Lifespan effects in male UM-HET3 mice treated with sodium thiosulfate, 16-hydroxyestriol, and late-start canagliflozin.

Genetically heterogeneous UM-HET3 mice born in 2020 were used to test possible lifespan effects of alpha-ketoglutarate (AKG), 2,4-dinitrophenol (DNP), hydralazine (HYD), nebivolol (NEBI), 16α-hydroxyestriol (OH_Est), and sodium thiosulfate (THIO), and to evaluate the effects of canagliflozin (Cana) when started at 16 months of age. OH_Est produced a 15% increase (p = 0.0001) in median lifespan in males but led to a significant (7%) decline in female lifespan. Cana, started at 16 months, also led to a significant increase (14%, p = 0.004) in males and a significant decline (6%, p = 0.03) in females. Cana given to mice at 6 months led, as in our previous study, to an increase in male lifespan without any change in female lifespan, suggesting that this agent may lead to female-specific late-life harm. We found that blood levels of Cana were approximately 20-fold higher in aged females than in young males, suggesting a possible mechanism for the sex-specific disparities in its effects. NEBI was also found to produce a female-specific decline (4%, p = 0.03) in lifespan. None of the other tested drugs provided a lifespan benefit in either sex. These data bring to 7 the list of ITP-tested drugs that induce at least a 10% lifespan increase in one or both sexes, add a fourth drug with demonstrated mid-life benefits on lifespan, and provide a testable hypothesis that might explain the sexual dimorphism in lifespan effects of the SGLT2 inhibitor Cana.

Significant Increase in Oxidative Stress Indices in Erythrocyte Membranes of Obese Patients with Metabolically-Associated Fatty Liver Disease.

Metabolic dysfunction-associated hepatic steatosis (MAFLD) indicates the metabolic risk associated with hepatic steatosis, overweight and obesity, and clinical evidence of metabolic dysregulation. Since MAFLD is one of the diseases that show a high frequency of alterations in the lipid content of cell membranes, the aim of this study was to evaluate the indices of oxidative damage of erythrocyte membranes in overweight and obese MAFLD subjects. The study was conducted on serum samples and red blood cell membranes of overweight and obese MAFLD subjects. For each patient, biochemical measurements and lipidomic analyses of erythrocytes membranes were performed. Significant differences in fatty acid profiles of RBC membranes were found between overweight and obese patients. In particular, the Peroxidation Index (PI) was higher in the erythrocyte membranes of obese subjects than in overweight subjects. The same behavior was observed for Unsaturation Index (UI) and Free Radical Stress Index (Free RSI), supporting the fact that the systemic increase in oxidative stress was associated with obesity. The study shows that there is a different susceptibility to erythrocyte membrane peroxidation for overweight and obese subjects, and the increased values of oxidative stress indices observed in the erythrocyte membranes of obese patients with MAFLD may be a possible indicator of pro-oxidative events occurring in obesity-related diseases.

A Family with EEC Syndrome in the Son and ADULT Syndrome in His Father Caused by the c.797G>A (p.Arg266Gln) Pathogenic Variant in the TP63 Gene.

Introduction: To our knowledge, there are few examples of intrafamilial variability involving two different TP63-linked morphopathies within a same family. Here, we describe a Mexican family in which the son had ectrodactyly, ectodermal dysplasia, and cleft lip/palate syndrome 3 (EEC3), and his father acro-dermato-ungual-lacrimal-tooth (ADULT) syndrome, both heterozygous for the p.Arg266Gln pathogenic variant in TP63. Additionally, we reviewed the clinical information reported for this TP63 genotype. Case Presentation: The son of this family presented ectodermal defects (thin and sparse hair, mild nail dysplasia), tetramelic ectrodactyly, syndactyly, and nasolacrimal duct obstruction (NLDO), indicative of an EEC3 diagnosis. His father, however, exhibited severe NLDO, facial freckling, dental abnormalities, mild nail dysplasia, and a history of micturition problems, compatible with ADULT syndrome. Both were heterozygous for the NM_003722.5(TP63):c.797G>A (p.Arg266Gln) pathogenic variant in TP63. Discussion: This report expands the spectrum of intrafamilial variability confirming that this can include the expression of distinct types of TP63-related disorders among different members of the same family, whose implications should be also considered in genetic counseling. From our review, we observed that p.Arg266Gln variant seems to correlate particularly with the presence of NLDO, sparse hair/eyebrows, ridged/dystrophic nails, anodontia/hypodontia, and micturition difficulties, as well as for a minor frequency of cleft lip/cleft palate.

