Enhanced ROS Production in Mitochondria from Prematurely Aging mtDNA Mutator Mice.

An increase in mitochondrial DNA (mtDNA) mutations and an ensuing increase in mitochondrial reactive oxygen species (ROS) production have been suggested to be a cause of the aging process ("the mitochondrial hypothesis of aging"). In agreement with this, mtDNA-mutator mice accumulate a large amount of mtDNA mutations, giving rise to defective mitochondria and an accelerated aging phenotype. However, incongruously, the rates of ROS production in mtDNA mutator mitochondria have generally earlier been reported to be lower - not higher - than in wildtype, thus apparently invalidating the "mitochondrial hypothesis of aging". We have here re-examined ROS production rates in mtDNA-mutator mice mitochondria. Using traditional conditions for measuring ROS (succinate in the absence of rotenone), we indeed found lower ROS in the mtDNA-mutator mitochondria compared to wildtype. This ROS mainly results from reverse electron flow driven by the membrane potential, but the membrane potential reached in the isolated mtDNA-mutator mitochondria was 33 mV lower than that in wildtype mitochondria, due to the feedback inhibition of succinate oxidation by oxaloacetate, and to a lower oxidative capacity in the mtDNA-mutator mice, explaining the lower ROS production. In contrast, in normal forward electron flow systems (pyruvate (or glutamate) + malate or palmitoyl-CoA + carnitine), mitochondrial ROS production was higher in the mtDNA-mutator mitochondria. Particularly, even during active oxidative phosphorylation (as would be ongoing physiologically), higher ROS rates were seen in the mtDNA-mutator mitochondria than in wildtype. Thus, when examined under physiological conditions, mitochondrial ROS production rates are indeed increased in mtDNA-mutator mitochondria. While this does not prove the validity of the mitochondrial hypothesis of aging, it may no longer be said to be negated in this respect. This paper is dedicated to the memory of Professor Vladimir P. Skulachev.

Antioxidants green tea extract and nordihydroguaiaretic acid confer species and strain-specific lifespan and health effects in Caenorhabditis nematodes.

The Caenorhabditis Intervention Testing Program (CITP) is an NIH-funded research consortium of investigators who conduct analyses at three independent sites to identify chemical interventions that reproducibly promote health and lifespan in a robust manner. The founding principle of the CITP is that compounds with positive effects across a genetically diverse panel of Caenorhabditis species and strains are likely engaging conserved biochemical pathways to exert their effects. As such, interventions that are broadly efficacious might be considered prominent compounds for translation for pre-clinical research and human clinical applications. Here, we report results generated using a recently streamlined pipeline approach for the evaluation of the effects of chemical compounds on lifespan and health. We studied five compounds previously shown to extend C. elegans lifespan or thought to promote mammalian health: 17α-estradiol, acarbose, green tea extract, nordihydroguaiaretic acid, and rapamycin. We found that green tea extract and nordihydroguaiaretic acid extend Caenorhabditis lifespan in a species-specific manner. Additionally, these two antioxidants conferred assay-specific effects in some studies-for example, decreasing survival for certain genetic backgrounds in manual survival assays in contrast with extended lifespan as assayed using automated C. elegans Lifespan Machines. We also observed that GTE and NDGA impact on older adult mobility capacity is dependent on genetic background, and that GTE reduces oxidative stress resistance in some Caenorhabditis strains. Overall, our analysis of the five compounds supports the general idea that genetic background and assay type can influence lifespan and health effects of compounds, and underscores that lifespan and health can be uncoupled by chemical interventions.

Improved Methods for Preparing Transverse Sections and Unrolled Whole Mounts of Maize Leaf Primordia for Fluorescence and Confocal Imaging.

