Clinical effectiveness and safety of time-lapse imaging systems for embryo incubation and selection in in-vitro fertilisation treatment (TILT): a multicentre, three-parallel-group, double-blind, randomised controlled trial.

BACKGROUND: Time-lapse imaging systems for embryo incubation and selection might improve outcomes of in-vitro fertilisation (IVF) and intracytoplasmic sperm injection (ICSI) treatment due to undisturbed embryo culture conditions, improved embryo selection, or both. However, the benefit remains uncertain. We aimed to evaluate the effectiveness of time-lapse imaging systems providing undisturbed culture and embryo selection, and time-lapse imaging systems providing only undisturbed culture, and compared each with standard care without time-lapse imaging. METHODS: We conducted a multicentre, three-parallel-group, double-blind, randomised controlled trial in participants undergoing IVF or ICSI at seven IVF centres in the UK and Hong Kong. Embryologists randomly assigned participants using a web-based system, stratified by clinic in a 1:1:1 ratio to the time-lapse imaging system for undisturbed culture and embryo selection (time-lapse imaging group), time-lapse imaging system for undisturbed culture alone (undisturbed culture group), and standard care without time-lapse imaging (control group). Women were required to be aged 18-42 years and men (ie, their partners) 18 years or older. Couples had to be receiving their first, second, or third IVF or ICSI treatment and could not participate if using donor gametes. Participants and trial staff were masked to group assignment, embryologists were not. The primary outcome was live birth. We performed analyses using the intention-to-treat principle and reported the main analysis in participants with primary outcome data available (full analysis set). The trial is registered on the International Trials Registry (ISRCTN17792989) and is now closed. FINDINGS: 1575 participants were randomly assigned to treatment groups (525 participants per group) between June 21, 2018, and Sept 30, 2022. The live birth rates were 33·7% (175/520) in the time-lapse imaging group, 36·6% (189/516) in the undisturbed culture group, and 33·0% (172/522) in the standard care group. The adjusted odds ratio was 1·04 (97·5% CI 0·73 to 1·47) for time-lapse imaging arm versus control and 1·20 (0·85 to 1·70) for undisturbed culture versus control. The risk reduction for the absolute difference was 0·7 percentage points (97·5% CI -5·85 to 7·25) between the time-lapse imaging and standard care groups and 3·6 percentage points (-3·02 to 10·22) between the undisturbed culture and standard care groups. 79 serious adverse events unrelated to the trial were reported (n=28 in time-lapse imaging, n=27 in undisturbed culture, and n=24 in standard care). INTERPRETATION: In women undergoing IVF or ICSI treatment, the use of time-lapse imaging systems for embryo culture and selection does not significantly increase the odds of live birth compared with standard care without time-lapse imaging. FUNDING: Barts Charity, Pharmasure Pharmaceuticals, Hong Kong OG Trust Fund, Hong Kong Health and Medical Research Fund, Hong Kong Matching Fund.

The emotional well-being of Long COVID patients in relation to their symptoms, social support and stigmatization in social and health services: a qualitative study.

BACKGROUND: Long COVID patients have experienced a decline in their quality of life due to, in part but not wholly, its negative emotional impact. Some of the most prevalent mental health symptoms presented by long COVID patients are anxiety, depression, and sleep disorders. As such, the need has arisen to analyze the personal experiences of these patients to understand how they are managing their daily lives while dealing with the condition. The objective of this study is to increase understanding about the emotional well-being of people diagnosed with long COVID. METHODS: A qualitative design was created and carried out using 35 patients, with 17 participants being interviewed individually and 18 of them taking part in two focus groups. The participating patients were recruited in November and December 2021 from Primary Health Care (PHC) centers in the city of Zaragoza (Northern Spain) and from the Association of Long COVID Patients in Aragon. The study topics were emotional well-being, social support networks, and experience of discrimination. All an inductive thematic content analyses were performed iteratively using NVivo software. RESULTS: The Long COVID patients identified low levels of self-perceived well-being due to their persistent symptoms, as well as limitations in their daily lives that had been persistent for many months. Suicidal thoughts were also mentioned by several patients. They referred to anguish and anxiety about the future as well as a fear of reinfection or relapse and returning to work. Many of the participants reported that they have sought the help of a mental health professional. Most participants identified discriminatory situations in health care. CONCLUSIONS: It is necessary to continue researching the impact that Long COVID has had on mental health, as well as to provide Primary Health Care professionals with evidence that can guide the emotional treatment of these patients.

