Sexually transmitted infections and the HPV-related burden: evolution of Italian epidemiology and policy.

Sexually transmitted infections (STIs) are a major public health problem worldwide, with a high prevalence between the ages of 15 and 25 in most Western countries. High notification rates of chlamydia, gonorrhea, and syphilis are reported in the WHO European Region, with differences between countries. In Italy, the total number of STIs alerts increased by 18% from 2020 to 2021. HPV is the most common sexually transmitted infection; globally one in seven women is infected by this virus, and certain sexual behaviors are important risk factors for HPV-related cancers, particularly cervical cancer (CC), anogenital cancers and cancers of the head and neck. The burden of CC is relevant worldwide, in particular in Europe CC is the third leading cause of cancer-related deaths in women aged 15-44. This HPV-related tumor is preventable through a combined strategy of vaccination and screening for precursor lesions. In Italy, the coverage of organized screening varies from region to region and the average HPV vaccination rate is still far from the expected optimal threshold of 95% at the age of 12. To address the challenges of health promotion and HPV prevention, priority actions are needed such as: promoting education and information at every level, from schools to healthcare professionals. In Italy, education of adolescents on sexual and reproductive health, still remains critical, regionally inhomogeneous and much lower than in other European countries. Equitable measures need to be taken, and schools are an important place for health promotion activities.

The Role of Pharmacists in Counteracting Vaccine Hesitancy: Effectiveness of the 2019 Carnia Project in Improving Adherence to Influenza Vaccination among Target Population.

Vaccine hesitancy has been included among the top ten threats to global health by the World Health Organization. Pharmacists can play a pivotal role in removing the individual barrier to vaccination, because of the relationship of trust they have with citizens and their ease of access. The aim of this study was to examine the impact of a pharmacy-based intervention to support the 2019 influenza vaccination campaign conducted in the Carnia district through one-to-one counseling. We analyzed data collected by pharmacists between 22 October 2019 and 20 January 2020, and trends in vaccination adherence in the context of the Local Health Authority and the entire province of Udine since 2016. The results showed that 77.2% of people who had not received an influenza vaccination in the previous year changed their minds about vaccination after receiving counseling. The pharmacy-based intervention improved influenza vaccination adherence in the target district (+13.4%), even when compared to the neighboring district of Gemona or considering the data in the broader local and provincial context, and this effect was particularly pronounced among those aged 65 to 74 years (p < 0.01). Considering these findings, pharmacies should be more effectively involved in the provision of public health services aimed at improving accessibility, timeliness, and equity.

Riboflavin-LSD1 axis participates in the in vivo tumor-associated macrophage morphology in human colorectal liver metastases.

Tumor-associated macrophages (TAMs) are key components of the tumor microenvironment (TME). In colorectal liver metastasis (CLM), TAM morphology correlates with prognosis, with smaller TAMs (S-TAMs) conferring a more favorable prognosis than larger TAMs (L-TAMs). However, the metabolic profile of in vivo human TAM populations remains unknown. Multiparametric flow cytometry was used to freshly isolate S- and L-TAMs from surgically resected CLM patients (n = 14S-, 14L-TAMs). Mass spectrometry-based metabolomics analyses were implemented for the metabolic characterization of TAM populations. Gene expression analysis and protein activity were used to support the biochemical effects of the enzyme-substrate link between riboflavin and (lysine-specific demethylase 1A, LSD1) with TAM morphologies. L-TAMs were characterized by a positive correlation and a strong association between riboflavin and TAM morphologies. Riboflavin in both L-TAMs and in-vitro M2 polarized macrophages modulates LSD1 protein expression and activity. The inflammatory stimuli promoted by TNFα induced the increased expression of riboflavin transporter SLC52A3 and LSD1 in M2 macrophages. The modulation of the riboflavin-LSD1 axis represents a potential target for reprogramming TAM subtypes, paving the way for promising anti-tumor therapeutic strategies.

