The effectiveness of visual-based interventions on health literacy in health care: a systematic review and meta-analysis.

BACKGROUND: Limited Health Literacy (HL) is an obstacle to accessing and receiving optimal health care and negatively impacts patients' quality of life, thus making it an urgent issue in the health care system. Visual-based interventions are a promising strategy to improve HL through the use of visual aids and pictorial materials to explain health-related concepts. However, a comprehensive summary of the literature on the topic is still scarce. METHODS: To fill this gap, we carried out a systematic review and meta-analysis with the aim to determine the effectiveness of visual-based interventions in improving comprehension of health related material in the clinical population. Independent studies evaluating the effectiveness of visual-based interventions on adults (> 18 years) and whose primary outcome was either health literacy (HL) or comprehension were eligible for the review. After a systematic literature search was carried out in five databases, 28 studies met the inclusion criteria and thus were included. Most of the studies were randomized controlled trials and they focused on HL and health knowledge as outcomes. RESULTS: The review and meta-analysis showed that visual-based interventions were most effective in enhancing the comprehension of health-related material compared to traditional methods. According to meta-analytic results, videos are more effective than traditional methods (Z = 5.45, 95% CI [0.35, 0.75], p < 0.00001) and than the employment of written material (Z = 7.59, 95% CI [0.48, 0.82], p < 0.00001). Despite this, no significant difference was found between video and oral discussion (Z = 1.70, 95% CI [-0.46, 0.53], p = 0.09). CONCLUSIONS: We conclude that visual-based interventions, particularly the ones using videos, are effective for improving HL and the comprehension of health-related material.

Physician Perspectives on Internet-Informed Patients: Systematic Review.

BACKGROUND: The internet has become a prevalent source of health information for patients. However, its accuracy and relevance are often questionable. While patients seek physicians' expertise in interpreting internet health information, physicians' perspectives on patients' information-seeking behavior are less explored. OBJECTIVE: This review aims to understand physicians' perceptions of patients' internet health information-seeking behavior as well as their communication strategies and the challenges and needs they face with internet-informed patients. METHODS: An initial search in PubMed, Scopus, CINAHL, Communication and Mass Media Complete, and PsycINFO was conducted to collect studies published from January 1990 to August 1, 2022. A subsequent search on December 24, 2023, targeted recent studies published after the initial search cutoff date. Two reviewers independently performed title, abstract, and full-text screening, adhering to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement guidelines. Thematic analysis was then used to identify key themes and systematically categorize evidence from both qualitative and quantitative studies under these themes. RESULTS: A total of 22 qualifying articles were identified after the search and screening process. Physicians were found to hold diverse views on patients' internet searches, which can be viewed as a continuous spectrum of opinions ranging from positive to negative. While some physicians leaned distinctly toward either positive or negative perspectives, a significant number expressed more balanced views. These physicians recognized both the benefits, such as increased patient health knowledge and informed decision-making, and the potential harms, including misinformation and the triggering of negative emotions, such as patient anxiety or confusion, associated with patients' internet health information seeking. Two communicative strategies were identified: the participative and defensive approaches. While the former seeks to guide internet-informed patients to use internet information with physicians' expertise, the latter aims to discourage patients from using the internet to seek health information. Physicians' perceptions were linked to their strategies: those holding positive views tended to adopt a participative approach, while those with negative views favored a defensive strategy. Some physicians claimed to shift between the 2 approaches depending on their interaction with a certain patient. We also identified several challenges and needs of physicians in dealing with internet-informed patients, including the time pressure to address internet-informed patient demands, a lack of structured training, and being uninformed about trustworthy internet sites that can be recommended to internet-informed patients. CONCLUSIONS: This review highlights the diverse perceptions that physicians hold toward internet-informed patients, as well as the interplay between their perceptions, communication strategies, and their interactions with individual patients. Incorporating elements into the medical teaching curriculum that introduce physicians to reliable internet health resources for patient guidance, coupled with providing updates on technological advancements, could be instrumental in equipping physicians to more effectively manage internet-informed patients. TRIAL REGISTRATION: PROSPERO CRD42022356317; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=356317.

The Arthroscopic Subscapular Sling Procedure Results in Low Recurrent Anterior Shoulder Instability at 24 Months of Follow-Up.

