"She's so pretty": The development of valuing personal attractiveness among young children.

The current study sought to understand gender differences in how much children value personal attractiveness, whether age is associated with valuing personal attractiveness, and the role of gender identity development. Three- to five-year-olds (N = 170; 89 girls, 81 boys, 0 other genders; primarily Latiné, multiethnic, and non-Hispanic White American) were recruited from child centers across the Los Angeles and Orange County metropolitan areas. Across several indicators (e.g., self-report, preference for appearance-related female-typed occupations and fancy gender-typed outfits, memory for fancy gender-typed clothing, and spontaneous reasons for liking a media character), girls highly valued personal attractiveness. Girls also valued personal attractiveness and tied their gender to personal attractiveness to a greater extent than boys. We discuss implications for later well-being and health.

A Modified Schirmer Tear Test in Clinically Normal Horses: Measurement at 30 Seconds versus 60 Seconds.

This study sought to compare the Schirmer Tear Test (STT)-1 results at 30 (STT30) versus 60 (STT60) seconds in healthy horses. This study included a total of 56 healthy horses. STT-1 was performed in both eyes, right eye first, and the wetting lengths were measured in STT30 and STT60. To evaluate the reduction of the initial reflex phase, the wetting length velocity was measured during the first 30 seconds. The effects of eye, age, weight, sex, and ambient temperature and humidity on STT values were evaluated. Mean (standard deviation) STT30 and STT60 were 19.06 (3.88) and 24.26 (4.50) mm. There was a linear correlation between the STT 30 and STT60, expressed according to the following equation: STT60 = 2.20 + 1.18 × STT30 (P = .001). STT30 or STT60 values did not vary between the sexes or correlate with age, weight, ambient temperature, or humidity. In conclusion, STT30 allows for an accurate, reliable, and applicable diagnosis of tear production compared with the standard STT60 value. The proposed method is shorter and may be a suitable alternative to the 1-min test.

Early Gender Differences in Valuing Strength.

Being strong is a prominent male stereotype that children learn early in life; however, it is unknown as to when children start to value being strong and when gender differences in valuing strength might emerge. In the current study, we interviewed an ethnically diverse sample of 168 3-5 year-olds (88 girls, 80 boys) to address this gap in the literature. Results showed that boys as young as age 3 generally valued strength more than girls: (1) boys, on average, said it was more important to be strong than girls did, and (2) boys were more likely to prefer strength-related occupations than girls. Boys were also more likely to select boys than girls as the gender who cares more about physical strength. Additionally, with age, both girls and boys demonstrated knowledge of the stereotype that boys care about physical strength, with girls also being less likely to associate being a girl with being strong. Overall, the results suggest that valuing physical strength starts in early childhood, and gender differences in valuing strength are evident at the eve of gender identity development. Possible implications for boys' later well-being and health are discussed.

SIRT6-CBP-dependent nuclear Tau accumulation and its role in protein synthesis.

Several neurodegenerative diseases present Tau accumulation as the main pathological marker. Tau post-translational modifications such as phosphorylation and acetylation are increased in neurodegeneration. Here, we show that Tau hyper-acetylation at residue 174 increases its own nuclear presence and is the result of DNA damage signaling or the lack of SIRT6, both causative of neurodegeneration. Tau-K174ac is deacetylated in the nucleus by SIRT6. However, lack of SIRT6 or chronic DNA damage results in nuclear Tau-K174ac accumulation. Once there, it induces global changes in gene expression, affecting protein translation, synthesis, and energy production. Concomitantly, Alzheimer's disease (AD) case subjects show increased nucleolin and a decrease in SIRT6 levels. AD case subjects present increased levels of nuclear Tau, particularly Tau-K174ac. Our results suggest that increased Tau-K174ac in AD case subjects is the result of DNA damage signaling and SIRT6 depletion. We propose that Tau-K174ac toxicity is due to its increased stability, nuclear accumulation, and nucleolar dysfunction.

SIRT6 is a DNA double-strand break sensor.

DNA double-strand breaks (DSB) are the most deleterious type of DNA damage. In this work, we show that SIRT6 directly recognizes DNA damage through a tunnel-like structure that has high affinity for DSB. SIRT6 relocates to sites of damage independently of signaling and known sensors. It activates downstream signaling for DSB repair by triggering ATM recruitment, H2AX phosphorylation and the recruitment of proteins of the homologous recombination and non-homologous end joining pathways. Our findings indicate that SIRT6 plays a previously uncharacterized role as a DNA damage sensor, a critical factor in initiating the DNA damage response (DDR). Moreover, other Sirtuins share some DSB-binding capacity and DDR activation. SIRT6 activates the DDR before the repair pathway is chosen, and prevents genomic instability. Our findings place SIRT6 as a sensor of DSB, and pave the road to dissecting the contributions of distinct DSB sensors in downstream signaling.

