Transmission-reducing and -enhancing monoclonal antibodies against Plasmodium vivax gamete surface protein Pvs48/45.

Gamete surface protein P48/45 has been shown to be important for male gamete fertility and a strong candidate for the development of a malaria transmission-blocking vaccine (TBV). However, TBV development for Plasmodium vivax homolog Pvs48/45 has been slow because of a number of challenges: availability of conformationally suitable recombinant protein; the lack of an in vivo challenge model; and the inability to produce P. vivax gametocytes in culture to test transmission-blocking activity of antibodies. To support ongoing efforts to develop Pvs48/45 as a potential vaccine candidate, we initiated efforts to develop much needed reagents to move the field forward. We generated monoclonal antibodies (mAbs) directed against Pvs48/45 and characterized putative functional domains in Pvs48/45 using recombinant fragments corresponding to domains D1-D3 and their biological functionality through ex vivo direct membrane feeding assays (DMFAs) using P. vivax parasites from patients in a field setting in Brazil. While some mAbs partially blocked oocyst development in the DMFA, one mAb caused a significant enhancement of the infectivity of gametocytes in the mosquitoes. Individual mAbs exhibiting blocking and enhancing activities recognized non-overlapping epitopes in Pvs48/45. Further characterization of precise epitopes recognized by transmission-reducing and -enhancing antibodies will be crucial to design an effective immunogen with optimum transmission-reducing potential.

Relationships of the very low birth weight infant microbiome with neurodevelopment at 2 and 4 years of age.

Very low birth weight (VLBW) infants (<1500 g) are at risk for poor neurodevelopmental outcomes depending on gestational age (GA), birth weight (BW), and morbidity in early life. The contribution of the gut microbiome is not well understood. Stool samples were collected weekly in the neonatal intensive care unit (NICU) from 24 VLBW infants for 6 weeks after admission and then again at 2 and 4 years of age. The Battelle Development Inventory-2 Screening Test (BDI-2 ST) was administered at 2- and 4-year time points. VLBW infants had dysbiotic microbiota in the NICU that progressed for most to an adult-type microbiota by 4 years of age. The BDI-2 ST results at age of 2 years triggered referral for further testing in 14 toddlers (70%), and by 4 years of age only seven of these 14 continued to require referral. Both NICU infant stool diversity and particular microbial amplicon sequence variants were associated with BDI-2 ST subscales, particularly for cognition, adaptive, and communication subscales, when controlled for GA, BW, and antibiotic exposure. Network analysis of the NICU infant stool microbial ecology showed differences in children needing neurodevelopmental referral. The results of this preliminary study indicate that the neonatal gut microbiome plays a role in early cognitive and behavioral neurodevelopment.

Pulmonary Crohn's Disease Masquerading as Lymphoma.

Although extraintestinal manifestations of inflammatory bowel disease (IBD) are common, pulmonary IBD is extremely rare. Owing to its nonspecific clinical, radiologic, and pathologic features, pulmonary IBD is difficult to diagnose and may mimic more concerning disease processes. We present a rare case of a patient with known Crohn's disease whose initial presentation was highly suspicious for malignancy before further investigation revealed pulmonary IBD.

A randomized controlled clinical trial to improve health outcomes in youth with type 1 diabetes: Study design and baseline characteristics.

Most adolescents with T1D do not meet glycemic recommendations or consistently perform the required self-management behaviors to prevent acute- and long-term deleterious health outcomes. In addition, most youth with T1D do not have access to behavioral health services to address T1D management barriers. Thus, delivering behavioral interventions during routine medical appointments may hold promise for improving T1D outcomes in adolescents. The overall objective of this study was to examine the effect of behavioral interventions, either a Personalized T1D Self-Management Behaviors Feedback Report or Problem-Solving Skills, delivered by a T1D behavioral health provider and a T1D medical provider during a joint, fully integrated appointment to improve health outcomes in youth with T1D. This paper describes the study rationale, design, and baseline characteristics for the 109 adolescent-caregiver dyads who participated. Primary and secondary outcomes include hemoglobin A1c (A1C), T1D self-management behaviors, and biological indicators of complications.

