Carbonic anhydrases reduce the acidity of the tumor microenvironment, promote immune infiltration, decelerate tumor growth, and improve survival in ErbB2/HER2-enriched breast cancer.

BACKGROUND: Carbonic anhydrases catalyze CO2/HCO3- buffer reactions with implications for effective H+ mobility, pH dynamics, and cellular acid-base sensing. Yet, the integrated consequences of carbonic anhydrases for cancer and stromal cell functions, their interactions, and patient prognosis are not yet clear. METHODS: We combine (a) bioinformatic analyses of human proteomic data and bulk and single-cell transcriptomic data coupled to clinicopathologic and prognostic information; (b) ex vivo experimental studies of gene expression in breast tissue based on quantitative reverse transcription and polymerase chain reactions, intracellular and extracellular pH recordings based on fluorescence confocal microscopy, and immunohistochemical protein identification in human and murine breast cancer biopsies; and (c) in vivo tumor size measurements, pH-sensitive microelectrode recordings, and microdialysis-based metabolite analyses in mice with experimentally induced breast carcinomas. RESULTS: Carbonic anhydrases-particularly the extracellular isoforms CA4, CA6, CA9, CA12, and CA14-undergo potent expression changes during human and murine breast carcinogenesis. In patients with basal-like/triple-negative breast cancer, elevated expression of the extracellular carbonic anhydrases negatively predicts survival, whereas, surprisingly, the extracellular carbonic anhydrases positively predict patient survival in HER2/ErbB2-enriched breast cancer. Carbonic anhydrase inhibition attenuates cellular net acid extrusion and extracellular H+ elimination from diffusion-restricted to peripheral and well-perfused regions of human and murine breast cancer tissue. Supplied in vivo, the carbonic anhydrase inhibitor acetazolamide acidifies the microenvironment of ErbB2-induced murine breast carcinomas, limits tumor immune infiltration (CD3+ T cells, CD19+ B cells, F4/80+ macrophages), lowers inflammatory cytokine (Il1a, Il1b, Il6) and transcription factor (Nfkb1) expression, and accelerates tumor growth. Supporting the immunomodulatory influences of carbonic anhydrases, patient survival benefits associated with high extracellular carbonic anhydrase expression in HER2-enriched breast carcinomas depend on the tumor inflammatory profile. Acetazolamide lowers lactate levels in breast tissue and blood without influencing breast tumor perfusion, suggesting that carbonic anhydrase inhibition lowers fermentative glycolysis. CONCLUSIONS: We conclude that carbonic anhydrases (a) elevate pH in breast carcinomas by accelerating net H+ elimination from cancer cells and across the interstitial space and (b) raise immune infiltration and inflammation in ErbB2/HER2-driven breast carcinomas, restricting tumor growth and improving patient survival.

Recommendations for the study of monoclonal gammopathies in the clinical laboratory. A consensus of the Spanish Society of Laboratory Medicine and the Spanish Society of Hematology and Hemotherapy. Part I: Update on laboratory tests for the study of monoclonal gammopathies.

Monoclonal gammopathies (MG) are characterized by the proliferation of plasma cells that produce identical abnormal immunoglobulins (intact or some of their subunits). This abnormal immunoglobulin component is called monoclonal protein (M-protein), and is considered a biomarker of proliferative activity. The identification, characterization and measurement of M-protein is essential for the management of MG. We conducted a systematic review of the different tests and measurement methods used in the clinical laboratory for the study of M-protein in serum and urine, the biochemistry and hematology tests necessary for clinical evaluation, and studies in bone marrow, peripheral blood and other tissues. This review included literature published between 2009 and 2022. The paper discusses the main methodological characteristics and limitations, as well as the purpose and clinical value of the different tests used in the diagnosis, prognosis, monitoring and assessment of treatment response in MG. Included are methods for the study of M-protein, namely electrophoresis, measurement of immunoglobulin levels, serum free light chains, immunoglobulin heavy chain/light chain pairs, and mass spectrometry, and for the bone marrow examination, morphological analysis, cytogenetics, molecular techniques, and multiparameter flow cytometry.

