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This article was updated to correct Ignacio Martinez Escobedo's name.
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Although the histone methyltransferase EZH2 and its product H3K27me3 are well studied in cancer, little is known about their role and potential as therapeutic targets in endometriosis. We have previously reported that endometriotic lesions are characterized by global enrichment of H3K27me3. Therefore, we aimed to (1) characterize the expression levels of EZH2 in endometriotic tissues; (2) assess H3K27me3 enrichment in candidate genes promoter regions; and (3) determine if pharmacological inhibition of EZH2 impacts migration, proliferation, and invasion of endometriotic cells. Immunohistochemistry of an endometriosis-focused tissue microarray was used to assess the EZH2 protein levels in tissues. Chromatin immunoprecipitation-qPCR was conducted to assess enrichment of H3K27me3 in candidate gene promoter regions in tissues. Immunofluorescence was performed to assess the effect of an EZH2-specific pharmacological inhibitor on H3K27me3 global enrichment in cell lines. To measure effects of the inhibitor in migration, proliferation, and invasion in vitro we used Scratch, BrdU, and Matrigel assays, respectively. Endometriotic lesions had significantly higher EZH2α nuclear immunostaining levels compared to eutopic endometrium from patients (glands, stroma) and controls (glands). H3K27me3 was enriched within promoter regions of candidate genes in some but not all of the endometriotic lesions. Inhibition of EZH2 reduced H3K27me3 levels in the endometriotic cells specifically, and also reduced migration, proliferation but not invasion of endometriotic epithelial cells (12Z). These findings support future preclinical studies to determine in vivo efficacy of EZH2 inhibitors as promising nonhormonal treatments for endometriosis, still an incurable gynecological disease.
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Endometriose/metabolismo , Endométrio/efeitos dos fármacos , Proteína Potenciadora do Homólogo 2 de Zeste/antagonistas & inibidores , Adulto , Linhagem Celular , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Endometriose/patologia , Endométrio/metabolismo , Endométrio/patologia , Inibidores Enzimáticos/farmacologia , Feminino , Humanos , Indazóis/farmacologia , Pessoa de Meia-Idade , Piridonas/farmacologiaRESUMO
ABSTRACT: A cross-sectional multinational collaborative study on women with endometriosis from Latin America and Spain uncovered high levels of painful symptomatology and high pain catastrophizing scores. Associations between pain perception/catastrophizing and race/ethnicity have been documented. This study was conducted to uncover factors moderating pelvic pain severity, including socioeconomic variables, self-identified race, and pain catastrophizing in women with endometriosis from Latin America and Spain, a population encompassing diverse racial and sociocultural contexts. Self-reported data on demographics, clinical history, Ob-Gyn history, pelvic pain intensity, and pain catastrophizing were collected with the Spanish World Endometriosis Research Foundation (WERF) Endometriosis Phenome Project (EPhect) Clinical Questionnaire (ECQ). Multiple logistic regression was conducted to analyze effects of self-identified race, demographic clusters (defined as countries with similar racial population distribution), socioeconomic factors, and pain catastrophizing on reporting severe vs moderate-mild levels of dysmenorrhea, dyspareunia, and pelvic pain. Self-identified race did not affect the likelihood of reporting severe pelvic pain; however, there were significant differences in reporting severe dysmenorrhea at worst among demographic clusters. Older age was associated with severe dyspareunia at worst and recent pelvic pain. Pain catastrophizing score was highly predictive of reporting most types of severe pelvic pain, regardless of race and demographic cluster. These results negate a role of racial categories as moderator of pain in women from Latin America and Spain and support integration of pain catastrophizing assessments and psychological interventions into the pain management plan to enhance therapeutic outcomes and QoL for patients with endometriosis.
