Uncovering the Role of Hormones in Enhancing Antioxidant Defense Systems in Stressed Tomato (Solanum lycopersicum) Plants.

Tomato is one of the most important fruits worldwide. It is widely consumed due to its sensory and nutritional attributes. However, like many other industrial crops, it is affected by biotic and abiotic stress factors, reducing its metabolic and physiological processes. Tomato plants possess different mechanisms of stress responses in which hormones have a pivotal role. They are responsible for a complex signaling network, where the antioxidant system (enzymatic and non-enzymatic antioxidants) is crucial for avoiding the excessive damage caused by stress factors. In this sense, it seems that hormones such as ethylene, auxins, brassinosteroids, and salicylic, jasmonic, abscisic, and gibberellic acids, play important roles in increasing antioxidant system and reducing oxidative damage caused by different stressors. Although several studies have been conducted on the stress factors, hormones, and primary metabolites of tomato plants, the effect of endogenous and/or exogenous hormones on the secondary metabolism is still poorly studied, which is paramount for tomato growing management and secondary metabolites production. Thus, this review offers an updated overview of both endogenous biosynthesis and exogenous hormone application in the antioxidant system of tomato plants as a response to biotic and abiotic stress factors.

Blood system ABO antigens as risk factor for severity of SARS-CoV-2 infection.

INTRODUCTION: Whether there is an influence of the ABO blood system on SARS-CoV-2 infection is unknown. OBJECTIVE: To analyze if there is an association between the ABO system antigens and susceptibility to and severity of SARS-CoV-2 infection. MATERIAL AND METHODS: The frequency of ABO system antigens was compared in 73 confirmed cases of SARS-CoV-2 infection and 52 clinically healthy donors. Infection severity was assessed by comparing the frequency of antigens by disease severity and mortality. RESULTS: The risk of suffering from SARS-CoV-2 infection increases in subjects with A vs. non-A antigen (OR = 1.45; 95 % CI: 1.061-1.921). Blood phenotype O reduces the risk of SARS-CoV-2 infection (OR = 0.686; 95 % CI: 0.522-0.903). No differences were found regarding disease severity. In critically ill patients, the risk of mortality increased in subjects with A vs. non-A antigen (OR = 3.34; 95 % CI: 1.417-8.159). CONCLUSION: Blood group A is a risk factor for SARS-CoV-2 infection, but not for disease severity, although in critically ill patients it is a risk factor for mortality.

INTRODUCCIÓN: Se desconoce si existe una influencia del sistema sanguíneo ABO en susceptibilidad y gravedad de la enfermedad. OBJETIVO: Analizar si existe una asociación entre los antígenos del sistema ABO y la susceptibilidad y gravedad de la infección por SARS-CoV-2. MATERIAL Y MÉTODOS: Se compararon las frecuencias de los antígenos del sistema ABO en 73 casos confirmados de infección por SARS-CoV-2 y 52 donadores clínicamente sanos. La gravedad de la infección se evaluó comparando la frecuencia de los antígenos por gravedad de la enfermedad y la mortalidad. RESULTADOS: El riesgo de padecer infección por SARS-CoV-2 se incrementa en sujetos con antígeno A vs los no-A (OR=1.45; IC95 %:1.061-1.921). El fenotipo sanguíneo O disminuye el riesgo de padecer infección por SARS-CoV-2 (OR=0.686; IC95 %: 0.522-0.903). No se encontraron diferencias entre la gravedad de la enfermedad. En los pacientes graves, el riesgo de mortalidad se incrementó en sujetos con antígeno A vs los no-A (OR= 3.34; IC95 %: 1.417-8.159). CONCLUSIÓN: El grupo sanguíneo A es un factor de riesgo para padecer infección por SARS-CoV-2, no así en la gravedad de la enfermedad, pero en los pacientes graves fue un factor de riesgo para la mortalidad.

Thermosonicated whey protein concentrate blends on quality attributes of reduced fat Panela cheese.

