Effect of individualized physical rehabilitation programs on respiratory function in women with post-mastectomy syndrome

Purpose: The purpose of this study was to determine the effectiveness of an individualized physical rehabilitation programs aimed at improving respiratory function in women with post-mastectomy syndrome. Methods: In a randomized controlled trial 50 women with post-mastectomy syndrome were enrolled in the experimental group (EG, n = 25) or the comparison group (CG, n = 25). The program for the EG included: aqua aerobics (i.e. aqua jogging, aqua building, and aqua stretching); conditional swimming; and recreational aerobics. The program for the CG included: conditional swimming and Pilates exercises. Both intervention groups attended individualized physical rehabilitation programs three times per week for 48 weeks. The primary outcome measure was spirometry of the patients measured before, 6 and 12 months after the intervention. Results: This study demonstrated that most of the respiratory function parameters increased significantly in both groups over the year of exercise training. After the year of training the individualized physical rehabilitation program for the EG was significantly better (p < 0.01) as compared with the CG, except for inspiratory reserve volume and maximal voluntary ventilation, which were not statistically different. Conclusions: The results of the study suggest that individual programs of physical rehabilitation could be considered effective for the improvement of respiratory function of the patients with post-mastectomy syndrome. The results obtained could serve as a basis for more widespread clinical program development.     

Loss-of-function mutations in caspase recruitment domain-containing protein 14 (CARD14) are associated with a severe variant of atopic dermatitis

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Treatment of diabetic foot complications]

Of 3721 patients with diabetic lesions of the foot treated 2416 (65%) patients have been operated. The rise of urgent hospitalization rate (over 90%) unfavourably influenced the results of the treatment and contributed to increased frequency of high amputations of the extremity. The proposed system for evaluation of the condition and scope of the combined treatment resulted in decrease of mortality among operated patients from 14.7% to 9.8% and among not operated ones--from 20.5% to 5.5%. The suggested classifications of complicated forms of the "diabetic foot" syndrome provided proper evaluation of the prognosis and individual approach to the choice of treatment measures.     

Partial characterization of a phosphorylated intermediate associated with the plasma membrane ATPase of corn roots

The phosphorylated protein associated with a deoxycholate-extracted plasma membrane fraction from corn (Zea mays L. var WF9 × Mol7) roots was characterized in order to correlate its properties with those of plasma membrane ATPase. Its phosphorylation, like that of plasma membrane ATPase, was dependent on Mg²⁺, substrate specific for ATP, insensitive to azide, oligomycin, or molybdate, and sensitive to N,N′-dicyclohexylcarbodiimide, diethylstilbestrol, or vanadate. Monovalent cations affected the phosphorylation of the protein in a manner consistent with their stimulatory effects on ATPase. For K⁺, this was shown to occur through an increase in the turnover of the phosphoenzyme. Analysis of the phosphorylated protein by NaDodSO₄/polyacrylamide gel electrophoresis revealed the presence of a single labeled polypeptide with a molecular weight of about 100,000. Phosphorylation of this polypeptide was dependent on Mg²⁺, sensitive to K⁺, and inhibited by vanadate. It is concluded that this polypeptide represents the catalytic subunit of the plasma membrane ATPase. These results are discussed in terms of a model for the coupling of metabolic energy to H⁺ and K⁺ transport in higher plants.     

The physiological significance of a coronary stenosis differentially affects contractility and mitochondrial function in viable chronically dysfunctional myocardium

The reversibility of viable dysfunctional myocardium after revascularization is variable and the reasons for this are unknown. Using 2D-DIGE, we tested the hypothesis that this could reflect the extent of molecular remodeling of myocardial tissue in the absence of infarction. Swine with a progressive left anterior descending (LAD) stenosis were studied 2 months (n = 18) or 3 months (n = 22) post-instrumentation. Coronary flow reserve (vasodilated/rest) was severely reduced at 2 months (LAD 2.6 ± 0.4 versus 5.1 ± 0.4 in normal, p < 0.05) and became critically impaired after 3 months (LAD 1.1 ± 0.2, p < 0.05 vs. 2 months). Despite progression in stenosis severity, reductions in wall thickening at 2 months (LAD 37 ± 4 % vs. remote 86 ± 9 %, p < 0.05) were unchanged at 3 months (LAD 32 ± 3 %, p = ns). Contractile dysfunction was primarily related to reductions (LAD/normal) in contractile proteins which were not affected by stenosis severity (e.g., troponin T, 2 months 0.82 ± 0.03 vs. 0.74 ± 0.03 at 3 months, p-ns). In contrast, mitochondrial function and proteins were normal at 2 months but declined with progression to a critical stenosis (state 3 respiration at 3 months 145 ± 13 vs. 216 ± 5 ng-atoms O₂ mg^?1 min^?1 at 2 months, p < 0.05). In a similar fashion, increases in stress (e.g., αB-crystalline 2.13 ± 0.2 vs. 1.17 ± 0.13 at 2 months, p < 0.05) and cytoskeletal proteins (e.g., desmin 1.63 ± 0.12 vs. 1.24 ± 0.10 at 2 months, p < 0.05) only developed with more advanced remodeling from a critical stenosis. We conclude that similar degrees of chronic contractile dysfunction can have diverse intrinsic molecular adaptations to ischemia. This spectrum of adaptations may underlie variability in the time course and extent of reversibility in viable chronically dysfunctional myocardium after revascularization.     

