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Peptide-based polymers are evolving as promising materials for various biomedical applications. Among peptide-based polymers, polytyrosine (PTyr)-based and l-tyrosine (Tyr)-derived polymers are unique, due to their excellent biocompatibility, degradability, and functional as well as engineering properties. To date, different polymerization techniques (ring-opening polymerization, enzymatic polymerization, condensation polymerization, solution-interfacial polymerization, and electropolymerization) have been used to synthesize various PTyr-based and Tyr-derived polymers. Even though the synthesis starts from Tyr, different synthesis routes yield different polymers (polypeptides, polyarylates, polyurethanes, polycarbonates, polyiminocarbonate, and polyphosphates) with unique functional characteristics, and these polymers have been successfully used for various biomedical applications in the past decades. This Review comprehensively describes the synthesis approaches, classification, and properties of various PTyr-based and Tyr-derived polymers employed in drug delivery, tissue engineering, and biosensing applications.
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Polímeros , Tirosina , Polímeros/química , Tirosina/química , Materiais Biocompatíveis/química , Engenharia Tecidual/métodos , Peptídeos , PolimerizaçãoRESUMO
BACKGROUND: Neuromuscular weakness may manifest subsequent to critical illness in intensive care unit (ICU) patients. This weakness termed as "ICU-acquired weakness" (ICUAW) has a significant bearing on the length of mechanical ventilation, duration of ICU stays, long-term disability, and survival rate. Early identification of ICUAW helps in planning appropriate strategies, as well as in predicting the prognosis and long-term outcomes of these patients. AIMS AND OBJECTIVES: To identify the incidence of new-onset neuromuscular weakness developing among patients admitted in the ICU (ICUAW) and study its clinical course and impact on the duration of ICU stay. METHODS: This prospective observational study evaluated patients admitted to the ICU over a period of 1 year and 3 months (November 1, 2015, to January 31, 2017). All patients fulfilling the inclusion and exclusion criteria were evaluated with the Medical Research Council (MRC) score for muscle strength. Patients with an average score <4 were diagnosed with ICUAW. Included patients were examined on alternate days to study the clinical progression of the weakness till ICU discharge or death of the patient. The duration of ICU stay was noted. RESULTS AND CONCLUSION: The study revealed a significant association of ICUAW with age, Acute Physiology And Chronic Health Evaluation (APACHE II) Score, duration of mechanical ventilation, and ICU mortality. The incidence of the weakness was found to be 7.83% among the patients who survived and 50% among those patients who did not survive critical illness. HOW TO CITE THIS ARTICLE: Baby S, George C, Osahan NM. Intensive Care Unit-acquired Neuromuscular Weakness: A Prospective Study on Incidence, Clinical Course, and Outcomes. Indian J Crit Care Med 2021;25(9):1006-1012.
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Eating disorders such as anorexia typically emerge during adolescence, are characterized by engagement in compulsive and detrimental behaviors, and are often comorbid with neuropsychiatric disorders and drug abuse. No effective treatments exist. Moreover, anorexia lacks adolescent animal models, contributing to a poor understanding of underlying age-specific neurophysiological disruptions. To evaluate the contribution of dopaminergic signaling to the emergence of anorexia-related behaviors during the vulnerable adolescent period, we applied an established adult activity-based anorexia (ABA) paradigm (food restriction plus unlimited exercise access for 4 to 5 days) to adult and adolescent rats of both sexes. At the end of the paradigm, measures of plasma volume, blood hormone levels, dopamine transporter (DAT) expression and function, acute cocaine-induced locomotion, and brain water weight were taken. Adolescents were dramatically more affected by the ABA paradigm than adults in all measures. In vivo chronoamperometry and cocaine locomotor responses revealed sex-specific changes in adolescent DAT function after ABA that were independent of DAT expression differences. Hematocrit, insulin, ghrelin, and corticosterone levels did not resemble shifts typically observed in patients with anorexia, though decreases in leptin levels aligned with human reports. These findings are the first to suggest that food restriction in conjunction with excessive exercise sex-dependently and age-specifically modulate DAT functional plasticity during adolescence. The adolescent vulnerability to this relatively short manipulation, combined with blood measures, evidence need for an optimized age-appropriate ABA paradigm with greater face and predictive validity for the study of the pathophysiology and treatment of anorexia. SIGNIFICANCE STATEMENT: Adolescent rats exhibit a distinctive, sex-specific plasticity in dopamine transporter function and cocaine response after food restriction and exercise access; this plasticity is both absent in adults and not attributable to changes in dopamine transporter expression levels. These novel findings may help explain sex differences in vulnerability to eating disorders and drug abuse during adolescence.
