Characterization of Telecare Conversations on Lifestyle Management and Their Relation to Health Care Utilization for Patients with Heart Failure: Mixed Methods Study.

BACKGROUND: Telehealth interventions where providers offer support and coaching to patients with chronic conditions such as heart failure (HF) and type 2 diabetes mellitus (T2DM) are effective in improving health outcomes. However, the understanding of the content and structure of these interactions and how they relate to health care utilization remains incomplete. OBJECTIVE: This study aimed to characterize the content and structure of telecare conversations on lifestyle management for patients with HF and investigate how these conversations relate to health care utilization. METHODS: We leveraged real-world data from 50 patients with HF enrolled in a postdischarge telehealth program, with the primary intervention comprising a series of telephone calls from nurse telecarers over a 12-month period. For the full cohort, we transcribed 729 English-language calls and annotated conversation topics. For a subcohort (25 patients with both HF and T2DM), we annotated lifestyle management content with fine-grained dialogue acts describing typical conversational structures. For each patient, we identified calls with unusually high ratios of utterances on lifestyle management as lifestyle-focused calls. We further extracted structured data for inpatient admissions from 6 months before to 6 months after the intervention period. First, to understand conversational structures and content of lifestyle-focused calls, we compared the number of utterances, dialogue acts, and symptom attributes in lifestyle-focused calls to those in calls containing but not focused on lifestyle management. Second, to understand the perspectives of nurse telecarers on these calls, we conducted an expert evaluation where 2 nurse telecarers judged levels of concern and follow-up actions for lifestyle-focused and other calls (not focused on lifestyle management content). Finally, we assessed how the number of lifestyle-focused calls relates to the number of admissions, and to the average length of stay per admission. RESULTS: In comparative analyses, lifestyle-focused calls had significantly fewer utterances (P=.01) and more dialogue acts (Padj=.005) than calls containing but not focused on lifestyle management. Lifestyle-focused calls did not contain deeper discussions on clinical symptoms. These findings indicate that lifestyle-focused calls entail short, intense discussions with greater emphasis on understanding patient experience and coaching than on clinical content. In the expert evaluation, nurse telecarers identified 24.2% (29/120) of calls assessed as concerning enough for follow-up. For these 29 calls, nurse telecarers were more attuned to concerns about symptoms and vitals (19/29, 65.5%) than lifestyle management concerns (4/29, 13.8%). The number of lifestyle-focused calls a patient had was modestly (but not significantly) associated with a lower average length of stay for inpatient admissions (Spearman ρ=-0.30; Padj=.06), but not with the number of admissions (Spearman ρ=-0.03; Padj=.84). CONCLUSIONS: Our approach and findings offer novel perspectives on the content, structure, and clinical associations of telehealth conversations on lifestyle management for patients with HF. Hence, our study could inform ways to enhance telehealth programs for self-care management in chronic conditions.

NeuroAiDTM-II (MLC901) Promoted Neurogenesis by Activating the PI3K/AKT/GSK-3ß Signaling Pathway in Rat Spinal Cord Injury Models.

Traumatic damage to the spinal cord (SCI) frequently leads to irreversible neurological deficits, which may be related to apoptotic neurodegeneration in nerve tissue. The MLC901 treatment possesses neuroprotective and neuroregenerative activity. This study aimed to explore the regenerative potential of MLC901 and the molecular mechanisms promoting neurogenesis and functional recovery after SCI in rats. A calibrated forceps compression injury for 15 s was used to induce SCI in rats, followed by an examination of the impacts of MLC901 on functional recovery. The Basso, Beattie, and Bresnahan (BBB) scores were utilized to assess neuronal functional recovery; H&E and immunohistochemistry (IHC) staining were also used to observe pathological changes in the lesion area. Somatosensory Evoked Potentials (SEPs) were measured using the Nicolet® Viking Quest™ apparatus. Additionally, we employed the Western blot assay to identify PI3K/AKT/GSK-3ß pathway-related proteins and to assess the levels of GAP-43 and GFAP through immunohistochemistry staining. The study findings revealed that MLC901 improved hind-limb motor function recovery, alleviating the pathological damage induced by SCI. Moreover, MLC901 significantly enhanced locomotor activity, SEPs waveform, latency, amplitude, and nerve conduction velocity. The treatment also promoted GAP-43 expression and reduced reactive astrocytes (GFAP). MLC901 treatment activated p-AKT reduced p-GSK-3ß expression levels and showed a normalized ratio (fold changes) relative to ß-tubulin. Specifically, p-AKT exhibited a 4-fold increase, while p-GSK-3ß showed a 2-fold decrease in T rats compared to UT rats. In conclusion, these results suggest that the treatment mitigates pathological tissue damage and effectively improves neural functional recovery following SCI, primarily by alleviating apoptosis and promoting neurogenesis. The underlying molecular mechanism of this treatment mainly involves the activation of the PI3K/AKT/GSK-3ß pathway.