Child and family health in the era of prevention: new opportunities and challenges

To maintain positive health outcomes over the life course, prevention efforts should begin early in childhood. Two research domains that significantly impact the trajectory of health over the life course are childhood obesity and early trauma and violence. Prevention strategies addressing multiple levels of influence are being adopted in these fields. Childhood obesity prevention efforts no longer focus solely on individuals, but embrace multiple ecological levels, such as family, school, and community. Similarly, research on early trauma and violence has broadened to consider risk and protective factors across domains of influence. Although we have improved our understanding and prevention of these two issues, gaps remain in research, practice, and policy. The purpose of this review is to relay relevant findings that could enhance prevention strategies. We describe early life and multilevel risk factors relevant to these areas of research. We also provide recommendations for future efforts to better ensure good health for generations to come.     

MAdCAM-1 expressed in chronic inflammatory liver disease supports mucosal lymphocyte adhesion to hepatic endothelium (MAdCAM-1 in chronic inflammatory liver disease)

Mucosal addressin cell adhesion molecule (MAdCAM-1) plays a pivotal role in T-lymphocyte homing to the gut. Given the strong association between the autoimmune liver diseases primary sclerosing cholangitis and autoimmune hepatitis and inflammatory bowel disease, we investigated the role of MAdCAM-1 in recruiting mucosal lymphocytes to the liver. MAdCAM-1 was strongly expressed on inflamed portal vein/sinusoidal endothelium in autoimmune mediated liver disease. In modified Stamper-Woodruff assays, MAdCAM-1 on hepatic vessels supported adhesion of alpha4beta7+ lymphocytes (i.e., gut-derived T cells) from patients with inflammatory bowel disease and primary sclerosing cholangitis. This adhesion was inhibited by pretreatment with blocking antibodies to MAdCAM-1, alpha4beta7, or the integrin alpha4 chain indicating that MAdCAM-1 in inflamed liver is functionally active. Circulating lymphocytes from patients with primary sclerosing cholangitis showed rolling adhesion on MAdCAM-1 transfectants in a flow-based adhesion assay that could be blocked by anti-MAdCAM-1 or anti-alpha4beta7 mAbs. These findings indicate that, under certain circumstances, vessels in the human liver support adhesion of alpha4beta7+ mucosal lymphocytes via binding to aberrantly expressed MAdCAM-1 on liver endothelium. This provides a mechanism to explain the hepatic recruitment of mucosal lymphocytes in inflammatory liver disease complicating inflammatory bowel disease.     

Novel MIR143‐NOTCH fusions in benign and malignant glomus tumors

Glomus tumors (GT) have been classified among tumors of perivascular smooth muscle differentiation, together with myopericytoma, myofibroma/tosis, and angioleiomyoma, based on their morphologic overlap. However, no molecular studies have been carried out to date to investigate their genetic phenotype and to confirm their shared pathogenesis. RNA sequencing was performed in three index cases (GT1, malignant GT; GT2, benign GT and M1, multifocal myopericytoma), followed by FusionSeq data analysis, a modular computational tool developed to discover gene fusions from paired‐end RNA‐seq data. A gene fusion involving MIR143 in band 5q32 was identified in both GTs with either NOTCH2 in 1p13 in GT1 or NOTCH1 in 9q34 in GT2, but none in M1. After being validated by FISH and RT‐PCR, these abnormalities were screened on 33 GTs, 6 myopericytomas, 9 myofibroma/toses, 18 angioleiomyomas and in a control group of 5 sino‐nasal hemangiopericytomas. Overall NOTCH2 gene rearrangements were identified in 52% of GT, including all malignant cases and one NF1‐related GT. No additional cases showed NOTCH1 rearrangement. As NOTCH3 shares similar functions with NOTCH2 in regulating vascular smooth muscle development, the study group was also investigated for abnormalities in this gene by FISH. Indeed, NOTCH3 rearrangements were identified in 9% of GTs, all present in benign soft tissue GT, one case being fused to MIR143. Only 1/18 angioleiomyomas showed NOTCH2 gene rearrangement, while all the myopericytomas and myofibroma/toses were negative. In summary, we describe novel NOTCH1–3 rearrangements in benign and malignant, visceral, and soft tissue GTs. © 2013 Wiley Periodicals, Inc.     

Blood Kidney Injury Molecule-1 Is a Biomarker of Acute and Chronic Kidney Injury and Predicts Progression to ESRD in Type I Diabetes

Currently, no blood biomarker that specifically indicates injury to the proximal tubule of the kidney has been identified. Kidney injury molecule-1 (KIM-1) is highly upregulated in proximal tubular cells following kidney injury. The ectodomain of KIM-1 is shed into the lumen, and serves as a urinary biomarker of kidney injury. We report that shed KIM-1 also serves as a blood biomarker of kidney injury. Sensitive assays to measure plasma and serum KIM-1 in mice, rats, and humans were developed and validated in the current study. Plasma KIM-1 levels increased with increasing periods of ischemia (10, 20, or 30 minutes) in mice, as early as 3 hours after reperfusion; after unilateral ureteral obstruction (day 7) in mice; and after gentamicin treatment (50 or 200 mg/kg for 10 days) in rats. In humans, plasma KIM-1 levels were higher in patients with AKI than in healthy controls or post-cardiac surgery patients without AKI (area under the curve, 0.96). In patients undergoing cardiopulmonary bypass, plasma KIM-1 levels increased within 2 days after surgery only in patients who developed AKI (P<0.01). Blood KIM-1 levels were also elevated in patients with CKD of varous etiologies. In a cohort of patients with type 1 diabetes and proteinuria, serum KIM-1 level at baseline strongly predicted rate of eGFR loss and risk of ESRD during 5–15 years of follow-up, after adjustment for baseline urinary albumin-to-creatinine ratio, eGFR, and Hb1Ac. These results identify KIM-1 as a blood biomarker that specifically reflects acute and chronic kidney injury.