State of the art of cervical cancer treatment in rare histologies.

The objective of this review is to summarize the current scientific evidence to formulate clinical recommendations regarding the classification, diagnostic approach, and treatment of rare histological subtypes of cervical cancer; neuroendocrine carcinoma, gastric-type mucinous adenocarcinoma, and glassy cell adenocarcinoma. These histological subtypes are generally characterized by their low frequency, aggressive biological behavior, certain chemoradioresistance, and consequently, high recurrence rates with a deleterious impact on survival. Molecular studies have identified several associated mutations in neuroendocrine carcinoma (PIK3CA, MYC, TP53, PTEN, ARID1A, KRAS, BRCA2) and gastric-type adenocarcinoma (KRAS, ARID1A, PTEN) that may serve as molecular targets. While adenocarcinomas are typically treated and classified based on squamous histology across early, locally advanced, and advanced stages, the treatment strategies for neuroendocrine carcinomas in early stages or locally advanced cases differ, particularly in the sequencing of administering chemotherapy, chemoradiotherapy, or surgery. The chemotherapy regimen is based on etoposide plus cisplatin (EP). Unlike squamous cell carcinomas, immune checkpoint inhibitors are yet to establish a standard role in the treatment of recurrent neuroendocrine carcinomas due to the absence of clinical trials. Regarding glassy cell adenocarcinomas and gastric-type adenocarcinoma, the potential use of immunotherapy in advanced stages/disease requires further evaluation through international collaborations, given the limited number of cases.

Methylation marks in blood DNA reveal breast cancer risk in patients fulfilling hereditary disease criteria.

Less than 15-20% of patients who meet the criteria for hereditary breast and ovarian cancer (HBOC) carry pathogenic coding genetic mutations, implying that other molecular mechanisms may contribute to the increased risk of this condition. DNA methylation in peripheral blood has been suggested as a potential epigenetic marker for the risk of breast cancer (BC). We aimed to discover methylation marks in peripheral blood associated with BC in 231 pre-treatment BC patients meeting HBOC criteria, testing negative for coding pathogenic variants, and 156 healthy controls, through methylation analysis by targeted bisulfite sequencing on 18 tumor suppressor gene promoters (330 CpG sites). We found i) hypermethylation in EPCAM (17 CpG sites; p = 0.017) and RAD51C (27 CpG sites; p = 0.048); ii) hypermethylation in 36 CpG-specific sites (FDR q < 0.05) in the BC patients; iii) four specific CpG sites were associated with a higher risk of BC (FDR q < 0.01, Bonferroni p < 0.001): cg89786999-FANCI (OR = 1.65; 95% CI:1.2-2.2), cg23652916-PALB2 (OR = 2.83; 95% CI:1.7-4.7), cg47630224-MSH2 (OR = 4.17; 95% CI:2.1-8.5), and cg47596828-EPCAM (OR = 1.84; 95% CI:1.5-2.3). Validation of cg47630224-MSH2 methylation in one Australian cohort showed an association with 3-fold increased BC risk (AUC: 0.929; 95% CI: 0.904-0.955). Our findings suggest that four DNA methylation CpG sites may be associated with a higher risk of BC, potentially serving as biomarkers in patients without detectable coding mutations.

IL-10 indirectly modulates functional activity of CD4+CD28null T-lymphocytes through LFA-3 and HLA class II inhibition.

Expansion of CD4+CD28null T-lymphocytes is common in chronic heart failure (CHF) patients. Its ability to produce high levels of proinflammatory cytokines is probably the key role of these cells in CHF. IL-10 is a candidate for limiting CD4+CD28null T-lymphocyte responses, whereas tumour necrosis factor (TNF) is the cytokine most closely involved in the loss of CD28 expression. Serum levels of TNF and IL-10 were measured in 65 CHF patients (mean age, 65.2 ± 13.84 years). Patients with an IL-10/TNF ratio ≥1 had significantly lower levels of CD4+CD28null T-lymphocytes than those with a ratio <1. In vitro, IL-10 reduced the frequency of proliferative CD4+CD28null T-lymphocytes stimulated with anti-CD3. Pre-treatment with IL-10 before anti-CD3 stimulation was required for the cytokine to inhibit TNF production by CD4+CD28null T-lymphocytes. In addition to the previously described effect of IL-10 on HLA-DR and ICAM-1 expression, LFA-3 protein and mRNA levels were reduced in the presence of the cytokine in monocytes. IL-10 inhibition on CD4+CD28null T-lymphocytes may be mediated by a reduction in HLA class II and LFA-3 expression because blocking interactions with these costimulators has similar effects to those of IL-10 treatment. Moreover, costimulation through CD2/LFA-3 interaction is enough to induce proliferation and cytokine production in CD4+CD28null T-lymphocytes.