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Anorexia/etiologia , Anorexia/metabolismo , Restrição Calórica , Proteínas da Membrana Plasmática de Transporte de Dopamina/metabolismo , Locomoção/fisiologia , Condicionamento Físico Animal/fisiologia , Fatores Etários , Animais , Restrição Calórica/métodos , Feminino , Masculino , Condicionamento Físico Animal/métodos , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Fatores SexuaisRESUMO
OBJECTIVE: Depression is an easily treatable yet frequently underdiagnosed affliction in palliative population with deleterious implications on their quality of life. It has been studied poorly in developing countries like India. METHODS: A cross-sectional study was done with 234 consenting subjects attending a palliative care unit. Patient Health Questionnaire-9 (PHQ-9), World Health Organization Quality of Life (WHOQOL-BREF), and semi-structured proforma were used by trained nonmental health professional to collect data. RESULTS: The prevalence of major depression was 70%. Being a resident of nuclear family (p = .004), absence of insurance coverage (p = .01), presence of financial difficulties (p = .002), and absence of cancer recurrence (p = .001) were significantly associated with major depression in univariate analysis. In multivariate analysis, presence of financial difficulties (OR = 3.9; 95% CI, 2.00-7.61) and absence of health insurance (OR = 1.92; 95% CI, 1.02-3.7) were independently associated with major depression. The presence of depression showed significant negative correlation with physical health (p = .03), psychological health (p = .002), and environmental (p = .002) domains of the WHOQOL-BREF. CONCLUSION: This study brings to the fore the high rates of depression and its negative impact on the quality of life of terminally ill cancer patients. An improvement in their quality of life requires measures to reduce the rate of underdiagnosed psychiatric morbidities, especially in those who are financially burdened and lack insurance coverage.
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Depressão/psicologia , Neoplasias/psicologia , Neoplasias/terapia , Cuidados Paliativos/psicologia , Qualidade de Vida/psicologia , Adolescente , Adulto , Estudos Transversais , Depressão/epidemiologia , Feminino , Humanos , Índia/epidemiologia , Masculino , Pessoa de Meia-Idade , Cuidados Paliativos/estatística & dados numéricos , Prevalência , Adulto JovemRESUMO
Originally, uptake-mediated termination of monoamine (e.g., serotonin and dopamine) signalling was believed to only occur via high-affinity, low-capacity transporters ("uptake1 ") such as the serotonin or dopamine transporters, respectively. Now, the important contribution of a second low-affinity, high-capacity class of biogenic amine transporters has been recognised, particularly in circumstances when uptake1 transporter function is reduced (e.g., antidepressant treatment). Pharmacologic or genetic reductions in uptake1 function can change locomotor, anxiety-like or stress-coping behaviours. Comparable behavioural investigations into reduced low-affinity, high-capacity transporter function are lacking, in part, due to a current dearth of drugs that selectively target particular low-affinity, high-capacity transporters, such as the plasma membrane monoamine transporter. Therefore, the most direct approach involves constitutive genetic knockout of these transporters. Other groups have reported that knockout of the low-affinity, high-capacity organic cation transporters 2 or 3 alters anxiety-like and stress-coping behaviours, but none have assessed behaviours in plasma membrane monoamine transporter knockout mice. Here, we evaluated adult male and female plasma membrane monoamine transporter wild-type, heterozygous and knockout mice in locomotor, anxiety-like and stress-coping behavioural tests. A mild enhancement of anxiety-related behaviour was noted in heterozygous mice. Active-coping behaviour was modestly and selectively increased in female knockout mice. These subtle behavioural changes support a supplemental role of plasma membrane monoamine transporter in serotonin and dopamine uptake, and suggest sex differences in transporter function should be examined more closely in future investigations.
