Splicing Machinery Is Impaired in Oral Squamous Cell Carcinomas and Linked to Key Pathophysiological Features.

Alternative splicing dysregulation is an emerging cancer hallmark, potentially serving as a source of novel diagnostic, prognostic, or therapeutic tools. Inhibitors of the activity of the splicing machinery can exert antitumoral effects in cancer cells. We aimed to characterize the splicing machinery (SM) components in oral squamous cell carcinoma (OSCC) and to evaluate the direct impact of the inhibition of SM-activity on OSCC-cells. The expression of 59 SM-components was assessed using a prospective case-control study of tumor and healthy samples from 37 OSCC patients, and the relationship with clinical and histopathological features was assessed. The direct effect of pladienolide-B (SM-inhibitor) on the proliferation rate of primary OSCC cell cultures was evaluated. A significant dysregulation in several SM components was found in OSCC vs. adjacent-healthy tissues [i.e., 12 out of 59 (20%)], and their expression was associated with clinical and histopathological features of less aggressiveness and overall survival. Pladienolide-B treatment significantly decreased OSCC-cell proliferation. Our data reveal a significantly altered expression of several SM-components and link it to pathophysiological features, reinforcing a potential clinical and pathophysiological relevance of the SM dysregulation in OSCC. The inhibition of SM-activity might be a therapeutic avenue in OSCC, offering a clinically relevant opportunity to be explored.

Altered splicing machinery in lung carcinoids unveils NOVA1, PRPF8 and SRSF10 as novel candidates to understand tumor biology and expand biomarker discovery.

BACKGROUND: Lung neuroendocrine neoplasms (LungNENs) comprise a heterogeneous group of tumors ranging from indolent lesions with good prognosis to highly aggressive cancers. Carcinoids are the rarest LungNENs, display low to intermediate malignancy and may be surgically managed, but show resistance to radiotherapy/chemotherapy in case of metastasis. Molecular profiling is providing new information to understand lung carcinoids, but its clinical value is still limited. Altered alternative splicing is emerging as a novel cancer hallmark unveiling a highly informative layer. METHODS: We primarily examined the status of the splicing machinery in lung carcinoids, by assessing the expression profile of the core spliceosome components and selected splicing factors in a cohort of 25 carcinoids using a microfluidic array. Results were validated in an external set of 51 samples. Dysregulation of splicing variants was further explored in silico in a separate set of 18 atypical carcinoids. Selected altered factors were tested by immunohistochemistry, their associations with clinical features were assessed and their putative functional roles were evaluated in vitro in two lung carcinoid-derived cell lines. RESULTS: The expression profile of the splicing machinery was profoundly dysregulated. Clustering and classification analyses highlighted five splicing factors: NOVA1, SRSF1, SRSF10, SRSF9 and PRPF8. Anatomopathological analysis showed protein differences in the presence of NOVA1, PRPF8 and SRSF10 in tumor versus non-tumor tissue. Expression levels of each of these factors were differentially related to distinct number and profiles of splicing events, and were associated to both common and disparate functional pathways. Accordingly, modulating the expression of NOVA1, PRPF8 and SRSF10 in vitro predictably influenced cell proliferation and colony formation, supporting their functional relevance and potential as actionable targets. CONCLUSIONS: These results provide primary evidence for dysregulation of the splicing machinery in lung carcinoids and suggest a plausible functional role and therapeutic targetability of NOVA1, PRPF8 and SRSF10.

The uprise of RNA biology in neuroendocrine neoplasms: altered splicing and RNA species unveil translational opportunities.