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Stress differentially affects hippocampal-dependent learning relevant to addiction and morphology in male and female rats. Mu opioid receptors (MORs), which are located in parvalbumin (PARV)-containing GABAergic interneurons and are trafficked in response to changes in the hormonal environment, play a critical role in promoting principal cell excitability and long-term potentiation. Here, we compared the effects of acute and chronic immobilization stress (AIS and CIS) on MOR trafficking in PARV-containing neurons in the hilus of the dentate gyrus in female and male rats using dual label immunoelectron microscopy. Following AIS, the density of MOR silver-intensified gold particles (SIGs) in the cytoplasm of PARV-labeled dendrites was significantly reduced in females (estrus stage). Conversely, AIS significantly increased the proportion of cytoplasmic MOR SIGs in PARV-labeled dendrites in male rats. CIS significantly reduced the number of PARV-labeled neurons in the dentate hilus of males but not females. However, MOR/PARV-labeled dendrites and terminals were significantly smaller in CIS females, but not males, compared with controls. Following CIS, the density of cytoplasmic MOR SIGs increased in PARV-labeled dendrites and terminals in females. Moreover, the proportion of near-plasmalemmal MOR SIGs relative to total decreased in large PARV-labeled dendrites in females. After CIS, no changes in the density or trafficking of MOR SIGs were seen in PARV-labeled dendrites or terminals in males. These data show that AIS and CIS differentially affect available MOR pools in PARV-containing interneurons in female and male rats. Furthermore, they suggest that CIS could affect principal cell excitability in a manner that maintains learning processes in females but not males.
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Giro Denteado/metabolismo , Interneurônios/metabolismo , Parvalbuminas/análise , Receptores Opioides mu/metabolismo , Estresse Psicológico/metabolismo , Animais , Membrana Celular/metabolismo , Citoplasma/metabolismo , Dendritos/metabolismo , Giro Denteado/citologia , Feminino , Interneurônios/química , Masculino , Transporte Proteico , Ratos , Ratos Sprague-Dawley , Receptores Opioides mu/genética , Caracteres SexuaisRESUMO
Introduction: We have previously shown that Environmental Enrichment (EE), a multi-modal psychosocial intervention consisting of increased social interaction, novelty, and open spaces, improved disease presentation, anxiety, and immune-related disturbances in the rat model of endometriosis. However, there is a knowledge gap regarding the effects of EE interventions in patients with this painful, inflammatory chronic disease. Aim: To adapt and test the efficacy of an EE intervention on pelvic pain, mental health, perceived stress, quality of life, and systemic inflammation in endometriosis patients through a randomized clinical trial (RCT). Materials and methods: A multidisciplinary team with expertise in physiology, neuroscience, psychology, and women's health adapted and implemented a two-arm RCT comparing an EE intervention with a wait-list control group. Six EE modules administered on alternate weeks were provided to patients in the intervention (N = 29); controls received education only. Survey data and biospecimens were collected at baseline, end-of-study, and 3-months post-intervention to assess pain (Brief Pain Inventory, BPI), endometriosis-related quality of life-QoL (Endometriosis Health Profile-30, EHP30), anxiety (Generalized Anxiety Disorder 7, GAD7), depression (Patient Health Questionnaire for Depression 8, PHQ8), pain catastrophizing (Pain Catastrophizing Score, PCS), stress (Perceived Stress Scale-14, PSS14), and saliva cortisol levels (AM, PM). Results: Compared to the wait-list controls, participants in the EE intervention showed significantly decreased GAD-7 scores at the end of the intervention and 3-month follow-up. Depression, perceived stress, and QoL improved at the 3-month follow-up compared to baseline. While pain levels did not improve, they significantly correlated with anxiety, depression, QoL and pain catastrophizing scores. Conclusion: This pilot RCT demonstrated significant improvements in anxiety and depressive symptoms, QoL, and perceived stress, supporting enriched environments as an integrative psychosocial intervention to be used as adjuvant to the standard of care for endometriosis pain.