In maize (Zea mays) and other grasses (Poaceae), the leaf primordia are deeply ensheathed and rolled within the leaf whorl, making it difficult to study early leaf development. Here, we describe methods for preparing transverse sections and unrolled whole mounts of maize leaf primordia for fluorescence and confocal imaging. The first method uses a wire stripper to remove the upper portions of older leaves, exposing the tip of the leaf primordium and allowing its measurement for more accurate transverse section sampling. The second method uses clear, double-sided nano tape to unroll and mount whole-leaf primordia for imaging. We show the utility of the two methods in visualizing and analyzing fluorescent protein reporters in maize. These methods provide a solution to the challenges presented by the distinctive morphology of maize leaf primordia and will be useful for visualizing and quantifying leaf anatomical and developmental traits in maize and other grass species.

Conversion Predictors of Clinically Isolated Syndrome to Multiple Sclerosis in Mexican Patients: A Prospective Study.

BACKGROUND: Clinically Isolated Syndrome (CIS) is the first clinical episode suggestive of Clinical Definite Multiple Sclerosis (CDMS). There are no reports on possible predictors of conversion to CDMS in Mexican mestizo patients. AIM OF THE STUDY: To investigate immunological markers, clinical and paraclinical findings, and the presence of herpesvirus DNA to predict the transition from CIS to CDMS in Mexican patients. METHODS: A single-center prospective cohort study was conducted with newly diagnosed patients with CIS in Mexico between 2006 and 2010. Clinical information, immunophenotype, serum cytokines, anti-myelin protein immunoglobulins, and herpes viral DNA were determined at the time of diagnosis. RESULTS: 273 patients diagnosed with CIS met the enrolment criteria; after 10 years of follow-up, 46% met the 2010 McDonald criteria for CDMS. Baseline parameters associated with conversion to CDMS were motor symptoms, multifocal syndromes, and alterations of somatosensory evoked potentials. The presence of at least one lesion on magnetic resonance imaging was the main factor associated with an increased risk of conversion to CDMS (RR 15.52, 95% CI 3.96-60.79, p = 0.000). Patients who converted to CDMS showed a significantly lower percentage of circulating regulatory T cells, cytotoxic T cells, and B cells, and the conversion to CDMS was associated with the presence of varicella-zoster virus and herpes simplex virus 1 DNA in cerebrospinal fluid and blood. CONCLUSION: There is scarce evidence in Mexico regarding the demographic and clinical aspects of CIS and CDMS. This study shows several predictors of conversion to CDMS to be considered in Mexican patients with CIS.

A Biomimicking and Multiarm Self-Indicating Nanoassembly for Site-Specific Photothermal-Potentiated Thrombolysis Assessed in Microfluidic and In Vivo Models.

Thrombolytic and antithrombotic therapies are limited by short circulation time and the risk of off-target hemorrhage. Integrating a thrombus-homing strategy with photothermal therapy are proposed to address these limitations. Using glycol chitosan, polypyrrole, iron oxide and heparin, biomimicking GCPIH nanoparticles are developed for targeted thrombus delivery and thrombolysis. The nanoassembly achieves precise delivery of polypyrrole, exhibiting biocompatibility, selective accumulation at multiple thrombus sites, and enhanced thrombolysis through photothermal activation. To simulate targeted thrombolysis, a microfluidic model predicting thrombolysis dynamics in realistic pathological scenarios is designed. Human blood assessments validate the precise homing of GCPIH nanoparticles to activated thrombus microenvironments. Efficient near-infrared phototherapeutic effects are demonstrated at thrombus lesions under physiological flow conditions ex vivo. The combined investigations provide compelling evidence supporting the potential of GCPIH nanoparticles for effective thrombus therapy. The microfluidic model also offers a platform for advanced thrombolytic nanomedicine development.

In Silico Study of Novel Cyclodextrin Inclusion Complexes of Polycaprolactone and Its Correlation with Skin Regeneration.

