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1.
J Immunol ; 212(5): 834-843, 2024 Mar 01.
Article in English | MEDLINE | ID: mdl-38231127

ABSTRACT

Chronic viral infections, such as HIV and hepatitis C virus, represent a major public health problem. Although it is well understood that neonates and adults respond differently to chronic viral infections, the underlying mechanisms remain unknown. In this study, we transferred neonatal and adult CD8+ T cells into a mouse model of chronic infection (lymphocytic choriomeningitis virus clone 13) and dissected out the key cell-intrinsic differences that alter their ability to protect the host. Interestingly, we found that neonatal CD8+ T cells preferentially became effector cells early in chronic infection compared with adult CD8+ T cells and expressed higher levels of genes associated with cell migration and effector cell differentiation. During the chronic phase of infection, the neonatal cells retained more immune functionality and expressed lower levels of surface markers and genes related to exhaustion. Because the neonatal cells protect from viral replication early in chronic infection, the altered differentiation trajectories of neonatal and adult CD8+ T cells is functionally significant. Together, our work demonstrates how cell-intrinsic differences between neonatal and adult CD8+ T cells influence key cell fate decisions during chronic infection.


Subject(s)
Lymphocytic Choriomeningitis , Mice , Animals , Persistent Infection , Lymphocytic choriomeningitis virus , CD8-Positive T-Lymphocytes , Cell Differentiation , Mice, Inbred C57BL , Chronic Disease
2.
Biochim Biophys Acta Mol Cell Biol Lipids ; 1869(3): 159451, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38191091

ABSTRACT

OBJECTIVE: Individuals with higher intrinsic cardiorespiratory fitness (CRF) experience decreased rates of cardiometabolic disease and mortality, and high CRF is associated with increased utilization of fatty acids (FAs) for energy. Studies suggest a complex relationship between CRF, diet, and sex with health outcomes, but this interaction is understudied. We hypothesized that FA utilization differences by fitness and sex could be detected in the plasma metabolome when rats or humans were fed a high carbohydrate (HC) or high fat (HF) diet. METHODS: Male and female rats selectively bred for low (LCR) and high (HCR) CRF were fed a chow diet or a sucrose-free HF (45 % fat) or HC (10 % fat) diet. Plasma samples were collected at days 0, 3, and 14. Human plasma data was collected from male and female participants who were randomized into a HC or HF diet for 21 days. Samples were analyzed using liquid chromatography-mass spectrometry and regression statistics were used to quantify the effect of diet, CRF, and sex on the lipidome. RESULTS: In rats, the baseline lipidome is more significantly influenced by sex than by CRF, especially as elevated diglycerides, triglycerides, phosphatidylcholines, and lysophosphatidylcholines in males. A dynamic response to diet was observed 3 days after diet, but after 14 days of either diet, the lipidome was modulated by sex with a larger effect size than by diet. Data from the human study also suggests a sex-dependent response to diet with opposite directionality of affect compared to rats, highlighting species-dependent responses to dietary intervention.


Subject(s)
Cardiorespiratory Fitness , Rats , Humans , Male , Female , Animals , Lipidomics , Diet, High-Fat/adverse effects , Triglycerides
3.
Dietetics (Basel) ; 2(4): 334-343, 2023 Dec.
Article in English | MEDLINE | ID: mdl-38107624