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BACKGROUND: Decades of research have shown the robust behavioral, structural, and molecular effects of environmental enrichment (EE) which predominantly improves neuropathological conditions. However, systematic examination of age and sex influences in response to EE is limited. OBJECTIVE: Examine the use of EE and evaluate where sex differences (or similarities) are described and whether critical developmental periods are addressed. A critical examination of review articles about EE will establish a framework for the context of the findings of EE-induced effects, improve the impact of future EE studies and improve translatability. ELIGIBILITY CRITERIA: Narrative, systematic reviews (not original reports) and meta-analyses of any animal species published during 2011 to 2021. Clinical and farming studies were excluded. SOURCES OF EVIDENCE: Indexed review articles in Pubmed and Psychinfo. RESULTS: Most studies examine EE during adulthood such as following an injury or following repeated addictive drug exposure. However, in various genetic models of disease states, little attention is paid to effects of EE at different ages. Only some reviews acknowledge that sex differences exist even when the disease state under study is known to be sexually dimorphic. Identified issues include lack of systematic reporting; status of the "control group" (i.e., isolation or pair housing); the use and reporting of proper statistical analyses. CONCLUSION: Reviews have concluded that EE is most effective when administered early in life but that EE during adulthood is certainly effective. Too few review studies have compared sexes for the effects of EE to make a statement about sex differences. Overall, articles reflect a lack of integration of information on age and sex differences in response to EE. Future studies of EE should examine both sexes and consider critical periods of the lifespan in the experimental models to facilitate the adequate translation of EE as a non-pharmaceutical intervention.
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Atenção , Caracteres Sexuais , Animais , Ingestão de Alimentos , Feminino , MasculinoRESUMO
INTRODUCTION: There is widespread use of all-terrain vehicles (ATVs) in the USA for both work-related and recreational activities. In this study, we aimed to determine the difference in injury severity, Glasgow Coma scales and length of stay between ATV-related injuries and injuries sustained from motorcycles (MOTOs) and automobiles (AUTOs). METHODS: We retrospectively analysed ATV, MOTO and AUTO injuries from a Level 2 Trauma Center between 01 January 2015 and 31 August 2020. Proportional odds regression analyses, as well as multivariable regression models, were used to analyse the data. RESULTS: There were significantly more male and paediatric patients that suffered ATV-related injuries compared with MOTO or AUTO injuries. Victims of ATV-related injuries were also more likely to have open fractures. Paediatric patients were less likely to sustain an injury from either AUTO or MOTO accidents compared with ATV accidents. Patients with no drug use during injury and those who used protective equipment such as seat belts and child seats were significantly associated with lower Injury Severity Scores and higher Glasgow Coma Scale scores, indicating less severe injuries. DISCUSSION: Paediatric patients are very likely to suffer sequela and long-term disability due to the severity of ATV-related injuries. Public awareness campaigns to educate our population, especially our youth, about the danger of ATV use are highly needed.
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Veículos Off-Road , Ferimentos e Lesões , Adolescente , Humanos , Masculino , Criança , Motocicletas , Automóveis , Estudos Retrospectivos , Tempo de Internação , Ferimentos e Lesões/epidemiologia , Ferimentos e Lesões/etiologia , Acidentes de TrânsitoRESUMO
Evidence for beneficial effects of corticotropin releasing hormone (CRH) antagonists in abdominal and pelvic organs is emerging in preclinical studies. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement a compilation of preclinical studies using CRH receptor antagonists as a treatment for abdominal and pelvic disease was carried out. The Animal Research: Reporting of In Vivo Experiments (ARRIVE) essential 10 guidelines were used to determine quality of the included studies. A total of 40 studies from the last 15 years studying irritable bowel syndrome, inflammatory bowel disease, endometriosis, enteritis, stress impact on gastrointestinal processes and exogenous CRH administration effects were included. Blockage of the CRH receptor 1 was mainly associated with beneficial effects while that of CRH receptor 2 worsened studied effects. However, time of administration, route of administration and the animal model used, all had an impact on the beneficial outcomes. Frequency of drugs administered indicated that astressin-2B, astressin and antalarmin were among the most utilized antagonists. Of concern, studies included were predominantly carried out in male models only, representing a gender discrepancy in preclinical studies compared to the clinical scenario. The ARRIVE score average was 13 with ~60% of the studies failing to randomize or blind the experimental units. Despite the failure to date of the CRH antagonists in moving across the clinical trials pipeline, there is evidence for their beneficial effects beyond mood disorders. Future pre-clinical studies should be tailored towards effectively predicting the clinical scenario, including reduction of bias and randomization.