Three novel biomaterials obtained via inclusion complexes of ß-cyclodextrin, 6-deoxi-6-amino-ß-cyclodextrin and epithelial growth factor grafted to 6-deoxi-6-amino-ß-cyclodextrin with polycaprolactone. Furthermore, some physicochemical, toxicological and absorption properties were predicted using bioinformatics tools. The electronic, geometrical and spectroscopical calculated properties agree with the properties obtained via experimental methods, explaining the behaviors observed in each case. The interaction energy was obtained, and its values were -60.6, -20.9 and -17.1 kcal/mol for ß-cyclodextrin/polycaprolactone followed by the 6-amino-ß-cyclodextrin-polycaprolactone complex and finally the complex of epithelial growth factor anchored to 6-deoxy-6-amino-ß-cyclodextrin/polycaprolactone. Additionally, the dipolar moments were calculated, achieving values of 3.2688, 5.9249 and 5.0998 Debye, respectively, and in addition the experimental wettability behavior of the studied materials has also been explained. It is important to note that the toxicological predictions suggested no mutagenic, tumorigenic or reproductive effects; moreover, an anti-inflammatory effect has been shown. Finally, the improvement in the cicatricial effect of the novel materials has been conveniently explained by comparing the poly-caprolactone data obtained in the experimental assessments.

PEDOT:PSS-Based Bioelectrodes for Multifunctional Drug Release and Electric Cell-Substrate Impedance Sensing.

Electric cell-substrate impedance sensing (ECIS) is an innovative approach for the label-free and real-time detection of cell morphology, growth, and apoptosis, thereby playing an essential role as both a viable alternative and valuable complement to conventional biochemical/pharmaceutical analysis in the field of diagnostics. Constant improvements are naturally sought to further improve the effective range and reliability of this technology. In this study, we developed poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonate) (PEDOT:PSS) conducting polymer (CP)-based bioelectrodes integrated into homemade ECIS cell-culture chamber slides for the simultaneous drug release and real-time biosensing of cancer cell viability under drug treatment. The CP comprised tailored PEDOT:PSS, poly(ethylene oxide) (PEO), and (3-glycidyloxypropyl)trimethoxysilane (GOPS) capable of encapsulating antitumor chemotherapeutic agents such as doxorubicin (DOX), docetaxel (DTX), and a DOX/DTX combination. This device can reliably monitor impedance signal changes correlated with cell viability on chips generated by cell adhesion onto a predetermined CP-based working electrode while simultaneously exhibiting excellent properties for both drug encapsulation and on-demand release from another CP-based counter electrode under electrical stimulation (ES) operation. Cyclic voltammetry curves and surface profile data of different CP-based coatings (without or with drugs) were used to analyze the changes in charge capacity and thickness, respectively, thereby further revealing the correlation between their drug-releasing performance under ES operation (determined using ultraviolet-visible (UV-vis) spectroscopy). Finally, antitumor drug screening tests (DOX, DTX, and DOX/DTX combination) were performed on MCF-7 and HeLa cells using our developed CP-based ECIS chip system to monitor the impedance signal changes and their related cell viability results.

Estrés académico autopercibido y factores relacionados en una escuela privada de odontología en Cartagena, Colombia / Self-perceived academic stress and related factors in a private dental school from Cartagena, Colombia / Estresse acadêmico auto-percebido e fatores relacionados em uma escola particular de odontologia em Cartagena, Colômbia

Introducción: El estrés académico surge de una interacción entre factores estresantes ambientales y las reacciones de los estudiantes, asociándose con frustración y fracaso académico. Además, algunos factores demográficos y familiares influyen en el estrés. Objetivo: Analizar estrés académico, factores demográficos y familiares en estudiantes de Odontología en Escuela privada de Cartagena. Materiales y métodos: Estudio descriptivo de corte transversal, en 158 estudiantes. Se aplicó cuestionario sociodemográfico, APGAR familiar e inventario SISCO. Se analizó los datos mediante estadística descriptiva y prueba X2. Resultados: Se encontró disfuncionalidad familiar y mal soporte de amigos en casi la mitad de los participantes, niveles de preocupación moderada cercana a 70%, alta frecuencia de demandas del entorno (estresores), reacciones comportamentales y presencia de síntomas ante estímulo estresor. Hubo asociación entre alta frecuencia de inquietud en situaciones cotidianas y pertenecer a semestres básicos, baja frecuencia de uso de estrategias de afrontamiento y sexo femenino, alta frecuencia de reacciones comportamentales y disfunción familiar. Conclusiones: Los principales factores identificados fueron pertenecer a semestres básicos, ser mujer y presencia de disfuncionalidad familiar. Los niveles de estrés y disfuncionalidad familiar sugieren una alerta para intervenir desde bienestar universitario, previniendo condiciones desfavorables en la salud y rendimiento académico de los estudiantes.