A review of in vitro stochastic and non-stochastic affinity maturation strategies for phage display derived monoclonal antibodies.

Monoclonal antibodies identified using display technologies like phage display occasionally suffers from a lack of affinity making it unsuitable for application. This drawback is circumvented with the application of affinity maturation. Affinity maturation is an essential step in the natural evolution of antibodies in the immune system. The evolution of molecular based methods has seen the development of various mutagenesis approaches. This allows for the natural evolutionary process during somatic hypermutation to be replicated in the laboratories for affinity maturation to fine-tune the affinity and selectivity of antibodies. In this review, we will discuss affinity maturation strategies for mAbs generated through phage display systems. The review will highlight various in vitro stochastic and non-stochastic affinity maturation approaches that includes but are not limited to random mutagenesis, site-directed mutagenesis, and gene synthesis.

Single high-dose intravenous injection of Wharton's jelly-derived mesenchymal stem cell exerts protective effects in a rat model of metabolic syndrome.

BACKGROUND: Metabolic syndrome (MetS) is a significant epidemiological problem worldwide. It is a pre-morbid, chronic and low-grade inflammatory disorder that precedes many chronic diseases. Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs) could be used to treat MetS because they express high regenerative capacity, strong immunomodulatory properties and allogeneic biocompatibility. This study aims to investigate WJ-MSCs as a therapy against MetS in a rat model. METHODS: Twenty-four animals were fed with high-fat high-fructose (HFHF) diet ad libitum. After 16 weeks, the animals were randomised into treatment groups (n = 8/group) and received a single intravenous administration of vehicle, that is, 3 × 106 cells/kg or 10 × 106 cells/kg of WJ-MSCs. A healthy animal group (n = 6) fed with a normal diet received the same vehicle as the control (CTRL). All animals were periodically assessed (every 4 weeks) for physical measurements, serum biochemistry, glucose tolerance test, cardiovascular function test and whole-body composition. Post-euthanasia, organs were weighed and processed for histopathology. Serum was collected for C-reactive protein and inflammatory cytokine assay. RESULTS: The results between HFHF-treated groups and healthy or HFHF-CTRL did not achieve statistical significance (α = 0.05). The effects of WJ-MSCs were masked by the manifestation of different disease subclusters and continuous supplementation of HFHF diet. Based on secondary analysis, WJ-MSCs had major implications in improving cardiopulmonary morbidities. The lungs, liver and heart show significantly better histopathology in the WJ-MSC-treated groups than in the untreated CTRL group. The cells produced a dose-dependent effect (high dose lasted until week 8) in preventing further metabolic decay in MetS animals. CONCLUSIONS: The establishment of safety and therapeutic proof-of-concept encourages further studies by improving the current therapeutic model.

A Comparative Study for Blockchain Applications in Nursing Informatics.

We explored blockchain's applications in nursing informatics, highlighting its potential to improve patient care and data management. We compared and analyzed eight studies focusing on blockchain in Electronic Health Records (EHR) management, nursing optimization, and research facilitation. Although most of these studies are in the proposal stage, blockchain's technical features show promise in enhancing nursing practices and supporting nursing informatics researchers with the integration of technologies.

Review of phage display: A jack-of-all-trades and master of most biomolecule display.

Phage display was first described by George P. Smith when it was shown that virus particles were capable of presenting foreign proteins on their surface. The technology has paved the way for the evolution of various biomolecules presentation and diverse selection strategies. This unique feature has been applied as a versatile platform for numerous applications in drug discovery, protein engineering, diagnostics, and vaccine development. Over the decades, the limits of biomolecules displayed on phage particles have expanded from peptides to proteomes and even alternative scaffolds. This has allowed phage display to be viewed as a versatile display platform to accommodate various biomolecules ranging from small peptides to larger proteomes which has significantly impacted advancements in the biomedical industry. This review will explore the vast array of biomolecules that have been successfully employed in phage display technology in biomedical research.

