Genetic Determinants of Pelvic Organ Prolapse among African American and Hispanic Women in the Women’s Health Initiative

Current evidence suggests a multifactorial etiology to pelvic organ prolapse (POP), including genetic predisposition. We conducted a genome-wide association study of POP in African American (AA) and Hispanic (HP) women from the Women’s Health Initiative Hormone Therapy study. Cases were defined as any POP (grades 1–3) or moderate/severe POP (grades 2–3), while controls had grade 0 POP. We performed race-specific multiple logistic regression analyses between SNPs imputed to 1000 genomes in relation to POP (grade 0 vs 1–3; grade 0 vs 2–3) adjusting for age at diagnosis, body mass index, parity, and genetic ancestry. There were 1274 controls and 1427 cases of any POP and 317 cases of moderate/severe POP. Although none of the analyses reached genome-wide significance (p<5x10^-8), we noted variants in several loci that met p<10⁻⁶. In race-specific analysis of grade 0 vs 2–3, intronic SNPs in the CPE gene (rs28573326, OR:2.14; 95% CI 1.62–2.83; p = 1.0x10^-7) were associated with POP in AAs, and SNPs in the gene AL132709.5 (rs1950626, OR:2.96; 95% CI 1.96–4.48, p = 2.6x10^-7) were associated with POP in HPs. Inverse variance fixed-effect meta-analysis of the race-specific results showed suggestive signals for SNPs in the DPP6 gene (rs11243354, OR:1.36; p = 4.2x10^-7) in the grade 0 vs 1–3 analyses and for SNPs around PGBD5 (rs740494, OR:2.17; p = 8.6x10^-7) and SHC3 (rs2209875, OR:0.60; p = 9.3x10^-7) in the grade 0 vs 2–3 analyses. While we did not identify genome-wide significant findings, we document several SNPs reaching suggestive statistical significance. Further interrogation of POP in larger minority samples is warranted.     

Composition of the Vaginal Microbiota in Women of Reproductive Age – Sensitive and Specific Molecular Diagnosis of Bacterial Vaginosis Is Possible?

Background and Objective

Bacterial vaginosis (BV) is the most common vaginal disorder, characterized by depletion of the normal lactobacillus-dominant microbiota and overgrowth of commensal anaerobic bacteria. This study aimed to investigate the composition of the vaginal microbiota in women of reproductive age (healthy women and women with BV), with the view of developing molecular criteria for BV diagnosis.

Materials and Methods

Vaginal samples from 163 women (79 control, 73 BV and 11 intermediate (Lactobacillary grade II flora) cases) were analyzed using 454 pyrosequencing of the hypervariable regions V3–V4 of the 16S rRNA gene and 16 quantitative bacterial species/genus-specific real-time PCR assays. Sensitivities and specificities of potential BV markers were computed using the Amsel criteria as reference standard for BV. The use of quantitative thresholds for prediction of BV, determined for both relative abundance measured with 454 pyrosequencing and bacterial load measured with qPCR, was evaluated.

Results

Relative to the healthy women, the BV patients had in their vaginal microbiota significantly higher prevalence, loads and relative abundances of the majority of BV associated bacteria. However, only Gardnerella vaginalis, Atopobium vaginae, Eggerthella, Prevotella, BVAB2 and Megasphaera type 1 detected at or above optimal thresholds were highly predictable for BV, with the best diagnostic accuracy shown for A. vaginae. The depletion of Lactobacillus species combined with the presence of either G. vaginalis or A. vaginae at diagnostic levels was a highly accurate BV predictor.

Conclusions

Quantitative determination of the presence of G. vaginalis, A. vaginae, Eggerthella, Prevotella, BVAB2 and Megasphaera type 1 as well as the depletion of Lactobacillus was highly accurate for BV diagnosis. Measurements of abundance of normal and BV microbiota relative to total bacteria in vaginal fluid may provide more accurate BV diagnosis, and be used for test-of-cure, rather than qualitative detection or absolute counts of BV related microorganisms.     

Is Body Mass Index a Measure of Adiposity in Elderly Women?

Objective: To evaluate the accuracy of body mass index (BMI) as a predictor of body fat in elderly women. Research Methods and Procedures: A total of 1423 women aged 67 ± 5 (mean ± SD, range: 60 to 88) years were consecutively enrolled into the study. Fat mass (FM) was measured using DXA. Results: BMI explained 72.9% of FM variance (p < 0.0001), with a root mean square error of estimate (RMSE) of 3.5 kg. After standardization of RMSE on the dependent variable as RMSE%, the prediction error equaled 15%. BMI explained 54.8% of FM% variance (p < 0.0001), with an RMSE of 4.1%, corresponding to an RMSE% of 11%. Discussion: The relatively high RMSE% of the FM and FM%‐BMI associations caution against the use of BMI as an adiposity index in individual elderly women. However, an error corresponding to 11% of FM% may be accepted for population studies of body fat in elderly women.     