Loss of RPTPγ primes breast tissue for acid extrusion, promotes malignant transformation and results in early tumour recurrence and shortened survival.

BACKGROUND: While cellular metabolism and acidic waste handling accelerate during breast carcinogenesis, temporal patterns of acid-base regulation and underlying molecular mechanisms responding to the tumour microenvironment remain unclear. METHODS: We explore data from human cohorts and experimentally investigate transgenic mice to evaluate the putative extracellular HCO3--sensor Receptor Protein Tyrosine Phosphatase (RPTP)γ during breast carcinogenesis. RESULTS: RPTPγ expression declines during human breast carcinogenesis and particularly in high-malignancy grade breast cancer. Low RPTPγ expression associates with poor prognosis in women with Luminal A or Basal-like breast cancer. RPTPγ knockout in mice favours premalignant changes in macroscopically normal breast tissue, accelerates primary breast cancer development, promotes malignant breast cancer histopathologies, and shortens recurrence-free survival. In RPTPγ knockout mice, expression of Na+,HCO3--cotransporter NBCn1-a breast cancer susceptibility protein-is upregulated in normal breast tissue but, contrary to wild-type mice, shows no further increase during breast carcinogenesis. Associated augmentation of Na+,HCO3--cotransport in normal breast tissue from RPTPγ knockout mice elevates steady-state intracellular pH, which has known pro-proliferative effects. CONCLUSIONS: Loss of RPTPγ accelerates cellular net acid extrusion and elevates NBCn1 expression in breast tissue. As these effects precede neoplastic manifestations in histopathology, we propose that RPTPγ-dependent enhancement of Na+,HCO3--cotransport primes breast tissue for cancer development.

Polypropylene and polyvinylidene fluoride transobturator slings for the treatment of female stress urinary incontinence: 1-Year outcomes from a multicentre randomized trial.

AIMS: To compare the effectiveness and safety of polypropylene (PP) and polyvinylidene fluoride (PVDF) transobturator tapes (TOT) for the treatment of female stress urinary incontinence (SUI). METHODS: This is a multicentre randomized trial. Women with SUI or stress-predominant mixed urinary incontinence and scheduled for a TOT procedure were randomized to PP or PVDF slings. The primary outcome was 1-year cure or improvement rate using composite criteria. Complications were also compared. Relationships with outcomes were analyzed using multivariable logistic regressions models. RESULTS: From April 2016 to January 2018 285 participants were randomized. PP and PVDF slings showed similar high cure or improvement rate (91.0% vs. 95.6%, p = .138). Improvement in validated questionnaires was also similar. PVDF slings were associated with a lower rate of de novo urgency incontinence (adjusted odds ratio = 0.35; 95% confidence interval = 0.15-0.80). We found no statistical differences in complications rates, although a higher incidence of long-term pain events were observed in the PP group. The study is underpowered to find differences in specific complications owing to the low number of events. CONCLUSION: PP and PVDF TOTs are equally effective, although PVDF is associated with fewer cases of de novo urgency incontinence. Further studies are needed to give robust conclusions on safety profiles.

[Prevalence of fear of falling and related factors in community-dwelling older people]. / Prevalencia del miedo a caer y factores asociados en personas mayores que viven en la comunidad.

