Socioeconomic Disadvantage is Associated with Probable Sarcopenia in Community-Dwelling Older Adults: Findings from the English Longitudinal Study of Ageing.

BACKGROUND: Sarcopenia is characterized by the accelerated loss of muscle strength, mass, and function in aging. The disease is a major public health issue with emerging evidence of a disproportionate burden in areas of socioeconomic disadvantage. OBJECTIVES: To estimate the prevalence of probable sarcopenia overall, and according to Socioeconomic Position (SEP). To explore the association between markers of SEP and probable sarcopenia. DESIGN: Cross-sectional analysis of the English Longitudinal Study of Ageing data. SETTING: England, United Kingdom (UK). PARTICIPANTS: This study comprised 6,052 older adult participants from Wave 6 of the English Longitudinal Study of Ageing (ELSA) aged 60 years and older. MEASUREMENTS: Probable sarcopenia was identified by the EWGSOP2 guidelines as low hand grip strength (females <16kg and males <27kg) or poor chair rise test performance (completion of 5 chair rises >15 seconds). Socioeconomic position was defined by educational attainment and subjective social status (SSS). Weighted multivariable regression analysis was employed to identify determinants of probable sarcopenia. RESULTS: Over one-third of older adults met the criteria for probable sarcopenia (33.7%; weighted, 36.1%) in the study population of mean age 70.7 (SD 7.7) years. When examined by SEP, the prevalence of probable sarcopenia was over 2-fold higher in adults in the most vs the least disadvantaged SEP groups (47.0% vs 20.6%, respectively, p<0.001). Multivariable regression analysis identified disadvantaged SEP, as measured by educational attainment and SSS, as independent predictors of probable sarcopenia, along with older age, physical inactivity, underweight BMI, chronic conditions, osteoarthritis, and minority group ethnicity. CONCLUSIONS: Disadvantaged SEP was associated with an increased likelihood of probable sarcopenia when controlled for other known risk factors. The findings suggest a need and opportunity for sarcopenia prevention and treatment strategies to address socioeconomic disadvantage in policies and practice.

Biogeography of Southern Ocean prokaryotes: a comparison of the Indian and Pacific sectors.

We investigated the Southern Ocean (SO) prokaryote community structure via zero-radius operational taxonomic unit (zOTU) libraries generated from 16S rRNA gene sequencing of 223 full water column profiles. Samples reveal the prokaryote diversity trend between discrete water masses across multiple depths and latitudes in Indian (71-99°E, summer) and Pacific (170-174°W, autumn-winter) sectors of the SO. At higher taxonomic levels (phylum-family) we observed water masses to harbour distinct communities across both sectors, but observed sectorial variations at lower taxonomic levels (genus-zOTU) and relative abundance shifts for key taxa such as Flavobacteria, SAR324/Marinimicrobia, Nitrosopumilus and Nitrosopelagicus at both epi- and bathy-abyssopelagic water masses. Common surface bacteria were abundant in several deep-water masses and vice-versa suggesting connectivity between surface and deep-water microbial assemblages. Bacteria from same-sector Antarctic Bottom Water samples showed patchy, high beta-diversity which did not correlate well with measured environmental parameters or geographical distance. Unconventional depth distribution patterns were observed for key archaeal groups: Crenarchaeota was found across all depths in the water column and persistent high relative abundances of common epipelagic archaeon Nitrosopelagicus was observed in deep-water masses. Our findings reveal substantial regional variability of SO prokaryote assemblages that we argue should be considered in wide-scale SO ecosystem microbial modelling.

Metabolic pathways inferred from a bacterial marker gene illuminate ecological changes across South Pacific frontal boundaries.

