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Background Risk prediction in haemodialysis (HD) patients is challenging due to the impact of the dialysis regime on the patient's volume status and the complex interplay with cardiac function, comorbidities and hypertension. Cardiac function as a key predictor of cardiovascular (CV) mortality in HD patients is challenging to assess in daily routine. Thus the aim of this study was to investigate the association of a novel, non-invasive relative index of systolic function with mortality and to assess its interplay with volume removal. Methods A total of 558 (373 male/185 female) HD patients with a median age of 66 years were included in this analysis. They underwent 24-hour ambulatory blood pressure monitoring, including wave intensity analysis [i.e. S:D ratio (SDR)]. All-cause and CV mortality served as endpoints and multivariate proportional hazards models were used for risk prediction. Intradialytic changes were analysed in tertiles according to ultrafiltration volume. During a follow-up of 37.8 months, 193 patients died (92 due to CV reasons). Results The SDR was significantly associated with all-cause {univariate hazard ratio [HR] 1.36 [95% confidence interval (CI) 1.20–1.54], P  < .001} and CV [univariate HR 1.41 (95% CI 1.20–1.67), P  < .001] mortality. The associations remained significant in multivariate analysis accounting for possible confounders. Changes in the SDR from pre-/early- to post-dialytic averages were significantly different for the three ultrafiltration volume groups. Conclusion This study provides well-powered evidence for the independent association of a novel index of systolic function with mortality. Furthermore, it revealed a significant association between intradialytic changes of the measure and intradialytic volume removal. [ABSTRACT FROM AUTHOR]

To identify correlations between disease recurrence and adherence to NCCN posttreatment surveillance guidelines in patients who develop recurrent uterine cancer. Retrospective analysis identified patients (n = 60) with recurrent uterine cancer and at least one surveillance visit with a gynecologic oncologist between 2011 and 2020. Adherence to NCCN guidelines and details of recurrence were recorded. Recurrent uterine cancer was identified in 60 patients with an average time to recurrence (TTR) of 25 months. Of those, 39 (65%) were adherent to NCCN surveillance guidelines and 36 (60%) were symptomatic at the time of recurrence diagnosis. Asymptomatic recurrence was diagnosed by imaging in 11 (46%), physical exam in 7 (29%), and blood work in 6 (25%) patients. Patients who were adherent to NCCN guidelines were diagnosed with recurrence on average 11 months earlier (p = 0.0336). Adherence was an independent predictor of TTR for all patients regardless of symptoms. There was no significant effect of age, race, primary language, or stage of disease on adherence. Adherence to NCCN posttreatment surveillance guidelines for uterine cancer is independently associated with an earlier diagnosis of recurrence. • Many patients are not adherent to NCCN surveillance guidelines at time of recurrence detection. • Physical exam is an important for detecting uterine cancer recurrence. • Non-NCCN directed imaging detected almost half of asymptomatic recurrences. • Asymptomatic recurrence is detected earlier in patients who adhere to NCCN posttreatment surveillance guidelines. [ABSTRACT FROM AUTHOR]

The article presents the discussion on unexpected reaction of the stock market to positive job market data released by the U.S. government in January 2023. Topics include paradox of market reactions to economic data, the role of deconstructive analysis in understanding economic narratives; and Alfred Korzybski's perspective on challenging false ideas.

Background: Older age is a substantial risk factor for serious illness from COVID-19. Moreover, isolation and quarantine are more likely to cause physical, mental and social deprivation in older age. Information and Communication Tools are means to prevent such consequences.Objective: This study aimed therefore to investigate the impact of the COVID-19 lockdown measures on the usage of an innovative technical support system deployed in Austria (AT) and Luxembourg (LU) consisting of several tools that allow independent living in older age.Methods: Thirty-nine older adults (11 male; 28 female) with a mean age of 74.3 (SD 7.3) years were included in the study. In total, 18 older people were recruited in AT and 21 in LU. Descriptive statistics were computed, and longitudinal models were fitted for technology use and self-reported mood.Results: The number of older adults using the system significantly decreased from the time before lockdown (39 [100%]) to during lockdown (26 [67%]) and thereafter (23 [59%]; p < 0.001). Multiple comparisons revealed a significant reduction in the average number of events for calendar and medication tools, but a substantial increase in communication and messaging events. Self-reported well-being declined during the lockdown and increased afterwards back to baseline levels.Conclusion: Communication was the main reason for using the support system. In addition, strategies and interventions are essential to support older adults when using information technology in the prolonged phases of the pandemic to sustain independent living.Clinical Trial Registration: The DAPAS protocol was published at www.researchgate.net. DOI: 10.13140/RG.2.2.24233.34401. [ABSTRACT FROM AUTHOR]

The development and use of medical devices are subject to regulations and approval activities to enter the market. These are mandatory for manufacturers and have important implications for all involved professionals. In fact, the innovation process, starting from a clinical need, includes the identification of a solution and its implementation, and requires taking into account crucial aspects according to regulatory requirements in each phase. These include exemplary validation or risk management. The aim of this work is to provide an overview of some key aspects of regulation and their implementation in medical devices for vascular ageing assessment. In particular, regulatory scenarios in Europe, Australia and the United States of America are described and examples of marketed medical devices for vascular ageing assessment are provided. Strong and active links among industry, research, clinical experts and governments adds value for the community, requiring the ability to communicate between different skills and backgrounds: this multidisciplinary and multi-partner collaboration can speed up the innovation process and can increase the system's efficiency related to both social and ethical impact. [ABSTRACT FROM AUTHOR]