AIM: To know, in the population over 70, independent for walking, the prevalence of the concern to fall according to the short version of the Short Falls Efficacy Scale-International (FES-I) questionnaire, in old people living in the community and their associated factors. DESIGN: Cross-sectional study. LOCATION: Centro de Salud El Greco, Getafe, Madrid, Spain. PARTICIPANTS: 189 patients ≥70years with a Barthel ≥60, independent for walking (walk 45minutes without help or with a cane). The study was offered to a total of 328 people, of these accepted 217 and rejected 111. MAIN MEASUREMENTS: The dependent variable, fear of falling (FOF), was evaluated by means of the short FES-I questionnaire, considering as a cut-off point for the positive screening of the MC a score ≥11. As independent variables we considered: Barthel index, Downton scale, the Short Physical Performance Battery (SPPB) fragility test, falls in the last year, injuries associated with falls, time since the last fall, sensory deficit, use of gait devices, comorbidity and pharmacological treatment. RESULTS: The prevalence of FOF was 42.9% (95%CI: 35.5-50.2). The factors associated with FOF in the final multivariate analysis were: female sex, living alone, high risk of falls, presence of frailty (SPPB≤9), use of hypotensive drugs, and injuries associated with previous falls. CONCLUSIONS: The prevalence of FOF in older people is high. Primary Care professionals should systematize the screening of this health problem, prioritizing especially in people who present the following risk factors: being a woman, living alone, having a low score on the SPPB (as an indicator of frailty) or presenting a high risk of falls.

The functional association between the sodium/bicarbonate cotransporter (NBC) and the soluble adenylyl cyclase (sAC) modulates cardiac contractility.

The soluble adenylyl cyclase (sAC) was identified in the heart as another source of cyclic AMP (cAMP). However, its cardiac physiological function is unknown. On the other hand, the cardiac Na+/HCO3- cotransporter (NBC) promotes the cellular co-influx of HCO3- and Na+. Since sAC activity is regulated by HCO3-, our purpose was to investigate the potential functional relationship between NBC and sAC in the cardiomyocyte. Rat ventricular myocytes were loaded with Fura-2, Fluo-3, or BCECF to measure Ca2+ transient (Ca2+i) by epifluorescence, Ca2+ sparks frequency (CaSF) by confocal microscopy, or intracellular pH (pHi) by epifluorescence, respectively. Sarcomere or cell shortening was measured with a video camera as an index of contractility. The NBC blocker S0859 (10 µM), the selective inhibitor of sAC KH7 (1 µM), and the PKA inhibitor H89 (0.1 µM) induced a negative inotropic effect which was associated with a decrease in Ca2+i. Since PKA increases Ca2+ release through sarcoplasmic reticulum RyR channels, CaSF was measured as an index of RyR open probability. The generation of CaSF was prevented by KH7. Finally, we investigated the potential role of sAC activation on NBC activity. NBC-mediated recovery from acidosis was faster in the presence of KH7 or H89, suggesting that the pathway sAC-PKA is negatively regulating NBC function, consistent with a negative feedback modulation of the HCO3- influx that activates sAC. In summary, the results demonstrated that the complex NBC-sAC-PKA plays a relevant role in Ca2+ handling and basal cardiac contractility.

Qualitative study of knowledge, perception, behavior and barriers associated with cardiovascular disease risk among overweight and obese Hispanic taxi drivers of South Bronx, NYC.

BACKGROUND: Taxi drivers are prone to developing cardiovascular disease (CVD) risk factors by adopting poor health behaviors due to their work environment. The population of Hispanic taxi drivers in inner city South Bronx, NYC, have not been studied. The goal of our qualitative study is to understand the perception, knowledge, behavior and barriers that influence CVD risk in overweight and obese inner-city Hispanic drivers. METHODS: A cross-sectional qualitative study was conducted among community-based taxi drivers in South Bronx, NYC. Hispanic taxi drivers with body mass index of greater than 25 kg/m2 were screened and recruited for the study. Focus groups were organized to evaluate CVD and obesity risk factors through open-ended questions. The discussions were recorded, transcribed and analyzed using standard qualitative techniques. The Health Belief Model framework was applied to understand and evaluate likelihood of promoting health behaviors in this population based on the findings from the focus groups. RESULTS: We conducted 3 focus groups (N = 25) and themes that emerged were evaluated. Through the Health Belief Model framework, Hispanic taxi driver participants reported demanding and stressful work shifts, barriers to better nutrition and good health, poor support systems, and low self-efficacy in overcoming barriers to improve their risk for CVD, due to lower perceived benefits and greater perceived barriers. CONCLUSIONS: Inner-city Hispanic NYC taxi drivers have several contributing factors and barriers leading to a poor CVD risk and high body weight profile. Understanding their knowledge, perception and barriers the drivers face in improving their CVD risk, underscores the importance of community outreach programs to develop a framework in empowering and improving the health of this population.

