“If you can’t see a dilemma in this situation you should probably regard it as a warning”. A metasynthesis and theoretical modeling of general practitioners’ opioid prescription experiences in primary care.

Background: The prescribing of opioids has increased internationally in developed countries in recent decades within primary and secondary care.1 The majority of patients with chronic non-malignant pain (CNMP) are managed by their GP.2 Recent qualitative studies have examined the issue of opioid prescribing for chronic non-malignant pain (CNMP) from a GP viewpoint. Several factors have been reported to influence the prescribing of opioids for CNMP including aetiology of pain condition, co-morbidities, access to specialised care, history of drug abuse and professional scrutiny. We require a better understanding of problems GP’s face when making opioid prescribing decisions, interventions to provide better supports in the prescribing of opioids for CNMP. The aim of this study is to identify and synthesize the qualitative literature describing the factors influencing the nature and extent of opioid prescribing in CNMP in primary care. A theoretical model is then proposed which seeks to explain the relationship between factors influencing prescribing of opioids for CNMP by GPs. Methods: MEDLINE, Embase, PsychINFO, Cochrane Database, International Pharmaceutical Abstracts, Database of Abstracts of Reviews of Effects, CINAHL and Web of Science were systematically searched from January 1986- Feb 2018. Two reviewers independently screened titles and abstracts. Studies were excluded from the review if they were non-English language, theoretical or methodological articles, policy documents, conference abstracts or presentations, as where quotations were not clearly attributed to GPs participating in the study. The reviewers then independently assessed the full text of the articles using the Critical Appraisal Skills Programme (CASP) tool for qualitative research. The papers were coded by two researcher and these codes organised using Thematic Network Analysis. Basis themes were defined initially, organising themes were then developed followed by global themes which summarised the key theories emerging from the articles. Finally, a theoretical model was derived by the researchers using the global themes to explain the interplay between factors influencing opioid prescribing decisions. Results: From 7020 records, 18 full text papers were assessed, and 13 studies included in the synthesis; 9 were from USA, 3 from UK and 1 from Sweden. Seven organising themes were identified including trust and mistrust, the importance of aetiology, monitoring of prescription use, physical, psychological and societal harm, consultation variables, inadequate pain management, stigma and stereotypes and system barriers to effective and safe prescribing such as limited access to specialist care or support from allied healthcare professionals in primary care. Four global themes emerged;suspicion, risk, agreement and encompassing systems level factors. These global themes are inter-related and capture the complex decision-making processes underlying the opioid prescribing whereby the physician both consciously and subconsciously quantifies the risk-benefit relationship associated with initiating or continuing an opioid prescription. Conclusion: Prescribing of opioids for CNMP is influenced by a myriad of factors. Rather, than a simple risk-benefit view of the process, it is more useful to view this as a dynamic process in which unique considerations such as the morality of opioid use exert an effect. Recognising the inherent complexity of the process and the limitations of healthcare systems, guidelines directed at GPs should offer more nuanced recommendations on managing opioid prescribing consultations in primary care

Androgenetic alopecia: a review

Androgenetic alopecia, commonly known as male pattern baldness, is the most common type of progressive hair loss disorder in men. The aim of this paper is to review recent advances in understanding the pathophysiology and molecular mechanism of androgenetic alopecia.Using the PubMed database, we conducted a systematic review of the literature, selecting studies published from 1916 to 2016.The occurrence and development of androgenetic alopecia depends on the interaction of endocrine factors and genetic predisposition. Androgenetic alopecia is characterized by progressive hair follicular miniaturization, caused by the actions of androgens on the epithelial cells of genetically susceptible hair follicles in androgen-dependent areas. Although the exact pathogenesis of androgenetic alopecia remains to be clarified, research has shown that it is a polygenetic condition. Numerous studies have unequivocally identified two major genetic risk loci for androgenetic alopecia, on the X-chromosome ARa"EDA2R locus and the chromosome 20p11 locus.Candidate gene and genome-wide association studies have reported that single-nucleotide polymorphisms at different genomic loci are associated with androgenetic alopecia development. A number of genes determine the predisposition for androgenetic alopecia in a polygenic fashion. However, further studies are needed before the specific genetic factors of this polygenic condition can be fully explained

Molecular diagnosis of SARS-CoV-2 in seminal fluid

Purpose Due to relevant repercussions on reproductive medicine, we aimed to evaluate feasibility of RT-PCR as a detection method of SARS-CoV-2 RNA in seminal fluid. Methods A qualitative determination of the RT-PCR assays in semen was performed through different approaches: (1) efficiency of RNA extraction from sperm and seminal plasma was determined using PRM1 and PRM2 mRNA and a heterologous system as control; (2) samples obtained by diluting viral preparation from a SARS-CoV-2 panel (virus cultured in Vero E6 cell lines) were tested; (3) viral presence in different fractions of seminal fluid (whole sample, seminal plasma and post-centrifugation pellet) was evaluated. Semen samples from mild and recovered COVID-19 subjects were collected by patients referring to the Infectious Disease Department of the Policlinico Umberto I Hospital - "Sapienza" University of Rome. Control subjects were recruited at the Laboratory of Seminology-Sperm Bank "Loredana Gandini'' of the same hospital. Results The control panel using viral preparations diluted in saline and seminal fluid showed the capability to detect viral RNA presence with C-t values depending on the initial viral concentration. All tested semen samples were negative for SARS-CoV-2, regardless of the nasopharyngeal swab result or seminal fluid fraction. Conclusion These preliminary data show that RT-PCR for SARS-CoV-2 RNA testing appears to be a feasible method for the molecular diagnosis of SARS-CoV-2 in seminal fluid, supported by results of the control panel. The ability to detect SARS-CoV-2 in semen is extremely important for reproductive medicine, especially in assisted reproductive technology and sperm cryopreservation