Applying the Participatory Slow Design Approach to a mHealth Application for Family Caregivers in Pediatric Ear, Nose, and Throat Surgery.

Pediatric ear, nose, and throat (ENT) surgery is very common, and its outcomes may improve with family education. In this regard, mobile health (mHealth) applications (apps), which are on the rise due to digital transformation, can be beneficial in healthcare. This study outlines the user-centered design and development of a mHealth app (version 5.15.0) to support family caregivers during the perioperative process of pediatric ENT surgery. Conducted over two years in an Italian maternal and child health hospital (January 2020-May 2022), the study employed a participatory design method based on the Information System Research (ISR) framework and guided by the principles of Slow Medicine. Utilizing the Relevance, Rigor, and Design cycles of the ISR framework, the mHealth app's content, functionalities, and technical features were defined and developed. A committee of fifteen experts guided the process with input from 25 family caregivers and 24 healthcare providers enrolled in the study. The mHealth app content was structured around five crucial educational moments characterizing the ENT perioperative period, providing evidence-based information on surgical procedures, strategies for preparing children for hospitalization and surgery, pain management, and post-discharge care. The mHealth app featured a function that sends customized notifications to guide caregivers at specific perioperative stages. The development of mHealth apps by implementing a rigorous, participatory, and Slow design process can foster accessible and family-centered information and care in the field of maternal and child health and beyond.

A look at the past to draw lessons for the future: how the case of an urgent ICU transfer taught us to always be ready with a plan B.

Objective: The urgent transfer of an intensive care unit (ICU) is particularly challenging because it carries a high clinical and infectious risk and is a critical node in a hospital's patient flow. In early 2017, exceptional rainfall damaged the roof of the tertiary hospital in Udine, necessitating the relocation of one of the three ICUs for six months. We decided to assess the impact of this transfer on quality of care and patient safety using a set of indicators, primarily considering the incidence of healthcare-associated infections (HAIs) and mortality rates. Methods: We performed a retrospective, observational analysis of structural, process, and outcome indicators comparing the pre- and posttransfer phases. Specifically, we analyzed data between July 2016 and June 2017 for the transferred ICU and examined mortality and the incidence of HAI. Results: Despite significant changes in structural and organizational aspects of the unit, no differences in mortality rates or cumulative incidence of HAIs were observed before/after transfer. We collected data for all 393 patients (133 women, 260 men) admitted to the ICU before (49.4%) and after transfer (50.6%). The mortality rate for 100 days in the ICU was 1.90 (34/1791) before and 2.88 (37/1258) after transfer (p = 0.063). The evaluation of the occurrence of at least one HAI included 304 patients (102 women and 202 men), as 89 of them were excluded due to a length of stay in the ICU of less than 48 h; again, there was no statistical difference between the two cumulative incidences (13.1% vs. 6.9%, p = 0.075). Conclusion: In the case studied, no adverse effects on patient outcomes were observed after urgent transfer of the injured ICU. The indicators used in this study may be an initial suggestion for further discussion.

Are adverse events related to the completeness of clinical records? Results from a retrospective records review using the Global Trigger Tool.

Clinical record (CR) is a tool for recording details about the patient and the most commonly used source of information for detecting adverse events (AEs). Its completeness is an indicator of the quality of care provided and may provide clues for improving professional practice. The primary aim of this study was to estimate the prevalence of AEs. The secondary aims were to determine the completeness of CRs and to examine the relationship between the two variables. We retrospectively reviewed randomly selected CRs of patients discharged from the Academic Hospital of Udine (Italy) in the departments of general surgery, internal medicine, and obstetrics between July and September 2020. Evaluation was performed using the Global Trigger Tool and a checklist to evaluate the completeness of CRs. The relationship between the occurrence of AEs and the completeness of CRs was analyzed using nonparametric tests. A binomial logistic regression analysis was also performed. We reviewed 291 CRs and identified 368 triggers and 56 AEs. Among them, 16.2% of hospitalizations were affected by at least one AE, with a higher percentage in general surgery. The most common AEs were surgical injuries (42.6%; 24) and care related (26.8%; 15). A significant positive correlation was found between the length of hospital stay and the number of AEs. The average completeness of CRs was 72.9% and was lower in general surgery. The decrease in CR completeness correlated with the increase in the total number of AEs (R = -0.14; P = .017), although this was not confirmed by regression analysis by individual departments. Our results seem to suggest that completeness of CRs may benefit patient safety, so ongoing education and involvement of health professionals are needed to maintain professional adherence to CRs.