Global oceanographic monitoring initiatives originally measured abiotic essential ocean variables but are currently incorporating biological and metagenomic sampling programs. There is, however, a large knowledge gap on how to infer bacterial functions, the information sought by biogeochemists, ecologists, and modelers, from the bacterial taxonomic information (produced by bacterial marker gene surveys). Here, we provide a correlative understanding of how a bacterial marker gene (16S rRNA) can be used to infer latitudinal trends for metabolic pathways in global monitoring campaigns. From a transect spanning 7000 km in the South Pacific Ocean we infer ten metabolic pathways from 16S rRNA gene sequences and 11 corresponding metagenome samples, which relate to metabolic processes of primary productivity, temperature-regulated thermodynamic effects, coping strategies for nutrient limitation, energy metabolism, and organic matter degradation. This study demonstrates that low-cost, high-throughput bacterial marker gene data, can be used to infer shifts in the metabolic strategies at the community scale.

Oceanographic Fronts Shape Phaeocystis Assemblages: A High-Resolution 18S rRNA Gene Survey From the Ice-Edge to the Equator of the South Pacific.

The cosmopolitan haptophyte Phaeocystis is recognized as a key contributor to marine biogeochemical cycling and important primary producer within polar marine environments. Yet, little is known about its solitary, non-colonial cell stages or its distribution during the colder, low-productivity seasons. We examined the biogeography of Phaeocystis along a high-resolution (0.5-degree latitudinal interval) transect from the Antarctic ice-edge to the equator of the South Pacific, in the austral autumn-winter. Using high-throughput 18S rRNA gene sequences with single nucleotide variable (zero-radius) operational taxonomic units (zOTUs) allowed us to explore the possibility of strain-level variation. From water samples within the upper water column, we show the presence of an abundant Phaeocystis assemblage that persisted during the colder months, contributing up to 9% of the microbial eukaryote community at high latitudes. The biogeography of Phaeocystis was strongly shaped by oceanographic boundaries, most prominently the polar and subantarctic fronts. Marked changes in dominant Phaeocystis antarctica zOTUs between different frontal zones support the concept that ecotypes may exist within the Phaeocystis assemblage. Our findings also show that the Phaeocystis assemblage did not abide by the classical latitudinal diversity gradient of increasing richness from the poles to the tropics; richness peaked at 30°S and declined to a minimum at 5°S. Another surprise was that P. globosa and P. cordata, previously thought to be restricted to the northern hemisphere, were detected at moderate abundances within the Southern Ocean. Our results emphasize the importance of oceanographic processes in shaping the biogeography of Phaeocystis and highlights the importance of genomics-based exploration of Phaeocystis, which have found the assemblage to be more complex than previously understood. The high winter relative abundance of the Phaeocystis assemblage suggests it could be involved in more complex ecological interactions during the less productive seasons, which should be considered in future studies to better understand the ecological role and strategies of this keystone species.

Congenital Glaucoma: a Novel Ocular Manifestation of Hajdu-Cheney Syndrome.

Hajdu-Cheney Syndrome (HSC) is a rare multisystem disease in which the phenotype involves acro-osteolysis, severe osteoporosis, short stature, wormian bones, facial dysmorphism, central neurological abnormalities, cardiovascular defects, and polycystic kidneys. We describe an infant with severe manifestations of HCS in whom congenital glaucoma was a significant early feature, which has not been reported to date. HCS cases reported to date have involved truncating mutations in exon 34 of NOTCH2 upstream the PEST domain that lead to the development of a truncated and stable NOTCH2 protein which upregluates notch signaling. We describe a hitherto undescribed missense mutation that is predicted to be pathogenic, with functional characterization remaining to be performed. Serpentine fibula-polycystic kidney syndrome (SFPKS) is allelic to HCS and commonly associated with missense NOTCH2 mutations. Our patient provides new ophthalmological manifestations of HCS and provides insight into the potential role of notch signaling in the anterior chamber development.

Oceanographic boundaries constrain microbial diversity gradients in the South Pacific Ocean.

