Risk of Ischaemic Heart Disease in Patients with Inflammatory Bowel Disease: Cohort Study Using the General Practice Research Database

ObjectivePatients with inflammatory bowel disease (IBD) demonstrate an inflammatory response which bears some similarities to that seen in ischaemic heart disease (IHD). The nature of the association of IBD with IHD is uncertain. We aimed to define the extent and direction of that association.DesignThis retrospective cohort study examined records from patients aged ≥ 15 years with IBD from 1987–2009 (n = 19163) who were age and gender matched with patients without IBD (n = 75735) using the General Practice Research Database. The primary outcome was the hazard ratio for IHD.ResultsA higher proportion of IBD patients had a recorded diagnosis of IHD ever, 2220 (11.6%) compared with 6504 (8.6%) of controls. However, the majority (4494, 51.5%) developed IHD prior to IBD diagnosis (1404 (63.2%) of IBD cases and 3090 (47.5%) of controls). There was increased IHD incidence in the first year after IBD diagnosis. Mean age at IHD diagnosis was statistically similar across all IBD groups apart from for those with Ulcerative Colitis (UC) who were slightly younger at diagnosis of angina compared to controls (64.5y vs. 67.0y, p = 0.008) and coronary heart disease (65.7y vs.67.9y, p = 0.015). Of those developing IHD following IBD diagnosis, UC patients were at higher risk of IHD (unadjusted HR 1.3 (95% CI 1.1–1.5), p<0.001) or MI (unadjusted HR 1.4 (95% CI 1.1–1.6), p = 0.004).ConclusionAlthough IHD prevalence was higher in IBD patients, most IHD diagnoses predated the diagnosis of IBD. This implies a more complex relationship than previously proposed between the inflammatory responses associated with IHD and IBD, and alternative models should be considered.     

Sex Differences and Emotion Regulation: An Event-Related Potential Study

Difficulties in emotion regulation have been implicated as a potential mechanism underlying anxiety and mood disorders. It is possible that sex differences in emotion regulation may contribute towards the heightened female prevalence for these disorders. Previous fMRI studies of sex differences in emotion regulation have shown mixed results, possibly due to difficulties in discriminating the component processes of early emotional reactivity and emotion regulation. The present study used event-related potentials (ERPs) to examine sex differences in N1 and N2 components (reflecting early emotional reactivity) and P3 and LPP components (reflecting emotion regulation). N1, N2, P3, and LPP were recorded from 20 men and 23 women who were instructed to “increase,” “decrease,” and “maintain” their emotional response during passive viewing of negative images. Results indicated that women had significantly greater N1 and N2 amplitudes (reflecting early emotional reactivity) to negative stimuli than men, supporting a female negativity bias. LPP amplitudes increased to the “increase” instruction, and women displayed greater LPP amplitudes than men to the “increase” instruction. There were no differences to the “decrease” instruction in women or men. These findings confirm predictions of the female negativity bias hypothesis and suggest that women have greater up-regulation of emotional responses to negative stimuli. This finding is highly significant in light of the female vulnerability for developing anxiety disorders.     

Isolated Aortocoronary Bypass Operations in Patients Over 70 Years of Age: A Comparison With Results in Patients 50 to 59 Years Old

The early and late morbidity, mortality and beneficial effects of isolated aortocoronary bypass operations in a group of 35 patients 70 years old or older were compared with those factors in patients 50 to 59 years old. The patients in both groups were matched according to the year in which the operation was done and the number of vessels bypassed. Left ventricular function, estimated by the angiographically calculated ejection fraction, was not statistically different in the two groups. Cardiac index, while adequate in both groups, was significantly lower in the older age group. Comparisons were made of “early” events, such as perioperative myocardial infarction, perioperative death and length of post-operative hospital stay; and of “late” events, including myocardial infarction, angina pectoris, congestive heart failure and death, which occurred after patients were discharged from the hospital. The mean length of follow-up of patients was similar in both groups.In comparing early events in the two groups, there was no statistically significant difference in the incidence of perioperative myocardial infarction, perioperative mortality or mean length of postoperative hospital stays. With regard to late events, there was no statistically significant difference in the incidences of myocardial infarction, angina pectoris or mortality.     