Developmental trajectories of socio-emotional outcomes of children and young people in out-of-home care - Insights from data of Pathways of Care Longitudinal Study (POCLS).

BACKGROUND: There has been a limited understanding of the longitudinal trajectory and determinants of socio-emotional outcomes among children in out-of-home care (OOHC). OBJECTIVES: This study aimed to examine child socio-demographics, pre-care maltreatment, placement, and caregiver factors associated with trajectories of socio-emotional difficulties of children in OOHC. PARTICIPANTS AND SETTING: The study sample (n = 345) included data from the Pathways of Care Longitudinal Study (POCLS), a prospective longitudinal cohort of children aged 3-17 years who entered the OOHC system in New South Wales (NSW) Australia, between 2010 and 2011. METHODS: Group-based trajectory models were used to identify distinct socio-emotional trajectory groups based on the Child Behaviour Check List (CBCL) Total Problem T-scores completed at all four Waves 1-4. Modified Poisson regression analysis was conducted to assess the association (risk ratios) of socio-emotional trajectory group membership with pre-care maltreatment, placement, and caregiver-related factors. RESULTS: Three trajectories of socio-emotional development were identified: 'persistently low difficulties' (average CBCL T-score changed from 40 to 38 over time), normal (average CBCL T-score changed from 52 to 55 over time), and clinical (average CBCL T-score remained at 68 over time) trajectories. Each trajectory presented a stable trend over time. Relative/kinship care, as compared with foster care, was associated with the "persistently low" socio-emotional trajectory. Being male, exposure to ≥8 pre-care substantiated risk of significant harm (ROSH) reports, placement changes, and caregiver's psychological distress (more than two-fold increased risk) were associated with the clinical socio-emotional trajectory. CONCLUSIONS: Early intervention to ensure children have a nurturing care environment and psychological support to caregivers are vital for positive socio-emotional development over time among children in long-term OOHC.

Astaxanthin and meclizine extend lifespan in UM-HET3 male mice; fisetin, SG1002 (hydrogen sulfide donor), dimethyl fumarate, mycophenolic acid, and 4-phenylbutyrate do not significantly affect lifespan in either sex at the doses and schedules used.

In genetically heterogeneous (UM-HET3) mice produced by the CByB6F1 × C3D2F1 cross, the Nrf2 activator astaxanthin (Asta) extended the median male lifespan by 12% (p = 0.003, log-rank test), while meclizine (Mec), an mTORC1 inhibitor, extended the male lifespan by 8% (p = 0.03). Asta was fed at 1840 ± 520 (9) ppm and Mec at 544 ± 48 (9) ppm, stated as mean ± SE (n) of independent diet preparations. Both were started at 12 months of age. The 90th percentile lifespan for both treatments was extended in absolute value by 6% in males, but neither was significant by the Wang-Allison test. Five other new agents were also tested as follows: fisetin, SG1002 (hydrogen sulfide donor), dimethyl fumarate, mycophenolic acid, and 4-phenylbutyrate. None of these increased lifespan significantly at the dose and method of administration tested in either sex. Amounts of dimethyl fumarate in the diet averaged 35% of the target dose, which may explain the absence of lifespan effects. Body weight was not significantly affected in males by any of the test agents. Late life weights were lower in females fed Asta and Mec, but lifespan was not significantly affected in these females. The male-specific lifespan benefits from Asta and Mec may provide insights into sex-specific aspects of aging.

Influence of puff topographies on e-liquid heating temperature, emission characteristics and modeled lung deposition of Puff Bar™.