Streptavidin-Coated Solid-Phase Extraction (SPE) Tips for Antibody Phage Display Biopanning.

Phage display is a technique that allows the presentation of unique proteins on the surface of bacteriophages. The phage particles are usually screened via repetitive rounds of antigen-guided selection and phage amplification. The main advantage of this approach lies in the physical linkage between phenotype and genotype. This feature allows the isolation of single unique clones from a panning campaign consisting of a highly diverse population of clones. Due to the high-throughput nature of this technique, different approaches have been developed to assist phage display selections. One of which involves utilizing a streptavidin-coated solid-phase extraction (SPE) tip that is mounted to an electronically controlled motorized multichannel pipette. In this chapter, we will entail the procedures involved in the adaptation of a commercial SPE tip (MSIA™ streptavidin D.A.R.T's®) as the solid phase. This protocol is an updated version of a previous protocol with some minor refinements.

Magnetic Nanoparticle-Based Semi-automated Panning for High-Throughput Antibody Selection.

Bio-panning is a common process involved in recombinant antibody selection against defined targets. The biopanning process aims to isolate specific antibodies against an antigen via affinity selection from a phage display library. In general, antigens are immobilized on solid surfaces such as polystyrene plastic, magnetic beads, and nitrocellulose. For high-throughput selection, semi-automated panning selection allows simultaneous panning against multiple target antigens adapting automated particle processing systems such as the KingFisher Flex. The system setup allows for minimal human intervention for pre- and post-panning steps such as antigen immobilization, phage rescue, and amplification. In addition, the platform is also adaptable to perform polyclonal and monoclonal ELISA for the evaluation process. This chapter will detail the protocols involved from the selection stage until the monoclonal ELISA evaluation with important notes attached at the end of this chapter for optimization and troubleshooting purposes.

Subtractive panning for the isolation of monoclonal PEPITEM peptide antibody by phage display.

Antibody phage display is a key tool for the development of monoclonal antibodies against various targets. However, the development of anti-peptide antibodies is a challenging process due to the small size of peptides for binding. This makes anchoring of peptides a preferred approach for panning experiments. A common approach is by using streptavidin as the anchor protein to present biotinylated peptides for panning. Here, we propose the use of recombinant expression of the target peptide and an immunogenic protein as a fusion for panning. The peptide inhibitor of trans-endothelial migration (PEPITEM) peptide sequence was fused to the Mycobacterium tuberculosis (Mtb) α-crystalline (AC) as an anchor protein. The panning process was carried out by subtractive selection of the antibody library against the AC protein first, followed by binding to the library to PEPITEM fused AC (PEPI-AC). A unique monoclonal scFv antibodies with good specificity were identified. In conclusion, the use of an alternative anchor protein to present the peptide sequence coupled with subtractive panning allows for the identification of unique monoclonal antibodies against a peptide target.

Risk analysis of the Unity 1.5 T MR-Linac adapt-to-position workflow.

BACKGROUND AND PURPOSE: Newer technologies allow for daily treatment adaptation, providing the ability to account for setup variations and organ motion but comes at the cost of increasing the treatment workflow complexity. One such technology is the adapt-to-position (ATP) workflow on the Unity MR-Linac. Prospective risk assessment of a new workflow allows clinics to catch errors before they occur, especially for processes that include novel and unfamiliar steps. METHODS: As part of a quality management program, failure modes and effects analysis was performed on the ATP treatment workflow following the recommendations of AAPM's Task Group 100. A multidisciplinary team was formed to identify and evaluate failure modes for all the steps taken during a daily treatment workflow. Failure modes of high severity and overall score were isolated and addressed. RESULTS: Mitigations were determined for high-ranking failure modes and implemented into the clinic. High-ranking failure modes existed in all steps of the workflow. Failure modes were then rescored to evaluate the effectiveness of the mitigations. CONCLUSION: Failure modes and effects analysis on the Unity MR-Linac highlighted areas in the ATP workflow that could be prone to failures and allowed our clinic to change the process to be more robust.

External validation of pulmonary radiotherapy toxicity models for ultracentral lung tumors.

