The impact of screen use on sleep health across the lifespan: A National Sleep Foundation consensus statement.

OBJECTIVE: To achieve consensus on whether screen-based digital media (1) in general, (2) via prebedtime content, and (3) via prebedtime light impairs sleep health in (a) childhood, (b) adolescence, and (c) adulthood. Furthermore, to address whether employing behavioral strategies and interventions may reduce the potential negative effects of screens on sleep health. METHODS: The National Sleep Foundation convened a 16-person multidisciplinary expert panel ("Panel"). Panelists met virtually 5 times throughout 2023, during which they followed a modified Delphi RAND/UCLA Appropriateness Method to reach consensus. RESULTS: The Panel conducted a literature review starting with 2209 articles, narrowed down to 522 relevant empirical articles and 52 relevant review articles. The search was refined to include 35 experimental/intervention studies that examined whether there was a causal link between screen-based digital media and sleep. In addition, panelists reviewed 5 recent relevant systematic review articles. After reviewing the summarized current literature, panelists voted on 10 candidate statements about whether screen use impairs sleep health. The Panel met virtually to discuss the results of the first round of votes, which was then followed by a second round of voting, ultimately achieving consensus on 5 out of the 10 statements. CONCLUSIONS: The Panel achieved consensus that (1) in general, screen use impairs sleep health among children and adolescents, (2) the content of screen use before sleep impairs sleep health of children and adolescents, and (3) behavioral strategies and interventions may attenuate the negative effects of screen use on sleep health.

Do Longer Fins Improve Ocean Rescues? A Comprehensive Investigation into Lifeguard Performance and Physiological Impact.

Coastal environments present dynamic challenges necessitating rapid and efficient responses during aquatic emergencies. Lifeguards, as pivotal links in the intervention chain, rely on various tools, with rescue time being paramount. The choice of fins, specifically long versus short ones, plays a critical role in optimizing lifeguard performance during rescues. This randomized cross-over study explores the impact of flipper size on ocean rescues, employing a sample of 14 lifeguards. Long fins (LFs) and short fins (SFs) were compared in terms of rescue time (RT) and physiological load (PL). Tests included ocean rescues without fins (R), with LF (R-LF), and with SF (R-SF). Variables recorded encompassed swim approach time, tow-in time, overall rescue time, perceived exertion rates (RPEs), and post-rescue lactate concentration. Long fins demonstrated superior performance in swim approach and tow-in times compared to both short fins and no fins (p < 0.001). Overall rescue time favored long fins significantly (p < 0.001), indicating their efficiency in practical ocean rescue scenarios. Physiologically, long fins induced lower perceived exertion in arms (p = 0.033) compared to short fins. Lactate concentrations post-rescue revealed no significant differences (p > 0.05). This study demonstrates that long fins significantly improve lifeguard performance during ocean rescues, reducing rescue times and alleviating arm fatigue.

Current Trends and Advancements in the Management of Hepatocellular Carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) remains a significant global health burden with a high mortality rate. Over the past 40 years, significant progress has been achieved in the prevention and management of HCC. SUMMARY: Hepatitis B vaccination programs, the development of direct acting antiviral drugs for Hepatitis C, and effective surveillance strategies provide a profound basis for the prevention of HCC. Advanced surgery and liver transplantation along with local ablation techniques potentially offer cure for the disease. Also, just recently, the introduction of immunotherapy opened a new chapter in systemic treatment. Finally, the introduction of the BCLC classification system for HCC, clearly defining patient groups and assigning reasonable treatment options, has standardized treatment and become the basis of almost all clinical trials for HCC. With this review, we provide a comprehensive overview of the evolving landscape of HCC management and also touch on current challenges. KEY MESSAGE: A comprehensive and multidisciplinary approach is crucial for effective HCC management. Continued research and clinical trials are imperative to further enhance treatment options and will ultimately reduce the global burden of this devastating disease.

Physicochemical Properties and Microbiome of Vineyard Soils from DOP Ribeiro (NW Spain) Are Influenced by Agricultural Management.