Puff Bar™, one of the latest designs of e-cigarettes, heats a mixture of liquid using a battery-powered coil at certain temperatures to emit aerosol. This study presents a mass-based characterization of emissions from seven flavors of Puff Bar™ devices by aerosolizing with three puff topographies [(puff volume: 55 < 65 < 75-mL) within 4-seconds at 30-seconds interval]. We evaluated the effects of puff topographies on heating temperatures; characterized particles using a cascade impactor; and measured volatile carbonyl compounds (VCCs). Modeled dosimetry and calculated mass median aerodynamic diameters (MMADs) were used to estimate regional, total respiratory deposition of the inhaled aerosol and exhaled fractions that could pose secondhand exposure risk. Temperatures of Puff Bar™ e-liquids increased with increasing puff volumes: 55mL (116.6 °C), 65 mL (128.3 °C), and 75mL (168.9 °C). Flavor types significantly influenced MMADs, total mass of particles, and VCCs (µg/puff: 2.15-2.30) in Puff Bar™ emissions (p < 0.05). Increasing puff volume (mL:55 < 65 < 75) significantly increased total mass (mg/puff: 4.6 < 5.6 < 6.2) of particles without substantially changing MMADs (~1µm:1.02~0.99~0.98). Aerosol emissions were estimated to deposit in the pulmonary region of e-cigarette user (41-44%), which could have toxicological importance. More than 2/3 (67-77%) of inhaled particles were estimated to be exhaled by users, which could affect bystanders. The VCCs measured contained carcinogens-formaldehyde (29.6%) and acetaldehyde (16.4%)-as well as respiratory irritants: acetone (23.9%), isovaleraldehyde (14.5%), and acrolein (4.9%). As Puff Bar™ emissions contain respirable particles and harmful chemicals, efforts should be made to minimize exposures, especially in indoor settings where people (including vulnerable populations) spend most of their life-time.

Skeletal muscle TFEB signaling promotes central nervous system function and reduces neuroinflammation during aging and neurodegenerative disease.

Skeletal muscle has recently arisen as a regulator of central nervous system (CNS) function and aging, secreting bioactive molecules known as myokines with metabolism-modifying functions in targeted tissues, including the CNS. Here, we report the generation of a transgenic mouse with enhanced skeletal muscle lysosomal and mitochondrial function via targeted overexpression of transcription factor E-B (TFEB). We discovered that the resulting geroprotective effects in skeletal muscle reduce neuroinflammation and the accumulation of tau-associated pathological hallmarks in a mouse model of tauopathy. Muscle-specific TFEB overexpression significantly ameliorates proteotoxicity, reduces neuroinflammation, and promotes transcriptional remodeling of the aged CNS, preserving cognition and memory in aged mice. Our results implicate the maintenance of skeletal muscle function throughout aging in direct regulation of CNS health and disease and suggest that skeletal muscle originating factors may act as therapeutic targets against age-associated neurodegenerative disorders.

Impaired aldehyde detoxification exacerbates motor deficits in an alpha-synuclein mouse model of Parkinson's disease.

INTRODUCTION: The discovery of biogenic aldehydes in the postmortem parkinsonian brain and the ability of these aldehydes to modify and cross-link proteins has called attention to their possible role in Parkinson's disease. For example, many in vitro studies have found that the aldehyde metabolite of dopamine, 3,4-dihydroxyphenylacetaldehyde (DOPAL), induces the formation of stable, neurotoxic alpha-synuclein oligomers. METHODS: To study this in vivo, mice deficient in the two aldehyde dehydrogenase enzymes (Aldh1a1 and Aldh2, DKO) primarily responsible for detoxification of DOPAL in the nigrostriatal pathway were crossed with mice that overexpress human wild-type alpha-synuclein. DKO overexpressing human wild-type alpha-synuclein (DKO/ASO) offspring were evaluated for impairment on motor tasks associated with Parkinsonism. RESULTS: DKO/ASO mice developed severe motor deficits greater than that of mice overexpressing human wild-type alpha-synuclein alone. CONCLUSION: These results provide evidence to support the idea that biogenic aldehydes such as DOPAL interact with human wild-type alpha-synuclein, directly or indirectly, in vivo to exacerbate locomotor deficits in Parkinson's disease.

CDKN2A deletion remodels lipid metabolism to prime glioblastoma for ferroptosis.

Malignant tumors exhibit heterogeneous metabolic reprogramming, hindering the identification of translatable vulnerabilities for metabolism-targeted therapy. How molecular alterations in tumors promote metabolic diversity and distinct targetable dependencies remains poorly defined. Here we create a resource consisting of lipidomic, transcriptomic, and genomic data from 156 molecularly diverse glioblastoma (GBM) tumors and derivative models. Through integrated analysis of the GBM lipidome with molecular datasets, we identify CDKN2A deletion remodels the GBM lipidome, notably redistributing oxidizable polyunsaturated fatty acids into distinct lipid compartments. Consequently, CDKN2A-deleted GBMs display higher lipid peroxidation, selectively priming tumors for ferroptosis. Together, this study presents a molecular and lipidomic resource of clinical and preclinical GBM specimens, which we leverage to detect a therapeutically exploitable link between a recurring molecular lesion and altered lipid metabolism in GBM.

Medical ozone arrests oxidative damage progression and regulates vasoactive mediator levels in elderly patients (60-70 years) with oxidative etiology diseases.