PURPOSE: To analyze the results of the subscapular sling procedure developed for anterior shoulder instability in patients with less than 10% anterior glenoid bone loss. METHODS: Patients were treated surgically with the arthroscopic subscapular sling procedure. A semitendinosus graft was used to reconstruct the anterior labrum and to establish a sling suspension around the upper part of the subscapularis tendon. The patients were followed up with radiographs (at 12 and 24 months). Magnetic resonance imaging (MRI) of the shoulder region and clinical examinations were performed at 3, 12, and 24 months. Recurrent dislocation was the primary endpoint. The Western Ontario Shoulder Instability Index (WOSI) and MRI results were secondary outcome measures. An independent physiotherapist assessed residual instability and range of motion. RESULTS: Fifteen patients were included with a dislocation rate of 0% after 24 months follow-up. There was a significant clinical improvement of the WOSI score from 57% (904) at baseline to 88% (241) at 24 months (P < .001). The proportion of patients with an improvement in the WOSI Total score larger than the estimated minimal clinically important difference was 100% both at 12 and 24 months. MRI showed an intact sling in all patients. External rotation was not significantly reduced (52° at baseline vs 47° at 24 months, P = .211). Flexion and abduction were significantly improved from 152° to 174° (P = .001) and 141° to 170° (P < .001) after 24 months. The surgical procedures were completed without any intraoperative complications. CONCLUSIONS: The subscapular sling procedure resulted in low recurrent shoulder instability and improved patient-reported outcome measures at 24 months of follow-up. LEVEL OF EVIDENCE: Level IV, case series.

Influenza and Covid-19 Vaccination in 2023: a descriptive analysis in two Italian Research and Teaching Hospitals. Is the On-Site strategy effective?

Introduction: Vaccinations represent an extremely effective tool for the prevention of certain infectious diseases - such as influenza and COVID-19 -, particularly for those categories at risk due to both their frail condition or professional exposure, such as healthcare workers. The aim of this study is to describe the course of the anti-influenza and anti-COVID-19 vaccination campaign at two Research Hospitals in Milan, Italy. Study design: Multicentre, cross-sectional study. Methods: For the 2023-24 vaccination campaign, the two facilities opted for two different approaches. At the Hospital A, two dif-ferent strategies for vaccinating healthcare workers were implemented: a fixed-site vaccination clinic and two mobile vaccination groups run by Public Health residents of the University of Milan. At the Hospital B, on the other hand, a single fixed-site outpatient clinic run by Public Health residents of the University of Milan was used. On the occasion of the campaign, a survey was also carried out using anonymous online questionnaires to investigate healthcare workers attitudes towards vaccination. Results: A total of 1,937 healthcare workers were vaccinated: 756 were immunized against influenza only, 99 against COVID-19 only, and 1,082 against both. The results show a substantial difference in vaccination adherence among medical and nursing staff compared to other professional categories. In particular, the category with the highest vaccination adhesion turned out to be that of medical doctors with 55.7% adhesion while, on the contrary, the category with the lowest adhesion turned out to be that of auxiliary personnel characterized by 7.4% adhesion. At the same time, the comparison between the two hospital facilities showed a double adherence rate by the staff of Hospital A as regards both the flu vaccine (40.6% and 20.1%) and the anti-COVID-19 vaccine (26.4% and 12.3%). Finally, the survey showed that the attitude towards influenza vaccination is lower among auxiliary staff in terms of both knowledge and vaccination attitude. Conclusions: The results of the study show a vaccination adherence in line with that of previous years, although lower than the values recommended by the principal national and international Organizations. The analysis of the differences between the two facilities and the surveys carried out will allow for the implementation of targeted interventions to increase adherence in future campaigns.

Immunohistochemical characterization of integrin alfa 6 in uterus and cervix of the cynomolgus monkeys (Macaca fascicularis) with MfPV3 infection.

BACKGROUND: Cervical cancer is an abnormal growth of cervical tissue epithelial cells due to persistent human papilloma virus (HPV) infection. Cynomolgus monkeys (Macaca fascicularis) can be naturally and spontaneously infected with M. fascicularis Papillomavirus Type 3 (MfPV3), a virus that is phylogenetically closely related to human oncogenic HPV (HPV-16 and HPV-34), and therefore a potentially beneficial for modeling HPV disease. This study aims to evaluate the expression of the integrin alpha 6 (ITGα6) receptor in cynomolgus monkeys spontaneously infected with MfPV3, which this receptor also found in human infected with HPV. METHODS: The study was done on archived Formalin-fixed Paraffin-Embedded (FFPE) samples of uterine and cervix tissue of cynomolgus monkeys. Immunohistochemistry was also performed to quantify the expression levels of ITGα6. RESULTS: The results showed 80% of the samples positive Cervical Intraepithelial Neoplasia (CIN) and increased expression of ITGα6 significantly in Positive-MfPV3 group than negative-MfPV3 group. CONCLUSIONS: This indicated the potential of cynomolgus monkeys as a spontaneous oncogenesis model of PV infection type.

