Reproductive factors and mammographic density within the International Consortium of Mammographic Density: A cross-sectional study.

BACKGROUND: Elevated mammographic density (MD) for a woman's age and body mass index (BMI) is an established breast cancer risk factor. The relationship of parity, age at first birth, and breastfeeding with MD is less clear. We examined the associations of these factors with MD within the International Consortium of Mammographic Density (ICMD). METHODS: ICMD is a consortium of 27 studies with pooled individual-level epidemiological and MD data from 11,755 women without breast cancer aged 35-85 years from 22 countries, capturing 40 country-& ethnicity-specific population groups. MD was measured using the area-based tool Cumulus. Meta-analyses across population groups and pooled analyses were used to examine linear regression associations of square-root (√) transformed MD measures (percent MD (PMD), dense area (DA), and non-dense area (NDA)) with parity, age at first birth, ever/never breastfed and lifetime breastfeeding duration. Models were adjusted for age at mammogram, age at menarche, BMI, menopausal status, use of hormone replacement therapy, calibration method, mammogram view and reader, and parity and age at first birth when not the association of interest. RESULTS: Among 10,988 women included in these analyses, 90.1% (n = 9,895) were parous, of whom 13% (n = 1,286) had ≥ five births. The mean age at first birth was 24.3 years (Standard deviation = 5.1). Increasing parity (per birth) was inversely associated with √PMD (ß: - 0.05, 95% confidence interval (CI): - 0.07, - 0.03) and √DA (ß: - 0.08, 95% CI: - 0.12, - 0.05) with this trend evident until at least nine births. Women who were older at first birth (per five-year increase) had higher √PMD (ß:0.06, 95% CI:0.03, 0.10) and √DA (ß:0.06, 95% CI:0.02, 0.10), and lower √NDA (ß: - 0.06, 95% CI: - 0.11, - 0.01). In stratified analyses, this association was only evident in women who were post-menopausal at MD assessment. Among parous women, no associations were found between ever/never breastfed or lifetime breastfeeding duration (per six-month increase) and √MD. CONCLUSIONS: Associations with higher parity and older age at first birth with √MD were consistent with the direction of their respective associations with breast cancer risk. Further research is needed to understand reproductive factor-related differences in the composition of breast tissue and their associations with breast cancer risk.

Selecting a Brief Cognitive Screening Test Based on Patient Profile: It Is Never Too Early to Start.

Introduction: Cognitive impairment, marked by a decline in memory and attention, is frequently underdiagnosed, complicating effective management. Cardiovascular risk factors (CVR) and anticholinergic burden (ACB) are significant contributors to dementia risk, with ACB often stemming from medications prescribed for neuropsychiatric disorders. This study evaluates cognitive profiles through three brief cognitive tests, analyzing the impact of CVR and ACB presence. Methods: This cross-sectional study was performed between 2019 and 2023 in community pharmacies and an outpatient clinic in Valencia, Spain. Eligible participants were patients with subjective memory complaints 50 years or older with clinical records of cardiovascular factors. Patients with conflicting information regarding diabetes diagnosis or not taking concomitant medications were excluded. Three brief cognitive tests (Memory Impairment Screening (MIS), Semantic Verbal Fluency Test, and SPMSQ) were assessed. CVR was calculated using the European SCORE2 table, and ACB was assessed using the CALS scale. Results: Among 172 patients with memory complaints and CVR factors, 60% failed at least one cognitive test. These patients were on significantly more medications and had higher blood pressure and HbA1c levels. An increase in CVR and ACB was associated with more failed tests. Additionally, elevated SCORE2 scores were associated with a greater failure rate on the MIS test, while patients with elevated ACB more frequently failed the SPMSQ test. Conclusions: Selecting an adequate brief cognitive test according to patients' characteristics offers an opportunity to screen patients who are probably cognitively impaired. Whereas the MIS test may be helpful for patients with cardiovascular risk, SPMSQ stands out among patients with significant ACB.

Health-Related Quality of Life in Long-Term Colorectal Cancer Survivors.