Introduction: Academic stress arises from an interaction between environmental stressors and student reactions, which are associated with academic frustration and academic failure. Likewise, there are demographic and family factors that affect stress. Objective: To analyze academic stress, demographic and family factors in Dentistry students at a private school in Cartagena. Materials and methods: A descriptive cross-sectional study with 158 students. The APGAR family sociodemographic questionnaire and SISCO inventory were used. Descriptive statistics and the X2 test were applied to analyze data. Results: Family dysfunction and low friend support were observed in almost half of the participants, 70% displayed moderate anxiety levels. Also, a high frequency of environmental demands (stressors), behavioral reactions, and the presence of symptoms in response to the stressors were found. There were associations between: high frequency of restlessness in everyday situations and belonging to initial semesters; low frequency of using coping strategies and female gender; and high frequency of behavioral reactions and family dysfunction. Conclusions: The main factors identified were belonging to initial semesters, being a woman, and family dysfunction. Levels of stress and family dysfunction can be used as a signal for university welfare services to intervene and prevent unfavorable student health and academic performance conditions.

Introdução: O estresse acadêmico surge de uma interação entre os estressores ambientais e as reações dos alunos, associados à frustração e ao fracasso acadêmico. Além disso, alguns fatores demográficos e familiares influenciam o estresse. Objetivo: Analisar o estresse acadêmico, fatores demográficos e familiares em estudantes de odontologia de uma escola particular de Cartagena. Materiais e métodos: Estudo transversal descritivo, em 158 estudantes. Questionários sociodemográficos, APGAR familiar e inventário SISCO foram aplicados. Os dados foram analisados por meio de estatística descritiva e teste X2. Resultados: Disfunção familiar e pouco apoio dos amigos foram encontrados em quase metade dos participantes, níveis de preocupação moderada próximos a 70 %, alta frequência de demandas do ambiente (estressores), reações comportamentais e presença de sintomas diante de estímulos estressantes. Houve associação entre alta frequência de inquietação em situações cotidianas e pertencimento aos semestres básicos, baixa frequência do uso de estratégias de enfrentamento e sexo feminino, alta frequência de reações comportamentais e disfunção familiar. Conclusões: Os principais fatores identificados foram pertencer aos semestres básicos, ser mulher e a presença de disfunção familiar. Os níveis de estresse e disfuncionalidade familiar sugerem um alerta para intervir da unidade de bem-estar da universidade para prevenir condições desfavoráveis na saúde e desempenho acadêmico dos estudantes.

Síndrome de Burnout en médicos residentes de medicina interna

Introducción: el síndrome de Burnout se define como una respuesta al estrés laboral crónico, integrado por actitudes y sentimientos negativos hacia las personas con las que se trabaja y hacia el propio rol profesional. Se considera como la fase avanzada del estrés profesional. Objetivos: evaluar la prevalencia del síndrome de Burnout en médicos residentes del área de medicina interna en un hospital de tercer nivel. Materiales y métodos: se realizó un estudio observacional, descriptivo y transversal mediante una encuesta en línea a través de Google Forms™, a médicos residentes del área de medicina interna aplicando el test Maslach Burnout Inventory (MBI). Resultados: de los 60 residentes, que incluyen a los de primer, segundo y tercer año, se obtuvo una participación de 71,6%. El 58,1% corresponde al sexo femenino y 41,9% al sexo masculino. El grupo etario con mayor participación (79,1%) tiene 26 a 30 años. Si se tiene en cuenta la presencia de 2 de 3 variables (cansancio emocional, despersonalización, falta de realización personal), la prevalencia de síndrome de Burnout fue 46,5% (20 de 43 encuestados). Conclusión: la prevalencia de síndrome de Burnout en base a 2 de sus 3 criterios fue 46,5%.