[Translated article] Pharmaceutical care in respiratory diseases: Current situation and opportunities for hospital pharmacy in Spain.

OBJECTIVE: Respiratory diseases present a challenge for the healthcare system due to their prevalence and clinical impact. The aim of this study was to explore the current situation of hospital pharmacy in the field of respiratory diseases. METHOD: Observational, cross-sectional study, with a national scope, divided into 2 parts. In an initial phase, the activity and level of pharmaceutical care in respiratory diseases was evaluated through an online questionnaire using REDCap. The survey was addressed to department chiefs and consisted of 17 items, divided into 2 modules: general data and general activity. The second phase was open to hospital pharmacists, with the aim of exploring their opinion on care, training, and improvement needs. The number of items in this phase was 19, divided into 5 modules: general data, pharmaceutical care, competencies, training, and degree of satisfaction. RESULTS: In the first phase, 23 hospitals were included. Most of them (n=20) had a pharmacist in charge of respiratory diseases. However, a large proportion of them dedicated less than 40% of their working day to this activity. The pharmacist's activity occurred at the level of external patients (n=21), hospitalised patients (n=16), and secondarily in management (n=8). Integration is greater in pathologies such as asthma, IPF, pulmonary hypertension, and bronchiectasis. Participation in committees was present in 15 hospitals, with variability in pathologies and degree of involvement. In the second phase, 164 pharmacists participated, who considered pharmaceutical care in cystic fibrosis, asthma, and lung transplant as a priority. 51% considered integration to be adequate and 91% considered it necessary to implement prioritisation criteria. Professional competencies ranged from 6.5 to 6.9 out of 10 points. Only 45% of participants had received specific training in the last 4 years, indicating greater priority for asthma, pulmonary hypertension, and IPF. CONCLUSIONS: Most centers have pharmacists specialised in respiratory diseases. However, there is room for improvement in terms of subspecialisation, participation in multidisciplinary committees, implementation of prioritisation criteria, diversification in pathologies treated, as well as greater specific training in this area.

Pre-exposure prophylaxis program in the Community of Madrid: Two years of experience.

INTRODUCTION: Pre-exposure prophylaxis (PrEP) against the human immunodeficiency virus (HIV) is an effective and safe preventive measure. However, it has not reached all target users who could benefit from it. The study aimed to understand the sociodemographic, clinical and behavioral baseline characteristics of PrEP users. As a secondary objective, the use of concomitant medication and drug consumption were described. METHODOLOGY: Observational, retrospective and descriptive study of the sociodemographic, clinical and behavioral characteristics of the users who were included in the PrEP program of the Community of Madrid during the first two years of experience. RESULTS: Two thousand two hundred fifty-six PrEP users were included, 99.0% men, with a mean age of 36.9 years (SD 8.68). 33.1% presented a sexually transmitted infection (STI) on the first visit, highlighting chlamydiasis and rectal gonococci. 70.4% reported using drugs associated with sex, and 42.4% participated in chemsex sessions in the last 3 months. A high percentage of users with concomitant medication was observed (37.6%), highlighting drugs related to mental health and alopecia. CONCLUSIONS: A multidisciplinary approach is required to cover all the needs of PrEP users, including mental health evaluation measures and addiction treatment with the clinical approach.

Antioxidant and antimicrobial extracts from grape stalks obtained with subcritical water. Potential use in active food packaging development.