Medical ozone reestablishes cellular redox balance so that it may be a valid therapeutic approach in the prevention and management of age-related diseases with oxidative etiology in older people. The aim of this study is to evaluate oxidative stress and some vasoactive substances in elderly (60-70 years) rheumatoid arthritis patients with diabetes and hypertension, as well as another group with bronchial asthma patients in order to demonstrate the beneficial effects of medical ozone in the prevention and therapy of age-related diseases in these age groups. A randomized clinical study with 45 older patients (60-70 years) was performed. Group I (n = 15) with rheumatoid arthritis + diabetes and hypertension received no ozone treatment, and group II (n = 30) was treated with medical ozone. This group was divided into two subgroups (n = 15 each), group IIa: the same as group I + medical ozone and group IIb: bronchial asthma patients. Indicators of RA in I and IIa groups were evaluated. Redox balance was assessed through defense and injury biomarkers. Thromboxane A2 (TXA2) and prostacyclin levels were assessed in group IIb patients. Medical ozone arrested oxidative injury progression in the Ia group and decreased thromboxane levels and the TXA2/6-keto PGF1α ratio in the IIb group. Medical ozone arrested the progression of oxidative damage and modulated those endogenous mechanisms that promote a suitable redox status and TXA2/PGI2 balance. These results suggest that medical ozone may become a standard approach in the prevention and management of age-related oxidative diseases in elderly people.

Usefulness of the MS-MLPA technique in the diagnosis of Beckwith-Wiedemann syndrome and Silver-Russell syndrome.

INTRODUCTION: Epigenetic and genomic imprinting alterations of the 11p15.5 region cause excessive or deficient growth, which result in Beckwith-Wiedemann syndrome (BWS) or Silver-Russell syndrome (SRS), respectively. OBJECTIVE: To evaluate the methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) methylation analysis technique in the diagnosis of BWS and SRS. METHODS: 11p15.5 methylation and variants were evaluated in patients with clinical diagnosis of BWS and SRS using the MS-MLPA technique in peripheral blood DNA. RESULTS: Paternal uniparental disomy and loss of maternal IC2 methylation were identified in two patients with BWS who had omphalocele and macroglossia, respectively. Paternal IC1hypomethylation was recorded in two patients with SRS of classic phenotype. CONCLUSIONS: Adequate genotype-phenotype correlation was observed with the methylation defects that were identified, which confirms the usefulness of MLPA as a first-line study in patients diagnosed with BWS and SRS.

INTRODUCCIÓN: Las alteraciones epigenéticas y genómicas de la región improntada 11p15.5 producen crecimiento excesivo o deficiente, que se manifiesta como síndrome de Beckwith-Wiedemann o síndrome de Silver-Russell, respectivamente. OBJETIVO: Evaluar la técnica de análisis de metilación MLPA (MS-MLPA, methylation-specific multiplex ligation-dependent probe amplification) en el diagnóstico de los síndromes de Beckwith-Wiedemann y de Silver-Russell. MÉTODOS: Se evaluó la metilación y las variantes de 11p15.5 en pacientes con diagnóstico clínico de síndrome de Beckwith-Wiedemann y síndrome de Silver-Russell mediante la técnica MS-MLPA en ADN de sangre periférica. RESULTADOS: Se identificó disomía uniparental paterna y pérdida de metilación del IC2 materno en dos pacientes con síndrome de Beckwith-Wiedemann, quienes presentaron onfalocele y macroglosia, respectivamente. Se registró hipometilación paterna del IC1 en dos pacientes con síndrome de Silver-Russell de fenotipo clásico. CONCLUSIONES: Se observó adecuada correlación genotipo-fenotipo con los defectos de metilación encontrados, lo que confirma la utilidad del MLPA como estudio de primera línea en pacientes con diagnóstico de síndrome de Beckwith-Wiedemann y síndrome de Silver-Russell.

Lifespan benefits for the combination of rapamycin plus acarbose and for captopril in genetically heterogeneous mice.