Aiming at producing a reduced fat cheese (RFC) as an alternative to full-fat Panela cheese, a highly consumed fresh Mexican dairy product, thermosonication (TS) processes (24 kHz, 400 W nominal power, 2, 4 and 6 min; 50, 55 and 60 °C) were evaluated to treat WPC (80% protein) blended with reduced-fat milk (1 and 2% fat), which were later LTLT pasteurized. TS blends were compared in terms of their technological properties (water holding capacity-WPC, gel firmness- GF, color, pH and titratable acidity) with those of a regular full fat (3%) LTLT pasteurized milk used as a control. Afterwards, a regression analysis was carried out with the obtained data in order to select the most appropriate conditions for cheesemaking purposes (similar GF, higher WHC with respect to the control), minimize both fat content and TS treatment duration to minimize energy expenses. According to these restrictions, the selected conditions were 1.5% fat milk-WPC blend, TS treated at 60 °C for 120 s; 1% fat milk-WPC blend, TS treated at 50 °C for 120 s and 1% fat milk-WPC blend, 50 °C for 144 s, which allowed preparing low fat cheeses (LFCs). These TS treatments were applied in a larger scale to elaborate Panela-type LFCs comparing different technological properties (cheese yield, syneresis, water content, texture profile analysis, color and titratable acidity) with those of a full fat variety, at day 1 and during 14 days of refrigerated storage. Results showed similar texture profiles of LFC cheeses and full fat milk cheeses throughout their storage period with significant changes in composition parameters (higher moisture, protein and salt contents, with low fat percentages), syneresis, selected color parameters (hue, b*), with no observed changes in cheese yield, TA and pH during cheese storage. These promising results are encouraging to develop LFCs with no physicochemical or technological defects using novel processing techniques that may help reducing calorie consumption without compromising sensory acceptability.

Antígenos del sistema sanguíneo ABO como factor de riesgo para la gravedad de la infección por SARS-CoV-2 / Blood system ABO antigens as risk factor for severity of SARS-CoV-2 infection

Resumen Introducción: Se desconoce si existe una influencia del sistema sanguíneo ABO en susceptibilidad y gravedad de la enfermedad. Objetivo: Analizar si existe una asociación entre los antígenos del sistema ABO y la susceptibilidad y gravedad de la infección por SARS-CoV-2. Material y métodos: Se compararon las frecuencias de los antígenos del sistema ABO en 73 casos confirmados de infección por SARS-CoV-2 y 52 donadores clínicamente sanos. La gravedad de la infección se evaluó comparando la frecuencia de los antígenos por gravedad de la enfermedad y la mortalidad. Resultados: El riesgo de padecer infección por SARS-CoV-2 se incrementa en sujetos con antígeno A vs los no-A (OR=1.45; IC95 %:1.061-1.921). El fenotipo sanguíneo O disminuye el riesgo de padecer infección por SARS-CoV-2 (OR=0.686; IC95 %: 0.522-0.903). No se encontraron diferencias entre la gravedad de la enfermedad. En los pacientes graves, el riesgo de mortalidad se incrementó en sujetos con antígeno A vs los no-A (OR= 3.34; IC95 %: 1.417-8.159). Conclusión: El grupo sanguíneo A es un factor de riesgo para padecer infección por SARS-CoV-2, no así en la gravedad de la enfermedad, pero en los pacientes graves fue un factor de riesgo para la mortalidad.

Abstract Introduction: Whether there is an influence of the ABO blood system on susceptibility to the disease and its severity is unknown. Objective: To analyze if there is an association between the ABO blood system phenotypes and susceptibility to SARS-CoV-2 infection and its severity. Material and methods: The frequency of ABO antigens was compared in 73 confirmed cases of SARS-CoV-2 infection and 52 clinically healthy donors. The severity of the infection was evaluated by comparing the frequency of antigens by severity of the disease and mortality. Results: The risk of SARS-CoV-2 infection is increased in subjects with antigen A vs non-A subjects (OR=1.45; 95 %: 1.061-1.921). Blood phenotype O decreases the risk of SARS-CoV-2 infection (OR= 0.686; 95 % CI: 0.522-0.903). No differences were found regarding disease severity. The mortality risk is increased in subjects antigen A vs non-A (OR= 3.34; 95% IC: 1.417-8.159). Conclusion: Blood group A is a risk factor for SARS-CoV-2 infection, but not for disease severity, although in critically ill patients it is a risk factor for mortality.