Classification of fetal and adult red blood cells based on hydrodynamic deformation and deep video recognition.

Flow based deformation cytometry has shown potential for cell classification. We demonstrate the principle with an injection moulded microfluidic chip from which we capture videos of adult and fetal red blood cells, as they are being deformed in a microfluidic chip. Using a deep neural network - SlowFast - that takes the temporal behavior into account, we are able to discriminate between the cells with high accuracy. The accuracy was larger for adult blood cells than for fetal blood cells. However, no significant difference was observed between donors of the two types.

Preferential Expansion of HPV16 E1-Specific T Cells from Healthy Donors' PBMCs after Ex Vivo Immunization with an E1E2E6E7 Fusion Antigen.

Persistent human papillomavirus (HPV) infection is responsible for practically all cervical and a high proportion of anogenital and oropharyngeal cancers. Therapeutic HPV vaccines in clinical development show great promise in improving outcomes for patients who mount an anti-HPV T-cell response; however, far from all patients elicit a sufficient immunological response. This demonstrates a translational gap between animal models and human patients. Here, we investigated the potential of a new assay consisting of co-culturing vaccine-transduced dendritic cells (DCs) with syngeneic, healthy, human peripheral blood mononuclear cells (PBMCs) to mimic a human in vivo immunization. This new promising human ex vivo PBMC assay was evaluated using an innovative therapeutic adenovirus (Adv)-based HPV vaccine encoding the E1, E2, E6, and E7 HPV16 genes. This new method allowed us to show that vaccine-transduced DCs yielded functional effector T cells and unveiled information on immunohierarchy, showing E1-specific T-cell immunodominance over time. We suggest that this assay can be a valuable translational tool to complement the known animal models, not only for HPV therapeutic vaccines, and supports the use of E1 as an immunotherapeutic target. Nevertheless, the findings reported here need to be validated in a larger number of donors and preferably in patient samples.

Predicting and Empowering Health for Generation Z by Comparing Health Information Seeking and Digital Health Literacy: Cross-Sectional Questionnaire Study.

BACKGROUND: Generation Z (born 1995-2010) members are digital residents who use technology and the internet more frequently than any previous generation to learn about their health. They are increasingly moving away from conventional methods of seeking health information as technology advances quickly and becomes more widely available, resulting in a more digitalized health care system. Similar to all groups, Generation Z has specific health care requirements and preferences, and their use of technology influences how they look for health information. However, they have often been overlooked in scholarly research. OBJECTIVE: First, we aimed to identify the information-seeking preferences of older individuals and Generation Z (those between the ages of 18 and 26 years); second, we aimed to predict the effects of digital health literacy and health empowerment in both groups. We also aimed to identify factors that impact how both groups engage in digital health and remain in control of their own health. METHODS: The Health Information National Trends Survey was adopted for further use in 2022. We analyzed 1862 valid data points by conducting a survey among Chinese respondents to address the research gap. A descriptive analysis, 2-tailed t test, and multiple linear regression were applied to the results. RESULTS: When compared with previous generations, Generation Z respondents (995/1862, 53.44%) were more likely to use the internet to find out about health-related topics, whereas earlier generations relied more on traditional media and interpersonal contact. Web-based information-seeking behavior is predicted by digital health literacy (Generation Z: ß=.192, P<.001; older population: ß=.337, P<.001). While this was happening, only seeking health information from physicians positively predicted health empowerment (Generation Z: ß=.070, P=.002; older population: ß=.089, P<.001). Despite more frequent use of the internet to learn about their health, Generation Z showed lower levels of health empowerment and less desire to look for health information, overall. CONCLUSIONS: This study examined and compared the health information-seeking behaviors of Generation Z and older individuals to improve their digital health literacy and health empowerment. The 2 groups demonstrated distinct preferences regarding their choice of information sources. Health empowerment and digital health literacy were both significantly related to information-seeking behaviors.

The "Loci" of Misinformation and Its Correction in Peer- and Expert-Led Online Communities for Mental Health: Content Analysis.