Outcomes among HIV-1 Infected Individuals First Starting Antiretroviral Therapy with Concurrent Active TB or Other AIDS-Defining Disease

Background

Tuberculosis (TB) is common among HIV-infected individuals in many resource-limited countries and has been associated with poor survival. We evaluated morbidity and mortality among individuals first starting antiretroviral therapy (ART) with concurrent active TB or other AIDS-defining disease using data from the “Prospective Evaluation of Antiretrovirals in Resource-Limited Settings” (PEARLS) study.

Methods

Participants were categorized retrospectively into three groups according to presence of active confirmed or presumptive disease at ART initiation: those with pulmonary and/or extrapulmonary TB (“TB” group), those with other non-TB AIDS-defining disease (“other disease”), or those without concurrent TB or other AIDS-defining disease (“no disease”). Primary outcome was time to the first of virologic failure, HIV disease progression or death. Since the groups differed in characteristics, proportional hazard models were used to compare the hazard of the primary outcome among study groups, adjusting for age, sex, country, screening CD4 count, baseline viral load and ART regimen.

Results

31 of 102 participants (30%) in the “TB” group, 11 of 56 (20%) in the “other disease” group, and 287 of 1413 (20%) in the “no disease” group experienced a primary outcome event (p = 0.042). This difference reflected higher mortality in the TB group: 15 (15%), 0 (0%) and 41 (3%) participants died, respectively (p<0.001). The adjusted hazard ratio comparing the “TB” and “no disease” groups was 1.39 (95% confidence interval: 0.93–2.10; p = 0.11) for the primary outcome and 3.41 (1.72–6.75; p<0.001) for death.

Conclusions

Active TB at ART initiation was associated with increased risk of mortality in HIV-1 infected patients.     

Framingham Risk Score with Cardiovascular Events in Chronic Kidney Disease

The Framingham Risk Score (FRS) was developed to predict coronary heart disease in various populations, and it tended to under-estimate the risk in chronic kidney disease (CKD) patients. Our objectives were to determine whether FRS was associated with cardiovascular events, and to evaluate the role of new risk markers and echocardiographic parameters when they were added to a FRS model. This study enrolled 439 CKD patients. The FRS is used to identify individuals categorically as “low” (<10% of 10-year risk), “intermediate” (10–20% risk) or “high” risk (≧ 20% risk). A significant improvement in model prediction was based on the −2 log likelihood ratio statistic and c-statistic. “High” risk (v.s. “low” risk) predicts cardiovascular events either without (hazard ratios [HR] 2.090, 95% confidence interval [CI] 1.144 to 3.818) or with adjustment for clinical, biochemical and echocardiographic parameters (HR 1.924, 95% CI 1.008 to 3.673). Besides, the addition of albumin, hemoglobin, estimated glomerular filtration rate, proteinuria, left atrial diameter >4.7 cm, left ventricular hypertrophy or left ventricular ejection fraction<50% to the FRS model significantly improves the predictive values for cardiovascular events. In CKD patients, “high” risk categorized by FRS predicts cardiovascular events. Novel biomarkers and echocardiographic parameters provide additional predictive values for cardiovascular events. Future study is needed to assess whether risk assessment enhanced by using these biomarkers and echocardiographic parameters might contribute to more effective prediction and better care for patients.     

