Bioadhesive grafted starch copolymers as platforms for peroral drug delivery: a study of theophylline release.

Nonirritant bioadhesive drug release systems based on starch-acrylic acid graft copolymers prepared by radiation of starch and acrylic acid mixtures with (60)Co were developed for buccal application. The release rate of theophylline (TPL), used as a model drug, depended on the ratio of starch to acrylic acid and on the presence of cations in the graft copolymers, but was practically not affected by the pH (between pH 3 and 7) of the dissolution medium nor by the type of starch used (corn, rice, or potato). Possible release mechanisms are discussed for specific conditions. In general, the release behavior of the graft copolymers was found to be non-Fickian, n value being between 0.6 and 0.96, suggesting that the release was controlled by a combination of tablet erosion and the diffusion of the drug from the swollen matrix. Incorporation of divalent cations into the graft copolymers led to a significant decrease in swelling erosion of the tablets as well as a substantial retardation of drug release. Highest work of adhesion was obtained with graft copolymers containing calcium ions as well as longer time of adhesion on dogs' gingiva.     

Verbal paired-associate learning by APOE genotype in non-demented older adults: fMRI evidence of a right hemispheric compensatory response

Previous studies of episodic memory report a greater extent of blood-oxygenation-level-dependent (BOLD) response in non-demented older adults with the apolipoprotein E epsilon-4 (APOE epsilon4) allele than in those without the allele. We conducted a functional MRI study to investigate whether APOE genotype is related to brain response to verbal paired-associate encoding and consolidation, particularly in the right hemisphere, among non-demented older adults. Structurally segmented volumes and BOLD response were measured in 13 non-epsilon4 and 12 epsilon4 subjects. The epsilon4 group displayed greater activation than the non-epsilon4 group in multiple right hemisphere regions for previously encoded word pairs relative to fixation. Activation within manually outlined hippocampal regions of interest also displayed genotype-specific dissociations consistent with whole brain analyses. Furthermore, this differential BOLD response occurred in the presence of equivalent behavioral and neuropsychological performances as well as comparable hippocampal and overall structural segmentation volumes between groups. Results implicate a widely distributed and interconnected network of right hemisphere brain regions that may be involved in compensating for APOE epsilon4-related deficiencies associated with verbal episodic memory encoding and consolidation.     

Improving program targeting to combat early-life mortality by identifying high-risk births: an application to India

Background

It is widely recognized that there are multiple risk factors for early-life mortality. In practice most interventions to curb early-life mortality target births based on a single risk factor, such as poverty. However, most premature deaths are not from the targeted group. Thus interventions target many births that are at not at high risk and miss many births at high risk.

Methods

Using data from the second wave of Demographic and Health Surveys from India and a hierarchical Bayesian model, we estimate infant mortality risk for 73.320 infants in India as a function of 4 risk factors. We show how this information can be used to improve program targeting. We compare our novel approach against common programs that target groups based on a single risk factor.

Results

A conventional approach that targets mothers in the lowest quintile of income correctly identifies only 30% of infant deaths. By contrast, using four risk factors simultaneously we identify a group of births of the same size that includes 57% of all deaths. Using the 2012 census to translate these percentages into numbers, there were 25.642.200 births in 2012 and 4.4% died before the age of one. Our approach correctly identifies 643.106 of 1.128.257 infant deaths while poverty only identifies 338.477 infant deaths.

Conclusion

Our approach considerably improves program targeting by identifying more infant deaths than the usual approach that targets births based on a single risk factor. This leads to more efficient program targeting. This is particularly useful in developing countries, where resources are lacking and needs are high.

     

Treatment efficacy of social communication skills training after traumatic brain injury: a randomized treatment and deferred treatment controlled trial

Dahlberg CA, Cusick CP, Hawley LA, Newman JK, Morey CE. Harrison-Felix CL, Whiteneck GG. Treatment efficacy of social communication skills training after traumatic brain injury: a randomized treatment and deferred treatment controlled trial.

Objective

To evaluate the efficacy of a replicable group treatment program to improve social communication skills after traumatic brain injury (TBI).

Design

Randomized treatment and deferred treatment controlled trial, with follow-up at 3, 6, and 9 months post-treatment.

Setting

Community.

Participants

Volunteer sample of 52 people with TBI who were at least 1 year postinjury, who received rehabilitation, and who had identified social communication deficits.

Intervention

Twelve weekly group sessions (1.5h each) to improve social communication.

Main Outcome Measures

The Profile of Functional Impairment in Communication (PFIC), Social Communication Skills Questionnaire–Adapted (SCSQ-A), Goal Attainment Scale (GAS), Craig Handicap Assessment and Reporting Technique–Short Form social integration and occupation subscales, Community Integration Questionnaire social integration and productivity subscales, and Satisfaction With Life Scale (SWLS).

Results

Independent samples t test analysis showed significant treatment effect compared with no treatment on 7 of 10 of the PFIC subscales (P range, .024 to <.001) and the SCSQ-A (P=.005) after the first 12 weeks of the study. After 12 weeks of treatment for all participants, repeated-measures analysis showed significant improvements from baseline on 9 of 10 PFIC subscales (P range, .01−.001), SCSQ-A (P≤.001), GAS (P≤.001), and SWLS (P=.011). At 6-month follow-up, scores were significantly better than baseline on 6 of 10 PFIC scales (P range, .01−.001), the SCSQ-A (P≤.001), GAS (P≤.001), and SWLS (P≤.001).