BACKGROUND: Mental health problems are recognized as a pressing public health issue, and an increasing number of individuals are turning to online communities for mental health to search for information and support. Although these virtual platforms have the potential to provide emotional support and access to anecdotal experiences, they can also present users with large amounts of potentially inaccurate information. Despite the importance of this issue, limited research has been conducted, especially on the differences that might emerge due to the type of content moderation of online communities: peer-led or expert-led. OBJECTIVE: We aim to fill this gap by examining the prevalence, the communicative context, and the persistence of mental health misinformation on Facebook online communities for mental health, with a focus on understanding the mechanisms that enable effective correction of inaccurate information and differences between expert-led and peer-led groups. METHODS: We conducted a content analysis of 1534 statements (from 144 threads) in 2 Italian-speaking Facebook groups. RESULTS: The study found that an alarming number of comments (26.1%) contained medically inaccurate information. Furthermore, nearly 60% of the threads presented at least one misinformation statement without any correction attempt. Moderators were more likely to correct misinformation than members; however, they were not immune to posting content containing misinformation, which was an unexpected finding. Discussions about aspects of treatment (including side effects or treatment interruption) significantly increased the probability of encountering misinformation. Additionally, the study found that misinformation produced in the comments of a thread, rather than as the first post, had a lower probability of being corrected, particularly in peer-led communities. CONCLUSIONS: The high prevalence of misinformation in online communities, particularly when left uncorrected, underscores the importance of conducting additional research to identify effective mechanisms to prevent its spread. This is especially important given the study's finding that misinformation tends to be more prevalent around specific "loci" of discussion that, once identified, can serve as a starting point to develop strategies for preventing and correcting misinformation within them.

Whole-exome sequencing of calcitonin-producing pancreatic neuroendocrine neoplasms indicates a unique molecular signature.

Introduction: Calcitonin-producing pancreatic neuroendocrine neoplasms (CT-pNENs) are an extremely rare clinical entity, with approximately 60 cases reported worldwide. While CT-pNENs can mimic the clinical and diagnostic features of medullary thyroid carcinoma, their molecular profile is poorly understood. Methods: Whole-exome sequencing (WES) was performed on tumor and corresponding serum samples of five patients with increased calcitonin serum levels and histologically validated calcitonin-positive CT-pNENs. cBioPortal analysis and DAVID gene enrichment analysis were performed to identify dysregulated candidate genes compared to control databases. Immunohistochemistry was used to detect the protein expression of MUC4 and MUC16 in CT-pNEN specimens. Results: Mutated genes known in the literature in pNENs like MEN1 (35% of cases), ATRX (18-20% of cases) and PIK3CA (1.4% of cases) were identified in cases of CT-pNENs. New somatic SNVs in ATP4A, HES4, and CAV3 have not been described in CT- pNENs, yet. Pathogenic germline mutations in FGFR4 and DPYD were found in three of five cases. Mutations of CALCA (calcitonin) and the corresponding receptor CALCAR were found in all five tumor samples, but none of them resulted in protein sequelae or clinical relevance. All five tumor cases showed single nucleotide variations (SNVs) in MUC4, and four cases showed SNVs in MUC16, both of which were membrane-bound mucins. Immunohistochemistry showed protein expression of MUC4 in two cases and MUC16 in one case, and the liver metastasis of a third case was double positive for MUC4 and MUC16. The homologous recombination deficiency (HRD) score of all tumors was low. Discussion: CT-pNENs have a unique molecular signature compared to other pNEN subtypes, specifically involving the FGFR4, DPYD, MUC4, MUC16 and the KRT family genes. However, a major limitation of our study was the relative small number of only five cases. Therefore, our WES data should be interpreted with caution and the mutation landscape in CT-pNENs needs to be verified by a larger number of patients. Further research is needed to explain differences in pathogenesis compared with other pNENs. In particular, multi-omics data such as RNASeq, methylation and whole genome sequencing could be informative.

The Insertion of an Evolutionary Lost Four-Amino-Acid Cytoplasmic Tail Peptide into a Syncytin-1 Vaccine Increases T- and B-Cell Responses in Mice.