In order to valorise winemaking grape stalks, subcritical water extraction at 160 and 180 °C has been carried out to obtain phenolic-rich extracts useful for developing active food packaging materials. Red (R) and white (W) varieties (from Requena, Spain) were used, and thus, four kinds of extracts were obtained. These were characterised as to their composition, thermal stability and antioxidant and antibacterial activity. The extracts were incorporated at 6 wt% into polylactic acid (PLA) films and their effect on the optical and barrier properties of the films and their protective effect against sunflower oil oxidation was analysed. Carbohydrates were the major compounds (25-38%) in the extracts that contained 3.5-6.6% of phenolic compounds, the R extracts being the richest, with higher radical scavenging capacity. Every extract exhibited antibacterial effect against Escherichia coli and Listeria innocua, while PLA films with extracts preserved sunflower oil against oxidation.

Clinical Comparative Study of Shade Measurement Using Two Methods: Dental Guides and Spectrophotometry.

Tooth color is a determining factor in the fabrication of dental prostheses. The aim of the present study is to compare two measurement methods used in the field of dentistry: dental guides and spectrophotometry. A total of 2768 natural teeth were measured using the Vita Classical and Vita 3D-Master dental guides (Vita-Zahnfabrik, Bad Säckingen, Germany), as well as a Vita Easyshade Compact spectrophotometer (Vita-Zahnfabrik). The measurements were carried out by one operator under suitable illumination conditions at 5500 degrees Kelvin. The obtained results show that the measurements obtained with the Vita Classical dental guide classifies teeth into the A-B categories, while the spectrophotometer preferentially classifies teeth into the B-C categories. The correlation coefficients obtained with the dental guides ranged from -0.32 to -0.39 (p < 0.01), while those for the spectrophotometer ranged from -0.35 to -0.55 (p < 0.01). Therefore, we can conclude that the spectrophotometer is more reliable and reproducible in its measurements than the dental guides.

Pharmaceutical care in respiratory diseases: Current situation and opportunities for Hospital Pharmacy in Spain. / Atención farmacéutica en enfermedades respiratorias: situación y oportunidades de la farmacia hospitalaria en España.

OBJECTIVE: Respiratory diseases present a challenge for the healthcare system due to their prevalence and clinical impact. The aim of this study was to explore the current situation of hospital pharmacy in the field of respiratory diseases. METHOD: Observational, cross-sectional study, with a national scope, divided into 2 parts. In an initial phase, the activity and level of pharmaceutical care in respiratory diseases was evaluated through an online questionnaire using REDCap. The survey was addressed to department chiefs and consisted of 17 items, divided into 2 modules: general data and general activity. The second phase was open to hospital pharmacists, with the aim of exploring their opinion on care, training, and improvement needs. The number of items in this phase was 19, divided into 5 modules: general data, pharmaceutical care, competencies, training and degree of satisfaction. RESULTS: In the first phase, 23 hospitals were included. Most of them (n=20) had a pharmacist in charge of respiratory diseases. However, a large proportion of them dedicated less than 40% of their working day to this activity. The pharmacist's activity occurred at the level of external patients (n=20), hospitalized patients (n=16), and secondarily in management (n=8). Integration is greater in pathologies such as asthma, IPF, pulmonary hypertension, and bronchiectasis. Participation in committees was present in 15 hospitals, with variability in pathologies and degree of involvement. In the second phase, 164 pharmacists participated, who considered pharmaceutical care in cystic fibrosis, asthma and lung transplant as a priority. Fifty-one percent considered integration to be adequate and 91% considered it necessary to implement prioritization criteria. Professional competencies ranged from 6.5-6.9 out of 10 points. Only 45% of participants had received specific training in the last four years, indicating greater priority for asthma, pulmonary hypertension and IPF. CONCLUSIONS: Most centers have pharmacists specialized in respiratory diseases. However, there is room for improvement in terms of sub specialization, participation in multidisciplinary committees, implementation of prioritization criteria, diversification in pathologies treated, as well as greater specific training in this area.

Exploring the intersection of gender identity and homoparental family structure: Implications for educational, family and personal well-being in Spanish students.