ABSTRACT

Systematic and random errors based on self-reported diet may bias estimates of dietary intake. The objective of this pilot study was to describe errors in self-reported dietary intake by comparing 24 h dietary recalls to provided menu items in a controlled feeding study. This feeding study was a parallel randomized block design consisting of a standard diet (STD; 15% protein, 50% carbohydrate, 35% fat) followed by either a high-fat (HF; 15% protein, 25% carbohydrate, 60% fat) or a high-carbohydrate (HC; 15% protein, 75% carbohydrate, 10% fat) diet. During the intervention, participants reported dietary intake in 24 h recalls. Participants included 12 males (seven HC, five HF) and 12 females (six HC, six HF). The Nutrition Data System for Research was utilized to quantify energy, macronutrients, and serving size of food groups. Statistical analyses assessed differences in 24 h dietary recalls vs. provided menu items, considering intervention type (STD vs. HF vs. HC) (Student's t-test). Caloric intake was consistent between self-reported intake and provided meals. Participants in the HF diet underreported energy-adjusted dietary fat and participants in the HC diet underreported energy-adjusted dietary carbohydrates. Energy-adjusted protein intake was overreported in each dietary intervention, specifically overreporting beef and poultry. Classifying misreported dietary components can lead to strategies to mitigate self-report errors for accurate dietary assessment.

5.
Pers Soc Psychol Bull ; : 1461672231198001, 2023 Sep 15.
Article in English | MEDLINE | ID: mdl-37712634

ABSTRACT

Empathy has the potential to bridge political divides. Here, we examine barriers to cross-party empathy and explore when and why these differ for liberals and conservatives. In four studies, U.S. and U.K. participants (total N = 4,737) read hypothetical scenarios and extended less empathy to suffering political opponents than allies or neutral targets. These effects were strongly shown by liberals but were weaker among conservatives, such that conservatives consistently showed more empathy to liberals than liberals showed to conservatives. This asymmetry was partly explained by liberals' harsher moral judgments of outgroup members (Studies 1-4) and the fact that liberals saw conservatives as more harmful than conservatives saw liberals (Studies 3 and 4). The asymmetry persisted across changes in the U.S. government and was not explained by perceptions of political power (Studies 3 and 4). Implications and future directions are discussed.

6.
J Neuropsychiatry Clin Neurosci ; 35(2): 192-201, 2023.
Article in English | MEDLINE | ID: mdl-35989572

ABSTRACT

OBJECTIVE: Emotional reactivity normally involves a synchronized coordination of subjective experience and facial expression. These aspects of emotional reactivity can be uncoupled by neurological illness and produce adverse consequences for patient and caregiver quality of life because of misunderstandings regarding the patient's presumed internal state. Frontotemporal dementia (FTD) is often associated with altered social and emotional functioning. FTD is a heterogeneous disease, and socioemotional changes in patients could result from altered internal experience, altered facial expressive ability, altered language skills, or other factors. The authors investigated how individuals with FTD subtypes differ from a healthy control group regarding the extent to which their facial expressivity aligns with their self-reported emotional experience. METHODS: Using a compound measure of emotional reactivity to assess reactions to three emotionally provocative videos, the authors explored potential explanations for differences in alignment of facial expressivity with emotional experience, including parkinsonism, physiological reactivity, and nontarget verbal responses. RESULTS: Participants with the three main subtypes of FTD all tended to express less emotion on their faces than they did through self-report. CONCLUSIONS: Exploratory analyses suggest that reasons for this incongruence likely differ not only between but also within diagnostic subgroups.


Subject(s)
Frontotemporal Dementia , Humans , Frontotemporal Dementia/psychology , Self Report , Facial Expression , Quality of Life , Emotions/physiology
7.
J Wildl Dis ; 58(4): 756-768, 2022 10 01.
Article in English | MEDLINE | ID: mdl-35917401

ABSTRACT

Only one virus, Avipox, has been documented previously in wild birds in Hawaii. Using immunohistochemistry and PCR, we found that two native threatened Hawaiian Geese (Branta sandvicensis), one with multicentric histiocytoma and the other with toxoplasmosis, and one Laysan Albatross (Phoebastria immutabilis) with avian pox were infected with reticuloendotheliosis virus (REV). The virus was isolated from one of the geese by cell culture. Surveys of other Hawaiian geese with various pathologies, avian pox cases, and pox viral isolates using PCR failed to reveal REV, suggesting that the virus is uncommon, at least in samples examined. The full genome of the Gag, Pol, and Env genes were sequenced for all three infected birds and revealed geographic divergence of the Pol gene, suggesting it to be under strong selective pressure. Our finding of REV in Hawaii makes this only the second virus documented in native Hawaiian birds associated with pathology. Moreover, the presence of REV in a pelagic seabird is unusual. Future surveys should seek the reservoir of the virus in efforts to trace its origins.


