Recruitment of Corticotropin-Releasing Hormone (CRH) Neurons in Categorically Distinct Stress Reactions in the Mouse Brain.

Corticotropin-releasing hormone (CRH) neurons in the paraventricular hypothalamic nucleus (PVH) are in the position to integrate stress-related information and initiate adaptive neuroendocrine-, autonomic-, metabolic- and behavioral responses. In addition to hypophyseotropic cells, CRH is widely expressed in the CNS, however its involvement in the organization of the stress response is not fully understood. In these experiments, we took advantage of recently available Crh-IRES-Cre;Ai9 mouse line to study the recruitment of hypothalamic and extrahypothalamic CRH neurons in categorically distinct, acute stress reactions. A total of 95 brain regions in the adult male mouse brain have been identified as containing putative CRH neurons with significant expression of tdTomato marker gene. With comparison of CRH mRNA and tdTomato distribution, we found match and mismatch areas. Reporter mice were then exposed to restraint, ether, high salt, lipopolysaccharide and predator odor stress and neuronal activation was revealed by FOS immunocytochemistry. In addition to a core stress system, stressor-specific areas have been revealed to display activity marker FOS. Finally, activation of CRH neurons was detected by colocalization of FOS in tdTomato expressing cells. All stressors resulted in profound activation of CRH neurons in the hypothalamic paraventricular nucleus; however, a differential activation of pattern was observed in CRH neurons in extrahypothalamic regions. This comprehensive description of stress-related CRH neurons in the mouse brain provides a starting point for a systematic functional analysis of the brain stress system and its relation to stress-induced psychopathologies.

Associations between ACA-related policies and a clinical recommendation with HPV vaccine initiation.

PURPOSE: We examined associations between the 2010 Affordable Care Act (ACA) provisions, 2011 Advisory Committee on Immunization Practices (ACIP) recommendation, and 2014 ACA-related health insurance reforms with HPV vaccine initiation rates by sex and health insurance type. METHODS: Using 2009-2015 public and private health insurance claims for 551,764 males and females aged 9-26 years (referred to as youth) from Maine, New Hampshire, and Massachusetts, we conducted linear regression models to examine the associations between three policy changes and HPV vaccine initiation rates by sex and health insurance type. RESULTS: In 2009, HPV vaccine initiation rates for males and females were 0.003 and 0.604 per 100 enrollees, respectively. Among males, the 2010 ACA provisions and ACIP recommendation were associated with significant increases in HPV vaccine uptake among those with private plans (0.207 [0.137, 0.278] and 0.419 [0.353, 0.486], respectively) and Medicaid (0.157 [0.083, 0.230] and 0.322 [0.257, 0.386], respectively). Among females, the 2010 ACA provisions were associated with significant increases in HPV vaccine uptake among Medicaid enrollees only (0.123 [0.033, 0.214]). The ACA-related health insurance reforms were associated with significant increases in HPV vaccine uptake for male and female Medicaid enrollees (0.257 [0.137, 0.377] and 0.214 [0.102, 0.327], respectively), but no differences among privately insured youth. By 2015, there were no differences in HPV vaccine initiation rates between males (0.278) and females (0.305). CONCLUSIONS: Both ACA provisions and the ACIP recommendation were associated with significant increases in HPV vaccine initiation rates among privately and publicly insured males in three New England states, closing the gender gap. In contrast, females and youth with private insurance did not exhibit the same changes in HPV vaccine uptake over the study period.

Associations between insurance-related affordable care act policy changes with HPV vaccine completion.