Neuroendocrine neoplasms (NENs) comprise a highly heterogeneous group of tumors arising from the diffuse neuroendocrine system. NENs mainly originate in gastrointestinal, pancreatic, and pulmonary tissues, and despite being rare, show rising incidence. The molecular mechanisms underlying NEN development are still poorly understood, although recent studies are unveiling their genomic, epigenomic and transcriptomic landscapes. RNA was originally considered as an intermediary between DNA and protein. Today, compelling evidence underscores the regulatory relevance of RNA processing, while new RNA molecules emerge with key functional roles in core cell processes. Indeed, correct functioning of the interrelated complementary processes comprising RNA biology, its processing, transport, and surveillance, is essential to ensure adequate cell homeostasis, and its misfunction is related to cancer at multiple levels. This review is focused on the dysregulation of RNA biology in NENs. In particular, we survey alterations in the splicing process and available information implicating the main RNA species and processes in NENs pathology, including their role as biomarkers, and their functionality and targetability. Understanding how NENs precisely (mis)behave requires a profound knowledge at every layer of their heterogeneity, to help improve NEN management. RNA biology provides a wide spectrum of previously unexplored processes and molecules that open new avenues for NEN detection, classification and treatment. The current molecular biology era is rapidly evolving to facilitate a detailed comprehension of cancer biology and is enabling the arrival of personalized, predictive and precision medicine to rare tumors like NENs.

Oxygenation Responses While Wearing the Elevation Training Mask During an Incremental Cycling Test.

ABSTRACT: Romero-Arenas, S, López-Pérez, E, Colomer-Poveda, D, and Márquez, G. Oxygenation responses while wearing the elevation training mask during an incremental cycling test. J Strength Cond Res 35(7): 1897-1904, 2021-The Elevation Training Mask 2.0 (ETM) is a commercial training mask that purportedly simulates altitude training, although their effects have not been conclusively demonstrated. Therefore, the purpose of this study was to evaluate the influence of wearing the ETM on muscle and brain oxygenation responses during a maximal incremental cycling test, as well as the influence of this device on the heart rate (HR) response, perception of effort (rating of perceived exertion [RPE]), arterial oxygen saturation (SaO2), blood lactate (La+), and performance (POpeak). Fourteen active males completed an incremental cycling test to volitional exhaustion in 2 separate and counterbalanced conditions, wearing the mask set at 9,000 feet (i.e., 2743 m) and a control condition (CTR, without ETM). During the trial, muscle and cerebral oxygenation were monitored continuously using near-infrared spectroscopy. Heart rate, RPE, and SaO2 were also recorded from the beginning of the test until the volitional exhaustion. La+ was measured at the end of each test. Wearing the ETM significantly reduced the POpeak by -6.9 ± 6.6% (p = 0.002) and this was accompanied by lower La+ values (-12.8 ± 21.6%; p = 0.027). SaO2 was also significantly lower at maximal intensity in comparison with the CTR condition (-1.5 ± 0.3%; p = 0.028). However, both HR and RPE showed a similar trend during both sessions, as well as muscle oxygenation. Nevertheless, the mask caused an increase in brain oxygenation compared with the CTR condition (p < 0.05). In conclusion, our findings suggest that wearing the ETM causes a pronounced increase in O2Hb and tHb in the frontoparietal cortex without any change in the muscle oxygenation.

Seminal Tenofovir Concentrations, Viral Suppression, and Semen Quality With Tenofovir Alafenamide, Compared With Tenofovir Disoproxil Fumarate (Spanish HIV/AIDS Research Network, PreEC/RIS 40).

BACKGROUND: This study assessed the penetration and efficacy of tenofovir alafenamide (TAF) in the male genital tract (MGT) and the semen quality of individuals infected with human immunodeficiency virus (HIV)-1 who were treated with a TAF-containing regimen. METHODS: This was a prospective, open-label, single-arm study of 14 virologically-suppressed, HIV-1-infected men on stable antiretroviral therapy with elvitegravir, cobicistat, emtricitabine (E/C/F) and tenofovir disoproxil fumarate (TDF) who switched to E/C/F and TAF. At baseline (pre-switch) and at 12 weeks post-switch, we measured HIV-1 RNA in seminal plasma (SP) and blood plasma (BP), tenofovir (TFV) in SP and BP, and TFV-diphosphate (dp) in peripheral blood mononuclear cells (PBMCs) and seminal mononuclear cells (SMCs) at the end of the dosing interval (C24h). Semen quality was assessed before switching and after 12 weeks on TAF. RESULTS: With TAF, TFV C24 was 11.9-fold higher in SP than in BP. This concentration was significantly lower than TFV C24 in SP with TDF, but 9.6-fold higher than the 50% inhibitory concentration (IC50) (11.5 ng/mL). By contrast, the median TFV-dp concentration achieved with TAF in SMCs was 6% that of TFV-dp in PBMCs. The TFV-dp SMC:PBMC ratio was also significantly lower with TAF. Nonetheless, TFV-dp C24 in SMC was comparable with TAF and TDF. All the patients had HIV-1 RNA <40 copies/mL in BP and SP at baseline and at 12 weeks post-switch. No significant differences were observed in semen quality between TAF and TDF. CONCLUSIONS: Extracellular and intracellular seminal TFV distribution differs between TAF and TDF. Nevertheless, both formulations, combined with elvitegravir/cobicistat/emtricitabine, maintained HIV-1 RNA suppression in semen. Differences in MGT distribution were not associated with differences in semen quality. CLINICAL TRIALS REGISTRATION: EudraCT: 2016-001371-69.

