Neonatal CD8+ T Cells Resist Exhaustion during Chronic Infection.

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.

Incongruences Between Facial Expression and Self-Reported Emotional Reactivity in Frontotemporal Dementia and Related Disorders.

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.

Resected WHO grade I meningioma and predictors of local control.

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.

Poor caregiver mental health predicts mortality of patients with neurodegenerative disease.

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.

An integrative group movement program for people with dementia and care partners together (Paired PLIÉ): initial process evaluation.

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.

Cligosiban, A Novel Brain-Penetrant, Selective Oxytocin Receptor Antagonist, Inhibits Ejaculatory Physiology in Rodents.

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.

Spheno-Orbital Meningiomas: An Analysis Based on World Health Organization Classification and Ki-67 Proliferative Index.

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.

Current techniques and outcomes in hysteroscopic sterilization: current evidence, considerations, and complications with hysteroscopic sterilization micro inserts.

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.

We can only be healthy if we love ourselves: Queer AIDS NGOs, kinship, and alternative families of care in China.

In this article, I draw from recent developments in the anthropological literatures on kinship and care to complicate and extend analyses of Chinese queer NGOs and AIDS activism. By highlighting the practical, moral, and political dimensions of daily life and work within Chinese queer NGOs, I argue that they constitute what I call "alternative families of care" by serving as important sources of material and emotional support and care for queer men, including increasing numbers of HIV-positive men who have sex with men, in a social climate that is still largely unsupportive and hostile toward both queerness and people living with HIV/AIDS. I also show how HIV/AIDS prevention and care are additionally regarded by many Chinese queer activists as an important political strategy for demonstrating the responsibility of queer men in the face of the AIDS crisis, achieving greater recognition from the government and society, and eventually attaining increased rights, including same-sex marriage.

Gynecologic Surgery in the Pediatric and Adolescent Populations: Review of Perioperative and Operative Considerations.

Gynecologists are often consulted on pediatric and adolescent patients who may require a surgical treatment for a gynecologic diagnosis. This patient population can present an interesting challenge for a nonpediatrician. It is helpful to review the differences in anatomy, alterations in drug dosing, surgical limitations, and counseling and consent requirements in this patient population before proceeding with a surgical treatment. This is a review of preoperative, intraoperative, and postoperative considerations for gynecologic surgery in the pediatric and adolescent patient population.

Dying for Money: The Effects of Global Health Initiatives on NGOs Working with Gay Men and HIV/AIDS in Northwest China.

Drawing on 17 months of ethnographic fieldwork (2007-2011), this article critically examines the consequences of two global health initiatives (GHIs), the Global Fund and the Gates Foundation, on NGOs engaged in HIV/AIDS prevention and treatment among gay men in northwest China. I argue that a short-term surge in funding provided by GHIs between 2008 and 2010 exacerbated preexisting conflicts between NGOs by promoting a neoliberal process in which the state outsourced public health services to civil society organizations, deliberately encouraging a climate of competition among NGOs. I also show how GHIs encouraged the bureaucratization and medicalization of one grassroots gay NGO, channeling its activities away from broader political and social objectives and compelling the group to develop a narrower and more entrepreneurial emphasis on HIV testing and treatment. This article contributes to a deeper ethnographic understanding of the complex and perhaps unintended consequences of GHIs.

Behavioral and metabolic contributions to thermoregulation in freely swimming leatherback turtles at high latitudes.

Leatherback turtles in the Northwest Atlantic Ocean have a broad geographic range that extends from nesting beaches near the equator to seasonal foraging grounds as far north as Canada. The ability of leatherbacks to maintain core body temperature (Tb) higher than that of the surrounding water is thought to be a key element of their biology that permits them to exploit productive waters at high latitudes. We provide the first recordings of Tb from freely swimming leatherbacks at a northern foraging ground, and use these data to assess the importance of behavioral adjustments and metabolic sources of heat for maintenance of the thermal gradient (Tg). The mean Tb for individual leatherbacks ranged from 25.4 ± 1.7 to 27.3 ± 0.3 °C, and Tg ranged from 10.7 ± 2.4 to 12.1 ± 1.7 °C. Variation in mean Tb was best explained by the amount of time that turtles spent in the relatively warm surface waters. A diel trend in Tb was apparent, with daytime cooling suggestive of prey ingestion and night-time warming attributable to endogenous heat production. We estimate that metabolic rates necessary to support the observed Tg are ~3 times higher than resting metabolic rate, and that specific dynamic action is an important source of heat for foraging leatherbacks.

Sex modulates the diet-induced changes to the plasma lipidome in a rat model of cardiorespiratory fitness.

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.

Recreational SCUBA divers' willingness to pay for marine biodiversity in Barbados.

The use of natural resources and the services they provide often do not have an explicit price and are therefore undervalued in decision-making, leading to environmental degradation. To 'monetize' the benefits from these services requires the use of non-market valuation techniques. Using a stated preference survey of recreational divers in Barbados conducted between 2007 and 2009, the economic value of marine biodiversity to recreational SCUBA divers in Barbados was estimated. In addition to a variety of demographic variables, divers were asked about their level of experience, expenditures related to travel and diving, and encounters with fish and sea turtles. Divers then completed a choice experiment, selecting between alternative dives with varying characteristics including price, crowding, fish diversity, encounters with sea turtles, and coral cover. Results indicate that divers in Barbados have a clear appreciation of reef quality variables. Willingness to pay for good coral cover, fish diversity and presence of sea turtles is significantly higher than prices paid for dives. In general, divers valued reef attributes similarly, although their appreciation of low density of divers at a site and high coral cover varied with prior diving experience. The results of this study demonstrate the economic value generated in Barbados by the recreational SCUBA diving industry and highlight the potential for substantial additional economic contributions with improvements to the quality of a variety of reef attributes. These results could inform management decisions regarding reef use and sea turtle conservation, and could aid in the development of informed 'win-win' policies aimed at maximizing returns from diving while reducing negative impacts often associated with tourism activities.

Empathic Conservatives and Moralizing Liberals: Political Intergroup Empathy Varies by Political Ideology and Is Explained by Moral Judgment.

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.

Comparing Self-Reported Dietary Intake to Provided Diet during a Randomized Controlled Feeding Intervention: A Pilot Study.

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.

Does prey size matter? Novel observations of feeding in the leatherback turtle (Dermochelys coriacea) allow a test of predator-prey size relationships.

Optimal foraging models predict that large predators should concentrate on large prey in order to maximize their net gain of energy intake. Here, we show that the largest species of sea turtle, Dermochelys coriacea, does not strictly adhere to this general pattern. Field observations combined with a theoretical model suggest that a 300 kg leatherback turtle would meet its energetic requirements by feeding for 3-4 h a day on 4 g jellyfish, but only if prey were aggregated in high-density patches. Therefore, prey abundance rather than prey size may, in some cases, be the overriding parameter for foraging leatherbacks. This is a classic example where the presence of small prey in the diet of a large marine predator may reflect profitable foraging decisions if the relatively low energy intake per small individual prey is offset by high encounter rates and minimal capture and handling costs. This study provides, to our knowledge, the first quantitative estimates of intake rate for this species.

Histotripsy for the Treatment of Uterine Leiomyomas: A Feasibility Study in Ex Vivo Uterine Fibroids.

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.

Lower activity linkage between caregivers and persons with neurodegenerative diseases is associated with greater caregiver anxiety.

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.