The aim of our study is to evaluate the relationship between sociodemographic and clinical characteristics of individuals with Colorectal Cancer (CRC), tumour-intrinsic characteristics and treatment received with health-related quality of life (HRQoL). METHODS: Cross-sectional analysis of data from 805 survivors from the MCC study was conducted. HRQoL was assessed through a general and specific questionnaire, SF-12 and FCSI (Colorectal Symptom Index). Statistical analyses were performed with linear regression with adjustment for sociodemographic variables, stage at diagnosis and histological grade. RESULTS: Participants had survived a median of 7.9 years from diagnosis (IQR 7.1-8.5 years). Age at diagnosis, sex and area showed a clear association with HRQoL in both physical and mental dimensions of the SF-12 questionnaire. A direct association between CRC recurrence was also found in the PCS-12 and MCS-12 dimensions and radical surgery in the PCS-12. Regarding the scores in FCSI questionnaire, statistically significant differences were observed by sex, age and area, with older women being the most impaired (p < 0.001). CONCLUSIONS: Age, sex and area was associated with lower scores of HRQoL among CRC survivors. Knowing the determinants related to HRQoL would allow us to lay the groundwork to develop strategies that help reduce morbidity and mortality, relapses and increase HRQoL.

Burden of postmenopausal breast cancer attributable to excess body weight: comparative study of body mass index and CUN-BAE in MCC-Spain study.

BACKGROUND: 10% of postmenopausal breast cancer cases are attributed to a high body mass index (BMI). BMI underestimates body fat, particularly in older women, and therefore the cancer burden attributable to obesity may be even higher. However, this is not clear. CUN-BAE (Clínica Universidad de Navarra-Body Adiposity Estimator) is an accurate validated estimator of body fat, taking into account sex and age. The objective of this study was to compare the burden of postmenopausal breast cancer attributable to excess body fat calculated using BMI and CUN-BAE. METHODS: This case-control study included 1033 cases of breast cancer and 1143 postmenopausal population controls from the multicase-control MCC-Spain study. Logistic regression models were used to calculate odds ratios (ORs). The population attributable fraction (PAF) of excess weight related to breast cancer was estimated with both anthropometric measures. Stratified analyses were carried out for hormone receptor type. RESULTS: Excess body weight attributable to the risk of breast cancer was 23.0% when assessed using a BMI value ≥30 kg/m2 and 38.0% when assessed using a CUN-BAE value of ≥40% body fat. Hormone receptor stratification showed that these differences in PAFs were only observed in hormone receptor positive cases, with an estimated burden of 19.9% for BMI and 41.9% for CUN-BAE. CONCLUSION: These findings suggest that the significance of excess body fat in postmenopausal hormone receptor positive breast cancer could be underestimated when assessed using only BMI. Accurate estimation of the cancer burden attributable to obesity is crucial for planning effective prevention initiatives.

Landscape of in situ cytokine expression, soluble C-type lectin receptors, and vitamin D in patients with recurrent vulvovaginal candidiasis.

The immunopathogenesis of recurrent vulvovaginal candidiasis (RVVC) is poorly understood. Recently, it was reported that patients with RVVC present a decrease in both the fungicidal capacity of neutrophils and the proliferative capability of peripheral blood mononuclear cells in response to Candida albicans infection, suggesting an alteration in the innate and adaptive immune response. The aim of this study was to determine the in-situ expression, in the vaginal mucosa, of genes associated with the immune response, as well as the serum concentrations of dectin-1, mannose-binding lectin (MBL), and vitamin D in patients with RVVC. A study was carried out on 40 patients with a diagnosis of RVVC and 26 healthy women. Vaginal scrapings were obtained, and the expression of genes that encode cytokines and transcription factors specific for Th1, Th2, Th17, Treg, pro-inflammatory profiles, and enzymes related to oxidative/microbicidal mechanisms was evaluated by quantitiative polymerase chain reaction (qPCR). Additionally, serum levels of vitamin D and the soluble receptors dectin-1 and MBL were determined by enzyme-linked immunosorbent assay (ELISA). In patients with RVVC, a decreased expression of T-bet, RORγ-T, IL-1ß, and IL-17, and an increase in the expression of FOXP3, IL-4, IL-8, IL-10, and IL-18 were observed when compared to healthy women: moreover, decreased levels of MBL were also observed in these patients. These results confirm that patients with RVVC present in-situ alterations in both the specific and adaptive immune response against Candida spp., a fact that could be associated with the exaggerated vaginal inflammatory response.