“Unwarranted survivals” and “anomalous deaths” from coronary heart disease: prospective survey of general population

ObjectivesTo assess survival in people who are at apparent high risk who do not develop coronary heart disease (“unwarranted survivals”) and mortality in people at low risk who die from the disease (“anomalous deaths”) and the extent to which these outcomes are explained by other, less visible, risk factors.DesignProspective general population survey.SettingRenfrew and Paisley, Scotland.Participants6068 men aged 45-64 years at screening in 1972-6, allocated to “visible” risk groups on the basis of body mass index and smoking.ResultsVisible risk was a good predictor of mortality: 13% (45) of men at low risk and 45% (86) of men at high risk had died by age 70 years. Of these deaths, 12 (4%) and 44 (23%), respectively, were from coronary heart disease. In the group at low visible risk other less visible risk factors accounted for increased risk in 83% (10/12) of men who died from coronary heart disease and 29% (84/292) of men who survived. In the high risk group 81/107 who survived (76%) and 19/44 (43%) who died from coronary heart disease had lower risk after other factors were considered. Different risk factors modified risk (beyond smoking and body mass index) in the two groups. Among men at low visible risk, poor respiratory function, diabetes, previous coronary heart disease, and socioeconomic deprivation modified risk. Among men at high visible risk, height and cholesterol concentration modified risk.ConclusionsDifferences in survival between these extreme risk groups are dramatic. Health promotion messages would be more credible if they discussed anomalies and the limits of prediction of coronary disease at an individual level.

What is already known on this topic

People pay attention to visible risk factors, such as smoking and weight, in explaining or predicting coronary events but are aware that these behavioural risk factors fail to explain some early deaths from coronary heart disease (in those with “low risk” lifestyles) and long survival (in those with “high risk” lifestyles)Such violations to notions of coronary candidacy undermine people''s belief in the worth of modifying behavioural risk factors for coronary heart disease

What this study adds

Visible risk status was a good marker for other coronary risk factors at the extremes of the risk distributionMost men at low visible risk (slim, never smoked) who died prematurely from coronary heart disease had poorer risk profiles on other less visible risk factors; similarly, men at high visible risk (obese, heavy smokers) who survived often had more favourable profiles on other risk factors     

Prenatal,Perinatal and Neonatal Risk Factors for Intellectual Disability: A Systemic Review and Meta-Analysis

BackgroundThe etiology of non-genetic intellectual disability (ID) is not fully known, and we aimed to identify the prenatal, perinatal and neonatal risk factors for ID.MethodPubMed and Embase databases were searched for studies that examined the association between pre-, peri- and neonatal factors and ID risk (keywords “intellectual disability” or “mental retardation” or “ID” or “MR” in combination with “prenatal” or “pregnancy” or “obstetric” or “perinatal” or “neonatal”. The last search was updated on September 15, 2015. Summary effect estimates (pooled odds ratios) were calculated for each risk factor using random effects models, with tests for heterogeneity and publication bias.ResultsSeventeen studies with 55,344 patients and 5,723,749 control individuals were eligible for inclusion in our analysis, and 16 potential risk factors were analyzed. Ten prenatal factors (advanced maternal age, maternal black race, low maternal education, third or more parity, maternal alcohol use, maternal tobacco use, maternal diabetes, maternal hypertension, maternal epilepsy and maternal asthma), one perinatal factor (preterm birth) and two neonatal factors (male sex and low birth weight) were significantly associated with increased risk of ID.ConclusionThis systemic review and meta-analysis provides a comprehensive evidence-based assessment of the risk factors for ID. Future studies are encouraged to focus on perinatal and neonatal risk factors and the combined effects of multiple factors.     

The Feasibility of Achieving Low-Sodium Intake in Diets That Are Also Nutritious,Low-Cost,and Have Familiar Meal Components

Objective

Given the importance of high sodium diets as a risk factor for disease burden (ranked 11^th in importance in the Global Burden of Disease Study 2010), we aimed to determine the feasibility of low-sodium diets that were also low-cost, nutritious and (for some scenarios) included familiar meals.

Methods

The mathematical technique of “linear programming” was used to model eight optimized daily diets (some with uncertainty), including some diets that contained “familiar meals” for New Zealanders or were Mediterranean-, Asian- and Pacific-style diets. Data inputs included nutrients in foods, food prices and food wastage.