Introduction: Burnout syndrome is defined as a response to chronic work stress, made up of negative attitudes and feelings towards the people with whom one works and towards one's own professional role. It is considered as the advanced phase of professional stress. Objectives: To evaluate the prevalence of Burnout syndrome in internal medicine residents in a tertiary level hospital. Materials and methods: An observational, descriptive and cross-sectional study was carried out by means of an online survey through Google Forms™ applied to resident physicians in the area of ​​internal medicine applying the Maslach Burnout Inventory (MBI) test. Results: Of the 60 residents, which include first, second and third-year students, 71.6% participated, 58.1% correspond to women and 41.9% to men. The age group with the highest participation (79.1%) is between 26 and 30 years old. If the presence of 2 of 3 variables is taken into account (emotional exhaustion, depersonalization, lack of personal fulfillment), the prevalence of Burnout syndrome was 46.5% (20 of 43 respondents). Conclusion: The prevalence of Burnout syndrome based on 2 of its 3 criteria was 46.5%.

Glycol chitosan/iron oxide/polypyrrole nanoclusters for precise chemodynamic/photothermal synergistic therapy.

Noninvasive photothermal therapy (PTT) represents a promising direction for more modern and precise medical applications. However, PTT efficacy is still not satisfactory due to the existence of heat shock proteins (HSPs) and poorly targeted delivery. Herein, the design of a nanosystem with improved delivery efficacy for anticancer treatment employing the synergetic effects of reactive oxygen species (ROS)-driven chemodynamic therapy (CDT) to inactivated HSPs with photothermal-hyperthermia was therefore achieved through the development of pH-targeting glycol chitosan/iron oxide enclosed core polypyrrole nanoclusters (GCPI NCs). The designed NCs effectively accumulated toward cancer cells due to their acidic microenvironment, initiating ROS generation via Fenton reaction at the outset and performing site-specific near infrared (NIR)-photothermal effect. A comprehensive analysis of both surface and bulk material properties of the CDT/PTT NCs as well as biointerface properties were ascertained via numerous surface specific analytical techniques by bringing together heightened accumulation of CDT/PTT NCs, which can significantly eradicate cancer cells thus minimizing the side effects of conventional chemotherapies. All of these attributes act in synergy over the cancer cells succeeding in fashioning NC's able to act as competent agents in the MRI-monitored enhanced CDT/PTT synergistic therapy. Findings in this study evoke attention in future oncological therapeutic strategies.

Determinación de anticuerpos antidiarrea viral bovina (DVB) en vacas lecheras de un municipio de Boyacá (Colombia) / Determination of Antibodies against Bovine Viral Diarrhea (BVD) in Diry Cows in a Municipality of Boyacá (Colombia)

Resumen La diarrea viral bovina (DVB) es una patología infecciosa generada por un pestivirus de distribución mundial, causante de problemas reproductivos y pérdidas económicas. El objetivo del presente estudio fue establecer la positividad al virus de diarrea viral bovina (vDVB) en vacas del municipio de Tuta (Boyacá, Colombia), y analizar los grupos etarios, raciales y las variables reproductivas y de manejo como posibles factores de riesgo. Se tomaron 374 muestras de sangre, a las cuales se les realizó la prueba ELISA indirecta, implementando el kit Serelisa® BVD p80 Ab Mono Blocking; los datos se procesaron con EpiInfo®. Se encontró una seroprevalencia del 41,7 %. Los cruces raciales y los bovinos >4 años presentaron la seroprevalencia más alta. Los animales >4 años (p= 0,0000001922) presentaron asociación estadística con la presencia de la enfermedad, y se consideró factor de riesgo para vDVB. Se deben establecer programas de control y prevención que dificulten su diseminación en la zona.

