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Residential posttraumatic stress disorder (PTSD) research in military samples generally shows that in aggregate, PTSD symptoms significantly improve over the course of treatment but can remain at elevated levels following treatment. Identifying individuals who respond to residential treatment versus those who do not, including those who worsen, is critical given the extensive resources required for such programs. This study examined predictors of treatment response among 282 male service members who received treatment in a U.S. Department of Defense residential PTSD program. Using established criteria, service members were classified as improved, indeterminate (referent), or worsened in terms of self-reported PTSD symptoms. Multinomial logistic regression results showed that for PTSD symptoms, higher levels of pretreatment PTSD symptom severity were associated with significantly lower odds of being in the improved group, adjusted odds ratio (aOR) = 0.955, p = .018. In addition, service members who completed treatment were significantly more likely to be in the improved group, aOR = 2.488, p = .048. Longer average pretreatment nightly sleep duration, aOR = 1.157, p = .035, and more severe pretreatment depressive symptoms, aOR = 1.109, p = .014, were associated with significantly higher odds of being in the improved group. These findings reveal clinical characteristics better suited for residential PTSD treatment and highlight implications for comorbid conditions.

Cognitive difficulties typically resolve within days to weeks following mild traumatic brain injury (mTBI); however, a sizable proportion of individuals continue to report cognitive symptoms months to years later that are often associated with posttraumatic stress disorder (PTSD) and depression to a greater degree than a history of mTBI. The current study sought to evaluate the prevalence of self-reported cognitive difficulties as well as the relative contributions of demographic, injury-related, and mental health variables in a large study of U.S. military personnel injured during deployment since 2001. Slightly fewer than half (42.0%) of participants reported elevated cognitive difficulties compared with a normative population; however, this was driven primarily by those who screened positive for PTSD or depression. Hierarchical linear regression revealed that various demographic and injury factors, including lower educational attainment, retired or separated military status, enlisted rank, and a history of deployment-related mTBI, were associated with more self-reported cognitive difficulties, f

The role of visual experience in the development of face processing has long been debated. We present a new angle on this question through a serendipitous study that cannot easily be repeated. Infants viewed short blocks of faces during fMRI in a repetition suppression task. The same identity was presented multiple times in half of the blocks (Repeat condition) and different identities were presented once each in the other half (Novel condition). In adults, the fusiform face area (FFA) tends to show greater neural activity for Novel vs. Repeat blocks in such designs, suggesting that it can distinguish same vs. different face identities. As part of an ongoing study, we collected data before the COVID-19 pandemic and after an initial State lockdown was lifted. The resulting sample of 12 infants (9–24 months) divided equally into pre- and post-lockdown groups with matching ages and data quantity/quality. The groups had strikingly different FFA responses: pre-lockdown infants showed repetition suppression (Novel>Repeat), whereas post-lockdown infants showed the opposite (Repeat>Novel), often referred to as repetition enhancement. These findings provide speculative evidence that altered visual experience during the lockdown, or other correlated environmental changes, may have affected face processing in the infant brain.

Intact native fish assemblages—those with all or most historical taxa present and a strong numerical dominance of native species—are rare in streams and other aquatic systems worldwide. Our sampling during four intervals from 1983 to 2007 showed that the Purgatoire River, a Great Plains stream in eastern Colorado, supported an assemblage that was 99.6% native taxa, and all but one rare species persisted through time. An additional rare Arkansas River native fish colonized the Purgatoire River and was widespread in 2006–2007, and only three nonnative taxa were detected. The perennial Purgatoire River supported all native fishes in the basin, while tributaries supported mainly native fishes that were tolerant of intermittent, harsh habitat. In the Purgatoire River, frequency and abundance of dominant species varied spatially during 2006–2007. Persistence of native fishes was unchanged over time in the Pinon Canyon reach of the river even though abundance varied substantially. Despite the presence of...

