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Dramatic advances in the care of patients with cancer have led to significant improvement in outcomes and survival. However, renal manifestations of the underlying cancer as well as the effects of anti-neoplastic therapies leave patients with significant morbidity and chronic kidney disease risks. The most common renal manifestations associated with cancer include acute kidney injury (AKI) in the setting of multiple myeloma, tumor lysis syndrome, post-hematopoietic stem cell therapy, and AKI associated with chemotherapy. Knowledge of specific risk factors, modification of risk and careful attention to rapid AKI diagnosis are critical for improving outcomes.

Background and aims: Acute kidney injury (AKI) is associated with higher mortality and length of stay (LOS) for hospitalized patients. To improve outcomes, an electronic detection system could be a useful tool for early diagnosis. Methods: A fully automated real-time system for detecting decreased glomerular filtration rate in adult patients was developed in our hospital, DETECT-H project. AKI was established according to KDIGO guidelines. Results: In six months, 1241 alerts from 11,022 admissions were issued. Overall incidence of AKI was 7.7%. Highest AKI stage reached was: stage 1 (49.8%), 2 (24.5%) and 3 (25.8%), in-hospital mortality was 10.9%, 22.7%, 33.9% respectively and 57.1% in AKI requiring dialysis; mortality in stable CKD was 4.3%. Median LOS was 8 days versus 5 days for all patients. AKI was associated with a mortality of 3.18 (95% CI 1.80–5.59) and a LOS 1.52 (1.11–2.08) times as high as that for admissions without AKI. Multivariate analysis indicated that a LOS higher than 8 days was associated with AKI. Previous CKD was noted in 31.9% and AKI in 45.3% at discharge. As compared to the use of the detect system, only one third of CKD patients and half of AKI episodes were identified. Conclusions: CKD and in-hospital AKI are under-recognized entities. Mortality and LOS are increased in-hospital patients with renal dysfunction. AKI severity was associated with higher mortality and LOS. An automated electronic detection system for identifying renal dysfunction would be a useful tool to improve renal outcomes. Resumen: Introducción y objetivos: El fracaso renal agudo (FRA) aumenta la mortalidad y la estancia hospitalarias (EH). El empleo de sistemas de detección electrónica podría ser una herramienta beneficiosa para mejorar estos resultados. Métodos: Se desarrolló un sistema de detección automático a tiempo real de pacientes ingresados con función renal alterada, denominado proyecto DETECT-H. El FRA se estableció de acuerdo con las guías KDIGO. Resultados: En 6 meses, 1.241 alertas fueron recogidas de 11.022 ingresos. La incidencia global del FRA fue del 7,7%. La distribución en función del estadio máximo del FRA alcanzado fue: estadio 1: 49,8%, estadio 2: 24,5% y estadio 3: 25,8%; con una mortalidad hospitalaria del 10,9, 22,7 y 33,9%, respectivamente. En el caso del FRA con necesidad de diálisis fue del 57,1%. La mortalidad en pacientes con enfermedad renal crónica (ERC) estable fue del 4,3%. La mediana de EH en pacientes detectados fue 8 vs. 5 días para todos los pacientes hospitalizados. El FRA se asoció con una mortalidad 3,18 (1,8-5,59) y una EH 1,52 (1,11-2,08) veces superior que aquellos ingresos sin FRA. El análisis multivariante indicó que el FRA se asociaba con la EH > 8 días.En los informes de alta, la presencia de ERC previa solo fue registrada en el 31,9% de los pacientes con ERC y el FRA hospitalario en el 45,3%. Conclusiones: La ERC y el FRA intrahospitalario son entidades infradiagnosticadas. La mortalidad y la EH están aumentadas en pacientes con disfunción renal. La gravedad del FRA se asoció con mayor mortalidad y EH. Un sistema de detección automático para identificarlos podría ser útil para mejorar estos resultados. Keywords: Acute kidney injury, Automated electronic detection system, Chronic kidney disease, Diagnosis, Health information technology, Mortality, Palabras clave: Fracaso renal agudo, Sistema de detección electrónica automática, Enfermedad renal crónica, Diagnóstico, Tecnología de información de la salud, Mortalidad