DNA is a double-stranded molecule in which the two strands run in opposite directions, like the lanes on a two-lane road. Also like a road, DNA can be damaged by use and adverse conditions. Double-strand breaks ­ where both strands of DNA snap at once ­ are the most dangerous type of DNA damage, so cells have systems in place to rapidly detect and repair this kind of damage. There are three confirmed sensors for double-strand break in human cells. A fourth protein, known as SIRT6, arrives within five seconds of DNA damage, and was known to make the DNA more accessible so that it can be repaired. However, it was unclear whether SIRT6 could detect the double-strand break itself, or whether it was recruited to the damage by another double-strand break sensor. To address this issue, Onn et al. blocked the three other sensors in human cells and watched the response to DNA damage. Even when all the other sensors were inactive, SIRT6 still arrived at damaged DNA and activated the DNA damage response. To find out how SIRT6 sensed DNA damage, Onn et al. examined how purified SIRT6 interacts with different kinds of DNA. This revealed that SIRT6 sticks to broken DNA ends, especially if the end of one strand slightly overhangs the other ­ a common feature of double-strand breaks. A closer look at the structure of the SIRT6 protein revealed that it contains a narrow tube, which fits over the end of one broken DNA strand. When both strands break at once, two SIRT6 molecules cap the broken ends, joining together to form a pair. This pair not only protects the open ends of the DNA from further damage, it also sends signals to initiating repairs. In this way, SIRT6 could be thought of acting like a paramedic who arrives first on the scene of an accident and works to treat the injured while waiting for more specialized help to arrive. Understanding the SIRT6 sensor could improve knowledge about how cells repair their DNA. SIRT6 arrives before the cell chooses how to fix its broken DNA, so studying it further could reveal how that critical decision happens. This is important for medical research because DNA damage builds up in age-related diseases like cancer and neurodegeneration. In the long term, these findings can help us develop new treatments that target different types of DNA damage sensors.

Impaired innate and conditioned social behavior in adult C57Bl6/J mice prenatally exposed to chlorpyrifos.

BACKGROUND: Signs of pervasive developmental disorder and social deficits were reported in toddlers and children whose mothers were exposed to organophosphate pesticides during pregnancy. Deficits in social preference were reported in adult male mice exposed to chlorpyrifos on gestational days 12-15. This study aimed (a) to test the hypothesis that adult female and male mice that were exposed prenatally to subtoxic doses of chlorpyrifos would be impaired in social behavior and (b) to determine if prenatal chlorpyrifos altered the expression of transcripts for oxytocin in the hypothalamus. Pregnant mice were treated by gavage with corn oil vehicle or 2.5 mg/kg or 5 mg/kg of CPF on gestational days 12-15. Social preference, social and non-social conditioned place preference tasks were tested in adults. Expression of oxytocin transcripts in hypothalamus was measured by qPCR. RESULTS: Chlorpyrifos (5 mg/kg on GD 12-15) reduced the innate preference for a conspecific in a dose and sex dependent manner. Adult males exposed prenatally to 5 mg/kg CPF showed a reduction in social preference. Socially conditioned place preference was impaired in offspring of dams treated with either dose of CPF. Non-social appetitive place conditioning was impaired in offspring of dams exposed to 2.5 mg/kg, but not to 5 mg/kg chlorpyrifos. Prenatal chlorpyrifos treatment did not alter the expression of the oxytocin mRNA in the hypothalamus, although expression was significantly lower in females. CONCLUSIONS: Prenatal chlorpyrifos induced innate and learned social deficits and non-specific conditioning deficits in adult mice in a sex-dependent manner. Males showed specific social deficits following the higher dose whereas both males and females showed a more generalized conditioning deficit following the intermediate dose.

Directed evolution of SIRT6 for improved deacylation and glucose homeostasis maintenance.

Mammalian SIRT6 is a well-studied histone deacetylase that was recently shown to exhibit high protein deacylation activity enabling the removal of long chain fatty acyl groups from proteins. SIRT6 was shown to play key roles in cellular homeostasis by regulating a variety of cellular processes including DNA repair and glucose metabolism. However, the link between SIRT6 enzymatic activities and its cellular functions is not clear. Here, we utilized a directed enzyme evolution approach to generate SIRT6 mutants with improved deacylation activity. We found that while two mutants show increased deacylation activity at high substrate concentration and improved glucose metabolism they exhibit no improvement and even abolished deacetylation activity on H3K9Ac and H3K56Ac in cells. Our results demonstrate the separation of function between SIRT6 catalytic activities and suggest that SIRT6 deacylation activity in cells is important for glucose metabolism and can be mediated by still unknown acylated cellular proteins.