This study explores the relationship among self-perceived gender, family type (heteroparental or homoparental) and socioeconomic factors concerning various educational, family and personal well-being domains. The data are derived from a large sample of 69,088 students from 465 schools (65% public; 35% private or semi-private) in Spain. Five separate multi-level generalized mixed (logistic or linear) regression models were calculated. Key findings include that non-binary students from homoparental families reported lower evaluations in multiple dimensions, suggesting the need for additional support. Likewise, students from homoparental families exhibited lower personal well-being and family relationship assessments, possibly due to perceived social stigmatization and peer bullying. This study sheds light on the complexities of gender identity and family type in educational settings, emphasizing the importance of addressing these issues for students' well-being and academic success.

Preoperative MRSA screening using a simple questionnaire prior elective total joint replacement.

INTRODUCTION: The purpose of this study was to evaluate the management and results of our standarized protocol for preoperative identification of MRSA colonisation in patients undergoing primary total hip and knee replacement procedures. METHODS: Following hospital protocol, between January 2016 and June 2019 37,745 patients awaiting elective joint replacement underwent a standardized questionnaire to assess the risk of MRSA infection, identifying patients requiring preoperative MRSA screening. An evaluation of the questionnaire identified effective questions for identifying infected patients. Furthermore, an analysis evaluated the impact of comorbidities or Charlson Comorbidity Index scores on positive MRSA colonization. Additionally, we evaluated the cost savings of targeted testing compared to testing all surgery patients. RESULTS: Of the 37,745 patients, 8.057 (21.3%) were swabbed, with a total of 65 (0.81%) positive tests. From this group 27 (36.48%) who were treated were negative before surgery. Some of the questionnaire results were consistently associated with a higher chance of colonization, including hospitalization during the past year (47,7%), previous history of MRSA (44,6%), and agriculture or cattle farming related work (15,4%). By selectively testing high-risk patients identified through the questionnaire, we achieved a 79% reduction in costs compared to universal MRSA screening. CONCLUSION: Our results suggest that the simple and standardized questionnaire is a valuable tool for preoperative screening, effectively identifying high-risk patients prone to MRSA colonisation. The risk of periprosthetic joint infection (PJI) and its associated sequelae may be reduced by this approach.

ANCUT1, a novel thermoalkaline cutinase from Aspergillus nidulans and its application on hydroxycinnamic acids lipophilization.

One of the four cutinases encoded in the Aspergillus nidulans genome, ANCUT1, is described here. Culture conditions were evaluated, and it was found that this enzyme is produced only when cutin is present in the culture medium, unlike the previously described ANCUT2, with which it shares 62% amino acid identity. The differences between them include the fact that ANCUT1 is a smaller enzyme, with experimental molecular weight and pI values of 22 kDa and 6, respectively. It shows maximum activity at pH 9 and 60 °C under assayed conditions and retains more than 60% of activity after incubation for 1 h at 60 °C in a wide range of pH values (6-10) after incubations of 1 or 3 h. It has a higher activity towards medium-chain esters and can modify long-chain length hydroxylated fatty acids constituting cutin. Its substrate specificity properties allow the lipophilization of alkyl coumarates, valuable antioxidants and its thermoalkaline behavior, which competes favorably with other fungal cutinases, suggests it may be useful in many more applications.

Single-cell analysis of the epitranscriptome: RNA modifications under the microscope.

The identification of mechanisms capable of modifying genetic information by the addition of covalent RNA modifications distinguishes a level of complexity in gene expression which challenges key long-standing concepts of RNA biology. One of the current challenges of molecular biology is to properly understand the molecular functions of these RNA modifications, with more than 170 different ones having been identified so far. However, it has not been possible to map specific RNA modifications at a single-cell resolution until very recently. This review will highlight the technological advances in single-cell methodologies aimed at assessing and testing the biological function of certain RNA modifications, focusing on m6A. These advances have allowed for the development of novel strategies that enable the study of the 'epitranscriptome'. Nevertheless, despite all these improvements, many challenges and difficulties still need fixing for these techniques to work efficiently.

Efficacy of amoxicillin/clavulanic acid after surgical drainage of perianal abscess in the prevention of the development of anal fistula (PERIQxA study): study protocol for a multicenter randomized, double-blind clinical trial.

