Search

Introduction Cancer is a prominent cause of mortality in today’s active duty service members (ADSMs), killing over 700 ADSMs between 2004 and 2015. Hence, more research is needed to better understand the survival of U.S. service members with cancer. Lymphoma is the most common hematologic malignancy diagnosed in ADSMs, serving as a good cancer type to study. Materials and Methods The Department of Defense tumor registry and the Surveillance, Epidemiology, and End Result (SEER) databases were retrospectively accessed to analyze overall survival (OS) of ADSMs with lymphoma and to compare outcomes with matched civilians. ADSMs with Hodgkin lymphoma (HL), diffuse large B-cell lymphoma (DLBCL), and indolent lymphoma diagnosed between 1997 and 2017 were included, and SEER comparator patients were matched by age, sex, race, stage, and year of diagnosis using a 4:1 ratio of civilians to ADSMs. Results There were 1,170, 443, and 284 ADSMs with HL, DLBCL, and indolent lymphoma, respectively, and all three groups had superior OS when compared to their matched civilian counterparts with 35%, 49%, and 48% reductions in the risk of death, respectively. There were no differences in ADSM survival based on race, sex, or rank, despite disparities being pervasive in the civilian sector. Conclusions Service members with lymphoma have superior survival than their matched civilian counterparts, without evident racial or sex disparities. Results of this study are favorable in terms of readiness. Further research on cancer mortality in ADSMs is needed to improve long-term outcomes.

Major Histocompatibility Complex I (MHC-I) function in the CNS is still being determined after previously being thought to be absent from the brain. MHC-I expression increases with brain aging in mouse, rat, and human whole tissue analyses. Neuronal MHC-I expression has been proposed to regulate developmental synapse elimination and tau pathology in Alzheimer’s disease (AD). However, the CNS cellular localization of MHC-I expression has been unclear. Across newly generated and publicly available ribosomal profiling, cell sorting, and single cell data, microglia were found to be the primary source of classical and non-classical MHC-I in mice and humans. TRAP-qPCR analysis of 3-6 m.o. and 18-22 m.o. mice revealed significant age-related induction of B2m, H2-D1, H2-K1, H2-M3, H2-Q6, and Tap1 in microglia but not in astrocytes and neurons. Across a timecourse from 12-23 m.o., microglial MHC-I gradually increases until 21 m.o. and then accelerates. MHC-I protein was also enriched in microglia and increased with aging. Expression of MHC-I binding Leukocyte Immunoglobulin-like (Lilr) and Paired immunoglobin-like type 2 (Pilr) receptors in microglia but not astrocytes or neurons opens the possibility of cell-autonomous signaling and are also increased with aging in mice and humans. Increased microglial MHC-I, Lilrs, and Pilrs were observed in mouse AD models and human data across numerous studies and in RNA-Seq of microglia from APP-PSEN1 mice. MHC-I expression occurred concurrently with p16 suggesting an association with cellular senescence. The conserved induction of MHC-I, Lilrs, and Pilrs with aging and AD open the possibility of cell-autonomous signaling to regulate microglial reactivation.

To determine the effectiveness of technetium-99m (Between June 2018 and October 2020 all patients with new indeterminate small renal masses (SRMs) underwentA total of 74 patients with SRMs were investigated with