Human endogenous retrovirus type W (HERV-W) is expressed in various cancers. We previously developed an adenovirus-vectored cancer vaccine targeting HERV-W by encoding an assembled HERV-W group-specific antigen sequence and the HERV-W envelope sequence Syncytin-1. Syncytin-1 is constitutively fusogenic and forms large multinucleated cell fusions when overexpressed. Consequently, immunising humans with a vaccine encoding Syncytin-1 can lead to the formation of extensive syncytia, which is undesirable and poses a potential safety issue. Here, we show experiments in cell lines that restoring an evolutionary lost cleavage site of the fusion inhibitory R-peptide of Syncytin-1 inhibit cell fusion. Interestingly, this modification of the HERV-W vaccine's fusogenicity increased the expression of the vaccine antigens in vitro. It also enhanced Syncytin-1-specific antibody responses and CD8+-mediated T-cell responses compared to the wildtype vaccine in vaccinated mice, with a notable enhancement in responses to subdominant T-cell epitopes but equal responses to dominant epitopes and similar rates of survival following a tumour challenge. The impairment of cell-cell fusion and the enhanced immunogenicity profile of this HERV-W vaccine strengthens the prospects of obtaining a meaningful immune response against HERV-W in patients with HERV-W-overexpressing cancers.

Buffering against exposure to mental health misinformation in online communities on Facebook: the interplay of depression literacy and expert moderation.

BACKGROUND: The proliferation of health misinformation on social media is a growing public health concern. Online communities for mental health (OCMHs) are also considered an outlet for exposure to misinformation. This study explored the impact of the self-reported volume of exposure to mental health misinformation in misinformation agreement and the moderating effects of depression literacy and type of OCMHs participation (expert vs. peer-led). METHODS: Participants (n = 403) were recruited in Italian-speaking OCMHs on Facebook. We conducted regression analyses using PROCESS macro (moderated moderation, Model 3). Measures included: the Depression Literacy Questionnaire (Griffiths et al., 2004), the self-reported misinformation exposure in the OCMHs (3 items), and misinformation agreement with the exposure items (3 items). Whether participants were members of expert or peer-led OCMHs was also investigated. RESULTS: The final model explained the 12% variance in the agreement. There was a positive and significant relationship between misinformation exposure and misinformation agreement (ß = 0.3221, p < .001), a significant two-way interaction between misinformation exposure and depression literacy (ß = - 0.2179, p = .0014 ), and between self-reported misinformation exposure and type of OCMH (ß = - 0.2322, p = .0254), such that at higher levels of depression literacy and in case of participation to expert-led OCMHs, the relationship misinformation exposure-misinformation agreement was weaker. Finally, a three-way interaction was found (ß = 0.2497, p = .0144) that showed that depression literacy moderated the positive relationship between misinformation exposure and misinformation agreement such that the more misinformation participants were exposed to, the more they agreed with it unless they had higher levels of depression literacy; this, however, occurred only if they participated in peer-led groups. CONCLUSIONS: Results provide evidence that the more members reported being exposed to mental health misinformation, the more they tended to agree with it, however this was only visible when participants had lower depression literacy and were participating in peer-led OCMHs. Results of this study suggest that both internal factors (i.e., high depression literacy) and external factors (the type of online community individuals were participating in) can buffer the negative effects of misinformation exposure. It also suggests that increasing depression literacy and expert community moderation could curb the negative consequences of misinformation exposure related to mental health. Results will guide interventions to mitigate the effects of misinformation in OCMHs, including encouraging health professionals in their administration and implementing health education programs.

Critical Test of the Beneficial Consequences of Lifting the Ban on Direct-to-Consumer Advertising for Prescription Drugs in Italy: Experimental Exposure and Questionnaire Study.

