SHIP1 modulation and proteome characterization of microglia.

Understanding microglial states in the aging brain has become crucial, especially with the discovery of numerous Alzheimer's disease (AD) risk and protective variants in genes such as INPP5D and TREM2, which are essential to microglia function in AD. Here we present a thorough examination of microglia-like cells and primary mouse microglia at the proteome and transcriptome levels to illuminate the roles these genes and the proteins they encode play in various cell states. First, we compared the proteome profiles of wildtype and INPP5D (SHIP1) knockout primary microglia. Our findings revealed significant proteome alterations only in the homozygous SHIP1 knockout, revealing its impact on the microglial proteome. Additionally, we compared the proteome and transcriptome profiles of commonly used in vitro microglia BV2 and HMC3 cells with primary mouse microglia. Our results demonstrated a substantial similarity between the proteome of BV2 and mouse primary cells, while notable differences were observed between BV2 and human HMC3. Lastly, we conducted targeted lipidomic analysis to quantify different phosphatidylinositols (PIs) species, which are direct SHIP1 targets, in the HMC3 and BV2 cells. This in-depth omics analysis of both mouse and human microglia enhances our systematic understanding of these microglia models. SIGNIFICANCE: Given the growing urgency of comprehending microglial function in the context of neurodegenerative diseases and the substantial therapeutic implications associated with SHIP1 modulation, we firmly believe that our study, through a rigorous and comprehensive proteomics, transcriptomics and targeted lipidomic analysis of microglia, contributes to the systematic understanding of microglial function in the context of neurodegenerative diseases.

Ovarian angiosarcoma: A systematic review of literature and survival analysis.

Ovarian angiosarcoma (OA) is rare, with only sporadic cases reported in English literature. We performed a systematic review of cases published in the PubMed, Science Direct, and Google Scholar databases with the aim of describing the reported clinicopathological features of OA. Fifty-three articles that reported 60 patients were reviewed. Of the 60 patients, 7 (11.6 %) were diagnosed with secondary (metastatic) ovarian angiosarcoma and 53 (88.3 %) were diagnosed with primary ovarian angiosarcoma. The mean age at presentation for ovarian angiosarcoma was 38.3±17.8 years. The average tumor size for ovarian angiosarcoma was 11.9±6.1 cm. Abdominal distention was reported in 45/60 (75 %). Microscopic examination revealed necrosis in 28/60 (46.7 %), pleomorphism in 32/59 (54.2 %), mitotic figures in 44/60 (73.3 %), spindle-shaped cells in 27/36 (75 %), epithelioid-shaped cells in 20/36 (55.5 %), and mixed epithelioid and spindle-shaped cells in 12/36 (33.3 %) patients. On immunohistochemistry CD 31 was positive in 41/41 (100 %), CD 34 in 38/39 (97.4 %), and Factor VIII related antigen in 18/21 (85.7 %) patients. Metastasis was present in 43/60 (71.6 %) patients. Chemotherapy and surgery was performed in 36/52 (69.2 %). The median follow-up time for ovarian angiosarcoma was 7 months (IQR1-IQR3:2-13.5 months). 24 (48 %) of the 50 patients with available survival data were alive and 26/50 (52 %) were dead of disease. Survival analyses (KM curves) revealed that the presence of necrosis (log-rank test; p = 0.05) and absence of spindle-shaped cells (log rank test; p = 0.04) on histopathology were associated with worse outcomes, while treatment with combined chemotherapy and surgical excision was associated with better survival (P < 0.001) therefore, prompt diagnosis and early treatment with combined chemotherapy and surgical excision can prolong survival in OA.

Capturing Recent Mycobacterium tuberculosis Infection by Tuberculin Skin Test vs. Interferon-Gamma Release Assay.

Reductions in tuberculosis (TB) incidence require identification of individuals at high risk of developing active disease, such as those with recent Mycobacterium tuberculosis (Mtb) infection. Using a prospective household contact (HHC) study in Kampala, Uganda, we diagnosed new Mtb infection using both the tuberculin skin test (TST) and interferon-gamma release assay (IGRA). Our study aimed to determine if the TST adds additional value to the characterization of IGRA converters. We identified 13 HHCs who only converted the IGRA (QFT-only converters), 39 HHCs who only converted their TST (TST-only converters), and 24 HHCs who converted both tests (QFT/TST converters). Univariate analysis revealed that TST-only converters were older. Additionally, increased odds of TST-only conversion were associated with older age (p = 0.02) and crowdedness (p = 0.025). QFT/TST converters had higher QFT quantitative values at conversion than QFT-only converters and a bigger change in TST quantitative values at conversion than TST-only converters. Collectively, these data indicate that TST conversion alone likely overestimates Mtb infection. Its correlation to older age suggests an "environmental" boosting response due to prolonged exposure to environmental mycobacteria. This result also suggests that QFT/TST conversion may be associated with a more robust immune response, which should be considered when planning vaccine studies.

