less diurnal variation (DVr%). In the PPD group, positive correlations were found between DVr% and myo-inositol (mI/Cr) levels, and between cortisol awakening response (CARi%) and glutamate + glutamine (Glx/Cr) levels. The correlation between CARi% and Glx/Cr remained significant even after controlling for the interval, in weeks, from birth and MR spectroscopy and to hormonal data collection, and the use of contraceptives. LIMITATIONS: The limitations of the study include the small sample size and the use of oral contraceptives by around half of the sample. CONCLUSIONS: In the remote postpartum period (mean 21.8 ±â€¯6.9 weeks) and in the presence of depressive episodes, the decreased responsiveness of the HPA axis after awakening and a smaller decrease in cortisol levels over the day were associated with lower levels of metabolites in the ACG. These results may contribute to the development of biological models to explain the etiology of PPD.

Prediction of pituitary stalk position in pituitary adenomas by visualization of the hypothalamo-hypophyseal tract using diffusion tensor imaging tractography.

The preservation of pituitary stalk during surgery is very important for neurosurgeons. Sometimes, it is hard to identify the pituitary stalk in the operation. The hypothalamo-hypophyseal tract (HHT) projects through the pituitary stalk to the posterior pituitary gland. If the HHT can be identified, the position of pituitary stalk will be visualized. The diffusion tensor imaging (DTI) fiber tracking technique has been widely used for the quantitative assessment of the white matter integrity and thus may be suitable for the evaluation of the HHT.DTI was used to track the HHT in 11 patients with pituitary adenoma, and the location of the tract was compared with the pituitary stalk of postoperative image in those patients.The fiber tracking and 3D visualization of the HHT were successfully carried out in all 11 patients. Comparison between the tract and pituitary stalk of postoperative magnetic resonance imaging (MRI) was carried out in 9 patients. The results revealed that the position of tract was consistent with the pituitary stalk of postoperative MRI image in 8 patients (88.9%). The properties of tract showed that the median number of tract was 5.18 ±â€Š7.00, the median fractional anisotropy (FA) was 0.14 ±â€Š0.04, and the median length was 28.81 ±â€Š7.94 mm.HHT can be tracked and visualized with the DTI-FT technique. It will be helpful to identify the location of pituitary stalk preoperatively.

Pituitary gland shrinkage in bipolar disorder: The role of gender.

BACKGROUND: Hyperactivity of the Hypothalamic-Pituitary-Adrenal Axis (HPAA) has been consistently reported in mood disorders. However, only few studies investigated the Pituitary gland (PG) in Bipolar Disorder (BD) and the results are so far contrasting. Therefore, the aim of this study is to explore the integrity of the PG as well as the role of gender and the impact of clinical measurements on this structure in a sample of BD patients compared to healthy controls (HC). METHODS: 34 BD patients and 41 HC underwent a 1.5 T MRI scan. PG volumes were manually traced for all subjects. Psychiatric symptoms were assessed by means of the Brief Psychiatry Rating Scale, the Hamilton Depression Rating Scale and the Bech Rafaelsen Mania Rating Scale. RESULTS: We found decreased PG volumes in BD patients compared to HC (F = 24.9, p < 0.001). Interestingly, after dividing the sample by gender, a significant PG volume decrease was detected only in female BD patients compared to female HC (F = 9.1, p < 0.001), but not in male BD compared to male HC (F = -0.12, p = 0.074). No significant correlations were observed between PG volumes and clinical variables. CONCLUSIONS: Our findings suggest that BD patients have decreased PG volumes, probably due to the long-term hyperactivity of the HPAA and to the consequent strengthening of the negative feedback control towards the PG volume itself. This alteration was particularly evident in females, suggesting a role of gender in affecting PG volumes in BD. Finally, the absence of significant correlations between PG volumes and clinical variables further supports that PG disruption is a trait feature of BD, being independent of symptoms severity and duration of treatment.

Predicting pituitary stalk position by in vivo visualization of the hypothalamo-hypophyseal tract in craniopharyngioma using diffusion tensor imaging tractography.

The pituitary stalk (PS) is crucial to endocrine function and water-electrolyte equilibrium. Preservation of the PS during craniopharyngioma (CP) surgery is critical; however, in a pathological state, it is difficult to identify. The hypothalamo-hypophyseal tract (HHT) connects the hypothalamus and the posterior pituitary gland and projects through the PS. Thus, visualization of the HHT can help locate the PS. Preoperative visualization of the neural fasciculus has been widely achieved using diffusion tensor imaging (DTI) tractography. Therefore, this study evaluated the use of DTI tractography to identify and characterize the human HHT. We used DTI tractography to track the HHT in 10 patients with CP and compared the location of the tract with the intraoperative view of the PS in these patients. We successfully tracked the HHT in nine patients, indicating that delineating and quantifying the tracked HHT using this method is feasible. In addition, we found that the tract was consistent with the intraoperative view of the PS in seven out of eight patients (87.50%). Finally, we found that the mean number of tracts was 7.11 ± 12.28, the mean fractional anisotropy (FA) was 0.11 ± 0.04, and the mean tract length was 24.22 ± 9.39 mm. Taken together, our results demonstrate that the HHT can be visualized and characterized with DTI even in a clinical application, which may aid in preoperative identification of the PS. Characterization of the tracked HHT with this technique could also be used to advance our understanding of the HHT.