Agricultural management influences the soil ecosystem by affecting its physicochemical properties, residues of pesticides and microbiome. As vineyards grow crops with the highest incidence of pesticides, the aim of this study was to evaluate the impact of conventional and sustainable management systems of vineyards from DOP Ribeiro on the soil's condition. Samples from soils under three different management systems were collected, and the main soil physicochemical properties were evaluated. A selection of 50 pesticides were investigated by liquid chromatography with tandem mass spectrometry. The bacterial and fungal microbiomes were characterized through amplicon sequencing. The results show that organic agriculture positively influences soil pH and the concentration of some nutrients compared to conventional management. Our microbiome analysis demonstrated that transitioning from conventional to organic management significantly improves several BeCrop® indexes related to key microbial metabolism and soil bio-sustainability. Such a transition does not affect soil alpha diversity, but leads to a higher interconnected microbial network structure. Moreover, differential core genera and species for each management system are observed. In addition, the correlation of the microbiome with geographical distance is evidence of the existence of different microbial terroirs within DOP Ribeiro. Indeed, sustainable management leads to higher nutrient availability and enhances soil health in the short term, while lowering pesticide usage.

[Mental health literacy in spanish adolescents and its relationship with sociodemographic characteristics]. / Alfabetización en salud mental en adolescentes españoles y su relación con las características sociodemográficas.

OBJECTIVE: Different studies identify mental health literacy as a protective factor for developing a mental health problem. The aim of this paper was to determine the degree of mental health literacy of the adolescent population of Barcelona, and its relationship with socio-demographic and educational variables. METHODS: A cross-sectional study was carried out in Barcelona during the 2017-2018 academic year. A total of 1,032 young people between thirteen and seventeen years of age participated. The following variables were collected: sex, age, nationality, socioeconomic status (RDHpc) and average school grade. The aim was to determine the degree of mental health literacy (knowledge, stigma and help-seeking) of the adolescent population of Barcelona, and its relationship with socio-demographic and educational variables. Multiple linear regression analysis was performed adjusting for the effect of sociodemographic variables on the score of each scale. RESULTS: The mean score (standard deviation) of the EMHL test was 7.28 (1.27) and 4.24 (1.14) respectively, with higher scores obtained by girls, high RDHpc, excellent score and Spanish nationality. The greatest difference in EMHL scores, adjusting for the rest of the variables, corresponded to adolescents with an excellent mean score and a high RDHpc index (with respect to the baseline category, beta=0.72 and 0.52 respectively). The mean stigma score was 27.6 (4.47) for CAMI and 8.83 (3.36) for RIBS. The variables related to a greater difference in score with respect to the baseline category and adjusted for the rest of the variables were: gender (boy=1.54) and academic grade (excellent=-2.38) for CAMI, and nationality (foreign=0.82) and academic grade (excellent=-1.30) for RIBS. The mean RIBS score was 8.83 (3.36) with the largest difference in score from baseline being foreign nationality (beta=0.82) and having a grade of excellent (1.30). Help-seeking was higher in parents and friends, with differences according to gender and nationality. CONCLUSIONS: The level of mental health literacy is medium-low. While gender, nationality and educational attainment are the factors that are related to knowledge and stigma, socio-economic status is only related to mental health literacy.