BACKGROUND: There are only two countries in the world (the United States and New Zealand) that allow the pharmaceutical branch to advertise prescription medication directly to consumers. There is pressure on governments to allow direct-to-consumer advertising (DTCA) for prescription drugs elsewhere too. One argument the industry uses frequently is the claim that exposure to DCTA, through various methods and occasions, is supposed to improve customers' knowledge of a disease and treatment. This argument has been part of the health care community's wider discussion of whether DTCA of prescription drugs benefits the population's general interest or is only an attempt to increase the sales of the pharmaceutical branch. Belief in true learning by DTCA is rooted in concepts of empowered consumers and their autonomous and empowered decision-making. OBJECTIVE: In this study, we tested the hypotheses that contact with DTCA increases recipients' literacy/knowledge, especially regarding the side effects of treatment (hypothesis 1), and empowerment (hypothesis 2). We further hypothesized that DTCA exposure would not increase depression knowledge (ie, about treatments, symptoms, and prevalence) (hypothesis 3). METHODS: A snowball sample of 180 participants was randomly split into three experimental groups receiving (1) a traditional information sheet, (2) a DTCA video clip for an antidepressant prescription drug, or (3) both. The video was original material from the United States translated into Italian for the experiment. Dependent variables were measures of depression knowledge (regarding treatments, symptoms and prevalence, and antidepressant side effects), depression literacy, and empowerment. RESULTS: None of the experimental groups differed significantly from the others in the empowerment measure (hypothesis 2 not confirmed). Partial confirmation of hypothesis 1 was obtained. Lower values on the depression literacy scale were obtained when participants had been given the video compared to the sheet condition. However, the general depression knowledge and its subscale on side effects reached higher scores when participants were exposed to the DTCA, alone or in combination with the information sheet. Finally, participants showed lower scores on knowledge about treatment and symptoms or prevalence after watching the video compared to the sheet condition (hypothesis 3 confirmed). Symptoms and prevalence knowledge increased only when the video was presented in combination with the sheet. CONCLUSIONS: There is no evidence for an increase in empowerment following DTCA exposure. An increase in knowledge of the side effects of the medication was observed in the group exposed to the DTCA video. This was the only result that confirmed the hypothesis of the beneficial effect of DTCA videos on knowledge. Written information proved to be the most suitable way to convey knowledge on treatments and symptoms prevalence. Our findings support the necessity of studying health literacy and patient empowerment together and the consequences of such an increase in knowledge in terms of help-seeking behavior.

Human Ad19a/64 HERV-W Vaccines Uncover Immunosuppression Domain-Dependent T-Cell Response Differences in Inbred Mice.

Expression of human endogenous retrovirus type W (HERV-W) has been linked to cancer, making HERV-W antigens potential targets for therapeutic cancer vaccines. In a previous study, we effectively treated established tumours in mice by using adenoviral-vectored vaccines targeting the murine endogenous retrovirus envelope and group-specific antigen (Gag) of melanoma-associated retrovirus (MelARV) in combination with anti-PD-1. To break the immunological tolerance to MelARV, we mutated the immunosuppressive domain (ISD) of the MelARV envelope. However, reports on the immunogenicity of the HERV-W envelope, Syncytin-1, and its ISD are conflicting. To identify the most effective HERV-W cancer vaccine candidate, we evaluated the immunogenicity of vaccines encoding either the wild-type or mutated HERV-W envelope ISD in vitro and in vivo. Here, we show that the wild-type HERV-W vaccine generated higher activation of murine antigen-presenting cells and higher specific T-cell responses than the ISD-mutated counterpart. We also found that the wild-type HERV-W vaccine was sufficient to increase the probability of survival in mice subjected to HERV-W envelope-expressing tumours compared to a control vaccine. These findings provide the foundation for developing a therapeutic cancer vaccine targeting HERV-W-positive cancers in humans.

An Endogenous Retrovirus Vaccine Encoding an Envelope with a Mutated Immunosuppressive Domain in Combination with Anti-PD1 Treatment Eradicates Established Tumours in Mice.

Endogenous retroviruses (ERVs) account for 8% of our genome, and, although they are usually silent in healthy tissues, they become reactivated and expressed in pathological conditions such as cancer. Several studies support a functional role of ERVs in tumour development and progression, specifically through their envelope (Env) protein, which contains a region described as an immunosuppressive domain (ISD). We have previously shown that targeting of the murine ERV (MelARV) Env using virus-like vaccine (VLV) technology, consisting of an adenoviral vector encoding virus-like particles (VLPs), induces protection against small tumours in mice. Here, we investigate the potency and efficacy of a novel MelARV VLV with a mutated ISD (ISDmut) that can modify the properties of the adenoviral vaccine-encoded Env protein. We show that the modification of the vaccine's ISD significantly enhanced T-cell immunogenicity in both prime and prime-boost vaccination regimens. The modified VLV in combination with an α-PD1 checkpoint inhibitor (CPI) exhibited excellent curative efficacy against large established colorectal CT26 tumours in mice. Furthermore, only ISDmut-vaccinated mice that survived CT26 challenge were additionally protected against rechallenge with a triple-negative breast cancer cell line (4T1), showing that our modified VLV provides cross-protection against different tumour types expressing ERV-derived antigens. We envision that translating these findings and technology into human ERVs (HERVs) could provide new treatment opportunities for cancer patients with unmet medical needs.

The Empowering Role of Web-Based Help Seeking on Depressive Symptoms: Systematic Review and Meta-analysis.