The study concerns the immune response of women with recurrent vulvovaginal candidiasis; we observed an alteration in the expression of genes that participate in the control of infection, a fact that could be associated with the exaggerated vaginal inflammatory response observed in those patients.

Anticipated prehospital decision delay in response to different symptom clusters in acute coronary syndrome: Results from the Spanish Cardiobarometer study.

BACKGROUND AND OBJECTIVE: Reducing patient decision delay - the time elapsed between symptom onset and the moment the patient decides to seek medical attention - can help improve acute coronary syndrome survival. Patient decision delay is typically investigated in retrospective studies of acute coronary syndrome survivors that are prone to several biases. To offer an alternative approach, the goal of this research was to investigate anticipated patient decision delay in the general population in response to different symptom clusters. METHODS: We developed scenarios representing four commonly experienced symptom clusters: classic (chest symptoms only), heavy (a large number of very intense symptoms including chest pain), diffuse (mild symptoms including chest pain), and weary (mild symptoms without clear chest involvement). The scenarios were administered in random order in a representative survey of 1002 adults ≥55 years old from the non-institutionalized general population in Spain. We measured help-seeking intentions, anticipated patient decision delay (waiting >30 min to seek help), and symptom attribution. RESULTS: Patient decision delay was most common in the diffuse scenario (55%), followed by the weary (34%), classic (22%), and heavy (11%) scenarios. Attributing the symptoms to a cardiovascular cause and intentions to call emergency services were least frequent in the weary and diffuse scenarios. Women were less likely to intend to seek help than men in the classic (OR = 0.48, [0.27, 0.85], diffuse (OR = 0.67, [0.48, 0.92]), and weary (OR = 0.66, [0.44, 0.98]) scenarios, despite being more likely to attribute symptoms to cardiovascular causes. Participants with traditional cardiovascular risk factors (e.g., diabetes, hypercholesterolemia, hypertension) reported faster help-seeking, whereas participants with obesity and history of depression were more likely to delay. DISCUSSION: The diverse manifestations of acute coronary syndrome generate fundamentally different appraisals. Anticipated patient decision delay varies as a function of socio-demographic characteristics and medical history, supporting findings from studies with patients who experienced ACS. Measuring anticipated patient decision delay in the general population can help reveal potential barriers to help-seeking and capture effects of population interventions.

Combined use of composite mesh and acellular dermal matrix graft for abdominal wall repair following tumour resection.

BACKGROUND: Surgeries for sarcomas in the abdominal wall require wide resections, often radical en bloc resections, which generate major defects involving a very complex repair. The combined use of porcine dermal xenografts, together with composite meshes, may assist in the repair of these defects with minimal complications. METHOD: We present a series of 19 patients (10 males and 9 females), with a mean age of 53.2 years (range: 11-86 years) treated in the Sarcoma Unit of the Virgen de la Arrixaca University Hospital from January 2015 to December 2021. Histopathologically, there were four chondrosarcomas (21%), three Ewing sarcomas (15.7%), two desmoid tumours (10.5%), two undifferentiated pleomorphic sarcomas (10.5%), two well-differentiated liposarcomas (10.5%), two leiomyosarcomas (10.5%), one synovial sarcoma, one dermatofibrosarcoma protuberans, one fibromyxoid sarcoma (or Evans tumour), and one metastasis from an adenocarcinoma of unknown origin. All the patients were resected following surgical oncology principles and reconstructed by means of the combined use of a composite mesh acting as a neoperitoneum and a porcine dermal xenograft acting as an abdominal neofascia. RESULTS: The mean size of the defects generated after surgery for tumour excision was 262.8 cm2 (range: 150-600 cm2). After a mean follow-up of 38 months, six patients (31.5%) developed complications-two cases of wound dehiscence, one case of surgical wound infection, one case of graft partial necrosis, one case of anastomotic leak and one death due to multiorgan failure secondary to massive bronchoaspiration. CONCLUSION: Surgeries for sarcomas of the abdominal wall require wide oncological resections, which generate major abdominal wall defects. The repair of these defects by means of the combined use of synthetic and biological meshes is a technique associated with minimal complications and excellent medium-term results.