Introduction: Pulmonary toxicity is dose-limiting in stereotactic body radiation therapy (SBRT) for tumors that abut the proximal bronchial tree (PBT), esophagus, or other mediastinal structures. In this work we explored published models of pulmonary toxicity following SBRT for such ultracentral tumors in an independent cohort of patients. Methods: The PubMed database was searched for pulmonary toxicity models. Identified models were tested in a cohort of patients with ultracentral lung tumors treated between 2008 and 2017 at one large center (N = 88). This cohort included 60 % primary and 40 % metastatic tumors treated to 45 Gy in 5 fractions (fx), 50 Gy in 5 fx, 60 Gy in 8 fx, or 60 Gy in 15 fx prescribed as 100 % dose to PTV. Results: Seven published NTCP models from two studies were identified. The NTCP models utilized PBT max point dose (Dmax), D0.2 cm3, V65, V100, and V130. Within the independent cohort, the ≥ grade 3 toxicity and grade 5 toxicity rates were 18 % and 7-10 %, respectively, and the Dmax models best described pulmonary toxicity. The Dmax to 0.1 cm3 model was better calibrated and had increased steepness compared to the Dmax model. A re-planning study minimizing PBT 0.1 cm3 to below 122 Gy in EQD23 (for a 10 % ≥grade 3 pulmonary toxicity) was demonstrated to be completely feasible in 4/6 patients, and dose to PBT 0.1 cm3 was considerably lowered in all six patients. Conclusions: Pulmonary toxicity models were identified from two studies and explored within an independent ultracentral lung tumor cohort. A modified Dmax to 0.1 cm3 PBT model displayed the best performance. This model could be utilized as a starting point for rationally constructed airways constraints in ultracentral patients treated with SBRT or hypofractionation.

Efficacy and safety of small extracellular vesicle interventions in wound healing and skin regeneration: A systematic review and meta-analysis of animal studies.

Small extracellular vesicles (sEVs) have been proposed as a possible solution to the current lack of therapeutic interventions for endogenous skin regeneration. We conducted a systematic review of the available evidence to assess sEV therapeutic efficacy and safety in wound healing and skin regeneration in animal models. 68 studies were identified in Web of Science, Scopus, and PubMed that satisfied a set of prespecified inclusion criteria. We critically analyzed the quality of studies that satisfied our inclusion criteria, with an emphasis on methodology, reporting, and adherence to relevant guidelines (including MISEV2018 and ISCT criteria). Overall, our systematic review and meta-analysis indicated that sEV interventions promoted skin regeneration in diabetic and non-diabetic animal models and influenced various facets of the healing process regardless of cell source, production protocol and disease model. The EV source, isolation methods, dosing regimen, and wound size varied among the studies. Modification of sEVs was achieved mainly by manipulating source cells via preconditioning, nanoparticle loading, genetic manipulation, and biomaterial incorporation to enhance sEV therapeutic potential. Evaluation of potential adverse effects received only minimal attention, although none of the studies reported harmful events. Risk of bias as assessed by the SYRCLE's ROB tool was uncertain for most studies due to insufficient reporting, and adherence to guidelines was limited. In summary, sEV therapy has enormous potential for wound healing and skin regeneration. However, reproducibility and comprehensive evaluation of evidence are challenged by a general lack of transparency in reporting and adherence to guidelines. Methodological rigor, standardization, and risk analysis at all stages of research are needed to promote translation to clinical practice.

Antimicrobial antibodies by phage display: Identification of antibody-based inhibitor against mycobacterium tuberculosis isocitrate lyase.

The increasing incidence reports of antibiotic resistance highlights the need for alternative approaches to deal with bacterial infections. This brought about the idea of utilizing monoclonal antibodies as an alternative antibacterial treatment. Majority of the studies are focused on developing antibodies to bacterial surface antigens, with little emphasis on antibodies that inhibit the growth mechanisms of a bacteria host. Isocitrate lyase (ICL) is an important enzyme for the growth and survival of Mycobacterium tuberculosis (MTB) during latent infection as a result of its involvement in the mycobacterial glyoxylate and methylisocitrate cycles. It is postulated that the inhibition of ICL can disrupt the life cycle of MTB. To this extent, we utilized antibody phage display to identify a single chain fragment variable (scFv) antibody against the recombinant ICL protein from MTB. The soluble a-ICL-C6 scFv clone exhibited good binding characteristics with high specificity against ICL. More importantly, the clone exhibited in vitro inhibitory effect with an enzymatic assay resulting in a decrease of ICL enzymatic activity. In silico analysis showed that the scFv-ICL interactions are driven by 23 hydrogen bonds and 13 salt bridges that might disrupt the formation of ICL subunits for the tertiary structure or the formation of active site ß domain. However, further validation is necessary to confirm if the isolated clone is indeed a good inhibitor against ICL for application against MTB.