Subject(s)
Reticuloendotheliosis virus , Animals , Hawaii/epidemiology
8.
Ultrasound Med Biol ; 48(8): 1652-1662, 2022 08.
Article in English | MEDLINE | ID: mdl-35641394

ABSTRACT

Uterine fibroids (leiomyomas), the most common benign tumors in women of reproductive age, are a frequent cause of abnormal vaginal bleeding and other reproductive complaints among women. This study investigates the feasibility of using histotripsy, a non-invasive, non-thermal focused ultrasound ablation method, to ablate uterine fibroids. Human fibroid samples (n = 16) were harvested after hysterectomy or myomectomy procedures at Carilion Memorial Hospital. Histotripsy was applied to ex vivo fibroids in two sets of experiments using a 700-kHz clinical transducer to apply multicycle histotripsy pulses and a prototype 500-kHz transducer to apply single-cycle histotripsy pulses. Ultrasound imaging was used for real-time treatment monitoring, and post-treatment ablation was quantified histologically using hematoxylin and eosin and Masson trichrome stains. Results revealed that multicycle histotripsy generated diffuse cavitation in targeted fibroids, with minimal cellular ablative changes after treatment with 2000 pulses/point. Single-cycle pulsing generated well-confined bubble clouds with evidence of early coagulative necrosis on histological assessment in samples treated with 2000 pulses/point, near-complete ablation in samples treated with 4000 pulses/point and complete tissue destruction in samples treated with 10,000 pulses/point. This study illustrates that histotripsy is capable of fibroid ablation under certain pulsing parameters and warrants further investigation as an improved non-invasive ablation method for the treatment of leiomyomas.


Subject(s)
High-Intensity Focused Ultrasound Ablation , Leiomyoma , Uterine Neoplasms , Feasibility Studies , Female , High-Intensity Focused Ultrasound Ablation/methods , Humans , Leiomyoma/surgery , Transducers , Ultrasonography , Uterine Neoplasms/surgery
9.
Psychophysiology ; 59(8): e14040, 2022 08.
Article in English | MEDLINE | ID: mdl-35315937

ABSTRACT

Physiological linkage refers to the degree to which two individuals' central/peripheral physiological activities change in coordinated ways. Previous research has focused primarily on linkage in the autonomic nervous system in laboratory settings, particularly examining how linkage is associated with social behavior and relationship quality. In this study, we examined how linkage in couples' daily somatic activity (e.g., synchronized movement measured from wrist sensors)-another important aspect of peripheral physiology-was associated with relationship quality and mental health. We focused on persons with neurodegenerative diseases (PWNDs) and their spousal caregivers, whose linkage might have direct implications for the PWND-caregiver relationship and caregiver's health. Twenty-two PWNDs and their caregivers wore wristwatch actigraphy devices that provided continuous measurement of activity over 7 days at home. PWND-caregiver activity linkage was quantified by the degree to which activity was "in-phase" or "anti-phase" linked (i.e., coordinated changes in the same or opposite direction) during waking hours, computed by correlating minute-by-minute activity levels averaged using a 10-min rolling window. Caregivers completed well-validated surveys that assessed their mental health (including anxiety and depression) and relationship quality with the PWND. We found that lower in-phase activity linkage, but not anti-phase linkage, was associated with higher caregiver anxiety. These dyad-level effects were robust, remaining significant after adjusting for somatic activity at the individual level. No effects were found for caregiver depression or relationship quality. These findings suggest activity linkage and wearables may be useful for day-by-day monitoring of vulnerable populations such as family caregivers. We offered several possible explanations for our findings.