Mice bred in 2017 and entered into the C2017 cohort were tested for possible lifespan benefits of (R/S)-1,3-butanediol (BD), captopril (Capt), leucine (Leu), the Nrf2-activating botanical mixture PB125, sulindac, syringaresinol, or the combination of rapamycin and acarbose started at 9 or 16 months of age (RaAc9, RaAc16). In male mice, the combination of Rapa and Aca started at 9 months and led to a longer lifespan than in either of the two prior cohorts of mice treated with Rapa only, suggesting that this drug combination was more potent than either of its components used alone. In females, lifespan in mice receiving both drugs was neither higher nor lower than that seen previously in Rapa only, perhaps reflecting the limited survival benefits seen in prior cohorts of females receiving Aca alone. Capt led to a significant, though small (4% or 5%), increase in female lifespan. Capt also showed some possible benefits in male mice, but the interpretation was complicated by the unusually low survival of controls at one of the three test sites. BD seemed to produce a small (2%) increase in females, but only if the analysis included data from the site with unusually short-lived controls. None of the other 4 tested agents led to any lifespan benefit. The C2017 ITP dataset shows that combinations of anti-aging drugs may have effects that surpass the benefits produced by either drug used alone, and that additional studies of captopril, over a wider range of doses, are likely to be rewarding.

Utilidad de la técnica de MS-MLPA en el diagnóstico de los síndromes de Beckwith-Wiedemann y Silver-Russell / Usefulness of the MS-MLPA technique in the diagnosis of Beckwith-Wiedemann syndrome and Silver-Russell syndrome

Resumen Introducción: Las alteraciones epigenéticas y genómicas de la región improntada 11p15.5 producen crecimiento excesivo o deficiente, que se manifiesta como síndrome de Beckwith-Wiedemann o síndrome de Silver-Russell, respectivamente. Objetivo: Evaluar la técnica de análisis de metilación MLPA (MS-MLPA, methylation-specific multiplex ligation-dependent probe amplification) en el diagnóstico de los síndromes de Beckwith-Wiedemann y de Silver-Russell. Métodos: Se evaluó la metilación y las variantes de 11p15.5 en pacientes con diagnóstico clínico de síndrome de Beckwith-Wiedemann y síndrome de Silver-Russell mediante la técnica MS-MLPA en ADN de sangre periférica. Resultados: Se identificó disomía uniparental paterna y pérdida de metilación del IC2 materno en dos pacientes con síndrome de Beckwith-Wiedemann, quienes presentaron onfalocele y macroglosia, respectivamente. Se registró hipometilación paterna del IC1 en dos pacientes con síndrome de Silver-Russell de fenotipo clásico. Conclusiones: Se observó adecuada correlación genotipo-fenotipo con los defectos de metilación encontrados, lo que confirma la utilidad del MLPA como estudio de primera línea en pacientes con diagnóstico de síndrome de Beckwith-Wiedemann y síndrome de Silver-Russell.

Abstract Introduction: Epigenetic and genomic imprinting alterations of the 11p15.5 region cause excessive or deficient growth, which result in Beckwith-Wiedemann syndrome (BWS) or Silver-Russell syndrome (SRS), respectively. Objective: To evaluate the methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) methylation analysis technique in the diagnosis of BWS and SRS. Methods: 11p15.5 methylation and variants were evaluated in patients with clinical diagnosis of BWS and SRS using the MS-MLPA technique in peripheral blood DNA. Results: Paternal uniparental disomy and loss of maternal IC2 methylation were identified in two patients with BWS who had omphalocele and macroglossia, respectively. Paternal IC1hypomethylation was recorded in two patients with SRS of classic phenotype. Conclusions: Adequate genotype-phenotype correlation was observed with the methylation defects that were identified, which confirms the usefulness of MLPA as a first-line study in patients diagnosed with BWS and SRS.

Evaluación de la calidad del Servicio de Estomatología General Integral. Policlínico Camilo Cienfuegos de Sancti Spíritus / Assessment of the comprehensive General Stomatology quality service. Camilo Cienfuegos Polyclinic of Sancti Spiritus

RESUMEN Fundamento: La calidad de la atención estomatológica se ha convertido actualmente en una necesidad. En Cuba, el Programa Nacional de Atención Estomatológica Integral a la Población tiene como propósito incrementar y perfeccionar la atención estomatológica. Objetivo: Evaluar la calidad del Servicio de Estomatología General Integral del policlínico Camilo Cienfuegos de Sancti Spíritus. Metodología: Se realizó una investigación observacional descriptiva de corte transversal en el Policlínico Camilo Cienfuegos de Sancti Spíritus en el período comprendido de septiembre de 2019 a enero de 2020. Se seleccionaron 19 estomatólogos de la unidad y 368 pacientes pertenecientes a los consultorios 8 y 9 del área de salud que cumplieron con los criterios de inclusión. Se utilizó la calidad como variable, la cual se operacionalizó en las dimensiones: estructura, proceso y resultados y sus criterios de medida. Se utilizaron métodos teóricos, empíricos y estadísticos y técnicas de recolección y análisis de datos. Se realizaron encuestas de satisfacción a pacientes y profesionales. Resultados: Las dimensiones estructura y proceso, con 20 y 10 puntos respectivamente, fueron evaluadas de regular, la dimensión resultado de bien por un valor alcanzado de 8 puntos. Conclusión: La calidad del Servicio de Estomatología General Integral del policlínico Camilo Cienfuegos de Sancti Spíritus fue evaluada de regular.