Early cryoprecipitate transfusion versus standard care in severe postpartum haemorrhage: a pilot cluster-randomised trial.

There is a lack of evidence evaluating cryoprecipitate transfusion in severe postpartum haemorrhage. We performed a pilot cluster-randomised controlled trial to evaluate the feasibility of a trial on early cryoprecipitate delivery in severe postpartum haemorrhage. Pregnant women (>24 weeks gestation), actively bleeding within 24 h of delivery and who required at least one unit of red blood cells were eligible. Women declining transfusion in advance or with inherited clotting deficiencies were not eligible. Four UK hospitals were randomly allocated to deliver either the intervention (administration of two pools of cryoprecipitate within 90 min of first red blood cell unit requested plus standard care), or the control group treatment (standard care, where cryoprecipitate is administered later or not at all). The primary outcome was the proportion of women who received early cryoprecipitate (intervention) vs. standard care (control). Secondary outcomes included consent rates, acceptability of the intervention, safety outcomes and preliminary clinical outcome data to inform a definitive trial. Between March 2019 and January 2020, 199 participants were recruited; 19 refused consent, leaving 180 for analysis (110 in the intervention and 70 in the control group). Adherence to assigned treatment was 32% (95%CI 23-41%) in the intervention group vs. 81% (95%CI 70-90%) in the control group. The proportion of women receiving cryoprecipitate at any time-point was higher in the intervention (60%) vs. control (31%) groups; the former had fewer red blood cell transfusions at 24 h (mean difference -0.6 units, 95%CI -1.2 to 0); overall surgical procedures (odds ratio 0.6, 95%CI 0.3-1.1); and intensive care admissions (odds ratio 0.4, 95%CI 0.1-1.1). There was no increase in serious adverse or thrombotic events in the intervention group. Staff interviews showed that lack of awareness and uncertainty about study responsibilities contributed to lower adherence in the intervention group. We conclude that a full-scale trial may be feasible, provided that protocol revisions are put in place to establish clear lines of communication for ordering early cryoprecipitate in order to improve adherence. Preliminary clinical outcomes associated with cryoprecipitate administration are encouraging and merit further investigation.

Effects of mesenchymal stem cell culture on radio sterilized human amnion or radio sterilized pig skin in burn wound healing.

Deep second and third degree burns treatment requires fibroblasts, keratinocytes and other skin cells in order to grow new dermis and epidermis. Cells can proliferate, secrete growth factors and extracellular matrix required to repair the damaged tissue. Radiosterilized human amnion and radiosterilized pig skin have been used as natural origin skin dressings for burned patients. Adipose-derived mesenchymal stem cells can differentiate into fibroblasts and keratinocytes and improve wound-healing progress. These cells can stimulate vascular tissue formation, release growth factors, synthetize new extracellular matrix and immunoregulate other cells. In this study, we developed mesenchymal stem cells-cellularized skin substitutes based from radiosterilized human amnion or pig skin. Third-degree burns were induced in mice animal models to evaluate the effect of cellularized skin substitutes on burn wound healing. Mesenchymal phenotype was immunophenotypically confirmed by flow cytometry and cell viability was close to 100%. Skin recovery was evaluated in burned mice after seven and fourteen days post-coverage with cellularized and non-cellularized sustitutes. Histological techniques and immunofluorescence were used to evaluate re-epithelization and type I collagen deposition. We determined that cellularized-human amnion or cellularized-pig skin in combination with mesenchymal stem cells improve extracellular matrix deposition. Both cellularized constructs increase detection of type I collagen in newly formed mouse skin and can be potentially used as skin coverage for further clinical treatment of burned patients.

