There is an obstetrical dilemma: Misconceptions about the evolution of human childbirth and pelvic form.

Compared to other primates, modern humans face high rates of maternal and neonatal morbidity and mortality during childbirth. Since the early 20th century, this "difficulty" of human parturition has prompted numerous evolutionary explanations, typically assuming antagonistic selective forces acting on maternal and fetal traits, which has been termed the "obstetrical dilemma." Recently, there has been a growing tendency among some anthropologists to question the difficulty of human childbirth and its evolutionary origin in an antagonistic selective regime. Partly, this stems from the motivation to combat increasing pathologization and overmedicalization of childbirth in industrialized countries. Some authors have argued that there is no obstetrical dilemma at all, and that the difficulty of childbirth mainly results from modern lifestyles and inappropriate and patriarchal obstetric practices. The failure of some studies to identify biomechanical and metabolic constraints on pelvic dimensions is sometimes interpreted as empirical support for discarding an obstetrical dilemma. Here we explain why these points are important but do not invalidate evolutionary explanations of human childbirth. We present robust empirical evidence and solid evolutionary theory supporting an obstetrical dilemma, yet one that is much more complex than originally conceived in the 20th century. We argue that evolutionary research does not hinder appropriate midwifery and obstetric care, nor does it promote negative views of female bodies. Understanding the evolutionary entanglement of biological and sociocultural factors underlying human childbirth can help us to understand individual variation in the risk factors of obstructed labor, and thus can contribute to more individualized maternal care.

Short report: Self-compassion and satisfaction with life in Danish adolescents with Developmental Language Disorder (DLD): `We are all in the same boat´.

BACKGROUND: Adolescents with Developmental Language Disorder (DLD) are at risk of emotional health problems and low self-esteem. However, little is known about their self-compassion (SC) and satisfaction with life (SWL). The present study compared self-compassion and satisfaction with life reported by Danish adolescents with DLD compared to typically developing (TD) peers, and whether severity of language difficulty is associated with SC and SWL. METHODS: Results were obtained from 10 Danish adolescents with DLD compared with 14 age-matched TD adolescents and 132 TD peers, aged 15 years. RESULTS: For SC and SWL results showed that adolescents with DLD reported more positive feelings compared to the TD adolescents. Interestingly for SC, the negative, but not the positive, domain differentiated the two groups, as adolescents with DLD reported less symptoms on self-judgment, isolation and overidentification. SC and SWL was strongly correlated with language abilities for the DLD group, but not for the TD group. CONCLUSIONS: Results from our pilot study showed that Danish adolescents with DLD reported being less harsh on themselves. Language abilities were associated with self-compassion for the DLD, but not for the TD group. Whether these group differences are due to environmental factors such as the specific Danish school setting of the DLD group or internal factors are discussed and requires further research.

An Integrated Approach for High-Shear Wet Granulation (HSWG) Processing of TPGS-Based Formulations: Demonstration of Process Robustness through Experimental Design Conditions.

The goal of this study was to understand the impact of high-shear wet granulation (HSWG) processing conditions on product attributes for a tablet formulation containing the non-ionic surfactant TPGS. The use of TPGS in oral solid drug products has been reported to be challenging due to the low melting temperature of TPGS. In addition, literature on TPGS-based HSWG formulations, especially practical processing and scale-up knowledge, is limited. Presented here is an extension of this TPGS application in a tablet formulation, with a focus on the HSWG processing and scale-up across different granulators. To understand the processing space for this TPGS-based HSWG formulation, two consecutive studies were conducted with different objectives. First, an exploratory study was conducted to understand the impact of extreme processing conditions on product attributes. Subsequently, a factorial design of experiment (DoE) study assessed the separate contributions and interactions from HSWG processing variables. The outcome of both studies led to a successful process scale-up and product transfer from lab to commercial development using different granulators. The TPGS-based formulation was demonstrated to provide robust downstream processing (improved flowability and reduced segregation potential) within a wide HSWG operating space, while having a minimal impact on product performance across different granulators.