The bii4africa dataset of faunal and floral population intactness estimates across Africa's major land uses.

Sub-Saharan Africa is under-represented in global biodiversity datasets, particularly regarding the impact of land use on species' population abundances. Drawing on recent advances in expert elicitation to ensure data consistency, 200 experts were convened using a modified-Delphi process to estimate 'intactness scores': the remaining proportion of an 'intact' reference population of a species group in a particular land use, on a scale from 0 (no remaining individuals) to 1 (same abundance as the reference) and, in rare cases, to 2 (populations that thrive in human-modified landscapes). The resulting bii4africa dataset contains intactness scores representing terrestrial vertebrates (tetrapods: ±5,400 amphibians, reptiles, birds, mammals) and vascular plants (±45,000 forbs, graminoids, trees, shrubs) in sub-Saharan Africa across the region's major land uses (urban, cropland, rangeland, plantation, protected, etc.) and intensities (e.g., large-scale vs smallholder cropland). This dataset was co-produced as part of the Biodiversity Intactness Index for Africa Project. Additional uses include assessing ecosystem condition; rectifying geographic/taxonomic biases in global biodiversity indicators and maps; and informing the Red List of Ecosystems.

Valuing the functionality of tropical ecosystems beyond carbon.

Land-based carbon sequestration projects, such as tree planting, are a prominent strategy to offset carbon emissions. However, we risk reducing natural ecosystems to one metric - carbon. Emphasis on restoring ecosystems to balance ecosystem services, biodiversity conservation, and carbon sequestration is a more appropriate strategy to protect their functioning.

La odontología verde / Green dentistry

El propósito del presente trabajo está orientado a generar una reflexión entre el gremio odontológico profesional y los estudiantes de las licenciaturas en Odontología respecto a la contaminación global que estamos generando y a la crítica situación del planeta, así como sus consecuencias ambientales y climatológicas, sobre lo importante que es educar bajo la perspectiva de una Odontología Verde y Sostenible a través de la ambientalización curricular en las escuelas y facultades de Odontología para generar un tipo de cultura y conciencia proambiental. De igual forma para señalar lo sencillo que es ambientalizar agradable y relajantemente nuestro entorno educativo y laboral, así como realizar algunas prácticas odontológicas ecológicas y ambientales en la práctica privada que cuestan poco o nada y que, por el contrario, el gran efecto positivo que éstas tendrán en el medio ambiente y la reducción de los niveles de contaminación actuales. Si realmente logramos generar una nueva cultura y conciencia que se preocupe por el medio ambiente en el campo de la Odontología, los resultados para todos se verán reflejados en un mejor ambiente social, educativo de trabajo y de salud (AU)

The purpose of this work is aimed at generating a reflection between the professional dental guild and the students of the Bachelor's Degrees in Dentistry regarding the global pollution that we are generating and the critical situation of the planet and its environmental and climatological consequences, on how important it is educate under the perspective of a Green and Sustainable Dentistry through the greening of the curriculum in the Schools and Faculties of Dentistry to generate a type of culture and pro-environmental awareness. Likewise, point out how simple it is to pleasantly and relaxingly green our educational and work environment, as well as perform some ecological and environment, as well perform some ecological and environment, dental practices in private practice that cost little or nothing and that, on the contrary, the great positive effect that these will have on the environment and the reduction of current pollution levels. If we truly manage to generate a new culture and awareness that cares about the environment in the field of Dentistry, the results for all will be reflected in a better social, educational, work and health environment (AU)

Exploring the chemical composition and coloring qualities of cacao fruit epicarp extracts.

Cacao pod husks (CHs), the most abundant by-product of cacao beans production, can potentially become a source of functional ingredients for the food, cosmetic, and pharmaceutical industries. Three pigment samples (yellow, red, and purple) from lyophilized and ground cacao pod husk epicarp (CHE), were isolated by ultrasound-assisted solvent extraction, with yields between 11 and 14 wt%. The pigments exhibited UV-Vis flavonoid-related absorption bands at 283 nm and 323 nm and, only for the purple extract, reflectance bands in the 400-700 nm range. As per the Folin-Ciocalteu method, the CHE extracts contain high yields of antioxidant phenolic compounds amounting to 161.6, 153.9, and 167.9 mg GAE per g extract for the yellow, red, and purple samples, respectively. Phloretin, quercetin, myricetin, jaceosidin, and procyanidin B1 were among the main flavonoids identified by MALDI-TOF MS. A biopolymeric bacterial-cellulose matrix can effectively retain up to 541.8 mg of CHE extract per g of cellulose in dry weight. Also, MTT assays revealed that CHE extracts are non-toxic and increase viability in cultured VERO cells.