Plants synthetize a large spectrum of secondary metabolites with substantial structural and functional diversity, making them a rich reservoir of new biologically active compounds. Among different plant lineages, the evolutionarily ancient branch of non-vascular plants (Bryophytes) is of particular interest as these organisms produce many unique biologically active compounds with highly promising antibacterial properties. Here, we characterized antibacterial activity of metabolites produced by different ecotypes (strains) of the model mosses Physcomitrium patens and Sphagnum fallax. Ethanol and hexane moss extracts harbor moderate but unstable antibacterial activity, representing polar and non-polar intracellular moss metabolites, respectively. In contrast, high antibacterial activity that was relatively stable was detected in soluble exudate fractions of P. patens moss. Antibacterial activity levels in P. patens exudates significantly increased over four weeks of moss cultivation in liquid culture. Interestingly, secreted moss metabolites are only active against a number of Gram-positive, but not Gram-negative, bacteria. Size fractionation, thermostability and sensitivity to proteinase K assays indicated that the secreted bioactive compounds are relatively small (less than

Background: Data from the 2009 influenza pandemic suggested asthma might protect from severe disease in hospitalized patients. Asthma does not appear to increase risk for hospitalization or mortality with COVID-19. Objective: This study was undertaken to see if atopy actually protected those hospitalized with COVID-19. Methods: Retrospective chart review on all patients testing positive for SARS-CoV-2 over 2 months at a major adult and pediatric tertiary referral center hospital. Charts were evaluated for history of atopic disease, as were the need for ICU admission, requirement for supplemental oxygen and/or intubation, and in hospital mortality. Results: No significant differences in outcomes for patients (n = 275) based on atopic disease were noted: ICU admission, 43% versus 44.7% (atopic versus no atopic disease, respectively; p = 0.84); supplemental oxygen use, 79.1% versus 73.6% (p = 0.36); intubation rate, 35.8% versus 36.5% (p = 0.92); and mortality rate, 13.4% versus 20.7% (p = 0.19). More patients with atopic disease had COPD listed as a diagnosis in their chart (38.8% versus 17.3%, p 0.2). Conclusion: Severity of COVID-19 in hospitalized patients does not differ based on atopic status. However, adjusting for presence of COPD led to a suggestion of possible reduced severity in patients with atopy but not asthma.

Abstract. Introduction:. The negative effects of chronic pain and obesity are compounded in those with both conditions. Despite this, little research has focused on the pathophysiology in pediatric samples. Objective:. To examine the effects of comorbid chronic pain and obesity on the concentration of circulating inflammatory biomarkers. Methods:. We used a multiple-cohort observational design, with 4 groups defined by the presence or absence of obesity and chronic pain: healthy controls, chronic pain alone, obesity alone, as well as chronic pain and obesity. Biomarkers measured were leptin, adiponectin, leptin/adiponectin ratio (primary outcome), tumor necrosis factor-alpha, interleukin 6, and C-reactive protein (CRP). Results:. Data on 125 adolescents (13–17 years) were analyzed. In females, there was an interaction between chronic pain and obesity such that leptin and CRP were higher in the chronic pain and obesity group than in chronic pain or obesity alone. Within the chronic pain and obesity group, biomarkers were correlated with worsened pain attributes, and females reported worse pain than males. The highest levels of interleukin 6 and CRP were found in youth with elevated weight and functional disability. We conclude that in adolescents, chronic pain and obesity interact to cause dysregulation of the inflammatory system, and this effect is more pronounced in females. Conclusion:. The augmented levels of inflammatory biomarkers are associated with pain and functional disability, and may be an early marker of future pain and disability.