Se and Hg in processed fish-derived products and their fish raw materials: Occurrence, Se:Hg molar ratio, HBVSe index, bioaccessibility and Caco-2 cells toxicity.

Processing conditions applied during food production could affect food component contents and bioaccessibility. Here, possible changes in Hg and Se total and species contents and bioaccessibility have been tracked in each stage of the production chain of processed fish-derived products. Therefore, Se:Hg molar ratio and Selenium Health Benefit Value (HBVSe) were calculated for final products and raw materials, resulting favorable in all cases, suggesting the safety of surimi-based products regarding mercury. Speciation studies revealed the presence of SeMeSeCys and SeMet in all samples. Thus, the integrity of the selenium species seems to be maintained. Moreover, in vitro gastrointestinal digestion model evidenced that Se bioaccessibility ranged between 20-39 % for all samples, while in case of Hg was between 8-37 %. Additionaly, SeMeSeCys and SeMet were also identified in the gastrointestinal extracts. Finally, no cytotoxicity was observed after exposure of Caco-2 cells to the gastrointestinal extracts.

Development of a fast and low-cost aqueous based-extraction protocol for the simultaneous extraction and characterization of SiO2 and TiO2 (nano)particles in confectionary products.

BACKGROUND: The determination of (nano)particulate content from food additives has been a long-standing concern for authorities since it is of vital importance for ensuring food safety, regulatory adherence, and transparent consumer information. Nonetheless, a critical step in these determinations is the refinement of a careful and quantitative extraction process for particles that may be found within complex matrices such as confectionery products. The development of new technologies and analysis methods for nanoparticles is ongoing. Whereas new technologies and analysis methods for nanoparticles are being developed, the extraction of (nano)particles of different nature has not been adequately addressed in the literature. RESULTS: A simple aqueous extraction procedure was found to be suitable for the simultaneous extraction of TiO2 and SiO2 (nano)particles from five confectionery products. Neither the extraction agents (water, lipase, pancreatin and Tris-HCl solutions) nor the methods (manual shaking, ultrasonic bath, ultrasonic probe and ultrafiltration) altered the size, morphology, or aggregation state of either type of particle, as revealed by the micrographs obtained by Transmission Electron Microscopy (TEM). Single-particle ICP-MS (spICP-MS) determined that the optimal conditions for extracting both types of particles involve manual shaking using water as the solvent. Furthermore, the use of enzymes seemed to hinder the determination of both types of particles by spICP-MS. (Nano)particles of TiO2 and SiO2 were detected in all the confectionaries, even though the E171 additive was only labeled in one of them. The average percentage of nanoparticulate TiO2 material in the evaluated products was 30 %, while no nanometer-sized particles of SiO2 were detected. SIGNIFICANCE: Ensuring food safety, regulatory compliance and transparent consumer information relies on getting reliable results that connect with the application of sample treatment procedures for detecting unaltered nanoparticles in food products. The presented research introduces an economical, swift, user-friendly, environmentally responsible, and harmonious extraction method for the concurrent analysis of TiO2 and SiO2 particles in confectionery samples. Furthermore, particles from additives not included in the labeling have been detected, characterized, and quantified in the confectionary products.

Intake Characteristics as Predictors of Psychotherapy Outcome in a Practice Research Network in Argentina.