A novel automated image analysis pipeline for quantifying morphological changes to the endoplasmic reticulum in cultured human cells.

BACKGROUND: In mammalian cells the endoplasmic reticulum (ER) comprises a highly complex reticular morphology that is spread throughout the cytoplasm. This organelle is of particular interest to biologists, as its dysfunction is associated with numerous diseases, which often manifest themselves as changes to the structure and organisation of the reticular network. Due to its complex morphology, image analysis methods to quantitatively describe this organelle, and importantly any changes to it, are lacking. RESULTS: In this work we detail a methodological approach that utilises automated high-content screening microscopy to capture images of cells fluorescently-labelled for various ER markers, followed by their quantitative analysis. We propose that two key metrics, namely the area of dense ER and the area of polygonal regions in between the reticular elements, together provide a basis for measuring the quantities of rough and smooth ER, respectively. We demonstrate that a number of different pharmacological perturbations to the ER can be quantitatively measured and compared in our automated image analysis pipeline. Furthermore, we show that this method can be implemented in both commercial and open-access image analysis software with comparable results. CONCLUSIONS: We propose that this method has the potential to be applied in the context of large-scale genetic and chemical perturbations to assess the organisation of the ER in adherent cell cultures.

Challenges for hospital management in supporting nurses to deliver humanized care.

Hospitals are paying increasing attention to the delivery of humanized care. The purpose of this study was to explore from the nursing perspective what hospital managers might do to facilitate this. A secondary analysis from a primary ethnographic study regarding dignity in nursing practice was conducted. Twenty interviews of internal medicine nurses from four hospitals were analyzed, and three main themes were identified: Management of nursing teams, Management of ethical values, and Management of the context. It is important for institutional values to be closely aligned with those of the nursing profession, and nurse managers play a key role in ensuring that the latter are applied in practice. The proposed actions offer a cost-effective framework through which nurses and managers may promote the delivery of humanized care.

Cerebellar Cognitive Affective Syndrome in Costa da Morte Ataxia (SCA36).

SCA36 is an autosomal dominant spinocerebellar ataxia (SCA) affecting many families from Costa da Morte, a northwestern region of Spain. It is caused by an intronic GGCCTG repeat expansion in NOP56. In order to characterize the cognitive and affective manifestations of this cerebellar disease, a group of 30 SCA36 mutation carriers (11 preataxic and 19 ataxic patients) were assessed with a comprehensive battery of standardized tests. Phonological verbal fluency - but not semantic fluency - was already mildly impaired in preataxic subjects. In ataxic patients, both phonological and semantic fluencies were significantly below normal. Depression, while more frequent and prominent in ataxic patients, was also often present in the preataxic stage. This is the first systematic study supporting the presence of a mild cerebellar cognitive and affective syndrome in SCA36. Routine evaluation of cognitive and emotional spheres in SCA36 patients as well as asymptomatic mutation carriers should allow early detection and timely therapeutic intervention.

Blockade of nitric oxide signalling promotes resilience to the effects of social defeat stress on the conditioned rewarding properties of MDMA in mice.

MDMA abuse continues being a serious problem in our society. Environmental factors, such as stress, increase the vulnerability of individuals to develop drug abuse and we have observed that exposure to social defeat (SD) stress alters the sensitivity of mice to the rewarding effects of MDMA in the conditioned place preference (CPP) paradigm. In the present study, we evaluated the role of the nitric oxide (NO) pathway in the effects of SD on the rewarding properties of MDMA. Three groups of mice were treated with an inhibitor of NO synthesis, 7-nitroindazole (0, 7.25 and 12.5 mg/kg), before each exposure to SD and place conditioning with MDMA (1.25 mg/kg) on PND 54, 56, 58, and 60. One control group was not exposed to SD before place conditioning. In addition, we studied the effects of SD on the levels of nitrites in the striatum, hippocampus and frontal cortex. Our results showed that the low dose of 7-nitroindazole blocked the effects of SD on the rewarding properties of MDMA. Moreover, SD exposure increased the nitrites in the prefrontal cortex and hippocampus. These results demonstrated the role of NO signalling in the effects of SD stress in mice and suggested that the inhibition of NO synthesis may confer resilience to the effects of social stress on the rewarding properties of MDMA. The manipulation of the NO signalling pathway could be a useful target for the treatment of MDMA-dependent subjects who experienced high levels of stress.