Human Aurora kinases, including Aurora kinase A (AURKA), B (AURKB), and C (AURKC), play an essential role in mitotic events such as monitoring of the mitotic checkpoint, creation of bipolar mitotic spindle and alignment of centrosomes on it, also regulating centrosome separation, bio-orientation of chromosomes and cytokinesis. AURKA and AURKB are key regulators of mitosis and centrosome via polymerizing microfilaments and controlling chromatid segregation. In particular, AURKA plays critical roles in the regulation of mitotic entry, centrosome function, bipolar spindle assembly, and chromosome segregation. AURKA has been found to be overexpressed in various solid and haematological cancers and has been linked with poor prognosis. Its important role in cancer initiation, growth, and metastasis has brought the focus to search for potent and selective AURKA inhibitors for cancer treatment. MLN8237, also known as alisertib, is one selective AURKA inhibitor that has shown remarkable anticancer effects in preclinical studies. Alisertib exhibits favourable pharmacokinetic properties. Alisertib has generally showed good partial response rates of 4-52% and good safety profiles in Phase I and II trials when it is solely administered as well as combined with cytotoxic chemotherapeutic drugs. Recently, the multicentre, randomized Phase III study of alisertib in patients with relapsed or refractory peripheral T-cell lymphoma has been discontinued due to unsatisfactory efficacy. The low risk of side effects, accessibility, and effectiveness of alisertib makes it a new promising anticancer therapy and further mechanistic and clinical studies are warranted.

The Na(+) /K(+) -translocating adenosine triphosphatase (ATPase) transports sodium and potassium across the plasma membrane and represents a potential target in cancer chemotherapy. Na(+) /K(+) -ATPase belongs to the P-type ATPase family (also known as E1-E2 ATPase), which is involved in transporting certain ions, metals, and lipids across the plasma membrane of mammalian cells. In humans, the Na(+) /K(+) -ATPase is a binary complex of an α-subunit that has four isoforms (α1 -α4 ) and a β-subunit that has three isoforms (β1 -β3 ). This review aims to update our knowledge on the role of Na(+) /K(+) -ATPase in cancer development and metastasis, as well as on how Na(+) /K(+) -ATPase inhibitors kill tumour cells. The Na(+) /K(+) -ATPase has been found to be associated with cancer initiation, growth, development, and metastasis. Cardiac glycosides have exhibited anticancer effects in cell-based and mouse studies via inhibition of the Na(+) /K(+) -ATPase and other mechanisms. Na(+) /K(+) -ATPase inhibitors may kill cancer cells via induction of apoptosis and autophagy, radical oxygen species production, and cell cycle arrest. They also modulate multiple signalling pathways that regulate cancer cell survival and death, which contributes to their antiproliferative activities in cancer cells. The clinical evidence supporting the use of Na(+) /K(+) -ATPase inhibitors as anticancer drugs is weak. Several phase I and phase II clinical trials with digoxin, Anvirzel, and huachansu (an intravenous formulated extract of the venom of the wild toad), either alone or more often in combination with other anticancer agents, have shown acceptable safety profiles but limited efficacy in cancer patients. Well-designed randomized clinical trials with reasonable sample sizes are certainly warranted to confirm the efficacy and safety of cardiac glycosides for the treatment of cancer.

INTRODUCTION AND AIMS: Research explored the effects of variability in negative and positive affect on alcohol consumption, specifying daily fluctuation in affect as a critical form of emotion dysregulation. Using daily process methodology allows for a more objective calculation of affect variability relative to traditional self-reports. The present study models within-person negative and positive affect variabilities as predictors of context-specific consumption (i.e. solitary vs. social drinking), controlling for mean levels of affect. DESIGN AND METHODS: A community sample of moderate-to-heavy drinkers (n = 47; 49% women) from a US metropolitan area reported on affect and alcohol consumption thrice daily for 30 days via a handheld electronic interviewer. Within-person affect variability was calculated using daily standard deviations in positive and negative affect. RESULTS: Within person, greater negative and positive variabilities are related to greater daily solitary and social consumption. Across study days, mean levels of negative and positive affect variabilities related to greater social consumption between persons; yet, aggregated negative affect variability was related to less solitary consumption. DISCUSSION AND CONCLUSIONS: Results affirm affect variability as a unique predictor of alcohol consumption, independent of mean affect levels. Yet, it is important to differentiate social context of consumption, as well as type of affect variability, particularly at the between-person level. These distinctions help clarify inconsistencies in the self-medication literature regarding associations between average levels of affect and consumption. Importantly, consistent within-person relationships for both variabilities support arguments that both negative and positive affect variabilities are detrimental and reflect an inability to regulate emotional experience. [Mohr CD, Arpin S, McCabe CT. Daily affect variability and context-specific alcohol consumption. Drug Alcohol Rev 2015]. Language: en