BACKGROUND: Although all 11- or 12-year-olds in the US were recommended to receive a 3-dose series of the human papillomavirus (HPV) vaccine within a 12-month period prior to 2016, rates of completion of the HPV vaccine series remained suboptimal. The effects of the Affordable Care Act (ACA), including private insurance coverage with no cost-sharing and health insurance expansions, on HPV vaccine completion are largely unknown. The aim of this study was to examine the associations between the ACA's 2010 provisions and 2014 insurance expansions with HPV vaccine completion by sex and health insurance type. METHODS: Using 2009-2015 public and private health insurance claims from Maine, New Hampshire, and Massachusetts, we identified 9-to-26-year-olds who had at least one HPV vaccine dose. We conducted a logistic regression model to examine the associations between the ACA policy changes with HPV vaccine completion (defined as receiving a 3-dose series within 12 months from the date of initiation) as well as interactions by sex and health insurance type. RESULTS: Over the study period, among females and males who initiated the HPV vaccine, 27.6 and 28.0%, respectively, completed the series within 12 months. Among females, the 2010 ACA provision was associated with a 4.3 percentage point increases in HPV vaccine completion for the privately-insured (0.043; 95% CI: 0.036-0.061) and a 5.7 percentage point increase for Medicaid enrollees (0.057; 95% CI: 0.032-0.081). The 2014 health insurance expansions were associated with a 9.4 percentage point increase in vaccine completion for females with private insurance (0.094; 95% CI: 0.082-0.107) and a 8.5 percentage point increase for Medicaid enrollees (0.085; 95% CI: 0.068-0.102). Among males, the 2014 ACA reforms were associated with a 5.1 percentage point increase in HPV vaccine completion for the privately-insured (0.051; 95% CI: 0.039-0.063) and a 3.4 percentage point increase for Medicaid enrollees (0.034; 95% CI: 0.017-0.050). In a sensitivity analysis, findings were similar with HPV vaccine completion within 18 months. CONCLUSIONS: Despite low HPV vaccine completion overall, both sets of ACA provisions were associated with increases in completion among females and males. Our results suggest that expanding Medicaid across the remaining states could increase HPV vaccine completion among publicly-insured youth and prevent HPV-related cancers.

Stress Adaptation and the Brainstem with Focus on Corticotropin-Releasing Hormone.

Stress adaptation is of utmost importance for the maintenance of homeostasis and, therefore, of life itself. The prevalence of stress-related disorders is increasing, emphasizing the importance of exploratory research on stress adaptation. Two major regulatory pathways exist: the hypothalamic-pituitary-adrenocortical axis and the sympathetic adrenomedullary axis. They act in unison, ensured by the enormous bidirectional connection between their centers, the paraventricular nucleus of the hypothalamus (PVN), and the brainstem monoaminergic cell groups, respectively. PVN and especially their corticotropin-releasing hormone (CRH) producing neurons are considered to be the centrum of stress regulation. However, the brainstem seems to be equally important. Therefore, we aimed to summarize the present knowledge on the role of classical neurotransmitters of the brainstem (GABA, glutamate as well as serotonin, noradrenaline, adrenaline, and dopamine) in stress adaptation. Neuropeptides, including CRH, might be co-localized in the brainstem nuclei. Here we focused on CRH as its role in stress regulation is well-known and widely accepted and other CRH neurons scattered along the brain may also complement the function of the PVN. Although CRH-positive cells are present on some parts of the brainstem, sometimes even in comparable amounts as in the PVN, not much is known about their contribution to stress adaptation. Based on the role of the Barrington's nucleus in micturition and the inferior olivary complex in the regulation of fine motoric-as the main CRH-containing brainstem areas-we might assume that these areas regulate stress-induced urination and locomotion, respectively. Further studies are necessary for the field.

BRCA1/2 Testing in Massachusetts Among Women With Private Insurance or Medicaid, 2011-2015.