OBJECTIVE: Diferentes estudios identifican la alfabetización en salud y/o salud mental (ASM) como factores protectores contra el desarrollo de un problema de salud mental. El objetivo de este trabajo fue determinar el grado de alfabetización en salud mental de la población adolescente de Barcelona, así como su relación con variables sociodemográficas y educativas. METHODS: Se realizó un estudio transversal en Barcelona durante el curso 2017-2018. Participaron 1.032 jóvenes entre trece y diecisiete años. Se recogieron las siguientes variables: sexo; edad; nacionalidad; nivel socioeconómico (RDHpc); y nota media escolar. La ASM se midió mediante los test de conocimientos EMHL (reconocimiento de problemas mentales y conocimientos en salud mental; rango 0-10 cada parte), estigma (CAMI: rango 10-50, y RIBS: rango 4-20) y búsqueda de ayuda (GHSQ: rango de 1 a 7). Se realizó análisis de regresión lineal múltiple ajustando el efecto de variables sociodemográficas sobre la puntuación de cada escala. RESULTS: La puntuación media (desviación típica) del EMHL test fue de 7,28 (1,27) y 4,24 (1,14), respectivamente, obteniendo mayor puntuación las chicas, RDHpc altas, nota excelente y con nacionalidad española. La mayor diferencia de puntuación en EMHL, ajustando por el resto de variables, correspondió a los adolescentes con nota media excelente y con índice RDHpc elevado (respecto a la categoría basal, beta=0,72 y 0,52, respectivamente). La puntuación media del estigma fue 27,6 (4,47) para CAMI y 8,83 (3,36) para RIBS. Las variables relacionadas con una mayor diferencia de puntuación respecto a la categoría basal y ajustado por el resto de variables fueron: sexo (chico=1,54) y nota académica (excelente=-2,38) para CAMI, y nacionalidad (extranjera=0,82) y nota académica (excelente=-1,30) para RIBS. La puntuación media de RIBS fue 8,83 (3,36), siendo la mayor diferencia de puntuación respecto a la categoría basal la nacionalidad extranjera (beta=0,82) y tener una nota de excelente (1,30). La búsqueda de ayuda fue mayor en padres/madres y amigos, con diferencias según sexo y nacionalidad. CONCLUSIONS: El nivel de alfabetización de salud mental es medio-bajo. Mientras que género, nacionalidad y resultados académicos son los factores que se relacionan con conocimientos y estigma, el nivel socioeconómico se relaciona únicamente con conocimientos en salud mental.

Comprehensive analysis of vitamin D3 impurities in oily drug products using supercritical fluid chromatography-mass spectrometry.

Vitamin D3 , an essential micronutrient, often requires supplementation via medicines or food supplements, which necessitate quality control (QC). This study presents the development of a method for detecting and quantifying seven impurities of vitamin D3 in oily drug products using supercritical fluid chromatography-mass spectrometry (SFC-MS). Targeted impurities include two esters of vitamin D3 and five non-esters including four that are isobaric to vitamin D3 . Firstly, a screening study highlighted the Torus 1-AA column and acetonitrile modifier as adequate for the separation, followed by optimization of the SFC conditions. Secondly, make-up solvent composition and MS settings were optimized to reach high sensitivity. For both the separation and MS response, the screening design of experiments proved useful. Lastly, a fast saponification and liquid-liquid extraction method was developed, enabling efficient sample cleanup and impurities recovery from the complex oily matrix. The SFC-MS method suitability was assessed in two validation studies. The first study employed the ICH Q2 guideline for impurity limit test to demonstrate method specificity and establish a limit of detection (LOD) and a limit of quantification (LOQ) at 0.2% and 0.5%, respectively, for ester impurities. The second study conducted a comprehensive quantitative assessment for three non-ester impurities using a total error approach, determining method validity through accuracy profiles. The validated method exhibited reliable performance across impurity concentrations from 0.1% to 2.0%, with estimated LODs ranging from 2 to 7 ng/mL. This study further promotes SFC-MS as a valuable, versatile, and green tool for routine pharmaceutical QC.

Alfabetización en salud mental en adolescentes españoles y su relación con las características sociodemográficas / Mental health literacy in spanish adolescents and its relationship with sociodemographic characteristics

Fundamentos: diferentes estudios identifican la alfabetización en salud y/o salud mental (asm) como factores protectores contra el desarrollo de un problema de salud mental. El objetivo de este trabajo fue determinar el grado de alfabetización en salud mental de la población adolescente de barcelona, así como su relación con variables sociodemográficas y educativas.métodos: se realizó un estudio transversal en barcelona durante el curso 2017-2018. Participaron 1.032 jóvenes entre trece y diecisiete años. Se recogieron las siguientes variables: sexo; edad; nacionalidad; nivel socioeconómico (rdhpc); y nota media escolar. La asm se midió mediante los test de conocimientos emhl (reconocimiento de problemas mentales y conocimientos en salud mental; rango 0-10 cada parte), estigma (cami: rango 10-50, y ribs: rango 4-20) y búsqueda de ayuda (ghsq: rango de 1 a 7). Se realizó análisis de regresión lineal múltiple ajustando el efecto de variables sociodemográficas sobre la puntuación de cada escala.resultados: la puntuación media (desviación típica) del emhl test fue de 7,28 (1,27) y 4,24 (1,14), respectivamente, obteniendo mayor pun-tuación las chicas, rdhpc altas, nota excelente y con nacionalidad española. La mayor diferencia de puntuación en emhl, ajustando por el resto de variables, correspondió a los adolescentes con nota media excelente y con índice rdhpc elevado (respecto a la categoría basal, beta=0,72 y 0,52, respectivamente). La puntuación media del estigma fue 27,6 (4,47) para cami y 8,83 (3,36) para ribs. Las variables relacionadas con una mayor diferencia de puntuación respecto a la categoría basal y ajustado por el resto de variables fueron: sexo (chico=1,54) y nota académica (excelente=-2,38) para cami, y nacionalidad (extranjera=0,82) y nota académica (excelente=-1,30) para ribs. La puntuación media de ribs fue 8,83 (3,36), siendo la mayor diferencia de puntuación respecto a la categoría basal la nacionalidad extranjera (beta=0,82) y tener una nota de excelente (1,30). La búsqueda de ayuda fue mayor en padres/madres y amigos, con diferencias según sexo y nacionalidad.conclusiones: el nivel de alfabetización de salud mental es medio-bajo. Mientras que género, nacionalidad y resultados académicos son los factores que se relacionan con conocimientos y estigma, el nivel socioeconómico se relaciona únicamente con conocimientos en salud mental.(AU)