Métodos combinados para incrementar la vida en anaquel de agua de coco obtenida de comercios no establecidos de la Ciudad de Puebla, México / Combined methods for increasing the shelf life of coconut water obtained from the non-established commerce of Puebla City, Mexico

RESUMEN Objetivo Evaluar el efecto de la aplicación de métodos combinados para incrementar la vida en anaquel de agua de coco. Métodos El agua de coco fue obtenida de comercios no establecidos en la Ciudad de Puebla, México. El agua de coco fue tratada con luz ultravioleta-C, vainillina o cinamaldehído y almacenada a 5 y 22°C. Se evaluó el efecto de estas tecnologías sobre el crecimiento microbiano de bacterias mesófilas aerobias, mohos y levaduras. Resultados El tratamiento con luz ultravioleta-C redujo la carga microbiana de bacterias mesófilas aerobias y mohos y levaduras en 3,2 y 2,9 ciclos logarítmicos, respectivamente. Durante el almacenamiento del agua de coco, la combinación de luz ultravioleta-C, cinamaldehído y baja temperatura mantuvo una carga microbiana en ambos grupos de microorganismos por debajo de 10 UFC/mL, durante 30 días. Conclusión La aplicación de métodos combinados puede ser una alternativa a bajo costo para la conservación de agua de coco.

ABSTRACT Objective To evaluate the effect of combined methods for increasing the shelf life of coconut water. Methods Coconut water was obtained from non-established commerce of Puebla City, Mexico. Coconut water was treated with ultraviolet-C light, vanillin or cinnamaldehyde, and stored at 5 and 22°C. The effect of combined methods was evaluated in the growth of aerobic mesophiles and molds plus yeasts. Results Ultraviolet-C light treatment reduced the microbial load of aerobic mesophiles and molds plus yeast in 3,2 and 2,9 log cycles, respectively. In stored coconut water, the combination of ultraviolet-C light, cinnamaldehyde and low temperature maintained the microbial load in both groups of microorganisms under 10 CFU/mL for 30 days. Conclusion Combined methods may be an alternative at a low cost for the conservation of coconut water.

[Toracotomía en el departamento de urgencias en una paciente con actividad eléctrica sin pulso no traumática: potencial ampliación del horizonte terapéutico de una intervención de alta especialidad]. / Emergency department thoracotomy in a patient with non-traumatic pulseless electrical activity: potential widening of the therapeutic horizon of a high-specialty intervention.

Instituida bajo recomendaciones objetivas, la toracotomía en el departamento de urgencias (TDU) se ha descrito como una maniobra quirúrgica salvatoria de la vida en pacientes traumatizados in extremis. Sin embargo, hay pocos reportes acerca de la experiencia con su empleo en la actividad eléctrica sin pulso no traumática. Describimos el caso de una paciente obstétrica exanguinada por sangrado masivo transoperatorio, en la que se realizó una TDU con un resultado óptimo para la vida y la función neurológica. Adicionalmente, evaluamos la literatura correspondiente al tema, que en lo mejor de nuestro conocimiento es crítica para expandir los protocolos de abordaje del ritmo de paro cardiaco no traumático en los hospitales de alto volumen.Instituted under objective recommendations, Emergency Department Thoracotomy (EDT) has been described as a life-saving surgical maneuver in trauma patients arriving "in extremis." Nevertheless, there are few reports related to the experience regarding the use of the procedure in non-traumatic cardiopulmonary arrest. We describe the case of an obstetric patient exsanguinated by operative massive bleeding, where EDT was instituted reaching an optimal result for the survival and neurologic function. Additionally, we evaluate the literature related to this issue, which to the best of our knowledge, is critical to expand protocols of approach in non-traumatic cardiac arrest rhythm in high-volume hospitals.

[Obstetric emergencies and non-emergencies at Central Military Hospital (I): Our vision and the epidemiologic horizon]. / Emergencias y urgencias obstétricas en el Hospital Central Militar (I): nuestra visión y el horizonte epidemiológico.

BACKGROUND: Maternal morbidity and mortality pose a significant impact on national public health, being medical attention of obstetric emergencies (OE) and non-emergencies (ONE) of capital importance. METHODS: Descriptive and epidemiologic analysis of OE/ONE at a 3rd level military echelon. RESULTS: During a 34-months span, 48 patients were approached at the emergency department (1.4 admissions/month). Mean age: 29 ± 3 years (17-41). Eight patients (17%) were considered OE and 40 (83%) ONE. Fifty-eight percent (n = 28) of patients were admitted to our institution; 32% (n = 9) were managed under non-surgically basis and 68% (n = 19) underwent surgical therapy. Most important cause of admission: postoperative hemorrhage (22%; n = 6). Most frequent operative interventions: surgical hemostasis maneuvers (31.5%; n = 6). Eighty-two percent (n = 23) of admissions required management at intensive care unit (ICU), with mean length of stay of 6.4 ± 4.9 days (2-21). Thirty-five percent (n = 8) required mechanical ventilation. Mean score of APACHE II at ICU: 19.4 ± 8.4; predicted probability of death: 35.5%. Global morbidity rate: 27% (1.8 complications/patient). Global mortality rate: 6.2%; specific mortality for pregnant patients 0% (n = 0) and for post-partum patients12.5% (n = 3). Mortality rate at ICU: 4.3% (n = 1). CONCLUSIONS: Central Military Hospital has delineated and defined several procedures to decrease maternal morbidity and mortality. Appropriate practice of these procedures contributes to reach the desired institutional objectives.