Subject(s)
Caregivers , Neurodegenerative Diseases , Anxiety/psychology , Caregivers/psychology , Depression/psychology , Humans , Mental Health , Surveys and Questionnaires
10.
J Rural Health ; 37(4): 788-800, 2021 09.
Article in English | MEDLINE | ID: mdl-33978989

ABSTRACT

PURPOSE: To determine the effectiveness of telephone motivational coaching delivered by veteran peers to improve mental health (MH) treatment engagement among veterans. METHODS: Veterans receiving primary care from primarily rural VA community-based outpatient clinics were enrolled. Veterans not engaged in MH treatment screening positive for ≥1 MH problem(s) were randomized to receive veteran peer-delivered feedback on MH screen results and referrals plus 4 sessions of telephone motivational coaching (intervention) versus veteran peer-delivered MH results and referrals without motivational coaching (control). Blinded telephone assessments were conducted at baseline, 8, 16, and 32 weeks. Cox proportional hazard models compared MH clinician-directed treatment initiation between groups; descriptive analyses compared MH treatment retention, changes in MH symptoms, quality of life, and self-care. FINDINGS: Among 272 veterans screening positive for ≥1 MH problem(s), 45% who received veteran peer telephone motivational coaching versus 46% of control participants initiated MH treatment (primary outcome) (hazard ratio: 1.09, 95% CI: 0.76-1.57), representing no between-group differences. In contrast, veterans receiving veteran peer motivational coaching achieved significantly greater improvements in depression, posttraumatic stress disorder and cannabis use scores, quality of life domains, and adoption of some self-care strategies than controls (secondary outcomes). Qualitative data revealed that veterans who received veteran peer motivational coaching may no longer have perceived a need for MH treatment. CONCLUSIONS: Among veterans with MH problems using predominantly rural VA community clinics, telephone peer motivational coaching did not enhance MH treatment engagement, but instead had positive effects on MH symptoms, quality of life indicators, and use of self-care strategies.


Subject(s)
Mentoring , Veterans , Humans , Mental Health , Quality of Life , Telephone
11.
J Neurooncol ; 152(1): 145-151, 2021 Mar.
Article in English | MEDLINE | ID: mdl-33420897

ABSTRACT

INTRODUCTION: Despite optimal surgical resection, meningiomas may recur, with increasing grade and the degree of resection being predictive of risk. We hypothesize that an increasing Ki67 correlates with a higher risk of recurrence of resected WHO grade I meningiomas. METHODS: The study population consisted of patients with resected WHO grade 1 meningiomas in locations outside of the base of skull. Digitally scanned slides stained for Ki67 were analyzed using automatic image analysis software in a standardized fashion. RESULTS: Recurrence was observed in 53 (17.7%) of cases with a median follow up time of 25.8 months. Ki67 ranged from 0 to 30%. Median Ki67 was 5.1% for patients with recurrence and 3.5% for patients without recurrence. In unadjusted analyses, high Ki-67 (≥ 5 vs. < 5) vs. ≥ 5) was associated with over a twofold increased risk of recurrence (13.1% vs. 27% respectively; HR 2.1731; 95% CI [1.2534, 3.764]; p = 0.006). After Adjusting for patient or tumor characteristics, elevated Ki-67 remained significantly correlated with recurrence. Grade 4 Simpson resection was noted in 71 (23.7%) of patients and it was associated with a significantly increased risk of recurrence (HR 2.56; 95% CI [1.41, 4.6364]; p = 0.002). CONCLUSIONS: WHO grade 1 meningiomas exhibit a significant rate of recurrence following resection. While Ki-67 is not part of the WHO grading criteria of meningiomas, a value greater than 5% is an independent predictor for increased risk of local recurrence following surgical resection.