Background: different studies identify mental health literacy as a protective factor for developing a mental health problem. The aim of this paper was to determine the degree of mental health literacy of the adolescent population of barcelona, and its relationship with socio-de-mographic and educational variables.methods: a cross-sectional study was carried out in barcelona during the 2017-2018 academic year. A total of 1,032 young people between thirteen and seventeen years of age participated. The following variables were collected: sex, age, nationality, socioeconomic status (rdhpc) and average school grade. The aim was to determine the degree of mental health literacy (knowledge, stigma and help-seeking) of the adolescent population of barcelona, and its relationship with socio-demographic and educational variables. Multiple linear regression analysis was performed adjusting for the effect of sociodemographic variables on the score of each scale.results: the mean score (standard deviation) of the emhl test was 7.28 (1.27) and 4.24 (1.14) respectively, with higher scores obtained by girls, high rdhpc, excellent score and spanish nationality. The greatest difference in emhl scores, adjusting for the rest of the variables, corresponded to adolescents with an excellent mean score and a high rdhpc index (with respect to the baseline category, beta=0.72 and 0.52 respectively). The mean stigma score was 27.6 (4.47) for cami and 8.83 (3.36) for ribs. The variables related to a greater difference in score with respect to the baseline category and adjusted for the rest of the variables were: gender (boy=1.54) and academic grade (excellent=-2.38) for cami, and nationality (foreign=0.82) and academic grade (excellent=-1.30) for ribs. The mean ribs score was 8.83 (3.36) with the largest difference in score from baseline being foreign nationality (beta=0.82) and having a grade of excellent (1.30). Help-seeking was higher in parents and friends, with differences according to gender and nationality.conclusions: the level of mental health literacy is medium-low. While gender, nationality and educational attainment are the factors that are related to knowledge and stigma, socio-economic status is only related to mental health literacy.(AU)

Pituitary metastasis arising from hepatocellular carcinoma: a case report and update of the literature.

Hepatocellular carcinoma (HCC) is the sixth most common neoplasia and the third leading cause of cancer-associated deaths worldwide. Most cases arise in patients with cirrhosis, and early detection through periodic screening can make it potentially curable. The presence of extrahepatic metastases (EHM) affects treatment decisions and curability. The lungs are the most common site for EHM, followed by lymph nodes, bones, and the adrenal glands. Interestingly, approximately only 15 cases of HCC metastasizing to the pituitary gland have been reported so far.The most common symptoms of pituitary metastasis (PM) arising from HCC are nerve palsies affecting the third, fourth, and sixth cranial nerves. Other symptoms, such as diabetes insipidus or pituitary insufficiencies, are present in a minority of cases. Detecting PM is difficult given its rarity. Gold-standard treatments for these patients have not yet been established, but the prognosis is dismal, with a median overall survival of only 4.5 months. In this paper, we present an interesting case of PM as the first symptom of an HCC in a 75-year-old female. We also present an overview of all cases reported to date with emphasis on symptom presentation and survival after diagnosis.Given the improvement of systemic therapy, more cases are diagnosed in both oligometastatic and palliative conditions. Therefore, better approaches and treatment modalities for extrahepatic metastases due to HCC should be defined.