Safety study of allogeneic mesenchymal stem cell therapy in animal model.

Intravenous (IV) infusion of mesenchymal stem cells (MSCs) from nascent tissues like Wharton's Jelly of the umbilical cord is reported to offer therapeutic effects against chronic diseases. However, toxicological data essential for the clinical application of these cells are limited. Thus, this study aimed to determine the safety of IV infusion of Wharton's Jelly derived MSCs (WJ-MSCs) in rats. Fifteen male Sprague-Dawley rats were randomised into the control or treatment group. Each group received an equal volume of saline or WJ-MSC (10 × 106 cell/kg) respectively. The animals were evaluated for physical, biochemical and haematological changes at Week 0, 2, 4, 8 and 12 during the 12-week study. Acute toxicity was performed during Week 2 and sub-chronic toxicity during Week 12. At the end of the study, the relative weight of organs was calculated and histology was performed for lung, liver, spleen and kidney. The findings from physical, serum biochemistry and complete blood count demonstrated no statistically significant differences between groups. However, pathological evaluation reported minor inflammation in the lungs for all groups, but visible healing and resolution of inflammation were observed in the treatment group only. Additionally, the histological images of the treatment group had significantly improved pulmonary structures compared to the control group. In summary, the IV administration of WJ-MSC was safe in the rats. Further studies are needed to determine the long-term safety of the WJ-MSC in both healthy and diseased animal models.

Low dietary diversity is associated with linear growth faltering and subsequent adverse child developmental outcomes in rural Democratic Republic of the Congo (REDUCE program).

The objective of this study was to investigate the association between dietary diversity, child growth and child developmental outcomes. This was a prospective cohort study. Developmental outcomes were assessed by communication, fine motor, gross motor, personal social, problem solving and combined developmental scores measured by the Extended Ages and Stages Questionnaire (EASQ) at a 6-month follow-up visit. Height and weight were measured at baseline and a 6-month follow-up. Baseline minimum dietary diversity (MDD) for children 6-23 months old was defined by consumption of five or more of the following food groups: (1) breast milk; (2) grains, roots and tubers; (3) legumes and nuts; (4) dairy products; (5) flesh foods; (6) eggs; (7) vitamin A-rich fruits and vegetables and (8) other fruits and vegetables. Participants were 117 children 6-23 months of age. Linear growth faltering was defined as a significant decline (p < 0.05) in length-for-age Z-scores (LAZ) between baseline and follow-up. Regression models were performed. The study was conducted in rural eastern Democratic Republic of the Congo (DRC). MDD was positively associated with change in LAZ (coefficient: 0.87 [95% confidence interval [CI]: 0.33, 1.40]), and a reduced odds of stunting (LAZ < -2) (odds ratio: 0.21 [95% CI: 0.07, 0.61]). MDD was also associated with a significantly higher combined EASQ-Z-scores (coefficient: 0.34 [95% CI: 0.003, 0.68], higher communication EASQ-Z-scores [0.50 {95% CI: 0.14, 0.85}], and higher personal social EASQ-Z-scores [0.46 {95% CI: 0.11, 0.82}]). This study provides further evidence demonstrating the need for interventions to improve dietary diversity among young children.

Assessing the reliability of phone surveys to measure reproductive, maternal and child health knowledge among pregnant women in rural India: a feasibility study.