ABSTRACT Background: Dental care quality has become a necessity. In Cuba, the National Program for the People´s Comprehensive Stomatology Care aims to increase and improve dental care. Objective: To assess the Comprehensive General Stomatology quality service at Camilo Cienfuegos polyclinic in Sancti Spíritus. Methodology: A cross-sectional descriptive observational research was conducted at Camilo Cienfuegos Polyclinic in Sancti Spíritus from September 2019 to January 2020. 19 stomatologists from the unit and 368 patients belonging to clinics 8 and 9 of the area were selected who met the inclusion criteria. Quality was used as a variable, and operationalized in the dimensions: structure, process and results and their measurement criteria. Theoretical, empirical and statistical methods and data collection also analysis techniques were used. Satisfaction surveys were conducted on patients and professionals. Results: Structure and process dimensions, with 20 and 10 points respectively, were evaluated as regular, the result dimension as good for an 8-point value. Conclusion: Comprehensive General Stomatology quality service at Camilo Cienfuegos polyclinic in Sancti Spíritus was evaluated as regular.

Model Predictions of Occupational Exposures to Diacetyl and 2,3-Pentanedione Emitted From Roasted Whole Bean and Ground Coffee: Influence of Roast Level and Physical Form on Specific Emission Rates.

Roasted coffee emits hazardous volatile organic compounds including diacetyl and 2,3-pentanedione. Workers in non-flavored coffee roasting and packaging facilities might inhale diacetyl and 2,3-pentanedione from roasted coffee above occupational exposure limits depending on their work activities and proximity to the source of emissions. Objectives of this laboratory study were to: (1) investigate factors affecting specific emission rates (SERs) of diacetyl and 2,3-pentanedione from freshly roasted coffee, (2) explore the effect of time on SERs of coffee stored in sealed bags for 10-days, and (3) predict exposures to workers in hypothetical workplace scenarios. Two roast levels (light and dark) and three physical forms (whole bean, coarse ground, and fine ground) were investigated. Particle size for whole bean and ground coffee were analyzed using geometric mean of Feret diameter. Emitted chemicals were collected on thermal desorption tubes and quantified using mass spectrometry analysis. SERs developed here coupled with information from previous field surveys provided model input to estimate worker exposures during various activities using a probabilistic, near-field/far-field model. For freshly roasted coffee, mean SER of diacetyl and 2,3-pentantedione increased with decreasing particle size of the physical form (whole bean < coarse ground < fine ground) but was not consistent with roast levels. SERs from freshly roasted coffee increased with roast level for diacetyl but did not change for 2,3-pentanedione. Mean SERs were greatest for diacetyl at 3.60 mg kg-1 h-1 for dark, fine ground and for 2,3-pentanedione at 3.88 mg kg-1 h-1 for light, fine ground. For storage, SERs of whole bean remained constant while SERs of dark roast ground coffee decreased and light roast ground coffee increased. Modeling demonstrated that near-field exposures depend on proximity to the source, duration of exposure, and air velocities in the near-field further supporting previously reported chemical air measurements in coffee roasting and packaging facilities. Control of source emissions using local exhaust ventilation especially around grinding activities as well as modification of work practices could be used to reduce exposures in this workforce.

The transcription factor Fli1 restricts the formation of memory precursor NK cells during viral infection.

Natural killer (NK) cells are innate lymphocytes that possess traits of adaptive immunity, such as memory formation. However, the molecular mechanisms by which NK cells persist to form memory cells are not well understood. Using single-cell RNA sequencing, we identified two distinct effector NK cell (NKeff) populations following mouse cytomegalovirus infection. Ly6C- memory precursor (MP) NK cells showed enhanced survival during the contraction phase in a Bcl2-dependent manner, and differentiated into Ly6C+ memory NK cells. MP NK cells exhibited distinct transcriptional and epigenetic signatures compared with Ly6C+ NKeff cells, with a core epigenetic signature shared with MP CD8+ T cells enriched in ETS1 and Fli1 DNA-binding motifs. Fli1 was induced by STAT5 signaling ex vivo, and increased levels of the pro-apoptotic factor Bim in early effector NK cells following viral infection. These results suggest that a NK cell-intrinsic checkpoint controlled by the transcription factor Fli1 limits MP NK formation by regulating early effector NK cell fitness during viral infection.