Testing against umbrella or tree orderings for binomial proportions with an adaptation of an insect resistance case.

Alternative hypotheses for order restrictions, such as umbrella or inverse umbrella (a.k.a tree) orderings, have been studied extensively in the literature, although less so when the studied response for each individual is the presence or absence of the event of interest. Two families of test statistics for solving the problem of testing against an umbrella or a tree ordering when the responses are binomial proportions are studied in this work and their asymptotic distributions are derived. A simulation study is conducted to compare the empirical power of some members of the derived families of test statistics with competing approaches. The methodology developed here was driven by an applied problem arising in stored products research where despite universal mortality in the case of doses of 1000 ppm of the insecticide phosphine, unexpected survival was noted at higher doses.

Role of NMDA and AMPA glutamatergic receptors in the effects of social defeat on the rewarding properties of MDMA in mice.

Exposure to social stress alters the response to drugs of abuse of experimental animals. Changes in the glutamatergic system seem to play a role in the effects of social defeat stress on the rewarding properties of cocaine and amphetamine. The aim of the present study was to evaluate the involvement of N-methyl-D-aspartate (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) glutamate receptors in the effects of social defeat on the conditioned place preference induced by 3,4-methylenedioxymethamphetamine (MDMA). Our hypothesis was that changes in these receptors could mediate the effects of social defeat on MDMA reward. Young adult male mice were exposed to an episode of social defeat with an aggressive conspecific immediately before each conditioning session with MDMA (1.25 mg/kg, four sessions on alternating days). According to the treatment received before defeats, six groups were used: saline, 5 or 10 mg/kg of memantine (NMDA antagonist) and 0.25, 1 or 5 mg/kg of 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) (AMPA antagonist). One control group was exposed to exploration before place conditioning. In two additional defeated and control groups, the membrane expression of NMDA and AMPA receptors was determined in the striatum and the hippocampus. Control and memantine-treated groups developed place preference, but not defeated mice treated with saline or CNQX, suggesting that the blockade of NMDA receptors reversed the effects of social defeat. Social defeat decreased the expression of several subunits of NMDA and AMPA receptors, mainly GluN1 and GluA1. These results demonstrated that glutamatergic plasticity is involved in the effects of social defeat stress on MDMA reward.

Cannabidiol Treatment Might Promote Resilience to Cocaine and Methamphetamine Use Disorders: A Review of Possible Mechanisms.

Currently, there are no approved pharmacotherapies for addiction to cocaine and other psychostimulant drugs. Several studies have proposed that cannabidiol (CBD) could be a promising treatment for substance use disorders. In the present work, the authors describe the scarce preclinical and human research about the actions of CBD on the effects of stimulant drugs, mainly cocaine and methamphetamine (METH). Additionally, the possible mechanisms underlying the therapeutic potential of CBD on stimulant use disorders are reviewed. CBD has reversed toxicity and seizures induced by cocaine, behavioural sensitization induced by amphetamines, motivation to self-administer cocaine and METH, context- and stress-induced reinstatement of cocaine and priming-induced reinstatement of METH seeking behaviours. CBD also potentiated the extinction of cocaine- and amphetamine-induced conditioned place preference (CPP), impaired the reconsolidation of cocaine CPP and prevented priming-induced reinstatement of METH CPP. Observational studies suggest that CBD may reduce problems related with crack-cocaine addiction, such as withdrawal symptoms, craving, impulsivity and paranoia (Fischer et al., 2015). The potential mechanisms involved in the protective effects of CBD on addiction to psychostimulant drugs include the prevention of drug-induced neuroadaptations (neurotransmitter and intracellular signalling pathways changes), the erasure of aberrant drug-memories, the reversion of cognitive deficits induced by psychostimulant drugs and the alleviation of mental disorders comorbid with psychostimulant abuse. Further, preclinical studies and future clinical trials are necessary to fully evaluate the potential of CBD as an intervention for cocaine and methamphetamine addictive disorders.