PURPOSE: Testing for BRCA1/2 mutations has increased among privately insured women in the United States. However, little is known about testing rates or trends among women with Medicaid. We sought to determine whether BRCA1/2 testing rates differed between women with private insurance compared with women with Medicaid in a state where both insurance types cover the test, and to compare testing trends from 2011 to 2015. METHODS: We conducted a retrospective cohort study of medical claims from January 2011 through June 2015. We included Massachusetts women aged 18-64 with private insurance or Medicaid and at least 12 months of continuous enrollment. We used multivariable linear regression to examine the association of insurance type, age, and time with testing rates. RESULTS: Mean monthly BRCA1/2 testing rates were lower among women with Medicaid compared with those with private insurance. Among privately insured women, mean monthly rates rose from 9.3 per 100,000 in 2011 to 18.4 per 100,000 in 2015, while among Medicaid-insured women, rates increased from 3.7 to 14.7. There was no difference in the monthly rate of increase in both groups (P=0.07). In adjusted analyses, rates were lower among Medicaid-insured women (7 fewer tests per month than privately insured women, P<0.001), and differed by age, with women aged 44-54 most likely to receive testing and women 18-34 the least likely. CONCLUSION: BRCA1/2 testing rates were lower among women insured by Medicaid compared with those with private insurance, though rates increased from 2011 to 2015 among both groups of women at a similar rate.

Gastrointestinal (non-systemic) antibiotic rifaximin differentially affects chronic stress-induced changes in colon microbiome and gut permeability without effect on behavior.

Chronic stress is often accompanied by gastrointestinal symptoms, which might be due to stress-induced shift of gut microbiome to pathogenic bacteria. It has been hypothesized that stress alters gut permeability and results in mild endotoxemia which exaggerates HPA activity and contributes to anxiety and depression. To reveal the relationship between microbiome composition, stress-induced gastrointestinal functions and behavior, we treated chronically stressed mice with non-absorbable antibiotic, rifaximin. The "two hits" stress paradigm was used, where newborn mice were separated from their mothers for 3 h daily as early life adversity (maternal separation, MS) and exposed to 4 weeks chronic variable stress (CVS) as adults. 16S rRNA based analysis of gut microbiome revealed increases of Bacteroidetes and Proteobacteria and more specifically, Clostridium species in chronically stressed animals. In mice exposed to MS + CVS, we found extenuation of colonic mucosa, increased bacterial translocation to mesenteric lymph node, elevation of plasma LPS levels and infiltration of F4/80 positive macrophages into the colon lamina propria. Chronically stressed mice displayed behavioral signs of anxiety-like behavior and neophobia. Rifaximin treatment decreased Clostridium concentration, gut permeability and LPS plasma concentration and increased colonic expression of tight junction proteins (TJP1, TJP2) and occludin. However, these beneficial effects of rifaximin in chronically stressed mice was not accompanied by positive changes in behavior. Our results suggest that non-absorbable antibiotic treatment alleviates stress-induced local pathologies, however, does not affect stress-induced behavior.

Thrombocytosis and Effects of IL-6 Knock-Out in a Colitis-Associated Cancer Model.

There is an increasing number of studies showing that thrombocytosis-accompanying a variety of solid tumors including colorectal cancer (CRC)-is associated with shorter survival and earlier development of metastases. The mechanisms of cancer-associated thrombocytosis are not completely understood yet. The aim of our study was to evaluate the role of IL-6 in tumor development and thrombocytosis in mice with inflammation-induced CRC, using a CRISPR/cas9 IL-6 knockout (KO) strain. Adult male FB/Ant mice (n = 39) were divided into four groups: (1) IL-6 KO controls (n = 5); (2) IL-6 KO CRC model group (n = 18); (3) Wild-type (WT) controls (n = 6); and (4) WT CRC model group (n = 10). CRC model animals in (2) and (4) received azoxymethane (AOM)/dextran sodium sulfate (DSS) treatment to induce inflammation-related CRC. Plasma and liver tissues were obtained to determine platelet counts, IL-6 and thrombopoietin-1 (TPO) levels. In 1 WT and 2 IL-6 KO mice in vivo confocal endomicroscopy and 18F-fluorodeoxyglucose (FDG) PET/MRI examinations were performed to evaluate the inflammatory burden and neoplastic transformation. At the end of the study, tumorous foci could be observed macroscopically in both CRC model groups. Platelet counts were significantly elevated in the WT CRC group compared to the IL-6 KO CRC group. TPO levels moved parallelly with platelet counts. In vivo fluorescent microscopy showed signs of disordered and multi-nuclear crypt morphology with increased mucus production in a WT animal, while regular mucosal structure was prominent in the IL-6 KO animals. The WT animal presented more intense and larger colonic FDG uptake than IL-6 KO animals. Our study confirmed thrombocytosis accompanying inflammation-related CRC and the crucial role of IL-6 in this process. Significantly higher platelet counts were found in the WT CRC group compared to both the control group and the IL-6 KO group. Concomitantly, the tumor burden of WT mice was also greater than that of IL-6 KO mice. Our findings are in line with earlier paraneoplastic IL-6 effect suggestions.