INTRODUCCIÓN: La morbimortalidad materna posee un significativo impacto en la salud pública nacional, siendo la atención médica de las emergencias obstétricas (EO) y urgencias obstétricas (UO) de capital importancia. MÉTODO: Análisis descriptivo y epidemiológico de EO/UO en un escalón militar de tercer nivel. RESULTADOS: Durante 34 meses se abordaron en el departamento de urgencias 48 pacientes (1.4 admisiones/mes). La edad media fue de 29 ± 3 años (rango: 17-41). Ocho pacientes (17%) se consideraron EO y 40 (83%) UO. El 58% (n = 28) de las pacientes se admitieron a la institución; el 32% (n = 9) se manejaron médicamente y el 68% (n = 19) con tratamiento quirúrgico. La causa más importante de admisión fue la hemorragia posoperatoria (22%; n = 6). Las intervenciones quirúrgicas más frecuentes fueron maniobras de hemostasia quirúrgica (31.5%; n = 6). El 82% (n = 23) de las admisiones requirieron manejo en la unidad de medicina intensiva (UMI), con una estancia media de 6.4 ± 4.9 días (rango: 2-21). El 35% (n = 8) requirieron ventilación mecánica. La puntuación media APACHE II en la UMI fue de 19.4 ± 8.4, y la probabilidad predicha de muerte fue del 35.5%. La tasa global de morbilidad fue del 27% (1.8 complicaciones/paciente). La tasa de mortalidad global fue del 6.2%; la mortalidad específica para pacientes embarazadas del 0% (n = 0) y para pacientes puérperas del 12.5% (n = 3). La tasa de mortalidad en la UMI fue del 4.3% (n = 1). CONCLUSIONES: El Hospital Central Militar ha delineado y definido diversos procedimientos para abatir la morbimortalidad maternas. La correcta práctica de estos procedimientos contribuirá a alcanzar los objetivos institucionales deseados.

Associations of Smoking, Physical Inactivity, Heavy Drinking, and Obesity with Quality-Adjusted Life Expectancy among US Adults with Depression.

OBJECTIVES: To examine associations between four health behaviors (smoking, physical inactivity, heavy alcohol drinking, and obesity) and three health indices (health-related quality of life, life expectancy, and quality-adjusted life expectancy (QALE)) among US adults with depression. METHODS: Data were obtained from the 2006, 2008, and 2010 Behavioral Risk Factor Surveillance System data. The EuroQol five-dimensional questionnaire (EQ-5D) health preference scores were estimated on the basis of extrapolations from the Centers for Disease Control and Prevention's healthy days measures. Depression scores were estimated using the eight-item Patient Health Questionnaire. Life expectancy estimates were obtained from US life tables, and QALE was estimated from a weighted combination of the EQ-5D scores and the life expectancy estimates. Outcomes were summarized by depression status for the four health behaviors (smoking, physical inactivity, heavy alcohol drinking, and obesity). RESULTS: For depressed adults, current smokers and the physically inactive had significantly lower EQ-5D scores (0.040 and 0.171, respectively), shorter life expectancy (12.9 and 10.8 years, respectively), and substantially less QALE (8.6 and 10.9 years, respectively). For nondepressed adults, estimated effects were similar but smaller. Heavy alcohol drinking among depressed adults, paradoxically, was associated with higher EQ-5D scores but shorter life expectancy. Obesity was strongly associated with lower EQ-5D scores but only weakly associated with shorter life expectancy. CONCLUSIONS: Among depressed adults, physical inactivity and smoking were strongly associated with lower EQ-5D scores, life expectancy, and QALE, whereas obesity and heavy drinking were only weakly associated with these indices. These results suggest that reducing physical inactivity and smoking would improve health more among depressed adults.

