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This article provides information on the efficacy and safety of cemiplimab, a drug used to treat advanced cutaneous squamous cell carcinoma (CSCC). The study conducted in Spain included 83 patients who received cemiplimab treatment, with an overall response rate of 56.6% and 33.7% experiencing complete responses. The study found that the presence of distant metastasis and a higher ECOG score were associated with a worse response to treatment. The article emphasizes the need for more real-world data on cemiplimab treatment for CSCC and highlights the importance of including patients from diverse ethnic backgrounds in clinical trials. [Extracted from the article]

Background: Patients with schizophrenia die decades earlier than the general population. Among the factors involved in this mortality gap, evidence suggests a telomere length shortening in this clinical population, which is associated with premature ageing. Recent studies support the use of strength-based training exercise programmes to maintain, or even elongate, telomere length in healthy elderly populations. However, studies aiming at modifying telomere length in severe mental illnesses, such as schizophrenia, are still very scarce., Aims: To investigate the effect of a strength-based physical exercise programme on the telomere length of individuals with schizophrenia., Method: We propose a pragmatic, randomised controlled trial including 40 patients aged ≥18 years, with a stable diagnosis of schizophrenia, attending the Complejo de Rehabilitación Psicosocial (CRPS, Psychosocial Rehabilitation Centre) in Salamanca, Spain. These patients will be randomly assigned (1:1) to either receive the usual treatment and rehabilitation programmes offered by CRPS (treatment-as-usual group) or these plus twice weekly sessions of an evidence-based, strength-based training exercise programme for 12 weeks (intervention group). The primary outcome will be effect on telomere length. Secondary outcomes will include impact on cognitive function, frailty and quality of life., Results: We expect to show the importance of implementing strength-based physical exercise programmes for patients with schizophrenia. We could find that such programmes induce biological and genetic changes that may lengthen life expectancy and decrease physical fragility., Conclusions: We anticipate that our trial findings could contribute to parity of esteem for mental health, reducing premature ageing in patients with severe mental illnesses, such as schizophrenia.

Purpose: Patients with Retinitis Pigmentosa (RP) commonly experience sleep-related issues and are susceptible to stress. Moreover, variatiaons in their vision are often linked to anxiety, stress and drowsiness, indicating that stress and sleep deprivation lead to a decline in vision, and vision improves when both are mitigated. The objective of this study was to investigate the utility of salivary biomarkers as biochemical indicators of anxiety and sleep deprivation in RP patients., Methods: Seventy-eight RP patients and 34 healthy controls were included in this observational study. Anxiety and sleep-quality questionnaires, a complete ophthalmological exam for severity grading and, the collection of salivary samples from participants were assessed for participants. The activity of biomarkers was estimated by ELISA, and statistical analysis was performed to determine associations between the parameters. Associations between underlying psychological factors, grade of disease severity, and biomarkers activity were also examined., Results: Fifty-two (67%) of patients had a severe RP, and 26 (33%) had a mild-moderate grade. Fifty-eight (58,9%) patients reported severe levels of anxiety and 18 (23.,1%) a high level. Forty-six (59%) patients obtained pathological values in sleep-quality questionaries and 43 (55.1%) in sleepiness. Patients with RP exhibited significant differences in testosterone, cortisol, sTNFαRII, sIgA and melatonin as compared to controls and patients with a mild-moderate and advanced stage of disease showed greater differences. In covariate analysis, patients with a severe anxiety level also showed greater differences in mean salivary cortisol, sTNFαRII and melatonin and male patients showed lower IgA levels than female., Conclusions: The present findings suggest that salivary biomarkers could be suitable non-invasive biochemical markers for the objective assessment of sleep deprivation and anxiety in RP patients. Further research is needed to characterize the effects of untreated negative psychological states and sleep deprivation on increased variability of vision and disease progression, if any., Competing Interests: NO authors have competing interests., (Copyright: © 2024 Mateos-Olivares et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction : Chronic non-communicable diseases, including diseases of mental origin such as Alzheimer's, affect all age groups and countries. These diseases have a major impact on the patient and their family environment. It is interesting that different questionnaires are measured in the same direction, given that different health questionnaires are used to measure caregiver burden. Objectives : To identify which type of intervention is the most appropriate to improve the health of the primary caregiver in patients with dementia. To understand the role played by the nurse within multidisciplinary teams and to know whether the different questionnaires used in the studies measure caregiver health in the same direction. Methods : A systematic search of the published and gray literature was carried out without restriction of the language used in the studies. Caregiver burden of patients with dementia, receiving an intervention to improve caregiver burden, was assessed. Standardized mean difference was used as the effect size measure, and there were possible causes of heterogeneity in the effect size. Results : In total, 1512 records were found, and 39 articles with 4715 participants were included. We found individual information with an effect of 0.48 (CI95%: 0.18; 0.79; I2 = 0%); group therapy with an effect of 0.20 (CI95%: 0.08; 0.31; I2 = 6%); workshops with an effect of 0.21 (CI95%: 0.01; I2 = 48%) and 0.32 (CI95%: 0.01; 0.54; I2 = 0%) when a nurse intervenes; respite care with an effect of 0.22 (CI95%: 0.05; 0.40; I2 = 66%); individual therapy with an effect of 0.28 (CI95%: 0.15; 0.4; I2 = 68%); and support groups with an effect of 0.07 (CI95%: 0; 0.15; I2 = 78%). Conclusions : The magnitude of the effects of the interventions has been low-moderate. Different instruments are not associated with the magnitude of the effect. The presence of nurses improves the effect of the intervention on caregivers when it is carried out in the form of workshops.