There are few studies exploring intake diagnostic characteristics as predictors of change in integrative naturalistic settings. The aim of this study is to explore baseline variables at the intake process and establish the predictive value of the individual trajectories of the patients. We recruited 259 patients undergoing an integrative psychotherapy network of psychotherapists from Buenos Aires, Argentina. Every therapist completed the intake form of each patient involved in the routine outcome monitoring. Thereafter step-wise regressions based on forward selection strategies were used, in order to identify meaningful baseline predictors of patients' clinical evolution, derived from the intake process. The selected predictors were social support network, subjective distress, the initial measure of clinical distress, unemployment, sociocultural status and reactance. When including those six variables in a multilevel model, the results indicate that social support network, subjective distress, and the initial measure of clinical distress were significant predictors of the trajectories of OQ-30, whereas unemployment, sociocultural status and reactance were not significant. The results regarding social support network are in line with the literature, while results of socioeconomic status (unemployment and sociocultural level) move in an opposite direction in comparison to the available evidence. Moreover, the mental health findings (initial OQ-30 and subjective distress) confirm the contradictory body of literature produced in this domain. Finally, reactance seems to be a significant predictor in previous study in contradiction of our results. Overall, this endeavor constitutes important but preliminary evidence to enhance the production of bottom-up science within practice research networks in the global south.

Cross-sectional and longitudinal associations of adherence to WCRF/AICR cancer prevention recommendations with health-related quality of life in breast cancer survivors. Health-EpiGEICAM study.

OBJECTIVES: Adherence to healthy lifestyle recommendations has been reported to improve health-related quality of life (HRQL) in breast cancer (BC) patients, but the influence of long-term behavioral changes remains unknown. We evaluated the association between adherence to the 2018 World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) cancer prevention recommendations and HRQL both, at BC diagnosis and the change 7-12 years later. DESIGN: Prospective cohort study. SETTINGS AND PARTICIPANTS: A total of 406 breast cancer survivors, from the EpiGEICAM study, were recruited in 16 Spanish hospitals. MEASUREMENTS: Epidemiological, clinical, dietary, physical activity and HRQL information was collected both at recruitment and 7-12 years later. A 7-item score to measure compliance with recommendations was assessed according to the 2018 WCRF/AICR scoring criteria. HRQL was evaluated using SF-36 questionnaire. Linear mixed models for longitudinal data were used to assess the cross-sectional and longitudinal association between adherence score and the physical and mental component summary scores. RESULTS: At diagnosis, for each unit increase in WCRF/AICR score adherence, the HRQL physical domain increased 0.78 points (95%CI: -0.04 to 1.60; P trend:0.06). The mean change in physical HRQL from diagnosis to follow-up per unit increase in within-subject adherence score was 0.73 points (95%CI: -0.18 to 1.65; P trend: 0.12). For the mental domain, no association was observed with compliance with the recommendations at diagnosis, nor with changes in adherence over time. CONCLUSIONS: Our results suggest that Increased adherence to WCRF/AICR cancer prevention recommendations over time could contribute to slightly improved long-term physical HRQoL in BC survivors.

Social networks use in the context of Schizophrenia: a review of the literature.

Schizophrenia is a persistent mental health condition that, while presenting challenges, underscores the dynamic nature of cognitive functions and encourages a unique perspective on how individuals engage with their surroundings. Social networks, as a means of communication of great importance at the present time, are for this type of people a way of interacting with their environment with a high level of security. The aim is to find out how schizophrenia is dealt with in different social networks and to differentiate between different types of articles dealing with the use of Facebook, X (former Twitter), YouTube, TikTok, Instagram, and Weibo. A total of 45 articles to i) Social networks used, ii) Country of analyzed users, iii) age of the users analyzed, iv) focus of the analyzed manuscript (mental health literacy, stigmatization, detection of patterns associated with schizophrenia, and Harmful substance use). It was observed that 45.45% of the studies analyzed were conducted in the USA population, followed by UK and China (13.64%). The most analyzed social networks were those based on audiovisual communication (60%). Furthermore, the two main foci addressed in these articles were: stigmatization of schizophrenia with 16 articles (35.55%), following by the prediction of schizophrenia-detecting patterns with 15 articles (33.33%) and the use of social networks to stigmatize people with schizophrenia (38%) and only 14 articles (31.11%) were focused on mental health literacy. Likewise, it was found that there is great potential in the use of the analysis of the content generated, as possible predictors of the presence of this disease, which would allow rapid detection and intervention for psychosis and schizophrenia.