Effectiveness of Shared Decision-Making for Elderly Depressed Minority Primary Care Patients.

OBJECTIVE: The authors assessed the impact of a shared decision-making (SDM) intervention among elderly depressed minority primary care patients not currently receiving treatment. METHODS: A total of 202 English and Spanish-speaking primary care participants aged 65 and older who scored positive on the Patient Health Questionnaire-9 (≥10) were randomized at the physician level to receive a brief SDM intervention or usual care (UC). Primary analyses focused on patient adherence to either psychotherapy or antidepressant medication, and reduction in depression severity (Hamilton Depression Rating Scale) over 12 weeks. RESULTS: Patients randomized to physicians in the SDM condition were significantly more likely than patients of physicians randomized to UC to receive a mental health evaluation or initiate some form of treatment (39% versus 21%), and to adhere to psychotherapy visits over 12 weeks. There were no differences between groups in adherence to antidepressant medication or in reduction of depressive symptoms. CONCLUSION: Among untreated elderly depressed minority patients from an inner-city municipal hospital, a brief SDM intervention was associated with greater initiation and adherence to psychotherapy. However, low treatment adherence rates across both groups and the intervention's lack of impact on clinical outcomes highlight the need to provide focused and accessible mental health services to patients choosing active treatments.

[Validation of an ammonia breath test for the diagnosis of Helicobacter pylori infection in patients with dyspepsia at Hospital Cayetano Heredia]. / Validación de una prueba de amonio en aliento para el diagnóstico de la infección por Helicobacter pylori en pacientes del Hospital Cayetano Heredia.

Objetive: To determine the diagnostic validity of an ammonia breath test for Helicobacter pylori infection in patients who undergo an upper gastrointestinal endoscopy at Hospital Cayetano Heredia. MATERIAL AND METHODS: From April to December 2014, 155 patients were evaluated with the ammonia breath test and compared with a histological evaluation of the gastric biopsies as the gold standard. Data were evaluated using Microsoft Excel and STATA 14 to build a ROC curve. RESULTS: The patients were predominantly female (71%), with a median age of 53 years (18-84) and a Helicobacter pylori prevalence of 51.6%. The ammonia breath test, when compared to the gastric biopsy has a 70% sensitivity, 36% specificity, 53.8% positive predictive value, 36% negative predictive value, 1.15 positive likelihood ratio and 0.75 negative likelihood ratio. According to the ROC curve, there is not an optimal cut off value and the area under the curve was 0.5517. CONCLUSIONS: The ammonia breath test evaluated on this study does not have diagnostic accuracy and is not recommended as a diagnostic tool for Helicobacter pylori infection.

The reduced myofilament responsiveness to calcium contributes to the negative force-frequency relationship in rat cardiomyocytes: role of reactive oxygen species and p-38 map kinase.

