OBJECTIVE To evaluate phrenic nerve motor amplitude (PhrenicAmp) as an independent predictor of functional decline in amyotrophic lateral sclerosis (ALS). We also assessed both PhrenicAmp and forced vital capacity (FVC) as predictors of functional loss in patients with bulbar dysfunction. METHODS We included consecutive ALS patients with PhrenicAmp and FVC at baseline. Participants were evaluated with the revised ALS Functional Rating Scale (ALSFRS-R) at inclusion and at, at least, one subsequent follow-up visit. The outcome measure of functional decline was the percentage reduction in ALSFRS-R from baseline.  https://www.selleckchem.com/products/sn-38.html  Bulbar dysfunction was defined by the presence of any relevant symptom on the ALSFRS-R bulbar sub-score. Correlations and mixed-effects regressions were used to study the relationship between functional decline and both PhrenicAmp and FVC baseline evaluations. RESULTS A total of 249 ALS patients were included; 64.2% of these had bulbar dysfunction. At inclusion, significant correlations were found between PhrenicAmp and FVC (p  less then  0.001), as well as between each respiratory measure and ALSFRS-R (all p  less then  0.001). The functional decline at first (median 3 months) and second (median 6 months) follow-up visits was significantly correlated with baseline values of both respiratory evaluations (all p  less then  0.01) in the entire ALS population, but only with baseline PhrenicAmp (all p  less then  0.05) in bulbar dysfunction cases. Regression analysis revealed that PhrenicAmp (all p  less then  0.05), but not FVC, was a significant independent predictor of functional decline in ALS patients and in those with bulbar dysfunction. CONCLUSION Baseline PhrenicAmp is an independent predictor of functional decline in ALS, whether or not bulbar dysfunction is present.BACKGROUND Plasma volume (PV) estimated from Duarte's formula (based on hemoglobin/hematocrit) has been associated with poor prognosis in patients with heart failure (HF). There are, however, limited data regarding the association of estimated PV status (ePVS) derived from hemoglobin/hematocrit with clinical profiles and study outcomes in patients with HF and preserved ejection fraction (HFpEF). METHODS AND RESULTS Patients from North and South America enrolled in the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist trial (TOPCAT) with available hemoglobin/hematocrit data were studied. The association between ePVS (Duarte formula and Hakim formula) and the composite of cardiovascular mortality, HF hospitalization, or aborted cardiac arrest was assessed. Among 1747 patients (age 71.6 years; males 50.1%), mean ePVS derived from Duarte formula was 4.9 ± 1.0 mL/g. Higher Duarte-derived ePVS was associated with prior HF admission, diabetes, more severe congestion, poor renal function, higher natriuretic peptide level, and E/e'. After adjustment for potential covariates including natriuretic peptide, higher Duarte-derived ePVS was associated with an increased rate of the primary outcome [highest vs. lowest ePVS quartile adjusted-HR (95%CI) = 1.79 (1.28-2.50), p  0.10 for all outcomes). CONCLUSION ePVS from Duarte's formula was associated with congestion status and improved risk stratification regardless of renal function. Our findings suggest that Duarte-derived ePVS is a useful congestion variable in patients with HFpEF.Postinflammatory hyperpigmentation (PIH) occurs following cutaneous injury and is common following resolution of acne especially in patients with skin of color. The objective of this study was to further validate a trichloroacetic acid (TCA)-induced PIH model and compare it to acne-induced PIH using topical bakuchiol, a botanical extract that has been shown to have antimicrobial, anti-inflammatory, antioxidant, and antiacne properties. A prospective, non-randomized clinical trial was conducted on subjects with skin phototypes IV-VI with a history of acne-induced PIH. Subjects applied bakuchiol or vehicle cream twice daily to 2 acne-induced and 2 TCA-induced PIH lesions for 28 days with a third lesion serving as a control in each group. Degree of improvement was defined as the change in the Investigator Global Assessment (IGA) score over 28 days of treatment. Twenty subjects (6 males, 14 females) completed the study. For TCA-induced PIH sites, there was a statistically significant (p  0.05). TCA-induced PIH sites were uniform in size and pigment intensity thereby allowing better comparison among sites. This emphasizes the relevance of using this model for PIH which may help reduce the barriers in clinical trials and help improve access to treatments for patients who suffer from PIH. The results suggest that topical bakuchiol may decrease the severity of PIH.PURPOSE Treatment for head and neck cancer is associated with multiple side effects, including loss of body mass, impaired physical function and reduced health-related quality of life. This study aimed to investigate the impact of treatment (radiation therapy ± concurrent chemotherapy) on (i) muscle strength, muscle cross-sectional area and patient-reported outcomes, and (ii) central and peripheral alterations during a whole-body exercise task. METHODS Ten people with head and neck cancer (4 female; 50 ± 9 years) completed a lab visit before and after (56 ± 30 days) completion of treatment. Participants performed a neuromuscular assessment (involving maximal isometric voluntary contractions in the knee extensors and electrical stimulation of the femoral nerve) before and during intermittent cycling to volitional exhaustion. Anthropometrics and patient-reported outcomes were also assessed. RESULTS From before to after treatment, maximal isometric muscle strength was reduced (P = 0.002, d = 0.73), as was potentiated twitch force (P  less then  0.001, d = 0.62), and muscle cross-sectional area (e.g., vastus lateralis P = 0.010, d = 0.64). Exercise time was reduced (P = 0.008, d = 0.62) and peripheral processes contributed to a reduction in maximal force due to cycling. After treatment, the severity of self-reported fatigue increased (P = 0.041, r = - 0.65) and health-related quality of life decreased (P = 0.012, r = - 0.79). CONCLUSION Neuromuscular function was impaired in patients with head and neck cancer after treatment. Whole-body exercise tolerance was reduced and resulted in predominantly peripheral, rather than central, disturbances to the neuromuscular system. Future research should evaluate strength training after treatment for head and neck cancer, with the overall aim of reducing fatigue and improving health-related quality of life.