Multicellular organisms have co-evolved with complex consortia of viruses, bacteria, fungi and parasites, collectively referred to as the microbiota.sup.1. In mammals, changes in the composition of the microbiota can influence many physiologic processes (including development, metabolism and immune cell function) and are associated with susceptibility to multiple diseases.sup.2. Alterations in the microbiota can also modulate host behaviours--such as social activity, stress, and anxiety-related responses--that are linked to diverse neuropsychiatric disorders.sup.3. However, the mechanisms by which the microbiota influence neuronal activity and host behaviour remain poorly defined. Here we show that manipulation of the microbiota in antibiotic-treated or germ-free adult mice results in significant deficits in fear extinction learning. Single-nucleus RNA sequencing of the medial prefrontal cortex of the brain revealed significant alterations in gene expression in excitatory neurons, glia and other cell types. Transcranial two-photon imaging showed that deficits in extinction learning after manipulation of the microbiota in adult mice were associated with defective learning-related remodelling of postsynaptic dendritic spines and reduced activity in cue-encoding neurons in the medial prefrontal cortex. In addition, selective re-establishment of the microbiota revealed a limited neonatal developmental window in which microbiota-derived signals can restore normal extinction learning in adulthood. Finally, unbiased metabolomic analysis identified four metabolites that were significantly downregulated in germ-free mice and have been reported to be related to neuropsychiatric disorders in humans and mouse models, suggesting that microbiota-derived compounds may directly affect brain function and behaviour. Together, these data indicate that fear extinction learning requires microbiota-derived signals both during early postnatal neurodevelopment and in adult mice, with implications for our understanding of how diet, infection, and lifestyle influence brain health and subsequent susceptibility to neuropsychiatric disorders. A diverse intestinal microbiota is required for mice to undergo extinction-related neuronal plasticity and normal fear extinction learning., Author(s): Coco Chu [sup.1] , Mitchell H. Murdock [sup.2] [sup.3] [sup.4] , Deqiang Jing [sup.3] [sup.4] [sup.5] , Tae Hyung Won [sup.6] , Hattie Chung [sup.7] , Adam M. Kressel [...]

For Hispanic women, the Breast Cancer Risk Assessment Tool (BCRAT; "Gail Model") combines 1990-1996 breast cancer incidence for Hispanic women with relative risks for breast cancer risk factors from non-Hispanic white (NHW) women. BCRAT risk projections have never been comprehensively evaluated for Hispanic women. We compared the relative risks and calibration of BCRAT risk projections for 6,353 Hispanic to 128,976 NHW postmenopausal participants aged 50 and older in the Women's Health Initiative (WHI). Calibration was assessed by the ratio of the number of breast cancers observed with that expected by the BCRAT (O/E). We re-evaluated calibration for an updated BCRAT that combined BCRAT relative risks with 1993-2007 breast cancer incidence that is contemporaneous with the WHI. Cox regression was used to estimate relative risks. Discriminatory accuracy was assessed using the concordance statistic (AUC). In the WHI Main Study, the BCRAT underestimated the number of breast cancers by 18% in both Hispanics (O/E = 1.18, P = 0.06) and NHWs (O/E = 1.18, P < 0.001). Updating the BCRAT improved calibration for Hispanic women (O/E = 1.08, P = 0.4) and NHW women (O/E = 0.98, P = 0.2). For Hispanic women, relative risks for number of breast biopsies (1.71 vs. 1.27, P = 0.03) and age at first birth (0.97 vs. 1.24, P = 0.02) differed between the WHI and BCRAT. The AUC was higher for Hispanic women than NHW women (0.63 vs. 0.58, P = 0.03). Updating the BCRAT with contemporaneous breast cancer incidence rates improved calibration in the WHI. The modest discriminatory accuracy of the BCRAT for Hispanic women might improve by using risk factor relative risks specific to Hispanic women.