BACKGROUND: For unvaccinated individuals with mild-to-moderate coronavirus disease 2019 (COVID-19), monoclonal antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) decrease the risk of severe disease and hospitalization. We describe the use of the monoclonal antibodies casirivimab and imdevimab for COVID-19 in pregnancy. CASE: Two unvaccinated pregnant individuals presented with moderate COVID-19, one in the second trimester and one in third trimester; both met criteria for outpatient management. To decrease the risk for severe disease, they were treated with casirivimab and imdevimab. Neither experienced an adverse drug reaction, and neither progressed to severe disease. CONCLUSION: Monoclonal antibodies such as casirivimab and imdevimab, approved under an emergency use authorization, should be considered in unvaccinated pregnant individuals with mild-to-moderate COVID-19 to decrease the risk of severe disease. Teaching Points 1. Pregnant individuals with mild-to-moderate COVID-19, especially those who are unvaccinated, are at high risk for severe disease and hospitalization. 2. In nonpregnant adults with mild-to-moderate COVID-19, use of the monoclonal antibodies casirivimab and imdevimab decreases the likelihood of severe disease and hospitalization. 3. To prevent severe disease in unvaccinated pregnant individuals with mild-to-moderate COVID-19, use of the monoclonal antibodies casirivimab and imdevimab should be considered. [ABSTRACT FROM AUTHOR]

A literary criticism of the book "Alfred Korzybski and… Warren Buffett" by Corey Anton and Lance Strate is presented. Topics include examines that they pursued their ideas outside mainstream institutions and Korzybski pursued with his institute, and Buffett first with his Buffett partnership and later with Berkshire Hathaway.

Background A novel in vitro test (T50 test) assesses ex vivo serum calcification propensity and predicts mortality in chronic kidney disease and haemodialysis (HD) patients. For the latter, a time-dependent decline of T50 was shown to relate to mortality. Here we assessed whether a 3-month switch to acetate-free, citrate-acidified, standard bicarbonate HD (CiaHD) sustainably improves calcification propensity. Methods T50 values were assessed in paired midweek pre-dialysis sera collected before and 3 months after CiaHD in 78 prevalent European HD patients. In all, 44 were then switched back to acetate. Partial correlation was used to study associations of changing T50 and changing covariates. Linear mixed effect models were built to assess the association of CiaHD and covariates with changing T50. Results A significant intra-individual increase of serum calcification resilience was found after 3 months on CiaHD (206  ±  56 to 242  ±  56 min; P < 0.001), but not after switching back to acetate (252  ±  63 to 243  ±  64 min; n  = 44; P = 0.29). CiaHD, Δ serum phosphate and Δ albumin but not Δ ionized calcium and magnesium were the strongest determinants of changing T50. Beneath T50, only serum albumin but not phosphate changed significantly during 3 months of CiaHD. Conclusion CiaHD dialysis favourably affected calcification propensity as measured by the T50 test. Whether this treatment, beyond established phosphate-directed treatments, has the potential to sustainably tip the balance towards a more anti-calcific serum milieu needs to be further investigated. [ABSTRACT FROM AUTHOR]

Objectives: Endometrial cancer due to loss of mismatch repair proteins may be caused by epigenetic or genetic factors. Complete profiling is not routinely performed in clinical practice. We sought to explore outcomes of women with mismatch repair deficiency (MMRd) due to epigenetic MLH-1 promoter hypermethylation (MMRd-MLH). We hypothesize that MMRd-MLH correlates with worse clinical outcomes in endometrial cancer. Methods: Under an IRB protocol, we retrospectively identified patients with endometrioid endometrial adenocarcinoma undergoing hysterectomy at our institution from 2016-2020. These patients underwent routine immunohistochemical testing for MMRd, with subsequent genetic testing or methylation studies for loss of MMR proteins. We examined patient data in three cohorts: MMR proficient (MMRp), MMRd-MLH, and MMRd deficiency due to germline mutation (MMRd-G). We excluded patients who did not undergo MMR testing and those who were MMR deficient due to other causes. We examined clinical data via univariate and multivariate tests and Kaplan-Meier survival analyses. Results: We identified 327 patients who met the criteria for review. The majority (243, 74%) were MMRp, 74 (23%) were MMRd-MLH, and ten (3%) were MMRd-G. On univariate analysis, we observed no differences in the history of post-menopausal hormone replacement therapy, family history of cancer, personal history of hypertension or diabetes mellitus, or body mass index. We found that when compared to the other two groups, MMRd-MLH patients were more like to have grade 2-3 tumors (p < 0.01) and LVSI (p < 0.001). We identified statistically significant associations between age at surgery (60, 67, and 60 years, respectively) and depth of invasion (0.41cm, 0.67cm, and 0.18cm). We did not observe significant differences in the stage. We identified that MMRd-MLH was associated with pathologic high-intermediate risk factors leading to increased adjuvant therapy in stage I disease (p=0.04). We observed a 4.1% recurrence rate in MMRp compared to 8.1% in the MMRd-MLH group compared to no recurrences in MMRd-G (p = NS). When comparing MMRp and MMRd-MLH in Kaplan-Meier analyses, we observed a statistical difference in disease-free survival favoring those who were MMRp (p = 0.02). Median survival was not reached. There were no significant differences in overall survival between MMRp and MMRd-MLH. We did not identify independent prognostic factors for recurrence when controlling for age, stage, grade, or MMR status. [Display omitted] Conclusions: MMRd-MLH is associated with LVSI, higher grade, deeper tumor invasion, and a significantly higher rate of adjuvant therapy. We observed patients with MMRd-MLH were more likely to recur despite adjuvant therapy. MMRd-MLH may represent a poor prognostic factor and a target for further adjuvant therapy. [ABSTRACT FROM AUTHOR]

