Patient age is related to decision-making, treatment selection, and perceived quality of life in breast cancer survivors

BACKGROUND: Patients with breast cancer must choose among a variety of treatment options when first diagnosed. Patient age, independent of extent of disease, is also related to quality of life. This study examined the impact of patient age on treatment selected, factors influencing this selection, and perceived quality of life. METHODS: A 62-question survey evaluating breast cancer treatment and quality of life was mailed to breast cancer survivors. Responses were stratified by age (<50, 50-65, >65 years) and extent of disease. RESULTS: Of the 1,131 surveys mailed, 402 were included for analysis. There were 104, 179, and 119 women aged <50, 50-65, and >65 years, respectively. The median patient age was 58 years, and the average interval from diagnosis to survey participation was 31.5 months. CONCLUSIONS: Young women were more likely to have undergone aggressive therapies and had better physical functioning than old women. Old patients reported good quality of life and body image. Clinicians should consider patient age when discussing breast cancer treatment options

Measurements of serum mullerian inhibiting substance in the evaluation of children with nonpalpable gonads

BACKGROUND: Mullerian inhibiting substance, produced constitutively by the prepubertal testes, promotes involution of the mullerian ducts during normal male sexual differentiation. In children with virilization and nonpalpable gonads, only those with testicular tissue should have detectable serum concentrations of mullerian inhibiting substance. METHODS: We measured serum mullerian inhibiting substance in 65 children with virilization at birth and nonpalpable gonads (age at diagnosis, 2 days to 11 years) and serum testosterone in 54 of them either after the administration of human chorionic gonadotropin or during the physiologic rise in testosterone that occurs in normal infants. RESULTS: The mean (+/-SD) serum mullerian inhibiting substance concentration in the 17 children with no testicular tissue was 0.7+/-0.5 ng per milliliter, as compared with 37.5+/-39.6 ng per milliliter in the 48 children with testes (P CONCLUSIONS: Measurements of serum mullerian inhibiting substance can be used to determine testicular status in prepubertal children with nonpalpable gonads, thus differentiating anorchia from undescended testes in boys with bilateral cryptorchidism and serving as a measure of testicular integrity in children with intersexual anomalies

PEER Testbed Study on a Laboratory Building: Exercising Seismic Performance Assessment

From 2002 to 2004 (years five and six of a ten-year funding cycle), the PEER Center organized the majority of its research around six testbeds. Two buildings and two bridges, a campus, and a transportation network were selected as case studies to “exercise” the PEER performance-based earthquake engineering methodology. All projects involved interdisciplinary teams of researchers, each producing data to be used by other colleagues in their research. The testbeds demonstrated that it is possible to create the data necessary to populate the PEER performancebased framing equation, linking the hazard analysis, the structural analysis, the development of damage measures, loss analysis, and decision variables. This report describes one of the building testbeds—the UC Science Building. The project was chosen to focus attention on the consequences of losses of laboratory contents, particularly downtime. The UC Science testbed evaluated the earthquake hazard and the structural performance of a well-designed recently built reinforced concrete laboratory building using the OpenSees platform. Researchers conducted shake table tests on samples of critical laboratory contents in order to develop fragility curves used to analyze the probability of losses based on equipment failure. The UC Science testbed undertook an extreme case in performance assessment—linking performance of contents to operational failure. The research shows the interdependence of building structure, systems, and contents in performance assessment, and highlights where further research is needed. The Executive Summary provides a short description of the overall testbed research program, while the main body of the report includes summary chapters from individual researchers. More extensive research reports are cited in the reference section of each chapter

Peripheral Administration of the Soluble TNF Inhibitor XPro1595 Modifies Brain Immune Cell Profiles, Decreases Beta-Amyloid Plaque Load, and Rescues Impaired Long-Term Potentiation in 5xFAD Mice