Concomitant Irradiation to Checkpoint Inhibitor Therapy of Hepatocellular Carcinoma Patients: A Systematic Retrospective, Single-Center Analysis.

INTRODUCTION: Immunotherapy has been established as the standard treatment option for patients with advanced hepatocellular carcinoma (aHCC). Despite the increased efficacy, disease progression occurs in a relevant proportion of patients even after an objective response. Combination concepts with locoregional therapy are currently under investigation for hepatic disease but are also in discussion for the control of distant metastasis. Radiotherapy is a highly effective treatment modality for local tumor control. It is also thought to increase the efficacy of checkpoint inhibition and sensitize distant lesions to the effects of immunotherapy, but may potentially increase adverse effects. In our center, few patients with aHCC treated with immune checkpoint inhibitors (ICIs) received concomitant radiotherapy for symptom or disease control. The aim of this study was to retrospectively analyze adverse effects and efficacy of concomitant radiotherapy in patients with aHCC treated with checkpoint inhibition. METHODS: To this aim, patients who received a combination of ICI and radiotherapy in our institution were retrospectively considered for analysis. The predefined inclusion criterion was radiotherapy after initiated checkpoint inhibition and continuation of ICI therapy for at least 8 weeks. Adverse effects and efficacy measurements were performed according to local standards. RESULTS: The database search of 2016-2021 revealed six consecutive patients fulfilling the predefined criteria for concomitant ICI and radiotherapy. Three patients received high-dose-rate brachytherapy (15 Gy) to treat progredient hepatic lesions. Two patients received stereotactic body radiotherapy (SBRT) (25-30 Gy) for symptom control, and 1 patient received brachytherapy and SBRT to treat metastases. No severe adverse events were reported in the period (<6 months) after concomitant radiotherapy. In 5 out of 6 cases, long-term tumor control could be achieved by this therapeutic combination. CONCLUSION: A good efficacy of concomitant radiotherapy and checkpoint inhibition has been achieved with no safety concerns. Further investigations should evaluate the safety, appropriate clinical context, and efficacy of this promising approach.

Effects of Voluntary Physical Exercise on the Neurovascular Unit in a Mouse Model of Alzheimer's Disease.

Alzheimer's disease (AD) is the most common neurodegenerative disorder worldwide. Histopathologically, AD presents two pathognomonic hallmarks: (1) neurofibrillary tangles, characterized by intracellular deposits of hyperphosphorylated tau protein, and (2) extracellular amyloid deposits (amyloid plaques) in the brain vasculature (cerebral amyloid angiopathy; CAA). It has been proposed that vascular amyloid deposits could trigger neurovascular unit (NVU) dysfunction in AD. The NVU is composed primarily of astrocytic feet, endothelial cells, pericytes, and basement membrane. Although physical exercise is hypothesized to have beneficial effects against AD, it is unknown whether its positive effects extend to ameliorating CAA and improving the physiology of the NVU. We used the triple transgenic animal model for AD (3xTg-AD) at 13 months old and analyzed through behavioral and histological assays, the effect of voluntary physical exercise on cognitive functions, amyloid angiopathy, and the NVU. Our results show that 3xTg-AD mice develop vascular amyloid deposits which correlate with cognitive deficits and NVU alteration. Interestingly, the physical exercise regimen decreases amyloid angiopathy and correlates with an improvement in cognitive function as well as in the underlying integrity of the NVU components. Physical exercise could represent a key therapeutic approach in cerebral amyloid angiopathy and NVU stability in AD patients.

Clinical Characterization of HCC/CCA Mixed Cancers in a Population-based Cohort.