Health professionals who have worked in COVID-19 immunization centers suffer the effects of violence.

Background: The phenomenon violence against health professionals has received increasing attention in recent years because of its frequency and significant impact on victims' mental health and disruption of health services. Despite this attention, little is known about the incidence of workplace violence in the highly politicized immunization services. Therefore, we decided to examine the prevalence of workplace violence in the COVID-19 immunization campaign, the risk and protective factors, and the impact on victims' mental health. Methods: Between March and April 2022, we conducted an anonymous online survey among health professionals working in COVID-19 vaccination centers in the Friuli-Venezia Giulia Region (Italy). We used the Questionnaire for Workplace Violence in Healthcare Settings and the Impact of Event Scale-Revised. Results: Of the 200 participants, 93 (46.5%) reported being victims of an act of violence during the vaccination campaign, 60 of them verbally and 7 physically. In 35.5% of cases, the IES score indicated a possible post-traumatic stress reaction in the victim. Opinions on measures to prevent violence and support workers in the workplace differed according to the sex of the health professional, with women emphasizing the need for self-defense training and improvement of security arrangements (p < 0.001). Conclusion: One-third of health professionals involved in the COVID-19 immunization campaign reported that their mental health was affected by workplace violence. Public health professionals dealing with politicized and debated issues such as immunization should receive more attention, as should the implementation of a more structured and multidisciplinary approach to the problem within healthcare organizations.

Fibronectin fragments generated by pancreatic trypsin act as endogenous inhibitors of pancreatic tumor growth.

BACKGROUND: The pancreatic microenvironment has a defensive role against cancer but it can acquire tumor-promoting properties triggered by multiple mechanisms including alterations in the equilibrium between proteases and their inhibitors. The identification of proteolytic events, targets and pathways would set the basis for the design of new therapeutic approaches. METHODS AND RESULTS: Here we demonstrate that spheroids isolated from human and murine healthy pancreas and co-transplanted orthotopically with pancreatic ductal adenocarcinoma (PDAC) in mouse pancreas inhibited tumor growth. The effect was mediated by trypsin-generated fibronectin (FN) fragments released by pancreatic spheroids. Tumor inhibition was observed also in a model of acute pancreatitis associated with trypsin activation. Mass spectrometry proteomic analysis of fragments and mAb against different FN epitopes identified the FN type III domain as responsible for the activity. By inhibiting integrin α5ß1, FAK and FGFR1 signaling, the fragments induced tumor cell detachment and reduced cell proliferation. Consistent with the mutual relationship between the two pathways, FGF2 restored both FGFR1 and FAK signaling and promoted PDAC cell adhesion and proliferation. FAK and FGFR inhibitors additively inhibited PDAC growth in vitro and in orthotopic in vivo models. CONCLUSIONS: This study identifies a novel role for pancreatic trypsin and fibronectin cleavage as a mechanism of protection against cancer by the pancreatic microenvironment. The finding of a FAK-FGFR cross-talk in PDAC support the combination of FAK and FGFR inhibitors for PDAC treatment to emulate the protective effect of the normal pancreas against cancer.

Anti-VEGF therapy selects for clones resistant to glucose starvation in ovarian cancer xenografts.