Background: Physical exercise is one of the main nonpharmacological treatments for most pathologies. In addition, physical exercise is beneficial in the prevention of various diseases. The impact of physical exercise has been widely studied; however, existing meta-analyses have included diverse and heterogeneous samples. Therefore, to our knowledge, this is the first meta-analysis to evaluate the impact of different physical exercise modalities on telomere length in healthy populations., Objective: In this review, we aimed to determine the effect of physical exercise on telomere length in a healthy population through a meta-analysis of randomized controlled trials., Methods: A systematic review with meta-analysis and meta-regression of the published literature on the impact of physical exercise on telomere length in a healthy population was performed. PubMed, Cochrane Library, SCOPUS, Web of Science, and Embase databases were searched for eligible studies. Methodological quality was evaluated using the Risk Of Bias In Nonrandomized Studies of Interventions and the risk-of-bias tool for randomized trials. Finally, the certainty of our findings (closeness of the estimated effect to the true effect) was evaluated using Grading of Recommendations, Assessment, Development, and Evaluations (GRADE)., Results: We included 9 trials that met the inclusion criteria with fair methodological quality. Random-effects model analysis was used to quantify the difference in telomere length between the exercise and sham groups. Meta-analysis showed that exercise did not significantly increase telomere length compared with the control intervention (mean difference=0.0058, 95% CI -0.05 to 0.06; P=.83). Subgroup analysis suggested that high-intensity interventional exercise significantly increased telomere length compared with the control intervention in healthy individuals (mean difference=0.15, 95% CI 0.03-0.26; P=.01). Furthermore, 56% of the studies had a high risk of bias. Certainty was graded from low to very low for most of the outcomes., Conclusions: The findings of this systematic review and meta-analysis suggest that high-intensity interval training seems to have a positive effect on telomere length compared with other types of exercise such as resistance training or aerobic exercise in a healthy population., Trial Registration: PROSPERO CRD42022364518; http://tinyurl.com/4fwb85ff., (©Juan Luis Sánchez-González, Juan Luis Sánchez-Rodríguez, Sergio Varela-Rodríguez, Rogelio González-Sarmiento, Cristina Rivera-Picón, Raúl Juárez-Vela, Clara Isabel Tejada-Garrido, Javier Martín-Vallejo, Víctor Navarro-López. Originally published in JMIR Public Health and Surveillance (https://publichealth.jmir.org), 09.01.2024.)