Objectives The initial step in certification by the American Board of Emergency Medicine (ABEM) requires passing a multiple-choice-question qualifying examination. The qualifying examination is typically taken in the first year after residency training. This study was undertaken to determine if a delay in taking the qualifying examination is associated with poorer performance. The authors also examined the relationship between in-training examination scores and qualifying examination scores. Methods This was a pooled time-series cross-section study. Primary measurements were initial qualifying examination scores, the timing of the qualifying examination, and in-training examination scores. The three groups, based on qualifying examination timing, were immediate, 1-year delay, and ≥2-year delay. In-training examination scores were analyzed to determine the relationship between intrinsic ability, examination timing, and qualifying examination scores. For analysis, a generic pooled ordinary least-squares dummy variable model with robust standard errors was used. A pre hoc level of significance was determined to be α < 0.01. Results There were 16,353 qualifying examination test administrations between 2000 and 2012. In-training examination scores were positively correlated with qualifying examination scores (p < 0.001). The group pass rates were 98.9% immediate, 95.6% 1-year delay, and 86.6% ≥2-year delay. After controlling for in-training examination scores, delay taking the qualifying examination of 1 year was associated with a decrease in score of –0.6 (p = 0.003). A delay in taking the qualifying examination ≥2 years was associated with a decrease in score of –2.5 points (p < 0.001). Conclusions After accounting for innate ability using in-training examination scores, delay taking the qualifying examination was associated with poorer performance. This effect was more pronounced if the delay was ≥2 years. Resumen Objetivos El paso inicial en la certificacion por la American Board of Emergency Medicine (ABEM) requiere aprobar un examen de cualificacion (EC) de preguntas de eleccion multiple. El EC se realiza habitualmente en el primer ano tras la formacion de la residencia. Este estudio se llevo a cabo para determinar si un retraso en la realizacion del EC esta asociado con un peor rendimiento. Tambien se examino la relacion entre las puntuaciones del examen durante la formacion (EDF) y las puntuaciones del EC. Metodologia Estudio transversal de series temporales sumatorias. Las mediciones principales fueron las puntuaciones iniciales del EC, el momento del EC y las puntuaciones del EDF. Los tres grupos, basados en el momento del EC fueron: inmediato, un ano de retraso y 2 o mas anos de retraso. Se analizaron las puntuaciones del EDF para determinar la relacion entre la capacidad intrinseca, el tiempo del examen y las puntuaciones del EC. Para el analisis, se utilizo un modelo variable de minimos cuadrados ordinarios sumatorio generico con errores estandar robustos. Se determino un nivel de significacion pre hoc de α < 0,01. Resultados Hubo 16.353 EC entre el 2000 y el 2012. Las puntuaciones del EDF se correlacionaron positivamente con las puntuaciones del EC (p < 0,001). La proporcion de aprobados de cada grupo fue: 98,9% para el grupo inmediato, 95,6% para 1 ano de retraso y 86,6% para 2 o mas anos de retraso. Tras ajustar por las puntuaciones de EDF, el retraso del EC un ano se asocio con un descenso en la puntuacion de -0,6 (p = 0,003). Un retraso de realizacion del EC de 2 o mas anos se asocio con descenso en la puntacion de -2,5 puntos (p < 0,001). Conclusiones Tras tener en cuenta las capacidades innatas mediante las puntuaciones del EDF, el retrasar la realizacion del EC se asocio con un peor rendimiento. Este efecto fue mas pronunciado si el retraso fue ≥ a 2 anos.