World-wide, nearly 40% of the adult population is classified as clinically obese. Central inflammation is highly correlated with obesity and increases morbidity and deterioration of health. The hypothalamus is a brain region that governs many facets of energy homeostasis, and melanocortins in the hypothalamus both decrease feeding and increase metabolism via melanocortin-4 receptors (MC4Rs). Although MC4Rs are present on neurons and astrocytes (aMC4R) previous work has focused almost exclusively on the neuronal population with the contribution of aMC4R on these processes largely unknown. Our objective was to determine the effects of hypothalamic aMC4R deletion on central and peripheral inflammation, as well as feeding and body weight homeostasis. Adult MC4R fl/fl mice were microinjected with an astrocyte-specific promoter driving Cre-expression (AAV-GFAP-GFP-Cre) or AAV-control (AAV-GFAP-GFP; n=4-7/group/sex) to produce a hypothalamic knock-down of aMC4R (KD). Body weight and composition were monitored throughout the study, and indirect calorimetry was conducted at 1 and 4 weeks after AAV injection. Acquisition of operant self-administration of palatable food was also examined. Mice were euthanized 7-8 weeks post AAV injection and brain and tissue samples were collected. We observed a significant increase in body weight, feeding, and energy balance in the KD group compared to control group. Inflammation was significantly increased centrally in KD mice within the hypothalamus, but not peripherally within serum. Additionally, aMC4R KD mice trended towards an increased reward learning for palatable food. This is the first demonstration that hypothalamic aMC4R, independent of neuronal MC4R, is important in modulating inflammation as well as contributing to energy balance. These results provide an integral understanding of the aMC4R system that will provide the foundation for future studies investigating the role of aMC4R in various disease states.

Objectives To examine how people living with dementia at home engage in meaningful activities, a critical component of quality of life. Design Ethnographic study design using semistructured interviews, participant-observation, and ethnographic analysis. Setting and Participants Home setting. People living with dementia were recruited through 3 geriatrics programs in the San Francisco Bay Area, along with 1 primary live-in care partner for each. Participants were purposively sampled to maximize heterogeneity of dementia severity and life experience. Measurements We asked participants to self-identify and report meaningful activity engagement prior to dementia onset and during the study period using a structured questionnaire, semistructured dyadic interviews, and observed engagement in activities. Home visits were audio-recorded, transcribed, and inductively analyzed using thematic analysis. Results Twenty-one people living with dementia (mean age 84 years, 38% women) and 20 care partners (59 years, 85% women), including 40% professionals, 35% spouse/partners, and 15% adult children. Overarching theme: specific activities changed over time but underlying sources of meaning and identity remained stable. As dementia progressed, meaningful activity engagement took 3 pathways. Pathway 1: Activities continued with minimal adaptation when engagement demanded little functional or cognitive ability (eg, watching football on TV). Pathway 2: care partners adapted or replaced activities when engagement required greater functional or cognitive abilities (eg, traveling overseas). This pathway was associated with caregiving experience, nursing training, and strong social support structures. Pathway 3: care partners discontinued meaningful activity engagement. Discontinuation was associated with severe caregiver burden, coupled with illness, injury, or competing caregiving demands severe enough to impact their ability to facilitate activities. Conclusions and Implications For people living with dementia at home, underlying sources of meaning and identity remains stable despite changes in meaningful activity engagement. Many of the factors associated with adaptation vs discontinuation over time are modifiable and can serve as targets for intervention.

Introduction:Stingray envenomation is a marine injury suffered by ocean goers throughout the world. No prospective studies exist on the various outcomes associated with these injuries.Study Objective:The aim of this study was to perform a prospective, observational study of human stingray injuries to determine the natural history, acute and subacute complications, prevalence of medical evaluation, and categories of medical treatment.Methods:This study prospectively studied a population of subjects who were injured by stingrays at Seal Beach, California (USA) from July 2012 through September 2016 and did not immediately seek emergency department evaluation. Subjects described their initial injury and provided information on their symptoms, medical evaluations, and medical treatment for the injury at one week and one month after the injury. This information was reported as descriptive statistics.Results:A total of 393 participants were enrolled in the study; 313 (80%) of those completed the one-week follow-up interview and 279 (71%) participants completed both the one-week and one-month follow-up interviews. Overall, 234 (75%) injuries occurred to the foot. One hundred sixty-three (52%) patients had complete resolution of their pain within one week and 261 (94%) had either complete resolution or improvement of pain by one month. Sixty-eight (22%) subjects reported being evaluated by a physician and a total of 49 (17%) subjects reported antibiotic treatment for their wound. None of the subjects required parenteral antibiotics or hospital admission.Conclusion:The majority of stingray victims recover from stingray injury without requiring antibiotics. A subset of subjects will have on-going wound pain after one month. The need for parenteral antibiotics or hospital admission is rare.