Multilayered heterogeneity as an intrinsic hallmark of neuroendocrine tumors.

Neuroendocrine tumors (NETs) comprise a complex and highly heterogeneous group of neoplasms that can arise all over the body, originating from neuroendocrine cells. NETs are characterized by a general lack of symptoms until they are in advanced phase, and early biomarkers are not as available and useful as required. Heterogeneity is an intrinsic, pivotal feature of NETs that derives from diverse causes and ultimately shapes tumor fate. The different layers that conform NET heterogeneity include a wide range of distinct characteristics, from the mere location of the tumor to its clinical and functional features, and from its cellular properties, to the core signaling and (epi)genetic components defining the molecular signature of the tumor. The importance of this heterogeneity resides in that it translates into a high variability among tumors and, hence, patients, which hinders a more precise diagnosis and prognosis and more efficacious treatment of these diseases. In this review, we highlight the significance of this heterogeneity as an intrinsic hallmark of NETs, its repercussion on clinical approaches and tumor management, and some of the possible factors associated to such heterogeneity, including epigenetic and genetic elements, post-transcriptional regulation, or splicing alterations. Notwithstanding, heterogeneity can also represent a valuable and actionable feature, towards improving medical approaches based on personalized medicine. We conclude that NETs can no longer be viewed as a single disease entity and that their diagnosis, prognosis and treatment must reflect and incorporate this heterogeneity.

[Predicting Care and Repercussions for Caregivers of Surgical Patients at Home]. / Predicción de cuidados y repercusiones en los cuidadores en el domicilio de pacientes quirúrgicos.

Objectives: To analyze the correlation between the state of health, knowledge, and social support of surgical patients' caregivers at home, with the intensity of nursing care and its consequences. Methods: A longitudinal observational study with follow-up at admission, discharge and 10 days following discharge at home, held in the surgical hospitalization unit at the Vic University Hospital, (Barcelona). A non-randomized and consecutive sample of 317 informal caregivers of surgical patients with abdominal surgery was included in the study. The characteristics of caregivers were studied using the Nursing Outcomes Classification indicators. The intensity of nursing care, consequences and impact on patient quality of life was evaluated through the validated ICUB97-R questionnaire. Results: Most of the caregivers were women, with an average age of 52,9 ± 13,7years, with no previous experience as caregivers. The greatest intensity of care and impact was observed on caregivers who attended dependent and/or cancer diagnosed patients at home, dedicating the largest time to provide care (p < 0,005). Predictor variables for the occurrence of consequences during convalescence at home were emotional health satisfaction, routine activity disruption, fear, sleep pattern and being a dependent patient. Conclusions: Emotional health satisfaction, routine activity disruption, fear, sleep pattern and being a dependent patient before surgery are strong predictive variables for the occurrence of consequences on caregivers during convalescence at home. There is a significant negative correlation between punctuations in the ICUB97-R questionnaire and the Nursing Outcomes Classification indicators.

[Medication adherence and use of health services in patients with psychosis in the region of Osona (Catalonia, Spain)]. / Adherencia al tratamiento y utilización de servicios de salud pacientes con psicosis.

