The etiologic relationship between wasting and stunting is poorly understood, largely because of a lack of high-quality longitudinal data from children at risk of undernutrition.
The aim of this ...study was to describe the interrelationships between wasting and stunting in children aged <2 y.
This study involved a retrospective cohort analysis, based on growth-monitoring records spanning 4 decades from clinics in rural Gambia. Anthropometric data collected at scheduled infant welfare clinics were converted to z scores, comprising 64,342 observations on 5160 subjects (median: 12 observations per individual). Children were defined as “wasted” if they had a weight-for-length z score <–2 against the WHO reference and “stunted” if they had a length-for-age z score <–2.
Levels of wasting and stunting were high in this population, peaking at approximately (girls–boys) 12–18% at 10–12 months (wasted) and 37–39% at 24 mo of age (stunted). Infants born at the start of the annual wet season (July–October) showed early growth faltering in weight-for-length z score, putting them at increased risk of subsequent stunting. Using time-lagged observations, being wasted was predictive of stunting (OR: 3.2; 95% CI: 2.7, 3.9), even after accounting for current stunting. Boys were more likely to be wasted, stunted, and concurrently wasted and stunted than girls, as well as being more susceptible to seasonally driven growth deficits.
We provide evidence that stunting is in part a biological response to previous episodes of being wasted. This finding suggests that stunting may represent a deleterious form of adaptation to more overt undernutrition (wasting). This is important from a policy perspective as it suggests we are failing to recognize the importance of wasting simply because it tends to be more acute and treatable. These data suggest that stunted children are not just short children but are children who earlier were more seriously malnourished and who are survivors of a composite process.
Extracellular matrix (ECM) is a dynamic tissue that contributes to organ integrity and function, and its regulation of cell phenotype is a major aspect of cell biology. However, standard in vitro ...culture approaches are of unclear physiologic relevance because they do not mimic the compositional, architectural, or distensible nature of a living organ. In the lung, fibroblasts exist in ECM-rich interstitial spaces and are key effectors of lung fibrogenesis.
To better address how ECM influences fibroblast phenotype in a disease-specific manner, we developed a culture system using acellular human normal and fibrotic lungs.
Decellularization was achieved using treatment with detergents, salts, and DNase. The resultant matrices can be sectioned as uniform slices within which cells were cultured.
We report that the decellularization process effectively removes cellular and nuclear material while retaining native dimensionality and stiffness of lung tissue. We demonstrate that lung fibroblasts reseeded into acellular lung matrices can be subsequently assayed using conventional protocols; in this manner we show that fibrotic matrices clearly promote transforming growth factor-β-independent myofibroblast differentiation compared with normal matrices. Furthermore, comprehensive analysis of acellular matrix ECM details significant compositional differences between normal and fibrotic lungs, paving the way for further study of novel hypotheses.
This methodology is expected to allow investigation of important ECM-based hypotheses in human tissues and permits future scientific exploration in an organ- and disease-specific manner.
Whereas regular exercise is associated with lower risk of cardiovascular disease and mortality, mechanisms of exercise-mediated health benefits remain less clear. We used metabolite profiling before ...and after acute exercise to delineate the metabolic architecture of exercise response patterns in humans.
Cardiopulmonary exercise testing and metabolite profiling was performed on Framingham Heart Study participants (age 53±8 years, 63% women) with blood drawn at rest (n=471) and at peak exercise (n=411).