Assistive technologies have the potential for supporting people with memory complaints in their daily life. User-centered interaction design research helps developers to create systems that are suitable for users. The aim of this work is to describe the methodology and the results of the usability test for the first Memento prototype involving users. In each country, 5 subjects with different levels of cognitive reserve and technical proficiency were enrolled in Italy, Austria and Spain, respectively (15 subjects; 6 M; 9 F, age 72.8 ± 10.8 years, MMSE score 25.6 ± 1.6). Observation methods, performance metrics and the System Usability Scale were used to collect data. The results are presented in terms of design, technical problems, target-group-related challenges and usability perception from the participant perspective. Suggestions for improvement were pointed out by the users. Considering the usability scores interpretation, the first prototype was classified as "OK" and "Good" by users. The results of the Lab Trials provide important information on usability and the users' needs in order to improve the Memento prototype and to create a final system to be evaluated during the Field Trials phase of the project. The MEMENTO project mission is to improve the quality of life of people in the early and middle stages of dementia, by supporting the management of daily activities that are usually affected by the loss of memory and cognition. The Lab Trial phase is essential to have feedback on the usability of the Memento prototype to allow a better understanding of users' needs and expectations. [ABSTRACT FROM AUTHOR]

Heart rate variability (HRV) is a non-invasive measurement based on the intervals between normal heart beats that characterize cardiac autonomic function. Decreased HRV is associated with increased risk of cardiovascular events. Characterizing HRV using only moment statistics fails to capture abnormalities in regulatory function that are important aspects of disease risk. Thus, entropy measures are a promising approach to quantify HRV for risk stratification. The purpose of this study was to investigate this potential for approximate, corrected approximate, sample, fuzzy, and fuzzy measure entropy and its dependency on the parameter selection. Recently, published parameter sets and further parameter combinations were investigated. Heart rate data were obtained from the "Cardiac Arrhythmia Suppression Trial (CAST) RR Interval Sub-Study Database" (Physionet). Corresponding outcomes and clinical data were provided by one of the investigators. The use of previously-reported parameter sets on the pre-treatment data did not significantly add to the identification of patients at risk for cardiovascular death on follow-up. After arrhythmia suppression treatment, several parameter sets predicted outcomes for all patients and patients without coronary artery bypass grafting (CABG). The strongest results were seen using the threshold parameter as a multiple of the data's standard deviation (r = 0.2 · σ). Approximate and sample entropy provided significant hazard ratios for patients without CABG and without diabetes for an entropy maximizing threshold approximation. Additional parameter combinations did not improve the results for pre-treatment data. The results of this study illustrate the influence of parameter selection on entropy measures' potential for cardiovascular risk stratification and support the potential use of entropy measures in future studies. [ABSTRACT FROM AUTHOR]

The relative contributions of the JNK subtypes in inflammatory β-cell failure and apoptosis are unclear. The JNK protein family consists of JNK1, JNK2, and JNK3 subtypes, encompassing many different isoforms. INS-1 cells express JNK1α1, JNK1α2, JNK1β1, JNK1β2, JNK2α1, JNK2α2, JNK3α1, and JNK3α2 mRNA isoform transcripts translating into 46 and 54 kDa isoform JNK proteins. Utilizing Lentiviral mediated expression of shRNAs against JNK1, JNK2, or JNK3 in insulin-producing INS-1 cells, we investigated the role of individual JNK subtypes in IL-1β-induced β-cell apoptosis. JNK1 knockdown prevented IL-1β-induced INS-1 cell apoptosis associated with decreased 46 kDa isoform JNK protein phosphorylation and attenuated Myc expression. Transient knockdown of Myc also prevented IL-1β-induced apoptosis as well as caspase 3 cleavage. JNK2 shRNA potentiated IL-1β-induced apoptosis and caspase 3 cleavage, whereas JNK3 shRNA did not affect IL-1β-induced β-cell death compared to nonsense shRNA expressing INS-1 cells. In conclusion, JNK1 mediates INS-1 cell death associated with increased Myc expression. These findings underline the importance of differentiated targeting of JNK subtypes in the development of inflammatory β-cell failure and destruction. [ABSTRACT FROM AUTHOR]

The relative contributions of the JNK subtypes in inflammatory β-cell failure and apoptosis are unclear. The JNK protein family consists of JNK1, JNK2, and JNK3 subtypes, encompassing many different isoforms. INS-1 cells express JNK1α1, JNK1α2, JNK1β1, JNK1β2, JNK2α1, JNK2α2, JNK3α1, and JNK3α2 mRNA isoform transcripts translating into 46 and 54 kDa isoform JNK proteins. Utilizing Lentiviral mediated expression of shRNAs against JNK1, JNK2, or JNK3 in insulin-producing INS-1 cells, we investigated the role of individual JNK subtypes in IL-1β-induced β-cell apoptosis. JNK1 knockdown prevented IL-1β-induced INS-1 cell apoptosis associated with decreased 46 kDa isoform JNK protein phosphorylation and attenuated Myc expression. Transient knockdown of Myc also prevented IL-1β-induced apoptosis as well as caspase 3 cleavage. JNK2 shRNA potentiated IL-1β-induced apoptosis and caspase 3 cleavage, whereas JNK3 shRNA did not affect IL-1β-induced β-cell death compared to nonsense shRNA expressing INS-1 cells. In conclusion, JNK1 mediates INS-1 cell death associated with increased Myc expression. These findings underline the importance of differentiated targeting of JNK subtypes in the development of inflammatory β-cell failure and destruction. [ABSTRACT FROM AUTHOR]