The assessment of psoriatic arthritis is complex and multidimensional. It is increasingly common to include the patient perspective using patient-reported outcomes. Although some research has explored sleep quality in patients with psoriatic arthritis, most studies have had small sample sizes, failed to assess sleep quality considering the inflammatory process together with the psychological well-being of patients, and have not described any use of sleep medication. Further, research to date has not provided data on the relationship of sleep quality with axial forms. In this context, the objective of this study was to assess sleep quality in patients with psoriatic arthritis and its relationship with clinical characteristics, disease activity, functioning, disease impact, fatigue and psychological status. A cross-sectional study was conducted including 247 consecutive patients with PsA recruited during 2021. Sleep quality was measured using the Pittsburgh Sleep Quality Index. We assessed correlations of Pittsburgh Sleep Quality Index score with peripheral disease activity (Disease Activity Index for PSoriatic Arthritis), axial disease activity (Ankylosing Spondylitis Disease Activity Score-C-reactive protein and Bath Ankylosing Spondylitis Disease Activity Index), functioning (Bath Ankylosing Spondylitis Functional Index and Health Assessment Questionnaire), impact (Psoriatic Arthritis Impact of Disease questionnaire), anxiety, depression (Hospital Anxiety and Depression Scale) and fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue) scores. A multiple linear regression model was constructed with PSQI as the dependent variable and as independent variables those that could influence sleep quality. Nearly two-thirds (63.15%) of patients had poor sleep quality. Poorer sleep quality was associated with being female, higher joint counts, greater peripheral and axial disease activity, fatigue, anxiety and depression, functioning and disease impact (p < 0.001). Multiple linear regression analysis found that pain (β: 0.3; p < 0.007) and fatigue β: - 0.1; p < 0.001 contributed 40% to the sleep quality model. Poor sleep quality was common among patients with psoriatic arthritis. Emotional factors (fatigue, anxiety) seemed more important than inflammatory factors in sleep quality., (© 2023. The Author(s).)

Competing Interests: None disclosed.

Malignant mesenchymal tumors of the female genital tract are uncommon gynecological cancers, particularly in the vagina. They are typically aggressive and often relapse, both locally and at distant sites. The treatment of choice for primary tumors is surgical excision as they are generally refractory to chemotherapy and radiotherapy. We describe the case of a vaginal leiomyosarcoma in a 43-year-old woman who presented with abnormal genital bleeding and discharge. The tumor was excised but recurred locally after just 11 months. It was removed by hysterectomy with double adnexectomy and partial vaginal excision., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: Health-related quality of life (HRQL), pain and sleep have been described as relevant traits in patients with human immunodeficiency virus (HIV). The aim of this study is to describe and evaluate HRQL, pain and sleep and their interdependence in HIV-positive patients. Methods: A cross-sectional study on HIV-infected patients was conducted. A set of five different questionnaires was used: two questionnaires addressing HRQL (Short Form 36 [SF-36] Health Survey and Medical Outcomes Study Short Form 30 [MOS-SF 30]), one on pain (McGill Pain Questionnaire) and one on sleep (Pittsburgh Sleep Quality Index [PSQI]). We also collected the sociodemographic and clinical characteristics of patients. Results: The sample included 109 patients (age: 46.08 ± 10.49 years; 68.8% male). The pain experience was independent of HRQL and sleep. Relationships among HRQL, pain and sleep associated to sociodemographic and clinical factors were not detected (p > 0.05). Patients with CDC category A showed moderate to high correlations among HRQL, pain and sleep. In CDC B-type patients, a moderate correlation was observed between pain and mental health. In CDC C patients, moderate correlations were observed between HRQL and sleep and pain and sleep, with no correlations between HRQL and pain. Conclusions: HRQL, pain and sleep are differently correlated in HIV patients depending on their clinical stage. Neither the nadir of CD4-T cells nor the current count of CD4-T cells was found to be related with HRQL, pain or sleep.

Silicone oil (SO) still represents the main choice for long-term intraocular tamponade in complicated vitreoretinal surgery. This review compared the complications associated with the use of SO and other vitreous substitutes after pars plana vitrectomy in patients with different underlying diseases. Meta-analysis was conducted in accordance with PRISMA guidelines. We retrieved randomized clinical trials (RCTs), retrospective case-control and cohort studies evaluating the risk of using SO, published between 1994 and 2020, conducting a computer-based search of the following databases: PubMed, Web of Science, Scopus and Embase. Primary outcome was the rate of complications such as intraocular hypertension, retinal re-detachment, unexpected vision loss or hypotony. Secondary outcome was to compare the rate of adverse events of different SO viscosities, especially emulsification. Forty-three articles were included. There were significant differences in intraocular hypertension (p = 0.0002, OR = 1.66; 95% CI = 1.27-2.18) and the rate of retinal re-detachment (p < 0.0009, OR = 0.65; 95% CI = 0.50-0.64) between SO and other agents, including placebo. However, there were no differences in other complication rates. Silicone oil (SO)-emulsification rate was non-significantly higher in low than high SO viscosity, and results from other complications were comparable in both groups. The high quality of most of the studies included in this study is noteworthy, which provides some certainty to the conclusions. Among them is the high variability of the SO residence time. The fact that ocular hypertension and not hypotension is related to SO use. A clear relationship is not found for the so-called unexplained vision loss, which affects a significant percentage of eyes. Re-detachment cases are less if SO is used and that surprisingly there does not seem to be a relationship in the percentage of emulsification between the low- and high-viscosity silicones. All these data warrant more standardized prospective studies., (© 2021 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)