Impacto del ejercicio aeróbico en enfermedades pulmonares intersticiales / Impact of aerobic exercise on patients with interstitial lung diseases

Resumen Introducción: El tratamiento integral para pacientes con enfermedades pulmonares intersticiales incluye entrenamiento físico, dados los efectos fisiológicos que se generan. El objetivo de este estudio es analizar el impacto del ejercicio aeróbico en el tratamiento para los pacientes con enfermedades pulmonares intersticiales. Métodos: Se realizaron búsquedas de ensayos clínicos (enero 2015- junio 2020) en bases de datos indexadas tales como: Ebsco, Scopus, Medline, Medscape, PubMed Central, EMBASE, Redalyc, DOAJ y OVID. Se utilizó la estrategia PICO, Cochrane y escala de PEDro en cada estudio seleccionado. Resultados: Se incluyeron 11 ensayos clínicos para esta revisión y la calidad de los estudios fue media-alta. Todos los estudios incluyeron el componente de entrenamiento con ejercicio aeróbico combinado con otras estrategias como el desarrollo de fuerza, resistencia y flexibilidad. Se demostraron cambios significativos en más del 50% de los estudios para el componente de la capacidad aeróbica, consumo máximo de oxígeno, función cardiovascular y calidad de vida. Sin embargo, otros estudios, no demostraron diferencias significativas en pruebas de función pulmonar, cambios en variables ventilatorias, de intercambio gaseoso o cardiovasculares tal como señalan algunos autores en los estudios realizados. Conclusiones: El ejercicio aeróbico demostró ser un componente que mejoró resultados en la capacidad aeróbica, evidenciados en la distancia y metros recorridos post caminata de 6 minutos, así como en la calidad de vida, consumo máximo de oxígeno, fuerza y resistencia, mas no en variables ventilatorias e intercambio gaseoso.

Abstract Introduction: Comprehensive treatment for patients with interstitial lung diseases includes physical training, given the physiological effects that are generated. The objective of this study is to analyze the impact of aerobic exercise in the treatment for patients with interstitial lung diseases. Methods: Clinical trials (January 2015- June 2020) were searched in indexed databases such as Ebsco, Scopus, Medline, Medscape, PubMed Central, EMBASE, Redalyc, DOAJ and OVID. PICO, Cochrane and PEDro scale were used in each selected study. Results: Eleven clinical trials were included for this review and the quality of the studies was medium to high. All studies included the training component of aerobic exercise combined with other strategies such as strength development, endurance, flexibility. Significant changes were demonstrated in over 50% of the studies for the aerobic capacity component, maximum oxygen consumption, cardiovascular function and quality of life. Other studies, however, did not demonstrate significant differences in lung function tests, changes in ventilatory, gas exchange or cardiovascular variables as indicated by some authors in the studies conducted. Conclusions: Aerobic exercise proved to be a component that improved results in aerobic capacity evidenced in distance and meters traveled after a 6-minute walk, as well as in quality of life, maximum oxygen consumption, strength and resistance, but not in ventilatory variables and exchange gaseous.

Perspectives of professionals on the safety and accessibility of aged care for Care Leavers and Forgotten Australians.

OBJECTIVES: Little is known about how prepared the aged care system is to meet the specific needs of Care Leavers and Forgotten Australians. We explored service provider and advocate perspectives about the barriers and facilitators for appropriate and safe care for this group. METHODS: Three focus groups with sixteen professional stakeholders examined the ways aged care support is accessible and inaccessible for Forgotten Australians. RESULTS: Participants noted structural and organisational features that act as barriers to best practice aged care. It was perceived that funding models and processes provide insufficient opportunity to develop trust with professionals and access tailored care. Once engaged with aged care services, the sector lacks the psychological literacy required to tailor care to manage the complex needs and preferences of Forgotten Australians. CONCLUSIONS: Systemic and organisational change that promotes increased flexibility, trauma-informed care and non-residential housing options will improve the safety and accessibility of aged care for Forgotten Australians.

Effect of Puffing Behavior on Particle Size Distributions and Respiratory Depositions From Pod-Style Electronic Cigarette, or Vaping, Products.