Failure of blood pressure (BP) to decline appropriately overnight (nondipping) is associated with increased risk. This may be due to inappropriately raised supine central BP and this study's first aim was to examine this hypothesis. Secondly, aortic stiffness, central hemodynamics, and left ventricular (LV) mass were measured as other possible mechanisms of higher risk. Brachial and central BP (supine and seated), aortic stiffness, central hemodynamics, and LV dimensions were measured in 95 patients with hypertension (mean age 62 +/- 8 standard deviation). Central hemodynamics were recorded by combined radial tonometry and 3-dimensional echocardiography. Seated brachial and central systolic BP (SBP) were similar between dippers (n=52) and nondippers (n=43). However, nondippers had higher supine brachial (132 +/- 14 mm Hg vs 126 +/- 11 mm Hg; P=.029) and central (121 +/- 15 mm Hg vs 115 +/- 11 mm Hg; P=.024) SBP. Aortic stiffness was not different between groups (P=.76), but LV mass index (33.0 +/- 6.2 vs 29.4 +/- 7.2 g/m(2.7); P=.019), stroke volume index (30.2 +/- 6.2 mL/m(2) vs 27.4 +/- 6.0 mL/m(2); P=.040), and LV stroke work (3246 +/- 815 mm Hg/mL/m(2) vs 2778 +/- 615 mm Hg/mL/m(2); P=.005) were all higher in nondippers. Dipper status independently predicted LV mass index (beta=3.61; P=.001). Nondippers have higher supine brachial and central SBP, significantly different central hemodynamics, and elevated LV mass index compared with dippers. These cardiovascular anomalies possibly contribute to increased mortality risk. J Clin Hypertens (Greenwich). 2011; 13: 557-562. (C)2011 Wiley Periodicals, Inc.

Antiepileptic drugs (AEDs) such as phenobarbital, phenytoin and valproic acid, when given in therapeutic doses to neonatal rats, cause pronounced neuronal apoptotic cell death. This effect is especially pronounced in the striatum and cortex during the second postnatal week; a period corresponding to the “brain growth spurt” (third trimester of gestation and early infancy) in humans. Of particular concern is the fact that phenobarbital is the most frequently used therapy for neonatal epilepsy. If AED-induced neuronal cell death leads to long-term functional impairment, then it becomes crucial to find therapies that avoid this neurotoxicity in the sensitive period. Here we examine short and long-term functional effects following exposure of neonatal rat pups to phenobarbital; the functions tested include striatal GABAergic synaptic responses and reflex development in pups, and fear conditioning, emotionality, and sensory-motor gating in adults. In all cases, phenobarbital exposure during the second postnatal week was sufficient to cause significant impairment. In contrast, adult animals exposed as pups to lamotrigine (given in a dose that does not cause apoptotic neuronal death) were not impaired on the tasks we examined. Our data suggest that treatments devoid of proapoptotic actions may be promising therapies for avoiding adverse outcomes after neonatal exposure. In addition, our findings identify early exposure to certain AEDs as an important potential risk factor contributing to psychiatric and neurological abnormalities later in life.

Objective To evaluate a novel coconut-derived emulsion (CDE) shampoo against head lice infestation in children. Design A school trial in which pupils were treated on days 0 and 7 and checked on days 8 and 15 and a family trial where product was applied by parents three times in 2 weeks or used as a cosmetic shampoo and checked on days 14 and days 70. Setting UK schools in Bristol and Western-super-Mare and families in Northern Somerset. Main outcome measure Numbers of children free from infestation after treatment. Results In the school trial, percentage cures at day 8 were 14% (permethrin, n = 7) and 61% (CDE, n = 37). In the family trial where all family members were treated, cure rate was 96% (n = 28), and if the shampoo was subsequently used as a cosmetic shampoo, only 1 of 12 children became re-infested after 10 weeks. Conclusion CDE shampoo is a novel effective method of controlling head lice and used after treatment as a cosmetic shampoo can aid in the reduction of re-infestation.