Background: The spread of cervical squamous cell carcinoma to the inner surface of the uterus with replacement of the endometrium is rare. Continuity of the lesion must be demonstrated to confirm superficial spread and rule out concomitant endometrial cancer., Case Presentation: We present the case of a 66-year-old white woman with superficial spreading squamous cell carcinoma of the cervix that involved the endometrium. Her relevant past history included conization of the cervix to treat cervical intraepithelial neoplasia III with positive margins. She subsequently had three negative cervical vaginal cytology results, each with a positive high-risk human papillomavirus test. Transvaginal ultrasound showed occupation of the entire uterine cavity by dense material consistent with pyometra in addition to myometrial thinning due to tension and cervical dilation. The patient presented with greenish vaginal discharge of 3 months' duration. The cervix was not visible during speculum examination. Access for endometrial sampling was not possible, raising suspicion of post-conization cervical stenosis. The patient was treated with laparoscopic hysterectomy with double adnexectomy. Histologic examination showed superficial squamous cell carcinoma invading the cervix to a depth of 2.8 mm; superficial spreading squamous cell carcinoma in situ was also observed in the lower uterine segment and endometrium. The patient was free of symptoms 12 months after surgery., Conclusions: Squamous cell carcinoma of the cervix with superficial spread to the endometrium is not included in the 2020 (fifth edition) World Health Organization Classification of Female Genital Tract Tumors or the 2018 International Federation of Gynecology and Obstetrics cervical cancer staging system. More clinical cases are needed to identify other prognostic factors and inform clinical practice guidelines on the management of this disease., (© 2022. The Author(s).)

Background: Determining predictive biomarkers for immune checkpoint inhibitors (ICIs) is a current challenge in oncology. Previous studies on non-small cell lung cancer (NSCLC) have shown how TP53 gene mutations are correlated with different responses to ICIs. Strong and diffuse immuno-expression of p53 by immunohistochemistry (IHC) is interpreted as a likely indicator of a TP53 gene mutation. We aimed to assess the p53 protein expression via IHC in NSCLC as a predictive biomarker of the response to ICIs., Methods: This was a retrospective hospital-based study of patients with NSCLC treated with Nivolumab in the University Hospital of Salamanca. All diagnostic biopsies were studied via IHC (measuring p53 protein expression, peroxidase anti-peroxidase immunohistochemistry technique using Leica BOND Polymer development kits). Survival analysis was performed by subgroups of expression of p53 and other factors using the Kaplan-Meier estimator and Cox proportional-hazards model., Results: Seventy-three patients were included (59 men and 14 women). The median age was 68 (44-84) years. Thirty-six biopsies were adenocarcinoma, 34 were squamous, and three were undifferentiated. In 41 biopsies (56.2%), the cellular expression of p53 was <5% (Group A), and in 32 biopsies (43.8%), the expression was ≥5% (Group B). In the general analysis, no differences were observed in overall survival (OS) (A: 12 months vs B: 20 months; p = 0.070) or progression-free survival (PFS) (A: 4 m vs B: 7 m; p = 0.064). Significant differences were observed in adenocarcinomas for both OS (A: 8 m vs B: median not reached; p = 0.002) and PFS (A: 3 m vs 8 m; p = 0.013). No differences in PFS and OS were observed in squamous cell carcinoma. Significant differences were observed in OS in the PD-L1 negative group (0% expression) (A: 13 m vs B: 39 m; p = 0.024), but not in PFS (A: 3 m vs B: 7 m; p = 0.70). No differences were observed in the PD-L1 positive group., Conclusions: A trend toward a greater response to ICIs was observed in the PFS and OS of patients with high expression of p53 by IHC ( TP53 mutation), especially in the PD-L1 negative adenocarcinoma subgroup. These results will make it possible to make future modifications to the clinical guidelines of NSCLC according to the expression of p53., Competing Interests: The authors declare no conflict of interest., (© 2022 The Author(s). Published by IMR Press.)

