Mitochondrial myopathy of childhood associated with depletion of mitochondrial DNA.

We have studied five children with mitochondrial myopathy manifesting within or soon after the first year of life. Muscle biopsies showed ragged-red fibers and decreased respiratory chain activity. All five patients had a severe decrease (2 to 34% of normal) in the amount of muscle mitochondrial DNA (mtDNA). The depletion of mtDNA correlated with absence of mtDNA-encoded translation products and with loss of cytochrome c oxidase enzyme activity in individual muscle fibers. This mitochondrial myopathy of childhood illustrates one phenotypic expression of a novel pathogenetic mechanism in mitochondrial diseases, the specific depletion of mtDNA in affected tissues.     

C heterochromatin variation in couples with recurrent early abortions.

The possible influence of the high polymorphic C heterochromatic regions of human chromosomes 1, 9, 16, and Y on meiotic chromosome segregation was investigated. Faulty chromosome segregation may be the result of either an abnormal quantity of C heterochromatin on the homologues, or disequilibrium between the homologues. The aim of our study was to determine whether either a variation in the amounts of total C heterochromatin or differences in the amounts of C heterochromatin between homologues could lead to faulty chromosome segregation. The study was performed on C banded metaphases obtained from peripheral lymphocyte cultures of 15 couples with recurrent early abortions and 15 control couples, all Caucasians. Analysis of variance was first performed on separate metaphases to measure intra-individual, inter-individual, and between population variation in a hierarchical model. Since the significant intra-individual differences covered the other parameters we performed, secondly, a one way analysis of variance on the mean values of metaphases per person in order to measure the inter-individual and between population variation. The results did not show a relationship between C heterochromatin lengths and occurrence of recurrent abortions.     

Success of Maternal and Child Health Pipeline Training Programs: Alumni Survey Results

Maternal and Child Health Journal - The Maternal and Child Health (MCH) Pipeline Training Program, promotes development of a diverse health workforce by training undergraduate students from...     

Association between electrical and mechanical remodeling after cardiac resynchronization therapy: systematic review and meta-analysis of observational studies

Heart Failure Reviews - Cardiac resynchronization therapy (CRT) may improve not only impaired left ventricular contractility but can also induce reverse remodeling of native conduction system....     

Is Long-Acting Reversible Contraceptive Use Increasing? Assessing Trends Among U.S. College Women, 2008–2013

Objective To assess LARC use trends among college women (18–24 years) and identify groups that have increased LARC use. Methods Data were extracted from the National College Health Assessment-II (NCHA-II) fall 2008–2013 surveys. Logistic regression statistics were used to assess LARC use. Results Although LARC use increased from 2008 to 2013 (aOR?=?2.62; 95% CI 2.23–3.07), less than half of the sample (44%) reported using contraception at last vaginal sex. Only 2.5% of college women in this study reported using a LARC method; of LARC users, 90% reported using an intrauterine device. Nearly all sociodemographic factors were significantly associated with increases in LARC use including: age, sexual orientation, and insurance status. Conclusions LARC use significantly increased among college women. However, less effective methods such as condoms and short-acting reversible contraceptives are used more frequently. Promoting LARC use for women who desire to effectively prevent pregnancy can reduce unintended pregnancy and improve health outcomes for women while in college. Future work should examine the importance of individual and lifestyle factors that influence college women’s decision to choose a LARC method and seek to eliminate barriers to college women choosing a contraceptive method they believe works best for them.     

The Impact of the Universal Infant Free School Meal Policy on Dietary Quality in English and Scottish Primary School Children: Evaluation of a Natural Experiment

The Universal Infant Free School Meal (UIFSM) policy was introduced in September 2014 in England and January 2015 in Scotland and offered all infant schoolchildren (ages 4–7 years) a free school lunch, regardless of income. Yet, impacts of UIFSM on dietary intakes or social inequalities are not known. A difference-in-differences study using the National Diet and Nutrition Survey assessed pooled pre-UIFSM (2010–2014) and post-UIFSM (2014–2017) dietary data. English or Scottish infant schoolchildren (4–7 years; n = 458) were the intervention group, with junior schoolchildren (8–11 years; n = 401) as controls. We found that implementation of UIFSM led to an increase in infant schoolchildren having a school meal. Impacts on key food groups such as fruit and vegetables or sweetened beverages were not seen. However, there was evidence that the UIFSM policy lowered consumption of foods associated with packed lunches, such as crisps, and some nutrients, such as total fat and sodium. Policy impacts differed by income group, with larger effect sizes in low-income children. In conclusion, evaluation of UIFSM demonstrated some improvements in dietary quality but the findings suggest school meal quality needs to be improved to fully realise the benefits of UIFSM.     

Vessel co‐option is common in human lung metastases and mediates resistance to anti‐angiogenic therapy in preclinical lung metastasis models

Anti‐angiogenic therapies have shown limited efficacy in the clinical management of metastatic disease, including lung metastases. Moreover, the mechanisms via which tumours resist anti‐angiogenic therapies are poorly understood. Importantly, rather than utilizing angiogenesis, some metastases may instead incorporate pre‐existing vessels from surrounding tissue (vessel co‐option). As anti‐angiogenic therapies were designed to target only new blood vessel growth, vessel co‐option has been proposed as a mechanism that could drive resistance to anti‐angiogenic therapy. However, vessel co‐option has not been extensively studied in lung metastases, and its potential to mediate resistance to anti‐angiogenic therapy in lung metastases is not established. Here, we examined the mechanism of tumour vascularization in 164 human lung metastasis specimens (composed of breast, colorectal and renal cancer lung metastasis cases). We identified four distinct histopathological growth patterns (HGPs) of lung metastasis (alveolar, interstitial, perivascular cuffing, and pushing), each of which vascularized via a different mechanism. In the alveolar HGP, cancer cells invaded the alveolar air spaces, facilitating the co‐option of alveolar capillaries. In the interstitial HGP, cancer cells invaded the alveolar walls to co‐opt alveolar capillaries. In the perivascular cuffing HGP, cancer cells grew by co‐opting larger vessels of the lung. Only in the pushing HGP did the tumours vascularize by angiogenesis. Importantly, vessel co‐option occurred with high frequency, being present in >80% of the cases examined. Moreover, we provide evidence that vessel co‐option mediates resistance to the anti‐angiogenic drug sunitinib in preclinical lung metastasis models. Assuming that our interpretation of the data is correct, we conclude that vessel co‐option in lung metastases occurs through at least three distinct mechanisms, that vessel co‐option occurs frequently in lung metastases, and that vessel co‐option could mediate resistance to anti‐angiogenic therapy in lung metastases. Novel therapies designed to target both angiogenesis and vessel co‐option are therefore warranted. © 2016 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.