Conclusions

TBI subjects who received social communication skills training had improved communication skills that were maintained on follow-up. Overall life satisfaction for participants was improved.     

Comparison of detrending methods for optimal fMRI preprocessing

Because of the inherently low signal to noise ratio (SNR) of fMRI data, removal of low frequency signal intensity drift is an important preprocessing step, particularly in those brain regions that weakly activate. Two known sources of drift are noise from the MR scanner and aliasing of physiological pulsations. However, the amount and direction of drift is difficult to predict, even between neighboring voxels. Further, there is no concensus on an optimal baseline drift removal algorithm. In this paper, five voxel-based detrending techniques were compared to each other and an auto-detrending algorithm, which automatically selected the optimal method for a given voxel time-series. For a significance level of P < 10(-6), linear and quadratic detrending moderately increased the percentage of activated voxels. Cubic detrending decreased activation, while a wavelet approach increased or decreased activation, depending on the dataset. Spline detrending was the best single algorithm. However, auto-detrending (selecting the best algorithm or none, if detrending is not useful) appears to be the most judicious choice, particularly for analyzing fMRI data with weak activations in the presence of baseline drift.     

Adrenal gland injury due to gunshot

Adrenal gland trauma is a rare phenomenon, due to the small size and retroperitoneal location of the organ. The majority of adrenal gland trauma is due to blunt force injury and is only rarely encountered due to the penetrating mechanisms. A 20-year-old male sustained a gunshot wound to the left abdomen. Upon exploration, he was found to have a through and through injury to the left adrenal gland, among other injuries. Injury to the adrenal gland due to penetrating trauma is exceptionally rare. The principles of management are to control bleeding from the gland with debridement and hemostasis rather than attempt to resect the entire organ. The management of a penetrating injury to the adrenal gland is straightforward and should not be a contributor to a patient''s morbidity or mortality.     

Insect-Specific Flavivirus Replication in Mammalian Cells Is Inhibited by Physiological Temperature and the Zinc-Finger Antiviral Protein

The genus Flavivirus contains pathogenic vertebrate-infecting flaviviruses (VIFs) and insect-specific flaviviruses (ISF). ISF transmission to vertebrates is inhibited at multiple stages of the cellular infection cycle, via yet to be elucidated specific antiviral responses. The zinc-finger antiviral protein (ZAP) in vertebrate cells can bind CpG dinucleotides in viral RNA, limiting virus replication. Interestingly, the genomes of ISFs contain more CpG dinucleotides compared to VIFs. In this study, we investigated whether ZAP prevents two recently discovered lineage II ISFs, Binjari (BinJV) and Hidden Valley viruses (HVV) from replicating in vertebrate cells. BinJV protein and dsRNA replication intermediates were readily observed in human ZAP knockout cells when cultured at 34 °C. In ZAP-expressing cells, inhibition of the interferon response via interferon response factors 3/7 did not improve BinJV protein expression, whereas treatment with kinase inhibitor C16, known to reduce ZAP’s antiviral function, did. Importantly, at 34 °C, both BinJV and HVV successfully completed the infection cycle in human ZAP knockout cells evident from infectious progeny virus in the cell culture supernatant. Therefore, we identify vertebrate ZAP as an important barrier that protects vertebrate cells from ISF infection. This provides new insights into flavivirus evolution and the mechanisms associated with host switching.     

What Do Medical Students Do and Want When Caring for “Difficult Patients”?

Phenomenon: Medical students, like physicians, experience negative emotions such as frustration when interacting with some patients, and many of these interactions occur for the first time during clinical clerkships. Students receive preclinical training in the social and behavioral sciences, often including learning about “difficult patient” interactions, yet little is known about their desire for training during clinical education. We explored students’ strategies in these difficult clinical interactions, whether they felt prepared by the curriculum, and what support they would have liked. These data inform proposed strategies for supporting clinical learning. Approach: We interviewed 4th-year students about interactions with patients toward whom they felt negative emotions and sought to identify strategies and supports needed in these interactions. Interviews ended when theoretical sufficiency was achieved. We used qualitative content analysis to organize strategies into themes about areas benefiting from curricular supports. We mapped students’ desired curricular support examples to cognitive apprenticeship teaching methods—modeling, coaching, reflection, scaffolding, exploration, and articulation—and aligned them with traditional pedagogical techniques. Findings: We interviewed 26 medical students (44 volunteered/180 invited). Their strategies formed five themes: finding empathy (with a subtheme of focusing on social determinants of health), using learned communication approaches, anticipating challenging interactions, seeking support, and considering it an opportunity for more responsibility. Students described ideal clinical teaching, including postinteraction debriefs with an emphasis on validating their emotional reactions and challenges. Students mentioned all cognitive apprenticeship teaching methods, most prominently modeling (observing supervisors in such interactions) and supported oral reflection. They also identified a need for faculty and resident development to enact these teaching methods. Insights: Although students use some learned strategies in interactions in which they feel negative emotions toward patients, they desire more preparation and support during their clinical rotations. Their desires map to traditional pedagogical techniques and to methods of cognitive apprenticeship. Our findings point to the need to use these techniques to enhance clinical learning for students who experience emotionally challenging patient interactions.