Femtosecond laser writing of photonic devices in borate glasses compositionally designed to be laser writable.

The design and performance of borate glass samples compositionally pre-designed to be femtosecond laser writable via laser-induced ion migration is reported in this Letter. It is demonstrated that borate glasses modified on purpose with small amounts of La2O3 and Na2O can be straightforwardly used to produce high-index contrast (Δn) waveguides by femtosecond-laser-assisted ion migration. The positive Δn of the waveguides is caused by the local enrichment of La2O3 in the guiding region with a slope of 8·10-3(mol.%)-1. The value of this is consistent with numerical aperture measurements of the waveguides and local compositional measurements at the guiding region performed by energy-dispersive x-ray micro-analysis. The maximum achievable Δn values can be controlled through the initial La2O3 content of the glass. Maximum Δn values >10-2 for samples with just 5.5 mol. % of La2O3 have been produced. This compositional design approach could be potentially used to produce highly efficient femtosecond laser writeable glasses in other glass families.

Silver-pig skin nanocomposites and mesenchymal stem cells: suitable antibiofilm cellular dressings for wound healing.

BACKGROUND: Treatment of severe or chronic skin wounds is an important challenge facing medicine and a significant health care burden. Proper wound healing is often affected by bacterial infection; where biofilm formation is one of the main risks and particularly problematic because it confers protection to microorganisms against antibiotics. One avenue to prevent bacterial colonization of wounds is the use of silver nanoparticles (AgNPs); which have proved to be effective against non-multidrug-resistant and multidrug-resistant bacteria. In addition, the use of mesenchymal stem cells (MSC) is an excellent option to improve wound healing due to their capability for differentiation and release of relevant growth factors. Finally, radiosterilized pig skin (RPS) is a biomatrix successfully used as wound dressing to avoid massive water loss, which represents an excellent carrier to deliver MSC into wound beds. Together, AgNPs, RPS and MSC represent a potential dressing to control massive water loss, prevent bacterial infection and enhance skin regeneration; three essential processes for appropriate wound healing with minimum scaring. RESULTS: We synthesized stable 10 nm-diameter spherical AgNPs that showed 21- and 16-fold increase in bacteria growth inhibition (in comparison to antibiotics) against clinical strains Staphylococcus aureus and Stenotrophomonas maltophilia, respectively. RPS samples were impregnated with different AgNPs suspensions to develop RPS-AgNPs nanocomposites with different AgNPs concentrations. Nanocomposites showed inhibition zones, in Kirby-Bauer assay, against both clinical bacteria tested. Nanocomposites also displayed antibiofilm properties against S. aureus and S. maltophilia from RPS samples impregnated with 250 and 1000 ppm AgNPs suspensions, respectively. MSC were isolated from adipose tissue and seeded on nanocomposites; cells survived on nanocomposites impregnated with up to 250 ppm AgNPs suspensions, showing 35% reduction in cell viability, in comparison to cells on RPS. Cells on nanocomposites proliferated with culture days, although the number of MSC on nanocomposites at 24 h of culture was lower than that on RPS. CONCLUSIONS: AgNPs with better bactericide activity than antibiotics were synthesized. RPS-AgNPs nanocomposites impregnated with 125 and 250 ppm AgNPs suspensions decreased bacterial growth, decreased biofilm formation and were permissive for survival and proliferation of MSC; constituting promising multi-functional dressings for successful treatment of skin wounds.

Spanish version validation of the Marihuana Motives Measure in a drug-consuming adolescent sample. / Propiedades psicométricas de la versión española del Marihuana Motives Measure en población adolescente consumidora.