A study of neuroendocrine dysfunction in patients of tuberculous meningitis.

BACKGROUND: Endocrine dysfunction is known to occur in various infectious diseases of the brain. The neuroendocrine dysfunction is not well studied in patients of Tuberculous meningitis (TBM). In this study, we aimed at knowing pattern of endocrine dysfunction in newly diagnosed patients of tuberculous meningitis, structural changes occurring in hypothalamic-pituitary region, assessing its predictors and correlative factors related to outcome. MATERIALS AND METHODS: This was a prospective observational study. All newly diagnosed patients of tuberculous meningitis were subjected to clinical, laboratory, and hormonal evaluation along with neuroimaging of hypothalamic-pituitary region. All the patients were treated with antituberculous drugs along with corticosteroids as per WHO guidelines. The clinical outcomes of the patients were assessed at the end of 3months. RESULTS: Out of 115 patients enrolled in the study, endocrine dysfunction was seen in 62 (53.9%) patients. Out of these 62 patients, single axis involvement was seen in 35 (30.4%) patients, while multiple axis dysfunction was observed in 27 (23.5%) patients. Most common hormonal axis involved was gonadotropic axis (33.9%) followed by hyperprolactinemia (22.6%), thyrotropic axis (17.4%), corticotropic axis (13%), SIADH (Syndrome of Inappropriate Antidiuretic Hormone secretion) (9.6%) and somatotropic axis (7.8%). None had diabetes insipidus. The presence of multiple cranial nerve palsies, hypotension, stage II and III of TBM, baseline MBI ≤12 and basal exudates were significantly higher in endocrine dysfunction group, while the presence of basal exudates independently predicted the occurrence of endocrine dysfunction on multivariate analysis. Though the poor outcome was significantly higher in endocrine dysfunction group at the end of 3months, on multivariate analysis factors independently associated with poor outcome were the presence of altered sensorium and stage III of TBM. CONCLUSION: Endocrine dysfunction occurs in a significant proportion of patients with tuberculous meningitis. The presence of basal exudates is significantly associated with the occurrence of endocrine dysfunction. Patients with endocrine dysfunction had a poorer outcome although it was not an independent predictor of the same nor associated with increased mortality.

HPA Axis Genes, and Their Interaction with Childhood Maltreatment, are Related to Cortisol Levels and Stress-Related Phenotypes.

Stress responses are controlled by the hypothalamus pituitary adrenal (HPA)-axis and maladaptive stress responses are associated with the onset and maintenance of stress-related disorders such as major depressive disorder (MDD). Genes that play a role in the HPA-axis regulation may likely contribute to the relation between relevant neurobiological substrates and stress-related disorders. Therefore, we performed gene-wide analyses for 30 a priori literature-based genes involved in HPA-axis regulation in 2014 subjects (34% male; mean age: 42.5) to study the relations with lifetime MDD diagnosis, cortisol awakening response, and dexamethasone suppression test (DST) levels (subsample N=1472) and hippocampal and amygdala volume (3T MR images; subsample N=225). Additionally, gene by childhood maltreatment (CM) interactions were investigated. Gene-wide significant results were found for dexamethasone suppression (CYP11A1, CYP17A1, POU1F1, AKR1D1), hippocampal volume (CYP17A1, CYP11A1, HSD3B2, PROP1, AVPRA1, SRD5A1), amygdala volume (POMC, CRH, HSD3B2), and lifetime MDD diagnosis (FKBP5 and CRH), all permutation p-values<0.05. Interactions with CM were found for several genes; the strongest interactions were found for NR3C2, where the minor allele of SNP rs17581262 was related to smaller hippocampal volume, smaller amygdala volume, higher DST levels, and higher odds of MDD diagnosis only in participants with CM. As hypothesized, several HPA-axis genes are associated with stress-related endophenotypes including cortisol response and reduced brain volumes. Furthermore, we found a pleiotropic interaction between CM and the mineralocorticoid receptor gene, suggesting that this gene plays an important moderating role in stress and stress-related disorders.

Posibles consecuencias en los niños del uso de gel de testosterona por sus padres / Potential consequences in children of a testosterone gel used by their fathers

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Adrenal crisis while on high-dose steroid treatment: what rheumatologist should consider?

Steroid treatment is commonly recommended for autoimmune disorders in rheumatology practice. While adrenal crisis may occur upon existence of an inducing factor in patients with known or unknown adrenal insufficiency as well as in those with a suppressed hypothalamic-pituitary-adrenal (HPA) axis due to chronic steroid use, addisonian crisis rarely develops in patients on supraphysiological doses of steroid and, when emerged, it might be very difficult to recognize. Here, we present a patient who developed adrenal crisis while receiving high-dose methylprednisolone treatment due to retroperitoneal fibrosis and we also discuss possible mechanisms with a brief literature review.