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Hormônio Liberador da Corticotropina , Receptores de Hormônio Liberador da Corticotropina , Animais , Ansiedade , Transtornos de Ansiedade , Hormônio Liberador da Corticotropina/farmacologia , Depressão , Feminino , Antagonistas de Hormônios , MasculinoRESUMO
Introduction: We have previously shown that Environmental Enrichment (EE)-consisting of social support, novelty, and open spaces-decreased disease progression and anxiety in a rat model of endometriosis. We developed a novel EE intervention to be tested in a pilot randomized clinical trial (RCT) in patients with endometriosis, a painful, stressful disease. Objective: To translate and evaluate the feasibility and acceptability of an adapted EE intervention as an adjuvant to standard-of-care for endometriosis patients. Methods: Feasibility was assessed through recruitment, enrollment, and adherence rates. Acceptability was evaluated through a post-intervention survey and focus group discussion 3-months after the end of the intervention. Results: Of the 103 subjects recruited, 64 were randomized to the intervention group and 39 to the control group. At the start of the intervention, the study groups consisted of 29 (intervention) and 27 (control) subjects. Enrollment rates were 45.3% and 69.2%, and adherence rates were 41.4% and 100% for the intervention and control groups, respectively. Delays resulting from natural events (earthquakes, the COVID-19 pandemic) impacted enrollment and adherence rates. The most common reasons for missing an intervention were period pain (39.1%) and work-study (34.8%). There was high acceptability (>80%) of the intervention's logistics. The majority (82.4%) of subjects would continue participating in support groups regularly, and 95.7% would recommend the intervention to other patients. Conclusions: We showed that EE could be translated into an acceptable integrative multi-modal therapy perceived as valuable among participants who completed the intervention. High attrition/low adherence indicates that additional refinements would be needed to improve feasibility. Acceptability data indicate that EE has the potential to be integrated into the clinical management of patients with endometriosis and other inflammatory, painful disorders. Studies are ongoing to assess the efficacy of EE in improving pain symptoms, mental health, and quality of life (QoL).
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Clinical and preclinical studies indicate that women and men differ in relapse vulnerability to drug-seeking behavior during abstinence periods. As relapse is frequently triggered by exposure of the recovered addict to objects previously associated with drug use and the formation of these associations requires memory systems engaged by the hippocampal formation (HF), studies exploring ovarian hormone modulation of hippocampal function are warranted. Previous studies revealed that ovarian steroids alter endogenous opioid peptide levels and trafficking of mu opioid receptors in the HF, suggesting cooperative interaction between opioids and estrogens in modulating hippocampal excitability. However, whether ovarian steroids affect the levels or trafficking of delta opioid receptors (DORs) in the HF is unknown. Here, hippocampal sections of adult male and normal cycling female Sprague-Dawley rats were processed for quantitative immunoperoxidase light microscopy and dual label fluorescence or immunoelectron microscopy using antisera directed against the DOR and neuropeptide Y (NPY). Consistent with previous studies in males, DOR-immunoreactivity (-ir) localized to select interneurons and principal cells in the female HF. In comparison to males, females, regardless of estrous cycle phase, show reduced DOR-ir in the granule cell layer of the dentate gyrus and proestrus (high estrogen) females, in particular, display reduced DOR-ir in the CA1 pyramidal cell layer. Ultrastructural analysis of DOR-labeled profiles in CA1 revealed that while females generally show fewer DORs in the distal apical dendrites of pyramidal cells, proestrus females, in particular, exhibit DOR internalization and trafficking towards the soma. Dual label studies revealed that DORs are found in NPY-labeled interneurons in the hilus, CA3, and CA1. While DOR colocalization frequency in NPY-labeled neuron somata was similar between animals in the hilus, proestrus females had fewer NPY-labeled neurons that co-labeled with DOR in stratum oriens of CA1 and CA3 when compared to males. Ultrastructural analysis of NPY-labeled axon terminals within stratum radiatum of CA1 revealed that NPY-labeled axon terminals contain DORs that are frequently found at or near the plasma membrane. As no differences were noted by sex or estrous cycle phase, DOR activation on NPY-labeled axon terminals would inhibit GABA release probability equally in males and females. Taken together, these findings suggest that ovarian steroids can impact hippocampal function through direct effects on DOR levels and trafficking in principal cells and broad indirect effects through reductions in DOR-ir in NPY-labeled interneurons, particularly in CA1.