Neuroprotective Functions for the Histone Deacetylase SIRT6.

The histone deacetylase SIRT6 promotes DNA repair, but its activity declines with age with a concomitant accumulation of DNA damage. Furthermore, SIRT6 knockout mice exhibit an accelerated aging phenotype and die prematurely. Here, we report that brain-specific SIRT6-deficient mice survive but present behavioral defects with major learning impairments by 4 months of age. Moreover, the brains of these mice show increased signs of DNA damage, cell death, and hyperphosphorylated Tau-a critical mark in several neurodegenerative diseases. Mechanistically, SIRT6 regulates Tau protein stability and phosphorylation through increased activation of the kinase GSK3α/ß. Finally, SIRT6 mRNA and protein levels are reduced in patients with Alzheimer's disease. Taken together, our results suggest that SIRT6 is critical to maintain genomic stability in the brain and that its loss leads to toxic Tau stability and phosphorylation. Therefore, SIRT6 and its downstream signaling could be targeted in Alzheimer's disease and age-related neurodegeneration.

Optimización del proceso de donación de tejidos en un hospital universitario: 10 años de experiencia / Optimising tissue donation process in a universiy hospital: 10 years of experience

Fundamento y objetivo: La necesidad de tejido para trasplante requiere un esfuerzo continuo en la detección y evaluación de las causas de fallecimiento de los sujetos potencialmente donantes de tejidos. El objetivo de este estudio fue evaluar la capacidad de optimizar la donación de tejidos tras la detección activa de fallecidos y la revisión exhaustiva de las causas de muerte de acuerdo con los estándares internacionales y locales de bancos de tejidos. Material y método. Desde el año 2002 se instauró un procedimiento de detección activa y precoz de fallecidos hospitalarios. Se estudió el incremento de potencialidad de donación modificando los criterios: edad (80 a 85 años), aceptación de facoemulsiones corneales, enfermedades autoinmunitarias y reevaluación de las sepsis. En la década 2002-2011 se mantuvieron los mismos criterios de exclusión absoluta. Se analizó la tasa de conversión de potenciales donantes a donantes reales de uno o varios tejidos. Resultados: Analizamos 16.531 fallecidos en parada cardiorrespiratoria. Cumplían criterios de exclusión absoluta 11.191 casos. La modificación de criterios incrementó los potenciales donantes: un 10,4% la edad, un 4,5% las enfermedades autoinmunitarias/facoemulsión y un 11,8% el criterio de sepsis (p < 0,00), con un incremento global del 16% (p < 0,00) al final del período de estudio. Se generaron un total de 2.371 donantes efectivos. La efectividad de generar donantes pasó del 11 al 21% durante la década (p < 0,00). Conclusiones: La combinación de un sistema de detección proactiva del fallecimiento y la revisión continua de los criterios de aceptación para cada tipo de tejido permite, en un medio hospitalario, incrementar el número de potenciales donantes (AU)

Background and objective: The demand of tissue for transplants requires a continuous effort in detecting potential donors and assessing the causes of death. We aimed to assess the capacity to optimise tissue donation rates with the implementation of an active detection system of hospital deaths alongside a comprehensive assessment of the causes of death according to current international and local tissue banks’ standards. Material and method: An early and pro-active detection programme of hospital deaths was implemented in 2002. The potential increase in donation was analysed according to modified criteria: age (80 to 85 years), acceptance of corneal phacoemulsification, autoimmune diseases, and sepsis reassessment. During the 2002-2011 decade, the criteria for absolute exclusion remained the same. The conversion rate from potential donors to actual donors of one or more tissue types was analysed. Results: A total of 16.531 cases of cardiac arrest were analysed, and 11.191 of the cases fulfilled criteria of absolute exclusion. The modification of criteria led to an increase of potential donors: 10.4% age factor, 4.5% autoimmune diseases/phacoemulsification factor, 11.8% sepsis factor (P < .00). The study indicated a total increase of 16% (P < .00). A total of 2.371 successful donations were generated. The efficiency to generate donors increased from 11 to 21% during the aforementioned decade (P < .00). Conclusion: A pro-active detection system of hospital deaths combined with a continuous re-assessment of the acceptance criteria for each tissue type in the hospital setting leads to an increase in the potential donors’ rate (AU)

[Optimising tissue donation process in a university hospital: 10 years of experience]. / Optimización del proceso de donación de tejidos en un hospital universitario: 10 años de experiencia.