The most widely accepted etiopathogenesis hypothesis of the origin of osteoporosis and its complications is that they are a consequence of bone aging and other environmental factors, together with a genetic predisposition. Evidence suggests that oxidative stress is crucial in bone pathologies associated with aging. The aim of this study was to determine whether genetic variants in oxidative stress-related genes modified the risk of osteoporotic fracture. We analysed 221 patients and 354 controls from the HORTEGA sample after 12-14 years of follow up. We studied the genotypic and allelic distribution of 53 SNPs in 24 genes involved in oxidative stress. The results showed that being a carrier of the variant allele of the SNP rs4077561 within TXNRD1 was the principal genetic risk factor associated with osteoporotic fracture and that variant allele of the rs1805754 M6PR, rs4964779 TXNRD1, rs406113 GPX6, rs2281082 TXN2 and rs974334 GPX6 polymorphisms are important genetic risk factors for fracture. This study provides information on the genetic factors associated with oxidative stress which are involved in the risk of osteoporotic fracture and reinforces the hypothesis that genetic factors are crucial in the etiopathogenesis of osteoporosis and its complications., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Osteoporosis and obesity are major public health problems that are closely correlated, as they share various features, including a genetic predisposition. A genetic correlation between obesity and osteoporosis due to the biological common pathways of bone and fat metabolism, which implies pleiotropic genes regulating has been described. The objective of our study was to analyse whether polymorphisms in obesity-related genes modify the risk of osteoporotic bone fracture., Methods: We studied 575 subjects from the Hortega Study. The subjects were followed-up for 12-14 years. 202 subjects were overweight, 143 obese and 221 had bone fractures. The distribution of 39 genetic variants in 22 obesity-related genes were studied., Results: The results showed a relationship between polymorphisms in the FTO and NEGR1 genes and the susceptibility to osteoporotic fracture. The variant genotype of the rs2568958 NEGR1 polymorphism and the rs6499649, rs3751812, and rs8044769 genetic variants in FTO were associated with susceptibility to bone fracture. In the best of our knowledge, this is the first time that these variants in NEGR1 and FTO genes have been associated with the susceptibility to osteoporotic bone fracture, supporting the hypothesis that the NEGR1 and FTO genes might be candidates for osteoporosis and bone fracture., Conclusions: In conclusion, this study associates obesity-related polymorphisms in the NEGR1 and FTO genes with osteoporotic bone fracture, reinforcing the hypothesis that obesity and bone metabolism are closely correlated genetically., Competing Interests: The authors declare no conflict of interest. RUM and JLPC are serving as guest editors in this journal. We declare that RUM and JLPC had no involvement in the peer review of this article and has no access to information regarding its peer review. Full responsibility for the editorial process for this article was delegated to AG., (© 2022 The Author(s). Published by IMR Press.)

Background: Physical exercise is an effective measure for preventing the onset of cognitive decline and has a direct influence on the aging process. The purpose of this study was to assess the effect of a 6-month physical exercise program on cognition and telomere length in adults over 65 years of age., Method: Seventy-four healthy women were separated into two groups: 41 were included in the intervention group (IG) (72.70 ± 4.127 years and 8.18 ± 1.551 years of education) and 33 in the control group (CG) (71.21 ± 4.127 years and 8.42 ± 2.562). The participants included within the IG carried out three sessions of physical exercise per week for six months. Cognitive function was assessed using the Mini-Mental State Examination (MMSE), the Stroop test and the Trail Making Test (TMT). Saliva samples were taken and analyzed and relative telomere length was calculated. Those conducting the analysis were blind to the group to which the participants had been assigned., Results: An improvement was observed in global cognitive function, in both attentional and executive functions, in the group of adults doing physical exercise as compared to the control group. Six months after the physical exercise program had finished, relative telomere length was found to have increased in the participants in the intervention group., Conclusion: Physical exercise programs can lead to an improvement in both cognitive functions and telomere length.

Objective: VA is currently considered the treatment of choice for patients with low and very low risk prostate cancer. We analyzed the evolution of this treatment strategy in our series and adherence to the protocol., Material and Methods: Ambispective study of patients in VA in our center between 2014- 2019. 237 meet inclusion criteria, of which 142 (60%) have a minimum of 12 months of follow- up. Mean age: 68.5 (4678), median PSA 6.37 ng / ml (1-33). 229 (96.6%) are ISUP 1 and 8 (3.4%) ISUP 2. Objectives are proposed to assess our adherence to the protocol. Descriptive statistics are used to communicate the results., Results: According to the classification by risk groups of the NCCN, 145 (61.2%), 49 (20.7%) and 42 (17.7%) were very low risk, low risk and favorable intermediate risk patients, respectively. The median of follow-up is 14 months (0-66). Of the patients with a minimum follow-up of 12 months, 107 (75.4%) were re-biopsied. 80 (33.8%) leave the protocol in these 5 years, 31.3% (25) by their own decision, 55% (44) due to medical criteria, and 11.3% (9) go to WW. After 5 years of follow-up, 99.2% of patients are still alive, 0.8% died of specific non-cancer causes. Of the objectives to assess adherence, 8 are achieved, 1 partially and 1 is not evaluable., Conclusions: VA in our center is already the treatment of choice for very low-risk patients, with a constant increase from year to year. Adherence to the protocol has been favorable during the period of time studied.