Objectives: Surveillance follow-up for women with vaginal and vulvar cancer, extrapolated by National Comprehensive Cancer Network (NCCN), includes a physical exam every 3-6 months during the first two years, followed by every 6-12 months for three to five years after treatment. For VAIN, general recommendations for follow-up suggest a physical exam every six months for the first two years and yearly after. For VIN, physical exams every six months for the first five years are recommended. Little is known regarding rates of retention for follow-up in these rare cancers and dysplasia. We sought to explore post-treatment retention for patients with vaginal and vulvar cancer and dysplasia at our institution. Methods: After IRB approval, we retrospectively identified patients treated for vaginal and/or vulvar intraepithelial neoplasia or carcinoma between 2011-2016. Baseline demographic, pathologic, treatment, surveillance, and recurrence data were collected. We examined the continuous and total retention of post-treatment surveillance visits for patients diagnosed with cancer VIN, VAIN, or concomitant VIN and VAIN. Continuous retention was defined as sequential visits no longer than one year apart. Descriptive statistics were used to analyze the data. Results: We identified 40 patients who met the criteria for review. The median age of treatment was 60 years old. Most patients were White (75%), followed by Asian (10%), Black (5%), other (8%), and American Indian (3%). The most common diagnoses were VIN III (25%), VAIN III (22%), and squamous cell carcinoma (22%). Most were treated with wide local excision (42.5%), followed by radical surgery (30%), and laser surgery (15%). The median times for total and continuous post-treatment retention were 27.5 and 21 months, respectively. The median number of visits and pap smears in the first post-treatment year were 2 and 1, respectively. The median number of visits and pap smears in the second post-treatment year were 1 and 1, respectively. Only 29% of patients continued with surveillance in the third post-treatment year. Recurrence was noted in ten patients (25%) with a median time of recurrence of 29 months with a range of 1-69 months. The most common primary diagnoses associated with recurrence were VIN III (40%), VAIN III (20%), VIN II (20%), and squamous cell carcinoma (20%). Conclusions: This is the first baseline assessment of post-treatment surveillance retention for VAIN, VIN, or vulvovaginal carcinoma. We observed that our population generally adheres to NCCN surveillance guidelines during the first year; however, the adherence drops in the following years with a median continuous retention rate of less than two years. Further work is needed to enhance post-treatment surveillance and identify barriers to follow-up for patients. [ABSTRACT FROM AUTHOR]

Low grade inflammation is present in pre-clinical and human type 2 diabetes. In this process, several cytokines like IL-1β and inflammatory cells like macrophages are activated and demonstrated to participate to the disease initiation and progression. IL-20 is a cytokine known to play non-redundant roles in progression of several inflammatory diseases. To address the therapeutic effect of inhibiting the IL-20 pathway in diabetes, diabetic db/db mice were treated with neutralizing anti-IL20 antibodies in vivo and both metabolic and inflammatory parameters were followed. Diabetic islets expressed the IL-20 cytokine and all IL-20 receptor components in elevated levels compared to resting non-diabetic islets. Islets were responsive to ex vivo IL-20 stimulation measured as SOCS induction and KC and IL-6 production. Neutralizing anti-IL20 treatment in vivo had no effect on HbA1c or weight although the slope of blood glucose increase was lowered. In contrast, anti-IL20 treatment significantly reduced the systemic low-grade inflammation and modulated the local pancreatic immunity. Significant reduction of the systemic IL-1β and MCP-1 was demonstrated upon anti-IL20 treatment which was orchestrated with a reduced RANTES, IL-16 and IL-2 but increased TIMP-1, MCP-1 and IL-6 protein expression locally in the pancreas. Interestingly, anti-IL20 treatment induced an expansion of the myeloid suppressor CD11bGr1int macrophage while reducing the number of CD8 T cells. Taken together, anti-IL20 treatment showed moderate effects on metabolic parameters, but significantly altered the low grade local and systemic inflammation. Hence, future combination therapies with anti-IL20 may provide beneficial therapeutic effects in type 2 diabetes through a reduction of inflammation. [ABSTRACT FROM AUTHOR]

Background: Heart rate variability is the variation of the time interval between consecutive heartbeats. Entropy is a commonly used tool to describe the regularity of data sets. Entropy functions are defined using multiple parameters, the selection of which is controversial and depends on the intended purpose. This study describes the results of tests conducted to support parameter selection, towards the goal of enabling further biomarker discovery. Methods: This study deals with approximate, sample, fuzzy, and fuzzy measure entropies. All data were obtained from PhysioNet, a free-access, on-line archive of physiological signals, and represent various medical conditions. Five tests were defined and conducted to examine the influence of: varying the threshold value r (as multiples of the sample standard deviation σ, or the entropy-maximizing rChon), the data length N, the weighting factors n for fuzzy and fuzzy measure entropies, and the thresholds rF and rL for fuzzy measure entropy. The results were tested for normality using Lilliefors’ composite goodness-of-fit test. Consequently, the p-value was calculated with either a two sample t-test or a Wilcoxon rank sum test. Results: The first test shows a cross-over of entropy values with regard to a change of r. Thus, a clear statement that a higher entropy corresponds to a high irregularity is not possible, but is rather an indicator of differences in regularity. N should be at least 200 data points for r = 0.2 σ and should even exceed a length of 1000 for r = rChon. The results for the weighting parameters n for the fuzzy membership function show different behavior when coupled with different r values, therefore the weighting parameters have been chosen independently for the different threshold values. The tests concerning rF and rL showed that there is no optimal choice, but r = rF = rL is reasonable with r = rChon or r = 0.2σ. Conclusions: Some of the tests showed a dependency of the test significance on the data at hand. Nevertheless, as the medical conditions are unknown beforehand, compromises had to be made. Optimal parameter combinations are suggested for the methods considered. Yet, due to the high number of potential parameter combinations, further investigations of entropy for heart rate variability data will be necessary. [ABSTRACT FROM AUTHOR]