Risk of prostate cancer in the proximity of industrial installations: A multicase-control study in Spain (MCC-Spain).

BACKGROUND: Prostate cancer (PC) is the second most frequent tumor in men worldwide; however, its etiology remains largely unknown, with the exception of age and family history. The wide variability in incidence/mortality across countries suggests a certain role for environmental exposures that has not yet been clarified. OBJECTIVE: To evaluate the association between risk of PC (by clinical profile) and residential proximity to pollutant industrial installations (by industrial groups, groups of carcinogens, and specific pollutants released), within the context of a Spanish population-based multicase-control study of incident cancer (MCC-Spain). METHODS: This study included 1186 controls and 234 PC cases, frequency matched by age and province of residence. Distances from participants' residences to the 58 industries located in the study area were calculated and categorized into "near" (considering different limits between ≤1 km and ≤ 3 km) or "far" (>3 km). Odds ratios (ORs) and 95 % confidence intervals (95%CIs) were estimated using mixed and multinomial logistic regression models, adjusted for potential confounders and matching variables. RESULTS: No excess risk was detected near the overall industries, with ORs ranging from 0.66 (≤2 km) to 1.11 (≤1 km). However, positive associations (OR; 95%CI) were found, by industrial group, near (≤3 km) industries of ceramic (2.54; 1.28-5.07), food/beverage (2.18; 1.32-3.62), and disposal/recycling of animal waste (2.67; 1.12-6.37); and, by specific pollutant, near plants releasing fluorine (4.65; 1.45-14.91 at ≤1.5 km) and chlorine (5.21; 1.56-17.35 at ≤1 km). In contrast, inverse associations were detected near industries releasing ammonia, methane, dioxins+furans, polycyclic aromatic hydrocarbons, trichloroethylene, and vanadium to air. CONCLUSIONS: The results suggest no association between risk of PC and proximity to the overall industrial installations. However, some both positive and inverse associations were detected near certain industrial groups and industries emitting specific pollutants.

Alleviating Heat Stress in Fattening Pigs: Low-Intensity Showers in Critical Hours Alter Body External Temperature, Feeding Pattern, Carcass Composition, and Meat Quality Characteristics.

Heat stress is a significant environmental problem that has a detrimental impact on animal welfare and production efficiency in swine farms. The current study was conducted to assess the effect of low-intensity showers, provided during critical high-temperature hours daily, on body external temperature, feeding pattern, and carcass and meat quality characteristics in fattening pigs. A total of 400 animals (200 barrows and 200 gilts) were randomly allotted in 40 pens. A shower nozzle was installed over 20 pens (half barrows and half gilts) where pigs received a low-intensity shower for 2 min in 30 min intervals from 12 to 19 h (SHO group). Another group without showers was also considered (CON). Feeder occupancy measurement, thermographic measures, and carcass and meat quality parameters were studied. In the periods with higher environmental temperatures, SHO animals showed an increase in the feeder occupancy rate compared to the CON group. A decrease in temperature was observed after the shower, regardless of the anatomical location (p < 0.005). The treatment with showers led to higher values than in the CON group of 4.72%, 3.87%, 11.8%, and 15.1% for hot carcass weight, lean meat yield, and fat thickness in Longissimus Dorsi (LD) and Gluteus Medius muscles, respectively (p < 0.01). Pork from CON showed a 14.9% higher value of drip loss, and 18.9% higher malondialdehyde concentration than SHO (p < 0.01); meanwhile, intramuscular fat content was 22.8% higher in SHO than in CON (p < 0.01). On the other hand, the CON group exhibited higher L* (2.13%) and lower a* and b* values (15.8% and 8.97%) compared to the SHO group. However, the pH20h of the CON group was significantly lower than that of the SHO group (p < 0.001), indicating a softer pH decrease. Related to fatty acids in subcutaneous outer and inner layers and intramuscular fat, the CON group showed higher ΣSFA and lower ΣMUFA and Δ9-desaturase indexes than SHO (p < 0.05). In conclusion, the amelioration of heat stress through showers at critical times should be considered an interesting tool that improves both carcass and meat quality, as well as animal welfare.