Findings

Using nutrient recommendations for men and a cost constraint of <NZ$9/d (US$6.84), the sodium intake levels in the eight optimized daily diets were all well below the 2300 mg/d (5.8 g salt/d) recommended maximum. The only diet to not consistently fall below the recommended “target” upper limit of 1600 mg/d included an evening meal with sausages (median  = 1640 mg/d, 95% simulation interval: 1551–1735 mg/d). Many additional nutritional aspects of these optimized low-sodium diets suggest that they would reduce cardiovascular disease risk in other ways (e.g., improved polyunsaturated to saturated fat ratio) and also reduce risk of cancer and other chronic diseases (e.g., via higher intakes of vegetables, fruits and dietary fiber). Even healthier diets (e.g., with higher intakes of fruit) occurred when the cost constraint was relaxed to $NZ15/d (US$11.40). Similar results were obtained when the modeling considered diets for women.

Conclusions

These results provide some reassurance for the feasibility of substantially reducing population sodium intake given currently available low-cost foods and while maintaining some level of familiar meals. Policy makers could consider ways to promote such optimized diets and foods, including regulations on maximum salt levels in processed foods, and taxes on alternative foods that are high in salt, sugar and saturated fat.     

Higher Risk of Wheeze in Female than Male Smokers. Results from the Swedish GA2LEN Study

Background

Women who smoke have higher risk of lung function impairment, COPD and lung cancer than smoking men. An influence of sex hormones has been demonstrated, but the mechanisms are unclear and the associations often subject to confounding. This was a study of wheeze in relation to smoking and sex with adjustment for important confounders.

Methods

In 2008 the Global Allergy and Asthma European Network (GA²LEN) questionnaire was mailed to 45.000 Swedes (age 16–75 years), and 26.851 (60%) participated. “Any wheeze”: any wheeze during the last 12 months. “Asthmatic wheeze”: wheeze with breathlessness apart from colds.

Results

Any wheeze and asthmatic wheeze was reported by 17.3% and 7.1% of women, vs. 15.8% and 6.1% of men (both p<0.001). Although smoking prevalence was similar in both sexes, men had greater cumulative exposure, 16.2 pack-years vs. 12.8 in women (p<0.001). Most other exposures and characteristics associated with wheeze were significantly overrepresented in men. Adjusted for these potential confounders and pack-years, current smoking was a stronger risk factor for any wheeze in women aged <53 years, adjusted odds ratio (aOR) 1.85 (1.56–2.19) vs. 1.60 (1.30–1.96) in men. Cumulative smoke exposure and current smoking each interacted significantly with female sex, aOR 1.02 per pack-year (p<0.01) and aOR 1.28 (p = 0.04) respectively. Female compared to male current smokers also had greater risk of asthmatic wheeze, aOR 1.53 vs. 1.03, interaction aOR 1.52 (p = 0.02). These interactions were not seen in age ≥53 years.

Discussion

In addition to the increased risk of COPD and lung cancer female, compared to male, smokers are at greater risk of significant wheezing symptoms in younger age. This became clearer after adjustment for important confounders including cumulative smoke exposure. Estrogen has previously been shown to increase the bioactivation of several compounds in tobacco smoke, which may enhance smoke-induced airway inflammation in fertile women.     

Effect of Larvae Treated with Mixed Biopesticide Bacillus thuringiensis - Abamectin on Sex Pheromone Communication System in Cotton Bollworm,Helicoverpa armigera

Third instar larvae of the cotton bollworm (Helicoverpa armigera) were reared with artificial diet containing a Bacillus thuringiensis - abamectin (BtA) biopesticide mixture that resulted in 20% mortality (LD₂₀). The adult male survivors from larvae treated with BtA exhibited a higher percentage of “orientation” than control males but lower percentages of “approaching” and “landing” in wind tunnel bioassays. Adult female survivors from larvae treated with BtA produced higher sex pheromone titers and displayed a lower calling percentage than control females. The ratio of Z-11-hexadecenal (Z11–16:Ald) and Z-9-hexadecenal (Z9–16:Ald) in BtA-treated females changed and coefficients of variation (CV) of Z11–16:Ald and Z9–16:Ald were expanded compared to control females. The peak circadian calling time of BtA-treated females occurred later than that of control females. In mating choice experiment, both control males and BtA-treated males preferred to mate with control females and a portion of the Bt-A treated males did not mate whereas all control males did. Our Data support that treatment of larvae with BtA had an effect on the sex pheromone communication system in surviving H.armigera moths that may contribute to assortative mating.     