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Estradiol/metabolismo , Ciclo Estral/metabolismo , Hipocampo/metabolismo , Interneurônios/metabolismo , Células Piramidais/metabolismo , Receptores Opioides delta/metabolismo , Análise de Variância , Animais , Axônios/metabolismo , Contagem de Células , Feminino , Imunofluorescência , Imuno-Histoquímica , Masculino , Microscopia Imunoeletrônica , Neuropeptídeo Y/metabolismo , Radioimunoensaio , Ratos , Ratos Sprague-DawleyRESUMO
Endometriosis is a complex disease characterized by inflammation and the growth of endometrial- like glands and stroma outside the uterine cavity. The pathophysiology of endometriosis is not entirely understood, however, with a prevalence of ~10% of women in their reproductive years, the disease symptoms significantly affect the quality of life of millions of women globally. Metabolomic studies have previously identified specific metabolites that could be a signature of endometriosis. This approach could potentially be used as a non-invasive tool for early diagnosis and provide a better understanding of endometriosis pathophysiology. This review aims to provide insight as to how endometriosis affects the metabolome by reviewing different studies that have used this approach to design follow-up studies. The search query included the term 'endometriosis' in combination with 'metabolomics', 'lipidomics', or 'sphingolipidomics' published between 2012 and 2020. We included studies in humans and animal models. Most studies reported differences in the metabolome of subjects with endometriosis in comparison to healthy controls and used samples taken from serum, endometrial tissue, follicular fluid, urine, peritoneal fluid, or endometrial fluid. Statistically significant metabolites contributed to group separation between patients and healthy controls. Reported metabolites included amino acids, lipids, organic acids, and other organic compounds. Differences in methods, analytical techniques, and the presence of confounding factors can interfere with results and interpretation of data. Metabolomics seems to be a promising tool for identifying significant metabolites in patients with endometriosis. Nonetheless, more investigation is needed in order to understand the significance of the study results. LAY SUMMARY: Endometriosis is a chronic disease affecting the quality of life in one out of every ten women during their reproductive years, causing pain and infertility. It is characterized by inflammation and growth of tissue like the endometrium (uterus lining) outside the uterine cavity. Studies have searched for a predictor of endometriosis-associated changes by observing small molecules necessary for metabolism on a large scale (metabolomics). Metabolomics could serve to resolve one of the biggest challenges that patients with endometriosis face: a delay in diagnosis. In this review, the authors summarize identified potential biomarkers from various bodily fluids and tissues that are characteristic of metabolic processes observed in endometriosis. Biomarkers include cell growth, cell survival, high energy demand, oxidative stress, and fatty acid levels. A metabolomics approach offers promise as a non-invasive tool to identify significant metabolite changes in patients with endometriosis, potentially leading to earlier diagnoses and new opportunities for back-translational strategies.
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Endometriose , Qualidade de Vida , Animais , Biomarcadores , Feminino , Humanos , Inflamação , MetabolômicaRESUMO
Acute compartment syndrome (ACS) is a medical emergency that remains under-recognized and understudied. This study aimed to identify risk factors for the traumatic and non-traumatic presentation of ACS within a majority Hispanic population. A four-year retrospective analysis of medical records in a single institution revealed 26 with traumatic and 21 non-traumatic patients presenting with ACS. Traumatic ACS occurred in younger males following fractures, as previously described in the field. After controlling for age differences, non-traumatic ACS occurred in older patients with multiple comorbidities, increased use of statins, and anticoagulants as compared to the traumatic ACS group. A large proportion (80%) of the non-traumatic ACS group also presented with hypertension. Patients taking anticoagulants and statins should be carefully monitored for ACS development after non-traumatic qualifying events and advanced age. Further studies should identify how statins interact with the patients' racial/ethnic profile and the incidence of comorbidities to promote earlier identification and reduce morbidities.