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Growth of any kind in the oropharynx poses a threat to the airway especially during anaesthesia. Being aware of the challenges and adequately equipped to handle the situation is the duty of the anesthesiologist. METHODS AND MATERIAL: An eight year old girl diagnosed case of multiple mucous cysts presented to the outpatient department for excision of a lower lip mucous cyst. So an ultrasound was done which revealed a large intramural mucous cyst. After a preanaesthetic checkup she was posted for the excision of the cyst. RESULTS: The girl was posted for Elective surgery and was induced without prior premedication as she had revealed a history of snoring in supine position. After preoxygenating with 100% oxygen, she was induced with Injection Ketamine and Sevoflurane. She started desaturated abruptly so nasal airway and finally # 2.5 LMA was inserted but SpO2 didn't improve. With backup of Ent and paediatric surgeons direct larngoscopy was attempted and #5 ETT was inserted successfully. Following which the huge vallecular cyst was removed.
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Cognitive changes that occur during mid-life and beyond are linked to both aging and the menopause transition. Studies in women suggest that the age at menopause onset can impact cognitive status later in life; yet, little is known about memory changes that occur during the transitional period to the postmenopausal state. The 4-vinylcyclohexene diepoxide (VCD) model simulates transitional menopause in rodents by depleting the immature ovarian follicle reserve and allowing animals to retain their follicle-deplete ovarian tissue, resulting in a profile similar to the majority of perimenopausal women. Here, Vehicle or VCD treatment was administered to ovary-intact adult and middle-aged Fischer-344 rats to assess the trajectory of cognitive change across time with normal aging and aging with transitional menopause via VCD-induced follicular depletion, as well as to evaluate whether age at the onset of follicular depletion plays a role in cognitive outcomes. Animals experiencing the onset of menopause at a younger age exhibited impaired spatial memory early in the transition to a follicle-deplete state. Additionally, at the mid- and post- follicular depletion time points, VCD-induced follicular depletion amplified an age effect on memory. Overall, these findings suggest that age at the onset of menopause is a critical parameter to consider when evaluating learning and memory across the transition to reproductive senescence. From a translational perspective, this study illustrates how age at menopause onset might impact cognition in menopausal women, and provides insight into time points to explore for the window of opportunity for hormone therapy during the menopause transition period. Hormone therapy during this critical juncture might be especially efficacious at attenuating age- and menopause- related cognitive decline, producing healthy brain aging profiles in women who retain their ovaries throughout their lifespan.
