The DSM diagnostic criteria for female orgasmic disorder

This is the post-print version of the article. The official published version can be found at the link below.This article reviews the DSM diagnostic criteria for Female Orgasmic Disorder (FOD). Following an overview of the concept of female orgasm, research on the prevalence and associated features of FOD is briefly reviewed. Specific aspects of the DSM-IV-TR criteria for FOD are critically reviewed and key issues that should be considered for DSM-V are discussed. The DSM-IV-TR text on FOD focused on the physiological changes that may (or may not) accompany orgasm in women; one of the major recommendations here is that greater emphasis be given to the subjective aspects of the experience of orgasm. Additional specific recommendations are made for revision of diagnostic criteria, including the use of minimum severity and duration criteria, and better acknowledgment of the crucial role of relationship factors in FOD

Business networks and localization effects for new Swedish technology-based firms’ innovation performance

This study examines the business networks and localization effects for new technology-based firms (NTBFs) in the context of innovation performance (the number of patents and product differentiation). In this regard, the study includes 28 variables. A survey was conducted in 2016 with 401 Swedish NTBFs that were small and young (the employment mean was 1.80 and the average age of each firm was 28.3\ua0months). The biggest category of NTBFs was knowledge-intensive high-technology services, followed by medium high-technology manufacturing, and high-technology manufacturing. Hypotheses on how business networks and localization are related to innovation performance were tested using principal component analysis, correlation analysis, and regression analysis. The results show that the primary significant factor for innovation performance regarding business networks and localization dimensions are professional network services, while industrial and regional areas also have a positive relationship on product differentiation. Our study also shows that innovation performance enhances firms’ abilities to access external financing through professional network services (e.g., venture capital companies)

Role of Lipids in Spheroidal High Density Lipoproteins

We study the structure and dynamics of spherical high density lipoprotein (HDL) particles through coarse-grained multi-microsecond molecular dynamics simulations. We simulate both a lipid droplet without the apolipoprotein A-I (apoA-I) and the full HDL particle including two apoA-I molecules surrounding the lipid compartment. The present models are the first ones among computational studies where the size and lipid composition of HDL are realistic, corresponding to human serum HDL. We focus on the role of lipids in HDL structure and dynamics. Particular attention is paid to the assembly of lipids and the influence of lipid-protein interactions on HDL properties. We find that the properties of lipids depend significantly on their location in the particle (core, intermediate region, surface). Unlike the hydrophobic core, the intermediate and surface regions are characterized by prominent conformational lipid order. Yet, not only the conformations but also the dynamics of lipids are found to be distinctly different in the different regions of HDL, highlighting the importance of dynamics in considering the functionalization of HDL. The structure of the lipid droplet close to the HDL-water interface is altered by the presence of apoA-Is, with most prominent changes being observed for cholesterol and polar lipids. For cholesterol, slow trafficking between the surface layer and the regimes underneath is observed. The lipid-protein interactions are strongest for cholesterol, in particular its interaction with hydrophobic residues of apoA-I. Our results reveal that not only hydrophobicity but also conformational entropy of the molecules are the driving forces in the formation of HDL structure. The results provide the first detailed structural model for HDL and its dynamics with and without apoA-I, and indicate how the interplay and competition between entropy and detailed interactions may be used in nanoparticle and drug design through self-assembly

Tracking a Medically Important Spider: Climate Change, Ecological Niche Modeling, and the Brown Recluse (Loxosceles reclusa)

Most spiders use venom to paralyze their prey and are commonly feared for their potential to cause injury to humans. In North America, one species in particular, Loxosceles reclusa (brown recluse spider, Sicariidae), causes the majority of necrotic wounds induced by the Araneae. However, its distributional limitations are poorly understood and, as a result, medical professionals routinely misdiagnose brown recluse bites outside endemic areas, confusing putative spider bites for other serious conditions. To address the issue of brown recluse distribution, we employ ecological niche modeling to investigate the present and future distributional potential of this species. We delineate range boundaries and demonstrate that under future climate change scenarios, the spider's distribution may expand northward, invading previously unaffected regions of the USA. At present, the spider's range is centered in the USA, from Kansas east to Kentucky and from southern Iowa south to Louisiana. Newly influenced areas may include parts of Nebraska, Minnesota, Wisconsin, Michigan, South Dakota, Ohio, and Pennsylvania. These results illustrate a potential negative consequence of climate change on humans and will aid medical professionals in proper bite identification/treatment, potentially reducing bite misdiagnoses