Comparing abundance distributions and range maps in spatial conservation planning for migratory species.

Most spatial conservation planning for wide-ranging or migratory species is constrained by poor knowledge of species' spatiotemporal dynamics and is only based on static species' ranges. However, species have substantial variation in abundance across their range and migratory species have important spatiotemporal population dynamics. With growing ecological data and advancing analytics, both of these can be estimated and incorporated into spatial conservation planning. However, there is limited information on the degree to which including this information affects conservation planning. We compared the performance of systematic conservation prioritizations for different scenarios based on varying the input species' distributions by ecological metric (abundance distributions versus range maps) and temporal sampling resolution (weekly, monthly, or quarterly). We used the example of a community of 41 species of migratory shorebirds that breed in North America, and we used eBird data to produce weekly estimates of species' abundances and ranges. Abundance distributions at a monthly or weekly resolution led to prioritizations that most efficiently protected species throughout the full annual cycle. Conversely, spatial prioritizations based on species' ranges required more sites and left most species insufficiently protected for at least part of their annual cycle. Prioritizations with only quarterly species ranges were very inefficient as they needed to target 40% of species' ranges to include 10% of populations. We highlight the high value of abundance information for spatial conservation planning, which leads to more efficient and effective spatial prioritization for conservation. Overall, we provide evidence that spatial conservation planning for wide-ranging migratory species is most robust and efficient when informed by species' abundance information from the full annual cycle.

Does breastfeeding duration decrease child obesity? An instrumental variables analysis.

BACKGROUND: Many studies have documented that breastfeeding is associated with a significant reduction in child obesity risk. However, a persistent problem in this literature is that unobservable confounders may drive the correlations between breastfeeding behaviors and child weight outcomes. OBJECTIVE: This study examines the effect of breastfeeding practices on child weight outcomes at age 2. METHODS: This study relied on population-based data for all births in Oregon in 2009 followed for two years. We used instrumental variables methods to exploit variations in breastfeeding by mothers immediately after delivery and the degree to which hospitals encouraged mothers to breastfeed in order to isolate the effect of breastfeeding practices on child weight outcomes. RESULTS: We found that for every extra week that the child was breastfed, the likelihood of the child being obese at age 2 declined by 0.82% [95% CI -1.8% to 0.1%]. Likewise, for every extra week that the child was exclusively breastfed, the likelihood of being obese declined by 0.66% [95% CI -1.4 to 0.06%]. While the magnitudes of effects were modest and marginally significant, the results were robust in a variety of specifications. CONCLUSION: The results suggest that hospital practices that support breastfeeding may influence childhood weight outcomes.

Hot, liquid glass injury as a novel mechanism for intraocular foreign body.

PURPOSE: To report the occurrence of a novel mechanism of IOFB with hot, liquefied glass injury. METHODS: Retrospective case series. RESULTS: Two patients suffered an injury to their eye with hot, liquefied glass. The ocular findings included a single scleral entry wound with multiple glass fragments located inside the eye. Fragments were found embedded in the retina, as well as mobile on the retinal surface. CONCLUSIONS: This distinctive mechanism involves an initial liquid state of glass causing injury, and results in multiple solidified glass IOFBs despite a single entrance wound. Though intraocular glass is typically inert, the unique characteristics of this injury may warrant a surgical approach. Surgical management proved successful in stabilizing vision and preventing further complications.

Cases of travel-acquired dengue fever in Denmark 2001-2009.

Dengue fever (DF) remains one of the most important emerging infectious diseases. Whereas DF is well recognized in endemic countries, there are indications that the disease is underdiagnosed among travellers to endemic regions. Here, we present the first descriptive survey on cases of travel-acquired DF imported to Denmark diagnosed at the national reference laboratory for dengue virus diagnostics during a 9-year period. In our study, 16 - 46 travel-acquired dengue virus infections were diagnosed per year. DF is mainly imported by adults, mostly men, returning from Southeast Asian countries. The minimum incidence of dengue virus infection among Danish travellers is estimated to be 4.9 per 100,000 travellers. Our results confirm and expand studies from other European countries, and underline the importance of surveillance based on relevant diagnostic analyses.