Herpes Simplex Virus type 1 inhibits autophagy in glial cells but requires ATG5 for the success of viral replication.

Herpes Simplex Virus type 1 (HSV-1) 1 is a neurotropic virus that has been associated with neurodegenerative disorders. The dysregulation of autophagy by HSV-1 has been proposed as a potential cause of neurodegeneration. While studies have extensively tackled the interaction between autophagy and HSV-1 in neurons, research in glial cells is currently limited. Our studies demonstrate that HSV-1 inhibits, but not completely blocks, the formation of autophagosomes in human oligodendroglioma- and astrocytoma- derived cell lines. These findings have been confirmed in murine oligodendrocyte precursor cells (OPCs). Finally, this study investigates the impact of autophagy on HSV-1 infection in glial cells. While the lack of basal autophagy in LC3B knockout glial cells does not have a significant effect on viral infection, cells without the autophagy-related protein ATG5 exhibit reduced viral production. The absence of ATG5 leads to a decrease in the transcription and replication of viral genes, as well as a delay in the initial stages of the formation of HSV-1 replication compartments. These findings indicate that while autophagy may not play a significant role in antiviral defense in glial cells, HSV-1 may be inhibiting autophagy to exploit non-canonical functions of certain components of the autophagic machinery, such as ATG5, to benefit its lifecycle.

Proceedings of the second international meeting on endemic mycoses of the Americas (IMEMA) and first international symposium on implantation mycoses (ISIM).

The second international meeting on endemic mycoses of the Americas (IMEMA) and the first international symposium on implantation mycoses (ISIM) took place in Santiago del Estero, Argentina, on September 25-27, 2023. The conference provided a platform for researchers, clinicians, and experts to discuss the latest developments in the field of endemic and implantation mycoses. Topics included epidemiology, diagnostic advances, treatment strategies, and the impact of environmental factors on the spread of these fungal diseases. IMEMA and ISIM contributed to the regional discourse on the mycoses, emphasizing the importance of international cooperation in addressing these public health challenges.

IMEMA/ISIM, held in Santiago del Estero, Argentina, convened experts to discuss endemic and implantation mycoses, covering topics such as epidemiology, diagnostics, treatment, and advocacy. The event highlighted ongoing efforts in combating these diseases.

Activation of Shh/Smo is sufficient to maintain oligodendrocyte precursor cells in an undifferentiated state and is not necessary for myelin formation and (re)myelination.

Myelination is the terminal step in a complex and precisely timed program that orchestrates the proliferation, migration and differentiation of oligodendroglial cells. It is thought that Sonic Hedgehog (Shh) acting on Smoothened (Smo) participates in regulating this process, but that these effects are highly context dependent. Here, we investigate oligodendroglial development and remyelination from three specific transgenic lines: NG2-CreERT2 (control), Smofl/fl/NG2-CreERT2 (loss of function), and SmoM2/NG2-CreERT2 (gain of function), as well as pharmacological manipulation that enhance or inhibit the Smo pathway (Smoothened Agonist (SAG) or cyclopamine treatment, respectively). To explore the effects of Shh/Smo on differentiation and myelination in vivo, we developed a highly quantifiable model by transplanting oligodendrocyte precursor cells (OPCs) in the retina. We find that myelination is greatly enhanced upon cyclopamine treatment and hypothesize that Shh/Smo could promote OPC proliferation to subsequently inhibit differentiation. Consistent with this hypothesis, we find that the genetic activation of Smo significantly increased numbers of OPCs and decreased oligodendrocyte differentiation when we examined the corpus callosum during development and after cuprizone demyelination and remyelination. However, upon loss of function with the conditional ablation of Smo, myelination in the same scenarios are unchanged. Taken together, our present findings suggest that the Shh pathway is sufficient to maintain OPCs in an undifferentiated state, but is not necessary for myelination and remyelination.

