Anthropometrical phenotypes are important when explaining obstructive sleep apnea in female bariatric cohorts

Central obesity is the main risk factor for obstructive sleep apnea (OSA). Whether there exists a central‐obesity anthropometric that better explains apnea–hypopnea index (AHI) variability in the general population and in sleep cohorts is unknown, and this is even less explored among increasing grades of obesity. The objective of the study is to investigate whether there is an anthropometric that better explains AHI variability in a sample of morbidly obese women awaiting bariatric surgery (BS). A prospective multicentre cross‐sectional study was conducted in consecutive women before BS. Demographic and anthropometric characteristics included age, body mass index (BMI), neck circumference (NC), waist circumference (WC), hip circumference (HC) and waist‐to‐hip ratio (WHR). OSA was diagnosed by polysomnography. The capacity of anthropometrics to explain AHI variance was investigated using regression linear models. A total of 115 women were evaluated: age, 44 ± 10 years; BMI, 46 ± 5 kg/m²; AHI, 35 ± 26 events/hr. AHI was associated with all anthropometrics except weight, height and HC. The best univariate predictor was WHR, which accounted for 15% of AHI variance. The simplest model (age + BMI) accounted for 9%, which increased to 20% when applying more complex measurements (age + BMI + NC + WC + HC). The explanatory capacity did not change significantly when applying a simpler model (age + WHR + NC, 19%). In this female morbidly obese cohort, anthropometrics explained one‐fifth of AHI variability. WHR is the best univariate parameter and models including waist and neck data provide more information than BMI when explaining AHI variability. Thus, even in young women with extreme obesity, OSA seems to be linked to a specific central‐obesity phenotype rather than to a whole‐obesity pattern.     

Co-crystal of tramadol-celecoxib: preclinical and clinical evaluation of a novel analgesic

Introduction: Pain management is a major unmet need due to the suboptimal efficacy and undesirable side effects of current analgesics. Multimodal therapies recruiting complementary mechanisms of action may help address this. Co-crystals incorporating two active pharmaceutical ingredients (APIs) constitute an innovative approach to multimodal therapy, particularly if modification of the physicochemical properties of constituent APIs can be translated into clinical benefits.

Areas covered: The preclinical and clinical profiles of Co-Crystal of Tramadol-Celecoxib (CTC), a novel API–API co-crystal (1:1 molecular ratio of rac-tramadol.hydrochloride and celecoxib) are described.

Expert opinion: CTC may provide a relevant addition to pain therapy due to its: i) unique co-crystal structure conferring differentiated intrinsic dissolution profiles on constituent APIs, ii) modified clinical pharmacokinetics (slower absorption of tramadol and faster absorption of celecoxib) compared with commercially available single-entity reference products (in agreement with modified dissolution rates), iii) superior benefit–risk ratio compared with reference products (suggested by preclinical synergistic antinociceptive effects, without potentiation of adverse effects), and iv) efficacy in a phase 2 trial of moderate to severe pain following extraction of ≥2 impacted third molars requiring bone removal, where CTC doses containing low doses of APIs exerted a significant effect. Phase 3 studies are currently ongoing.     

MacroH2A – An epigenetic regulator of cancer

Epigenetic regulation is one of the most promising and expanding areas of cancer research. One of the emerging, but least understood aspects of epigenetics is the facultative and locus-specific incorporation of histone variants and their function in chromatin. With the characterization of the first loss of function phenotypes of the macroH2A histone variants, previously unrecognized epigenetic mechanisms have now moved into the spotlight of cancer research. Here, we summarize data supporting different molecular mechanisms that could mediate the primarily tumor suppressive function of macroH2A. We further discuss context-dependent and isoform-specific functions. The aim of this review is to provide guidance for those assessing macroH2A’s potential as biomarker or therapeutic intervention point.     