BACKGROUND: Genetic and metabolic heterogeneity are well-known features of cancer and tumors can be viewed as an evolving mix of subclonal populations, subjected to selection driven by microenvironmental pressures or drug treatment. In previous studies, anti-VEGF therapy was found to elicit rewiring of tumor metabolism, causing marked alterations in glucose, lactate ad ATP levels in tumors. The aim of this study was to evaluate whether differences in the sensitivity to glucose starvation existed at the clonal level in ovarian cancer cells and to investigate the effects induced by anti-VEGF therapy on this phenotype by multi-omics analysis. METHODS: Clonal populations, obtained from both ovarian cancer cell lines (IGROV-1 and SKOV3) and tumor xenografts upon glucose deprivation, were defined as glucose deprivation resistant (GDR) or glucose deprivation sensitive (GDS) clones based on their in vitro behaviour. GDR and GDS clones were characterized using a multi-omics approach, including genetic, transcriptomic and metabolic analysis, and tested for their tumorigenic potential and reaction to anti-angiogenic therapy. RESULTS: Two clonal populations, GDR and GDS, with strikingly different viability following in vitro glucose starvation, were identified in ovarian cancer cell lines. GDR clones survived and overcame glucose starvation-induced stress by enhancing mitochondrial oxidative phosphorylation (OXPHOS) and both pyruvate and lipids uptake, whereas GDS clones were less able to adapt and died. Treatment of ovarian cancer xenografts with the anti-VEGF drug bevacizumab positively selected for GDR clones that disclosed increased tumorigenic properties in NOD/SCID mice. Remarkably, GDR clones were more sensitive than GDS clones to the mitochondrial respiratory chain complex I inhibitor metformin, thus suggesting a potential therapeutic strategy to target the OXPHOS-metabolic dependency of this subpopulation. CONCLUSION: A glucose-deprivation resistant population of ovarian cancer cells showing druggable OXPHOS-dependent metabolic traits is enriched in experimental tumors treated by anti-VEGF therapy.

Implication of metabolism in the polarization of tumor-associated-macrophages: the mass spectrometry-based point of view.

Tumor-associated macrophages (TAMs) represent one of the main tumor-infiltrating immune cell types and are generally categorized into either of two functionally contrasting subtypes, namely classical activated M1 macrophages and alternatively activated M2 macrophages. TAMs showed different activation states that can be represent by the two extremes of the complex profile of macrophages biology, the M1-like phenotype (pro-inflammatory activity) and the M2-like phenotype (anti-inflammatory activity). Based on the tumor type, and grades, TAMs can acquire different functions and properties; usually, the M1-like phenotype is typical of early tumor stages and is associated to an anti-tumor activity, while M2-like phenotype has a pro-inflammatory activity and is related to a poor patients' prognosis. The classification of macrophages into M1/M2 groups based on well-defined stimuli does not model the infinitely more complex tissue milieu where macrophages (potentially of different origin) would be exposed to multiple signals in different sequential order. This review aims to summarize the recent mass spectrometry-based (MS-based) metabolomics findings about the modifications of metabolism in TAMs polarization in different tumors. The published data shows that MS-based metabolomics is a promising tool to help better understanding TAMs metabolic phenotypes, although it is still poorly applied for TAMs metabolism. The knowledge of key metabolic alterations in TAMs is an essential step for discovering TAMs polarization novel biomarkers and developing novel therapeutic approaches targeting TAM metabolism to repolarize TAMs towards their anti-tumor phenotype.

Study protocol for a randomised controlled trial to determine the effectiveness of a mHealth application as a family supportive tool in paediatric otolaryngology perioperative process (TONAPP).