Insulin detemir improves glycaemic control with less hypoglycaemia and no weight gain in patients with type 2 diabetes who were insulin naive or treated with NPH or insulin glargine: clinical practice experience from a German subgroup of the PREDICTIVE study.

AIM: The Predictable Results and Experience in Diabetes through Intensification and Control to Target: An International Variability Evaluation (PREDICTIVE) Study is a large, multi-centre, observational study assessing the safety and efficacy of insulin detemir in everyday clinical practice. METHODS: This subgroup analysis of the German cohort of PREDICTIVE evaluates over 3 months, patients with type 2 diabetes who were transferred to insulin detemir +/- oral antidiabetic drugs (OADs) from an OAD-only regimen (n = 1321), NPH insulin +/- OADs (n = 251) or insulin glargine +/- OADs (n = 260). RESULTS: Among all groups, 3 months after starting treatment with insulin detemir, total, daytime and nocturnal hypoglycaemic events/patient were reduced by 84, 80 and 90%, respectively, from baseline. No major hypoglycaemic events were reported during treatment with insulin detemir. HbAlc was significantly reduced from baseline in each of the subgroups (-1.29,-0.60 and-0.59% for patients previously taking OADs only, NPH insulin +/- OADs and insulin glargine +/- OADs respectively; p < 0.0001), as was fasting blood glucose (FBG) (-58.1,-29.1 and-24.6 mg/dl; p < 0.0001) and FBG variability-8.2 mg/dl,-5.7 mg/dl; p < 0.0001 and -5.1 mg/dl; p = 0.0008). All subgroups combined lost an average of 0.9 kg of body weight (p < 0.0001) during the study. Total daily basal insulin dose increased slightly from baseline for those patients on a prior insulin regimen, and in this study 79% of patients used insulin detemir once daily. CONCLUSIONS: These data confirm the short-term safety and efficacy of insulin detemir +/- OADs in a real-world scenario and support the findings of randomized controlled clinical trials with insulin detemir, including its limited effects on body weight.

Fabry disease--a metabolic disorder with a challenge for endocrinologists?

OBJECTIVE: To revisit Fabry disease, a rare X-linked metabolic glycosphingolipid storage disease caused by a deficiency of the lysosomal enzyme alpha-galactosidase A (alpha-gal A). METHOD: Summary of the existing knowledge of Fabry disease including the clinical feature of Fabry disease and the recent breakthrough in the treatment of Fabry patients with the development of recombinant human alpha-gal A. CONCLUSION: The diffuse organ manifestations of Fabry disease resemble medical endocrinological diseases, and medical endocrinology might be an appropriate speciality to manage the treatment in collaboration with other specialists and clinical geneticists.

Maternal caffeine intake and intrauterine growth retardation.

This study estimates the effect of maternal caffeine consumption throughout pregnancy on fetal growth. We studied 2,714 women who delivered a liveborn infant between 1988 and 1991. Detailed information regarding coffee, tea, and soda drinking during the first and third trimesters of pregnancy was obtained. Average caffeine intake during month 1 of pregnancy was higher than for month 7 (72.4 vs 54.0 mg per day). Consumption of >300 mg caffeine per day during month 1 (adjusted odds ratio = 0.91; 95% confidence interval = 0.44--1.90) and during month 7 (adjusted odds ratio = 1.00; 95% confidence interval = 0.37--2.70) was not associated with intrauterine growth retardation. There was little evidence for any effect modification due to cigarette smoking on the caffeine associations. This study provides evidence that antenatal caffeine consumption has no adverse effect on fetal growth.