BACKGROUND: Most research on web-based help seeking for mental health problems has focused on the antecedents of this behavior. Therefore, little is known about the outcomes of web-based help seeking in general or in specific mental health issues. OBJECTIVE: This study was a systematic review and meta-analysis of the literature on the antecedents and consequences of web-based help-seeking behaviors for depressive symptoms. METHODS: A systematic literature search was carried out in 6 scientific databases, leading to 48 studies (for a total of 314,921 participants) included in the qualitative synthesis and 19 included in the meta-analysis. RESULTS: The results indicated a positive relationship between depressive symptoms and web-based help-seeking behaviors through online support groups (r=0.089; P=.009), and Generation Z (r=0.102; P=.008) tended to participate in support groups more than previous generations. In addition, web-based help seeking was positively related to empowerment (r=0.245; P=.004). Other forms of support reported included the internet and specific self-help tools, but no significant relationships were found with depressive symptoms. CONCLUSIONS: More studies examining the outcomes are needed, together with a more rigorous assessment of web-based help-seeking behaviors. Ultimately, we propose a summary framework for the literature on this topic, including the antecedents, patterns of use, and outcomes of web-based help seeking in the context of depressive symptoms.

Efficacy and Synergy with Cisplatin of an Adenovirus Vectored Therapeutic E1E2E6E7 Vaccine against HPV Genome-Positive C3 Cancers in Mice.

Human papillomavirus (HPV) infections are the main cause of cervical and oropharyngeal cancers. As prophylactic vaccines have no curative effect, an efficient therapy would be highly desired. Most therapeutic vaccine candidates target only a small subset of HPV regulatory proteins, namely, E6 and E7, and are therefore restricted in the breadth of their immune response. However, research has suggested E1 and E2 as promising targets to fight HPV+ cancer. Here, we report the design of adenoviral vectors efficiently expressing HPV16 E1 and E2 in addition to transformation-deficient E6 and E7. Vaccination elicited vigorous CD4+ and CD8+ T-cell responses against all encoded HPV16 proteins in outbred mice and against E1 and E7 in C57BL/6 mice. Therapeutic vaccination of C3 tumor-bearing mice led to significantly reduced tumor growth and enhanced survival for both small and established tumors. Tumor biopsies revealed increased numbers of tumor-infiltrating CD8+ T cells in treated mice. Cisplatin enhanced the effect of therapeutic vaccination, accompanied by enhanced infiltration of dendritic cells into the tumor. CD8+ T cells were identified as effector cells in T-cell depletion assays, seemingly under regulation by FoxP3+CD4+ regulatory T cells. Finally, therapeutic vaccination with Ad-Ii-E1E2E6E7 exhibited significantly enhanced survival compared with vaccination with two peptides each harboring a known E6/E7 epitope. We hypothesize that this difference could be due to the induction of additional T-cell responses against E1. These results support the use of this novel vaccine candidate targeting an extended set of antigens (Ad-Ii-E1E2E6E7), in combination with cisplatin, as an advanced strategy to combat HPV+ cancers.

Safety and efficacy of purified clinoptilolite-tuff treatment in patients with irritable bowel syndrome with diarrhea: Randomized controlled trial.

BACKGROUND: Irritable bowel syndrome (IBS) is a highly prevalent gastrointestinal disorder with poor response to treatment. IBS with predominant diarrhea (IBS-D) is accompanied by abdominal pain as well as high stool frequency and urgency. Purified clinoptilolite-tuff (PCT), which is approved by the Food and Drug Administration for use as a dietary supplement with the brand name G-PUR®, has previously shown therapeutic potential in other indications based on its physical adsorption capacity. AIM: To assess whether symptoms of IBS-D can be ameliorated by oral treatment with PCT. METHODS: In this randomized, placebo-controlled, double-blind pilot study, 30 patients with IBS-D diagnosis based on Rome IV criteria were enrolled. Following a 4-wk run-in phase, 14 patients were randomized to receive a 12-wk treatment with G-PUR® (2 g three times daily), and 16 patients received placebo. The relief from IBS-D symptoms as measured by the proportion of responders according to the Subject's Global Assessment (SGA) of Relief was assessed as the primary outcome. For the secondary outcomes, validated IBS-D associated symptom questionnaires, exploratory biomarkers and microbiome data were collected. RESULTS: The proportions of SGA of Relief responders after 12 wk were comparable in both groups, namely 21% in the G-PUR® group and 25% in the placebo group. After 4 wk of treatment, 36% of patients in the G-PUR® group vs 0% in the placebo group reported complete or considerable relief. An improvement in daily abdominal pain was noted in 94% vs 83% (P = 0.0353), and the median number of days with diarrhea per week decreased by 2.4 d vs 0.3 d in the G-PUR® and placebo groups, respectively. Positive trends were observed for 50% of responders in the Bristol Stool Form Scale. Positive trends were also noted for combined abdominal pain and stool consistency response and the Perceived Stress Questionnaire score. Only 64% in the G-PUR® group compared to 86% in the placebo group required rescue medication intake during the study. Stool microbiome studies showed a minor increase in diversity in the G-PUR® group but not in the placebo group. No PCT-related serious adverse events were reported. CONCLUSION: In this randomized, double-blind, placebo-controlled study, the PCT product, G-PUR®, demonstrated safety and clinical benefit towards some symptoms of IBS-D, representing a promising novel treatment option for these patients.