INTRODUCTION: Cannabis is the illicit drug mostly widely consumed by adolescents in Spain. The understanding of consumption motives is an important factor for intervention. In Spain, there are no available instruments for their evaluation, hence, the goal of this paper is to study the psychometric properties of the Marihuana Motives Measure (MMM) in a sample of adolescent consumers. MATERIAL AND METHOD: Firstly, translation and back-translation was performed. A total of 228 adolescent consumers of cannabis were evaluated. Factorial analysis was conducted, and the reliability of the total scores and of each scale of the questionnaire was studied through Cronbach's alpha. Test-retest reliability was analyzed through interclass correlations. Validity evidence of the MMM was examined through correlations between current cannabis use, subjective consumption effects measured with the Addiction Research Center Inventory (ARCI), and personality measured with the Millon Adolescent Clinical Inventory (MACI). RESULTS: High reliability was observed in total score of the MMM (Cronbach α = .86), and high and moderate reliability for each of the five factors obtained in the factorial analysis of the MMM, Social = .82, Enhancement = .72, Coping = .83, Expansion = .74, and Conformity = .64. Significant correlations were also observed between cannabis consumption motives and subjective effects, and between consumption motives and personality. CONCLUSION: The Spanish version of the MMM shows a similar factorial structure as the one obtained by the original author, and its measures are reliable and valid for the study of cannabis consumption motives in adolescent consumer population.

Introducción: El cannabis es la sustancia ilegal que más consumen los adolescentes españoles. Entender los motivos de consumo es un factor importante para la intervención. Actualmente no existe en España un instrumento para su evaluación. El objetivo del presente trabajo es estudiar las propiedades psicométricas de la versión española del cuestionario Marihuana Motives Measure (MMM) en una población de adolescentes consumidores. Material y Métodos: Se llevó a cabo una traducción y retrotraducción del MMM. Un total de 228 adolescentes consumidores de cánnabis fueron evaluados. Se realizó un análisis factorial y se estudió la fiabilidad de la puntuación total y de cada una de las escalas del cuestionario a partir del Alfa de Cronbach. El estudio de la evidencia de validez del MMM se realizó mediante el examen de las correlaciones entre el uso actual de cánnabis, los efectos subjetivos del consumo través del cuestionario ARCI (Addiction Research Center Inventory) y la personalidad, mediante el cuestionario MACI (Millon Adolescent Clinical Inventory). Resultados: Se observó una alta fiabilidad de la puntuación total del MMM (Alfa de Cronbach= 0,86) y entre alta y moderada para cada uno de los cinco factores obtenidos al realizar el análisis factorial del MMM, Social = 0,82; Enhancement = 0,72; Coping = 0,83; Expansion = 0,74; Conformity = 0,64. Además, se observaron correlaciones significativas tanto entre motivos de consumo de cannabis y efectos subjetivos, así como entre motivos de consumo y personalidad. Conclusiones: La versión española del MMM muestra una estructura factorial similar a la obtenida por el autor original y sus medidas resultan fiables y válidas para el estudio de los motivos de consumo de cánnabis en población adolescente consumidora.

Secreted factors derived from obese visceral adipose tissue regulate the expression of breast malignant transformation genes.