BACKGROUND AND AIMS: Primary liver cancer (PLC) ranks among of the most common cancers worldwide. Within this group, a minority of cases displays characteristics of both hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA), known as combined hepatocellular cholangiocarcinoma (cHCC- CCA). Currently, there is no specific standardized therapy for these mixed tumors. Therefore, the aim of our study was to analyze the clinical course, treatment and outcome of cHCC-CCA patients in a European population-based registry. METHODS: We investigated 9,144 patients with PLC (6,622 HCC, 2,356 iCCA, and 166 cHCC-CCA) diagnosed between 2009 and 2020. All data were obtained from Clinical Cancer Registry of Baden-Württemberg (BW), Germany. RESULTS: In all three groups patients were predominantly male (82%, 57%, and 68% for HCC, iCCA and cHCC-CCA groups, respectively). 48% of cHCC-CCA patients were diagnosed as stage IV cancers, which was more than for HCC (31%) but less compared to CCA (64%). Overall median survival of cHCC-CCA patients was worse compared to HCC (9-13 months vs. 15.5 months, p<0.001) and rather comparable to CCA (11.8 months). CONCLUSIONS: Our data demonstrated that cHCC-CCA tumors appear to have a distinct clinical course with worse overall survival compared to HCC. Thus, identification of these cancers by histopathology is essential in order to further characterize this tumor entity and to provide accurate treatment to these patients.

Study of metal and organic contaminants transported by microplastics in the Lebanese coastal environment using ICP MS, GC-MS, and LC-MS.

An untargeted study of multiclass contaminants associated with microplastics (MPs) in the East Mediterranean was carried out. Samples were collected in 2020-2021 from the shoreline at 14 different locations, along the Lebanese coast. Attenuated Total Reflectance (ATR) FTIR spectroscopy showed the predominant presence of polyethylene and polypropylene among plastic debris. The non-polar and polar organic compounds sorbed on the MPs were identified and quantified by GC - TOF MS and LC - electrospray MS/MS, respectively. Deconvolution of accurate GC-MS scan data allowed the identification of >130 organic pollutants, 64 of which could be confirmed by matching with the authentic standards, among which a number of previously unreported in targeted GC-MS(MS) methods. In addition to highly toxic, legacy chlorinated pollutants, high levels (average values from 0.8 to 4.0 µg g-1) of some musks, UV filters and UV absorbers were detected. Untargeted LC-MS demonstrated the persistence of several pesticides (i.e., chlorpyrifos) and pharmaceuticals, such as phenacetin and minoxidil, which were quantified. In addition, a study of metals associated with microplastics using ICP-MS confirmed the high potential of microplastics to act as a vector of, among others, toxic metals, such as Cd, Pb, Bi or Hg.

Clostridial diarrheas in piglets: A review.

Clostridium perfringens type C and Clostridioides difficile are the main enteric clostridial pathogens of swine and are both responsible for neonatal diarrhea in this species. The role of Clostridum perfringes type A is under discussion. History, clinical signs, gross lesions and histological findings are the basis for a presumptive diagnosis of C. perfringens type C or C. difficile infection. Confirmation is based upon detection of beta toxin of C. perfringens type C or toxin A/B of C. difficile, respectively, in intestinal contents or feces. Isolation of C. perfringens type C and/or C. difficile is highly suggestive of infection by these microorganisms but it is not enough to confirm a diagnosis as they may be found in the intestine of some healthy individuals. Diagnosis of C. perfringens type A-associated diarrhea is more challenging because the diagnostic criteria have not been well defined and the specific role of alpha toxin (encoded by all strains of this microorganism) and beta 2 toxin (produced by some type A strains) is not clear. The goal of this paper is to describe the main clostridial enteric diseases of piglets, including etiology, epidemiology, pathogenesis, clinical signs, pathology and diagnosis.

Alzheimer's Disease: An Updated Overview of Its Genetics.

Alzheimer's disease (AD) is the most common neurodegenerative disease in the world. It is classified as familial and sporadic. The dominant familial or autosomal presentation represents 1-5% of the total number of cases. It is categorized as early onset (EOAD; <65 years of age) and presents genetic mutations in presenilin 1 (PSEN1), presenilin 2 (PSEN2), or the Amyloid precursor protein (APP). Sporadic AD represents 95% of the cases and is categorized as late-onset (LOAD), occurring in patients older than 65 years of age. Several risk factors have been identified in sporadic AD; aging is the main one. Nonetheless, multiple genes have been associated with the different neuropathological events involved in LOAD, such as the pathological processing of Amyloid beta (Aß) peptide and Tau protein, as well as synaptic and mitochondrial dysfunctions, neurovascular alterations, oxidative stress, and neuroinflammation, among others. Interestingly, using genome-wide association study (GWAS) technology, many polymorphisms associated with LOAD have been identified. This review aims to analyze the new genetic findings that are closely related to the pathophysiology of AD. Likewise, it analyzes the multiple mutations identified to date through GWAS that are associated with a high or low risk of developing this neurodegeneration. Understanding genetic variability will allow for the identification of early biomarkers and opportune therapeutic targets for AD.