BACKGROUND: Anorectal fistula, which is a relatively common pathology, is the chronic manifestation of the acute perirectal process that forms an anal abscess. The development of a fistula after incision and drainage of an anal abscess is seen in approximately 26-37%. Its treatment is a relevant topic, and the role of the use of antibiotic therapy in its prevention remains controversial, after the publication of several studies with contradictory results and several methodological limitations. Our hypothesis is that the combination of amoxicillin and clavulanic acid will reduce the incidence of anal fistula. METHOD: The aim of this study is to evaluate the efficacy of antibiotherapy after surgical drainage of perianal abscess in the development of perianal fistula. The PERIQxA study is a multicenter, randomized, double-blind controlled trial. The study has been designed to include 286 adult patients who will be randomly (1:1) assigned to either the experimental (amoxicillin/clavulanic acid 875/125 mg TDS for 7 days) or the control arm (placebo). The primary outcome measure is the percentage of patients that develop perianal fistula after surgery and during follow-up (6 months). DISCUSSION: This clinical trial is designed to evaluate the efficacy and safety of amoxicillin/clavulanic in the prevention of perianal fistula. The results of this study are expected to contribute to stablish the potential role of antibiotherapy in the therapeutics for anal abscess. TRIAL REGISTRATION: EudraCT Number: 2021-003376-14. Registered on November 26, 2021.

Gastric inflammatory myofibroblastic tumor, a rare mesenchymal neoplasm: A case report.

BACKGROUND: The inflammatory myofibroblastic tumor (IMT) is a rare mesenquimal tumor of doubtful biological behaviour. It's characterised for affecting mainly children and young adults, although it can appear at any age, being the lungs the primary affected organ (in children it represents 20% of all primary pulmonary tumors). CASE SUMMARY: We present the case of a 45 year old woman, with a computed tomography (CT) finding of injury on the anterior surface of the fundus/gastric body and a solid perigastric injury of 12 mm in the ecoendoscopy. The case is presented in the tumor committee deciding to perform a laparoscopic wedge resection. The histological diagnosis was a IMT. The diagnosis is based on imaging tests like the abdominal CT, abdominal ecography and the ecoendoscopy but to confirm the diagnosis a pathological study is necessary. CONCLUSION: Due to the unpredictable nature of this tumor, surgical resection is the best therapeutic option.

Study protocol: assessment of the usefulness and practicability of a psychoeducational intervention to prevent the negative psychological impact of the COVID-19 pandemic on primary care health workers.

BACKGROUND: The COVID-19 pandemic has constituted an extraordinarily stressful situation for healthcare professionals and has led to psychological distress and an increase in various mental disorders. In the post-pandemic context, it is necessary to provide professionals with strategies and skills to manage this stressful situation and prevent or minimize its negative impact. METHODS: Aims: To assess the feasibility and clinical effects of a group psychoeducational program focused on preventing the adverse psychological and emotional effects of the pandemic on primary care workers, and to explore the experience and perceptions of participants with regard to the program from a qualitative perspective. DESIGN: A single-arm, before-and-after study conducted in primary care. SETTING: The 332 primary care centers of the Catalan Institute of Health (Catalonia, Spain) Participants: The target population of the intervention is primary care workers, including clinical profiles (e.g., nurses and doctors), and non-clinical profiles (e.g., administrative staff). The implementation strategy will also involve community psychologists, who will lead the psychoeducational groups, and the health organization promoting the implementation. INTERVENTION: A group psychoeducational program targeting primary care workers to promote emotional well-being and the ability to cope with stressful situations. Community psychologists will deliver it in the primary care centers they are linked to. MEASURES: Mixed-methods evaluation, combining quantitative and qualitative research. A prospective assessment of the main outcomes (professional quality of life, psychological state, and resilience) will be performed using online questionnaires before and immediately after the intervention, and at 3 and 6 months. A qualitative study will be conducted, comprising focus groups and individual in-depth interviews with the participants in the intervention and the psychologists who provide it. ETHICS: The Research Ethics Committee of the Jordi Gol Primary Care Research Institute (IDIAP) has approved the protocol (22/086-PCV). DISCUSSION: This project proposes an intervention to promote mental health and psychological well-being in primary care workers by learning skills and integrating them into personal and professional life. The expected results will allow us to determine the usefulness and effectiveness of this psychoeducational intervention under the conditions of real clinical practice, provide data to model and perfect it, and promote its dissemination. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05720429; registered on 09/02/2023.