ApTOLL: A new therapeutic aptamer for cytoprotection and (re)myelination after multiple sclerosis.

BACKGROUND AND PURPOSE: ApTOLL is an aptamer selected to antagonize toll-like receptor 4 (TLR4), a relevant actor for innate immunity involved in inflammatory responses in multiple sclerosis (MS) and other diseases. The currently available therapeutic arsenal to treat MS is composed of immunomodulators but, to date, there are no (re)myelinating drugs available in clinics. In our present study, we studied the effect of ApTOLL on different animal models of MS. EXPERIMENTAL APPROACH: The experimental autoimmune encephalomyelitis (EAE) model was used to evaluate the effect of ApTOLL on reducing the inflammatory component. A more direct effect on oligodendroglia was studied with the cuprizone model and purified primary cultures of murine and human oligodendrocyte precursor cells (OPCs) isolated through magnetic-activated cell sorting (MACS) from samples of brain cortex. Also, we tested these effects in an ex vivo model of organotypic cultures demyelinated with lysolecithin (LPC). KEY RESULTS: ApTOLL treatment positively impacted the clinical symptomatology of mice in the EAE and cuprizone models, which was associated with better preservation plus restoration of myelin and oligodendrocytes in the demyelinated lesions of animals. Restoration was corroborated on purified cultures of rodent and human OPCs. CONCLUSION AND IMPLICATIONS: Our findings reveal a new therapeutic approach for the treatment of inflammatory and demyelinating diseases such as MS. The molecular nature of the aptamer exerts not only an anti-inflammatory effect but also neuroprotective and remyelinating effects. The excellent safety profile demonstrated by ApTOLL in animals and humans opens the door to future clinical trials in MS patients.

Moving Forward on Tumor Pathology Research Reporting: A Guide for Pathologists From the World Health Organization Classification of Tumors Living Evidence Gap Map by Tumour Type Group.

Evidence-based medicine (EBM) can be an unfamiliar territory for those working in tumor pathology research, and there is a great deal of uncertainty about how to undertake an EBM approach to planning and reporting histopathology-based studies. In this article, reviewed and endorsed by the Word Health Organization International Agency for Research on Cancer's International Collaboration for Cancer Classification and Research, we aim to help pathologists and researchers understand the basics of planning an evidence-based tumor pathology research study, as well as our recommendations on how to report the findings from these. We introduce some basic EBM concepts, a framework for research questions, and thoughts on study design and emphasize the concept of reporting standards. There are many study-specific reporting guidelines available, and we provide an overview of these. However, existing reporting guidelines perhaps do not always fit tumor pathology research papers, and hence, here, we collate the key reporting data set together into one generic checklist that we think will simplify the task for pathologists. The article aims to complement our recent hierarchy of evidence for tumor pathology and glossary of evidence (study) types in tumor pathology. Together, these articles should help any researcher get to grips with the basics of EBM for planning and publishing research in tumor pathology, as well as encourage an improved standard of the reports available to us all in the literature.

Five years of advances in electrochemical analysis of protein biomarkers in lung cancer: a systematic review.

Lung cancer is the leading cause of cancer death in both men and women. It represents a public health problem that must be addressed through the early detection of specific biomarkers and effective treatment. To address this critical issue, it is imperative to implement effective methodologies for specific biomarker detection of lung cancer in real clinical samples. Electrochemical methods, including microfluidic devices and biosensors, can obtain robust results that reduce time, cost, and assay complexity. This comprehensive review will explore specific studies, methodologies, and detection limits and contribute to the depth of the discussion, making it a valuable resource for researchers and clinicians interested in lung cancer diagnosis.