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Envelhecimento/psicologia , Cognição/fisiologia , Menopausa/psicologia , Reserva Ovariana/fisiologia , Ovário/fisiologia , Memória Espacial/fisiologia , Animais , Cicloexenos/farmacologia , Feminino , Menopausa/efeitos dos fármacos , Folículo Ovariano/citologia , Folículo Ovariano/efeitos dos fármacos , Reserva Ovariana/efeitos dos fármacos , Ovário/citologia , Ovário/efeitos dos fármacos , Ratos , Ratos Endogâmicos F344 , Memória Espacial/efeitos dos fármacos , Compostos de Vinila/farmacologiaRESUMO
Background: There is a dearth of research on risk factors of delirium among elderly inpatients in nonintensive low resource settings. Aim: To determine the risk factors of delirium in elderly inpatients in a nonintensive care unit setting. Materials and Methods: Sixty two elderly patients with delirium (cases) and 62 patients without delirium (controls) were administered a semi-structured proforma with socio-demographic variables and putative predisposing and precipitating risk factors and the Vellore screening instrument for dementia. Results: On univariate analysis, factors such as past cognitive impairment, history of nocturnal confusion and delirium, diminished daily living activities, severe medical illness, history of psychiatric illness, presence of dementia, infection, fever above 1000F, abnormal electrolytes abnormal RFT, leukocytes in urine, hypoxia, anticholinergics and benzodiazepines, emergency admission, use of physical restraints, bladder catheterization, more than routine investigations, intensive care unit admission, surgery, and duration of hospital stay more than 10 days were found to be significantly associated with delirium. On multivariate analysis with binary logistic regression, bladder catheterization (odds ratio [OR] = 13.85; confidence interval [CI] = 1.44-133.14), abnormal electrolytes (OR = 5.12; CI = 1.11-23.69), and hypoxia (OR = 75.52; CI = 4.64-1.134E3) were detected to be independently associated with delirium. Conclusion: Acute modifiable rather than long-term factors were risk factors for delirium among the elderly. An awareness of modifiable risk factors has the potential of developing targeted interventions for the early mitigation of delirium.
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[This corrects the article DOI: 10.1016/j.bjao.2023.100207.].
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[This corrects the article DOI: 10.1016/j.bjao.2023.100207.].
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In this letter, we highlight the considerable diversity in undergraduate dermatology training in the United Kingdom and acknowledge the barriers faced in implementing the revised national undergraduate curriculum provided by the British Association of Dermatologists (BAD). We provide a pragmatic approach of ensuring that our dermatology placement aligns with the BAD national undergraduate curriculum and Medical Licensing Assessment (MLA) content map, in the face of limited clinician time and placement length. We urge other medical schools to adopt our approach of curriculum mapping, particularly in light of the upcoming MLA, and sustainable educational resource development.
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A boy in his middle childhood with severe haemophilia reported with facial swelling following dental treatment for a carious upper primary molar done at a private dental clinic elsewhere. On presentation, he had a large, tense and tender swelling of the left cheek and a haematoma on the buccal mucosa adjacent to the treated tooth. The child was found to have a low haemoglobin level. He was taken for an emergency procedure under general anaesthesia for dental extraction with incision and drainage, and simultaneously underwent packed cells and factor replacement. He recovered in the ward postoperatively with no complications and with a gradual reduction of the swelling. This report highlights the importance of caries prevention in children, especially those with haemophilia. They need to be educated about restricting cariogenic foods in their diet and maintaining good oral hygiene. Management of such patients should be carefully coordinated to minimise undesirable outcomes.
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Cárie Dentária , Hemofilia A , Masculino , Humanos , Criança , Hemofilia A/complicações , Dieta , Alimentos , Assistência Odontológica , Cárie Dentária/etiologia , Cárie Dentária/cirurgiaRESUMO
Approximately one-third of women diagnosed with melanoma are of child-bearing age. The annual incidence of melanoma has risen steadily over the last 40 years, resulting in increasing numbers of women diagnosed with melanoma both during pregnancy, and post-partum. To date, there are no formal guidelines on the management of pregnancy associated melanoma (PAM), both early stage and metastatic. This article reviews the existing literature and provides a framework for the investigation and multidisciplinary management of PAM.