Abstract Bovine viral diarrhea (BVD) is an infectious pathology generated by a pestivirus of worldwide distribution, which causes reproductive problems and economic losses. The objective of this study was to establish bovine viral diarrhea virus (BVDV) positivity in cows from the municipality of Tuta (Boyacá, Colombia), and to analyze age and racial groups and reproductive and management variables as possible risk factors. A total of 374 blood samples were taken and the indirect ELISA test was performed using the Serelisa® BVD p80 Ab Mono Blocking kit; the data were processed with EpiInfo®. A seroprevalence of 41.7% was found. Crossbreds and cattle >4 years had the highest seroprevalence. Animals >4 years old (p= 0.0000001922) were statistically associated with the presence of the disease and were considered a risk factor for BVDV. Control and prevention programs should be established to hinder its dissemination in the area.

Longitudinal Functional Study of Murine Aging: A Resource for Future Study Designs.

Aging is characterized by systemic declines in tissue and organ functions. Interventions that slow these declines represent promising therapeutics to protect against age-related disease and improve the quality of life. In this study, several interventions associated with lifespan extension in invertebrates or improvement of age-related disease were tested in mouse models to determine if they were effective in slowing tissue aging in a broad spectrum of functional assays. Benzoxazole, which extends the lifespan of Caenorhabditis elegans, slowed age-related femoral bone loss in mice. Rates of change were established for clinically significant parameters in untreated mice, including kyphosis, blood glucose, body composition, activity, metabolic measures, and detailed parameters of skeletal aging in bone. These findings have implications for the study of preclinical physiological aging and therapies targeting aging. Finally, an online application was created that includes the calculated rates of change and that enables power and variance to be calculated for many clinically important metrics of aging with an emphasis on bone. This resource will help in future study designs employing novel interventions in aging mice. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC. on behalf of American Society for Bone and Mineral Research.

[Clozapine in epilepsy and psychosis: effects on seizures and metabolic profile]. / Clozapina en epilepsia y psicosis: efectos en las crisis epilépticas y en el perfil metabólico.

Background: Clozapine (CZP) is an antipsychotic used in resistant psychosis, but has adverse metabolic effects and is associated with new onset or worsening of epileptic seizures (ES). There is not enough information available regarding its effect on metabolic variables and on ES in patients with epilepsy. Objective: To describe the effect of CZP on the metabolic and hematologic profiles, and on ES in patients with epilepsy and with psychosis and/or aggressive behavior. Methods: A case series of patients with epilepsy and psychosis and/or aggressive behavior that received CZP with an 18-week follow-up. Clinical records were assessed from 2008-2018. 30 patients with epilepsy that received CZP were included. A paired analysis (Student's t-test or Wilcoxon signed rank test) was performed with metabolic variables (glucose, cholesterol, and triglycerides), hematologic variables, weight, body mass index (BMI), and monthly ES before and after CZP administration. Results: The median age to CZP initiation was 31.9 ± 16.07 years. Median CZP dosage was 193 mg/day. There were changes on BMI (p = 0.001; 3.2 kg/m2 increase, median = 3.08), triglycerides (p = 0.002) and glucose (p = 0.030). Weight increase was 7 kg (p = 0.292; median = 4 kg). Monthly ES mean was decreased from 4.9 (median = 2) to 2.04 (median = 1; p = 0.001). Conclusions: This study provide information regarding the security profile of CZP in patients with epilepsy with psychosis and/or aggressive behavior. A decrease on monthly ES was observed, as well as moderate increases in triglycerides, glucose and BMI, which coincide with that described by other authors.