Evidence for the therapeutic effect of the organic content in Szigetvár thermal water on osteoarthritis: a double-blind, randomized, controlled clinical trial.

The therapeutic effects of mineral waters have been attributed to the inorganic components alone; however, biologically active organic components are also present. We aimed to investigate whether the healing effect of Szigetvár thermal mineral water could relate to the organic matter in patients suffering from osteoarthritis of the hips and the knees. XAD macroreticular resins were used to prepare the organic fraction. Patients received a 30-min thermal water (34 °C) treatment in a bath tub, five times a week for 3 weeks. After randomization, patients were divided into three groups: tap water, mineral water, and organic fraction group. Primary outcomes were range of movement (ROM), Western Ontario and McMaster University Osteoarthritis Index (WOMAC), and visual analog scale (VAS) for pain severity, and the Short Form 36 (SF-36) questionnaire was used. These scores and indices were measured at baseline, after the last treatment, and at the end of the 3-month follow-up period. Seventy-four patients (age 67.3 ± 4.48 years) were enrolled: tap water n = 24, mineral water n = 26, and organic fraction n = 24. Treatment with the redissolved organic fraction significantly improved ROM, WOMAC, and SF-36 scores compared to the tap water. Our clinical trial provided evidence for the beneficial health effects of the organic fraction of Szigetvár medicinal water.

Minimal clinically important differences for the experiences of daily living parts of movement disorder society-sponsored unified Parkinson's disease rating scale.

BACKGROUND: The minimal clinically important difference is the smallest change of scores clinically meaningful to patients. OBJECTIVES: We aimed to calculate these threshold values in association with the International Parkinson and Movement Disorder Society UPDRS (MDS-UPDRS) Parts I and II and to evaluate the feasibility of the composite score of Part I and II (MDS-UPDRS I+II) as an outcome. METHODS: Nine hundred eighty-five paired investigations of 365 patients were reviewed, implementing three different techniques simultaneously. RESULTS: Based on the ordinal regression modeling, the MDS-UPDRS I+II score is an applicable outcome measure. Any improvement greater than 2.64 points or any worsening more than 2.45 points on MDS-UPDRS Part I represent a minimal, yet clinically meaningful change. In reference to Part II, the smallest changes considered clinically relevant were 3.05 and 2.51 points for improvement and deterioration, respectively. The thresholds for MDS-UPDRS I+II were 5.73 points for improvement and 4.70 points for worsening. CONCLUSIONS: Our minimal clinically important difference thresholds can be utilized in clinical practice in judging clinical relevance. © 2016 International Parkinson and Movement Disorder Society.

Changes in Quality of Life in Parkinson's Disease: How Large Must They Be to Be Relevant?

BACKGROUND: Minimal clinically important difference (MCID) is the smallest change in an outcome, which a patient identifies as meaningful. Although the 2 most frequently applied Parkinson's disease (PD) "quality of life" questionnaires (the PDQ-39 and PDQ-8) provide encouragingly similar results, their MCID thresholds appear to be vastly different. Our aim was to calculate the MCID estimates for both PDQ-39 and PDQ-8 Summary Indices (PDQ-39-SI and PDQ-8-SI) by the utilization of both anchor- and distribution-based techniques. METHODS: Nine hundred eighty-five paired investigations of 365 patients were included. Three different techniques were used simultaneously to calculate the MCID values. RESULTS: First, we replicated the previously published results demonstrating how both PDQ-39-SI and PDQ-8-SI provide similar values and respond in a similar way to changes. Subsequently, we calculated the MCID thresholds. The most optimal estimates for MCID thresholds for PDQ-39-SI were -4.72 and +4.22 for detecting minimal clinically important improvement and worsening. For PDQ-8-SI, these estimates were -5.94 and +4.91 points for detecting minimal clinically important improvement and worsening respectively. CONCLUSIONS: Our study is the first one that directly compared the MCID estimates for both PDQ-39-SI and PDQ-8-SI on a large pool of patients including all disease severity stages. These MICD estimates varied across PD severity.