Oxytocin enhances observational fear in mice.

Empathy is fundamental to human relations, but its neural substrates remain largely unknown. Here we characterize the involvement of oxytocin in the capacity of mice to display emotional state-matching, an empathy-like behavior. When exposed to a familiar conspecific demonstrator in distress, an observer mouse becomes fearful, as indicated by a tendency to freeze and subsequent efforts to escape. Both intranasal oxytocin administration and chemogenetic stimulation of oxytocin neurons render males sensitive to the distress of an unfamiliar mouse. Acute intranasal oxytocin penetrates the brain and enhances cellular activity within the anterior cingulate cortex, whereas chronic administration produces long-term facilitation of observational fear and downregulates oxytocin receptor expression in the amygdala. None of these manipulations affect fear acquired as a result of direct experience with the stressor. Hence, these results implicate oxytocin in observational fear in mice (rather than fear itself) and provide new avenues for examining the neural substrates of empathy.

Schizophrenia spectrum personality disorders in psychometrically identified schizotypes at two-year follow-up.

Earlier (Bolinskey et al., 2015), we reported that psychometrically identified schizotypes displayed greater symptom levels and higher incidences of schizophrenia spectrum (schizotypal, schizoid, paranoid, and avoidant) personality disorders (PDs). In this study, 49 schizotypes and 39 matched controls participated in follow-up assessments after two years. Participants were previously identified as schizotypes or controls based on scores on the Chapman Psychosis Proneness Scales (CPPS), and were interviewed at baseline and follow-up with the Personality Disorder Interview for DSM-IV (PDI-IV). At follow-up, schizotypes displayed significantly higher symptom levels compared to controls, with medium to large effects, and appeared to meet criteria for diagnosis of each PD more often than controls, although significant differences were only observed for paranoid PD. Overall, schizotypes were more likely to have met criteria for a diagnosis at either baseline or follow-up. Finally, we observed a widening disparity over time between schizotypes and controls in avoidant and schizoid PDs. These results suggest that schizophrenia spectrum PDs, as well as subthreshold symptoms of these disorders, can represent a greater liability for schizophrenia in individuals identified as at-risk on the basis of psychometric means only. Furthermore, these findings demonstrate that such differences persist, and in some cases increase, over time.

Stratifying empiric risk of schizophrenia among first degree relatives using multiple predictors in two independent Indian samples.

BACKGROUND: Schizophrenia (SZ) has an estimated heritability of 64-88%, with the higher values based on twin studies. Conventionally, family history of psychosis is the best individual-level predictor of risk, but reliable risk estimates are unavailable for Indian populations. Genetic, environmental, and epigenetic factors are equally important and should be considered when predicting risk in 'at risk' individuals. OBJECTIVE: To estimate risk based on an Indian schizophrenia participant's family history combined with selected demographic factors. METHODS: To incorporate variables in addition to family history, and to stratify risk, we constructed a regression equation that included demographic variables in addition to family history. The equation was tested in two independent Indian samples: (i) an initial sample of SZ participants (N=128) with one sibling or offspring; (ii) a second, independent sample consisting of multiply affected families (N=138 families, with two or more sibs/offspring affected with SZ). RESULTS: The overall estimated risk was 4.31±0.27 (mean±standard deviation). There were 19 (14.8%) individuals in the high risk group, 75 (58.6%) in the moderate risk and 34 (26.6%) in the above average risk (in Sample A). In the validation sample, risks were distributed as: high (45%), moderate (38%) and above average (17%). Consistent risk estimates were obtained from both samples using the regression equation. CONCLUSIONS: Familial risk can be combined with demographic factors to estimate risk for SZ in India. If replicated, the proposed stratification of risk may be easier and more realistic for family members.

Understanding autism and other neurodevelopmental disorders through experimental translational neurobehavioral models.

Neurodevelopmental disorders (NDDs) are highly prevalent and severely debilitating brain illnesses caused by aberrant brain growth and development. Resulting in cognitive, social, motor, language and affective disabilities, common NDDs include autism spectrum disorder (ASD), intellectual disability, communication/speech disorders, motor/tic disorders and attention deficit hyperactivity disorder. Affecting neurogenesis, glia/neuronal proliferation and migration, synapse formation and myelination, aberrant neural development occurs over a substantial period of time. Genetic, epigenetic, and environmental factors play a key role in NDD pathogenesis. Animal models are an indispensable tool to study NDDs. Paralleling clinical findings, we comprehensively evaluate various preclinical tests and models which target key (social, cognitive, motor) neurobehavioral domains of ASD and other common NDDs. Covering both traditional (rodent) and alternative NDD models, we outline the emerging areas of research and emphasize how preclinical models play a key role in gaining translational and mechanistic insights into NDDs and their therapy.