Type 2 diabetes (T2D) is evolving into a global disease and patients have a systemic low-grade inflammation, yet the role of this inflammation is still not established. One plausible mechanism is enhanced expression and activity of the innate immune system. Therefore, we evaluated the expression and the function of the toll-like receptor 4 (TLR4) on pancreatic β-cells in primary mouse islets and on the murine β-cell line MIN6 in the presence or absence of macrophages. Diabetic islets have 40% fewer TLR4 positive β-cells, but twice the number of TLR4 positive macrophages as compared to healthy islets. Healthy and diabetic islets respond to a TLR4 challenge with enhanced production of cytokines (5–10-fold), while the TLR4 negative β-cell line MIN6 fails to produce cytokines. TLR4 stimulation induces β-cell dysfunction in mouse islets, measured as reduced glucose stimulated insulin secretion. Diabetic macrophages from 4-months old mice have acquired a transient enhanced capacity to produce cytokines when stimulated with LPS. Interestingly, this is lost in 6-months old diabetic mice. TLR4 activation alone does not induce apoptosis in islets or MIN-6 cells. In contrast, macrophages mediate TLR4-dependent cell-contact dependent (3-fold) as well as cell-contact independent (2-fold) apoptosis of both islets and MIN-6 cells. Importantly, diabetic macrophages have a significantly enhanced capacity to induce β-cell apoptosis compared to healthy macrophages. Taken together, the TLR4 responsiveness is elevated in the diabetic islets and mainly mediated by newly recruited macrophages. The TLR4 positive macrophages, in both a cell-contact dependent and independent manner, induce apoptosis of β-cells in a TLR4 dependent fashion and TLR4 activation directly induces β-cell dysfunction. Thus, targeting either the TLR4 pathway or the macrophages provides a novel attractive treatment regime for T2D. [ABSTRACT FROM AUTHOR]

Abstract: Insulin plays a key role in the maintenance of nutrient homeostasis through central regulation of neuropeptides. Neuropeptide Y (NPY) and agouti-related peptide (AgRP) are vital orexigenic peptides that are regulated by insulin, although the processes utilized are unknown. Using a hypothalamic, clonal cell line, mHypoE-46, which endogenously expresses NPY, AgRP and the insulin receptor, we studied the mechanisms involved in the regulation of the NPY/AgRP neuron by insulin. We determined that insulin has direct actions on the neurons and acts to repress NPY/AgRP gene expression through a MAPK MEK/ERK-dependent pathway. Transient transfection analysis determined that human NPY and AgRP 5′ flanking gene regions were not regulated by insulin in the mouse cell line, while sequence comparison analysis indicated only a 50% sequence similarity between human and mouse NPY and AgRP 5′ flanking regions. These experiments indicate that insulin acts directly on specific hypothalamic neurons to regulate neuropeptide transcription. [Copyright &y& Elsevier]

Abstract: The hypothalamus is the control center for most physiological processes; yet has been difficult to study due to the inherent heterogeneity of this brain region. For this reason, researchers have turned towards cell models. Primary hypothalamic cultures are difficult to maintain, are heterogeneous neuronal and glial cell populations and often contain a minimal number of viable peptide-secreting neurons. In contrast, immortalized, clonal cell lines represent an unlimited, homogeneous population of neurons that can be manipulated using a number of elegant molecular techniques. Cell line studies and in vivo experimentation are complementary and together provide a powerful tool to drive scientific discovery. This review focuses on three key neuroendocrine systems: energy homeostasis, reproduction, and circadian rhythms; and the use of hypothalamic cell lines to dissect the complex pathways utilized by individual neurons in these systems. [Copyright &y& Elsevier]

The article relates mortgage rates charged to minority subprime mortgage borrowers and the mortgage pricing and risk variables disclosed by Loan Performance. It elaborates on the racial ethnic and gender considerations in mortgage lending that have a bearing on the mortgage risk profile and the features of property's location.

Abstract: The aim of the presented work has been the development of an algorithm for a non-invasive, portable, easy-to-use, and affordable device for measuring systemic cardiovascular parameters such as cardiac output and peripheral resistance. The data acquisition is based on a common oscillometric measurement using an occlusive blood pressure cuff, and no additional calibration is necessary. The novel algorithm introduced here combines several simulation techniques like neural networks or differential equations, which will be explained briefly. The determination of the hemodynamical parameters is based on the idea that the ejection work of the left ventricle is subject to an optimization principle. This kind of model needs no additional external calibration and opens therefore good perspectives for non-expert use in cardiovascular risk stratification and hypertension therapy optimization. To verify the approach we present some clinical results and a relevant discussion on it, followed by a view of future work. [Copyright &y& Elsevier]

