Obstetric anesthesia for the obese and morbidly obese patient: an ounce of prevention is worth more than a pound of treatment

Background: The incidence of obesity has been dramatically increasing across the globe. Anesthesiologists, are increasingly faced with the care for these patients. Obesity in the pregnant woman is associated with a broad spectrum of problems, including dramatically increased risk for cesarean delivery, diabetes, hypertension and pre-eclampsia. A thorough understanding of the physiology, associated conditions and morbidity, available options for anesthesia and possible complications is therefore important for today's anesthesiologist. Methods: This is a personal review in which different aspects of obesity in the pregnant woman, that are relevant to the anesthesiologist, are discussed. An overview of maternal and fetal morbidity and physiologic changes associated with pregnancy and obesity is provided and different options for labor analgesia, the anesthetic management for cesarean delivery and potential post-partum complications are discussed in detail. Results and Conclusion: The anesthetic management of the morbidly obese parturient is associated with special hazards. The risk for difficult or failed intubation is exceedingly high. The early placement of an epidural or intrathecal catheter may overcome the need for general anesthesia, however, the high initial failure rate necessitates critical block assessment and catheter replacement when indicated

SLC25A12 Missense Variant in Nova Scotia Duck Tolling Retrievers Affected by Cerebellar Degeneration—Myositis Complex (CDMC)

We investigated two litters of distantly related Nova Scotia Duck Tolling Retrievers (NSDTR), of which four puppies were affected by cerebellar signs with or without neuromuscular weakness. The phenotype was termed cerebellar degeneration—myositis complex (CDMC). We suspected a heritable condition and initiated a genetic analysis. The genome of one affected dog was sequenced and compared to 565 control genomes. This search yielded a private protein-changing SLC25A12 variant in the affected dog, XM_038584842.1:c.1337C>T, predicted to result in the amino acid change XP_038440770.1:(p.Pro446Leu). The genotypes at the variant co-segregated with the phenotype as expected for a monogenic autosomal recessive mode of inheritance in both litters. Genotyping of 533 additional NSDTR revealed variant allele frequencies of 3.6% and 1.3% in a European and a North American cohort, respectively. The available clinical and biochemical data, together with current knowledge about SLC25A12 variants and their functional impact in humans, mice, and dogs, suggest the p.Pro446Leu variant is a candidate causative defect for the observed phenotype in the affected dogs

Disasters and History

Disasters and History offers the first comprehensive historical overview of hazards and disasters. Drawing on a range of case studies, including the Black Death, the Lisbon earthquake of 1755 and the Fukushima disaster, the authors examine how societies dealt with shocks and hazards and their potentially disastrous outcomes. They reveal the ways in which the consequences and outcomes of these disasters varied widely not only between societies but also within the same societies according to social groups, ethnicity and gender. They also demonstrate how studying past disasters, including earthquakes, droughts, floods and epidemics, can provide a lens through which to understand the social, economic and political functioning of past societies and reveal features of a society which may otherwise remain hidden from view

A large meteoritic event over Antarctica ca. 430 ka ago inferred from chondritic spherules from the Sør Rondane Mountains

Large airbursts, the most frequent hazardous impact events, are estimated to occur orders of magnitude more frequently than crater-forming impacts. However, finding traces of these events is impeded by the difficulty of identifying them in the recent geological record. Here, we describe condensation spherules found on top of Walnumfjellet in the Sør Rondane Mountains, Antarctica. Affinities with similar spherules found in EPICA Dome C and Dome Fuji ice cores suggest that these particles were produced during a single-asteroid impact ca. 430 thousand years (ka) ago. The lack of a confirmed crater on the Antarctic ice sheet and geochemical and 18O-poor oxygen isotope signatures allow us to hypothesize that the impact particles result from a touchdown event, in which a projectile vapor jet interacts with the Antarctic ice sheet. Numerical models support a touchdown scenario. This study has implications for the identification and inventory of large cosmic events on Earth

Mutations in the Spliceosome Component CWC27 Cause Retinal Degeneration with or without Additional Developmental Anomalies

Pre-mRNA splicing factors play a fundamental role in regulating transcript diversity both temporally and spatially. Genetic defects in several spliceosome components have been linked to a set of non-overlapping spliceosomopathy phenotypes in humans, among which skeletal developmental defects and non-syndromic retinitis pigmentosa (RP) are frequent findings. Here we report that defects in spliceosome-associated protein CWC27 are associated with a spectrum of disease phenotypes ranging from isolated RP to severe syndromic forms. By whole-exome sequencing, recessive protein-truncating mutations in CWC27 were found in seven unrelated families that show a range of clinical phenotypes, including retinal degeneration, brachydactyly, craniofacial abnormalities, short stature, and neurological defects. Remarkably, variable expressivity of the human phenotype can be recapitulated in Cwc27 mutant mouse models, with significant embryonic lethality and severe phenotypes in the complete knockout mice while mice with a partial loss-of-function allele mimic the isolated retinal degeneration phenotype. Our study describes a retinal dystrophy-related phenotype spectrum as well as its genetic etiology and highlights the complexity of the spliceosomal gene network

Age- and Tumor Subtype-Specific Breast Cancer Risk Estimates for CHEK2*1100delC Carriers.

PURPOSE: CHEK2*1100delC is a well-established breast cancer risk variant that is most prevalent in European populations; however, there are limited data on risk of breast cancer by age and tumor subtype, which limits its usefulness in breast cancer risk prediction. We aimed to generate tumor subtype- and age-specific risk estimates by using data from the Breast Cancer Association Consortium, including 44,777 patients with breast cancer and 42,997 controls from 33 studies genotyped for CHEK2*1100delC. PATIENTS AND METHODS: CHEK2*1100delC genotyping was mostly done by a custom Taqman assay. Breast cancer odds ratios (ORs) for CHEK2*1100delC carriers versus noncarriers were estimated by using logistic regression and adjusted for study (categorical) and age. Main analyses included patients with invasive breast cancer from population- and hospital-based studies. RESULTS: Proportions of heterozygous CHEK2*1100delC carriers in controls, in patients with breast cancer from population- and hospital-based studies, and in patients with breast cancer from familial- and clinical genetics center-based studies were 0.5%, 1.3%, and 3.0%, respectively. The estimated OR for invasive breast cancer was 2.26 (95%CI, 1.90 to 2.69; P = 2.3 × 10(-20)). The OR was higher for estrogen receptor (ER)-positive disease (2.55 [95%CI, 2.10 to 3.10; P = 4.9 × 10(-21)]) than it was for ER-negative disease (1.32 [95%CI, 0.93 to 1.88; P = .12]; P interaction = 9.9 × 10(-4)). The OR significantly declined with attained age for breast cancer overall (P = .001) and for ER-positive tumors (P = .001). Estimated cumulative risks for development of ER-positive and ER-negative tumors by age 80 in CHEK2*1100delC carriers were 20% and 3%, respectively, compared with 9% and 2%, respectively, in the general population of the United Kingdom. CONCLUSION: These CHEK2*1100delC breast cancer risk estimates provide a basis for incorporating CHEK2*1100delC into breast cancer risk prediction models and into guidelines for intensified screening and follow-up.NIH