[VALIDATION OF THE HUNGARIAN UNIFIED DYSKINESIA RATING SCALE]. / AZ EGYSÉGESÍTETT DYSKINESIA-PONTOZÓSKÁLA MAGYAR NYELVI VALIDÁCIÓJA.

BACKGROUND: The Unified Dyskinesia Rating Scale (UDysRS) was published in 2008. It was designed to be simultaneous valid, reliable and sensitive to therapeutic changes. The Movement Disorder Society organizing team developed guidelines for the development of official non-English translations consisting of four steps: translation/back-translation, cognitive pretesting, large field testing, and clinimetric analysis. The aim of this paper was to introduce the new UDysRS and its validation process into Hungarian. METHODS: After the translation of UDysRS into Hungarian and back-translated into English, it was reviewed by the UDysRS translation administration team. Subsequent cognitive pretesting was conducted with ten patients. For the large field testing phase, the Hungarian official working draft version of UDysRS was tested with 256 patients with Parkinson's disease having dyskinesia. Confirmatory factor analyses (CFA) determined whether the factor structure for the valid Spanish UDysRS could be confirmed in data collected using the Hungarian Official Draft Version. To become an official translation, the Comparative Fit Index (CFI) had to be ≥ 0.90 compared to the Spanish-language version. RESULTS: For the Hungarian UDysRS the CFI was 0.98. CONCLUSION: The overall factor structure of the Hungarian version was consistent with that of the Spanish version based on the high CFIs for the UDysRS in the CFA; therefore, this version was designated as the Official Hungarian Version Of The UDysRS.

[VALIDATION OF THE HUNGARIAN MDS-UPDRS: WHY DO WE NEED A NEW PARKINSON SCALE?]. / AZ MDS-UPDRS MAGYAR VALIDáCIóJA: MIéRT SZüKSéGES UJABB PARKINSON-PONTOZOSKáLA?

BACKGROUND: The Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) has been published in 2008 as the successor of the original UPDRS. The MDS-UPDRS organizing team developed guidelines for the development of official non-English translations consisting of four steps: translation/back-translation, cognitive pretesting, large field testing, and clinimetric analysis. The aim of this paper was to introduce the new MDS-UPDRS and its validation process into Hungarian. METHODS: Two independent groups of neurologists translated the text of the MDS-UPDRS into Hungarian and subsequently back-translated into English. After the review of the back-translated English version by the MDS-UPDRS translation administration team, cognitive pretesting was conducted with ten patients. Based on the results of the initial cognitive pretesting, another round was conducted. For the large field testing phase, the Hungarian official working draft version of MDS-UPDRS was tested with 357 patients with Parkinson's disease (PD). Confirmatory factor analyses (CFA) determined whether the factor structure for the English-language MDS-UPDRS could be confirmed in data collected using the Hungarian Official Draft Version. To become an official translation, the Comparative Fit Index (CFI) had to be ≥ 0.90 compared to the English-language version. RESULTS: For all four parts of the Hungarian MDS-UPDRS, the CFI was ≥ 0.94. CONCLUSION: The overall factor structure of the Hungarian version was consistent with that of the English version based on the high CFIs for all the four parts of the MDS-UPDRS in the CFA; therefore, this version was designated as the "OFFICIAL GUNGARIAN VERSION OF THE MDS-UPDRS'.