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Melanoma , Complicações Neoplásicas na Gravidez , Neoplasias Cutâneas , Feminino , Humanos , Incidência , Melanoma/diagnóstico , Melanoma/epidemiologia , Melanoma/terapia , Gravidez , Complicações Neoplásicas na Gravidez/diagnóstico , Complicações Neoplásicas na Gravidez/terapia , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/epidemiologia , Neoplasias Cutâneas/terapiaRESUMO
Background: Linear morphoea is a severe morphoea subtype associated with extracutaneous manifestations, potentially permanent disfigurement and functional impairment. Linear morphoea is more prevalent in paediatric patients, and knowledge of disease in adults is limited. The objective of this study was to compare paediatric- and adult-onset linear morphoea, in an exclusively adult population. Methodology: This was a retrospective cohort study of adult patients with linear morphoea seen over a 3-year period at a single-site adult tertiary-referral Connective Tissue Disease centre. Clinical markers of disease severity and course, including anatomical distribution, extracutaneous manifestations, cutaneous symptoms, associated autoimmunity, inflammatory blood parameters, Dermatology Life Quality Index scores, treatment requirements and modified Localised Scleroderma Activity Tool were assessed and compared in paediatric- and adult-onset linear morphoea. Results: Of 298 patients with morphoea seen during the study period, 135 had linear morphoea and 133 were included in the study. Most were female (78.9%), the mean age was 36.5 years and almost half (43.6%) had adult-onset disease. Disease was similarly severe between groups with regard to anatomical distribution, cutaneous symptoms (n = 89, 66.9%), extracutaneous manifestations (n = 76, 57.1%), antinuclear antibody-positivity (n = 40, 40.4%), raised erythrocyte sedimentation rate (n = 27, 25.0%) and associated autoimmune diagnoses (n = 15, 11.3%). Prescribed treatments were similar between groups; 73.7% receiving methotrexate and almost one-third (32.3%) requiring more than one steroid-sparing agent. Those with paediatric-onset had more disease-related damage, with a mean modified Localised Scleroderma Skin Damage Index score of 19.5 (95% confidence interval: 17.0-22.0) versus 8.1 (95% confidence interval: 4.4-11.8; p < 0.001). Significantly more patients with adult-onset linear morphoea had quiescent disease (p = 0.0332), and even after correcting for disease duration, paediatric-onset patients still had 2.6 times greater odds of active disease (odds ratio = 2.59, 95% confidence interval: 0.9-7.6; p = 0.083). Conclusion: Linear morphoea in adults can be a severe disease with extracutaneous, autoimmune and systemic features. Adults with paediatric-onset disease appear to have more severe cumulative damage, greater functional impairment and ongoing disease activity. This patient subgroup may require particularly close monitoring and more aggressive therapy.
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BACKGROUND: Postnatal depression is a highly prevalent disorder with serious implications on maternal and child outcomes. There are few studies examining feasible interventions in low-middle-income community settings. AIMS: To assess the effectiveness of a low intensity group intervention led by lay workers during the antenatal period in reducing postnatal depression at 6-2 weeks postpartum. METHODS: A parallel group design with both positive and negative controls was employed. 1 community site was allocated to each of the 3 arms. The active intervention consisted of problem based sessions with cognitive behavioural components. The primary outcome was the presence of depression on CIS-R and secondary outcome measures where Global Assessment of Functioning (GAF) scores, EPNDS scores and participant perceptions. RESULTS: 69, 75 and 70 women received active, positive control and negative control interventions respectively. Post partum depression diagnosed with the CIS-R was present in 14.06% (C.I.- 5.55%-22.57%) and 22.62% (C.I.15.62%-29.63%) in the active arm and two control (combined) arms respectively. There was a 1/3 lower proportion of postpartum depression and impaired functioning in the intervention group, though statistical significance was not reached (pâ¯=â¯0.30). There were high levels of satisfaction reported for the active intervention. CONCLUSION: There were trends for the possible effectiveness for this low intensity intervention and conclusions regarding its effectiveness can't be made as the sample size was small. There is a need to explore and develop locally relevant, innovative and feasible strategies for prevention of postnatal depression in resource constrained enviroments.