Introducción: La clozapina (CZP) es un antipsicótico efectivo en la psicosis que no responde a otros antipsicóticos, pero tiene efectos metabólicos adversos y se relaciona con la generación de crisis epilépticas (CE). Existe poca información sobre su efecto en variables metabólicas y sobre las CE en pacientes con epilepsia. Objetivo: Describir el efecto de la CZP en el perfil metabólico, el perfil hematológico y la frecuencia de CE en pacientes con epilepsia y con psicosis o agresividad. Método: Serie de casos de pacientes con epilepsia y psicosis o agresividad que recibieron CZP con un seguimiento de 18 semanas. Se revisaron los expedientes clínicos de 2008-2018. Se incluyeron 30 pacientes con epilepsia que recibieron CZP. Se hizo una comparación pareada (prueba t de Student o de signo y rango de Wilcoxon), antes y después del inicio de la CZP, de las variables metabólicas (glucosa, colesterol y triglicéridos) y hematológicas, el peso, el índice de masa corporal (IMC) y las CE mensuales. Resultados: La edad media al iniciar la CZP fue de 31.9 ± 16.07 años. La dosis media fue 193 mg/día. Hubo incremento en el IMC (p = 0.001; aumento de 3.2 kg/m2; mediana = 3.08), los triglicéridos (p = 0.002) y la glucosa (p = 0.030). La ganancia de peso fue de 7 ± 10.4 kg (p = 0.292; mediana = 4 kg). El promedio de CE mensuales se redujo de 4.9 (mediana = 2) a 2.04 (p = 0.001; mediana = 1). Conclusiones: Este estudio aporta información del perfil de seguridad del uso de CZP en pacientes con epilepsia y psicosis o agresividad. Se observó una disminución en la frecuencia mensual de CE, así como aumentos moderados de los triglicéridos, la glucosa y el IMC, que coinciden con lo descrito por otros autores.

Dual-Targeting Glycol Chitosan/Heparin-Decorated Polypyrrole Nanoparticle for Augmented Photothermal Thrombolytic Therapy.

Near-infrared (NIR)-light-modulated photothermal thrombolysis has been investigated to overcome the hemorrhage danger posed by clinical clot-busting substances. A long-standing issue in thrombosis fibrinolytics is the lack of lesion-specific therapy, which should not be ignored. Herein, a novel thrombolysis therapy using photothermal disintegration of a fibrin clot was explored through dual-targeting glycol chitosan/heparin-decorated polypyrrole nanoparticles (GCS-PPY-H NPs) to enhance thrombus delivery and thrombolytic therapeutic efficacy. GCS-PPY-H NPs can target acidic/P-selectin high-expression inflammatory endothelial cells/thrombus sites for initiating lesion-site-specific thrombolysis by hyperthermia using NIR irradiation. A significant fibrin clot-clearance rate was achieved with thrombolysis using dual-targeting/modality photothermal clot disintegration in vivo. The molecular level mechanisms of the developed nanoformulations and interface properties were determined using multiple surface specific analytical techniques, such as particle size distribution, zeta potential, electron microscopy, Fourier-transform infrared spectroscopy (FTIR), wavelength absorbance, photothermal, immunofluorescence, and histology. Owing to the augmented thrombus delivery of GCS-PPY-H NPs and swift treatment time, dual-targeting photothermal clot disintegration as a systematic treatment using GCS-PPY-H NPs can be effectively applied in thrombolysis. This novel approach possesses a promising future for thrombolytic treatment.

A Comprehensive Analysis of COVID-19 Impact in Latin America.