The force-frequency relationship (FFR) is an important intrinsic regulatory mechanism of cardiac contractility. However, a decrease (negative FFR) or no effect (flat FFR) on contractile force in response to an elevation of heart rate is present in the normal rat or in human heart failure. Reactive oxygen species (ROS) can act as intracellular signaling molecules activating diverse kinases as calcium-calmodulin-dependent protein kinase II (CaMKII) and p-38 MAP kinase (p-38K). Our aim was to elucidate the intracellular molecules implicated in the FFR of isolated rat ventricular myocytes. The myocytes were field-stimulated via two-platinum electrodes. Sarcomere length was recorded with a video camera. Ca2+ transients and intracellular pHi were recorded by epifluorescence. Increasing frequency from 0.5 to 3 Hz decreased cell shortening without changes in pHi. This negative FFR was changed to positive FFR when the myocytes were pre-incubated with the ROS scavenger MPG, the NADPH oxidase blocker apocynin, or by inhibiting mitochondrial ROS production with 5-HD. Similar results were obtained when the cells were pre-incubated with the CaMKII blocker, KN-93, or the p-38K inhibitor, SB-202190. Consistently, the levels of phosphorylation of p-38K and the oxidation of CaMKII were significantly higher at 2 Hz than at 0.5 Hz. Despite the presence of positive inotropic effect during stimulation frequency enhancement, Ca2+ transient amplitudes were reduced in MPG- and SB-202190-treated myocytes. In conclusion, our results indicate that the activation of the intracellular pathway involving ROS-CaMKII-p-38K contributes to the negative FFR of rat cardiomyocytes, likely by desensitizing the response of contractile myofilaments to Ca2+.

Hepatitis C seroprevalence in an at-risk population in the southwest Madrid region of Spain. / Seroprevalencia de hepatitis C en población con factores de riesgo del suroeste de la Comunidad de Madrid.

INTRODUCTION: The estimated seroprevalence of hepatitis C virus (HCV) in Spain is 1.7%, but is much higher in the at-risk population. The most efficient national screening strategy is unclear. AIMS: To estimate the prevalence of HCV among the at-risk population seen in primary care (PC), and to determine their epidemiological profile. MATERIALS AND METHODS: Cross-sectional descriptive prevalence study that included adult patients with risk factors for HCV infection seen in PC in the southwest Madrid region between 2010 and 2012. RESULTS: A total of 158 patients (men=51.3%), mean age 46 years (SD=16.6), were included. The most common risk factors were hypertransaminasaemia (44.3%) and major surgery (13.3%). Immigration, unsafe sexual practices, and tattoos or body piercing were more prevalent in patients younger than 45 years of age. Fifteen patients (9.5%) were positive for anti-HCV; 9 of these (5.7%) were HCV-ARN positive. Of the positive patients, 4 (44.4%) had significant fibrosis at diagnosis (F3-F4). Male patients had a higher rate of positive anti-HCV results (13.8 vs. 5.3%; P=.072), as did patients older than 45 years of age (12.8 vs. 6.3%; P=.167). Intravenous and intranasal drug use were associated with a higher rate of positive anti-HCV results (50 vs. 8.5%; P=.005 and 66.7 vs. 8.4%; P=.001, respectively). CONCLUSIONS: Patients with risk factors for HCV infection have high seroprevalence. Screening programmes must therefore be implemented to detect HCV infection in this population in PC.

Aldosterone stimulates the cardiac sodium/bicarbonate cotransporter via activation of the g protein-coupled receptor gpr30.

Some cardiac non-genomic effects of aldosterone (Ald) are reported to be mediated through activation of the classic mineralocorticoid receptor (MR). However, in the last years, it was proposed that activation of the novel G protein-coupled receptor GPR30 mediates certain non-genomic effects of Ald. The aim of this study was to elucidate if the sodium/bicarbonate cotransporter (NBC) is stimulated by Ald and if the activation of GPR30 mediates this effect. NBC activity was evaluated in rat cardiomyocytes perfused with HCO3(-)/CO2 solution in the continuous presence of HOE642 (sodium/hydrogen exchanger blocker) during recovery from acidosis using intracellular fluorescence measurements. Ald enhanced NBC activity (% of ΔJHCO3(-); control: 100±5.82%, n=7 vs Ald: 151.88±11.02%, n=5; P<0.05), which was prevented by G15 (GPR30 blocker, 90.53±7.81%, n=7). Further evidence for the involvement of GPR30 was provided by G1 (GPR30 agonist), which stimulated NBC (185.13±18.28%, n=6; P<0.05) and this effect was abrogated by G15 (124.19±10.96%, n=5). Ald- and G1-induced NBC stimulation was abolished by the reactive oxygen species (ROS) scavenger MPG and by the NADPH oxidase inhibitor apocynin. In addition, G15 prevented Ald- and G1-induced ROS production. Pre-incubation of myocytes with wortmannin (PI3K-AKT pathway blocker) prevented Ald- or G1-induced NBC stimulation. In summary, Ald stimulates NBC by GPR30 activation, ROS production and AKT stimulation.

