The metabolic syndrome, cardiopulmonary fitness, and subcutaneous trunk fat as independent determinants of arterial stiffness: the Amsterdam Growth and Health Longitudinal Study

BACKGROUND: The mechanisms that link the metabolic syndrome to increased cardiovascular risk are incompletely understood, especially in young people. We therefore examined whether the metabolic syndrome was associated with arterial stiffness and whether any such associations were independent of cardiopulmonary fitness and subcutaneous trunk fat. METHODS: Cross-sectional analyses of data on 364 men and women aged 36 years from the Amsterdam Growth and Health Longitudinal Study (ninth follow-up measurement, year 2000). The prevalence of the metabolic syndrome was defined by a slightly modified National Cholesterol Education Program (NCEP) definition. Arterial stiffness was ultrasonically estimated by distensibility and compliance of the carotid, femoral, and brachial arteries and by the carotid elastic modulus. RESULTS: The prevalence of the metabolic syndrome in this young adult population was 18.3% in men and 3.2% in women. Individuals with the syndrome compared with individuals without risk factors had 11.2% and 17.0% less distensibility and 9.0% and 18.2% less compliance of the carotid and femoral arteries, respectively, and 15.9% higher carotid elastic modulus. After adjustment for cardiopulmonary fitness and subcutaneous trunk fat, the metabolic syndrome remained significantly associated with stiffness of the carotid but not the femoral artery. In addition, poor cardiopulmonary fitness and high subcutaneous trunk fat were associated with arterial stiffness, and this was independent of the metabolic syndrome. CONCLUSIONS: A modified NCEP definition of the metabolic syndrome identified young individuals with increased arterial stiffness. The mechanisms that link the metabolic syndrome, poor cardiopulmonary fitness, and high subcutaneous trunk fat to greater arterial stiffness overlap but are partly independent of each other.     

The high mobility group protein Abf2p influences the level of yeast mitochondrial DNA recombination intermediates in vivo

Abf2p is a high mobility group (HMG) protein found in yeast mitochondria that is required for the maintenance of wild-type (ρ⁺) mtDNA in cells grown on fermentable carbon sources, and for efficient recombination of mtDNA markers in crosses. Here, we show by two-dimensional gel electrophoresis that Abf2p promotes or stabilizes Holliday recombination junction intermediates in ρ⁺ mtDNA in vivo but does not influence the high levels of recombination intermediates readily detected in the mtDNA of petite mutants (ρ⁻). mtDNA recombination junctions are not observed in ρ⁺ mtDNA of wild-type cells but are elevated to detectable levels in cells with a null allele of the MGT1 gene (Δmgt1), which codes for a mitochondrial cruciform-cutting endonuclease. The level of recombination intermediates in ρ⁺ mtDNA of Δmgt1 cells is decreased about 10-fold if those cells contain a null allele of the ABF2 gene. Overproduction of Abf2p by ≥ 10-fold in wild-type ρ⁺ cells, which leads to mtDNA instability, results in a dramatic increase in mtDNA recombination intermediates. Specific mutations in the two Abf2p HMG boxes required for DNA binding diminishes these responses. We conclude that Abf2p functions in the recombination of ρ⁺ mtDNA.     

Intracoronary stent implantation and left ventricular function in primary PTCA in acute myocardial infarct