Audience retention on educational dermatological videos: an exploratory study using a dermatologist-led experimental YouTube channel.

BACKGROUND: Patients increasingly search for dermatological information on YouTube; however, the successful presence of dermatologists on this platform is limited. Audience retention is essential to ensure success, as the YouTube algorithm considers it to rank videos. To the best of our knowledge, this is the first study in dermatology that focuses on audience retention on YouTube. It is based on a real-life dermatologist-led channel. AIM: To determine factors that influence audience retention on a dermatologist-led YouTube channel and provide insights that can help dermatologists create engaging content that becomes successful. METHODS: This research studied 137 videos. First, multiple linear regression was performed to test whether the specific video characteristics significantly predicted audience retention. Second, moments of peak retention (spikes) were identified, and their content was analysed to determine what was particularly interesting for viewers. As the videos were educational, spikes were classified into conceptual or procedural knowledge. RESULTS: The average audience retention was 41.7%. Longer video length and increasing number of days from release had a negative and significant effect on audience retention, with the effect of video length (ß = -0.6979; P < 0.001) being strong and that of days from release being weak (ß = -0.1948; P = 0.02). Spikes were observed in 76 videos (55.5%), 68.2% of which were classified as procedural knowledge. CONCLUSION: These data indicate that audience retention increases as video length decreases, and that viewers are essentially interested in practical information. Consequently, to increase audience retention, dermatologists should design succinct videos and deliver procedural knowledge that creates value for the public.

What do Patients Want to See on Social Media? Evidence From a Two-Year Experiment.

INTRODUCTION: Dermatological information on social media is dominated by misleading and potentially harmful content from nonexperts. Literature suggests that, to address this issue, dermatologists should develop an online presence. However, the successful presence of dermatologists on social media has been criticized for focusing on cosmetic dermatology and not representing the broad spectrum of the specialty. OBJECTIVES: The aim of this study was to systematically analyze which dermatological topics interest the public most, and to find out whether it is feasible for a dermatologist to become influential on social media while presenting all dermatological topics equally. METHODS: The study was performed on an educational dermatology YouTube channel. The 101 videos published in a two-year period were divided into cosmetic (51 videos) and medical dermatology (50 videos). Student's t-test was conducted to determine whether there were significant differences in views. Medical dermatology videos were then classified into three categories: Acne, facial dermatoses (excluding acne) and other dermatological diseases. A Kruskal-Wallis test was used to compare these three categories and cosmetic dermatology. RESULTS: When comparing cosmetic and medical dermatology, no significant differences were found. When comparing the four categories, cosmetic dermatology and acne were found to generate significantly more views that other dermatological diseases. CONCLUSIONS: The public seems to be particularly interested in cosmetic dermatology and acne. This might make it challenging to become successful on social media while presenting a balanced portrayal of dermatology. However, focusing on popular topics can provide a real chance to be influential and protect vulnerable people from misinformation.

American Heart Association's life simple 7 and the risk of atrial fibrillation in the PREDIMED study cohort.

BACKGROUND AND AIMS: The American Heart Association proposed 7 ideal cardiovascular health metrics (Life's Simple 7 [LS7]) namely, not smoking, body mass index <25 kg/m2, healthy diet, moderate physical activity ≥150 min/week, total blood cholesterol <200 mg/dL, blood pressure <120/80 mmHg and fasting blood glucose <100 mg/dL. Our objective was to assess the association between these LS7 metrics and the incidence of atrial fibrillation (AF). METHODS AND RESULTS: A total of 6,479 participants of the PREDIMED study were included. We calculated the participants' baseline LS7 index ranging 0-7 points to categorize them according to their adherence to these LS7 health metrics. Multivariable Cox regression models were used to estimate Hazard Ratios (HR) and their 95% Confidence Intervals (95% CI). After a median follow-up of 4.8 years, we identified 250 incident cases of AF. After adjusting for potential confounders, adherence to LS7 index was not associated with the incidence of AF (adjusted HR 0.90 [95% CI: 0.56-1.45] for highest vs. lowest LS7 categories). Body mass index <25 kg/m2 was the only health metric individually associated with a lower risk of AF (HR 0.36 [95% CI: 0.16-0.78]). CONCLUSIONS: In a high cardiovascular risk Spanish population, adherence to American Heart Association's LS7 metrics was not associated with the risk of incident AF. CLINICAL TRIALS NUMBER: ISRCTN35739639.