BACKGROUND: Otorhinolaryngology (ORL) surgery is common in children, but hospitalisation, surgery, and home care after discharge are stressful experiences for young patients and their family caregivers. Findings from literature highlight a lack of time in hospitals to support ORL surgery children and their caregivers through the perioperative process, along with the risks of caregivers' autonomous web or social media resources investigation. Therefore, this study aims to evaluate the effectiveness of a mobile health application with content to support ORL patients and their caregivers in the perioperative period to reduce caregiver anxiety and child distress compared to standard care. METHODS: An open-label, two-arm randomised control trial design is being adopted. The intervention consists of a mobile health application with content to support ORL patients and their caregivers during the perioperative period. One hundred eighty participants will be enrolled and randomly assigned to the experimental group using the mHealth application or the control group. The control group receives standard information and education about the ORL perioperative period from healthcare providers orally or through brochures. The primary outcome is the difference between the intervention and control groups in preoperative caregiver state anxiety. Secondary outcome measures include children's distress before surgery and family preparation for hospitalisation. DISCUSSION: The results of this study will be critical to the implementation of a new and safe model for the management of care and education in paediatrics. This model can achieve positive organisational and health outcomes by supporting continuity of care and empowering citizens to have informed participation and satisfaction in paediatric health promotion and management. TRIAL REGISTRATION: Trial identifier: NCT05460689 registry name: ClinicalTrials.gov. Date of registration: July 15, 2022. Last update posted: February 23, 2023.

Psychological impact of COVID-19 on healthcare leaders: a cross-sectional survey in Friuli-Venezia Giulia, Italy.

INTRODUCTION: Although several studies highlighted the psychological burden of 2019 coronavirus disease (COVID-19) pandemic, no data are available regarding professionals leading healthcare organisations. This study aims to assess the psychological impact of COVID-19 on healthcare leaders (HeLs), along with the leadership skills and coping strategies needed for successful leadership. METHODS: A cross-sectional survey was conducted in Friuli-Venezia Giulia (Italy) between October and November 2020. We assessed the presence of depressive symptoms (DS), anxiety symptoms (AS), perceived stress (PS) and insomnia using internationally validated tools. Coping strategies and skills needed to overcome the crisis were examined, along with the most challenging phases. RESULTS: A total of 48 HeLs participated. The prevalence of DS and AS was 14.6% and 12.5%, respectively. Moderate and severe insomnia was found in 12.5% and 6.3% of them, respectively. Leaders showed moderate (45.8%) and high 4,2%) level of PS. The two most challenging phases were recognised in early recognition (45.2%) and peak phase (31.0%). Concerning healthcare leaders' skills required to manage with pandemic, the most reported were communication (35.1%) and decision-making (25.5%). CONCLUSION: The high level of PS, insomnia, DS and AS experienced by healthcare leaders shows the COVID-19 pandemic's psychological impact. The two most challenging phases identified enhances the importance of public health surveillance and monitoring systems, and communication appeared a critical success skill for healthcare leaders. Given the key role these professional play in addressing the current crisis in healthcare organisations, their mental health and well-being deserve greater attention.

What do hospital-based health professionals need and expect from an mHealth app to support the first 1000 days of life? Results from a cross sectional study.

BACKGROUND: Several attempts have been made to introduce mHealth solutions to support maternal, newborn, and child health (MNCH). However, most of the available apps do not meet the needs of end-users, underscoring the urgency of involving them in the co-design of telehealth interventions. OBJECTIVE: With this in mind, we investigated the needs and expectations of hospital-based health professionals (i.e., secondary users) providing care to pregnant women and new mothers with their babies for a hypothetical mHealth app to support the first 1000 days of life. METHODS: From November 2021 to March 2022, we surveyed health professionals using a questionnaire that explored the perceived importance of specific content, functionalities, and technical features of the proposed app. We also collected sociodemographic information from secondary users. We performed descriptive analysis and then used Ward hierarchical clustering method to classify respondents according to their response patterns. RESULTS: We recorded the needs and expectations of 145 hospital-based health professionals from obstetrics/gynecology, nursery/neonatology, and pediatrics. We found general agreement with the proposed content of the app, particularly general information about health during pregnancy (92%) and potential risky infections during pregnancy (91%). Three clusters emerged from the analysis, with the high and medium demanding clusters rating the importance of app content and technical features as very high and high, respectively, while low demanding cluster expressing more skepticism, especially about some of the proposed functionalities of the app. CONCLUSIONS: Assessing the needs and expectations of end-users is an essential process for developing tailored and effective mHealth solutions. This study has shown that hospital-based health professionals generally recognize the value of the proposed app, suggesting their propensity to integrate such a telehealth solution into mainstream clinical practice.