In acute myocardial infarction intracoronary stenting is superior to PTCA regarding interventional success and occurrence of cardiac events. It is, however, uncertain whether myocardial function also improves with stenting. We, therefore, assessed angiographic parameters of myocardial function in patients with acute myocardial infarction who were treated with primary PTCA and received additional stenting in case of an unsatisfactory angiographic result (provisional stenting). Nineteen patients with acute myocardial infarction, in whom a "stent-like" angiographic result was achieved by PTCA alone, were compared with an equal number of patients receiving provisional stenting. The groups were exactly matched with respect to severity of coronary heart disease, segment of coronary occlusion, Killip class, and TIMI flow after intervention. We only included patients without inhospital cardiac events, in whom repeat angiography after ten days revealed a patent target vessel. There were no differences between both groups regarding age, gender, enzymatic infarction size, duration of ischemia (< or = 12 h), and cardiac risk factors. Myocardial function was assessed by ventriculography and was analyzed quantitatively by the center-line method. The group treated by intracoronary stenting showed a significantly improved ejection fraction (60.3 +/- 2.1% vs. 52.6 +/- 2.9%). All parameters of regional wall motion also indicated significantly less functional disturbance in the stented group compared to PTCA alone (circumferential extend of hypokinesia: 7.4 +/- 2.4% vs. 16.1 +/- 3.4% chords, maximum hypokinesia in the central infarct region: -0.98 +/- 0.20 vs. -1.52 +/- 0.15 SD, severity of regional hypokinesia: 7.3 +/- 2.6 vs. 21.9 +/- 5.4 area). In summary, these results in patients undergoing primary PTCA in acute myocardial infarction indicate that intracoronary stenting is superior to PTCA alone with respect to myocardial recovery, even if an angiographically "stent-like" result can be achieved. Probably, stenting results in a more efficient reperfusion.     

Subtyping Cryptosporidium ubiquitum,a Zoonotic Pathogen Emerging in Humans

Cryptosporidium ubiquitum is an emerging zoonotic pathogen. In the past, it was not possible to identify an association between cases of human and animal infection. We conducted a genomic survey of the species, developed a subtyping tool targeting the 60-kDa glycoprotein (gp60) gene, and identified 6 subtype families (XIIa–XIIf) of C. ubiquitum. Host adaptation was apparent at the gp60 locus; subtype XIIa was found in ruminants worldwide, subtype families XIIb–XIId were found in rodents in the United States, and XIIe and XIIf were found in rodents in the Slovak Republic. Humans in the United States were infected with isolates of subtypes XIIb–XIId, whereas those in other areas were infected primarily with subtype XIIa isolates. In addition, subtype families XIIb and XIId were detected in drinking source water in the United States. Contact with C. ubiquitum–infected sheep and drinking water contaminated by infected wildlife could be sources of human infections.Key words: Cryptosporidiosis, Cryptosporidium, zoonoses, epidemiology, molecular typing,whole genome sequencing, genomics, ruminants, rodents, horse, raccoon, sifaka, parasites, humansCryptosporidium infection is a leading cause of diarrhea in humans (1). Five Cryptosporidium species—C. hominis, C. parvum, C. meleagridis, C. felis, and C. canis—are responsible for most cases of cryptosporidiosis in humans. Among them, C. hominis and C. parvum are the most common etiologic agents, and the latter is responsible for most zoonotic infections (2). In recent years, C. ubiquitum, previously known as the cervine genotype, has been emerging as another major zoonotic species that infects persons. It has been found in humans worldwide, primarily in industrialized nations (3–11). In the United Kingdom, more human cases of cryptosporidiosis have been attributed to C. ubiquitum than to C. canis (9).C. ubiquitum is of public health concern because of its wide geographic distribution and broad host range. Of all Cryptosporidium spp. identified by molecular diagnostic tools, it infects the greatest variety of host species (12). C. ubiquitum has been commonly detected in domestic and wild ruminants (sheep, goats, mouflon sheep, blesboks, nyalas, white-tailed deer, Père David’s deer, sika deer, ibexes, buffalos, and yaks), rodents (squirrels, chipmunks, woodchucks, beavers, porcupines, deer mice, house mice, and gerbils), carnivores (raccoons), and primates (lemurs and humans) (12–16). It has also been found in drinking source water, storm water runoff, stream sediment, and wastewater in various geographic locations (17–22).Thus far, showing an association between human and animal cases of C. ubiquitum infection has not been possible because of the lack of suitable genetic markers for subtyping. For C. parvum, C. hominis, and some genetically related species, the most commonly used marker for subtyping is the 60-kDa glycoprotein gene (gp60, also called gp40/15). Sequence analysis of the gp60 gene has been used in studies of the genetic diversity, host adaptation, infection sources, and transmission dynamics of these Cryptosporidium spp. (2). However, it has been suggested that a single locus, such as gp60, is not a reliable marker of C. parvum and C. hominis population structure because genetic recombination may occur (23).Because C. ubiquitum is genetically distant from C. hominis and C. parvum, its homologue of the gp60 gene has thus far not been identified (24). In this study, we identified the gp60 gene of C. ubiquitum by whole-genome sequencing and used it to develop a subtyping technique to characterize specimens from humans, various animals, and drinking source water.     