Marine microbes along with microeukaryotes are key regulators of oceanic biogeochemical pathways. Here we present a high-resolution (every 0.5° of latitude) dataset describing microbial pro- and eukaryotic richness in the surface and just below the thermocline along a 7,000-km transect from 66°S at the Antarctic ice edge to the equator in the South Pacific Ocean. The transect, conducted in austral winter, covered key oceanographic features including crossing of the polar front (PF), the subtropical front (STF), and the equatorial upwelling region. Our data indicate that temperature does not determine patterns of marine microbial richness, complementing the global model data from Ladau et al. [Ladau J, et al. (2013) ISME J 7:1669-1677]. Rather, NH4+, nanophytoplankton, and primary productivity were the main drivers for archaeal and bacterial richness. Eukaryote richness was highest in the least-productive ocean region, the tropical oligotrophic province. We also observed a unique diversity pattern in the South Pacific Ocean: a regional increase in archaeal and bacterial diversity between 10°S and the equator. Rapoport's rule describes the tendency for the latitudinal ranges of species to increase with latitude. Our data showed that the mean latitudinal ranges of archaea and bacteria decreased with latitude. We show that permanent oceanographic features, such as the STF and the equatorial upwelling, can have a significant influence on both alpha-diversity and beta-diversity of pro- and eukaryotes.

Ocular Manifestations of a Novel Proximal 19p13.3 Microdeletion.

Microdeletions at 19p13.3 are rarely reported in the medical literature with significant phenotypic variability. Among the reported cases, common clinical manifestations have included developmental delay, facial dysmorphism, and hypotonia. Herein we described a child with a de novo 19p13.3 microdeletion, proximal to the reported cases of 19p13.3 microdeletion/duplication, with ocular manifestations of bilateral ocular colobomata complicated with microphthalmos and cataract, associated with short stature. This case highlights the phenotypic heterogeneity of deletions in the 19p13.3 region.

Pre-pregnancy counseling for women with heart disease: A prospective study.

BACKGROUND: Women with cardiac disease and their infants are at a greater risk of mortality and morbidity during pregnancy. Expert groups recommend preconception counseling (PCC) for all women with cardiac disease so they are made aware of these risks. We have run a specialist maternal cardiac clinic since 1996. The aim of this study was to evaluate the experience of women who have received PCC within an established multidisciplinary tertiary clinic and to establish their views regarding the counseling they received. METHODS: Single centre prospective study using a patient questionnaire was given to women attending a specialist cardiac preconception counseling clinic from November 2015 to August 2016, with analysis of descriptive data and free text comments from the questionnaire responders. RESULTS: 40/65 returned patient questionnaires. Prior to the consultation fewer than half felt well informed regarding how their heart disease could impact upon pregnancy but a similar proportion felt nonetheless that they would be able to have a healthy pregnancy. Women reported two main areas of concerns, their own health (whether they would survive a pregnancy) and the health of their child. 15% of women reported that these concerns had prevented them from pursuing a pregnancy. Women reported high satisfaction rates with the clinic. CONCLUSIONS: There is an increasing demand for PCC services for women with cardiac disease; our study is the first attempt to determine both the acceptability and the impact of PCC from the patient perspective. Patients reported a high level of satisfaction with the service provided.

Common long-term complications of adult congenital heart disease: avoid falling in a H.E.A.P.

Advances in cardiology and cardiac surgery have transformed the outlook for patients with congenital heart disease (CHD) so that currently 85% of neonates with CHD survive into adult life. Although early surgery has transformed the outcome of these patients, it has not been curative. Heart failure, endocarditis, arrhythmias and pulmonary hypertension are the most common long term complications of adults with CHD. Adults with CHD benefit from tertiary expert care and early recognition of long-term complications and timely management are essential. However, it is as important that primary care physicians and general adult cardiologists are able to recognise the signs and symptoms of such complications, raise the alarm, referring patients early to specialist adult congenital heart disease (ACHD) care, and provide initial care. In this paper, we provide an overview of the most commonly encountered long-term complications in ACHD and describe current state of the art management as provided in tertiary specialist centres.

Maternal cardiac and obstetric performance in consecutive pregnancies in women with heart disease.

