Intratumoral drug-releasing microdevices allow in situ high-throughput pharmaco phenotyping in patients with gliomas.

The lack of reliable predictive biomarkers to guide effective therapy is a major obstacle to the advancement of therapy for high-grade gliomas, particularly glioblastoma (GBM), one of the few cancers whose prognosis has not improved over the past several decades. With this pilot clinical trial (number NCT04135807), we provide first-in-human evidence that drug-releasing intratumoral microdevices (IMDs) can be safely and effectively used to obtain patient-specific, high-throughput molecular and histopathological drug response profiling. These data can complement other strategies to inform the selection of drugs based on their observed antitumor effect in situ. IMDs are integrated into surgical practice during tumor resection and remain in situ only for the duration of the otherwise standard operation (2 to 3 hours). None of the six enrolled patients experienced adverse events related to the IMD, and the exposed tissue was usable for downstream analysis for 11 out of 12 retrieved specimens. Analysis of the specimens provided preliminary evidence of the robustness of the readout, compatibility with a wide array of techniques for molecular tissue interrogation, and promising similarities with the available observed clinical-radiological responses to temozolomide. From an investigational aspect, the amount of information obtained with IMDs allows characterization of tissue effects of any drugs of interest, within the physiological context of the intact tumor, and without affecting the standard surgical workflow.

Immunophenotyping of Monocyte Migration Markers and Therapeutic Effects of Selenium on IL-6 and IL-1ß Cytokine Axes of Blood Mononuclear Cells in Preoperative and Postoperative Coronary Artery Disease Patients.

Multivessel coronary artery disease (CAD) is characterized by underlying chronic vascular inflammation and occlusion in the coronary arteries, where these patients undergo coronary artery bypass grafting (CABG). Since post-cardiotomy inflammation is a well known phenomenon after CABG, attenuation of this inflammation is required to reduce perioperative morbidity and mortality. In this study, we aimed to phenotype circulating frequencies and intensities of monocyte subsets and monocyte migration markers, respectively, and to investigate the plasma level of inflammatory cytokines and chemokines between preoperative and postoperative CAD patients and later, to intervene the inflammation with sodium selenite. We found a higher amplitude of inflammation, postoperatively, in terms of CCR1high monocytes and significantly increased pro-inflammatory cytokines, IL-6, IL-8, and IL-1RA. Further, in vitro intervention with selenium displayed mitigating effects on the IL-6/STAT-3 axis of mononuclear cells derived from postoperative CAD patients. In addition, in vitro selenium intervention significantly reduced IL-1ß production as well as decreased cleaved caspase-1 (p20) activity by preoperative (when stimulated) as well as postoperative CAD mononuclear cells. Though TNF-α exhibited a positive correlation with blood troponin levels in postoperative CAD patients, there was no obvious effect of selenium on the TNF-α/NF-κB axis. In conclusion, anti-inflammatory selenium might be utilized to impede systemic inflammatory cytokine axes to circumvent aggravating atherosclerosis and further damage to the autologous bypass grafts during the post-surgical period.

Proper Emotion Recognition, Dysfunctional Emotion Regulation.

OBJECTIVE: A considerable number of adolescents exhibit severe self-regulation deficits in affect and behavior, which are referred to as affective dysregulation (AD). AD may be conceptualized as a dimensional trait that, in its extreme form, resembles the diagnostic categories of severe mood dysregulation (SMD) or disruptive mood dysregulation disorder (DMDD). Assuming a shared pathway of psychopathology in AD and SMD, similar underlying dysfunctional mechanisms in emotion processing, particularly emotion recognition (RECOG) and regulation (REGUL), may be postulated. METHOD: Adolescent inpatients with AD (CAD, N = 35), without AD (CCG, N = 28), and nonclinical controls (NCG; N = 28) were administered a morphed facial recognition task (RECOG). REGUL abilities, levels of irritability as well as depressive symptoms were also assessed. RESULTS: We found no significant group differences in accuracy and thresholds for RECOG abilities. Patients with AD reported more dysfunctional REGUL strategies than did CCG and NCG. Both depression and AD, but not irritability, influenced the overall degree of maladaptive REGUL. CONCLUSION: The broad phenotype of AD does not involve the deficits in RECOG reported for adolescents with a narrow phenotype (SMD); regarding REGUL strategies, AD seems to be associated with specific impairments.

Tackling vitamin A deficiency with biofortified sweetpotato in sub-Saharan Africa.

Orange-fleshed sweetpotato (OFSP) is a rich plant-based source of beta-carotene, which the body converts into vitamin A. In sub-Saharan Africa, sweetpotato is known as a food security crop but most varieties grown are high dry matter white-fleshed types, lacking beta-carotene. In 1995, researchers recognized the potential of OFSP varieties to address widespread vitamin A deficiency in SSA using an integrated agriculture-nutrition approach. With their partners, they confronted conventional wisdom concerning food-based approaches and institutional barriers, to build the evidence base and breed 42 OFSP varieties adapted to farmer needs and consumer preferences. Subsequently, a multi-partner, multi-donor initiative, launched in 2009, has already reached 2.8 million households. This review summarizes that effort describing how the changing policy environment influenced the process.