Radiotherapy and palliative care outpatient clinic: a new healthcare integrated model in Italy

Background On the basis of substantial evidence demonstrate that palliative care combined with standard care improves patient, caregiver, and society outcomes, we have developed a new healthcare model called radiotherapy and palliative care (RaP) outpatient clinic were a radiation oncologist and a palliative care physician make a joint evaluation of advanced cancer patients. Methods We performed a monocentric observational cohort study on advanced cancer patients referred for evaluation at the RaP outpatient clinic. Measures of quality of care were carried out. Results Between April 2016 and April 2018, 287 joint evaluations were performed and 260 patients were evaluated. The primary tumor was lung in 31.9% of cases. One hundred fifty (52.3%) evaluations resulted in an indication for palliative radiotherapy treatment. In 57.6% of cases was used a single dose fraction of radiotherapy (8 Gy). All the irradiated cohort completed the palliative radiotherapy treatment. An 8% of irradiated patients received the palliative radiotherapy treatment in the last 30 days of life. A total of 80% of RaP patients received palliative care assistance until the end of life. Conclusion At the first descriptive analysis, the radiotherapy and palliative care model seem to respond to the need of multidisciplinary approach in order to obtain an improvement on quality of care for advanced cancer patients

Don't stand so close to me: Competitive pressures, proximity and inter-organizational collaboration

This paper investigates how geographical proximity moderates the nonmonotonic relation between niche overlap and the propensity of organizations to collaborate. The main prediction is that the strength of this relation is different for organizations with low versus high levels of geographical proximity. Proposed hypotheses are tested by using data collected within a community of hospital organizations serving more than five million residents in one of the largest Italian geographical regions. After controlling for internal resource complementarities and differences in organizational forms, behavioural orientations and institutional constraints among hospitals, this paper finds strong empirical support to the research hypotheses

"You see yourself like in a mirror”: The effects of internet-mediated personal networks on body image and eating disorders

Body image issues associated with eating disorders involve attitudinal and perceptual components: individuals’ dissatisfaction with body shape or weight, and inability to assess body size correctly. While prior research has mainly explored social pressures produced by the media, fashion, and advertising industries, this paper focuses on the effects of personal networks on body image, particularly in the context of internet communities. We use data collected on a sample of participants to websites on eating disorders, and map their personal networks. We specify and estimate a model for the joint distribution of attitudinal and perceptual components of body image as a function of network-related characteristics and attributional factors. Supported by information gathered through in-depth interviews, the empirical estimates provide evidence that personal networks can be conducive to positive body image development, and that the influence of personal networks varies significantly by body size. We situate our discussion in current debates about the effects of computer-mediated and face-to-face communication networks on eating disorders and related behaviors

5-HTR3 and 5-HTR4 located on the mitochondrial membrane and functionally regulated mitochondrial functions

5-HT has been reported to possess significant effects on cardiac activities, but activation of 5-HTR on the cell membrane failed to illustrate the controversial cardiac reaction. Because 5-HT constantly comes across the cell membrane via 5-HT transporter (5-HTT) into the cytoplasm, whether 5-HTR is functional present on the cellular organelles is unknown. Here we show 5-HTR3 and 5-HTR4 were located in cardiac mitochondria, and regulated mitochondrial activities and cellular functions. Knock down 5-HTR3 and 5-HTR4 in neonatal cardiomyocytes resulted in significant increase of cell damage in response to hypoxia, and also led to alternation in heart beating. Activation of 5-HTR4 attenuated mitochondrial Ca2+ uptake under the both normoxic and hypoxic conditions, whereas 5-HTR3 augmented Ca2+ uptake only under hypoxia. 5-HTR3 and 5-HTR4 exerted the opposite effects on the mitochondrial respiration: 5-HTR3 increased RCR (respiration control ratio), but 5-HTR4 reduced RCR. Moreover, activation of 5-HTR3 and 5-HTR4 both significantly inhibited the opening of mPTP. Our results provided the first evidence that 5-HTR as a GPCR and an ion channel, functionally expressed in mitochondria and participated in the mitochondria function and regulation to maintain homeostasis of mitochondrial [Ca2+], ROS, and ATP generation efficiency in cardiomyocytes in response to stress and O2 tension

NQO1-Dependent Redox Cycling of Idebenone: Effects on Cellular Redox Potential and Energy Levels

Short-chain quinones are described as potent antioxidants and in the case of idebenone have already been under clinical investigation for the treatment of neuromuscular disorders. Due to their analogy to coenzyme Q10 (CoQ10), a long-chain quinone, they are widely regarded as a substitute for CoQ10. However, apart from their antioxidant function, this provides no clear rationale for their use in disorders with normal CoQ10 levels. Using recombinant NAD(P)H:quinone oxidoreductase (NQO) enzymes, we observed that contrary to CoQ10 short-chain quinones such as idebenone are good substrates for both NQO1 and NQO2. Furthermore, the reduction of short-chain quinones by NQOs enabled an antimycin A-sensitive transfer of electrons from cytosolic NAD(P)H to the mitochondrial respiratory chain in both human hepatoma cells (HepG2) and freshly isolated mouse hepatocytes. Consistent with the substrate selectivity of NQOs, both idebenone and CoQ1, but not CoQ10, partially restored cellular ATP levels under conditions of impaired complex I function. The observed cytosolic-mitochondrial shuttling of idebenone and CoQ1 was also associated with reduced lactate production by cybrid cells from mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS) patients. Thus, the observed activities separate the effectiveness of short-chain quinones from the related long-chain CoQ10 and provide the rationale for the use of short-chain quinones such as idebenone for the treatment of mitochondrial disorders