Brain-Derived Neurotrophic Factor, Kynurenine Pathway, and Lipid-Profiling Alterations as Potential Animal Welfare Indicators in Dairy Cattle.

Complete animal welfare evaluation in intensive farming is challenging. With this study, we investigate new biomarkers for animal physical and mental health by comparing plasma expression of biochemical indicators in dairy cows reared in three different systems: (A) semi-intensive free-stall, (B) non-intensive tie-stall, and (C) intensive free-stall. Additionally, protein levels of mature brain-derived neurotrophic factor (mBDNF) and its precursor form (proBDNF) and indoleamine 2,3-dioxygenase (IDO1) specific activity were evaluated in brain samples collected from 12 cattle culled between 73 and 138 months of age. Alterations in plasma lipid composition and in the kynurenine pathway of tryptophan metabolism were observed in the tie-stall-reared animals. The total plasma BDNF concentration was higher in tie-stall group compared to the two free-housing groups. Brain analysis of the tie-stall animals revealed a different mBDNF/proBDNF ratio, with a higher level of proBDNF (p < 0.001). Our data are similar to previous studies on animal models of depression, which reported that inhibition of the conversion of proBDNF in its mature form and/or elevated peripheral kynurenine pathway activation may underlie cerebral biochemical changes and induce depressive-like state behavior in animals.

A Web Tool to Help Counter the Spread of Misinformation and Fake News: Pre-Post Study Among Medical Students to Increase Digital Health Literacy.

BACKGROUND: The COVID-19 pandemic was accompanied by the spread of uncontrolled health information and fake news, which also quickly became an infodemic. Emergency communication is a challenge for public health institutions to engage the public during disease outbreaks. Health professionals need a high level of digital health literacy (DHL) to cope with difficulties; therefore, efforts should be made to address this issue starting from undergraduate medical students. OBJECTIVE: The aim of this study was to investigate the DHL skills of Italian medical students and the effectiveness of an informatics course offered by the University of Florence (Italy). This course focuses on assessing the quality of medical information using the "dottoremaeveroche" (DMEVC) web resource offered by the Italian National Federation of Orders of Surgeons and Dentists, and on health information management. METHODS: A pre-post study was conducted at the University of Florence between November and December 2020. First-year medical students participated in a web-based survey before and after attending the informatics course. The DHL level was self-assessed using the eHealth Literacy Scale for Italy (IT-eHEALS) tool and questions about the features and quality of the resources. All responses were rated on a 5-point Likert scale. Change in the perception of skills was assessed using the Wilcoxon test. RESULTS: A total of 341 students participated in the survey at the beginning of the informatics course (women: n=211, 61.9%; mean age 19.8, SD 2.0) and 217 of them (64.2%) completed the survey at the end of the course. At the first assessment, the DHL level was moderate, with a mean total score of the IT-eHEALS of 2.9 (SD 0.9). Students felt confident about finding health-related information on the internet (mean score of 3.4, SD 1.1), whereas they doubted the usefulness of the information they received (mean score of 2.0, SD 1.0). All scores improved significantly in the second assessment. The overall mean score of the IT-eHEALS significantly increased (P<.001) to 4.2 (SD 0.6). The item with the highest score related to recognizing the quality of health information (mean score of 4.5, SD 0.7), whereas confidence in the practical application of the information received remained the lowest (mean of 3.7, SD 1.1) despite improvement. Almost all students (94.5%) valued the DMEVC as an educational tool. CONCLUSIONS: The DMEVC tool was effective in improving medical students' DHL skills. Effective tools and resources such as the DMEVC website should be used in public health communication to facilitate access to validated evidence and understanding of health recommendations.