The aetiology of essential hypertension is complex and involves both environmental and genetic factors. Approximately 30% of the inter-individual variability in blood pressure is genetically determined. It has been shown that numerous vasoconstrictors stimulate RhoA in local populations of vascular SMCs that, in turn, promote localised constriction of arterial blood vessels and elevations in blood pressure. The VAV3 gene encodes for VAV3 protein, a Rho GEF factor. VAV3-AS1 gene, a lncRNA, may regulate VAV3 expression. We performed an observational prospective case-control study, including patients attending in the Vascular Risk Unit from the University Hospital Salamanca for 6 months. A replication study was performed with data from The Kaiser Permanent database of the University of California. The results suggest that T allele of the VAV3 rs7528153 and G allele of the VAV3-AS1 rs11185222 polymorphisms are associated with an increased risk of developing hypertension. We hypothesise that these polymorphisms could modify blood pressure, likely through a modification in the Rho/Rac pathway. Our results suggest that those polymorphisms could be useful genetic markers of susceptibility to suffering hypertension., Competing Interests: Declaration of Competing Interest All authors declare no conflicts of interest. In the same way the correspondence author, and responsible for the article, declares no conflicts of interest., (Copyright © 2020 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

Background: Isolated fallopian tube torsion associated with hydrosalpinx is a rare condition in the pediatric population. We present this unusual clinical case study in a sexually inactive girl., Case Presentation: a12-year-old Caucasian girl presented symptoms of acute abdominal pain. Pelvic ultrasound revealed a normal looking uterus and ovaries and next to left ovary a imaging compatible with hydrosalpinx. She was discharged 48 hours later after clinical monitoring with oral analgesia and normal blood workup. At 3 weeks, she was readmitted for acute abdominal pain. Leukocytosis with left shift and raised C-reactive protein were observed. Her clinical condition worsened, and complication of the preexisting hydrosalpinx was suspected. Exploratory laparoscopy confirmed torsion of the fallopian tube. Left salpingectomy was performed. Histopathologic study confirmed a fallopian tube with hemorrhagic infarct., Conclusion: Torsion of the fallopian tube must be considered in the event of acute abdominal pain. Early diagnosis and trying conservative management with a view to preserving fertility in this group of patients are essential.