Nutritional Factors Associated with Antenatal Depressive Symptoms in the Early Stage of Pregnancy Among Urban South Indian Women

Many women of reproductive age from developing countries have poor nutritional status, and the prevalence of depression during pregnancy is high. The objective of the present study was to assess the prevalence of antenatal depressive symptoms in early pregnancy, and to identify the demographic and nutritional factors associated with these symptoms in a sample of urban South Indian pregnant women. This cross-sectional study was the baseline assessment of a prospective randomized controlled trial of vitamin B₁₂ supplementation in urban pregnant south Indian women between the ages of 18 and 40 years (www.clinicaltrials.gov: NCT00641862). 365 women in their first trimester of pregnancy were screened for depressive symptoms at an urban clinic in Karnataka, South India, using the Kessler Psychological Distress Scale (K-10). Nutritional, clinical and biochemical factors were also assessed. Mean (SD) age of the cohort was 22.6 (3.7) years and mean (SD) BMI was 20.4 (3.3) kg/m². 121 (33 %) of the women in the 1st trimester had symptoms consistent with depression (K-10 score >6). In multivariate log binomial regression analysis, presence of antenatal depressive symptoms in the first trimester were positively associated with vomiting, prevalence ratio (PR) = 1.54 (95 % CI 1.10, 2.16) and negatively with anemia, PR = 0.67 (95 % CI 0.47, 0.96). Nutrient intakes, serum vitamin B₁₂, methylmalonic acid, homocysteine and red cell folate levels were not associated with measures of depression. Antenatal depressive symptoms in early pregnancy are highly prevalent in urban Indian women and are more common in women with vomiting and without anemia. In this cross-sectional data, blood concentrations of vitamin B₁₂ and folate were not associated with depressive symptoms. The relationship between nutritional status and depressive symptoms may require larger and longitudinal studies.     

Development of anonymous nuclear markers from Illumina paired-end data for Seychelles caecilian amphibians (Gymnophiona: Indotyphlidae)

Anonymous nuclear markers were developed for Seychelles caecilian amphibians. Using a previously published bioinformatics pipeline (developed for Roche 454 data), 36 candidate anonymous nuclear loci (ANL) of at least 180 bp length were identified from Illumina MiSeq next generation sequencing data for five Seychelles species. We designed primer pairs for the 36 candidate ANL and tested these by PCR and Sanger sequencing. Seven ANL amplified and sequenced well for at least five of the six nominal Seychelles caecilian species (in three genera), and represent potentially useful markers for systematics and conservation.     

Can Regional Anesthesia and Analgesia Prolong Cancer Survival After Orthopaedic Oncologic Surgery?

Background

The perioperative period of major oncologic surgery is characterized by immunosuppression, angiogenesis, and an increased load of circulating malignant cells. It is a window period in which cancer cells may seed, invade, and proliferate. Thus, it has been hypothesized that the use of regional anesthesia with the goal of reducing surgical stress and opioid and volatile anesthetic consumption would avoid perioperative immune suppression and angiogenesis and ultimately cancer recurrence.