Subject(s)
Meningeal Neoplasms/pathology , Meningioma/pathology , Mitotic Index , Neoplasm Recurrence, Local/pathology , Adult , Aged , Aged, 80 and over , Biomarkers, Tumor/analysis , Female , Humans , Ki-67 Antigen/analysis , Male , Meningeal Neoplasms/surgery , Meningioma/surgery , Middle Aged , Neoplasm Grading , Retrospective Studies , World Health Organization
12.
Appl Immunohistochem Mol Morphol ; 29(1): e1-e4, 2021 01.
Article in English | MEDLINE | ID: mdl-31135447

ABSTRACT

Crystal-storing histiocytosis (CSH) is a non-neoplastic histiocytic proliferation containing crystalline material, usually associated with an underlying lymphoproliferative or plasmacytic disorder. The crystalline structures are typically derived from kappa light chain immunoglobulins. The lesions of CSH are comprised of sheets of histiocytes with abundant eosinophilic cytoplasm containing variably prominent, elongated crystals. This rare phenomenon is important to recognize, as it is known to morphologically obscure an underlying neoplasm. Histologically, the cells of CSH may closely mimic Gaucher cells, as well as the "pseudo-Gaucher" cells sometimes encountered in chronic myeloid leukemia. The distinction between the cells of CSH and that of histologic mimics may be made more definitively through the use of electron microscopy, as the crystalline inclusions seen in CSH display characteristic size, shape, and localization within the cells. Here, we report 2 rare cases of CSH diagnosed by morphology, immunohistochemistry, and ultrastructural examination. The first case presented was diagnosed concurrently with plasma cell myeloma, and the second case discussed was diagnosed in association with marginal zone lymphoma.


Subject(s)
Histiocytosis , Immunoglobulin kappa-Chains/metabolism , Plasma Cells , Aged , Aged, 80 and over , Female , Histiocytosis/metabolism , Histiocytosis/pathology , Humans , Immunohistochemistry , Male , Microscopy, Electron , Plasma Cells/metabolism , Plasma Cells/ultrastructure
13.
Aging Ment Health ; 24(6): 971-977, 2020 06.
Article in English | MEDLINE | ID: mdl-30744387

ABSTRACT

Objectives: To understand feedback from participants in Paired PLIÉ (Preventing Loss of Independence through Exercise), a novel, integrative group movement program for people with dementia and their care partners, in order to refine the intervention and study procedures.Method: Data sources included daily logs from the first Paired PLIÉ RCT group, final reflections from the second Paired PLIÉ RCT group, and responses to requests for feedback and letters of support from Paired PLIÉ community class participants. All data are reports from care partners. The qualitative coding process was iterative and conducted with a multidisciplinary team. The coding team began with a previously established framework that was modified and expanded to reflect emerging themes. Regular team meetings were held to confirm validity and to reach consensus around the coding system as it was developed and applied. Reliability was checked by having a second team member apply the coding system to a subset of the data.Results: Key themes that emerged included care partner-reported improvements in physical functioning, cognitive functioning, social/emotional functioning, and relationship quality that were attributed to participation in Paired PLIÉ. Opportunities to improve the intervention and reduce study burden were identified. Care partners who transitioned to the community class after participating in the Paired PLIÉ study reported ongoing benefits.Conclusion: These qualitative results show that people with dementia and their care partners can participate in and benefit from community-based programs like Paired PLIÉ that include both partners, and focus on building skills to maintain function and quality of life.


Subject(s)
Caregivers , Dementia , Dementia/therapy , Exercise , Humans , Quality of Life , Reproducibility of Results
14.
J Gerontol B Psychol Sci Soc Sci ; 74(6): 975-987, 2019 08 21.
Article in English | MEDLINE | ID: mdl-29385515