It is established that increases in neuropeptide Y (NPY) expression are associated with hyperphagia and obesity. These effects can be reversed by estrogen, a recognized anorexigen. We found that 17β-estradiol (E2 ) regulates biphasic NPY gene expression in a clonal, immortalized hypothalamic cell line, N-38, through estrogen receptor (ER) action at the level of the NPY promoter. However, rapid, nongenomic actions of estrogen, linked to the phosphatidylinositol 3-kinase (PI3-K)/Akt and ERK1/2 mitogen-activated protein kinase (MAPK) pathways, may also play a role. We therefore examined the changes in the phosphorylation status of Akt, ERK1/2, and cAMP response element-binding protein (CREB) after treatment with 10 nM E2 in the N-38 neurons and found activation of these signaling proteins within 5-30 min. We also demonstrated possible cross talk between the estrogen-activated PI3-K/Akt and MAPK/extracellular signal-regulated kinase pathways using pharmacological inhibitors. We find that only ERα is involved in the early signaling events using the ERβ agonist 4,4',4"-(4-propyl-[1H]-pyrazole-1,3,5-triyl)trisphenol and the ERβ agonist 2,3-bis(4-hydroxyphenyl)-propionitrile. Furthermore, we can detect colocalization of ERα and caveolin-1, a membrane-associated signaling protein. Remarkably, we find that the membrane-mediated events are critical for the long-term estrogen-mediated repression of NPY gene expression that can be mapped to within -97 bp of the NPY promoter. To link the early signaling events to downstream effectors, we detected induction of c-fos and inactivation of MSK-1 by estrogen and binding of CREB to this minimal promoter region. These observations suggest that rapid estrogenmediated signaling is mediated by ERα, and the signal transduction events potentiate the genomic actions of estrogen on NPY gene expression in the N-38 NPY neurons. [ABSTRACT FROM AUTHOR]

Focuses on school funding equalization and residential location for children and the elderly in the U.S. Definition of Tiebout sorting; Factors that affect the location decisions of households with children; Analysis of issues related to household sorting and school finance reforms.

The mechanisms dictating the developmental expression of individual neuropeptides within the hypothalamus have not yet been elucidated. In this paper we have studied the cis-acting elements involved in the repression of neuropeptide Y (NPY) gene expression in a gonadotropin-releasing hormone (GnRH) neuronal cell model, GT1-7 cells. Using transient transfection of the human NPY 5′ regulatory region into the GT1-7 neurons, we have found a repressor region located between −867 and −1078. DNase I footprint analysis of this region revealed three specific protein binding elements. Further analysis of the region between −942 and −922 bp using electrophoretic mobility shift assays revealed that four different transcription factor-DNA complexes form with GT1-7 nuclear proteins, whereas only three complexes are detected using baby hamster kidney (BHK) cell nuclear extract. Mutation of the consensus binding sequence abolishes all complex formation on the −924/−922 oligonucleotide. Antibody supershift assays revealed that Oct-1 and Pbx-1 antibodies were able to eliminate the appearance of two specific complexes. Therefore we suggest that this region may be important for transcriptional repression of the NPY gene in a heterologous cell model, through complex, coordinate protein–protein interactions. [Copyright &y& Elsevier]

Presents information on a study which examined how U.S. government regulation affects the dynamics of the low-income housing stock. Framework of the filtering model to explain the effect of restrictions on new construction and rent control on the movement in units of low-income housing stock; Review of related literature; Examination of rent control through metropolitan statistical areas; Data on land-use regulation from the Wharton Urban Decentralization Project Data Set.

A letter to the editor is presented in response to the article "Military Professionalism & Private Military Contractors" by Scott Efflandt that was published in the previous issue.

Presents a commentary on papers written by James Orr and Richard Peach and Joseph Gyourko and Joseph Tracy with focus on issues related to home ownership. Discussion of the findings; Analysis of the results; Policies to encourage home ownership; Conclusion.

Presents an empirical model of housing supply that reflects the land development process consistent with the time-series characteristics of the data. Theoretical issues in modeling new construction; Empirical model; Testing for evidence of a credit crunch.

Discusses evidence from a variety of sources exploring the impact of location on the earnings of American households. Summary of trends in segregation by race and income; Exploration of reasons for the continuing racial and income segregation; Impact of spatial isolation on residents of poor neighborhoods.

Attempts to identify the impact of amenities on housing price levels within Eastern Massachusetts since 1982. Divides the Eastern Massachusetts region into small groups of similar towns and examines the pattern of price changes across those groups during the economic boom, bust, and recovery periods. Finding that housing affordability was the most important factor explaining price changes during the boom period; Other factors.

Discusses various aspects of home purchasing practices and how these items relate to housing market behavior in general. Description of typical first-time home buyer scenarios; Family transfers.

Demonstrates a large potential market for reverse mortgages and gives demand and supply explanations on the reasons for the small number of reverse mortgages. Types of reverse mortgages; Sample data; Reverse mortgage model; Benefits of the reverse mortgage; Difficulties in developing the reverse mortgage market. INSET: Computing the reverse mortgage payment..

Background The CDC reported in 2017 that 21% of new HIV diagnoses were composed of persons 13–24 years old. New York State (NYS) is addressing this with the Ending the Epidemic initiative, started in 2014, which emphasized pre-exposure prophylaxis (PrEP) for persons at risk of acquiring HIV. Though PrEP can effectively prevent HIV transmission, NYS minors were only granted capacity to accept PrEP in 2017. The Adolescent Medicine Trials Network found clinicians had varying perceptions on whether mental health diagnoses (MHD) were a barrier to adolescent PrEP utilization. This study aims to test the hypothesis that patients with MHD do not differ in PrEP retention length when compared with adolescents without MHD. Methods This is a retrospective single-center study analyzing self-reported visit data for adolescent enrolled on PrEP (n = 27) in the Capital District, NY. MHD were confirmed with clinician notes and retention to PrEP was defined as attending appointments. Between-group differences were compared using Fisher's Exact Test (FET). Kaplan–Meier curves were compared using the log-rank test. Results Of the 27 adolescents enrolled on PrEP between Sep 2015-March 2019, most self-identified as males (93%), MSM (85%), white (74%), and 13 (48%) had a MH diagnosis. Anxiety was the most common MHD (69%), followed by depression (38%). The mean age was 20.3 years (16–24). The average PrEP retention for patients with and without MHD were 262±136 and 292±138 days, respectively (P = 0.575). For patients with MHD, follow-up at 1-month, 3-months and 1-year was 10 (77%), 8 (62%), and 5 (39%), respectively. For patients without MHD, follow-up at 1-month, 3-months, and 1-year was 11 (79%), 10 (71%), 5 (36%), respectively. Follow-up between adolescents with and without MHD was compared at 1-month (P = 0.086, FET), 3-months (P = 0.695, FET), and 1-year (P = 1.0, FET). Adolescents' retention on PrEP was depicted on Kaplan–Meier curves (Figure 1). Log-rank test indicated that PrEP retention is not significantly associated with MHD (χ2(1) = 0.1, P = 0.727). Conclusion Adolescents with and without MHD did not significantly differ in PrEP retention outcomes. The RAMP study elucidates a potentially incorrect provider bias regarding PrEP retention and MHD. Future investigation should be done prospectively with larger sample size. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]