OBJECTIVE: To describe and analyze sociodemographic and clinical characteristics, medication adherence and use of health resources by country of birth of psychosis diagnosed patients treated with long-term antipsychotic injectable drugs in the region of Osona (Catalonia, Spain). METHOD: Descriptive observational study in psychosis diagnosed patients over 18 years old, receiving long-term antipsychotic injectable treatment and treated at a Mental Health Center for adults in Vic (Catalonia, Spain). RESULTS: 185 patients were included, of them: 163 (88.1%) were born in Spain and 22 (17.9%) abroad. The sample was gender homogeneous with differences in age, employment status, family situation and diagnosis (p < 0.05). Findings about medication adherence to long-term antipsychotic injectable ambulatory treatment reflected good compliance in both populations. 57.7% of Spain-born patients and 9.1% of abroad-born patients received the injectable treatment at Primary Care Center (p < 0.001). The rest of them received the treatment at Mental Health Center for adults. 22 patients (711.9%) were admitted at psychiatry hospitalization ward, 16 (9.8%) of them were born in Spain and 6 (27.3%) abroad (p = 0.012). CONCLUSIONS: All patients diagnosed with psychosis, either born or not in Spain, describe good adherence to long-term antipsychotic injectable treatment, with similar use of health resources from a quantitative point of view and some differences in the type of visits.

[Surgical patients hospital home care program: two years evaluation]. / Programa de hospitalización domiciliara de pacientes quirúrgicos: evaluación de los dos años de funcionamiento.

OBJECTIVE: To evaluate the results after two years of the implementation of surgical patients' hospital home care program in Consort. Hospitalari de Vic. METHOD: Longitudinal study conducted between January 2011 and December 2012 on patients enrolled in hospital home care program patients. Sociodemographic, clinical, financial, management and patients experience variables were analysed. Data were obtained from hospital home care program records and Hospital Information Systems in addition to telephone surveys. We performed a univariate descriptive analysis using the statistical package SPSS Statistics 19. RESULTS. 691 patients were assessed, and 80.75% were included in hospital home care program. The average hospital length of stay was 5.01 days, with a 3.05% of readmission rate. A higher number of male patients were treated; patients under general surgery, orthopaedics and urology specialties were the more prevalence in the program. 82% of patients were assigned to the care plan "surgical patient", and the most recorded potential complications were pain (539) and infection (436). The mean overall satisfaction score with care was 8.67 +/- 1.37 out of 10. CONCLUSIONS: The results objectively reflect the impact of hospital home care program in our context. Moreover, it highlights the importance of the advanced nursing role.

#4Corners4Health Social Media Cancer Prevention Campaign for Emerging Adults: Protocol for a Randomized Stepped-Wedge Trial.

BACKGROUND: Many emerging adults (EAs) are prone to making unhealthy choices, which increase their risk of premature cancer morbidity and mortality. In the era of social media, rigorous research on interventions to promote health behaviors for cancer risk reduction among EAs delivered over social media is limited. Cancer prevention information and recommendations may reach EAs more effectively over social media than in settings such as health care, schools, and workplaces, particularly for EAs residing in rural areas. OBJECTIVE: This pragmatic randomized trial aims to evaluate a multirisk factor intervention using a social media campaign designed with community advisers aimed at decreasing cancer risk factors among EAs. The trial will target EAs from diverse backgrounds living in rural counties in the Four Corners states of Arizona, Colorado, New Mexico, and Utah. METHODS: We will recruit a sample of EAs (n=1000) aged 18 to 26 years residing in rural counties (Rural-Urban Continuum Codes 4 to 9) in the Four Corners states from the Qualtrics' research panel and enroll them in a randomized stepped-wedge, quasi-experimental design. The inclusion criteria include English proficiency and regular social media engagement. A social media intervention will promote guideline-related goals for increased physical activity, healthy eating, and human papillomavirus vaccination and reduced nicotine product use, alcohol intake, and solar UV radiation exposure. Campaign posts will cover digital and media literacy skills, responses to misinformation, communication with family and friends, and referral to community resources. The intervention will be delivered over 12 months in Facebook private groups and will be guided by advisory groups of community stakeholders and EAs and focus groups with EAs. The EAs will complete assessments at baseline and at 12, 26, 39, 52, and 104 weeks after randomization. Assessments will measure 6 cancer risk behaviors, theoretical mediators, and participants' engagement with the social media campaign. RESULTS: The trial is in its start-up phase. It is being led by a steering committee. Team members are working in 3 subcommittees to optimize community engagement, the social media intervention, and the measures to be used. The Stakeholder Organization Advisory Board and Emerging Adult Advisory Board were formed and provided initial input on the priority of cancer risk factors to target, social media use by EAs, and community resources available. A framework for the social media campaign with topics, format, and theoretical mediators has been created, along with protocols for campaign management. CONCLUSIONS: Social media can be used as a platform to counter misinformation and improve reliable health information to promote health behaviors that reduce cancer risks among EAs. Because of the popularity of web-based information sources among EAs, an innovative, multirisk factor intervention using a social media campaign has the potential to reduce their cancer risk behaviors. TRIAL REGISTRATION: ClinicalTrials.gov NCT05618158; https://classic.clinicaltrials.gov/ct2/show/NCT05618158. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/50392.