Osteoporosis is the most common bone disorder worldwide and is associated with a reduced quality of life with important clinical and economic consequences. The most widely accepted etiopathogenic hypothesis on the origin of osteoporosis and its complications is that they are a consequence of the synergic action of environmental and genetic factors. Bone is constantly being remodelled through anabolic and catabolic pathways in which inflammation, the NF-kB pathway and the renin-angiotensin-aldosterone system (RAAS) are crucial. The aim of our study was to determine whether polymorphisms in genes implicated in inflammation, the NF-kB pathway and RAAS modified the risk of osteoporotic fracture. We analysed 221 patients with osteoporotic fracture and 354 controls without fracture from the HORTEGA sample after 12-14 years of follow up. In addition, we studied the genotypic distribution of 230 single nucleotide polymorphisms (SNPs) in genes involved in inflammation, NF-kB pathway and RAAS. Our results showed that be carrier of the C allele of the rs2228145 IL6R polymorphism was the principal genetic risk factor associated with osteoporotic fracture. The results also showed that variant genotypes of the rs4762 AGT, rs4073 IL8, rs2070699 END1 and rs4291 ACE polymorphisms were important genetic risk factors for fracture. The study provides information about the genetic factors associated with inflammation, the NF-kB pathway and RAAS, which are involved in the risk of osteoporotic fracture and reinforces the hypothesis that genetic factors are crucial in the etiopathogenesis of osteoporosis and its complications., Competing Interests: Declaration of competing interest The authors report no potential conflicts of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: Dulaglutide is an agonist of "glucagon-like peptide type 1″ receptors (arGLP1). The clinical efficacy of this molecule is based on reductions in glycosylated hemoglobin (HbA1c) and weight, data shown in the pivotal AWARD studies., Methods: We propose a retrospective and multicenter study that allows evaluating the effectiveness of dulaglutide at 24 months after treatment began, under conditions of usual clinical practice, and comparing the results obtained with those that are reflected in the controlled trials., Results: The results show a reduction in the HbA1c levels -1.4% at 6 M and this reduction were maintained throughout 12 M and 24 M (p < 0.001). Plasma glucose showed significant reductions around -30 mg / dL at 6 months (p < 0.001) that remained until the end of the follow-up at 12 and 24 M, respectively. The weight decreased significantly at 6 M (p < 0.001) but continued decreasing at 12 and 24 M, showing statistically significant differences (p: 0.001)., Conclusions: Our results are similar to those obtained in pivotal clinical trials and confirm these benefits in real life., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background and Aims: Heterozygous familial hypercholesterolemia (FH) is a genetic disorder characterized by high levels of low-density lipoprotein cholesterol (LDL-C). The magnitude of atherosclerotic cardiovascular disease (ASCVD) risk in FH patients is highly variable, and this can result from genetic factors. The aim of our study was to characterize whether polymorphisms in VEGFR2 and OPG genes could influence the expression of ASCVD in FH patients., Methods: We studied 318 FH patients from the SAFEHEART registry, without clinical diagnosis of ASCVD. A coronary tomographic angiography (CTA) was performed to determine and evaluate the presence of coronary stenosis and coronary artery calcium, as measured by coronary calcium score (CCS). Genotyping of OPG rs2073618 and VEGFR2 rs2071559 polymorphisms was performed using TaqMan 5'-exonuclease allelic discrimination assays., Results: Homozygous GG genotype and G allele of VEGFR2 rs2071559 polymorphism were associated with decreased risk of developing coronary artery stenosis. In the analysis of OPG rs2073618 and VEGFR2 rs2071559 polymorphisms, according to the presence of coronary artery calcium, we found significant differences in both polymorphisms. Homozygous GG genotype and G allele of VEGFR2 rs2071559 polymorphism were associated with decreased risk of accumulation of coronary artery calcium measured by CCS in CTA. Moreover, being a carrier of the GG genotype and G allele of the OPG rs2073618 polymorphism increased the risk of the presence of coronary artery calcium measured by CCS in CTA., Conclusions: Polymorphisms in VEGFR2 and OPG genes modify the risk of ASCVD in FH patients., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Multiple-trait experiments with mixed phenotypes (binary, ordinal and continuous) are not rare in animal and plant breeding programs. However, there is a lack of statistical models that can exploit the correlation between traits with mixed phenotypes in order to improve prediction accuracy in the context of genomic selection (GS). For this reason, when breeders have mixed phenotypes, they usually analyze them using univariate models, and thus are not able to exploit the correlation between traits, which many times helps improve prediction accuracy. In this paper we propose applying deep learning for analyzing multiple traits with mixed phenotype data in terms of prediction accuracy. The prediction performance of multiple-trait deep learning with mixed phenotypes (MTDLMP) models was compared to the performance of univariate deep learning (UDL) models. Both models were evaluated using predictors with and without the genotype × environment (G×E) interaction term (I and WI, respectively). The metric used for evaluating prediction accuracy was Pearson's correlation for continuous traits and the percentage of cases correctly classified (PCCC) for binary and ordinal traits. We found that a modest gain in prediction accuracy was obtained only in the continuous trait under the MTDLMP model compared to the UDL model, whereas for the other traits (1 binary and 2 ordinal) we did not find any difference between the two models. In both models we observed that the prediction performance was better for WI than for I. The MTDLMP model is a good alternative for performing simultaneous predictions of mixed phenotypes (binary, ordinal and continuous) in the context of GS., (Copyright © 2019 Montesinos-López et al.)

Genomic selection is revolutionizing plant breeding. However, still lacking are better statistical models for ordinal phenotypes to improve the accuracy of the selection of candidate genotypes. For this reason, in this paper we explore the genomic based prediction performance of two popular machine learning methods: the Multi Layer Perceptron (MLP) and support vector machine (SVM) methods vs. the Bayesian threshold genomic best linear unbiased prediction (TGBLUP) model. We used the percentage of cases correctly classified (PCCC) as a metric to measure the prediction performance, and seven real data sets to evaluate the prediction accuracy, and found that the best predictions (in four out of the seven data sets) in terms of PCCC occurred under the TGLBUP model, while the worst occurred under the SVM method. Also, in general we found no statistical differences between using 1, 2 and 3 layers under the MLP models, which means that many times the conventional neuronal network model with only one layer is enough. However, although even that the TGBLUP model was better, we found that the predictions of MLP and SVM were very competitive with the advantage that the SVM was the most efficient in terms of the computational time required., (Copyright © 2019 Montesinos-López et al.)