Novel bioengineered collagen with Manuka honey and hydroxyapatite sheet for the treatment of lower extremity chronic wounds in an urban hospital wound care setting.

INTRODUCTION: A novel BCMH sheet has been shown to achieve improved wound closure rates in chronic and acute wounds when compared with SOC. OBJECTIVE: This retrospective evaluation assessed chronic wound closure rates with SOC or treatment with the BCMH sheet in an urban hospital wound clinic. METHODS: Forty-seven chronic wounds were treated with SOC or the BCMH sheet. The primary endpoint was time to closure. For wounds that did not close, investigations were conducted to determine the reason. RESULTS: Twenty wounds were treated with SOC, which varied in usage of multiple products and/or therapies, and 27 wounds were treated with the BCMH sheet. The average initial wound size was not statistically different between the groups. In both groups, most wounds that were treated did not close. For wounds that did close, the average time to closure was 2x faster in the BCMH group compared with the SOC group (7.4 weeks and 14.8 weeks, respectively; P < .05). CONCLUSIONS: This retrospective evaluation showed average time to wound closure to be significantly faster with BCMH compared with SOC in patients who maintained adherence with regular visits.

Preliminary Clinical Evaluation Using a Novel Bioengineered Wound Product to Treat Lower Extremity Ulcers.

Diabetes mellitus affects hundreds of millions of people worldwide, each of which have up to a 25% risk of developing a diabetic foot ulcer (DFU) during their lifetime. With poor DFU healing rates using standard of care, advanced treatments are introduced to attempt to close the wound. The objective of this preliminary clinical evaluation was to evaluate lower extremity ulcers treated with a novel bioengineered wound product (BWP). The BWP, a solid absorbable and conformable sheet composed of gelatin, Manuka honey, and hydroxyapatite, was applied on 12 patients with lower extremity ulcers. The patients in this evaluation spanned across 4 sites and had complicated medical histories, including little to no progression of healing with standard of care or treatment with other biomaterials. The ulcers were treated with debridement, BWP placement, dressing, appropriate compression, and offloading as necessary. Weekly follow-up visits were recommended for evaluation, debridement, and BWP reapplication. Nine patients had the BWP applied to aid in full closure. These patients achieved 100% closure within 8 weeks, with a mean closure time of 4.1 weeks. At 4 weeks, the mean percent wound closure was 94%. Three patients had the BWP applied to aid in achieving a healthy wound bed for continued treatment (eg, splitthickness skin graft) and to cover (epithelialization over) an exposed tendon. In all 12 cases, no treatment site infections were observed. The results and observations from this preliminary clinical evaluation suggest that the BWP supports rapid wound closure, a predictor of complete healing for DFUs.

The effectiveness of a "EspaiJove.net"- a school-based intervention programme in increasing mental health knowledge, help seeking and reducing stigma attitudes in the adolescent population: a cluster randomised controlled trial.