Development of Antimicrobial Defined Daily Dose (DDD) for the Pediatric Population.

Antimicrobial stewardship programs (ASPs) optimize antimicrobial use, improve patient outcomes, and reduce resistance. To assess the effectiveness of ASPs, it is necessary to have indicators that can be widely used. Defined daily dose (DDD) was designed by WHO for the adult population as a consumption indicator. However, there are no DDDs adapted to the pediatric population. The main objective of this study is to establish the most appropriate DDD values in this population. An observational, retrospective, multicenter study was conducted. Antimicrobial prescriptions were collected from pediatric wards of seven Spanish tertiary hospitals for 2 years. The DDDs obtained from the prescriptions were compared with the theoretical DDDs agreed upon in the first stage. To select the optimal DDD, the following were analyzed: power value, magnitude obtained from the differences in the DDD, statistical significance, and degree of agreement in the stipulated doses. A total of 4788 prescriptions were collected. Pediatric DDD was defined for 30 different antimicrobials. A potency >80% was obtained in 24 antibiotics. 51.2% of the selected DDD correspond to Phase I and 39.5% from Phase II. Pediatric DDD of different antimicrobials was obtained, providing an indicator that can be used globally in different hospitals to analyze the consumption and efficacy of ASPs.

Pyrolysis Kinetics of Byrsonima crassifolia Stone as Agro-Industrial Waste through Isoconversional Models.

This study is aimed at the analysis of the pyrolysis kinetics of Nanche stone BSC (Byrsonima crassifolia) as an agro-industrial waste using non-isothermal thermogravimetric experiments by determination of triplet kinetics; apparent activation energy, pre-exponential factor, and reaction model, as well as thermodynamic parameters to gather the required fundamental information for the design, construction, and operation of a pilot-scale reactor for the pyrolysis this lignocellulosic residue. Results indicate a biomass of low moisture and ash content and a high volatile matter content (≥70%), making BCS a potential candidate for obtaining various bioenergy products. Average apparent activation energies obtained from different methods (KAS, FWO and SK) were consistent in value (~123.8 kJ/mol). The pre-exponential factor from the Kissinger method ranged from 105 to 1014 min-1 for the highest pyrolytic activity stage, indicating a high-temperature reactive system. The thermodynamic parameters revealed a small difference between EA and ∆H (5.2 kJ/mol), which favors the pyrolysis reaction and indicates the feasibility of the energetic process. According to the analysis of the reaction models (master plot method), the pyrolytic degradation was dominated by a decreasing reaction order as a function of the degree of conversion. Moreover, BCS has a relatively high calorific value (14.9 MJ/kg) and a relatively low average apparent activation energy (122.7 kJ/mol) from the Starink method, which makes this biomass very suitable to be exploited for value-added energy production.

Crystal structure of active CDK4-cyclin D and mechanistic basis for abemaciclib efficacy.

Despite the biological and therapeutic relevance of CDK4/6 for the treatment of HR+, HER2- advanced breast cancer, the detailed mode of action of CDK4/6 inhibitors is not completely understood. Of particular interest, phosphorylation of CDK4 at T172 (pT172) is critical for generating the active conformation, yet no such crystal structure has been reported to date. We describe here the x-ray structure of active CDK4-cyclin D3 bound to the CDK4/6 inhibitor abemaciclib and discuss the key aspects of the catalytically-competent complex. Furthermore, the effect of CDK4/6 inhibitors on CDK4 T172 phosphorylation has not been explored, despite its role as a potential biomarker of CDK4/6 inhibitor response. We show mechanistically that CDK4/6i stabilize primed (pT172) CDK4-cyclin D complex and selectively displace p21 in responsive tumor cells. Stabilization of active CDK4-cyclin D1 complex can lead to pathway reactivation following alternate dosing regimen. Consequently, sustained binding of abemaciclib to CDK4 leads to potent cell cycle inhibition in breast cancer cell lines and prevents rebound activation of downstream signaling. Overall, our study provides key insights demonstrating that prolonged treatment with CDK4/6 inhibitors and composition of the CDK4/6-cyclin D complex are both critical determinants of abemaciclib efficacy, with implications for this class of anticancer therapy.