Is Early Tuberculosis Death Associated with Increased Tuberculosis Transmission?

Introduction

Tuberculosis (TB) is now a relatively uncommon disease in high income countries. As such, its diagnosis may be missed or delayed resulting in death before or shortly after the introduction of treatment. Whether early TB death is associated with increased TB transmission is unknown. To determine the transmission risk attributable to early TB death we undertook a case-control study.

Methods

All adults who were: (1) diagnosed with culture-positive pulmonary TB in the Province of Alberta, Canada between 1996 and 2012, and (2) died a TB-related death before or within the first 60 days of treatment, were identified. For each of these “cases” two sets of “controls” were randomly selected from among culture-positive pulmonary TB cases that survived beyond 60 days of treatment. “Controls” were matched by age, sex, population group, +/- smear status. Secondary cases of “cases” and “controls” were identified using conventional and molecular epidemiologic tools and compared. In addition, new infections were identified and compared in contacts of “cases” that died before treatment and contacts of their smear-matched “controls”. Conditional logistic regression was used to find associations in both univariate and multivariate analysis.

Results

“Cases” were as, but not more, likely than “controls” to transmit. This was so whether transmission was measured in terms of the number of “cases” and smear-unmatched or -matched “controls” that had a secondary case, the number of secondary cases that they had or the number of new infections found in contacts of “cases” that died before treatment and their smear-matched “controls”.

Conclusion

In a low TB incidence/low HIV prevalence country, pulmonary TB patients that die a TB-related death before or in the initial phase of treatment and pulmonary TB patients that survive beyond the initial phase of treatment are equally likely to transmit.     

The Relationship between Sexual Selection and Sexual Conflict

Evolutionary conflicts of interest arise whenever genetically different individuals interact and their routes to fitness maximization differ. Sexual selection favors traits that increase an individual’s competitiveness to acquire mates and fertilizations. Sexual conflict occurs if an individual of sex A’s relative fitness would increase if it had a “tool” that could alter what an individual of sex B does (including the parental genes transferred), at a cost to B’s fitness. This definition clarifies several issues: Conflict is very common and, although it extends outside traits under sexual selection, sexual selection is a ready source of sexual conflict. Sexual conflict and sexual selection should not be presented as alternative explanations for trait evolution. Conflict is closely linked to the concept of a lag load, which is context-dependent and sex-specific. This makes it possible to ask if one sex can “win.” We expect higher population fitness if females win.Many published studies ask if sexual selection or sexual conflict drives the evolution of key reproductive traits (e.g., mate choice). Here we argue that this is an inappropriate question. By analogy, G. Evelyn Hutchinson (1965) coined the phrase “the ecological theatre and the evolutionary play” to capture how factors that influence the birth, death, and reproduction of individuals (studied by ecologists) determine which individuals reproduce, and “sets the stage” for the selective forces that drive evolutionary trajectories (studied by evolutionary biologists). The more modern concept of “eco-evolutionary feedback” (Schoener 2011) emphasizes that selection changes the character of the actors over time, altering their ecological interactions. No one would sensibly ask whether one or the other shapes the natural world, when obviously both interact to determine the outcome.So why have sexual conflict and sexual selection sometimes been elevated to alternate explanations? This approach is often associated with an assumption that sexual conflict affects traits under direct selection, favoring traits that alter the likelihood of a potential mate agreeing or refusing to mate because it affects the bearer’s immediate reproductive output, whereas “traditional” sexual selection is assumed to favor traits that are under indirect selection because they increase offspring fitness. These “traditional” models are sometimes described as “mutualistic” (e.g., Pizzari and Snook 2003; Rice et al. 2006), although this term appears to be used only when contrasting them with sexual conflict models. The investigators of the original models never describe them as “mutualistic,” which is hardly surprising given that some males are rejected by females.In this review, we first define sexual conflict and sexual selection. We then describe how the notion of a “lag load” can reveal which sex currently has greater “power” in a sexual conflict over a specific resource. Next, we discuss why sexual conflict and sexual selection are sometimes implicitly (or explicitly) presented as alternative explanations for sexual traits (usually female mate choice/resistance). To illustrate the problems with the assumptions made to take this stance, we present a “toy model” of snake mating behavior based on a study by Shine et al. (2005). We show that empirical predictions about the mating behavior that will be observed if females seek to minimize direct cost of mating or to obtain indirect genetic benefits were overly simplistic. This allows us to make the wider point that whom a female is willing to mate with and how often she mates are often related questions. Finally, we discuss the effect of sexual conflict on population fitness.     