BACKGROUND/OBJECTIVES: Obese adipose tissue, especially the visceral depot, exhibits altered production of several molecules that could have a role on the initiation/promotion of breast cancer development. The aim of this work was to evaluate the effect of excess adipose tissue and its secreted factors on the expression of genes involved in the early steps of tumor promotion on the mammary gland. SUBJECTS AND METHODS: Carcinogenesis-related gene expression was evaluated in mammary gland tissue from female diet-induced obese (DIO) Sprague-Dawley rats and circulating leukocytes isolated from a group of breast cancer diagnosed and non-diagnosed obese women and compared with their normal weight counterparts. In addition, the human non-tumoral mammary epithelial cell line MCF10A was treated in vitro with the visceral (retroperitoneal adipose tissue (RPAT)) or subcutaneous adipose tissue (SAT) secretome and with rising concentrations of the lipid peroxidation by-product 4-hydroxynonenal (4-HNE). RESULTS: DIO rats were classified as susceptible to DIO (DIO-S) or partially resistant to DIO (DIO-R) according to the maximum fat mass gain of the lean group as a cut-off. As compared with lean and DIO-R, the DIO-S group showed a higher fat mass and lower lean mass. The anatomical characteristic of DIO-S was correlated with differential expression of cellular proliferation (ALDH3A1 and MYC) and antioxidant and DNA protection (GSTM2, SIRT1), and tumor suppression (TP53, PTEN, TGFB1) genes. Remarkably, this carcinogenesis-related gene expression pattern was reproduced in MCF10A treated with the RPAT secretome from DIO-S rats and with the lipid peroxidation by-product 4-HNE. Moreover, this pattern was also detected in leukocytes from obese women compared with normal weight women without evidence of breast cancer. CONCLUSIONS: Lipid peroxides secreted by the obese visceral adipose tissue could be among the relevant factors that promote changes involved in the early steps of tumor development in mammary gland. These changes can be detected even before histological alterations and in circulating leukocytes.

Irisin: 'fat' or artefact.

Soon after the discovery of the muscle-derived factor irisin, a great controversy arose in the literature regarding certain inconsistencies in the regulation of the fibronectin type III domain containing 5 protein (FNDC5/irisin) after exercise, as well as the unpredicted association of circulating irisin levels with parameters of adiposity in humans. Due to these questionable findings, doubts as to the identity of the soluble portion of FNDC5 as well as the real role of irisin and its possible therapeutic applications in the treatment of obesity and diabetes have proliferated. We recently postulated that FNDC5/irisin is an adipokine expressed and secreted by white adipose tissue in rats and humans. Its circulating concentration correlates with adiposity in humans among independent cohorts of patients. Further analysis, focused on obesity-related metabolic disorders, has shown that irisin could play a role in promoting insulin resistance or act as an adaptive response to counteract disturbances in glucose and lipid homoeostasis in obesity. Overall, this leads us to raise the question whether the new factor, increased in circulation of obese patients, is really irisin-reflecting fat mass or it is an artefact. Therefore, the current review is focused on the potential participation of adipose tissue in irisin circulating levels, and the role of irisin in metabolic pathologies associated with obesity in an attempt to clarify the controversy generated by these recently published reports.

Minimally invasive spine surgery in spinal infections.

Infections of the spine have been a constant throughout history. At present there are infections in the spine fostered in part by the same advances in medicine: there are a lot of immunocompromised patients, the life expectancy of patients with chronic diseases is augmented and the increasing number of complex spinal surgeries can result in secondary infection. In this review the main types of infection of the spine and its treatment highlighting techniques in minimally invasive surgery are discussed. Spontaneous pyogenic and nonpyogenic spine infections as well as iatrogenic infections can be treated in a different manner depending on its extension, location and microorganism involved. We will review the use and the indication of percutaneous image-guided techniques, endoscopic and microsurgical techniques with or without use of tubular retractors. We conclude that techniques in minimally invasive surgery in spine infections are safe, effective and have benefits in morbidity of the approach and subsequent patient recovery.

Determinants associated with activation in patients with oral anticoagulant treatment: A cross-sectional study.

AIMS: The terms "patient activation" and "patient empowerment" are used to describe the extent to which individuals are able to manage their own healthcare. Health outcomes and quality of life improve in patients who are more active in health care. The aim of this study was to identify sociodemographic, clinical, sociological and psychological determinants associated with activation in a group of chronically anticoagulated patients. METHODS: Cross-sectional study of patients treated with oral antivitamin-k drugs attended at a specialized outpatient anticoagulant unit between November 2021 and June 2022. The main dependent variable was the level of patient activation according to the 13-item Patient Activation Measure (PAM-13). Simple and multiple linear regression models were conducted to identify the determinants associated with PAM-13 score. RESULTS: A total of 137 patients who met all the inclusion criteria were recruited for the study. The mean age was 59.6 years (SD 13.8; range 22-86) and 60.6% were male. Sixty per cent presented a level IV of activation according to the PAM-13 scale. Mean patient activation score was 73.9 (SD 15.4). The factors independently associated with significantly lower activation were: emergency department visits in the past 12 months, intermediate social risk, anxiety symptoms, stress symptoms and low self-efficacy. CONCLUSIONS: Five determinants were found to be associated with activation. Knowing the factors that modify the level of activation can help to identify subgroups of chronic anticoagulated patients who are less likely to engage in self-management and are therefore candidates for tailored educational interventions.