The research and implementation continuum of biofortified sweet potato and maize in Africa.

The enhancement of sweet potato and maize with provitamin A carotenoids has been part of HarvestPlus's research continuum since the formation of the biofortification project. This review includes case studies of biofortification strategies used for sweet potato in Uganda and orange maize in Zambia. The current status of the science and release of biofortified varieties was reviewed by three scientists who were part of the HarvestPlus program for more than a decade with input from a scientist who experienced orange maize dissemination in Zambia. High ß-carotene varieties of sweet potato were introduced into South Africa and Mozambique, and efficacy and effectiveness studies, respectively, showed promise to improve vitamin A status, followed by dissemination efforts in Uganda. A randomized, controlled effectiveness trial tested extension models to promote sweet potato and assessed vitamin A intake among Ugandans. Orange maize breeding was initially a challenge, but considering that the carotenoid biosynthetic pathway was present in maize germplasm, breeders quickly bred higher amounts of provitamin A into the maize that was ultimately released in Zambia. Initial resistance occurred because orange maize was associated with yellow maize, which had negative connotations associated with food aid and animal feed, and consumers preferred white maize. Currently, both orange crops are available on the market.

Functional cerebral lateralization and interhemispheric interaction in patients with callosal agenesis.

OBJECTIVE: The corpus callosum (CC), the largest commissure in the human brain, is thought to play an essential part in the formation and maintenance of lateralized cognitive and motor functions. In particular, it has been suggested that inhibition of the subdominant hemisphere via commissural fiber tracts plays a crucial role for functional lateralization. However, many studies supporting this idea have either been conducted in nonhuman model species or used indirect measures of callosal functioning. METHOD: In order to directly assess the impact of the presence or absence of the CC on both the existence and the extent of functional hemispheric asymmetries, we investigated handedness and language lateralization, as well as interhemispheric information integration, in 6 high-functioning individuals with partial or complete agenesis of the CC (AgCC). Performance was compared with that of 30 IQ- and age-matched controls with intact CC. RESULTS: We found a stronger predisposition for ambidexterity in individuals with AgCC. Similarly, the typical right ear advantage in the dichotic listening task was significantly reduced in AgCC. Furthermore, AgCC patients generally reacted slower than controls in a test of interhemispheric information integration, and showed reduced accuracy in trials that required interhemispheric integration. CONCLUSIONS: These findings indicate that reduced hemispheric specialization in the acallosal brain might be due to a higher degree of hemispheric autonomy in AgCC.

The type of implicit motive enactment is modulated by sex hormones in naturally cycling women.

Sex hormones have been reported to dynamically modulate the expression of implicit motives, a concept that has previously been thought to be relatively stable over time. This study investigates to what extent the need for affiliation, power, and achievement, as well as the form of enactment of these needs as measured with the Operant Motive Test (OMT), is affected by cycle-phase dependent sex hormone fluctuations. In addition to measuring the strength of motive expression, the OMT also captures different forms of motive enactment. In an intra-subject design with repeated measures, no evidence for cycle-phase related variation in overall motive scores was found. However, when different forms of motive enactment were considered, an effect of menstrual cycle was observed. The incentive-based inhibition of the power motive was significantly reduced at the time of ovulation, compared to the menstrual and to the mid-luteal phase, in naturally cycling women. In women with relatively stable hormone concentrations (due to using hormonal contraceptives), no significant changes in the form of motive enactment were evident. The results indicate a specific hormonal influence on motive-related cognitive processes that are related to inhibitive processes in behavior control.

Multisensory integration across the menstrual cycle.

Evidence suggests that spatial processing changes across time in naturally cycling women, which is likely due to neuromodulatory effects of steroid hormones. Yet, it is unknown whether crossmodal spatial processes depend on steroid hormones as well. In the present experiment, the crossmodal congruency task was used to assess visuo-tactile interactions in naturally cycling women, women using hormonal contraceptives and men. Participants adopted either a crossed or uncrossed hands posture. It was tested whether a postural effect of hand crossing on multisensory interactions in the crossmodal congruency task is modulated by women's cycle phase. We found that visuotactile interactions changed according to cycle phase. Naturally cycling women showed a significant difference between the menstrual and the luteal phase for crossed, but not for uncrossed hands postures. The two control groups showed no test sessions effects. Regression analysis revealed a positive relation between estradiol levels and the size of crossmodal congruency effects (CCE), indicating that estradiol seems to have a neuromodulatory effect on posture processing.

A community development approach to service-learning: building social capital between rural youth and adults.