ABSTRACT

OBJECTIVE: Providing care for a spouse with dementia is associated with an increased risk for poor mental health. To determine whether this vulnerability in caregivers is related to the expression of positive emotion, we examined 57 patients with Alzheimer's disease and behavioral variant frontotemporal dementia and their spouses as they discussed a marital conflict. METHOD: Facial behavior during the discussion was objectively coded to identify Duchenne (i.e., genuine) smiles and non-Duchenne (i.e., polite) smiles. Caregiver mental health was measured using the Medical Outcomes Survey. RESULTS: Greater expression of Duchenne smiles by patients was associated with better caregiver mental health, even when accounting for covariates (i.e., diagnosis, patient cognitive functioning, and caregiver marital satisfaction). Greater expression of non-Duchenne smiles by patients was associated with worse caregiver health, but only when covariates were entered in the model. Expression of Duchenne and non-Duchenne smiles by caregivers was not associated with caregiver mental health. DISCUSSION: Patients' expression of Duchenne and non-Duchenne smiles may reveal important aspects of the emotional quality of the patient-caregiver relationship that influence caregiver burden and mental health.


Subject(s)
Alzheimer Disease/psychology , Caregivers/psychology , Emotions , Facial Expression , Frontotemporal Dementia/psychology , Mental Health , Smiling/psychology , Spouses/psychology , Aged , Alzheimer Disease/nursing , Female , Frontotemporal Dementia/nursing , Humans , Male , Middle Aged , Personal Satisfaction
15.
Soc Cogn Affect Neurosci ; 14(12): 1453-1465, 2019 12 30.
Article in English | MEDLINE | ID: mdl-31993653

ABSTRACT

Frontotemporal dementia (FTD), a neurodegenerative disease broadly characterized by socioemotional impairments, includes three clinical subtypes: behavioral variant FTD (bvFTD), semantic variant primary progressive aphasia (svPPA) and non-fluent variant primary progressive aphasia (nfvPPA). Emerging evidence has shown emotional reactivity impairments in bvFTD and svPPA, whereas emotional reactivity in nfvPPA is far less studied. In 105 patients with FTD (49 bvFTD, 31 svPPA and 25 nfvPPA) and 27 healthy controls, we examined three aspects of emotional reactivity (physiology, facial behavior and subjective experience) in response to a sad film. In a subset of the sample, we also examined the neural correlates of diminished aspects of reactivity using voxel-based morphometry. Results indicated that all three subtypes of FTD showed diminished physiological responding in respiration rate and diastolic blood pressure; patients with bvFTD and svPPA also showed diminished subjective experience, and no subtypes showed diminished facial behavior. Moreover, there were differences among the clinical subtypes in brain regions where smaller volumes were associated with diminished sadness reactivity. These results show that emotion impairments extend to sadness reactivity in FTD and underscore the importance of considering different aspects of sadness reactivity in multiple clinical subtypes for characterizing emotional deficits and associated neurodegeneration in FTD.


Subject(s)
Brain/physiopathology , Frontotemporal Dementia/physiopathology , Sadness/physiology , Sadness/psychology , Aged , Emotions/physiology , Female , Humans , Male , Middle Aged , Neurodegenerative Diseases
16.
J Sex Med ; 15(12): 1698-1706, 2018 12.
Article in English | MEDLINE | ID: mdl-30527053