OBJECTIVE: Second pregnancies are usually less complicated than first pregnancies, and have a better outcome in terms of fetal growth. We studied a group of women with heart disease to assess whether their second pregnancy was less complicated and resulted in a larger baby. DESIGN: Retrospective case control study. SETTING: Tertiary referral academic obstetric unit. POPULATION: First and second pregnancies in 77 women with congenital and acquired heart disease and in 154 control women were identified. METHODS: Data were collected from medical and obstetric records. MAIN OUTCOME MEASURES: Cardiac complications, obstetric complications, intra-partum events, birthweight and perinatal complications. RESULTS: The rate of obstetric complication was greater in first pregnancies in both the heart disease and the control groups (38% versus 26%, cf. 20% versus 17%). In the heart disease group, the rate of cardiac complications was similar in first and second pregnancies (9% versus 6%). Overall, significantly more perinatal complications were seen in the heart disease group, with no significant difference between first and second pregnancies (36% versus 27%, cf. 14% versus 12%). Median birthweight was significantly higher in second pregnancies in the control group (3308 versus 3519 g P < 0.001), but not significantly different between pregnancies in the heart disease group (3014 versus 3133 g, P = 0.19). CONCLUSIONS: This case control study demonstrates that women with mild to moderate heart disease have similar pregnancy outcomes in consecutive pregnancies. However, while the median birthweight was higher in the control second pregnancies, it was not increased in the women with heart disease. TWEETABLE ABSTRACT: A study of women with heart disease to assess whether their second pregnancy was less complicated.

Prevalence and prognostic implication of restenosis or dilatation at the aortic coarctation repair site assessed by cardiovascular MRI in adult patients late after coarctation repair.

BACKGROUND: Cardiovascular magnetic resonance (CMR) is ideal for assessing patients with repaired aortic coarctation (CoA). Little is known on the relation between long-term complications of CoA repair as assessed by CMR and clinical outcome. We examined the prevalence of restenosis and dilatation at the repair site and the long-term outcome in patients with repaired CoA. METHODS AND RESULTS: CMR imaging and clinical data for adult CoA patients (247 patients aged 33.0 ± 12.8 years, 60% male), were analyzed. The diameter of the aorta at the repair site was measured on CMR and its ratio to the aortic diameter at the diaphragm (repair site-diaphragm ratio, RDR) was calculated. Restenosis (RDR≤70%) was present in 31% of patients (and significant in 9% [RDR<50%]), and dilatation (RDR>150%) in 13.0%. A discrete aneurysm at the repair site was observed in 9%. Restenosis was more likely after resection and end-end anastomosis, whereas dilatation after patch repair. Systemic hypertension was present in 69% of patients. Of the hypertensive patients, blood pressure (133 ± 20/73 ± 10 mm Hg) was well controlled in 93% with antihypertensive therapy. Mortality rate over a median length of 5.9 years was low (0.69% per year, 95% CI: 0.33-1.26), but significantly higher than age-matched healthy controls (standardised mortality ratio 2.86, CI 1.43-5.72, p<0.001). CONCLUSION: Restenosis or dilatation at the CoA repair site as assessed by CMR is not uncommon. Medium term survival remains good, however, albeit lower than in the general population. Life-long follow-up and optimal blood pressure control are likely to secure a good longer term outlook in these patients.

Marfan syndrome and pregnancy: maternal and neonatal outcomes.