[Treatment of tardive syndromes]. / Atardív szindrómák kezelési lehetoségei.

Tardive syndromes associated with dopamine-receptor blocking agents have heterogeneous appearance. The treatment of tardive dyskinesia, dystonia, myoclonus, tourettism, tremor and akathisia is challenging for both psychiatrists and neurologists. Lack of randomized and controlled examinations for many routinely applied clinical therapeutic options make the development of clinical guidelines difficult. The present review article summarizes the available evidence for the treatment of tardive syndromes. According to the treatment guideline published by the American Academy of Neurology in 2013, the usage of clonazepam, ginkgo biloba, amantadine and tetrabenazine has enough evidence to draw conclusions. Although lowering or stopping the eliciting agent, changing to atypical antipsychotics, and adding anticholinergics are widely used techniques, there are no convincing controlled studies available to support their efficacy. The usage of Vitamin E, levetiracetam, propranolol, botulinum toxin and deep brain stimulation may be promising treatment options in the future.

[Cooperation between the health visitor and the physician as one of the pillars of the 108-year-old Hungarian Health Visitor Service]. / A védono-orvos együttmuködés mint a 108 éve sikeresen muködo Magyar Védonoi Szolgálat egyik alappilére.

INTRODUCTION: Despite the more than 100-year history of the Hungarian Health Visitor Service, no study has yet been carried out that looked back at the cooperation between health visitors and physicians. OBJECTIVE: Our aim was 1) to explore the professional advances of the health visitor service and the cooperation between health visitor and physician by examining historical documents, legal and professional regulations governing the work of health visitor, furthermore, 2) to investigate whether there are compulsory training elements in today's training for health visitors that prepare students for health visitor and physician collaboration, moreover, 3) to search for old tools and documents used by health visitors and doctors in the North-West of Transdanubia. METHOD: A literature search was carried out to identify documents relating to the development of the work of health visitors, the cooperation between health visitors and physicians, past and current legal and professional regulations, the current regulation on training of health visitors. Through field research, we tracked down old tools and documents of health visitors and physicians. RESULTS: The establishment of the Hungarian Health Visitor Service is associated with the names of professors of medicine. The historical documents and regulations testify the development of the work of the health visitor, the expansion of her competences and the importance of the health visitor and physician cooperation. The training competences required for the cooperation between health visitors and physicians, health visitors and specialists are regulated by the regulation on training of health visitors. We have found many old objects and documents used in the work of the health visitor and doctor. DISCUSSION: The documents that have preserved almost invariably describe the health visitor as a person working alongside the physician, in cooperation with the physician. Nowadays, the regulation of cooperation covers for all specialties in the field of health visitor. CONCLUSION: Based on our research, it is fair to say that the health visitor-physician cooperation is an important pillar of the 108-year-old Hungarian Health Visitor Service. Orv Hetil. 2023; 164(33): 1311-1318.

ACA and Medicaid Expansion Increased Breast Pump Claims and Breastfeeding for Women with Public and Private Insurance.