The Earth’s magnetosphere is the outermost layer of the geospace system deflecting energetic charged particles from the Sun and solar wind. The solar wind has major impacts on the Earth’s magnetosphere, but it is unclear whether the same holds for solar flares—a sudden eruption of electromagnetic radiation on the Sun. Here we use a recently developed whole geospace model combined with observational data from the 6 September 2017 X9.3 solar flare event to reveal solar flare effects on magnetospheric dynamics and on the electrodynamic coupling between the magnetosphere and its adjacent ionosphere, the ionized part of Earth’s upper atmosphere. We observe a rapid and large increase in flare-induced photoionization of the polar ionospheric E-region at altitudes between 90 km and 150 km. This reduces the efficiency of mechanical energy conversion in the dayside solar wind–magnetosphere interaction, resulting in less Joule heating of the Earth’s upper atmosphere, a reconfiguration of magnetosphere convection, as well as changes in dayside and nightside auroral precipitation. This work thus demonstrates that solar flare effects extend throughout the geospace via electrodynamic coupling, and are not limited—as previously believed—to the atmospheric region where radiation energy is absorbed1. The solar wind affects the magnetosphere, but whether this holds true for solar flares was unclear. By combining geospace modelling with observations, solar flares are shown to influence the dynamics of the magnetosphere and its ionosphere coupling.

Subauroral polarization streams (SAPS) typically refer to an enhanced westward plasma flow channel in the duskside subauroral ionosphere. SAPS overlap with the low-latitude part of downward Region-2 field-aligned currents (FACs). The relatively low subauroral conductance in this region requires a strong electric field for current closure, which drives the fast sunward plasma flow. Observations have shown dynamic variability of SAPS under various solar wind and interplanetary magnetic field (IMF) conditions, which are related to the variability of FACs and auroral precipitation, as well as their source regions in the ring current and plasmasheet. In this study, we use satellite observations and numerical simulations with the state-of-the-art Multiscale Atmosphere Geospace Environment (MAGE) model to investigate: 1) The role of diffuse electron precipitation in the formation of SAPS; 2) SAPS variability under IMF BY; and 3) Dawnside (as opposed to the more conventional duskside) SAPS as a unique feature of major geomagnetic storms. With data-model comparison, we will demonstrate that SAPS result from the different behaviors of ring current ions and plasma sheet electrons, and the corresponding self-consistent response of the ionosphere-thermosphere system via electrodynamic and particle coupling with the magnetosphere. We conclude that SAPS distribution and variability represent a fundamental feature of the geospace response to solar disturbances during storm time.

The role of diffuse electron precipitation in forming subauroral polarization streams (SAPS) is investigated with the Multiscale Atmosphere-Geospace Environment (MAGE) model. Diffuse precipitation ...

As part of the Whole Heliosphere and Planetary Interactions (WHPI) initiative, contrasting drivers of radiation belt electron response at solar minimum have been investigated with MHD-test particle...

Among contemporary liberal political theorists in the West, there appears to be a standoff between two camps. One camp promotes tighter social bonds through collective responsibility and patriotic fellow-feeling while the other insists on the need for relaxed social bonds through respect for individual freedom. This essay shows how two Vietnamese thinkers—Ho Chi Minh (1872–1969) and Nguyen Manh Tuong (1909–1997)—can help move this intractable debate about collective responsibility and individual freedom beyond statements of principle to a more pragmatic discussion of what should be done to maintain a healthy polity. They present an alternative to the static standoff, arguing that dynamic oscillation between two activities can forge national fraternal solidarity while also respecting individual freedom when the needs arise: ‘criticism and self-criticism' which tightens social bonds, and ‘liberal self-exploration' which relaxes social bonds.