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Agentes Comunitários de Saúde , Serviços Comunitários de Saúde Mental , Depressão Pós-Parto/prevenção & controle , Serviços de Saúde Materna , Psicoterapia de Grupo/métodos , Adulto , Feminino , Humanos , Índia , Gravidez , Resultado do TratamentoRESUMO
BACKGROUND: Medical students are subjected to various challenges, which are possibly etiological in the onset and persistence of depression. There is inadequate research on the longitudinal pattern and correlates of the emotional health of medical students in India. We aim to delineate the longitudinal pattern of depression among medical students and the factors predictive of depression. METHODS: An 18-month follow-up design with 350 students (2012 intake) from two medical colleges in Kerala, India, was employed. A semistructured questionnaire and the Patient Health Questionnaire 9 were administered 2, 8, and 18 months into the course. RESULTS: Depression was present in 42.80%, 36.20%, and 42.50% of the students at the three assessments. Variables significantly associated with depression on univariate analysis were the course not being of the student's choice at the first assessment; having an unemployed parent (mother) at the second assessment; alcohol use and male gender at the third assessment. On multivariate analysis, male gender (OR = 1.95[1.11-3.41]) and the presence of depression at 2 months (OR = 2.30[1.31-4.05]) and 8 months (OR = 2.48[1.39-4.44]) were predictive of depression at 18 months. CONCLUSIONS: The high rates of depression and the pattern of high rates early in the course among the medical students contrasts with that reported from other countries. Early depression and male gender were predictive of depression later in the course. The implications of this are to be taken into consideration when undergraduate intervention programs are planned.
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Pyoderma gangrenosum (PG) is a reactive non-infectious inflammatory dermatosis falling under the spectrum of the neutrophilic dermatoses. There are several subtypes, with 'classical PG' as the most common form in approximately 85% cases. This presents as an extremely painful erythematous lesion which rapidly progresses to a blistered or necrotic ulcer. There is often a ragged undermined edge with a violaceous/erythematous border. The lower legs are most frequently affected although PG can present at any body site. Other subtypes include bullous, vegetative, pustular, peristomal and superficial granulomatous variants. The differential diagnosis includes all other causes of cutaneous ulceration as there are no definitive laboratory or histopathological criteria for PG. Underlying systemic conditions are found in up to 50% of cases and thus clinicians should investigate thoroughly for such conditions once a diagnosis of PG has been made. Treatment of PG remains largely anecdotal, with no national or international guidelines, and is selected according to severity and rate of progression. Despite being a well-recognised condition, there is often a failure to make an early diagnosis of PG. This diagnosis should be actively considered when assessing ulcers, as prompt treatment may avoid the complications of prolonged systemic therapy, delayed wound healing and scarring.
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Pioderma Gangrenoso , Diagnóstico Diferencial , Diagnóstico Precoce , Humanos , Pioderma Gangrenoso/diagnóstico , Pioderma Gangrenoso/patologia , Pioderma Gangrenoso/terapiaRESUMO
Deficits in cognitive flexibility, i.e. the ability to modify behavior in response to changes in the environment, are present in several psychiatric disorders and are often refractory to treatment. However, improving treatment response has been hindered by a lack of understanding of the neurobiology of cognitive flexibility. Using a rat model of chronic stress (chronic intermittent cold stress, CIC) that produces selective deficits in reversal learning, a form of cognitive flexibility dependent on orbitofrontal cortex (OFC) function, we have previously shown that JAK2 signaling is required for optimal reversal learning. In this study we explore the molecular basis of those effects. We show that, within the OFC, CIC stress reduces the levels of phosphorylated JAK2 and of ciliary neurotrophic factor (CNTF), a promoter of neuronal survival and an activator of JAK2 signaling, and that neutralizing endogenous CNTF with an intra-OFC microinjection of a specific antibody is sufficient to produce reversal-learning deficits similar to stress. Intra-OFC delivery of recombinant CNTF to CIC-stressed rats, at a dose that induces JAK2 and Akt but not STAT3 or ERK, ameliorates reversal-learning deficits, and Akt blockade prevents the positive effects of CNTF. Further analysis revealed that CNTF may exert its beneficial effects by inhibiting GSK3ß, a substrate of Akt and a regulator of protein degradation. We also revealed a novel mechanism of CNTF action through modulation of p38/Mnk1/eIF4E signaling. This cascade controls translation of select mRNAs, including those encoding several plasticity-related proteins. Thus, we suggest that CNTF-driven JAK2 signaling corrects stress-induced reversal learning deficits by modulating the steady-state levels of plasticity-related proteins in the OFC.