Development and Characterization of Thermoformed Bilayer Trays of Paper and Renewable Succinic Acid Derived Biopolyester Blends and Their Application to Preserve Fresh Pasta.

The present study reports on the development by thermoforming of highly sustainable trays based on a bilayer structure composed of paper substrate and a film made of a blend of partially bio-based poly(butylene succinate) (PBS) and poly(butylene succinate-co-adipate) (PBSA). The incorporation of the renewable succinic acid derived biopolyester blend film slightly improved the thermal resistance and tensile strength of paper, whereas its flexural ductility and puncture resistance were notably enhanced. Furthermore, in terms of barrier properties, the incorporation of this biopolymer blend film reduced the water and aroma vapor permeances of paper by two orders of magnitude, while it endowed the paper structure with intermediate oxygen barrier properties. The resultant thermoformed bilayer trays were, thereafter, originally applied to preserve non-thermally treated Italian artisanal fresh pasta, "fusilli calabresi" type, which was stored under refrigeration conditions for 3 weeks. Shelf-life evaluation showed that the application of the PBS-PBSA film on the paper substrate delayed color changes and mold growth for 1 week, as well as reduced drying of fresh pasta, resulting in acceptable physicochemical quality parameters within 9 days of storage. Lastly, overall migration studies performed with two food simulants demonstrated that the newly developed paper/PBS-PBSA trays are safe since these successfully comply with current legislation on plastic materials and articles intended to come into contact with food.

Preliminary Findings of the Efficacy of Botulinum Toxin in Temporomandibular Disorders: Uncontrolled Pilot Study.

Temporomandibular disorders are a common pathology affecting up to 70% of the population, with a maximum incidence in young patients. We used a sample of twenty patients recruited in the Maxillofacial Surgery Service of the University Hospital of Salamanca (Spain), who met the inclusion criteria, with unilateral painful symptomatology of more than three months' duration. All patients were randomly treated by intramuscular and intra-articular injections of botulinum toxin (100 U) in eight predetermined points. Pain symptomatology was assessed by the visual analog scale (VAS) at the different locations, together with joint symptomatology, at baseline and six weeks after treatment. Adverse effects were also evaluated. In 85% of the patients, pain upon oral opening improved and 90% showed improvement in pain upon mastication. A total of 75% of the patients reported improvement in joint clicking/noise. Headaches improved or disappeared in 70% of the patients treated. Despite the limitations of the study and the preliminary results, intramuscular and intra-articular infiltrations with botulinum toxin were effective in the treatment of symptoms associated with temporomandibular disorders (TMDs), with minimal adverse effects.

Lid Films of Poly(3-hydroxybutyrate-co-3-hydroxyvalerate)/Microfibrillated Cellulose Composites for Fatty Food Preservation.

The present work evaluates the food packaging performance of previously developed films of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) reinforced with atomized microfibrillated cellulose (MFC) compatibilized by a reactive melt-mixing process. To this end, the novel green composite films were originally applied herein as lids in aluminum trays to preserve two dissimilar types of fatty foods, namely minced pork meat and sunflower oil. Results indicated that the PHBV/MFC films effectively preserved the physicochemical and microbiological quality of pork meat for one week of storage at 5 °C. In particular, the compatibilized green composite lid film yielded the lowest weight loss and highest oxidative stability, showing values of 0.935% and 0.78 malonaldehyde (MDA)/kg. Moreover, none of the packaged meat samples exceeded the acceptable Total Aerobial Count (TAC) level of 5 logs colony-forming units (CFU)/g due to the improved barrier properties of the lids. Furthermore, the green composite films successfully prevented sunflower oil oxidation in accelerated oxidative storage conditions for 21 days. Similarly, the compatibilized PHBV/MFC lid film led to the lowest peroxide value (PV) and conjugated diene and triene contents, with respective values of 19.5 meq O2/kg and 2.50 and 1.44 g/100 mL. Finally, the migration of the newly developed PHBV-based films was assessed using two food simulants, proving to be safe since their overall migration levels were in the 1-3 mg/dm2 range and, thus, below the maximum level established by legislation.