Multi-trait and multi-environment data are common in animal and plant breeding programs. However, what is lacking are more powerful statistical models that can exploit the correlation between traits to improve prediction accuracy in the context of genomic selection (GS). Multi-trait models are more complex than univariate models and usually require more computational resources, but they are preferred because they can exploit the correlation between traits, which many times helps improve prediction accuracy. For this reason, in this paper we explore the power of multi-trait deep learning (MTDL) models in terms of prediction accuracy. The prediction performance of MTDL models was compared to the performance of the Bayesian multi-trait and multi-environment (BMTME) model proposed by Montesinos-López et al. (2016), which is a multi-trait version of the genomic best linear unbiased prediction (GBLUP) univariate model. Both models were evaluated with predictors with and without the genotype×environment interaction term. The prediction performance of both models was evaluated in terms of Pearson's correlation using cross-validation. We found that the best predictions in two of the three data sets were found under the BMTME model, but in general the predictions of both models, BTMTE and MTDL, were similar. Among models without the genotype×environment interaction, the MTDL model was the best, while among models with genotype×environment interaction, the BMTME model was superior. These results indicate that the MTDL model is very competitive for performing predictions in the context of GS, with the important practical advantage that it requires less computational resources than the BMTME model., (Copyright © 2018 Montesinos-López et al.)

The study of the heterogeneity of effect sizes is a key aspect of ecological meta-analyses. Here we propose a meta-analytic methodology to study the influence of moderators in effect sizes by splitting heterogeneity: meta-partition. To introduce this methodology, we performed a meta-partition of published data about the traits that influence species sensitivity to habitat loss, that have been previously analyzed through meta-regression. Thus, here we aim to introduce meta-partition and to make an initial comparison with meta-regression. Meta-partition algorithm consists of three steps. Step 1 is to study the heterogeneity of effect sizes under the assumption of fixed effect model. If heterogeneity is found, we perform step 2, that is, to partition the heterogeneity by the moderator that minimizes heterogeneity within a subset while maximizing heterogeneity between subsets. Then, if effect sizes of the subset are still heterogeneous, we repeat step 1 and 2 until we reach final subsets. Finally, step 3 is to integrate effect sizes of final subsets, with fixed effect model if there is homogeneity, and with random effects model if there is heterogeneity. Results show that meta-partition is valuable to assess the importance of moderators in explaining heterogeneity of effect sizes, as well as to assess the directions of these relations and to detect possible interactions between moderators. With meta-partition we have been able to evaluate the importance of moderators in a more objective way than with meta-regression, and to visualize the complex relations that may exist between them. As ecological issues are often influenced by several factors interacting in complex ways, ranking the importance of possible moderators and detecting possible interactions would make meta-partition a useful exploration tool for ecological meta-analyses.

Background: Clinicians should be able to weigh the role of the main risk factors associated with early implant failure., Purpose: The aim of this meta-analysis was to assess the influence of different patient-related and implant-related risk factors on the occurrence of early implant failure., Materials and Methods: In July, 2014 the main electronic databases were searched for studies reporting on early failures. Relevant papers were selected by 2 independent authors using predefined selection criteria. Three authors independently scored the included studies for quality assessment. The estimated odds ratios of the main risk factors from the selected papers were subjected to meta-analysis., Results: Nine studies were included. A total of 18,171 implants were meta-analyzed, of which 10,921 were analyzed for smoking, 15,260 for implant diameter, 16,075 for implant length, and 16,711 for implant location (maxilla vs mandible). The main significant risk factors for early implant failures were the smoking habit (odds ratio [OR], 1.7; 95% confidence interval [CI], 1.3, 2.3), implants shorter than 10 mm (OR, 1.6; 95% CI, 1.2, 2.2) and implants placed in the maxilla (OR, 1.3; 95% CI, 1.0, 1.6)., Conclusions: Clinicians should be aware of the increased risk of early failure in the presence of smokers, implants with reduced length, and implant-supported maxillary rehabilitation.