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Fator Neurotrófico Ciliar/farmacologia , Deficiências da Aprendizagem/tratamento farmacológico , Córtex Pré-Frontal/efeitos dos fármacos , Reversão de Aprendizagem/efeitos dos fármacos , Estresse Psicológico/psicologia , Animais , Fator Neurotrófico Ciliar/administração & dosagem , Fator Neurotrófico Ciliar/metabolismo , Cognição/efeitos dos fármacos , Temperatura Baixa , Feminino , Janus Quinase 2/metabolismo , Masculino , Ratos , Ratos Sprague-Dawley , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais/efeitos dos fármacosRESUMO
Stress-related neuropsychiatric (e.g., anxiety, depression) and cardiovascular diseases are frequently comorbid, though discerning the directionality of their association has been challenging. One of the most controllable risk factors for cardiovascular disease is salt intake. Though high salt intake is implicated in neuropsychiatric diseases, its direct neurobehavioral effects have seldom been explored. We reported that elevated salt intake in mice augments neuroinflammation, particularly after an acute stressor. Here, we explored how high salt consumption affected behavioral responses of mice to mildly arousing environmental and social tests, then assessed levels of the stress-related hormone corticosterone. Unexpectedly, anxiety-related behaviors in the elevated plus maze, open field, and marble burying test were unaffected by increased salt intake. However, nest building was diminished in mice consuming high salt, and voluntary social interaction was elevated, suggesting reduced engagement in ethologically-relevant behaviors that promote survival by attenuating threat exposure. Moreover, we observed significant positive correlations between social preference and subsequent corticosterone only in mice consuming increased salt, as well as negative correlations between open arm exploration in the elevated plus maze and corticosterone selectively in mice in the highest salt condition. Thus, heightened salt consumption reduces behavioral inhibition under relatively low-threat conditions, and enhances circulating corticosterone proportional to specific behavioral shifts. Considering the adverse health consequences of high salt intake, combined with evidence that increased salt consumption impairs inhibition of context-inappropriate behaviors, we suggest that prolonged high salt intake likely promulgates maladaptive behavioral and cardiovascular responses to perceived stressors that may explain some of the prevalent comorbidity between cardiovascular and neuropsychiatric diseases.
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Approximately one-third of women experience hysterectomy, or the surgical removal of the uterus, by 60 years of age, with most surgeries occurring prior to the onset of natural menopause. The ovaries are retained in about half of these surgeries, whereas for the other half hysterectomy occurs concurrently with oophorectomy. The dogma is that the nonpregnant uterus is dormant. There have been no preclinical assessments of surgical variations in menopause, including hysterectomy, with and without ovarian conservation, on potential endocrine and cognitive changes. We present a novel rat model of hysterectomy alongside sham, ovariectomy (Ovx), and Ovx-hysterectomy groups to assess effects of surgical menopause variations. Rats without ovaries learned the working memory domain of a complex cognitive task faster than did those with ovaries. Moreover, uterus removal alone had a unique detrimental impact on the ability to handle a high-demand working memory load. The addition of Ovx, that is, Ovx-hysterectomy, prevented this hysterectomy-induced memory deficit. Performance did not differ amongst groups in reference memory-only tasks, suggesting that the working memory domain is particularly sensitive to variations in surgical menopause. Following uterus removal, ovarian histology and estrous cycle monitoring demonstrated that ovaries continued to function, and serum assays indicated altered ovarian hormone and gonadotropin profiles by 2 months after surgery. These results underscore the critical need to further study the contribution of the uterus to the female phenotype, including effects of hysterectomy with and without ovarian conservation, on the trajectory of brain and endocrine aging to decipher the impact of common variations in gynecological surgery in women. Moreover, findings demonstrate that the nonpregnant uterus is not dormant, and indicate that there is an ovarian-uterus-brain system that becomes interrupted when the reproductive tract has been disrupted, leading to alterations in brain functioning.