The Exon Junction Complex component EIF4A3 plays a splicing-linked oncogenic role in pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers, underscoring the urgent need for in-depth biological research. The phenomenon of alternative RNA splicing dysregulation is a common hallmark in cancer, including PDAC, presenting new avenues for understanding and developing diagnostic and therapeutic tools. Our research focuses on EIF4A3, a core component of the Exon Junction Complex intimately linked to RNA splicing, and its role in PDAC. EIF4A3 is overexpressed in PDAC tissue and associated to clinical parameters of malignancy and poorer patient survival. Mechanistically, exploration of PDAC RNA-seq data unveiled the link of EIF4A3 to diverse malignancy processes, consistent with its association to key molecular pathways. EIF4A3 targeting in vitro decreased essential functional tumor features such as proliferation, migration, colony formation and sphere formation, while its in vivo targeting reduced tumor growth. EIF4A3 silencing in PDAC cell lines severely altered its transcriptional and spliceosomic landscapes, as shown by RNA-seq analyses, suggesting a role for EIF4A3 in maintaining RNA homeostasis. Our results indicate that EIF4A3 dysregulation in PDAC has a pleiotropic regulatory role on RNA biology, influencing key cellular functions. This paves the way to explore its potential as novel biomarker and actionable target candidate for this lethal cancer.

Altered CELF4 splicing factor enhances pancreatic neuroendocrine tumors aggressiveness influencing mTOR and everolimus response.

Pancreatic neuroendocrine tumors (PanNETs) comprise a heterogeneous group of tumors with growing incidence. Recent molecular analyses provided a precise picture of their genomic and epigenomic landscape. Splicing dysregulation is increasingly regarded as a novel cancer hallmark influencing key tumor features. We have previously demonstrated that splicing machinery is markedly dysregulated in PanNETs. Here, we aimed to elucidate the molecular and functional implications of CUGBP ELAV-like family member 4 (CELF4), one of the most altered splicing factors in PanNETs. CELF4 expression was determined in 20 PanNETs, comparing tumor and non-tumoral adjacent tissue. An RNA sequencing (RNA-seq) dataset was analyzed to explore CELF4-linked interrelations among clinical features, gene expression, and splicing events. Two PanNET cell lines were employed to assess CELF4 function in vitro and in vivo. PanNETs display markedly upregulated CELF4 expression, which is closely associated with malignancy features, altered expression of key tumor players, and distinct splicing event profiles. Modulation of CELF4 influenced proliferation in vitro and reduced in vivo xenograft tumor growth. Interestingly, functional assays and RNA-seq analysis revealed that CELF4 silencing altered mTOR signaling pathway, enhancing the effect of everolimus. We demonstrate that CELF4 is dysregulated in PanNETs, where it influences tumor development and aggressiveness, likely by modulating the mTOR pathway, suggesting its potential as therapeutic target.

Spliceosomic dysregulation in pancreatic cancer uncovers splicing factors PRPF8 and RBMX as novel candidate actionable targets.

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal cancer, characterized by late diagnosis and poor treatment response. Surgery is the only curative approach, only available to early-diagnosed patients. Current therapies have limited effects, cause severe toxicities, and minimally improve overall survival. Understanding of splicing machinery alterations in PDAC remains incomplete. Here, we comprehensively examined 59 splicing machinery components, uncovering dysregulation in pre-mRNA processing factor 8 (PRPF8) and RNA-binding motif protein X-linked (RBMX). Their downregulated expression was linked to poor prognosis and malignancy features, including tumor stage, invasion and metastasis, and associated with poorer survival and the mutation of key PDAC genes. Experimental modulation of these splicing factors in pancreatic cancer cell lines reverted their expression to non-tumor levels and resulted in decreased key tumor-related features. These results provide evidence that the splicing machinery is altered in PDAC, wherein PRPF8 and RBMX emerge as candidate actionable therapeutic targets.