OBJECTIVE: To report outcomes in a recent series of pregnancies in women with Marfan syndrome (MFS). DESIGN: Retrospective case note review. SETTING: Tertiary referral unit (Chelsea and Westminster and Royal Brompton Hospitals). SAMPLE: Twenty-nine pregnancies in 21 women with MFS between 1995 and 2010. METHODS: Multidisciplinary review of case records. MAIN OUTCOME MEASURES: Maternal and neonatal mortality and morbidity of patients with MFS and healthy controls. RESULTS: There were no maternal deaths. Significant cardiac complications occurred in five pregnancies (17%): one woman experienced a type-A aortic dissection; two women required cardiac surgery within 6 months of delivery; and a further two women developed impaired left ventricular function during the pregnancy. Women with MFS were also more likely to have obstetric complications (OR 3.29, 95% CI 1.30-8.34), the most frequent of which was postpartum haemorrhage (OR 8.46, 95% CI 2.52-28.38). There were no perinatal deaths, although babies born to mothers with MFS were delivered significantly earlier than those born to the control group (median 39 versus 40 weeks of gestation, Mann-Whitney U-test, P = 0.04). These babies were also significantly more likely to be small for gestational age (24% in the MFS group versus 6% in the controls; OR 4.95, 95% CI 1.58-15.55). CONCLUSIONS: Pregnancy in women with MFS continues to be associated with significant rates of maternal, fetal, and neonatal complications. Effective pre-pregnancy counselling and meticulous surveillance during pregnancy, delivery, and the puerperium by an experienced multidisciplinary team are warranted for women with MFS.

How Do Community Physical and Occupational Therapists Classify Frailty? A pilot Study.

BACKGROUND: Frailty is a complex geriatric syndrome that is often difficult to diagnose, especially by healthcare professionals working in the community. Objectives, Measurements: This study examined how physical and occupational therapists classified community-dwelling clients using categories of 'nonfrail', 'prefrail' or 'frail' as compared to measurements of established frailty criteria from the Cardiovascular Health Study frailty index (CHSfi). RESULTS: Results indicate that community therapists underestimate frailty in comparison to the CHSfi. Therapists' classification of frailty suggested their perceptions of frailty may not only relate to client's functional capacity, but the context in which the client receives care. CONCLUSION: A multi-dimensional approach is required to capture all aspects of frailty across the healthcare continuum that accounts for how the client thrives within their personal environment.

Pulmonary hypertension and pregnancy--a review of 12 pregnancies in nine women.

OBJECTIVE: To report outcomes in a recent series of pregnancies in women with pulmonary hypertension (PH). DESIGN: Retrospective case note review. SETTING: Tertiary referral unit (Chelsea and Westminster and Royal Brompton Hospitals). SAMPLE: Twelve pregnancies in nine women with PH between 1995 and 2010. METHODS: Multidisciplinary review of case records. MAIN OUTCOME MEASURES: Maternal and neonatal mortality and morbidity. RESULTS: There were two maternal deaths (1995 and 1998), one related to pre-eclampsia and one to arrhythmia. Maternal morbidity included postpartum haemorrhage (five cases), and one post-caesarean evacuation of a wound haematoma. There were no perinatal deaths, nine live births and three first-trimester miscarriages. Mean birthweight was 2197 g, mean gestational age was 34 weeks (range 26-39), and mean birthweight centile was 36 (range 5-60). Five babies required admission to the neonatal intensive care unit, but were all eventually discharged home. All women were delivered by caesarean section (seven elective and two emergency deliveries), under general anaesthetic except for one emergency and one elective caesarean performed under regional block. CONCLUSIONS: Maternal and fetal outcomes for women with PH may be improving. However, the risk of maternal mortality remains significant, so that early and effective counselling about contraceptive options and pregnancy risks should continue to play a major role in the management of such women when they reach reproductive maturity.

Transcatheter device closure of atrial septal defects in the elderly: technical considerations and short-term outcomes.

BACKGROUND: Device closure of an atrial septal defect (ASD) results in symptom-reduction, right heart remodelling and lower pulmonary artery pressures. However it is unclear if there is a chronological limit to these benefits and whether device closure is safe in elderly subjects. The aim of this study was, therefore, to assess the safety and efficacy of device closure in patients >60 years. METHODS: Retrospective study of Amplatzer Septal Occluder device closures from a single institution (May 1999-August 2002). RESULTS: Fifty subjects aged >60 years (range 60-85 years) had ASD device closure (27% of the total cohort). Defect size and shunt size were similar for both younger and older groups (2.2:1 in both groups, p=0.9) as were procedural duration, fluoroscopy time and device size deployed. Baseline right ventricular (RV) systolic pressure ((younger vs. older) 39 vs. 49 mmHg, p<0.001) and right ventricular size (45 vs. 51 mm, p<0.001) were greater in the older group. Following closure RV systolic pressure (49 vs. 45 mmHg, p<0.01) and RV size (51 vs. 44 mm, p=0.01) decreased in the older group. CONCLUSION: Device closure of an ASD can be performed safely in older patients. The right heart shows signs of remodelling even in elderly subjects.