We observed changes in circulating levels for 502 of 588 measured metabolites from rest to peak exercise (exercise duration 11.9±2.1 minutes) at a 5% false discovery rate. Changes included reductions in metabolites implicated in insulin resistance (glutamate, -29%;
=1.5×10
; dimethylguanidino valeric acid DMGV, -18%;
=5.8×10
) and increases in metabolites associated with lipolysis (1-methylnicotinamide, +33%;
=6.1×10
), nitric oxide bioavailability (arginine/ornithine + citrulline, +29%;
=2.8×10
), and adipose browning (12,13-dihydroxy-9Z-octadecenoic acid +26%;
=7.4×10
), among other pathways relevant to cardiometabolic risk. We assayed 177 metabolites in a separate Framingham Heart Study replication sample (n=783, age 54±8 years, 51% women) and observed concordant changes in 164 metabolites (92.6%) at 5% false discovery rate. Exercise-induced metabolite changes were variably related to the amount of exercise performed (peak workload), sex, and body mass index. There was attenuation of favorable excursions in some metabolites in individuals with higher body mass index and greater excursions in select cardioprotective metabolites in women despite less exercise performed. Distinct preexercise metabolite levels were associated with different physiologic dimensions of fitness (eg, ventilatory efficiency, exercise blood pressure, peak Vo
). We identified 4 metabolite signatures of exercise response patterns that were then analyzed in a separate cohort (Framingham Offspring Study; n=2045, age 55±10 years, 51% women), 2 of which were associated with overall mortality over median follow-up of 23.1 years (
≤0.003 for both).
In a large sample of community-dwelling individuals, acute exercise elicits widespread changes in the circulating metabolome. Metabolic changes identify pathways central to cardiometabolic health, cardiovascular disease, and long-term outcome. These findings provide a detailed map of the metabolic response to acute exercise in humans and identify potential mechanisms responsible for the beneficial cardiometabolic effects of exercise for future study.
Background Although hypoalbuminemia has been associated with decreased survival in chronic systolic heart failure (HF), its role for prognosticating outcomes in those with acutely decompensated heart ...failure (ADHF) has not been established. Methods and Results 438 consecutive patients with ADHF (mean age 75 ± 13 years, mean left ventricular ejection fraction 41% ± 20%) admitted to a large community hospital were studied. The mean serum albumin level for the group was 3.4 g/dL; quintile analysis demonstrated an inflection of risk for death below this value. Patients with hypoalbuminemia (defined as a serum albumin <3.4 g/dL; N = 236, 54% overall) were more likely to have prior HF, more severe HF symptoms, more likely to be edematous, and had more prevalent prognostically meaningful laboratory abnormalities, such as a higher frequency of renal dysfunction and elevated B-type natriuretic peptide. Independent associations between anemia, hyponatremia, lack of therapy with vasodilators at presentation, prior history of obstructive airways disease, severe tricuspid regurgitation, low serum cholesterol, and the presence of a pleural effusion on chest radiography were found with reduced serum albumin; interestingly, body mass index was not predictive of albumin levels. In Cox proportional hazards analysis, hypoalbuminemia predicted 1-year mortality (hazard ratio HRadjusted = 2.05, 95% CI 1.10-3.81, P = .001). Reduced serum albumin concentrations were prognostic across a wide range of body mass index but had highest HR in obese patients (HRadjusted = 4.39 95% CI = 1.66 to 11.60, P = .003). As well, hypoalbuminemia was mainly predictive of outcomes among those with systolic HF (HRadjusted = 5.00, 95% CI = 2.17-11.5, P < .001). Conclusion Hypoalbuminemia is common among patients with ADHF and is independently associated with increased one year mortality in patients admitted with ADHF.
Biopharmaceuticals, such as monoclonal antibodies (mAbs), need to maintain their chemical and physical stability in formulations throughout their lifecycle. It is known that exposure of mAbs to ...light, particularly UV, triggers chemical and physical degradation, which can be exacerbated by trace amounts of photosensitizers in the formulation. Although routine assessments of degradation following defined UV dosages are performed, there is a fundamental lack of understanding regarding the intermediates, transient reactive species, and radicals formed during illumination, as well as their lifetimes and immediate impact post-illumination. In this study, we used light-coupled NMR spectroscopy to monitor in situ live spectral changes in sealed samples during and after UV-A illumination of different formulations of four mAbs without added photosensitizers. We observed a complex evolution of spectra, reflecting the appearance within minutes of transient radicals during illumination and persisting for minutes to tens of minutes after the light was switched off. Both mAb and excipient signals were strongly affected by illumination, with some exhibiting fast irreversible photodegradation and others exhibiting partial recovery in the dark. These effects varied depending on the mAb and the presence of excipients, such as polysorbate 80 (PS80) and methionine. Complementary ex situ high-performance size-exclusion chromatography analysis of the same formulations post-UV exposure in the chamber revealed significant loss of purity, confirming formulation-dependent degradation. Both approaches suggested the presence of degradation processes initiated by light but continuing in the dark. Further studies on photoreaction intermediates and transient reactive species may help mitigate the impact of light on biopharmaceutical degradation.