Mucosal Healing and the Risk of Ischemic Heart Disease or Atrial Fibrillation in Patients with Celiac Disease; A Population-Based Study

Background

Patients with celiac disease (CD), characterized histologically by villous atrophy (VA) of the small intestine, have an increased risk of ischemic heart disease (IHD) and atrial fibrillation (AF), risks that persist for years after commencing the gluten-free diet. It is unknown whether persistent VA on follow-up biopsy, rather than mucosal healing, affects the risk of IHD or AF.

Methods

We identified patients with histologic evidence of CD diagnosed at all 28 pathology departments in Sweden. Among patients who underwent a follow-up small intestinal biopsy, we compared patients with persistent VA to those who showed histologic improvement, with regard to the development of IHD (angina pectoris or myocardial infarction) or AF.

Results

Among patients with CD and a follow-up biopsy (n = 7,440), the median age at follow-up biopsy was 25 years, with 1,063 (14%) patients who were ≥60 years at the time of follow-up biopsy. Some 196 patients developed IHD and 205 patients developed AF. After adjusting for age, gender, duration of CD, calendar period, and educational attainment, there was no significant effect of persistent VA on IHD (adjusted HR 0.97; 95%CI 0.73–1.30). Adjusting for diabetes had a negligible effect (adjusted HR 0.98; 95%CI 0.73–1.31). There was no significant association between persistent VA and the risk of AF (adjusted HR 0.98; 95%CI 0.74–1.30).

Conclusions

In this population-based study of patients with CD, persistent VA on follow-up biopsy was not associated with an increased risk of IHD or AF. Failed mucosal healing does not influence the risk of these cardiac events.     

Dangers in the Use of Some Potent Drugs

The chief dangers reported with some common drugs are reviewed. Hazards of antibiotic therapy include: the increasing incidence of sensitization to penicillin with occasional anaphylactic reactions; aplastic anemia with chloramphenicol, and the poor tolerance of infants for chloramphenicol; staphylococcal enterocolitis; unnecessary “prophylactic” use of antibiotics. Thiazide diuretics may precipitate potassium depletion, skin reactions, pancreatitis, blood dyscrasias, gout, diabetes mellitus and hepatic coma. Reserpine can increase gastric acidity, induce mental depression, and when used with digitalis lead to ventricular premature beats. Hydralazine may aggravate angina pectoris, cause tachycardia, and bring about a syndrome resembling disseminated lupus erythematosus. Guanethidine may result in loose stools, impotence, and postural hypotension. Hazards of phenothiazines include jaundice, parkinsonian states and tremors, convulsions, hypotension, and blood dyscrasias. The butanediols have numerous side effects including gastrointestinal, cutaneous and hypotensive reactions. Prolonged corticosteroid therapy introduces a new danger in surgical treatment. The progesterone-like drugs may induce masculinization of the female fetus.     