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To evaluate the effects of COVID-19 and stay-at-home orders in traumatic hip fractures presentation, we conducted a retrospective chart review cohort study from March 13 to June 13 in 2020 compared to 2019 from a single-hospital Trauma Level 2 Center. Males and females, 18 years of age and older presenting with a diagnosis of displaced or nondisplaced, intracapsular, or extracapsular hip fracture, underwent standard of care-comparative analysis of the patient's characteristics and clinical outcomes. The primary study outcomes included age, sex, ethnicity, and body mass index, the onset of injury, date of arrival, payer, the primary type of injury and comorbidities, mechanism of injury, treatment received, postoperative complications, days in an intensive care unit (ICU), discharge disposition, pre- and postinjury functional status, and COVID-19 test. Age, sex, ethnicity, and body mass index were similar in the patients in 2019 compared to 2020. The patients' average age was 76 years old, 80% reported Hispanic ethnicity, and 63% of the patients were females. Most injuries (90%) occurred due to falls. On average, patients in 2020 presented 4.8 days after the injury onset as compared to 0.7 days in 2019 (p < 0.05). There was an increase in displaced fractures in 2019 compared to 2020 and an increase in patients' disposition into rehabilitation facilities compared to skilled nursing facilities. Despite the delay in presentation, length of stay, days in the ICU, or functional outcomes of the patients were not affected. Although the patients showed a delayed presentation after hip fracture, this does not appear to significantly interfere with the short-term or the 6-month mortality outcomes of the patients, suggesting the possibility of guided delayed care during times of national emergency and increased strain in hospital resources.
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Traumatic brain injury (TBI) and cerebrovascular accidents (CVA) are two of the leading causes of disability in the United States. Robotic exoskeletons (RE) have been approved for rehabilitation by the Federal Drug Administration (FDA) for use after a CVA, and recently received approval for use in patients with TBI. The aim of the study was to determine which factors predict the improvement in functional independence measure (FIM) score after using RE rehabilitation in a population of patients with CVA or TBI. We carried out a retrospective chart-review analysis of the use of the RE (Ekso® GT) in the rehabilitation of patients with TBI and CVA using data from a single, private rehabilitation hospital for patients admitted and discharged between 01/01/2017 and 04/30/2020. From the medical records, we collected presentation date, Glasgow Coma Scale score (GCS) on the date of injury, rehabilitation start date, age, diabetes status on presentation (Yes or No), injury category (TBI or CVA), and both admission and discharge FIM scores. Matching algorithms resulted in one TBI patient matched to three CVA patients resulting in a sample size of 36. The diabetic and non-diabetic populations showed significant differences between age and days from injury to the start of rehabilitation. A multivariate linear regression assessed predictors for discharge motor FIM and found admission motor FIM score and total RE steps to be statistically significant predictors. For each point scored higher on the admission motor FIM the discharge FIM was increased by 1.19 FIM points, and for each 1,000 steps taken in the RE, the discharge motor FIM increased by three points. The type of acquired brain injury (CVA or TBI) was not found to affect functional outcome. The presented results show that key clinic-biologic factors including diabetic status, together with start to rehabilitation play key roles in discharge FIM scores for patients using RE. Clinical Trial Registration: ClinicalTrials.gov, NCT04465019.
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OBJECTIVE: There is a paucity of evidence about traumatic injuries and their sequelae sustained due to equestrian injuries nationally. METHODS: Retrospective study analyzing National Trauma Data Bank data from 2007 to 2016. Variables collected included age, sex, race, payer status, Injury Severity Score (ISS), hospital length of stay, Glasgow Coma Scale, systolic blood pressure (SBP) at presentation, discharge disposition, and mortality. Patient data were analyzed by anatomic region. RESULTS: The most frequent type of injury was in the thorax, but head and neck injuries produced the highest mortality. Increased ISS and an SBP of less than 90 mm Hg were also significant predictors of mortality. CONCLUSIONS: The risk of hospital admission from equestrian injuries is higher than football, motor vehicle racing, and skiing. Preventive measures and campaigns should be instituted to highlight safety practices and the use of personal protective equipment while on horseback either for sports, leisure, or work. LEVEL OF EVIDENCE: Level IV. Retrospective study.