Dual-factor models of mental health are increasingly supported but little is known about longitudinal trends in dual-factor mental health. The current study used latent profile analysis (LPA) to ...empirically identify dual-factor mental health classes at each of Grades 9 through 12 and latent transition analysis (LTA) to examine stability of classes over four academic years. A sample of 875 adolescents from two cohorts reported on their social-emotional strengths and psychological distress. Cross-sectional LPAs for each grade year resulted in four mental health classes: complete mental health, moderately mentally healthy, symptomatic but content, and troubled. An LTA model indicated that the complete mental health class exhibited the most stability, followed by moderately mentally healthy and symptomatic but content classes. The troubled class exhibited the least stability. Less than 24% of participants remained in the same mental health class across all years. Findings support regular monitoring of students' dual-factor mental health to accurately inform mental health promotion, prevention, and intervention efforts.
Background
Endocrine therapy reduces recurrence risk and improves survival in women with hormone receptor-positive breast cancer; however, side effects can decrease quality of life, leading to ...reduced treatment adherence. Sarcopenia is the loss of skeletal muscle mass that happens with age; it is associated with worse survival and reduced chemotherapy adherence in patients with breast cancer. The impact of sarcopenia on endocrine therapy tolerance has not been investigated. The current study evaluates the associations of sarcopenia with endocrine therapy toxicity and treatment tolerance.
Methods
Skeletal muscle mass was measured by bioelectrical impedance spectrometry. Skeletal muscle index (SMI) was calculated to assess for sarcopenia: SMI = (SMM kg)/(patient height, m
2
). Patients with SMI ≤ 6.75 kg/m
2
were considered sarcopenic. A chart review was performed to obtain patient characteristics, endocrine therapy toxicity, and early treatment change or termination. Fisher's exact test was performed to associate patient characteristics and outcomes with sarcopenia status.
Results
Four hundred eighty-two patients with stage I–III breast cancer were prescribed endocrine therapy and had undergone sarcopenia evaluation. The median age was 61 years (29–88 years). Sarcopenia was identified in 35% of patients. Twelve percent of patients experienced grade 3–4 endocrine-related toxicities. On multivariable logistic analysis, sarcopenia was associated with increased odds of experiencing endocrine-related side effects (
p
= 0.006). In addition, patients with sarcopenia stopped or changed their medication due to side effects more often than those without sarcopenia (
p
= 0.03).
Conclusion
The presence of sarcopenia in patients with EBC represents a potentially modifiable risk factor for more significant endocrine therapy side effects and reduced treatment tolerance.
Background
Breast cancer is a disease that requires multimodality treatment, and surgical resection of the tumor is a critical component of curative intent treatment. Obesity, defined as a body mass ...index (BMI) > 30, has been associated with increased surgical complications. Additionally, sarcopenia, a condition of gradual loss of muscle mass, has been associated with worse breast cancer treatment outcomes. Sarcopenia occurs with increased age, inactivity, and poor diet leading to patient frailty, which can increase medical treatment complications. Even patients with high BMI can have sarcopenia (termed sarcopenic obesity). We investigated the association of sarcopenia with surgical complications for breast cancer.