Using 4-H and FFA case study findings, this article explores how community service-learning supports the building of social capital between rural youth and adults and the positive effects on community viability. Key elements of practice form a community development approach to service-learning, which opens up doorways for youth to partner with adult leaders and decision makers, gain credibility as resources and problem solvers, address community issues, and raise awareness of the value of school- and community-based youth programs. Case study evidence suggests that rural 4-H and FFA youth and adults benefit from the bonding relationships they form through working together to solve community issues over time. Positive community outcomes are noted as well, including increased community capacity and community recognition. By focusing on social capital as a key outcome of community service-learning, 4-H youth and community development extension professionals, educators, and other practitioners have contributed to the viability of rural communities.

Variability in ratings of trustworthiness across the menstrual cycle.

This study investigated how trusting behavior varies in naturally cycling women, as a function of sex and attractiveness of players in a trust game, at three distinct phases of the menstrual cycle. Women acted more cautiously in an investment game at the preovulatory phase, compared to the menstrual and the mid-luteal phase. Reduced willingness to trust in strangers was particularly expressed toward male players at this time. The increase of estradiol levels from menses to the preovulatory phase was negatively correlated with trust in attractive male other players, whereas the increase of progesterone levels from menses to the mid-luteal phase was positively associated with trust in unattractive female other players. No particular contribution of a single hormone level could be identified for the generally reduced willingness to trust in strangers in the preovulatory phase. Thus, the results emphasize the impact of the menstrual cycle on interpersonal trust, although the exact mode of hormonal action needs to be further investigated.

Visuotactile interactions in the congenitally acallosal brain: evidence for early cerebral plasticity.

Studies in patients with an isolated, congenital agenesis of the corpus callosum have documented potentials and limits of brain plasticity. Literature suggests that early reorganization mechanisms can compensate for the absence of the corpus callosum in unisensory tasks that involve interhemispheric transfer. It is unknown, however, how the congenitally acallosal brain processes multisensory information, which presumably requires interhemispheric transfer of modality-specific input. Therefore, we tested five patients with total and one patient with partial agenesis of the corpus callosum in a visuotactile interference task (the "crossmodal congruency task") with uncrossed and crossed hands and compared their performance to that of 31 healthy controls. We found that congruency effects followed the hands in space not only in healthy, but also in congenitally acallosal individuals. Remarkably, this was also true when patients' hands crossed the vertical visual meridian and stimuli were presented at the same hand. These results suggest that callosal connectivity is not required for remapping of visuotactile space. We conclude that early brain plasticity allows for compensation of the developmental absence of the corpus callosum in a visuotactile interference task.

Measuring interprofessional team collaboration in expanded school mental health: Model refinement and scale development.

Expanded school mental health (ESMH) utilizes interprofessional collaboration to implement learning support and mental health promotion strategies in schools. This study reports on the early development and initial psychometric examination of a new scale, the Index of Interprofessional Team Collaboration for Expanded School Mental Health (IITC-ESMH), for measuring the functioning of interprofessional teams. Exploratory factor analysis results, using data collected from 436 members of interprofessional teams in schools, yielded a 26-item scale with a four-factor model (a) Reflection on Process, (b) Professional Flexibility, (c) Newly Created Professional Activities, and (d) Role Interdependence. Cronbach's alphas for the four factors were .91, .91, .84, and .80 respectively. The findings from this study provide evidence to support the IITC-ESMH as a reliable instrument for measuring interprofessional collaboration.

Making the connections: AIDS and water.

OBJECTIVE: Acknowledging AIDS as a crosscutting development issue, a Zambian rural water supply project that provides safe accessible water to rural communities embarked on a new initiative to mainstream AIDS into the water sector. SETTING AND PARTICIPANTS: The work of providing safe water takes the predominantly male workforce away from their spouses and families, into the rural villages of Zambia's Eastern Province, for long periods of time. With an HIV prevalence rate of 16.1%, the risk of HIV exposure exists for both employees and rural villagers. AIDS mainstreaming activities were designed to target both groups. INTERVENTION: An AIDS mainstreaming strategy was developed by identifying components that could be influenced in the external domain (the organization's usual work) and the internal domain (the workplace). Basic questions were addressed such as: how does AIDS affect the organization, how might the usual work aggravate susceptibility to HIV infection, and where is the comparative advantage? OUTCOMES: A workplace program including peer education, employee health education (including condoms) and a workplace policy was established for employees. For the target population, a series of five messages connecting safe water and AIDS was developed and disseminated through educational drama, community meetings and trainings, and integrated into the regular water, sanitation and hygiene activities. CONCLUSIONS: As an efficient utilization of resources that makes a broad impact, AIDS mainstreaming does not change the sector's mandate but takes advantage of the extensive geographic coverage and natural distribution system of water projects to disseminate AIDS information and make linkages with AIDS partners.