Talks about the impact of monetary policy on housing investment in the U.S. as of May 2002. Demand factors for housing; Structural changes in the mortgage market.

Atrial fibrillation (AF), the most common cardiac arrhythmia, is associated with adverse CV outcomes. Vascular aging (VA), which is defined as the progressive deterioration of arterial function and structure over a lifetime, is an independent predictor of both AF development and CV events. A timing identification and treatment of early VA has therefore the potential to reduce the risk of AF incidence and related CV events. A network of scientists and clinicians from the COST Action VascAgeNet identified five clinically and methodologically relevant questions regarding the relationship between AF and VA and conducted a narrative review of the literature to find potential answers. These are: (1) Are VA biomarkers associated with AF? (2) Does early VA predict AF occurrence better than chronological aging? (3) Is early VA a risk enhancer for the occurrence of CV events in AF patients? (4) Are devices measuring VA suitable to perform subclinical AF detection? (5) Does atrial-fibrillation-related rhythm irregularity have a negative impact on the measurement of vascular age? Results showed that VA is a powerful and independent predictor of AF incidence, however, its role as risk modifier for the occurrence of CV events in patients with AF is debatable. Limited and inconclusive data exist regarding the reliability of VA measurement in the presence of rhythm irregularities associated with AF. To date, no device is equipped with tools capable of detecting AF during VA measurements. This represents a missed opportunity to effectively perform CV prevention in people at high risk. Further advances are needed to fill knowledge gaps in this field. [ABSTRACT FROM AUTHOR]

Introduction: Geographic and transportation barriers are associated with poorer HIV‐related health outcomes in sub‐Saharan Africa, but data on the impact of these barriers on prevention interventions are limited. We estimated the association between distance to clinic and other transportation‐related barriers on pre‐exposure prophylaxis (PrEP) uptake and initial clinic visit attendance in a rural community in southwestern Uganda enrolled in the ongoing SEARCH study (NCT01864603). Methods: Community‐wide HIV testing was conducted and offered to adult (≥15 years) participants in Ruhoko. Participants were eligible for PrEP based on an empiric risk score, having an HIV‐discordant partner, or self‐referral at either the community health campaign or during home‐based testing from March to April 2017. We collected data from PrEP‐eligible households on GPS‐measured distance to clinic, walking time to clinic and road difficulty. A sample of participants was also asked to identify their primary barriers to PrEP use with a semi‐quantitative questionnaire. We used multivariable logistic regression to evaluate the association between transportation barriers and (1) PrEP uptake among PrEP‐eligible individuals and (2) four‐week clinic visit attendance among PrEP initiators. Results: Of the 701 PrEP‐eligible participants, 272 (39%) started PrEP within four weeks; of these, 45 (17%) were retained at four weeks. Participants with a distance to clinic of ≥2 km were less likely to start PrEP (aOR 0.34; 95% CI 0.15 to 0.79, p = 0.012) and less likely to be retained on PrEP once initiated (aOR 0.29; 95% CI 0.10 to 0.84; p = 0.024). Participants who were deemed eligible during home‐based testing and did not have the option of same‐day PrEP start were also substantially less likely to initiate PrEP (aOR 0.16, 95% CI 0.07 to 0.37, p < 0.001). Of participants asked to name barriers to PrEP use (N = 98), the most frequently cited were "needing to take PrEP every day" (N = 18) and "low/no risk of getting HIV" (N = 18). Transportation‐related barriers, including "clinic is too far away" (N = 6) and "travel away from home" (N = 4) were also reported. Conclusions: Distance to clinic is a significant predictor of PrEP uptake and four‐week follow‐up visit attendance in a community in rural Uganda. Interventions that address geographic and transportation barriers may improve PrEP uptake and retention in sub‐Saharan Africa. [ABSTRACT FROM AUTHOR]

This article challenges the concept of a fixed target weight in hemodialysis (HD) patients. The authors conducted a study with 25 HD patients and used bioimpedance spectroscopy (BIS) measurements to analyze fluid status and body composition. They found that the patients' euvolemic body weight varied longitudinally, indicating that target weight might need to be adjusted in individual HD patients. The authors suggest that a soft target weight prescription could be more physiological and potentially reduce complications such as intradialytic hypotension. However, there are limitations to the study, including a small sample size and non-standardized recording of pre-dialysis weight. [Extracted from the article]