Prepubertal children with a history of extra-uterine growth restriction exhibit low-grade inflammation.

Intra-uterine growth restriction (IUGR) may induce significant metabolic and inflammatory anomalies, increasing the risk of obesity and CVD later in life. Similarly, alterations in the adipose tissue may lead to metabolic changes in children with a history of extra-uterine growth restriction (EUGR). These mechanisms may induce alterations in immune response during early life. The aim of the present study was to compare pro-inflammatory markers in prepubertal EUGR children with those in a reference population. A total of thirty-eight prepubertal children with a history of EUGR and a reference group including 123 healthy age- and sex-matched children were selected. Perinatal data were examined. In the prepubertal stage, the concentrations of inflammatory biomarkers were measured in both groups. The serum concentrations of C-reactive protein (CRP) and plasma concentrations of hepatocyte growth factor (HGF), IL-6, IL-8, monocyte chemotactic protein type 1 (MCP-1), neural growth factor, TNF-α and plasminogen activator inhibitor type 1 were determined. The plasma concentrations of inflammatory biomarkers CRP, HGF, IL-8, MCP-1 and TNF-α were higher in the EUGR group than in the reference group (P< 0·001). After adjustment for gestational age, birth weight and length, blood pressure values and TNF-α concentrations remained higher in the EUGR group than in the reference group. Therefore, further investigations should be conducted in EUGR children to evaluate the potential negative impact of metabolic, nutritional and pro-inflammatory changes induced by the EUGR condition.

Perioperative nutritional support.

The relationship between preoperative malnutrition and morbi-mortality has been documented for years. Despite the existence of tools that allow its detection, and therefore treat this entity, their introduction into clinical practice is not wide-spread. Both perioperative insulin resistance and hyperglycemia are associated with increased perioperative morbidity and length of hospital stay. The intake of carbohydrate-rich drinks 2-4h prior to surgery reduces insulin resistance. In the immediate postoperative period, the enteral route is safe and well tolerated and its early use reduces hospital stay and postoperative complications compared with parenteral nutritional support. Inmunonutrition has been proven effective to decrease postoperative complications and hospital stay. In view of these data we opted for the adoption of these measures replacing bowel rest and the indiscriminate use of postoperative parenteral nutrition.

Emotion regulation and cognitive function as mediating factors for the association between lifetime abuse and risky behaviors in women of color.

BACKGROUND: The relationship between lifetime abuse (i.e., childhood abuse, intimate partner violence) and risky behaviors is well established. One proposed mechanism is poor emotion regulation and executive functioning, as a potential mechanism that may explain the relationship between lifetime abuse and risky behaviors. However, research on executive functioning and emotion regulation as mediators of this relationship has been limited. In the present study, we examined this association. We hypothesized that lifetime abuse would be significantly associated with executive function and emotion regulation which in turn would be associated with greater alcohol use and risky sex. METHODS: This cross-sectional study included 150 women with a history of lifetime abuse who were assessed for hazardous alcohol use using the AUDIT Score; emotion regulation was measured using the Difficulties with Emotion Regulation Scale (DERS); risky sex was measured using the question: "in the last 90 days, how many people did you have anal or vaginal sex without using a condom? Executive function was assessed using the NIH Toolbox. RESULTS: The mediation model followed the self-regulation theory, which proposes executive function as the higher-order cognitive process. Results showed that executive function deficit and poor emotion regulation significantly mediated the relationship between lifetime abuse and hazardous alcohol use (indirect effect = .097, SE .031, 95% CI = .035 to .158). CONCLUSION: Our findings suggest a higher-order cognitive process with executive function promoting emotion regulation as a potential mechanism for alcohol problems in women of color who experienced lifetime abuse.