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There is strong evidence from humans and animal models showing that abnormal functioning of the hypothalamic-pituitary-adrenal (HPA) axis and/or the inflammatory response system disrupts feedback regulation of both neuroendocrine and immune systems, contributing to disease. Stress is known to affect the physiology of pelvic organs and to disturb the HPA axis leading to chronic, painful, inflammatory disorders. A link between stress and disease has already been documented for many chronic conditions. Endometriosis is a complex chronic gynecological disease associated with severe pelvic pain and infertility that affects 10% of reproductive-aged women. Patients report the negative impact of endometriosis symptoms on quality of life, work/study productivity, and personal relationships, which in turn cause high levels of psychological and emotional distress. The relationship between stress and endometriosis is not clear. Still, we have recently demonstrated that stress increases the size and severity of the lesions as well as inflammatory parameters in an animal model. Furthermore, the "controllability" of stress influences the pathophysiology in this model, offering the possibility of using stress management techniques in patients. The crosstalk between stress-inflammation-pain through HPA axis activity indicates that stress relief should alleviate inflammation and, in turn, decrease painful responses. This opens up the opportunity of altering brain-body-brain pathways as potential new therapeutic option for endometriosis. The goal of this review is to gather the research evidence regarding the interaction between stress (psychological and physiological) and the development and progression of endometriosis on the exacerbation of its symptoms with the purpose of proposing new lines of emerging research and possible treatment modalities for this still incurable disease.
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Endometriose/fisiopatologia , Sistema Hipotálamo-Hipofisário/fisiopatologia , Sistema Hipófise-Suprarrenal/fisiopatologia , Estresse Psicológico/fisiopatologia , Animais , Modelos Animais de Doenças , Feminino , HumanosRESUMO
The identification and treatment of paroxysmal sympathetic hyperactivity (PSH) still present a significant challenge. We assessed the efficacy of pharmacological agents in treating PSH symptoms and the validity of the diagnostic scales in a cohort of Hispanic patients. A retrospective chart review of cases from a single hospital was conducted in 464 records. Exclusion criteria included underlying conditions such as severe infection. Only nine patients remained in the cohort after examining their clinical records, corresponding to the following diagnoses: traumatic brain injury, subdural hemorrhage, anoxic or ischemic encephalopathy, pneumocephalus, and cerebral palsy. Using the PSH likelihood scale, six of the nine patients were identified with a score of 17 or higher, corresponding to a "probable" PSH, and three patients obtained a score between 8 and 16, corresponding to a "possible" PSH diagnosis. The top three classes of medications used were beta-blockers, antipyretics, and opioids. Benzodiazepines and neuromodulators were also frequently used in patients with trauma, but not in the ones with non-traumatic injuries. Interestingly, 75% of the patients have prescribed levothyroxine as a home medication after the PSH presentation. Medication administration did not follow a specific pattern, suggesting high variability in the management of PSH within our setting, requiring further research. Our results suggest that the pituitary axis might be involved in the progression of PSH. Establishing a specific medical code (e.g., ICD-10) describing PSH as a single entity is essential for appropriate identification and management.
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Endometriosis is a chronic inflammatory disorder in which endometrial tissue is found outside the uterine cavity. Previous reports suggest that there is a dysregulation of the hypothalamic pituitary adrenal axis during the progression of endometriosis. Our previous report showed that a short-term treatment with antalarmin, a corticotrophin releasing hormone receptor type 1 (CRHR1) antagonist decreases the number and size of endometriotic vesicles in the auto-transplantation rat model of endometriosis. Our current goal was to examine the mRNA expression of intra-adrenal receptors to better understand the mechanisms of the hypothalamic pituitary adrenal (HPA) axis involvement in endometriosis. We used two groups of female rats. The first received sham surgery or endometriosis surgery before collecting the adrenals after 7 days of the disease progression. The second group of animals received endometriosis surgery and a treatment of either vehicle or antalarmin (20 mg/kg, i.p.) during the first 7 days after endometriosis induction and then the disease was allowed to progress until day 60. Rats with sham surgery served as controls. Results showed that the mRNA expression of the mineralocorticoid (MRC2) receptor was lower in the rats after 7 days of endometriosis surgery and in rats with endometriosis that received antalarmin. In addition, the CRHR1 was significantly elevated in animals that received antalarmin and this was counteracted by a non-significant elevation in CRHR2 mRNA. The glucocorticoid receptor mRNA within the adrenals was not affected by endometriosis or antalarmin treatment. This report is one of the first to explore intra-adrenal mRNA for receptors involved in the HPA axis signaling as well as in the sympatho-adrenal signaling, calling for additional research towards understanding the role of the adrenal glands in chronic inflammatory diseases such as endometriosis.