Habilitation of Patients with Congenital Malformations Associated with Thalidomide: Surgery of Limb Defects

The deformities commonly seen in “thalidomide babies” are described. These vary from relatively uncomplicated radial-ray defects to complete phocomelia of all four extremities. It is suggested that the care of these children is best carried out in a clinic accustomed to dealing with juvenile amputee problems. A plea is made for very early fitting of upper-extremity prostheses (at approximately three months of age) in cases of unilateral upper-limb deficiencies. A “bucket” for sitting should be supplied for children with quadrilateral phocomelia to sit in when they reach seven or eight months of age. Children with severe upper-limb malformations will be candidates for some form of externally powered prostheses.     

Speaker Sex Influences Processing of Grammatical Gender

Spoken words carry linguistic and indexical information to listeners. Abstractionist models of spoken word recognition suggest that indexical information is stripped away in a process called normalization to allow processing of the linguistic message to proceed. In contrast, exemplar models of the lexicon suggest that indexical information is retained in memory, and influences the process of spoken word recognition. In the present study native Spanish listeners heard Spanish words that varied in grammatical gender (masculine, ending in -o, or feminine, ending in -a) produced by either a male or a female speaker. When asked to indicate the grammatical gender of the words, listeners were faster and more accurate when the sex of the speaker “matched” the grammatical gender than when the sex of the speaker and the grammatical gender “mismatched.” No such interference was observed when listeners heard the same stimuli, but identified whether the speaker was male or female. This finding suggests that indexical information, in this case the sex of the speaker, influences not just processes associated with word recognition, but also higher-level processes associated with grammatical processing. This result also raises questions regarding the widespread assumption about the cognitive independence and automatic nature of grammatical processes.     

The Dynamics of Sex Ratio Evolution: From the Gene Perspective to Multilevel Selection

The new dynamical game theoretic model of sex ratio evolution emphasizes the role of males as passive carriers of sex ratio genes. This shows inconsistency between population genetic models of sex ratio evolution and classical strategic models. In this work a novel technique of change of coordinates will be applied to the new model. This will reveal new aspects of the modelled phenomenon which cannot be shown or proven in the original formulation. The underlying goal is to describe the dynamics of selection of particular genes in the entire population, instead of in the same sex subpopulation, as in the previous paper and earlier population genetics approaches. This allows for analytical derivation of the unbiased strategic model from the model with rigorous non-simplified genetics. In effect, an alternative system of replicator equations is derived. It contains two subsystems: the first describes changes in gene frequencies (this is an alternative unbiased formalization of the Fisher-Dusing argument), whereas the second describes changes in the sex ratios in subpopulations of carriers of genes for each strategy. An intriguing analytical result of this work is that the fitness of a gene depends on the current sex ratio in the subpopulation of its carriers, not on the encoded individual strategy. Thus, the argument of the gene fitness function is not constant but is determined by the trajectory of the sex ratio among carriers of that gene. This aspect of the modelled phenomenon cannot be revealed by the static analysis. Dynamics of the sex ratio among gene carriers is driven by a dynamic “tug of war” between female carriers expressing the encoded strategic trait value and random partners of male carriers expressing the average population strategy (a primary sex ratio). This mechanism can be called “double-level selection”. Therefore, gene interest perspective leads to multi-level selection.     

Changing patterns in drug therapy for ischemic heart disease

To determine the possible influence of studies on β-blocker therapy following myocardial infarction and the introduction of calcium-channel blockers on the prescribing habits of physicians in a large urban centre, the drug therapy received by 100 patients with ischemic heart disease (IHD) (50 with myocardial infarction and 50 with unstable angina) admitted to a university teaching hospital in 1980 was compared with that received by another such group of 100 patients admitted in 1983-84. The proportion of patients with myocardial infarction receiving drug therapy was significantly higher in 1983-84, at the time of both admission (p < 0.01) and discharge (p < 0.001). Much of the increase was due to greater use of β-blockers. Of the 50 patients with unstable angina in 1983-84, 20 were taking calcium-channel blockers when admitted, and 29 were taking them when discharged. In both 1980 and 1983-84 unstable angina was treated more vigorously than myocardial infarction. The results suggest that physicians have developed a more aggressive approach to drug therapy for IHD since the publication of the β-blocker studies and the introduction of calcium-channel blockers.     