ABSTRACT

INTRODUCTION: Few treatments are available for men with premature ejaculation (PE); oxytocin (OT) receptor antagonism in the central nervous system (CNS) is a potential new approach. AIM: To determine if cligosiban selectively inhibits human OT receptors, penetrates the CNS, shows pharmacology in the CNS, and effects ejaculatory physiology in pre-clinical systems. METHODS: Experiments complied with United Kingdom legislation and were subject to local ethical review. In vitro potency and selectivity of cligosiban was assessed using recombinant and native OT receptor systems including both neuronal and non-neuronal cell types. Selectivity was determined over neighboring V1A, V1B, and V2 vasopressin receptors using a combination of recombinant and native vasopressin receptor assay systems. To determine an effect on central OT receptors and on ejaculation, cligosiban was evaluated in 2 anesthetized rat models-the electromyography model of ejaculatory physiology and a model of OT-mediated CNS neuronal firing. The CNS penetration of cligosiban was also determined by measuring cerebrospinal fluid and plasma drug concentrations following an intravenous (IV) infusion in rats. MAIN OUTCOME MEASURE: These were functional measures of pharmacology in vitro, in cell lines and tissues, and in vivo in rats. RESULTS: Cligosiban is a potent OT receptor antagonist, with a base dissociation constant of 5.7 nmol/L against native human uterine smooth muscle cell OT receptors. Cligosiban displays similar antagonistic potency against human recombinant and rat native OT receptors, including neuronal OT receptors. Cligosiban demonstrates >100-fold selectivity over human V1A, V1B, and V2 vasopressin receptors. In the electromyography model, cligosiban (0.9 mg/kg, IV bolus) reduced the bulbospongiosum burst pattern and contraction amplitude associated with ejaculation. In the anesthetized CNS neuronal firing model, the same dosing regimen of cligosiban (0.9 mg/kg IV bolus) modulated the OT-mediated response in the nucleus tractus solitarius. After systemic dosing to rats, cligosiban showed good CNS penetration. CLINICAL IMPLICATIONS: As the first highly selective and centrally penetrant OT receptor antagonist, cligosiban represents a promising compound to test the clinical hypothesis that antagonism of central OT receptors may be of therapeutic benefit in the treatment of PE. STRENGTH & LIMITATIONS: The pharmacology and selectivity of cligosiban is determined using functional assays in recombinant cell lines, native cell lines, and tissue. Functional outcomes in in vivo systems are linked to CNS measures of pharmacology. The translation of the animal models of ejaculation to PE in man is unproven. CONCLUSION: Cligosiban, a potent, selective OT receptor antagonist, demonstrated CNS penetration and pharmacology and, using the same dosing regimen, inhibited apomorphine-induced ejaculation in rats. Cligosiban is a promising compound to test the clinical hypothesis that antagonism of central OT receptors may be of therapeutic benefit in the treatment of PE. Wayman C, Russell R, Tang K, et al. Cligosiban, A Novel Brain Penetrant Selective Oxytocin Receptor Antagonist, Inhibits Ejaculatory Physiology in Rodents. J Sex Med 2018;15:1698-1706.


Subject(s)
Ejaculation/drug effects , Oxytocin/pharmacology , Premature Ejaculation/drug therapy , Receptors, Oxytocin/antagonists & inhibitors , Receptors, Vasopressin/drug effects , Animals , Brain/metabolism , Dose-Response Relationship, Drug , Hormone Antagonists/pharmacology , Humans , Male , Rats , Rodentia , United Kingdom
17.
Ophthalmic Plast Reconstr Surg ; 34(2): 143-150, 2018.
Article in English | MEDLINE | ID: mdl-28350689

ABSTRACT

PURPOSE: To evaluate the clinical behavior of spheno-orbital meningiomas with regard to World Health Organization (WHO) tumor grade and Ki-67, a cellular marker of proliferation. METHODS: A retrospective review over a 16-year period of the demographic, clinical, radiographic, and surgical data of all patients with spheno-orbital meningioma who underwent surgical resection. Tumor specimens were examined histologically using the current WHO 2016 classification and immunohistochemically using Ki-67/MIB-1 monoclonal antibody. RESULTS: Thirty-eight patients met all inclusion criteria: 78.9% of tumors were WHO grade I with a mean Ki-67 of 3.76, and 93% of patients were clinically stable at last follow up; 10.5% of lesions were WHO grade II (atypical) with a mean Ki-67 of 14.93, and 10.5% of lesions were WHO grade III (anaplastic) with a mean Ki-67 of 58.3. All grade II and III meningiomas exhibited an aggressive clinical course. There were statistically significant correlations between disease clinical progression and WHO tumor grade (p < 0.001), between disease clinical progression and Ki-67 (p < 0.001), and between increasing Ki-67 index and higher WHO grade (p < 0.001). For WHO grade I lesions, a Ki-67 of ≥3.3 correlated with recurrence (p = 0.0256). Overall, disease-specific mortality occurred in 5 (13%) patients. CONCLUSIONS: Ki-67 index is a valuable marker to use in conjunction with WHO grade to predict meningioma behavior, particularly in histologically borderline lesions, and possibly to identify a subset of WHO grade I tumors at risk of recurrence. This combination of methods can aid in tailoring treatment and surveillance strategies.