Epigenetic assimilation in the aging human brain.

BACKGROUND: Epigenetic drift progressively increases variation in DNA modification profiles of aging cells, but the finale of such divergence remains elusive. In this study, we explored the dynamics of DNA modification and transcription in the later stages of human life. RESULTS: We find that brain tissues of older individuals (>75 years) become more similar to each other, both epigenetically and transcriptionally, compared with younger individuals. Inter-individual epigenetic assimilation is concurrent with increasing similarity between the cerebral cortex and the cerebellum, which points to potential brain cell dedifferentiation. DNA modification analysis of twins affected with Alzheimer's disease reveals a potential for accelerated epigenetic assimilation in neurodegenerative disease. We also observe loss of boundaries and merging of neighboring DNA modification and transcriptomic domains over time. CONCLUSIONS: Age-dependent epigenetic divergence, paradoxically, changes to convergence in the later stages of life. The newly described phenomena of epigenetic assimilation and tissue dedifferentiation may help us better understand the molecular mechanisms of aging and the origins of diseases for which age is a risk factor.

Genetic and environmental modulation of neurodevelopmental disorders: Translational insights from labs to beds.

Neurodevelopmental disorders (NDDs) are a heterogeneous group of prevalent neuropsychiatric illnesses with various degrees of social, cognitive, motor, language and affective deficits. NDDs are caused by aberrant brain development due to genetic and environmental perturbations. Common NDDs include autism spectrum disorder (ASD), intellectual disability, communication/speech disorders, motor/tic disorders and attention deficit hyperactivity disorder. Genetic and epigenetic/environmental factors play a key role in these NDDs with significant societal impact. Given the lack of their efficient therapies, it is important to gain further translational insights into the pathobiology of NDDs. To address these challenges, the International Stress and Behavior Society (ISBS) has established the Strategic Task Force on NDDs. Summarizing the Panel's findings, here we discuss the neurobiological mechanisms of selected common NDDs and a wider NDD+ spectrum of associated neuropsychiatric disorders with developmental trajectories. We also outline the utility of existing preclinical (animal) models for building translational and cross-diagnostic bridges to improve our understanding of various NDDs.

A Danish Twin Study of Schizophrenia Liability: Investigation from Interviewed Twins for Genetic Links to Affective Psychoses and for Cross-Cohort Comparisons.

We studied schizophrenia liability in a Danish population-based sample of 44 twin pairs (13 MZ, 31 DZ, SS plus OS) in order to replicate previous twin study findings using contemporary diagnostic criteria, to examine genetic liability shared between schizophrenia and other disorders, and to explore whether variance in schizophrenia liability attributable to environmental factors may have decreased with successive cohorts exposed to improvements in public health. ICD-10 diagnoses were determined by clinical interview. Although the best-fitting, most parsimonious biometric model of schizophrenia liability specified variance attributable to additive genetic and non-shared environmental factors, this model did not differ significantly from a model that also included non-additive genetic factors, consistent with recent interview-based twin studies. Schizophrenia showed strong genetic links to other psychotic disorders but much less so for the broader category of psychiatric disorders in general. We also observed a marginally significant decline in schizophrenia variance attributable to environmental factors over successive Western European cohorts, consistent perhaps with improvements in diagnosis and in prenatal and perinatal care and with a secular decline in the prevalence of schizophrenia in that region.

Classical and Molecular Genetic Research on General Cognitive Ability.

Arguably, no psychological variable has received more attention from behavioral geneticists than what has been called "general cognitive ability" (as well as "general intelligence" or "g"), and for good reason. GCA has a rich correlational network, implying that it may play an important role in multiple domains of functioning. GCA is highly correlated with various indicators of educational attainment, yet its predictive utility is not limited to academic achievement. It is also correlated with work performance, navigating the complexities of everyday life, the absence of various social pathologies (such as criminal convictions), and even health and mortality. Although the causal basis for these associations is not always known, it is nonetheless the case that research on GCA has the potential to provide insights into the origins of a wide range of important social outcomes. In this essay, our discussion of why GCA is considered a fundamentally important dimension of behavior on which humans differ is followed by a look at behavioral genetics research on CGA. We summarize behavioral genetics research that has sought to identify and quantify the total contributions of genetic and environmental factors to individual differences in GCA as well as molecular genetic research that has sought to identify genetic variants that underlie inherited effects.