BACKGROUND AND OBJECTIVE: The demand of tissue for transplants requires a continuous effort in detecting potential donors and assessing the causes of death. We aimed to assess the capacity to optimise tissue donation rates with the implementation of an active detection system of hospital deaths alongside a comprehensive assessment of the causes of death according to current international and local tissue banks' standards. MATERIAL AND METHOD: An early and pro-active detection programme of hospital deaths was implemented in 2002. The potential increase in donation was analysed according to modified criteria: age (80 to 85 years), acceptance of corneal phacoemulsification, autoimmune diseases, and sepsis reassessment. During the 2002-2011 decade, the criteria for absolute exclusion remained the same. The conversion rate from potential donors to actual donors of one or more tissue types was analysed. RESULTS: A total of 16.531 cases of cardiac arrest were analysed, and 11.191 of the cases fulfilled criteria of absolute exclusion. The modification of criteria led to an increase of potential donors: 10.4% age factor, 4.5% autoimmune diseases/phacoemulsification factor, 11.8% sepsis factor (P<.00). The study indicated a total increase of 16% (P<.00). A total of 2.371 successful donations were generated. The efficiency to generate donors increased from 11 to 21% during the aforementioned decade (P<.00). CONCLUSION: A pro-active detection system of hospital deaths combined with a continuous re-assessment of the acceptance criteria for each tissue type in the hospital setting leads to an increase in the potential donors' rate.

Adecuación de un sistema de triaje y del circuito asistencial en urgencias al paciente intoxicado / Triage and assignment of responsibility for care in cases of acute intoxication in the emergency department

Objetivo: Valorar la calidad del triaje y del circuito asistencial de las intoxicaciones. Método: Durante tres meses, se han revisado los informes de triaje de las intoxicaciones agudas. Se incluyeron variables demográficas, toxicológicas, clínicas, nivel de triajeotorgado por el Modelo Andorrano de Triaje (MAT), demora asistencial y área de primera asistencia. Se valoró en cada caso la adecuación en la priorización de la asistencia y en la elección del área de primera asistencia. Los resultados fueron comparados con aquellos que fueron atendidos en urgencias. Resultados: Se han incluido 123 intoxicados, con una edad media de 41,6 años (DE:15). El 51% fueron mujeres. El sistema clasificó a los intoxicados como nivel I el 1,6%, II el 20,5%, III el 36,9%, IV el 32% y V el 9%. Tras el triaje, la asistencia se demoró menos de 5 min (19%), entre 5-10 min en el 27% o más de 10 min (54%). Cuando se compararon estos resultados con los de las urgencias en general, no se observaron diferencias significativas en cuanto a la estratificación de la prioridad asistencial, pero sí respecto alárea de primera asistencia, que es preferentemente medicina (60%) o psiquiatría (37%) en el caso de los intoxicados (p < 0,001). Cuando se compararon las intoxicaciones y las urgencias generales respecto a la demora entre triaje y asistencia, se constató que la demora asistencial fue menor en las intoxicaciones (p < 0,001). El 13,3% de los intoxicados tributarios de descontaminación digestiva fueron clasificados de forma inadecuada por no priorizar la asistencia. Por el mismo motivo, el área de primera (..) (AU)

Objective: To evaluate the quality of triage and care assignment in cases of acute intoxication.Methods: Three months of triage reports for cases of acute intoxication were reviewed. Patient demographic variables,toxicology screen, symptoms, triage level assigned using the Andorran Medical Triage (MAT) scoring system, delay inproviding care, and department assigned to be responsible for care were included in the analysis. We evaluated the appropriateness of the priority level assigned and the choice of responsible department. The results were compared to those for all emergencies attended. Results: The cases of 123 patients with acute intoxication (mean [SD] age, 41.6 [15] years) were included. Fifty-onepercent were female. Priority classifications were as follows: level 1, 1.6%; level 2, 20.5%; level 3, 36.9%; level 4, 32%,and level 5, 9%. Care was delayed after triage for less than 5 minutes in 19% of the cases, between 5 and 10 minutes in 27%, and longer than 10 minutes in 54%. The distribution of priority levels did not differ significantly from the distribution of other emergency department cases. However, assignment of the department responsible for providing care did differ (P<.001); 60% of the acute intoxication cases were assigned to the internal medicine department and 37% to the psychiatry department. The delay in providing care after triage was shorter in intoxication cases than inother emergencies (P<.001). Of the cases sent for gastrointestinal decontamination, an inappropriate level of priority was assigned in 13.3%. The department assigned to be responsible for care was also inappropriate in those 13.3% of (..) (AU)