BACKGROUND: The Patient Protection and Affordable Care Act (ACA) required new private insurance plans to provide breast pumps with no cost sharing beginning August 2012, and in January 2014 expanded this requirement to Marketplace plans and expanded Medicaid coverage. We first examined the associations between the ACA reforms in 2012 and 2014 with rates of breast pump claims between Medicaid enrollees and those with private insurance. We next examined the associations between the monthly rate of breast pump claims with breastfeeding initiation and duration by insurance type. METHODS: Using 2011-2015 public and private health insurance claims in All-Payer Claims Databases from Massachusetts, Maine, and New Hampshire, we conducted a linear regression model to evaluate the associations between the 2012 and 2014 ACA health insurance reforms with rates of breast pump claims by health insurance status. We then linked the monthly rates of breast pump claims per 1,000 live births to the Pregnancy Risk Assessment Monitoring System with self-reported breastfeeding initiation and duration. We estimated probit regression models to examine the associations between monthly rates of breast pump claims per state, insurance type, age group, and breastfeeding outcomes. RESULTS: For the 2012 ACA reform, breast pump claims increased by 183.4 (143.7-223.1) per 1,000 live births for women with private insurance, but decreased for Medicaid enrollees (-99.3 [-139.0 to -59.6]). For the 2014 ACA reforms, the opening of health insurance Marketplaces had no effect on breast pump claims for women with private insurance (8.3 [-43.6 to 60.2]), whereas Medicaid expansion increased claims by 119.4 (67.5-171.3) per 1,000 live births for Medicaid enrollees. Every additional 10 breast pump claims per 1,000 live births was associated with a 1.08 percentage point increase in breastfeeding initiation among women with private insurance (0.108 [0.018-0.198]), but not Medicaid enrollees (0.076 [-0.078 to 0.230]). In contrast, every additional 10 breast pump claims per 1,000 live births was associated with a 1.79 percentage point increase in breastfeeding for 4 or more weeks for women with private insurance (0.179 [0.063-0.294]) and a 2.05 percentage point increase among women with public insurance (0.205 [0.033-0.376]). Interaction analysis revealed no significant differences in associations by insurance type across breastfeeding outcomes. CONCLUSIONS: The ACA breastfeeding coverage requirements fill a gap for women wanting to obtain a breast pump to support breastfeeding. The monthly rate of breast pump claims, as an indicator of access, translated into higher levels of breastfeeding for women with private and public insurance with the potential to reduce socioeconomic disparities.

The metabolic stress response: Adaptation to acute-, repeated- and chronic challenges in mice.

There is a strong relationship between stress and metabolism. Because acute traumatic- and chronic stress events are often accompanied with metabolic pathophysiology, it is important to understand the details of the metabolic stress response. In this study we directly compared metabolic effects of acute stress with chronic repeated- and chronic unpredictable stress in mouse models. All types of adversities increased energy expenditure, chronic stress exposure decreased body weight gain, locomotor activity and differentially affected fuel utilization. During chronic exposure to variable stressors, carbohydrates were the predominant fuels, whereas fatty acids were catabolized in acutely and repeatedly restrained animals. Chronic exposure to variable stressors in unpredictable manner provoked anxiety. Our data highlight differences in metabolic responses to acute- repeated- and chronic stressors, which might affect coping behavior and underlie stress-induced metabolic and psychopathologies.

Early Phase of the COVID-19 Outbreak in Hungary and Post-Lockdown Scenarios.

COVID-19 epidemic has been suppressed in Hungary due to timely non-pharmaceutical interventions, prompting a considerable reduction in the number of contacts and transmission of the virus. This strategy was effective in preventing epidemic growth and reducing the incidence of COVID-19 to low levels. In this report, we present the first epidemiological and statistical analysis of the early phase of the COVID-19 outbreak in Hungary. Then, we establish an age-structured compartmental model to explore alternative post-lockdown scenarios. We incorporate various factors, such as age-specific measures, seasonal effects, and spatial heterogeneity to project the possible peak size and disease burden of a COVID-19 epidemic wave after the current measures are relaxed.

Ecto-nucleoside triphosphate diphosphohydrolase 3 in the ventral and lateral hypothalamic area of female rats: morphological characterization and functional implications.