How Effective Is Help on the Doorstep? A Longitudinal Evaluation of Community-Based Organisation Support

Community-based responses have a lengthy history. The ravages of HIV on family functioning has included a widespread community response. Although much funding has been invested in front line community-based organisations (CBO), there was no equal investment in evaluations. This study was set up to compare children aged 9–13 years old, randomly sampled from two South African provinces, who had not received CBO support over time (YC) with a group of similarly aged children who were CBO attenders (CCC). YC baseline refusal rate was 2.5% and retention rate was 97%. CCC baseline refusal rate was 0.7% and retention rate was 86.5%. 1848 children were included—446 CBO attenders compared to 1402 9–13 year olds drawn from a random sample of high-HIV prevalence areas. Data were gathered at baseline and 12–15 months follow-up. Standardised measures recorded demographics, violence and abuse, mental health, social and educational factors. Multivariate regression analyses revealed that children attending CBOs had lower odds of experiencing weekly domestic conflict between adults in their home (OR 0.17; 95% CI 0.09, 0.32), domestic violence (OR 0.22; 95% CI 0.08, 0.62), or abuse (OR 0.11; 95% CI 0.05, 0.25) at follow-up compared to participants without CBO contact. CBO attenders had lower odds of suicidal ideation (OR 0.41; 95% CI 0.18, 0.91), fewer depressive symptoms (B = -0.40; 95% CI -0.62, -0.17), less perceived stigma (B = -0.37; 95% CI -0.57, -0.18), fewer peer problems (B = -1.08; 95% CI -1.29, -0.86) and fewer conduct problems (B = -0.77; 95% CI -0.95, -0.60) at follow-up. In addition, CBO contact was associated with more prosocial behaviours at follow-up (B = 1.40; 95% CI 1.13, 1.67). No associations were observed between CBO contact and parental praise or post-traumatic symptoms. These results suggest that CBO exposure is associated with behavioural and mental health benefits for children over time. More severe psychopathology was not affected by attendance and may need more specialised input.     

Differential Renal Function Study—An Aid in Preoperative Evaluation of Hypertensive Patients

Non-occlusive ureteral catheters were placed bilaterally in the renal pelves of 30 patients known to have hypertension. Samples of urine were collected under conditions of normal hydration, of urea-PAH-saline diuresis and, in some cases, mannitol diuresis. The samples were analyzed for indications of impaired flow of blood to the kidneys. Aortograms were obtained in all cases.This placement of non-occlusive catheters up into the renal pelves was felt to have caused only minimal disturbance of renal function, and was not accompanied by ureteral edema with the concomitant complications caused by occlusive catheters. Under conditions of normal hydration, leakage was insignificant.Of the 20 patients in whom urea-PAH-saline infusion revealed an ischemic pattern, 19 had an ischemic pattern under conditions of normal hydration. Since in the one exception an aortographic examination did not show a surgically reparable renal lesion, it may be inferred that the use of urea-PAH-saline diuresis is not essential in the preoperative evaluation of hypertensive renal disease.Correlation of the results of differential renal function studies and aortographic findings was possible in 19 of the 30 patients. Lack of correlation in the remaining 11 patients emphasized the importance of obtaining both types of study.Aortographic examination combined with differential renal function studies, using small ureteral catheters under conditions of normal hydration, should give the urologist a practical and yet accurate method of determining differential renal blood flow. If desired, further verification could be obtained by administering contrast medium and performing serial measurements of urine density.     

How Is Meaning Grounded in the Organism?

In this paper we address the interrelated questions of why and how certain features of an organism’s environment become meaningful to it. We make the case that knowing the biology is essential to understanding the foundation of meaning-making in organisms. We employ Miguel Nicolelis et al’s seminal research on the mammalian somatosensory system to enrich our own concept of brain-objects as the neurobiological intermediary between the environment and the consequent organismic behavior. In the final section, we explain how brain-objects advance the ongoing discussion of what constitutes a biosemiotic system. In general, this paper acknowledges Marcello Barbieri’s call for biology to make room for meaning, and makes a contribution to that end.     