Violencia doméstica: preguntar para detectar

AimsTo assess whether key questions can detect domestic violence (DV), and find out the prevalence in primary care (PC) and women's care (WC).DesignIntervention Study with random assignment.LocationPC and WC clinics (Sant Boi de Llobregat Barcelona).ParticipantsSystematic random selection of women in PC (not know if battered) and women who came for the first time to the WC service. Age-matched controls were selected. A total of 400 women were interviewed.InterventionsAnamnesis was performed and a questionnaire filled in. In the control group (CG) there was one question concerning DV, in the intervention group (IG) there were 6 key questions: relationship of their parents, partner's parents, if the partner had suffered abuse, relationship with her partner, if sexual relations were consensual or got angry if they were not. When DV was detected, asked about type, features and duration.ResultsA total of 101(25.3%) cases of violence were detected, 58(29.4%) in IG and 43(21.2%) in CG (odds ratio (OR)=1.55, confidence interval (CI): 0.96–2.51, P=0.06). WC rates were 32.7% and 17.5% (OR: 2.3, CI: 1.2–4.5, P:0.007) and PC 25.3% and 25.8% (OR: 0.97, CI: 0.47–2.02, P=0.5), respectively.Different characteristics were observed depending on whether they were from PC or WC, but were similar between IG and CG, except mental disability, more common in IG.23.5% suffered from a psychiatric disorder, 15% in non-battered and 44% in the battered, in 68% of these the disorder appeared after the abuse.ConclusionsAbuse is a Public Health problem. When women visit for the first time it is necessary to use indirect questions to make communication easier, if the woman and the professional know each other, a single question is enough to detect it.     

Heritability of human cranial dimensions: comparing the evolvability of different cranial regions

Quantitative craniometrical traits have been successfully incorporated into population genetic methods to provide insight into human population structure. However, little is known about the degree of genetic and non-genetic influences on the phenotypic expression of functionally based traits. Many studies have assessed the heritability of craniofacial traits, but complex patterns of correlation among traits have been disregarded. This is a pitfall as the human skull is strongly integrated. Here we reconsider the evolutionary potential of craniometric traits by assessing their heritability values as well as their patterns of genetic and phenotypic correlation using a large pedigree-structured skull series from Hallstatt (Austria). The sample includes 355 complete adult skulls that have been analysed using 3D geometric morphometric techniques. Heritability estimates for 58 cranial linear distances were computed using maximum likelihood methods. These distances were assigned to the main functional and developmental regions of the skull. Results showed that the human skull has substantial amounts of genetic variation, and a t -test showed that there are no statistically significant differences among the heritabilities of facial, neurocranial and basal dimensions. However, skull evolvability is limited by complex patterns of genetic correlation. Phenotypic and genetic patterns of correlation are consistent but do not support traditional hypotheses of integration of the human shape, showing that the classification between brachy- and dolicephalic skulls is not grounded on the genetic level. Here we support previous findings in the mouse cranium and provide empirical evidence that covariation between the maximum widths of the main developmental regions of the skull is the dominant factor of integration in the human skull.     

Synaptic activity‐related classical protein kinase C isoform localization in the adult rat neuromuscular synapse

Protein kinase C (PKC) is essential for signal transduction in a variety of cells, including neurons and myocytes, and is involved in both acetylcholine release and muscle fiber contraction. Here, we demonstrate that the increases in synaptic activity by nerve stimulation couple PKC to transmitter release in the rat neuromuscular junction and increase the level of α, βI, and βII isoforms in the membrane when muscle contraction follows the stimulation. The phosphorylation activity of these classical PKCs also increases. It seems that the muscle has to contract in order to maintain or increase classical PKCs in the membrane. We use immunohistochemistry to show that PKCα and PKCβI were located in the nerve terminals, whereas PKCα and PKCβII were located in the postsynaptic and the Schwann cells. Stimulation and contraction do not change these cellular distributions, but our results show that the localization of classical PKC isoforms in the membrane is affected by synaptic activity. J. Comp. Neurol. 518:211–228, 2010. © 2009 Wiley‐Liss, Inc.