BACKGROUND: Based on its distribution in the brain, ecto-nucleoside triphosphate diphosphohydrolase 3 (NTPDase3) may play a role in the hypothalamic regulation of homeostatic systems, including feeding, sleep-wake behavior and reproduction. To further characterize the morphological attributes of NTPDase3-immunoreactive (IR) hypothalamic structures in the rat brain, here we investigated: 1.) The cellular and subcellular localization of NTPDase3; 2.) The effects of 17beta-estradiol on the expression level of hypothalamic NTPDase3; and 3.) The effects of NTPDase inhibition in hypothalamic synaptosomal preparations. METHODS: Combined light- and electron microscopic analyses were carried out to characterize the cellular and subcellular localization of NTPDase3-immunoreactivity. The effects of estrogen on hypothalamic NTPDase3 expression was studied by western blot technique. Finally, the effects of NTPDase inhibition on mitochondrial respiration were investigated using a Clark-type oxygen electrode. RESULTS: Combined light- and electron microscopic analysis of immunostained hypothalamic slices revealed that NTPDase3-IR is linked to ribosomes and mitochondria, is predominantly present in excitatory axon terminals and in distinct segments of the perikaryal plasma membrane. Immunohistochemical labeling of NTPDase3 and glutamic acid decarboxylase (GAD) indicated that gamma-amino-butyric-acid- (GABA) ergic hypothalamic neurons do not express NTPDase3, further suggesting that in the hypothalamus, NTPDase3 is predominantly present in excitatory neurons. We also investigated whether estrogen influences the expression level of NTPDase3 in the ventrobasal and lateral hypothalamus. A single subcutaneous injection of estrogen differentially increased NTPDase3 expression in the medial and lateral parts of the hypothalamus, indicating that this enzyme likely plays region-specific roles in estrogen-dependent hypothalamic regulatory mechanisms. Determination of mitochondrial respiration rates with and without the inhibition of NTPDases confirmed the presence of NTPDases, including NTPDase3 in neuronal mitochondria and showed that blockade of mitochondrial NTPDase functions decreases state 3 mitochondrial respiration rate and total mitochondrial respiratory capacity. CONCLUSION: Altogether, these results suggest the possibility that NTPDases, among them NTPDase3, may play an estrogen-dependent modulatory role in the regulation of intracellular availability of ATP needed for excitatory neuronal functions including neurotransmission.

Neuroimaging and cognitive changes during déjà vu.

OBJECTIVE: The cause or the physiological role of déjà vu (DV) in healthy people is unknown. The pathophysiology of DV-type epileptic aura is also unresolved. Here we describe a 22-year-old woman treated with deep brain stimulation (DBS) of the left internal globus pallidus for hemidystonia. At certain stimulation settings, DBS elicited reproducible episodes of DV. METHODS: Neuropsychological tests and single-photon-emission computed tomography (SPECT) were performed during DBS-evoked DV and during normal DBS stimulation without DV. RESULTS: SPECT during DBS-evoked DV revealed hyperperfusion of the right (contralateral to the electrode) hippocampus and other limbic structures. Neuropsychological examinations performed during several evoked DV episodes revealed disturbances in nonverbal memory. CONCLUSION: Our results confirm the role of mesiotemporal structures in the pathogenesis of DV. We hypothesize that individual neuroanatomy and disturbances in gamma oscillations or in the dopaminergic system played a role in DBS-elicited DV in our patient.

[Up-to-date classification and multidisciplinary symptoms of Ehlers-Danlos syndromes]. / Az Ehlers­Danlos-szindrómák korszeru osztályozása és multidiszciplináris tünettana.

In this review article, the authors summarize the clinical aspects of the novel classification of Ehlers-Danlos syndrome, which is a group of rare, hereditary connective tissue disorders. The leading symptom of the Ehlers-Danlos syndrome group is joint hypermobility, skin hyperextensibility and generalized tissue fragility. Ehlers-Danlos syndrome displays a high clinical and genetic heterogeneity and harbors many multidisciplinary properties. Certain subtypes only affect the quality of life, while other forms may lead to severe, even fatal vascular or intestinal complications. Last year, based on the data of various international genotype-phenotype correlation studies of large populations, a new classification of the syndrome's clinical subtypes was introduced. The novel international nosology of Ehlers-Danlos syndromes published in 2017 delineates 13 clinical subtypes, describes their genetic background and defines major and minor diagnostic criteria for each subtype. We gathered the complex, multidisciplinary symptoms of Ehlers-Danlos syndromes in a table to assist the diagnosis from a differential diagnostic point of view. In the clinical practice, the proper diagnosis of patients affected by the Ehlers-Danlos syndrome group is essential to give optimal clinical care and to prevent the development of severe complications. Orv Hetil. 2019; 160(16): 603-612.