Impacts of Self-Efficacy on Food and Dietary Choices during the First COVID-19 Lockdown in China.

The COVID-19 pandemic has caused a global public health emergency, increasing the prevalence of emotional distress, and potentially leading to altered diet behavior. Self-efficacy measures various aspects of perceiving and understanding emotions. The present study was carried out with the objective of understanding the effect of emotional self-efficacy on dietary behavior and quality. It also shed light on which elements contributed to the link between food-related behavior and perceived dietary quality during the first lockdown of the COVID-19 pandemic. Based on the factor analysis of nineteen food groups, choices, consumption, and socioeconomic status were examined in a sample of 441 Chinese participants. Multiple linear regression examined the association between food consumption, dietary quality, and self-efficacy. Contrary to prior research, the intake of salty snacks and alcoholic beverages dropped by 3.3% and 2.8%, respectively, during the first lockdown. Emotional self-efficacy negatively mediated the relationship between socioeconomic status and dietary quality. In conclusion, emotional self-efficacy is a well-established tool for evaluating how Chinese people cope with negative emotions. As an individual's dietary quality was affected during the imposed lockdown, the present study offers valuable insight into psychosocial factors that may contribute to health disparities by advocating for organized nutritional support in future epidemic-related quarantines.

Misinformation in Italian Online Mental Health Communities During the COVID-19 Pandemic: Protocol for a Content Analysis Study.

BACKGROUND: Social media platforms are widely used by people suffering from mental illnesses to cope with their conditions. One modality of coping with these conditions is navigating online communities where people can receive emotional support and informational advice. Benefits have been documented in terms of impact on health outcomes. However, the pitfalls are still unknown, as not all content is necessarily helpful or correct. Furthermore, the advent of the COVID-19 pandemic and related problems, such as worsening mental health symptoms, the dissemination of conspiracy narratives, and medical distrust, may have impacted these online communities. The situation in Italy is of particular interest, being the first Western country to experience a nationwide lockdown. Particularly during this challenging time, the beneficial role of community moderators with professional mental health expertise needs to be investigated in terms of uncovering misleading information and regulating communities. OBJECTIVE: The aim of the proposed study is to investigate the potentially harmful content found in online communities for mental health symptoms in the Italian language. Besides descriptive information about the content that posts and comments address, this study aims to analyze the content from two viewpoints. The first one compares expert-led and peer-led communities, focusing on differences in misinformation. The second one unravels the impact of the COVID-19 pandemic, not by merely investigating differences in topics but also by investigating the needs expressed by community members. METHODS: A codebook for the content analysis of Facebook communities has been developed, and a content analysis will be conducted on bundles of posts. Among 14 Facebook groups that were interested in participating in this study, two groups were selected for analysis: one was being moderated by a health professional (n=12,058 members) and one was led by peers (n=5598 members). Utterances from 3 consecutive calendar years will be studied by comparing the months from before the pandemic, the months during the height of the pandemic, and the months during the postpandemic phase (2019-2021). This method permits the identification of different types of misinformation and the context in which they emerge. Ethical approval was obtained by the Università della Svizzera italiana ethics committee. RESULTS: The usability of the codebook was demonstrated with a pretest. Subsequently, 144 threads (1534 utterances) were coded by the two coders. Intercoder reliability was calculated on 293 units (19.10% of the total sample; Krippendorff α=.94, range .72-1). Aside from a few analyses comparing bundles, individual utterances will constitute the unit of analysis in most cases. CONCLUSIONS: This content analysis will identify deleterious content found in online mental health support groups, the potential role of moderators in uncovering misleading information, and the impact of COVID-19 on the content. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/35347.