Populism vs. elitism: social consensus and social status as bases of attitude certainty.

This study examined the effects of social consensus and social status on attitude certainty that is conceptualized multi-dimensionally as perceived clarity and correctness of one's attitude. In a mock opinion exchange about a social issue, participants were either supported (high consensus) or opposed (low consensus) by most of the confederates. They were informed that their opinion (high status) or their opponents' opinion (low status) had the alleged psychological significance indicative of future success. Post-experimental attitude clarity was significantly greater when attitudinal position was associated with high rather than low status. Attitude correctness was interactively affected by social status and social consensus. Supporting the compensatory effect hypothesis, attitude correctness was comparable across the levels of social consensus as long as they were associated with high status, and across the levels of social status as long as they were associated with high social consensus.

Whole slide imaging and colorectal carcinoma: A validation study for tumor budding and stromal differentiation.

Whole slide imaging (WSI) has recently received FDA approval for sign out in surgical pathology and some anticipate this to mature into the gold standard. During this transition, it will be important to validate WSI for its intended use. And many studies have validated whole slide imaging by comparing diagnostic accuracy with that of conventual light microscopy (CLM); however, the assessment of histopathologic markers is prone to much more discrepancy. One of the best examples being tumor-bud scoring in colorectal carcinoma. Other signatures, including stromal differentiation or desmoplastic reaction; could better represent the epithelial-mesenchymal transition. The findings in our study suggest stromal differentiation on both digital and glass slides to be much more reproducible (0.3585-0.9368) when compared to tumor budding (0.0968-0.7871). When comparing interobserver variation between glass and digital slides for three observers; stromal differentiation was more reliable on glass slides (0.4492), when compared to its digital counterpart (0.3016). On the other hand, interobserver variation for tumor bud scoring was more reliable on digital (0.1661), than glass slides (0.1026). Overall, there is significant variation between different observers and reproducibility issues present on conventual light microscopy transfer to digital slides. Although it is possible that too much emphasis is being placed on the concordance of WSI with CLM. In future, applications in artificial intelligence may be key to diagnostic precision and improved patient outcomes.

Sources of stress for students in high school college preparatory and general education programs: group differences and associations with adjustment.

Navigating puberty while developing independent living skills may render adolescents particularly vulnerable to stress, which may ultimately contribute to mental health problems (Compas, Orosan, & Grant, 1993; Elgar, Arlett, & Groves, 2003). The academic transition to high school presents additional challenges as youth are required to interact with a new and larger peer group and manage greater academic expectations. For students enrolled in academically rigorous college preparatory programs, such as the International Baccalaureate (IB) program, the amount of stress perceived may be greater than typical (Suldo, Shaunessy, & Hardesty, 2008). This study investigated the environmental stressors and psychological adjustment of 162 students participating in the IB program and a comparison sample of 157 students in general education. Factor analysis indicated students experience 7 primary categories of stressors, which were examined in relation to students' adjustment specific to academic and psychological functioning. The primary source of stress experienced by IB students was related to academic requirements. In contrast, students in the general education program indicated higher levels of stressors associated with parent-child relations, academic struggles, conflict within family, and peer relations, as well as role transitions and societal problems. Comparisons of correlations between categories of stressors and students' adjustment by curriculum group reveal that students in the IB program reported more symptoms of psychopathology and reduced academic functioning as they experienced higher levels of stress, particularly stressors associated with academic requirements, transitions and societal problems, academic struggles, and extra-curricular activities. Applied implications stem from findings suggesting that students in college preparatory programs are more likely to (a) experience elevated stress related to academic demands as opposed to more typical adolescent concerns, and (b) manifest worse outcomes in the face of stress.