Splicing alterations in pancreatic ductal adenocarcinoma: a new molecular landscape with translational potential.

Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal cancers worldwide, mainly due to its late diagnosis and lack of effective therapies, translating into a low 5-year 12% survival rate, despite extensive clinical efforts to improve outcomes. International cooperative studies have provided informative multiomic landscapes of PDAC, but translation of these discoveries into clinical advances are lagging. Likewise, early diagnosis biomarkers and new therapeutic tools are sorely needed to tackle this cancer. The study of poorly explored molecular processes, such as splicing, can provide new tools in this regard. Alternative splicing of pre-RNA allows the generation of multiple RNA variants from a single gene and thereby contributes to fundamental biological processes by finely tuning gene expression. However, alterations in alternative splicing are linked to many diseases, and particularly to cancer, where it can contribute to tumor initiation, progression, metastasis and drug resistance. Splicing defects are increasingly being associated with PDAC, including both mutations or dysregulation of components of the splicing machinery and associated factors, and altered expression of specific relevant gene variants. Such disruptions can be a key element enhancing pancreatic tumor progression or metastasis, while they can also provide suitable tools to identify potential candidate biomarkers and discover new actionable targets. In this review, we aimed to summarize the current information about dysregulation of splicing-related elements and aberrant splicing isoforms in PDAC, and to describe their relationship with the development, progression and/or aggressiveness of this dismal cancer, as well as their potential as therapeutic tools and targets.

Spliceosomic dysregulation unveils NOVA1 as a candidate actionable therapeutic target in pancreatic neuroendocrine tumors.

Dysregulation of the splicing machinery is emerging as a hallmark in cancer due to its association with multiple dysfunctions in tumor cells. Inappropriate function of this machinery can generate tumor-driving splicing variants and trigger oncogenic actions. However, its role in pancreatic neuroendocrine tumors (PanNETs) is poorly defined. In this study we aimed to characterize the expression pattern of a set of splicing machinery components in PanNETs, and their relationship with aggressiveness features. A qPCR-based array was first deployed to determine the expression levels of components of the major (n = 13) and minor spliceosome (n = 4) and associated splicing factors (n = 27), using a microfluidic technology in 20 PanNETs and non-tumoral adjacent samples. Subsequently, in vivo and in vitro models were applied to explore the pathophysiological role of NOVA1. Expression analysis revealed that a substantial proportion of splicing machinery components was altered in tumors. Notably, key splicing factors were overexpressed in PanNETs samples, wherein their levels correlated with clinical and malignancy features. Using in vivo and in vitro assays, we demonstrate that one of those altered factors, NOVA1, is tightly related to cell proliferation, alters pivotal signaling pathways and interferes with responsiveness to drug treatment in PanNETs, suggesting a role for this factor in the aggressiveness of these tumors and its suitability as therapeutic target. Altogether, our results unveil a severe alteration of the splicing machinery in PanNETs and identify the putative relevance of NOVA1 in tumor development/progression, which could provide novel avenues to develop diagnostic biomarkers and therapeutic tools for this pathology.

[Descriptive study of the results of nursing interventions applied to surgical patients]. / Pacientes quirúrgicos e intervenciones enfermeras estandarizadas. Estudio descriptivo sobre resultados.

OBJECTIVES: Knowing the evolution of health outcomes of surgical patients during their hospital stay, evaluating NOC outcome criteria at admission and discharge. MATERIAL AND METHODS: Prospective observational study conducted in the surgical hospital wards of the Hospital General de Vic, with patients who required surgical intervention of any specialty, of 18 or more years old and anesthetic risk levels I, II or III. The main outcome variables were indicators associates with each NOC of a standard of care based on the "patient type" concept. RESULTS: Four hundred and six patients participated. Of these, 69 (15%) were operated of the musculoskeletal system and 391 (85%) were operated on the digestive or urinary systems, male/ female genitalia, skin, integuments, and endocrine system. NOC scores high of all patients were maintained or improved, never worse and in all patients the number of falls and recurrent infections was constant, virtually no patient fell or became infected. CONCLUSIONS: The majority of surgical patients at the time of hospital discharge improves or maintain their conditions of admission and patients who never worse substantially.