How Accurate Is MOLLI T1 Mapping In Vivo? Validation by Spin Echo Methods

T₁ mapping is a promising quantitative tool for assessing diffuse cardiomyopathies. The purpose of this study is to quantify in vivo accuracy of the Modified Look-Locker Inversion Recovery (MOLLI) cardiac T₁ mapping sequence against the spin echo gold standard, which has not been done previously. T₁ accuracy of MOLLI was determined by comparing with the gold standard inversion recovery spin echo sequence in the calf muscle, and with a rapid inversion recovery fast spin echo sequence in the heart. T₁ values were obtained with both conventional MOLLI fitting and MOLLI fitting with inversion efficiency correction. In the calf (n = 6), conventional MOLLI fitting produced inconsistent T₁ values with error ranging from 8.0% at 90° to 17.3% at 30°. Modified MOLLI fitting with inversion efficiency correction improved error to under 7.4% at all flip angles. In the heart (n = 5), modified MOLLI fitting with inversion correction reduced T₁ error to 5.5% from 14.0% by conventional MOLLI fitting. This study shows that conventional MOLLI fitting can lead to significant in vivo T₁ errors when not accounting for the lower adiabatic inversion efficiency often experienced in vivo.     

How Accurate and Robust Are the Phylogenetic Estimates of Austronesian Language Relationships?

We recently used computational phylogenetic methods on lexical data to test between two scenarios for the peopling of the Pacific. Our analyses of lexical data supported a pulse-pause scenario of Pacific settlement in which the Austronesian speakers originated in Taiwan around 5,200 years ago and rapidly spread through the Pacific in a series of expansion pulses and settlement pauses. We claimed that there was high congruence between traditional language subgroups and those observed in the language phylogenies, and that the estimated age of the Austronesian expansion at 5,200 years ago was consistent with the archaeological evidence. However, the congruence between the language phylogenies and the evidence from historical linguistics was not quantitatively assessed using tree comparison metrics. The robustness of the divergence time estimates to different calibration points was also not investigated exhaustively. Here we address these limitations by using a systematic tree comparison metric to calculate the similarity between the Bayesian phylogenetic trees and the subgroups proposed by historical linguistics, and by re-estimating the age of the Austronesian expansion using only the most robust calibrations. The results show that the Austronesian language phylogenies are highly congruent with the traditional subgroupings, and the date estimates are robust even when calculated using a restricted set of historical calibrations.     

Is Beauty in the Eyes of the Beholder? Aesthetic Quality versus Technical Skill in Movement Evaluation of Tai Chi

The aim of this study was to compare experts to naïve practitioners in rating the beauty and the technical quality of a Tai Chi sequence observed in video-clips (of high and middle level performances). Our hypothesis are: i) movement evaluation will correlate with the level of skill expressed in the kinematics of the observed action but ii) only experts will be able to unravel the technical component from the aesthetic component of the observed action. The judgments delivered indicate that both expert and non-expert observers are able to discern a good from a mediocre performance; however, as expected, only experts discriminate the technical from the aesthetic component of the action evaluated and do this independently of the level of skill shown by the model (high or middle level performances). Furthermore, the judgments delivered were strongly related to the kinematic variables measured in the observed model, indicating that observers rely on specific movement kinematics (e.g. movement amplitude, jerk and duration) for action evaluation. These results provide evidence of the complementary functional role of visual and motor action representation in movement evaluation and underline the role of expertise in judging the aesthetic quality of movements.     

How Accurate Are the Fusion of Cone-Beam CT and 3-D Stereophotographic Images?

Background

Cone-beam Computed Tomography (CBCT) and stereophotography are two of the latest imaging modalities available for three-dimensional (3-D) visualization of craniofacial structures. However, CBCT provides only limited information on surface texture. This can be overcome by combining the bone images derived from CBCT with 3-D photographs. The objectives of this study were 1) to evaluate the feasibility of integrating 3-D Photos and CBCT images 2) to assess degree of error that may occur during the above processes and 3) to identify facial regions that would be most appropriate for 3-D image registration.

Methodology

CBCT scans and stereophotographic images from 29 patients were used for this study. Two 3-D images corresponding to the skin and bone were extracted from the CBCT data. The 3-D photo was superimposed on the CBCT skin image using relatively immobile areas of the face as a reference. 3-D colour maps were used to assess the accuracy of superimposition were distance differences between the CBCT and 3-D photo were recorded as the signed average and the Root Mean Square (RMS) error.

Principal Findings:

The signed average and RMS of the distance differences between the registered surfaces were −0.018 (±0.129) mm and 0.739 (±0.239) mm respectively. The most errors were found in areas surrounding the lips and the eyes, while minimal errors were noted in the forehead, root of the nose and zygoma.