Sex and Breed-Dependent Organ Development and Metabolic Responses in Foetuses from Lean and Obese/Leptin Resistant Swine

The present study aimed to determine the effects of breed and sex on growth patterns and metabolic features of advanced-pregnancy foetuses exposed to the same environmental conditions. Thus, at Day 62 of pregnancy, swine foetuses from an obese breed with leptin resistance (Iberian breed) were compared to lean crossbred foetuses (25% Large White ×25% Landrace ×50% Pietrain). There were differential developmental patterns in foetuses with leptin resistance, mainly a higher relative weight of the brain resembling “brain-sparing effect”. Prioritization of brain growth may be protective for the adequate growth and postnatal survival of the Iberian individuals, an ancient breed reared in extensive semi-feral conditions for centuries. There were also clear sex-related differences in foetal development and metabolism in the Iberian breed. Female Iberian foetuses were similar in size and weight to male littermates but had a significantly higher relative liver to body weight ratio resembling “liver-sparing effect” and a trend for a higher relative intestine to body ratio. Moreover, the availability of triglycerides, cholesterol and IL-6 in female Iberian foetuses was similar to that of lean crossbred foetuses. Overall, these features may favour a better postnatal survival and development of females, the sex more critical for the species survival. These findings set the basis for future translational studies aimed at increasing the knowledge on the interaction between genetic and environmental factors in the early programming of the adult phenotype.     

Chorioamnionitis and Patent Ductus Arteriosus: A Systematic Review and Meta-Analysis

Background

Chorioamnionitis has recently been reported as a risk factor for various neonatal diseases, including cerebral palsy, bronchopulmonary dysplasia, and necrotizing enterocolitis, but its effect on patent ductus arteriosus (PDA) is unclear. We performed a systematic review and meta-analysis to evaluate the effect of chorioamnionitis on PDA.

Methods

We searched PubMed, EMBASE, Cochrane Library, and KoreaMed databases using the terms: “intrauterine infection” or “maternal infection” or “antenatal infection” or “chorioamnionitis” or “placenta inflammation” or “placenta pathology” or “neonatal outcome” or “neonatal morbidity” or “PDA or patent ductus arteriosus” or “ductus arteriosus,” and “prematurity” or “very low birth weight infant.” Studies were included if they were randomized controlled trials, case–control studies, or cohort studies that included information relating to chorioamnionitis and PDA.

Results

Among 1,571 studies, a total of 23 studies (17,708 cases) were included in the meta-analysis to analyze the relationship between chorioamnionitis and PDA, except one study that only included PDA requiring surgical ligation. The association between chorioamnionitis and PDA was statistically significant (odds ratio [OR] 1.43; 95% confidence interval [CI] 1.19, 1.72; P < 0.0001). In subgroup analysis, clinical chorioamnionitis was not associated with PDA (OR 1.28; 95% CI 1.00, 1.64, 1.790; P = 0.05), whereas histologic chorioamnionitis (OR 1.54; 95% CI 1.10, 2.15; P = 0.01) and chorioamnionitis diagnosed from both clinical and histologic findings (OR 1.75; 95% CI 1.07, 2.86; P = 0.03) showed significant associations with PDA. Chorioamnionitis did not increase the risk of PDA requiring surgical ligation (OR 1.23; 95% CI 0.69, 2.17; P = 0.48), and antenatal steroid use reduced the risk of PDA (OR 0.62; 95% CI 0.42, 0.90; P = 0.01) after chorioamnionitis.

Conclusions

The results from this meta-analysis support an association between maternal chorioamnionitis and PDA in offspring.