Background: Latin America has now become the epicenter of the global coronavirus disease 2019 (COVID-19) pandemic. In the ongoing COVID -19 pandemic, a profound burden of SARS-COV-2 infection has been reported in Latin America. In the present study, we aim to determine the profiles that are associated with this disease in Latin America. We analyzed symptoms, morbidities and gastrointestinal (GI) manifestations by country. Methods: We analyzed data from SARS-CoV-2 positive patients evaluated at healthcare centers and hospitals of 8 Latin American countries including Brazil, Peru, Mexico, Argentina, Colombia, Venezuela, Ecuador, and Bolivia between March 1 and July 30, 2020. These countries consist of a total population that exceeds 519 million. Demographics, comorbidities and clinical symptoms were collected. Statistical descriptive analysis and correlation analyses of symptoms, comorbidities and lethality were performed. Results: A total of 728,282 patients tested positive for COVID-19 across all the 8 Latin American countries. Of these, 52.6% were female. The average age was 48.4 years. Peru had the oldest cohort with 56.8 years old and highest rate of females (56.8%) while Chile had the youngest cohort (39 years old). Venezuela had the highest male prevalence (56.7%). Most common symptoms were cough with 60.1% (Bolivia had the highest rate 78%), fatigue/tiredness with 52.0%, sore throat with 50.3%, and fever with 44.2%. Bolivia had fever as the top symptom (83.3%). GI symptoms including diarrhea (highest in Mexico with 22.9%), nausea, vomiting, and abdominal pain were not associated with higher mortality.Hypertension was among the top (12.1%) comorbidities followed by diabetes with 8.3% and obesity 4.5%. In multivariable analyses, the leading and significant comorbidities were hypertension (r=0.83, p=0.02), diabetes (r=0.91, p=0.01), and obesity (r=0.86, p=0.03). Asthma (r=0.37, p=0.54) and increasing age (0.13 p=0.81) were not independently associated with higher mortality. Lethality was highest in Mexico (16.6%) and lowest in Venezuela (0.9%) among the analyzed cohorts. Conclusion: Nearly, 10.5%-53% of patients with COVID-19 have GI manifestations. Differential clinical symptoms were associated with COVID-19 in Latin America countries. Metabolic syndrome components were the main comorbidities associated with poor outcome. Country-specific management and prevention plans are needed. Country-specific management and prevention plans can be established from this meta-analysis.

Alpha-Ketoglutarate, an Endogenous Metabolite, Extends Lifespan and Compresses Morbidity in Aging Mice.

Metabolism and aging are tightly connected. Alpha-ketoglutarate is a key metabolite in the tricarboxylic acid (TCA) cycle, and its levels change upon fasting, exercise, and aging. Here, we investigate the effect of alpha-ketoglutarate (delivered in the form of a calcium salt, CaAKG) on healthspan and lifespan in C57BL/6 mice. To probe the relationship between healthspan and lifespan extension in mammals, we performed a series of longitudinal, clinically relevant measurements. We find that CaAKG promotes a longer, healthier life associated with a decrease in levels of systemic inflammatory cytokines. We propose that induction of IL-10 by dietary AKG suppresses chronic inflammation, leading to health benefits. By simultaneously reducing frailty and enhancing longevity, AKG, at least in the murine model, results in a compression of morbidity.

Automated lifespan determination across Caenorhabditis strains and species reveals assay-specific effects of chemical interventions.

The goal of the Caenorhabditis Intervention Testing Program is to identify robust and reproducible pro-longevity interventions that are efficacious across genetically diverse cohorts in the Caenorhabditis genus. The project design features multiple experimental replicates collected by three different laboratories. Our initial effort employed fully manual survival assays. With an interest in increasing throughput, we explored automation with flatbed scanner-based Automated Lifespan Machines (ALMs). We used ALMs to measure survivorship of 22 Caenorhabditis strains spanning three species. Additionally, we tested five chemicals that we previously found extended lifespan in manual assays. Overall, we found similar sources of variation among trials for the ALM and our previous manual assays, verifying reproducibility of outcome. Survival assessment was generally consistent between the manual and the ALM assays, although we did observe radically contrasting results for certain compound interventions. We found that particular lifespan outcome differences could be attributed to protocol elements such as enhanced light exposure of specific compounds in the ALM, underscoring that differences in technical details can influence outcomes and therefore interpretation. Overall, we demonstrate that the ALMs effectively reproduce a large, conventionally scored dataset from a diverse test set, independently validating ALMs as a robust and reproducible approach toward aging-intervention screening.