The Utility of Routine Ultrasound in the Diagnosis and Management of Adolescents with Abnormal Uterine Bleeding.

STUDY OBJECTIVE: Despite the fact that most cases of abnormal uterine bleeding (AUB) in adolescence are due to an immature hypothalamic-pituitary-ovarian (HPO) axis, the current approach to investigating adolescents who present with AUB often includes pelvic ultrasound to exclude rare structural causes. The aim of this study was to determine whether an ultrasound ordered for the investigation of AUB in adolescents detects any significant anatomic pathology or alters diagnosis and management. DESIGN, SETTING, PARTICIPANTS, AND INTERVENTIONS: A retrospective chart review of 230 patients younger than 18 years of age who presented with AUB to the gynecology clinic at the Hospital for Sick Children in Toronto, Canada between January 2010 and December 2012 was completed. MAIN OUTCOME MEASURES: Findings on pelvic ultrasound and any further imaging as well as management choices for these patients were examined. RESULTS: Of all patients, 67.8% (156/230) had ultrasound done as part of their AUB workup. The most common diagnosis for the patients who received ultrasound examinations and the patients who did not was AUB due to an immature HPO axis. Of the patients who received an ultrasound examination, 72.4% (113/156) had normal findings; incidental findings were identified in 17.9% (28/156) and polycystic ovary syndrome morphology in 6.4% (10/156). Structural causes of AUB were found in only 2 (1.3%) of the adolescents imaged. No patient had a change in her AUB management plan because of ultrasound findings. CONCLUSION: Our results strongly suggest that pelvic ultrasound examination is not required in the initial investigation of AUB in the adolescent population because it did not alter treatment in any of our patients.

Circadian and homeostatic modulation of functional connectivity and regional cerebral blood flow in humans under normal entrained conditions.

Diurnal rhythms have been observed in human behaviors as diverse as sleep, olfaction, and learning. Despite its potential impact, time of day is rarely considered when brain responses are studied by neuroimaging techniques. To address this issue, we explicitly examined the effects of circadian and homeostatic regulation on functional connectivity (FC) and regional cerebral blood flow (rCBF) in healthy human volunteers, using whole-brain resting-state functional magnetic resonance imaging (rs-fMRI) and arterial spin labeling (ASL). In common with many circadian studies, we collected salivary cortisol to represent the normal circadian activity and functioning of the hypothalamic-pituitary-adrenal (HPA) axis. Intriguingly, the changes in FC and rCBF we observed indicated fundamental decreases in the functional integration of the default mode network (DMN) moving from morning to afternoon. Within the anterior cingulate cortex (ACC), our results indicate that morning cortisol levels are negatively correlated with rCBF. We hypothesize that the homeostatic mechanisms of the HPA axis has a role in modulating the functional integrity of the DMN (specifically, the ACC), and for the purposes of using fMRI as a tool to measure changes in disease processes or in response to treatment, we demonstrate that time of the day is important when interpreting resting-state data.

An ultrasonographic study of ovarian antral follicular dynamics in prepubertal gilts during the expected activation of the hypothalamo-pituitary-ovarian axis.

Daily transrectal ultrasonography was carried out in eight 4-5-month-old Polish Large White×Polish Landrace gilts for 42 days to monitor the growth of individual ovarian antral follicles≥2 mm in diameter. In total, 52.4±16.2 and 123.0±6.7 follicles per gilt (mean±SD) that grew to ≥4 mm were identified during the first and second 21-day study periods, respectively (P<0.01). Four follicular waves (defined as the synchronous growth of a group of follicles from 2-3 mm to ≥4 mm) emerged during the first period, and five waves emerged during the second period. The maximum diameters attained by the largest follicles of waves were 5.7±0.6 and 7.0±0.5 mm (first and second periods, respectively; P<0.01). The present results provide direct evidence for the rhythmic, wave-like pattern of antral follicle recruitment in prepubertal gilts. The number of follicles and maximum diameter they attain increase significantly during the expected activation of the hypothalamo-pituitary-ovarian axis in prepubescent gilts.

Severe hypothalamopituitary dysfunction accompanied by influenza-associated encephalopathy: report of two pediatric cases.

Severe influenza infection may lead to neurological damage, such as encephalopathy. This may, in turn, cause acquired hypothalamopituitary dysfunction, which can result in severe morbidity and even death. We herein report two pediatric patients who developed influenza-associated hypopituitarism and were subsequently diagnosed with encephalopathy. They were diagnosed with acute necrotizing encephalopathy and postresuscitation encephalopathy, respectively. Both showed evidence of endocrine dysfunction, and hormone replacement therapy of adrenal, thyroid, and antidiuretic hormones are resulting in continued cardiac activity and resulted in prolonged survival. Screening for endocrine function is important in patients with severe central nervous system dysfunction.