[Cutaneous hyperpigmentation as a manifestation in acute on chronic liver failure]. / Hiperpigmentación cutánea como manifestación poco reconocida en falla hepática aguda sobre crónica.

Background: The acquired cutaneous pigmentation represents a little recognized clinical manifestation in liver disorders, both acute and chronic, and can occur in the exacerbation processes of preexisting hepatopathies, as in the context of acute-on-chronic liver failure. Several hypotheses about the increase in pigment at skin and mucous membranes have been developed; some try to explain it as a defect in the degradation of melanin with secondary accumulation at tissues; others, on the other hand, describe it as a consequence of the release of fibroblast growth factors like endothelial growth factor and hepatocyte growth factor, which are produced under the stimulation of liver regeneration and cause a melanogenesis stimulation. The aim of this article is to study pigmentary skin changes in the background of liver diseases. Clinical cases: We described two clinical cases of patients with acuteon chronic liver failure secondary to different clinical scenarios are presented, who have in common the development of acquired pigmentary skin changes. Conclusion: In hepatopathies, the cutaneous hyperpigmentation is a sign with unknown etiology, so further studies are required to know the accurate pathophysiology. Reporting this finding is useful for physicians, since timely identification can help in the early diagnosis of underlying liver diseases.

Introducción: la hiperpigmentación cutánea adquirida representa una manifestación clínica poco reconocida en los trastornos hepáticos, tanto agudos como crónicos, y puede presentarse tanto en procesos de agudización de hepatopatías preexistentes como en el contexto de la falla hepática aguda sobre crónica. Se han desarrollado diversas hipótesis sobre el aumento de pigmento a nivel piel y mucosas, algunas tratan de explicarlo por un defecto en la degradación de la melanina, lo cual genera su acumilación en los tejidos; otras, en cambio, describen la liberación de factores de crecimiento derivados de fibroblastos, como el factor de crecimiento endotelial y el factor de crecimiento de hepatocitos, los cuales son producidos bajo el estímulo de la regeneración hepática y, a su vez, provocan una estimulación de la melanogénesis. El objetivo de este trabajo es estudiar la hiperpigmentación cutánea en el contexto de enfermedades hepáticas. Casos clínicos: se presentan dos casos clínicos de pacientes con falla hepática aguda sobre crónica secundaria a diferentes escenarios clínicos, quienes tienen en común el desarrollo pigmentación cutánea adquirida. Conclusiones: en las enfermedades hepáticas, la hiperpigmentación cutánea es un hallazgo presente cuya etiología aún no es dilucidada, por lo que se requieren más estudios para conocer la fisiopatología exacta. El reporte de este hallazgo es de utilidad para el personal médico, ya que la identificación oportuna puede ayudar a el diagnóstico temprano de hepatopatías subyacentes.

Co-limitation towards lower latitudes shapes global forest diversity gradients.

The latitudinal diversity gradient (LDG) is one of the most recognized global patterns of species richness exhibited across a wide range of taxa. Numerous hypotheses have been proposed in the past two centuries to explain LDG, but rigorous tests of the drivers of LDGs have been limited by a lack of high-quality global species richness data. Here we produce a high-resolution (0.025° × 0.025°) map of local tree species richness using a global forest inventory database with individual tree information and local biophysical characteristics from ~1.3 million sample plots. We then quantify drivers of local tree species richness patterns across latitudes. Generally, annual mean temperature was a dominant predictor of tree species richness, which is most consistent with the metabolic theory of biodiversity (MTB). However, MTB underestimated LDG in the tropics, where high species richness was also moderated by topographic, soil and anthropogenic factors operating at local scales. Given that local landscape variables operate synergistically with bioclimatic factors in shaping the global LDG pattern, we suggest that MTB be extended to account for co-limitation by subordinate drivers.

Low-Complexity Alternatives to the Optimal Linear Coding Scheme for Transmitting ARMA Sources.

In the era of the Internet of Things, there are many applications where numerous devices are deployed to acquire information and send it to analyse the data and make informed decisions. In these applications, the power consumption and price of the devices are often an issue. In this work, analog coding schemes are considered, so that an ADC is not needed, allowing the size and power consumption of the devices to be reduced. In addition, linear and DFT-based transmission schemes are proposed, so that the complexity of the operations involved is lowered, thus reducing the requirements in terms of processing capacity and the price of the hardware. The proposed schemes are proved to be asymptotically optimal among the linear ones for WSS, MA, AR and ARMA sources.