Subject(s)
Biomarkers, Tumor/metabolism , Ki-67 Antigen/metabolism , Meningioma , Orbital Neoplasms , Sphenoid Bone , Adult , Aged , Aged, 80 and over , Antibodies, Antinuclear/metabolism , Antibodies, Monoclonal/metabolism , Female , Humans , Immunohistochemistry , Male , Meningioma/classification , Meningioma/metabolism , Meningioma/pathology , Middle Aged , Orbital Neoplasms/classification , Orbital Neoplasms/metabolism , Orbital Neoplasms/pathology , Retrospective Studies , World Health Organization
18.
Proc Natl Acad Sci U S A ; 114(28): 7319-7324, 2017 07 11.
Article in English | MEDLINE | ID: mdl-28655841

ABSTRACT

Dementia and other neurodegenerative diseases cause profound declines in functioning; thus, many patients require caregivers for assistance with daily living. Patients differ greatly in how long they live after disease onset, with the nature and severity of the disease playing an important role. Caregiving can also be extremely stressful, and many caregivers experience declines in mental health. In this study, we investigated the role that caregiver mental health plays in patient mortality. In 176 patient-caregiver dyads, we found that worse caregiver mental health predicted greater patient mortality even when accounting for key risk factors in patients (i.e., diagnosis, age, sex, dementia severity, and patient mental health). These findings highlight the importance of caring for caregivers as well as patients when attempting to improve patients' lives.


Subject(s)
Caregivers/psychology , Mental Disorders/diagnosis , Mental Health , Neurodegenerative Diseases/mortality , Neurodegenerative Diseases/therapy , Activities of Daily Living , Aged , Alzheimer Disease , Anxiety/complications , Cost of Illness , Depression/complications , Female , Humans , Male , Middle Aged , Risk Factors , Severity of Illness Index , Surveys and Questionnaires , United States
19.
Curr Opin Obstet Gynecol ; 29(4): 218-224, 2017 Aug.
Article in English | MEDLINE | ID: mdl-28537948

ABSTRACT

PURPOSE OF REVIEW: To describe the current data regarding effectiveness, complications, postoperative evaluation, and surgical interventions associated with Essure hysteroscopic sterilization. RECENT FINDINGS: Hysteroscopic sterilization is a commonly performed procedure that is offered as a well tolerated, effective, outpatient method of permanent sterilization. Over the past several years, concerns have been raised regarding correct placement and postoperative complications. This has led to statements by both the Food and Drug Administration (FDA) in October, 2016 and American Association of Gynecologic Laparoscopists in February, 2017, as a significant portion of women seek removal of these devices. A current black-box warning issued by the FDA in 2016 recommends discussion of 'the probabilities of rates or events' of adverse outcomes associated with Essure placement. SUMMARY: Although hysteroscopic sterilization is usually a safe, effective option for permanent contraception, new evidence regarding complications has emphasized the need for proper education and counseling. Appropriate patient selection and knowledge of potential complications is paramount to ensuring patients, and medical providers are well informed and have realistic expectations regarding potential placement and postoperative issues.


Subject(s)
Hysteroscopy/methods , Sterilization, Reproductive/methods , Sterilization, Tubal/methods , Contraception/adverse effects , Female , Humans , Hysteroscopy/adverse effects , Intrauterine Devices/adverse effects , Laparoscopy , Patient Education as Topic , Patient Selection , Postoperative Complications , Pregnancy , Risk Factors , Societies, Medical , Sterilization, Reproductive/adverse effects , Sterilization, Tubal/adverse effects , Treatment Outcome , United States , United States Food and Drug Administration
20.
J Minim Invasive Gynecol ; 24(7): 1062, 2017.
Article in English | MEDLINE | ID: mdl-28132872
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