Conclusions

CBCT and 3-D photographic data can be successfully fused with minimal errors. When compared to RMS, the signed average was found to under-represent the registration error. The virtual 3-D composite craniofacial models permit concurrent assessment of bone and soft tissues during diagnosis and treatment planning.     

Extent of Pelvic Lymph Node Dissection During Radical Cystectomy: Is Bigger Better?

Pelvic lymph node dissection (PLND) is a standard component of radical cystectomy (RC) for bladder cancer. The optimal anatomic PLND template remains undefined. An extended PLND template can potentially improve survival through the eradication of micrometastatic disease and improved pathologic staging. However, this benefit could be compromised by a potential increase in perioperative complications and cost. Two randomized controlled clinical trials that will clarify this question are ongoing. Many important retrospective studies have provided insights into the optimal PLND extent. Here the authors review the key evidence that informs how urologists may tailor the PLND template during RC depending on patient and tumor characteristics.Key words: Pelvic lymph node dissection, Radical cystectomy, Template, Micrometastatic diseaseAs described by Whitmore and Marshall in 1962,¹ the original pelvic lymph node dissection (PLND) template during radical cystectomy (RC) included nodal/lymphatic tissue bounded by the external iliac artery, the distal ureter, and Cooper’s ligament. The nodal tissue enveloping the external iliac vein and occupying the obturator fossa nodes was also removed, followed by removal of the lymphatic tissue surrounding the internal iliac vessels and posterior pelvis, including presacral nodes.²In the ensuing decades, urologists at different centers have modified the original template. However, to date, no level I evidence exists to address the value of one dissection template over another; published guidelines, accordingly, are vague.³ Several names have been given to different templates and nodal regions. The limited template includes perivesical nodes and lymphatic tissue in the obturator fossa, limited laterally by the external iliac vein and medially by the obturator nerve.^4–6 A larger limited lymphadenectomy template (referred to as standard by some) is bounded distally by the circumflex iliac vein and Cloquet’s node, laterally by the genitofemoral nerve, medially by the bladder and internal iliac vessels, posteriorly by the obturator fossa, and proximally by the bifurcation of (or distal aspect of) the common iliac artery.^5–8Extended PLND has been variously defined to include a more cephalad proximal boundary located at or above the aortic bifurcation and may also include presacral and presciatic nodes.^7,9,10 The extended template bounded proximally by the crossing of the ureter and external iliac artery^6,11 is referred to as standard/extended in this review. Still others define the extended template to extend as proximally as the origin of the inferior mesenteric artery and also include lymphatic tissues in the triangle of Marcille, which involves medial retraction of the external iliac artery to reveal the space medial to the psoas major; dissection of this space reveals the proximal aspect of the obturator nerve as it emanates from the psoas.^4,11,12An alternative nomenclature system for PLND defines three levels of operative intervention: levels I, II, and III (Figure 1).¹³ The level I template is similar to a standard template—the proximal extent of this is the common iliac bifurcation. Level II nodes are lateral to the common iliac artery, include presacral nodes, and extend proximally to the aortic bifurcation. Level III nodes are located between the ureters and great vessels and extend proximally to the inferior mesenteric artery. Investigators have also referred to super-extended PLND, which is the template that would include all level I, II, and III nodes (Figure 2).^2,11,14Open in a separate windowFigure 1Anatomic pelvic lymph node dissection levels: I, II, and III. Percentages of patients with lymph node metastases at each level are shown (from a series of 290 patients who had super-extended PLND including levels I, II, and III). Adapted from Leissner J et al.¹³Open in a separate windowFigure 2(A) Super-extended pelvic lymph node dissection template (levels I, II, and III). (B) Standard/extended template (level I plus level II up to crossing of ureter and external iliac artery). Adapted from Zehnder P et al.¹¹     

The Influence of Body Mass Index on Outcomes in Patients Undergoing Cardiac Surgery: Does the Obesity Paradox Really Exist?

Purpose

Obesity influences risk stratification in cardiac surgery in everyday practice. However, some studies have reported better outcomes in patients with a high body mass index (BMI): this is known as the obesity paradox. The aim of this study was to quantify the effect of diverse degrees of high BMI on clinical outcomes after cardiac surgery, and to assess the existence of an obesity paradox in our patients.

Methods

A total of 2,499 consecutive patients requiring all types of cardiac surgery with cardiopulmonary bypass between January 2004 and February 2009 were prospectively studied at our institution. Patients were divided into four groups based on BMI: normal weight (18.5–24.9 kg∙m⁻²; n = 523; 21.4%), overweight (25–29.9kg∙m⁻²; n = 1150; 47%), obese (≥30–≤34.9kg∙m⁻²; n = 624; 25.5%) and morbidly obese (≥35kg∙m⁻²; n = 152; 6.2%). Follow-up was performed in 2,379 patients during the first year.