Clinical and animal model studies have implicated inflammation and peripheral immune cell responses in the pathophysiology of Alzheimer’s disease (AD). Peripheral immune cells including T cells circulate in the cerebrospinal fluid (CSF) of healthy adults and are found in the brains of AD patients and AD rodent models. Blocking entry of peripheral macrophages into the CNS was reported to increase amyloid burden in an AD mouse model. To assess inflammation in the 5xFAD (Tg) mouse model, we first quantified central and immune cell profiles in the deep cervical lymph nodes and spleen. In the brains of Tg mice, activated (MHCII+, CD45high, and Ly6Chigh) myeloid-derived CD11b+ immune cells are decreased while CD3+ T cells are increased as a function of age relative to non-Tg mice. These immunological changes along with evidence of increased mRNA levels for several cytokines suggest that immune regulation and trafficking patterns are altered in Tg mice. Levels of soluble Tumor Necrosis Factor (sTNF) modulate blood-brain barrier (BBB) permeability and are increased in CSF and brain parenchyma post-mortem in AD subjects and Tg mice. We report here that in vivo peripheral administration of XPro1595, a novel biologic that sequesters sTNF into inactive heterotrimers, reduced the age-dependent increase in activated immune cells in Tg mice, while decreasing the overall number of CD4+ T cells. In addition, XPro1595 treatment in vivo rescued impaired long-term potentiation (LTP) measured in brain slices in association with decreased Aβ plaques in the subiculum. Selective targeting of sTNF may modulate brain immune cell infiltration, and prevent or delay neuronal dysfunction in AD

Effectiveness of a large-scale distribution programme of free nicotine patches: a prospective evaluation

Abstract BACKGROUND: After an increase in cigarette taxes and implementation of smoke-free workplace legislation, the New York City Department of Health and Mental Hygiene, the New York State Department of Health, and the Roswell Park Cancer Institute undertook large-scale distribution of free nicotine replacement therapy (NRT). We did a 6 month follow-up survey to assess the success of this programme in improving smoking cessation on a population basis. METHODS: 34,090 eligible smokers who phoned a toll-free quitline were sent a 6-week course of nicotine patches (2 weeks each of 21 mg, 14 mg, and 7 mg per day). Brief follow-up counselling calls were attempted. At 6 months after treatment, we assessed smoking status of 1305 randomly sampled NRT recipients and a non-randomly selected comparison group of eligible smokers who, because of mailing errors, did not receive the treatment. NRT recipients were compared with local survey-derived data for heavy smokers in New York City. FINDINGS: An estimated 5% of all adults in New York City who smoked ten cigarettes or more daily received NRT; most (64%) recipients were non-white, foreign-born, or resided in a low-income neighbourhood. Of individuals contacted at 6 months, more NRT recipients than comparison group members successfully quit smoking (33%vs 6%, p\u3c0.0001), and this difference remained significant after adjustment for demographic factors and amount smoked (odds ratio 8.8, 95% CI 4.4-17.8). Highest quit rates were associated with those who were foreign born (87 [39%]), older than 65 years (40 [47%]), and smoked less than 20 cigarettes per day (116 [35%]). Those who received a counselling call were more likely to stop smoking than those who did not (246 [38%] vs 189 [27%], p=0.001). With the conservative assumption that every 6-month follow-up survey non-respondent continued to smoke, the stop rate among NRT recipients was 20%. At least 6038 successful quits were attributable to NRT receipt, and cost was 464 US dollars per quit. INTERPRETATION: Easy access to cessation medication for diverse populations could help many more smokers to stop

Effects of Changing Work Environments on Employer Support for Physical Activity During COVID-19

COVID-19 dramatically accelerated evolving changes in the way we define the “work environment” in the United States. In response to COVID-19, many employers have offered increased flexibility for where employees work, including remote (an employee’s workstation is at home) and hybrid work (an employee works both at the employer worksite and remotely, on predetermined schedules). Accordingly, worksite physical activity (PA) and sedentary behaviors (SB) such as extended sitting time (ST) may have changed.1,2 However, little is known about whether these work arrangements are associated with changes in employer support for PA. Interviews were conducted to assess this gap in understanding. Because little is known about employer support for equity with respect to PA and SB, this study sought to identify potential strategies to assure equity in PA opportunities across work environments

Progranulin Loss Results in Sex-Dependent Dysregulation of the Peripheral and Central Immune System