Glucocorticoids contribute to the heritability of leptin in Scottish adult female twins.

OBJECTIVE: The precise interactions between glucocorticoids and leptin are complex and poorly understood. The aim of the study was to investigate whether the glucocorticoid/leptin interaction is influenced by shared environmental or genetic factors. DESIGN: We investigated the heritability of body mass index (BMI), circulating leptin and urinary glucocorticoid metabolites [tetrahydrocortisol (THF), alloTHF and tetrahydrocortisone (THE)] in 54 monozygotic (MZ) and 39 dizygotic (DZ) female twins. Analysis was performed using a structural equation modelling package Mx, developed by Neale. RESULTS: Leptin and BMI showed substantial heritability (68.3% and 71.3%, respectively). Bivariate analysis indicated that the genetic determinants of BMI and leptin are partly shared. Total cortisol metabolites (THF + alloTHF + THE), the (THE + alloTHF)/THE ratio [a marker of 11beta-hydroxysteroid dehydrogenase (11HSD) activity] and the alloTHF/THF ratio (marker for 5alpha-reductase activity) followed an environmental pattern. The heritability of leptin was significantly lowered to 63.8% (P = 0.012) when values were corrected for the influence of total cortisol metabolites but unaffected by markers of 11HSD and 5alpha-reductase activity. CONCLUSIONS: We confirm that the genetic influence on both BMI and the circulating leptin concentration is substantial and show that these genetic determinants are highly correlated. These genetic factors, which are more likely to be dominant than additive, can be modestly but significantly modified by urinary total cortisol metabolites implying an adrenal influence.

Altered cellular distribution of iron in rat cerebral cortex during the oestrous cycle.

Iron levels in blood, liver and the substantia nigra fluctuate during the oestrous cycle but it is not known whether the cellular distribution also changes. This study shows that during dioestrus, when serum levels of oestradiol are low, the amount of histochemically detectable iron in the cerebral cortex is significantly lower than in proestrus when oestradiol levels are highest. During dioestrus iron is concentrated within neurones, and the transition to proestrus is associated with a shift in iron localisation from neurones to vascular endothelial cells and oligodendrocytes. These data raise the possibility that changes in the concentration of serum oestrogen (or other reproductive hormones) during the oestrous cycle can influence the intercellular transport of iron in the brain.

The genetic determination of left ventricular mass in healthy adults.

AIMS: The extent to which left ventricular (LV) mass, an independent cardiovascular risk factor, is determined by genetic factors is unclear. The aim of this study was to assess the heritability of LV mass and its association with three potential candidate genes. METHODS: A population-based adult twin study model was utilized. Echocardiographic assessment of LV mass was performed in 110 twin pairs (mean age 55.9+/-10.9 years). An estimate of genetic determination, heritability, was calculated for the main echocardiographic parameters. The cohort were genotyped for the G-protein beta-3, aldosterone synthase, and beta-1 adrenoceptor genes. RESULTS: The intra-class correlation coefficients for LV mass were 0.69 for monozygotic (r-MZ) twins and 0.32 for dizygotic (r-DZ) twins, P=0.008 (heritability estimate of 0.69). This pattern persisted following correction for known confounding factors. Within-pair differences in the monozygotic, discordant and concordant dizygotic twins showed no differences for the three genes with respect to left ventricular wall thickness or mass. There was a non-significant trend towards a relationship between LV mass and the beta-1 adrenoceptor genotype. CONCLUSION: Within a normal population left ventricular mass has a significant genetic determination. Further investigation of potential candidate genes is required.