Results

After adjusting for confounding factors, patients with higher BMI presented worse oxygenation and better nutritional status, reflected by lower PaO₂/FiO₂ at 24h and higher albumin levels 48h after admission respectively. Obese patients showed a higher risk for Perioperative Myocardial Infarction (OR: 1.768; 95% CI: 1.035–3.022; p = 0.037) and septicaemia (OR: 1.489; 95% CI: 1.282–1.997; p = 0.005). In-hospital mortality was 4.8% (n = 118) and 1-year mortality was 10.1% (n = 252). No differences were found regarding in-hospital mortality between BMI groups. The overweight group showed better 1-year survival than normal weight patients (91.2% vs. 87.6%; Log Rank: p = 0.029. HR: 1.496; 95% CI: 1.062–2.108; p = 0.021).

Conclusions

In our population, obesity increases Perioperative Myocardial Infarction and septicaemia after cardiac surgery, but does not influence in-hospital mortality. Although we found better 1-year survival in overweight patients, our results do not support any protective effect of obesity in patients undergoing cardiac surgery.     

How Do Women Prepare for Pregnancy? Preconception Experiences of Women Attending Antenatal Services and Views of Health Professionals

Main objective

To determine the extent to which women plan and prepare for pregnancy.

Methods

Cross-sectional questionnaire survey of pregnant women attending three maternity services in London about knowledge and uptake of preconception care; including a robust measure of pregnancy planning, and phone interviews with a range of health care professionals.

Main results

We recruited 1173/1288 (90%) women, median age of 32 years. 73% had clearly planned their pregnancy, 24% were ambivalent and only 3% of pregnancies were unplanned. 51% of all women and 63% of those with a planned pregnancy took folic acid before pregnancy. 21% of all women reported smoking and 61% reported drinking alcohol in the 3 months before pregnancy; 48% of smokers and 41% of drinkers reduced or stopped before pregnancy. The 51% of all women who reported advice from a health professional before becoming pregnant were more likely to adopt healthier behaviours before pregnancy [adjusted odds ratios for greatest health professional input compared with none were 2.34 (95% confidence interval 1.54–3.54) for taking folic acid and 2.18 (95% CI 1.42–3.36) for adopting a healthier diet before pregnancy]. Interviews with 20 health professionals indicated low awareness of preconception health issues, missed opportunities and confusion about responsibility for delivery of preconception care.

Significance of the findings

Despite a high level of pregnancy planning, awareness of preconception health among women and health professionals is low, and responsibility for providing preconception care is unclear. However, many women are motivated to adopt healthier behaviours in the preconception period, as indicated by halving of reported smoking rates in this study. The link between health professional input and healthy behaviour change before pregnancy is a new finding that should invigorate strategies to improve awareness and uptake of pre-pregnancy health care, and bring wider benefits for public health.     

What Is the Accurate Prevalence of Obesity in Sweden in the 21st Century? Methodological Experiences From the Skaraborg Project

Objective: To examine the impact of non‐response to self‐reported body weight and height in health questionnaires for the estimation of obesity prevalence. Methods and Procedures: A cross‐sectional population‐based health survey in the community of Vara with 16,009 residents (in year 2002) in South‐western Sweden. Participants randomly selected in strata by sex and age among residents being 30–74 years old were consecutively invited to the local health care center for a health examination, including two visits. Self‐reported information on body weight and height were obtained by health questionnaires at the first visit, and measured information on both variables at the second visit. For this study 1,809 subjects (904 men and 905 women) completed both visits (participation rate 81%), and a nurse measured body weight and height of all at visit two. Participants not self‐reporting body weight and/or height at the first visit were defined as non‐responders. Results: Both male and female non‐responders were significantly older than responders. Female non‐responders had significantly higher BMI (29.8 ± 5.8 kg/m²) than female responders (26.6 ± 5.3 kg/m²), (P < 0.001). No similar findings were seen in men. Non‐responders were more likely to be obese than responders both in men (odds ratio (OR) 2.06, 95% confidence interval (CI) 1.03–4.11) and in women (OR 2.24, 95% CI 1.25–4.02). Discussion: Non‐responders to self‐reported body weight and height in health questionnaires contribute to the underestimation of obesity. Measured body weight and height are to prefer when describing the accurate prevalence of obesity in populations.