Endophenotypes for Alcohol Use Disorder: An Update on the Field.

The endophenotype concept was first proposed as a strategy to use (purportedly) genetically simpler phenotypes in gene identification studies for psychiatric disorders, and is distinct from the closely related concept of intermediate phenotypes. In the area of alcohol use disorder (AUD) research, two candidate endophenotypes have produced replicable genetic associations: level of response to alcohol and neurophysiology markers (e.g., event-related oscillations and event-related potentials). Additional candidate endophenotypes from the cognitive, sensory, and neuroimaging literatures show promise, although more evidence is needed to fully evaluate their potential utility. Translational approaches to AUD endophenotypes have helped characterize the underlying neurobiology and genetics of AUD endophenotypes and identified relevant pharmacological interventions. Future research that capitalizes on the polygenic nature of endophenotypes and emphasizes endophenotypes that may change across development will enhance the usefulness of this concept to understand the genetically-influenced pathways toward AUD.

Targeting drug sensitivity predictors: New potential strategies to improve pharmacotherapy of human brain disorders.

One of the main challenges in medicine is the lack of efficient drug therapies for common human disorders. For example, although depressed patients receive powerful antidepressants, many often remain resistant to psychopharmacotherapy. The growing recognition of complex interplay between the drug targets and the predictors of drug sensitivity requires an improved understanding of these two key aspects of drug action and their potentially shared molecular networks. Here, we apply the concept of endophenotypes and their interplay to drug action and sensitivity. Based on these analyses, we postulate that novel drugs may be developed by targeting specific molecular pathways that integrate drug targets with drug sensitivity predictors.

Screening whole spine magnetic resonance imaging in multiple myeloma.

BACKGROUND: Magnetic resonance imaging (MRI) is the most sensitive method for detecting focal spinal disease (FSD) in multiple myeloma (MM). It is unclear whether whole spine MRI (WS-MRI) should be employed as a screening test at diagnosis of MM. AIM: To determine the utility of screening WS-MRI at diagnosis of MM. METHODS: A retrospective analysis of data from January 2008 to January 2013 at the Townsville Hospital was performed. At this centre, WS-MRI is used routinely in all newly diagnosed MM. The findings of WS-MRI in patients with and without an agreed guideline indication for WS-MRI were compared. Clinical predictors of FSD were determined. RESULTS: Seventy-one patients were included in the analysis. Forty-four (62%) had an agreed indication for MRI; 33 (75%) of these had FSD. Within this group, 17 required urgent intervention and 13 had spinal plasmacytomas. Within a second group without a guideline indication, 4 of 27 (15%) were found to have FSD on MRI - none required urgent intervention and or had plasmacytomas. Three of eight smouldering myeloma patients were reclassified as symptomatic myeloma by documenting lytic lesions not identified on plain film. The strongest predictors of FSD were back pain (P < 0.001) and vertebral compression fracture (P = 0.003). CONCLUSION: WS-MRI in patients without a guideline indication did not detect any lesions that threatened the spinal cord. WS-MRI is essential in those with guideline indications. WS-MRI is of benefit to patients with smouldering myeloma where documentation of lesions not seen on plain film will result in treatment rather than observation.

Targeting dynamic interplay among disordered domains or endophenotypes to understand complex neuropsychiatric disorders: Translational lessons from preclinical models.

Contemporary biological psychiatry uses clinical and experimental (animal) models to increase our understanding of brain pathogenesis. Modeling psychiatric disorders is currently performed by targeting various key neurobehavioral clusters of phenotypic traits (domains), including affective, cognitive, social, motor and reward. Analyses of such domains and their 'smaller units' - individual endophenotypes - are critical for the study of complex brain disorders and their neural underpinnings. The spectrum nature of brain disorders and the importance of pathogenetic linkage among various disordered domains or endophenotypes have also been recognized as an important strategic direction of translational research. Here, we discuss cross-domain analyses of animal models, and focus on their value for mimicking the clinical overlap between disordered neurobehavioral domains in humans. Based on recent experimental evidence, we argue that understanding of brain pathogenesis requires modeling the clinically relevant inter-relationships between various individual endophenotypes (or their domains).