Questions/purposes

We performed a systematic review of the literature on the use of regional anesthesia and postoperative analgesia to improve cancer-related survival after oncologic surgery. Our primary topic of interest is survival after orthopaedic oncologic surgery, but because that literature is limited, we also have systematically reviewed the question of survival after breast, gastrointestinal, and genitourologic cancers.

Methods

We searched the PubMed and Embase databases with the search terms: “anesthesia and analgesia”, “local neoplasm recurrence”, “cancer recurrence”, “loco-regional neoplasm recurrence”, “disease-free survival”, and “cumulative survival rates”. Our initial search of the two databases provided 836 studies of which 693 were rejected. Of the remaining 143 studies, only 13 articles qualified for inclusion in this systematic review, based on defined inclusion criteria. All these studies had retrospective design. Due to the high heterogeneity among the identified studies and the complete absence of randomized controlled trials from the literature on this topic, the results of a meta-analysis would be heavily confounded; hence, we instead performed a systematic review of the literature.

Results

No eligible studies addressed the question of whether regional anesthesia and analgesia have an impact on survival after musculoskeletal cancer surgery. Only one relevant clinical study was identified on regional breast cancer survival; it suggested a benefit. The literature on gastrointestinal and genitourinary surgery was larger but mixed, although some preliminary studies do suggest a benefit of regional anesthesia on survival after oncologic surgery in those patient populations.

Conclusions

Although basic science studies suggest a potential benefit of regional anesthesia and stress response reduction in cancer formation, we found little clinical evidence to support the theory that regional anesthesia and analgesia improve overall patient survival after oncologic surgery.     

Short-term Wear Evaluation of Thin Acetabular Liners on 36-mm Femoral Heads

Background

Dislocation remains the leading cause of revision THA. One approach to decreasing prosthetic dislocation risk has been the use of larger femoral head component sizes. The upper limit of head size in metal-on-polyethylene hip arthroplasty has historically been limited because of concerns about increased wear on thin polyethylene components. It is not known to what degree this concern should apply to more wear-resistant polyethylene components.

Questions/purposes

We therefore determined (1) in vitro wear rates of polyethylene liners of varying thicknesses, (2) whether there were differences in the microscopic wear characteristics as a function of polyethylene thickness, and (3) whether thin polyethylene components resulted in early catastrophic failures.

Methods

We used a hip wear simulator to compare the wear performance of 12 highly crosslinked polyethylene acetabular inserts. The internal diameter of all components was 36 mm, and there were three samples tested of each thickness (1.9, 3.9, 5.9, or 7.9 mm). Testing was conducted for 2.4 million cycles. Gravimetric mass loss was converted to volumetric loss, which was subsequently converted to theoretical linear penetration rates.

Results

Wear rates decreased with increasing polyethylene thickness. Mean ± SD wear rates for the 1.9-, 3.9-, 5.9-, and 7.9-mm groups were 5.0 ± 0.5, 3.2 ± 0.3, 2.5 ± 1.1, and 2.2 ± 1.3 mm³/million cycles, respectively (p < 0.016). Calculated penetration rates were 0.015, 0.012, 0.011, and 0.010 mm/million cycles, respectively (p < 0.016). There were no catastrophic failures in any group.

Conclusions

Thinner polyethylene components demonstrated higher wear rates, although even the highest wear rate observed in the thinnest polyethylene specimen was lower than that commonly reported for noncrosslinked polyethylene components. While encouraging, these findings should be validated in vivo before clinical recommendations can be made.     

Bereavement: Course,Consequences, and Care

This paper discusses each of several potential consequences of bereavement. First, we describe ordinary grief, followed by a discussion of grief gone awry, or complicated grief (CG). Then, we cover other potential adverse outcomes of bereavement, each of which may contribute to, but are not identical with, CG: general medical comorbidity, mood disorders, post-traumatic stress disorder, anxiety, and substance use.