Near-infrared (NIR) genetically encoded calcium ion (Ca2+) indicators (GECIs) can provide advantages over visible wavelength fluorescent GECIs in terms of reduced phototoxicity, minimal spectral cross talk with visible light excitable optogenetic tools and fluorescent probes, and decreased scattering and absorption in mammalian tissues. Our previously reported NIR GECI, NIR-GECO1, has these advantages but also has several disadvantages including lower brightness and limited fluorescence response compared to state-of-the-art visible wavelength GECIs, when used for imaging of neuronal activity. Here, we report 2 improved NIR GECI variants, designated NIR-GECO2 and NIR-GECO2G, derived from NIR-GECO1. We characterized the performance of the new NIR GECIs in cultured cells, acute mouse brain slices, and Caenorhabditis elegans and Xenopus laevis in vivo. Our results demonstrate that NIR-GECO2 and NIR-GECO2G provide substantial improvements over NIR-GECO1 for imaging of neuronal Ca2+ dynamics.

Background Repeated assessment of cardiorespiratory fitness (CRF) improves mortality risk predictions in apparently healthy adults. Accordingly, the American Heart Association suggests routine clinical assessment of CRF using, at a minimum, nonexercise prediction equations. However, the accuracy of nonexercise prediction equations over time is unknown. Therefore, we compared the ability of nonexercise prediction equations to detect changes in directly measured CRF. Methods and Results The sample included 987 apparently healthy adults from the BALL ST (Ball State Adult Fitness Longitudinal Lifestyle Study) cohort (33% women; average age, 43.1±10.4 years) who completed 2 cardiopulmonary exercise tests ≥3 months apart (3.2±5.4 years of follow‐up). The change in estimated CRF (eCRF) from 27 distinct nonexercise prediction equations was compared with the change in directly measured CRF. Analysis included Pearson product moment correlations, SEE values, intraclass correlation coefficient values, Cohen's κ coefficients, γ coefficients, and the Benjamini‐Hochberg procedure to compare eCRF with directly measured CRF. The change in eCRF from 26 of 27 equations was significantly associated to the change in directly measured CRF (P

IntroductionCardiorespiratory fitness (CRF) is a strong independent predictor of cardiovascular disease (CVD) and CVD mortality. However, little is known in regards to how CRF has trended in apparently healthy adults over the past several decades.PurposeTo analyze trends in CRF and CVD risk factors over the last 50 years in a population of apparently healthy adult men and women.MethodsParticipants were 4,214 apparently healthy adults (2,390 men and 1,824 women) from the Ball State Adult Fitness Longitudinal Lifestyle STudy (BALL ST) that performed maximal cardiopulmonary exercise testing between 1970-2019 for the assessment of CRF defined as VO2max (ml/kg/min). Participants were self-referred either to a community-based exercise program, fitness testing, or were research subjects in exercise related studies and were placed into groups by decade based on testing date.ResultsCRF showed a general trend to decline (PConclusionCRF declined from 1970 through the 2000s in a cohort of apparently healthy men and women which was associated with worsening CVD risk profiles. However, the decline in CRF was attenuated over the past decade which may have a positive impact on future CVD in the population. Promoting physical activity to increase CRF should be a primary aspect of CVD prevention programs.

ObjectiveTo develop a tool for estimating the 10-year risk of death from other causes in men with localized prostate cancer.Subjects and methodsWe identified 2,425 patients from the Surveillance Epidemiology and End Results-Medicare Health Outcomes Survey database, age ResultsOver a median follow-up of 7.7 years, 76 men died of prostate-specific causes and 465 died of other causes. The strongest predictors of 10-year other cause mortality risk included increasing age at diagnosis, higher approximated Charlson Comorbidity Index score, worse patient-reported general health (fair or poor vs. excellent-good), smoking at diagnosis, and marital status (all other vs. married) (all pConclusionsWe provide a tool for estimating the 10-year risk of dying from other causes when making decisions about treating prostate cancer using pre-treatment patient-reported characteristics.