Arterial pulse waves (PWs) such as blood pressure and photoplethysmogram (PPG) signals contain a wealth of information on the cardiovascular (CV) system that can be exploited to assess vascular age and identify individuals at elevated CV risk. We review the possibilities, limitations, complementarity, and differences of reduced-order, biophysical models of arterial PW propagation, as well as theoretical and empirical methods for analyzing PW signals and extracting clinically relevant information for vascular age assessment. We provide detailed mathematical derivations of these models and theoretical methods, showing how they are related to each other. Finally, we outline directions for future research to realize the potential of modeling and analysis of PW signals for accurate assessment of vascular age in both the clinic and in daily life. [ABSTRACT FROM AUTHOR]

Introduction: Prescribing the ultrafiltration in hemodialysis patients remains challenging and might benefit from the information on absolute blood volume, estimated by intradialytic dialysate bolus administration. Here, we aimed at determining the relationship between absolute blood volume, normalized for body mass (specific blood volume, Vs), and ultrafiltration‐induced decrease in relative blood volume (∆RBV) as well as clinical parameters including body mass index (BMI). Methods: This retrospective analysis comprised 77 patients who had their dialysate bolus‐based absolute blood volume extracted routinely with an automated method. Patient‐specific characteristics and ∆RBV were analyzed as a function of Vs, dichotomizing the data above or below a previously proposed threshold of 65 ml/kg for Vs. Statistical methodology comprised descriptive analyses, two‐group comparisons, and correlation analyses. Findings: Median Vs was 68.6 ml/kg (54.9 ml/kg [Quartile 1], 83.4 ml/kg [Quartile 3]). Relative blood volume decreased by 6.3% (2.6%, 12.2%) over the entire hemodialysis session. Vs correlated inversely with BMI (rs = −0.688, p < 0.001). ∆RBV was 9.8% in the group of patients with Vs <65 ml/kg versus 6.0% in the group of patients with Vs ≥65 ml/kg (p = 0.024). The two groups did not differ significantly regarding their specific ultrafiltration volume, normalized for body mass, which amounted to 34.1 ml/kg and 36.0 ml/kg in both groups, respectively (p = 0.630). ∆RBV correlated inversely with Vs (rs = −0.299, p = 0.008). Discussion: The present study suggests that patients with higher BMI and lower Vs experience larger blood volume changes, despite similar ultrafiltration requirements. These results underline the clinical plausibility and importance of dialysate bolus‐based absolute blood volume determination in the assessment of target weight, especially in view of a previous study where intradialytic morbid events could be decreased when the target weight was adjusted, based on Vs. [ABSTRACT FROM AUTHOR]

The Covid-19 pandemic necessitated a decrease in non-Covid-19 related diagnostic and therapeutic procedures in many countries. We explored the impact on tertiary hypertension care. We conducted an electronic survey regarding 6 key procedures in hypertension care within the Excellence Center network of the European Society of Hypertension. Overall, 54 Excellence Centers from 18 European and 3 non-European countries participated. From 2019 to 2020, there were significant decreases in the median number per centre of ambulatory blood pressure monitorings (ABPM: 544/289 for 2019/2020), duplex ultrasound of renal arteries (Duplex RA: 88.5/55), computed tomographic/magnetic resonance imaging angiography of renal arteries (CT/MRI RA: 66/19.5), percutaneous angioplasties of renal arteries (PTA RA: 5/1), laboratory tests for catecholamines (116/67.5) and for renin/aldosterone (146/83.5) (p < 0.001 for all comparisons, respectively). While reductions in all assessed diagnostic and therapeutic procedures were observed in all annual 3-months periods in the comparisons between 2019 and 2020, the most pronounced reduction occurred between April and June 2020, which was the period of the first wave and the first lockdown in most affected countries. In this period, the median reductions in 2020, as compared to 2019, were 50.7% (ABPM), 47.1% (Duplex RA), 50% (CT/MRI RA), 57.1% (PTA RA), 46.9% (catecholamines) and 41.0% (renin/aldosterone), respectively. Overall differences in reduction between 3-month time intervals were statistically highly significant. Diagnostic and therapeutic procedures related to hypertension were dramatically reduced during the first year of the Covid-19 pandemic, with the largest reduction during the first lockdown. The long-term consequences regarding blood pressure control and, ultimately, cardiovascular events remain to be investigated. [ABSTRACT FROM AUTHOR]

Examines whether capitalization of school spending into house prices can encourage residents to support spending on schools in the U.S. Percentage of children enrolled in public schools; Differences across communities in the extent of house price capitalization; Increase in school expenditures in the country.

Objectives: Arterial stiffness and wave reflection parameters assessed from both invasive and non-invasive pressure and flow readings are used as surrogates for ventricular and vascular load. They have been reported to predict adverse cardiovascular events, but clinical assessment is laborious and may limit widespread use. This study aims to investigate measures of arterial stiffness and central hemodynamics provided by arterial tonometry alone and in combination with aortic root flows derived by echocardiography against surrogates derived by a mathematical pressure and flow model in a healthy middle-aged cohort. Methods: Measurements of carotid artery tonometry and echocardiography were performed on 2226 ASKLEPIOS study participants and parameters of systemic hemodynamics, arterial stiffness and wave reflection based on pressure and flow were measured. In a second step, the analysis was repeated but echocardiography derived flows were substituted by flows provided by a novel mathematical model. This was followed by a quantitative method comparison. Results: All investigated parameters showed a significant association between the methods. Overall agreement was acceptable for all parameters (mean differences: -0.0102 (0.033 SD) mmHg*s/ml for characteristic impedance, 0.36 (4.21 SD) mmHg for forward pressure amplitude, 2.26 (3.51 SD) mmHg for backward pressure amplitude and 0.717 (1.25 SD) m/s for pulse wave velocity). Conclusion: The results indicate that the use of model-based surrogates in a healthy middle aged cohort is feasible and deserves further attention. [ABSTRACT FROM AUTHOR]