[Home birth. A reflection on bioethics and human rights]. / Nacer en casa. Una reflexión sobre bioética y derechos humanos.

This article discusses the situation of childbirth in general and home birth in particular from a legal perspective. Taking the context of the social, health and bioethical crisis brought about by Covid-19 as a starting point, we examine the principles that should guide birth care and analyse obstetric violence as denial of these principles. In light of abuse of medicalisation and medical interventionism, it seeks to find the best ways to humanise and dignify the care for the whole birth process. To this end, we consider the main pronouncements on the subject by international and domestic institutions and courts, as well as the case law of the European Court of Human Rights, with emphasis on rulings concerning home births, which deal with possible violations of rights and, in particular, the right to respect for private and family life.

Differences in Free-Living Patterns of Sedentary Behaviour between Office Employees with Diabetes and Office Employees without Diabetes: A Principal Component Analysis for Clinical Practice.

AIMS: To identify principal components of free-living patterns of sedentary behaviour in office employees with type 2 diabetes (T2D) compared to normal glucose metabolism (NGM) office employees, using principal component analysis (PCA). METHODS: 213 office employees (n = 81 with T2D; n = 132 with NGM) wore an activPAL inclinometer 24 h a day for 7 consecutive days. Comparions of sedentary behaviour patterns between adults with T2D and NGM determined the dimensions that best characterise the sedentary behaviour patterns of office employees with T2D at work, outside work and at weekends. RESULTS: The multivariate PCA technique identified two components that explained 60% of the variability present in the data of sedentary behaviour patterns in the population with diabetes. This was characterised by a fewer number of daily breaks and breaks in time intervals of less than 20 min both at work, outside work and at weekends. On average, adults with T2D took fewer 31 breaks/day than adults without diabetes. CONCLUSION: Effective interventions from clinical practice to tackle prolonged sedentary behaviour in office employees with T2D should focus on increasing the number of daily sedentary breaks.

Cytokines and Lymphoid Populations as Potential Biomarkers in Locally and Borderline Pancreatic Adenocarcinoma.

Despite its relative low incidence, PDAC is one of the most aggressive and lethal types of cancer, being currently the seventh leading cause of cancer death worldwide, with a 5-year survival rate of 10.8%. Taking into consideration the necessity to improve the prognosis of these patients, this research has been focused on the discovery of new biomarkers. For this purpose, patients with BL and resectable disease were recruited. Serum cytokines and growth factors were monitored at different time points using protein arrays. Immune cell populations were determined by flow cytometry in peripheral blood as well as by immunohistochemistry (IHC) in tumor tissues. Several cytokines were found to be differentially expressed between the study subgroups. In the BL disease setting, two different scores were proven to be independent prognostic factors for progression-free survival (PFS) (based on IL-10, MDC, MIF, and eotaxin-3) and OS (based on eotaxin-3, NT-3, FGF-9, and IP10). In the same context, CA19-9 was found to play a role as independent prognostic factor for OS. Eotaxin-3 and MDC cytokines for PFS, and eotaxin-3, NT-3, and CKß8-1 for OS, were shown to be predictive biomarkers for nab-paclitaxel and gemcitabine regimen. Similarly, oncostatin, BDNF, and IP10 cytokines were proven to act as predictive biomarkers regarding PFS, for FOLFIRINOX regimen. In the resectable cohort, RANTES, TIMP-1, FGF-4, and IL-10 individually differentiated patients according to their cancer-associated survival. Regarding immune cell populations, baseline high levels of circulating B lymphocytes were related to a significantly longer OS, while these levels significantly decreased as progression occurred. Similarly, baseline high levels of helper lymphocytes (CD4+), low levels of cytotoxic lymphocytes (CD8+), and a high CD4/CD8 ratio, were related to a significantly longer PFS. Finally, high levels of CD4+ and CD8+ intratumoural infiltration was associated with significantly longer PFS. In conclusion, in this study we were able to identify several prognostic and predictive biomarker candidates in patients diagnosed of resectable or BL PDAC.