Methods
A retrospective review was performed of patients diagnosed with breast cancer who received bioelectrical impedance spectrometry analysis of skeletal muscle mass and had surgery at our institution. Patient characteristics, treatment data, surgical type and complications were obtained from medical records. Multivariate logistic regression models were used to associate sarcopenia status and BMI with surgical complications, adjusted for other patient characteristics.
Results
We analyzed 682 patients with stage I to III breast cancer. On multivariable logistic regression controlling for age, BMI, comorbidities, and types of surgeries (lumpectomy, mastectomy with or without reconstruction), sarcopenia (p = 0.66) was not associated with surgical complications. Obesity was associated with a higher rate of surgical complications in patients who received mastectomy with reconstruction (p = 0.01). More complex surgical approaches were associated with a higher risk of surgical complications in our series.
Conclusion
Compared with those undergoing lumpectomy or mastectomy without reconstruction, patients undergoing mastectomy with reconstruction were more likely to experience postoperative complications and obesity was associated with higher risk of complication in the latter group. We did not identify a correlation between sarcopenia and rate of adverse surgical outcomes.
Objectives The aim of this study was to evaluate whether chronic heart failure (HF) therapy guided by concentrations of amino-terminal pro–B-type natriuretic peptide (NT-proBNP) is superior to ...standard of care (SOC) management. Background It is unclear whether standard HF treatment plus a goal of reducing NT-proBNP concentrations improves outcomes compared with standard management alone. Methods In a prospective single-center trial, 151 subjects with HF due to left ventricular (LV) systolic dysfunction were randomized to receive either standard HF care plus a goal to reduce NT-proBNP concentrations ≤1,000 pg/ml or SOC management. The primary endpoint was total cardiovascular events between groups compared using generalized estimating equations. Secondary endpoints included effects of NT-proBNP–guided care on patient quality of life as well as cardiac structure and function, assessed with echocardiography. Results Through a mean follow-up period of 10 ± 3 months, a significant reduction in the primary endpoint of total cardiovascular events was seen in the NT-proBNP arm compared with SOC (58 events vs. 100 events, p = 0.009; logistic odds for events 0.44, p = 0.02); Kaplan-Meier curves demonstrated significant differences in time to first event, favoring NT-proBNP–guided care (p = 0.03). No age interaction was found, with elderly patients benefitting similarly from NT-proBNP–guided care as younger subjects. Compared with SOC, NT-proBNP–guided patients had greater improvements in quality of life, demonstrated greater relative improvements in LV ejection fraction, and had more significant improvements in both LV end-systolic and -diastolic volume indexes. Conclusions In patients with HF due to LV systolic dysfunction, NT-proBNP–guided therapy was superior to SOC, with reduced event rates, improved quality of life, and favorable effects on cardiac remodeling. (Use of NT-proBNP Testing to Guide Heart Failure Therapy in the Outpatient Setting; NCT00351390 )
Objective: To assess the feasibility of backward cycling for people with Parkinson’s disease. Secondary objectives were to assess changes in gait and balance following a 6-week program. Design: A ...single-group prospective pre-test, post-test study with 1-month follow-up. Subjects/Patients: Twenty-six people with Parkinson’s disease (mean age: 69 (7.74) years, gender: 83% males, time since diagnosis: 6 (4.44) years). Methods: Participants pedaled backward on a stationary bicycle for 30 minutes at moderate intensity twice a week for 6 weeks. Feasibility was assessed by acceptability, suitability, and burden. Data collected at pre- and post-intervention with 1-month follow-up included backward stepping response variables, forward/backward gait variables, Mini-Balance Evaluation Systems Test (MBT), and 6 Minute Walk Test. Results: There was a high retention rate (95.8%) and adherence rate (100%) with one adverse event and minimal burden. Significant improvements were seen in step count and excursion distance during backward stepping responses, forward and backward gait velocity, forward step length, and the Mini-BESTest. Conclusion: Backward cycling was a feasible intervention for people with Parkinson’s disease, demonstrating low burden with high retention and adherence rates, and it is a safe exercise with the potential for benefits in gait and balance variables.
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