The Evolution of Psychological Distress Levels in University Students in Spain during Different Stages of the COVID-19 Pandemic: Risk and Protective Factors.

The present study assesses the evolution of stressful events and psychological distress in male and female students over three different time periods of the COVID-19 pandemic in Spain: the initial "lockdown", with no face-to-face teaching; the "new normality" period, when classes were resumed; and two years after the first wave of the pandemic. The participants were 1200 Spanish university students who were assessed for psychological distress, COVID-19-associated stressful events, social support, and self-esteem. Female students reported more stressful events and higher levels of psychological distress than male students during the "lockdown" and "new normality" time periods of the first wave of the pandemic. However, these differences disappeared in the third period tested, two years after the first wave of the pandemic, with female and male students showing no differences in psychological distress or in the number of stressful events. The main risk predictors of psychological distress during the first wave of the pandemic were lower self-esteem and having suffered a high number of stressful events. The last variable, number of stressful events associated with COVID-19, lost most its effect two years later, when only self-esteem presented a strong and highly significant predictive role.

Prognostic significance of long-period heart rate rhythms in chronic heart failure.

BACKGROUND: Abnormalities in autonomic control are a feature of neuroendocrine activation in HF and are responsible for dysregulation of biological rhythms. The purpose was to investigate the presence and the prognostic significance of long-period heart rate (HR) rhythms in heart failure (HF) patients. METHODS AND RESULTS: In the study, 92 HF patients were enrolled (age 53 ± 14 years and left ventricular ejection fraction [LVEF] 37 ± 10%). A rhythmometric analysis was used to assess the HR rhythms in 7-days (7D) Holter recordings. Rhythms properties were quantified by mesor and amplitude, in beats/min and by acrophase, in hours. Cardiac death or HF decompensation were registered. All patients had 24-h rhythm, 61 patients (77%) had 8-h rhythm, and 66 patients (83%) had 7D rhythm. Twelve patients (15%) experienced events. Among rhythm parameters only 7D median amplitude was different between patients with or without events: 1.1 beats/min [0.5-1.5] vs. 2.0 beats/min [0.0-3.9], P=0.049 respectively. After multivariate adjustment, LVEF (per 1%, hazard ratio 0.92, 95% confidence interval (CI) 0.87 to 0.98, P=0.01), N-terminal portion of pro-natriuretic hormone type B (per 100 pg/ml, hazard ratio 1.036, 95% CI 1.005-1.069, P=0.022), and 7D amplitude of the HR ≤1.71 beats/min (hazard ratio 5.4, 95% CI 1.2-34.4, P=0.047) were independent predictors of events. CONCLUSIONS: A 7D HR rhythm is present in most patients with HF, and has prognostic significance.

Intimate Partner Violence and Breastfeeding Behaviors: Does the Source of Breastfeeding Information Affect the Associations Between Prepregnancy or Prenatal IPV and Breastfeeding Behaviors of Women in the United States? A PRAMS 2018 Study.