Occipital neuralgia (ON) is a condition defined as a headache characterized by paroxysmal burning and stabbing pain located in the distribution of the greater occipital nerve (GON), lesser occipital nerve (LON), or third occipital nerves (TON). This condition can be severely impairing in symptomatic patients and is known to have numerous etiologies deriving from various origins such as trauma, anatomical abnormalities, tumors, infections, and degenerative changes. This study reports four cases of a previously undescribed anatomical variant in which the (spinal) accessory nerve (SAN) fuses with the LON before piercing the sternocleidomastoid (SCM). The fusion of these two nerves and their route through the SCM points to a potential location for nerve compression within the SCM and, in turn, another potential source of ON. This anatomical presentation has clinical significance as it provides clinicians with another possible cause of ON to consider when diagnosing patients who present with complaints of a headache. Additionally, this study explores the prevalence of piercing anatomy of the LON and GAN and discusses their clinical implications.

Abstract The National Cancer Institute (NCI) sponsored a 2-day workshop, “Next Steps in Studying the Human Microbiome and Health in Prospective Studies,” in Bethesda, Maryland, May 16–17, 2017. The workshop brought together researchers in the field to discuss the challenges of conducting microbiome studies, including study design, collection and processing of samples, bioinformatics and statistical methods, publishing results, and ensuring reproducibility of published results. The presenters emphasized the great potential of microbiome research in understanding the etiology of cancer. This report summarizes the workshop and presents practical suggestions for conducting microbiome studies, from workshop presenters, moderators, and participants.

The purpose of this paper is to help readers choose an appropriate observational study design for measuring an association between an exposure and disease incidence. We discuss cohort studies, sub-samples from cohorts (case-cohort and nested case-control designs), and population-based or hospital-based case-control studies. Appropriate study design is the foundation of a scientifically valid observational study. Mistakes in design are often irremediable. Key steps are understanding the scientific aims of the study and what is required to achieve them. Some designs will not yield the information required to realise the aims. The choice of design also depends on the availability of source populations and resources. Choosing an appropriate design requires balancing the pros and cons of various designs in view of study aims and practical constraints. We compare various cohort and case-control designs to estimate the effect of an exposure on disease incidence and mention how certain design features can reduce threats to study validity.

Objective: The focus of this study was the association between the metabolic syndrome (MetSyn) and cardiorespiratory fitness (CRF) defined as maximal oxygen uptake (VO2max). Although previous research has shown a relationship between MetSyn and CRF, most studies are based on less objective measures of CRF and different cardiometabolic risk factor thresholds from earlier guidelines. Participants and Methods: The metabolic markers included in the present study were central obesity, elevated plasma triglycerides, elevated fasting high-density lipoprotein cholesterol, impaired fasting plasma glucose, hypertension, or pharmacologic treatment for diagnosed hypertension, hypertriglyceridemia, low high-density lipoprotein cholesterol, or diabetes. A cohort of 3636 adults (1629 women, 2007 men; mean ± SD age, 44.7±12.3 years) completed CRF and metabolic risk factor assessment between January 1, 1971, and November 1, 2016. The CRF was defined as a measured VO2max from a cardiopulmonary exercise test on a treadmill, with a respiratory exchange ratio value of 1.0 or more. Results: Prevalence of MetSyn (≥3 factors) was 26% (n=953) in the cohort, with men having a greater likelihood for MetSyn compared with women (P

Abstract Sepsis is the leading cause of acute kidney injury (AKI) in the intensive care unit (ICU). Septic AKI is a complex and multifactorial process that is incompletely understood. During sepsis, the disruption of the mucus membrane barrier, a shift in intestinal microbial flora, and microbial translocation may lead to systemic inflammation, which further alters host immune and metabolic homeostasis. This altered homeostasis may promote and potentiate the development of AKI. As part of this vicious cycle, when AKI develops, the clearance of inflammatory mediators and metabolic products is decreased. This will lead to further gut injury and breakdown in mucous membrane barriers. Thus, changes in the gut during sepsis can initiate and propagate septic AKI. This deleterious gut–kidney crosstalk may be a potential target for therapeutic maneuvers. This review analyses the underlying mechanisms in gut–kidney crosstalk in septic AKI.