DNA primase acts as a molecular brake in DNA replication

A hallmark feature of DNA replication is the coordination between the continuous polymerization of nucleotides on the leading strand and the discontinuous synthesis of DNA on the lagging strand. This synchronization requires a precisely timed series of enzymatic steps that control the synthesis of an RNA primer, the recycling of the lagging-strand DNA polymerase, and the production of an Okazaki fragment. Primases synthesize RNA primers at a rate that is orders of magnitude lower than the rate of DNA synthesis by the DNA polymerases at the fork. Furthermore, the recycling of the lagging-strand DNA polymerase from a finished Okazaki fragment to a new primer is inherently slower than the rate of nucleotide polymerization. Different models have been put forward to explain how these slow enzymatic steps can take place at the lagging strand without losing coordination with the continuous and fast leading-strand synthesis. Nonetheless, a clear picture remains elusive. Here we use single-molecule techniques to study the kinetics of a multiprotein replication complex from bacteriophage T7 and to characterize the effect of primase activity on fork progression. We observe the synthesis of primers on the lagging strand to cause transient pausing of the highly processive leading-strand synthesis. In the presence of both leading- and lagging-strand synthesis, we observe the formation and release of a replication loop on the lagging strand. Before loop formation, the primase acts as a molecular brake and transiently halts progression of the replication fork. This observation suggests a mechanism that prevents leading-strand synthesis from outpacing lagging-strand synthesis during the slow enzymatic steps on the lagging strand

Heterogeneous treatment effects of therapeutic-dose heparin in patients hospitalized for COVID-19

Importance Randomized clinical trials (RCTs) of therapeutic-dose heparin in patients hospitalized with COVID-19 produced conflicting results, possibly due to heterogeneity of treatment effect (HTE) across individuals. Better understanding of HTE could facilitate individualized clinical decision-making. Objective To evaluate HTE of therapeutic-dose heparin for patients hospitalized for COVID-19 and to compare approaches to assessing HTE. Design, Setting, and Participants Exploratory analysis of a multiplatform adaptive RCT of therapeutic-dose heparin vs usual care pharmacologic thromboprophylaxis in 3320 patients hospitalized for COVID-19 enrolled in North America, South America, Europe, Asia, and Australia between April 2020 and January 2021. Heterogeneity of treatment effect was assessed 3 ways: using (1) conventional subgroup analyses of baseline characteristics, (2) a multivariable outcome prediction model (risk-based approach), and (3) a multivariable causal forest model (effect-based approach). Analyses primarily used bayesian statistics, consistent with the original trial. Exposures Participants were randomized to therapeutic-dose heparin or usual care pharmacologic thromboprophylaxis. Main Outcomes and Measures Organ support–free days, assigning a value of −1 to those who died in the hospital and the number of days free of cardiovascular or respiratory organ support up to day 21 for those who survived to hospital discharge; and hospital survival. Results Baseline demographic characteristics were similar between patients randomized to therapeutic-dose heparin or usual care (median age, 60 years; 38% female; 32% known non-White race; 45% Hispanic). In the overall multiplatform RCT population, therapeutic-dose heparin was not associated with an increase in organ support–free days (median value for the posterior distribution of the OR, 1.05; 95% credible interval, 0.91-1.22). In conventional subgroup analyses, the effect of therapeutic-dose heparin on organ support–free days differed between patients requiring organ support at baseline or not (median OR, 0.85 vs 1.30; posterior probability of difference in OR, 99.8%), between females and males (median OR, 0.87 vs 1.16; posterior probability of difference in OR, 96.4%), and between patients with lower body mass index (BMI 90% for all comparisons). In risk-based analysis, patients at lowest risk of poor outcome had the highest propensity for benefit from heparin (lowest risk decile: posterior probability of OR >1, 92%) while those at highest risk were most likely to be harmed (highest risk decile: posterior probability of OR <1, 87%). In effect-based analysis, a subset of patients identified at high risk of harm (P = .05 for difference in treatment effect) tended to have high BMI and were more likely to require organ support at baseline. Conclusions and Relevance Among patients hospitalized for COVID-19, the effect of therapeutic-dose heparin was heterogeneous. In all 3 approaches to assessing HTE, heparin was more likely to be beneficial in those who were less severely ill at presentation or had lower BMI and more likely to be harmful in sicker patients and those with higher BMI. The findings illustrate the importance of considering HTE in the design and analysis of RCTs. Trial Registration ClinicalTrials.gov Identifiers: NCT02735707, NCT04505774, NCT04359277, NCT0437258