BACKGROUND: The aim of this study is to evaluate the short- and long-term effects of the universal mental health literacy intervention "EspaiJove.net" in increasing mental health knowledge, help seeking and reducing stigma attitudes in the adolescent population. We also examine whether these effects depend on the intervention intensity.  METHODS: A clustered school-based randomised controlled trial (cRCT) design. SUBJECTS: 1,298 secondary pupils aged 13 and 14 were recruited from 18 schools in Barcelona (Spain) between September 2016 and January 2018. INTERVENTION: Three programmes were assessed: 1) Sensitivity Programme (SP; 1 h); 2) Mental Health Literacy (MHL; 6 h); 3) MHL plus a first-person Stigma Reduction Programme (MHL + SR; 7 h); 4) Control group (CG): waiting list. OUTCOME MEASURES: 1) MHL: EspaiJove.net EMHL Test (First part and Second Part); 2) Stigma: RIBS and CAMI; 3) Help-seeking and use of treatment: GHSQ. ANALYSIS: The data was collected at baseline, post-intervention and 6 and 12 months later. An intention-to-treat analysis and imputation method was used to analyse the missing data. Intervention effects were analysed using multilevel modelling. RESULTS: One thousand thirty-two students were included (SP = 225; MHL = 261; MHL + SR = 295 and CG = 251). The MHL and MHL + SR interventions showed short- and long-term an increase in knowledge compared to SP and CG, but no significant change post-intervention or over time (First part p = 0.52 and Second part p = 0.62) between intervention groups and CG. No significant changes were found in stigma scores post-intervention or over time (CAMI p = 0.61 and RIBS p = 0.98) or in help-seeking scores (parent p = 0.69; teacher p = 0.23 and healthcare professional p = 0.75). The MHL + SR intervention was the best valued and recommended (p < 0.005). CONCLUSIONS: The three interventions of the EspaiJove.net programme (SP, MHL and MHL + SR) seem not to be effective in terms MHL, Stigma and help-seeking behaviours. The contact with a person who has experimented mental illness first-hand did not reduce stigma attitudes. Further research should deal with the heterogeneity of MHL interventions (concept, duration and measures) and identify which components of stigma interventions are effective. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03215654 (registration date 12 July 2017).

A Preliminary Direct Comparison of the Inflammatory Reduction and Growth Factor Production Capabilities of Three Commercially Available Wound Products: Collagen Sheet, Manuka Honey Sheet, and a Novel Bioengineered Collagen Derivative + Manuka Honey + Hydroxyapatite Sheet.

Many commercially available wound products focus on improving one stage of the wound healing cascade. While this targeted approach works for specific wounds, there is a need for products that can reliably and comprehensively progress a wound through multiple stages. This preliminary in vitro study was performed to directly compare the inflammatory reduction and growth factor production effects of three commercially available wound care products: a collagen sheet (COL), a Manuka Honey Calcium Alginate sheet (MH), and a novel bioengineered sheet comprised of a collagen derivative (gelatin), Manuka honey, and hydroxyapatite (BCMH). Macrophages and human dermal fibroblasts were directly seeded on all three commercial products, and supernatants were analyzed for inflammatory markers and growth factors, respectively. Comparing the MMP-9/TIMP-1 ratio, BCMH resulted in 11× lower levels of this inflammation biomarker compared to COL, and 3× lower levels compared to MH. Both the COL and BCMH products created an environment conducive to expression and release of relevant growth factors, while the MH product showed the lowest levels of growth factor expression of all three commercially available products tested. The favorable 11× lower MMP-9/TIMP-1 ratio observed with the BCMH product compared to the COL product suggests that the BCMH products provided a superior comprehensive approach to healthy progression of the wounds by providing an additional benefit of reducing the inflammatory response in vitro.

Chlorhexidine residues in sludge from municipal wastewater treatment plants: analytical determination and toxicity evaluation.

In this work, a procedure for the sensitive and selective determination of chlorhexidine in sludge from municipal sewage treatment plants (STPs) based on matrix solid-phase dispersion (MSPD) and liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) was optimized and validated. Analysis of sewage sludge samples, obtained from different STPs in Northwest Spain from 2018 to 2021, showed that chlorhexidine was ubiquitous in this environmental compartment with concentrations between 0.3 and 16 µg g-1. The toxicity of this pollutant was assessed in in vitro assays considering three different model organisms: Candida albicans, Escherichia coli, and Staphylococcus aureus. C. albicans was the most sensitive of the tested microorganisms to chlorhexidine with a lethal threshold concentration of 0.1 mg L-1. Thus, the lowest observed sludge residue was 3 times higher than the acute toxicity threshold measured for C. albicans. Moreover, E. coli and S. aureus were also affected at chlorhexidine concentrations around 1.8 mg L-1 and 0.5 mg L-1, respectively. So, chlorhexidine residues might affect the population of microorganisms existing in STPs. In addition, the potential phytotoxicity of the compound was evaluated with germination experiments using different model seeds. At the evaluated dose (10 µg g-1 dried soil), chlorhexidine did not affect the germination of Sorghum saccharatum, Lepidium sativum, or Sinapis alba seeds. Thus, amending agriculture soils with chlorhexidine containing sludge is unlikely to affect the germination of plants.