The current fourth generation ("pod-style") electronic cigarette, or vaping, products (EVPs) heat a liquid ("e-liquid") contained in a reservoir ("pod") using a battery-powered coil to deliver aerosol into the lungs. A portion of inhaled EVP aerosol is estimated as exhaled, which can present a potential secondhand exposure risk to bystanders. The effects of modifiable factors using either a prefilled disposable or refillable pod-style EVPs on aerosol particle size distribution (PSD) and its respiratory deposition are poorly understood. In this study, the influence of up to six puff profiles (55-, 65-, and 75-ml puff volumes per 6.5 and 7.5 W EVP power settings) on PSD was evaluated using a popular pod-style EVP (JUUL® brand) and a cascade impactor. JUUL® brand EVPs were used to aerosolize the manufacturers' e-liquids in their disposable pods and laboratory prepared "reference e-liquid" (without flavorings or nicotine) in refillable pods. The modeled dosimetry and calculated aerosol mass median aerodynamic diameters (MMADs) were used to estimate regional respiratory deposition. From these results, exhaled fraction of EVP aerosols was calculated as a surrogate of the secondhand exposure potential. Overall, MMADs did not differ among puff profiles, except for 55- and 75-ml volumes at 7.5 W (p < 0.05). For the reference e-liquid, MMADs ranged from 1.02 to 1.23 µm and dosimetry calculations predicted that particles would deposit in the head region (36-41%), in the trachea-bronchial (TB) region (19-21%), and in the pulmonary region (40-43%). For commercial JUUL® e-liquids, MMADs ranged from 0.92 to 1.67 µm and modeling predicted that more particles would deposit in the head region (35-52%) and in the pulmonary region (30-42%). Overall, 30-40% of the particles aerosolized by a pod-style EVP were estimated to deposit in the pulmonary region and 50-70% of the inhaled EVP aerosols could be exhaled; the latter could present an inhalational hazard to bystanders in indoor occupational settings. More research is needed to understand the influence of other modifiable factors on PSD and exposure potential.

Embarazo en la adolescencia como reto para el primer nivel de atención / Pregnancy in Adolescence as a Challenge for the First Level of Healthcare

Introducción: El embarazo en la adolescencia es el ocurrido en el lapso de vida entre los 10 y 19 años de edad; se presenta antes de que la madre haya alcanzado la suficiente madurez emocional para asumir la compleja tarea de la maternidad. A nivel mundial, se reconoce un aumento de la actividad sexual de los adolescentes, es un problema social que afecta, en mayor o menor proporción, a todas las regiones del mundo. Objetivo: Definir el alcance y la naturaleza de la literatura científica existente sobre el embarazo en la adolescencia, prevención y sus complicaciones. Métodos: Revisión bibliográfica sistemática para hacer un análisis crítico reflexivo de documentos, donde se incluyeron libros, tesis de doctorado, de maestría, artículos originales y de revisión. La estrategia de búsqueda utilizada en cada base de datos, SciELO y Google académico se reunió mediante la aceptación de los descriptores Adolescencia, Embarazo, Prevención y Complicaciones, con los operadores booleanos AND y OR. Conclusiones: Para la prevención del embarazo en la adolescencia, se necesita de una mayor divulgación de sus consecuencias y formas de evitarlo que podría lograrse con la puesta en práctica de estrategias educativas de forma didácticas y agradables, que puedan constituir interés para los adolescentes(AU)

Introduction: Pregnancy in adolescence is that one occurring in the period of life from the age of ten to nineteen years old. It occurs before the mother has reached enough emotional maturity to take on the complex task of motherhood. Worldwide, an increase in adolescent sexual activity is recognized; it is a social concern that affects, to a greater or lesser extent, all regions of the world. Objective: To define the scope and nature of the existing scientific literature on adolescent pregnancy, as well as its prevention and complications. Methods: Systematic bibliographic review carried out in view of a reflective-critical analysis of documents, which included books, doctoral and master's theses, as well as original and review articles. The search strategy used in each database, SciELO and Google Scholar, was designed by accepting the descriptors Adolescencia [Adolescence], Embarazo [Pregnancy], Prevención [Prevention] and Complicaciones [Complications], with the Boolean operators AND and OR. Conclusions: For the prevention of pregnancy in adolescence, greater spread of its consequences and ways for avoiding it is needed, which could be achieved with the implementation of educational strategies in a didactic and pleasant way, in order for it to become of interest to adolescents(AU)