Thermospheric mass density perturbations are commonly observed during geomagnetic storms. The sources of these perturbations have long been controversial. In this study, we investigated the thermos...

Unidirectional blood flow in the left side of the heart is regulated by the mitral valve. To better understand the mitral valve function, researchers have examined the structural and mechanical properties of the mitral valve leaflets; however, limitations of the previous studies include the use of mechanics- and structure-altering tissue modifications (e.g., optical clearing) that limit the ability to quantify the unique load-dependent reorientation and realignment of the collagen fibers as well as their interrelation with the valve tissue mechanics. Herein, we aimed to circumvent these limitations by utilizing an integrated polarized-light imaging and biaxial testing system for understanding the mechanics-microstructure interrelationship for porcine mitral valve leaflets. We further performed constitutive modeling and evaluated the accuracy of the affine fiber kinematics theory. From the tissue mechanics perspective, the posterior leaflet was more extensible in the radial direction than the anterior leaflet (14.2% difference in radial tissue stretch), while exhibiting smaller collagen and elastin moduli based on the determined constitutive model parameters. From the collagen microstructure's standpoint, the posterior leaflet had smaller increases in optical anisotropy (closely related to the degree of fiber alignment) than the anterior leaflet (32.8±7.7% vs. 50.0±19.7%). Further, the leaflets were found to possess two distinct fiber families - one family oriented along the circumferential tissue direction, and another more disperse family with a 30°-40° offset from the first fiber family. Finally, affine fiber kinematics consistently underpredicted the collagen fiber reorientations Overall, this study improved our understanding of the mitral valve leaflets that is essential for facilitating tissue-emulated valve replacement and cardiac valve modeling frameworks.

Introduction: Emerging evidence suggests central systolic blood pressure (cSBP) and augmentation index are superior predictors of adverse cardiovascular outcomes as compared to peripheral systolic blood pressure (pSBP). Enhanced external counterpulsation (EECP) is a non-invasive treatment modality approved for the management of refractory angina. The degree of benefit from EECP on central hemodynamics and arterial stiffness remains unknown. This meta-analysis evaluated the effect of EECP on peripheral (office) blood pressure and central hemodynamic parameters. Methods: A comprehensive literature search was conducted in Pubmed, CINAHL, and Cochrane Library databases. All prospective clinical trials assessing the impact of EECP in patients with stable angina and CAD were included. Studies were excluded for not completing a full course of EECP, having a baseline peripheral systolic blood pressure &lt100 mmHg, or not reporting adequate data for analysis. The primary endpoint was the change in cSBP before and after EECP. The change in pSBP, pDBP, cDBP, and augmentation index before and after EECP were also assessed. The weighted mean difference using the DerSimonian and Laird random-effect model was utilized for determining the change in each parameter before and after EECP. Statistical heterogeneity was evaluated using the Egger’s bias statistic. Results: Five studies containing 137 unique patients were included for the cSBP analysis. cSBP was reduced significantly by -7.56 mmHg (95% CI -11.83 to -3.28; Cochrane Q=1.81) post-EECP. In the same set of studies, pSBP was reduced significantly by -9.65 mmHg (95% CI -14.32 to -4.98) post-EECP. pDBP [-4.67 mmHg (95% CI -8.56 to -0.77)] was reduced post-EECP, while no changes were evident in cDBP. Augmentation index was reduced by -3.74% (95% CI -7.05 to -0.43) post-EECP. Two studies included a sham-EECP intervention arm and demonstrated no significant changes in cSBP [0.67 mmHg (95% CI -5.66 to 7.01)] or other parameters. Conclusion: EECP significantly reduced cSBP and pSBP by approximately 8 mmHg and 10 mmHg respectively. EECP also demonstrated a mild improvement in arterial stiffness, which translates to reduced wasted left ventricular energy and myocardial oxygen demand. In patients with stable angina and CAD, EECP exerts beneficial effects in both peripheral and central hemodynamics but whether these benefits are sustained over a longer duration need further exploration.