The effect of surfactant on birthweight-specific neonatal mortality rate, New York City.

PURPOSE: Surfactant has been shown to cause decreased neonatal mortality rate (NMR) in randomized studies of preterm infants. It is not clear whether the introduction of surfactant caused a decrease in neonatal mortality in a community. This study explores the hypothesis that the introduction of surfactant in 1990 to 1991 explains a decrease in neonatal mortality in New York City (NYC) among infants with birthweight of 500 to 1499 g. METHODS: For each of the 20 hospitals in New York City that began using surfactant in 1990 or 1991, we compared the NMR in the 2 years before the introduction of surfactant with the NMR in the 2 years after its introduction. Poisson regression models were fit to the death rates, adjusting for birthweight and other determinants of neonatal mortality. RESULTS: NMR in the 20 hospitals decreased by 13.7% (from 231.3 to 199.6 neonatal deaths per 1000 live births). This decrease remained significant after adjusting for birthweight and other risk factors. Infants with birthweight 1000 to 1249 grams benefited most from the introduction of surfactant; their NMR decreased by 19.6%. After adjusting for birthweight, those born before the introduction of surfactant were 1.18 times as likely to die in the first 27 days as those born after the introduction of surfactant (95% CI 1.04, 1.33). CONCLUSION: It appears that surfactant had a significant impact on NMR in NYC among very low birthweight babies.

Mutations in cartilage oligomeric matrix protein causing pseudoachondroplasia and multiple epiphyseal dysplasia affect binding of calcium and collagen I, II, and IX.

Mutations in type 3 repeats of cartilage oligomeric matrix protein (COMP) cause two skeletal dysplasias, pseudoachondroplasia (PSACH) and multiple epiphyseal dysplasia (MED). We expressed recombinant wild-type COMP that showed structural and functional properties identical to COMP isolated from cartilage. A fragment encompassing the eight type 3 repeats binds 14 calcium ions with moderate affinity and high cooperativity and presumably forms one large disulfide-bonded folding unit. A recombinant PSACH mutant COMP in which Asp-469 was deleted (D469 Delta) and a MED mutant COMP in which Asp-361 was substituted by Tyr (D361Y) were both secreted into the cell culture medium of human cells. Circular dichroism spectroscopy revealed only small changes in the secondary structures of D469 Delta and D361Y, demonstrating that the mutations do not dramatically affect the folding and stability of COMP. However, the local conformations of the type 3 repeats were disturbed, and the number of bound calcium ions was reduced to 10 and 8, respectively. In addition to collagen I and II, collagen IX also binds to COMP with high affinity. The PSACH and MED mutations reduce the binding to collagens I, II, and IX and result in an altered zinc dependence. These interactions may contribute to the development of the patient phenotypes and may explain why MED can also be caused by mutations in collagen IX genes.

Five novel mutations in fourteen patients with Fabry Disease.

Fabry disease is an X-linked disorder caused by a deficiency of the lysosomal enzyme alpha-galactosidase A. The mutations responsible for Fabry disease are diverse and include large rearrangements as well as single base substitutions, and they are dispersed throughout the seven exons of the gene. In this study, we found five novel mutations in four different exons. We have detected the mutations by the PCR-SSCP method and then analysed them by direct sequencing. Three of the novel mutations were deletions: 1205delA, 1238del26 and 5236del18. We also found one novel nonsense mutation: W162X. The final novel mutation was an insertion combined with a deletion: 10995ins24del4.

Sildenafil.

Case reports have documented the utility of sildenafil for sexual dysfunction caused by selective serotonin-reuptake inhibitors (SSRIs) and have suggested its potential utility for women and men with various iatrogenic sexual dysfunctions. This brief review summarizes the psychopharmacology of sildenafil, discusses possible interactions with SSRIs, reviews side effects and risks, highlights the need for concomitant psychological counseling, reviews sildenafil's possible mechanisms of action for iatrogenic sexual dysfunctions, and suggests areas for future research.