INTRODUCTION: Progranulin (PGRN) is a secreted glycoprotein, the expression of which is linked to several neurodegenerative diseases. Although its specific function is still unclear, several studies have linked it with lysosomal functions and immune system regulation. Here, we have explored the role of PGRN in peripheral and central immune system homeostasis by investigating the consequences of PGRN deficiency on adaptive and innate immune cell populations. METHODS: First, we used gene co-expression network analysis of published data to test the hypothesis that RESULTS: Male PGRN KO mice exhibited a lower abundance of microglial cells with higher MHC-II expression, increased CD44 expression on monocytes in the brain, and more CNS-associated CD8 DISCUSSION: Our data suggest that PGRN and GPNMB jointly regulate the peripheral and the central immune system in a sex-specific manner; thus, understanding their associated mechanisms could pave the way for developing new neuroprotective strategies to modulate central and peripheral inflammation to lower risk for neurodegenerative diseases and possibly delay or halt progression

Identification and validation of clinical predictors for the risk of neurological involvement in children with hand, foot, and mouth disease in Sarawak

Background: Human enterovirus 71 (HEV71) can cause Hand, foot, and mouth disease (HFMD) with neurological complications, which may rapidly progress to fulminant cardiorespiratory failure, and death. Early recognition of children at risk is the key to reduce acute mortality and morbidity. Methods: We examined data collected through a prospective clinical study of HFMD conducted between 2000 and 2006 that included 3 distinct outbreaks of HEV71 to identify risk factors associated with neurological involvement in children with HFMD. Results: Total duration of fever ≥ 3 days, peak temperature ≥ 38.5°C and history of lethargy were identified as independent risk factors for neurological involvement (evident by CSF pleocytosis) in the analysis of 725 children admitted during the first phase of the study. When they were validated in the second phase of the study, two or more (≥ 2) risk factors were present in 162 (65%) of 250 children with CSF pleocytosis compared with 56 (30%) of 186 children with no CSF pleocytosis (OR 4.27, 95% CI2.79–6.56, p < 0.0001). The usefulness of the three risk factors in identifying children with CSF pleocytosis on hospital admission during the second phase of the study was also tested. Peak temperature ≥ 38.5°C and history of lethargy had the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of 28%(48/174), 89%(125/140), 76%(48/63) and 50%(125/251), respectively in predicting CSF pleocytosis in children that were seen within the first 2 days of febrile illness. For those presented on the 3rd or later day of febrile illness, the sensitivity, specificity, PPV and NPV of ≥ 2 risk factors predictive of CSF pleocytosis were 75%(57/ 76), 59%(27/46), 75%(57/76) and 59%(27/46), respectively. Conclusion: Three readily elicited clinical risk factors were identified to help detect children at risk of neurological involvement. These risk factors may serve as a guide to clinicians to decide the need for hospitalization and further investigation, including cerebrospinal fluid examination, and close monitoring for disease progression in children with HFMD

Impact of cryopreservation on tetramer, cytokine flow cytometry, and ELISPOT

BACKGROUND: Cryopreservation of PBMC and/or overnight shipping of samples are required for many clinical trials, despite their potentially adverse effects upon immune monitoring assays such as MHC-peptide tetramer staining, cytokine flow cytometry (CFC), and ELISPOT. In this study, we compared the performance of these assays on leukapheresed PBMC shipped overnight in medium versus cryopreserved PBMC from matched donors. RESULTS: Using CMV pp65 peptide pool stimulation or pp65 HLA-A2 tetramer staining, there was significant correlation between shipped and cryopreserved samples for each assay (p ≤ 0.001). The differences in response magnitude between cryopreserved and shipped PBMC specimens were not significant for most antigens and assays. There was significant correlation between CFC and ELISPOT assay using pp65 peptide pool stimulation, in both shipped and cryopreserved samples (p ≤ 0.001). Strong correlation was observed between CFC (using HLA-A2-restricted pp65 peptide stimulation) and tetramer staining (p < 0.001). Roughly similar sensitivity and specificity were observed between the three assays and between shipped and cryopreserved samples for each assay. CONCLUSION: We conclude that all three assays show concordant results on shipped versus cryopreserved specimens, when using a peptide-based readout. The assays are also concordant with each other in pair wise comparisons using equivalent antigen systems