Background: Most countries do not meet World Health Organization's breastfeeding recommendations, and exposure to intimate partner violence (IPV) hinders positive breastfeeding behaviors. One in four U.S. women (43.6 million women) experiences IPV. This study aims to assess relationships between IPV, and breastfeeding initiation, duration, and early cessation among women in 42 U.S. states; and to evaluate possible modifying effect(s) of different breastfeeding information sources. Methods: Centers for Disease Control and Prevention's 2016-2018 Pregnancy Risk Assessment Monitoring System data (n = 105,230) were used to assess relationships between prepregnancy/prenatal IPV and breastfeeding initiation, duration, and early cessation; and modify effects of various breastfeeding information sources on study associations using multilogistic regression models. Results: About 1.4% of women experienced prenatal IPV with reduced odds of breastfeeding for 6 months or more (odds ratio [OR] = 0.74; 95% confidence interval = 0.58-0.94). Receiving breastfeeding information from baby's doctor modified early cessation (0.37 [0.18-0.78]) (p for interaction = 0.009) with prenatal IPV exposure. Among women exposed to prenatal IPV, breastfeeding initiation was stronger in women who received breastfeeding information from family/friends (2.46, [1.24-4.88]) (p for interaction = 0.010) or from breastfeeding support groups (3.03 [1.17-7.88]) (p for interaction = 0.023) compared to those who did not. Breastfeeding information from family/friends modified association between prepregnancy IPV and breastfeeding duration (0.67 [0.45-0.99]) (p for interaction = 0.042). Conclusions: Prenatal IPV is a risk factor for short-duration breastfeeding. Receiving information from doctors, nurses, support groups, and family/friends may improve breastfeeding behavior among IPV-exposed women. Interventions promoting breastfeeding information dissemination by family/friends, support groups, and doctors/nurses during hospital visits are encouraged.

A Randomized Controlled Trial to Increase Cancer Screening and Reduce Depression Among Low-Income Women.

Low-income women of color receive fewer cancer screenings and have higher rates of depression, which can interfere with cancer screening participation. This study assessed the comparative effectiveness of two interventions for improving colorectal, breast, and cervical cancer screening participation and reducing depression among underserved women in Bronx, NY, with depression. This comparative effectiveness randomized controlled trial (RCT) with assessments at study entry, 6, and 12 months utilized an intent-to-treat statistical approach. Eligible women were aged 50 to 64, screened positive for depression, and were overdue for ≥ 1 cancer screening (colorectal, breast, and/or cervical). Participants were randomized to a collaborative depression care plus cancer screening intervention (CCI + PCM) or cancer screening intervention alone (PCM). Interventions were telephone-based, available in English or Spanish, delivered over 12 months, and facilitated by a skilled care manager. Cancer screening data were extracted from electronic health records. Depression was measured with a validated self-report instrument (PHQ-9). Seven hundred fifty seven women consented and were randomized (CCI + PCM, n = 378; PCM, n = 379). Analyses revealed statistically significant increases in up-to-date status for all three cancer screenings; depression improved in both intervention groups. There were no statistically significant differences between the interventions in improving cancer screening rates or reducing depression. CCI and PCM both improved breast, cervical, and colorectal cancer screening and depression in clinical settings in underserved communities; however, neither intervention showed an advantage in outcomes. Decisions about which approach to implement may depend on the nature of the practice and alignment of the interventions with other ongoing priorities and resources.

Maritime-oriented foragers during the Late Pleistocene on the eastern costa del sol (Southeast Iberia): Cueva Victoria (Málaga, Spain).

The Mediterranean coast of Spain is marked by several clusters of Palaeolithic sites: to the south of the Pyrenees, in the area around the Ebro River, in the central part, and on the south coast, one of the southernmost regions in Europe. The number of sites is small compared with northern Iberia, but like that region, the Palaeolithic occupations are accompanied by several rock art ensembles. The archaeological material (both biotic and abiotic resources) and radiocarbon dates presented here were obtained during archaeological fieldwork of professor J. Fortea in the Late Pleistocene deposits in Cueva Victoria, located near the modern coastline and about 150 km north of the Strait of Gibraltar. In the three occupation phases, marine resources were acquired by shell-fishing (focusing almost exclusively on the clam Ruditapes decussatus), fishing, and the use of beached marine mammals. This contrasts with the limited data about the exploitation of terrestrial resources by hunting and gathering animals and plants. The study is completed by the study of artefacts (lithic and bone industry and objects of adornment) that help to understand the subsistence strategies of the cave occupants and enable a comparison with other groups inhabiting the Mediterranean coasts of the Iberian Peninsula during Greenland Interstadial 1, between ca. 15.1 and 13.6 cal BP.