An Automated Imaging-Based Screen for Genetic Modulators of ER Organisation in Cultured Human Cells.

Hereditary spastic paraplegias (HSPs) are a heterogeneous group of mono-genetic inherited neurological disorders, whose primary manifestation is the disruption of the pyramidal system, observed as a progressive impaired gait and leg spasticity in patients. Despite the large list of genes linked to this group, which exceeds 80 loci, the number of cellular functions which the gene products engage is relatively limited, among which endoplasmic reticulum (ER) morphogenesis appears central. Mutations in genes encoding ER-shaping proteins are the most common cause of HSP, highlighting the importance of correct ER organisation for long motor neuron survival. However, a major bottleneck in the study of ER morphology is the current lack of quantitative methods, with most studies to date reporting, instead, on qualitative changes. Here, we describe and apply a quantitative image-based screen to identify genetic modifiers of ER organisation using a mammalian cell culture system. An analysis reveals significant quantitative changes in tubular ER and dense sheet ER organisation caused by the siRNA-mediated knockdown of HSP-causing genes ATL1 and RTN2. This screen constitutes the first attempt to examine ER distribution in cells in an automated and high-content manner and to detect genes which impact ER organisation.

Osteogenic-angiogenic coupled response of cobalt-containing mesoporous bioactive glasses in vivo.

The incorporation of cobalt ions into the composition of bioactive glasses has emerged as a strategy of interest for bone regeneration purposes. In the present work, we have designed a set of bioactive mesoporous glasses SiO2-CaO-P2O5-CoO (Co-MBGs) with different amounts of cobalt. The physicochemical changes introduced by the Co2+ ion, the in vitro effects of Co-MBGs on preosteoblasts and endothelial cells and their in vivo behaviour using them as bone grafts in a sheep model were studied. The results show that Co2+ ions neither destroy mesoporous ordering nor inhibit in vitro bioactive behaviour, exerting a dual role as network former and modifier for CoO concentrations above 3 % mol. On the other hand, the activity of Co-MBGs on MC3T3-E1 preosteoblasts and HUVEC vascular endothelial cells is dependent on the concentration of CoO present in the glass. For low Co-MBGs concentrations (1mg/ml) cell viability is not affected, while the expression of osteogenic (ALP, RUNX2 and OC) and angiogenic (VEGF) genes is stimulated. For Co-MBGs concentration of 5 mg/ml, cell viability decreases as a function of the CoO content. In vivo studies show that the incorporation of Co2+ ions to the MBGs improves the bone regeneration activity of these materials, despite the deleterious effect that this ion has on bone-forming cells for any of the Co-MBG compositions studied. This contradictory effect is explained by the marked increase in angiogenesis that takes place inside the bone defect, leading to an angiogenesis-osteogenesis coupling that compensates for the partial decrease in osteoblast cells. STATEMENT OF SIGNIFICANCE: The development of new bone grafts implies to address the need for osteogenesis-angiogenesis coupling that allows bone regeneration with viable tissue in the long term. In this sense the incorporation of cobalt ions into the composition of bioactive glasses has emerged as a strategy of great interest in this field. Due to the potential cytotoxic effect of cobalt ions, there is an important controversy regarding the suitability of their incorporation in bone grafts. In this work, we address this controversy after the implantation of cobalt-doped mesoporous bioactive glasses in a sheep model. The incorporation of cobalt ions in bioactive glasses improves the bone regeneration ability of these bone grafts, due to enhancement of the angiogenesis-osteogenesis coupling.