Exploring the Needs and Expectations of Expectant and New Parents for an mHealth Application to Support the First 1000 Days of Life: Steps toward a Co-Design Approach.

To improve maternal and child health, it is essential to adhere to health-promoting and preventive measures. However, reliable information as well as effective tools are not easy to identify in this field. Our cross-sectional study investigated the needs and expectations of expectant and new mothers and fathers as potential primary users of a hypothetical application supporting the first 1000 days of life. Between May and August 2022, we recruited expectant and new parents by administering an 83-item 5-point Likert scale questionnaire related to the content, functionalities, and technical features of the hypothetical app. We stratified responses using sociodemographic characteristics and then performed ward hierarchical clustering. The 94 women and 69 men involved in our study generally agreed with the proposed content, but expressed low interest in certain app functionalities or features, including those related to the interaction mechanism and interactivity. Women were generally more demanding than men. Our findings, resulting from the engagement of end-users, may be useful for designers and technology providers to implement mHealth solutions that, in addition to conveying reliable information, are tailored to the needs and preferences of end-users in the first 1000 days of life.

CARE 1000: randomized controlled trial for the evaluation of the effectiveness of a mHealth app for supporting the first 1000 days of life.

BACKGROUND: Recent developments in eHealth and mobile health (mHealth), as well as the introduction of information and communication technology innovations in clinical practice, such as telemedicine, telemonitoring, and remote examinations, are already changing the current scenario and will continue to generate innovations in the coming decades. The widespread use of mobile devices, with an estimated nearly 30 billion devices and more than 325,000 apps worldwide, will provide various opportunities for people to take control of their own health. Already in 2017, most of the apps available were focused on pregnancy support, more than any other medical field. There have been some reported experiences with social media and mHealth that could benefit the promotion of maternal physical and mental health during pregnancy. However, many apps targeting the first 1000 days of a child's life do not consider the continuity between the prenatal and postnatal periods and their joint impact on maternal and child health. The aim of this study is to evaluate the effectiveness of this mHealth app to support women during the first 1000 days (from conception to 24 months of age) and to improve health prevention behaviours such as immunizations during pregnancy, weight gain during pregnancy, abstinence from smoking and alcohol consumption, and adherence to the routine childhood immunization schedule. In addition, the study aims to understand the level of appreciation of this mHealth app as a tool to overcome information and communication gaps between patients and institutions. METHODS: Conduction of a randomized controlled trial. DISCUSSION: Our results will be relevant for improving this mHealth app to promote health and prevention and to support the first 1000 days of life for both mother and child. Our results will be relevant to the future expansion of such an mHealth app to promote positive health-related outcomes in patients and co-user satisfaction and to support the organization of health services. TRIAL REGISTRATION: ClinicalTrials.gov NCT05500339.

NSCLC Cells Resistance to PI3K/mTOR Inhibitors Is Mediated by Delta-6 Fatty Acid Desaturase (FADS2).

Hyperactivation of the phosphatidylinositol-3-kinase (PI3K) pathway is one of the most common events in human cancers. Several efforts have been made toward the identification of selective PI3K pathway inhibitors. However, the success of these molecules has been partially limited due to unexpected toxicities, the selection of potentially responsive patients, and intrinsic resistance to treatments. Metabolic alterations are intimately linked to drug resistance; altered metabolic pathways can help cancer cells adapt to continuous drug exposure and develop resistant phenotypes. Here we report the metabolic alterations underlying the non-small cell lung cancer (NSCLC) cell lines resistant to the usual PI3K-mTOR inhibitor BEZ235. In this study, we identified that an increased unsaturation degree of lipid species is associated with increased plasma membrane fluidity in cells with the resistant phenotype and that fatty acid desaturase FADS2 mediates the acquisition of chemoresistance. Therefore, new studies focused on reversing drug resistance based on membrane lipid modifications should consider the contribution of desaturase activity.