OBJECTIVES: Efforts to understand the factors influencing the uptake of reproductive, maternal, newborn, child health and nutrition (RMNCH&N) services in high disease burden low-resource settings have often focused on face-to-face surveys or direct observations of service delivery. Increasing access to mobile phones has led to growing interest in phone surveys as a rapid, low-cost alternatives to face-to-face surveys. We assess determinants of RMNCH&N knowledge among pregnant women with access to phones and examine the reliability of alternative modalities of survey delivery. PARTICIPANTS: Women 5-7 months pregnant with access to a phone. SETTING: Four districts of Madhya Pradesh, India. DESIGN: Cross-sectional surveys administered face-to-face and within 2 weeks, the same surveys were repeated among two random subsamples of the original sample: face-to-face (n=205) and caller-attended telephone interviews (n=375). Bivariate analyses, multivariable linear regression, and prevalence and bias-adjusted kappa scores are presented. RESULTS: Knowledge scores were low across domains: 52% for maternal nutrition and pregnancy danger signs, 58% for family planning, 47% for essential newborn care, 56% infant and young child feeding, and 58% for infant and young child care. Higher knowledge (≥1 composite score) was associated with older age; higher levels of education and literacy; living in a nuclear family; primary health decision-making; greater attendance in antenatal care and satisfaction with accredited social health activist services. Survey questions had low inter-rater and intermodal reliability (kappa<0.70) with a few exceptions. Questions with the lowest reliability included true/false questions and those with unprompted, multiple response options. Reliability may have been hampered by the sensitivity of the content, lack of privacy, enumerators' and respondents' profile differences, rapport, social desirability bias, and/or enumerator's ability to adequately convey concepts or probe. CONCLUSIONS: Phone surveys are a reliable modality for generating population-level estimates data about pregnant women's knowledge, however, should not be used for individual-level tracking. TRIAL REGISTRATION NUMBER: NCT03576157.

Synovial fluid proteome profile of surgical versus chemical induced osteoarthritis in rabbits.

BACKGROUND: Animal models are significant for understanding human osteoarthritis (OA). This study compared the synovial fluid proteomics changes in surgical and chemical induced OA models. METHODS: Thirty rabbits either had anterior cruciate ligament transection (ACLT) procedure or injected intra-articularly with monosodium iodoacetate (MIA, 8 mg) into the right knee. The joints were anatomically assessed, and the synovial fluid proteins analyzed using two-dimensional polyacrylamide gel electrophoresis (2DGE) and MALDI TOF/TOF mass spectrometry analysis at 4, 8 and 12 weeks. The proteins' upregulation and downregulation were compared with control healthy knees. RESULTS: Seven proteins (histidine-rich glycoprotein, beta-actin-like protein 2 isoform X1, retinol-binding protein-4, alpha-1-antiproteinase, gelsolin isoform, serotransferrin, immunoglobulin kappa-b4 chain-C-region) were significantly expressed by the surgical induction. They characterized cellular process (27%), organization of cellular components or biogenesis (27%), localization (27%) and biological regulation (18%), which related to synovitis, increased cellularity, and subsequently cartilage damage. Three proteins (apolipoprotein I-IV precursor, serpin peptidase inhibitor and haptoglobin precursor) were significantly modified by the chemical induction. They characterized stimulus responses (23%), immune responses (15%), biological regulations (15%), metabolism (15%), organization of cellular components or biogenesis (8%), cellular process (8%), biological adhesions (8%) and localization (8%), which related to chondrocytes glycolysis/death, neovascularization, subchondral bone necrosis/collapse and inflammation. CONCLUSIONS: The surgical induced OA model showed a wider range of protein changes, which were most upregulated at week 12. The biological process proteins expressions showed the chemical induced joints had slower OA progression compared to surgical induced joints. The chemical induced OA joints showed early inflammatory changes, which later decreased.

Fecal Contamination in Child Play Spaces and on Child Hands Are Associated with Subsequent Adverse Child Developmental Outcomes in Rural Democratic Republic of the Congo: REDUCE Prospective Cohort Study.

The objective of the Reducing Enteropathy, Undernutrition, and Contamination in the Environment (REDUCE) program is to identify exposure pathways to fecal pathogens that are significant contributors to morbidity among young children in the Democratic Republic of the Congo (DRC), and on developing and evaluating scalable interventions to reduce fecal contamination from these pathways. This prospective cohort study of 270 children under 5 years of age was conducted in rural South Kivu, DRC, to investigate the association between Escherichia coli in hand rinse, soil, food, object, surface, stored water, and water source samples and child developmental outcomes. Child developmental outcomes were assessed by communication, fine motor, gross motor, personal social, problem-solving, and combined scores measured by the Extended Ages and Stages Questionnaire (EASQ) at a 6-month follow-up. Children having E. coli present in the soil in their play spaces had significantly lower combined EASQ z scores (coefficient: -0.38 (95% CI: -0.73, -0.03)). E. coli on children's hands was associated with lower communication EASQ z scores (-0.37 (95% CI: -0.0.10, -0.01), and E. coli in stored drinking water was associated with lower gross motor EASQ z scores (-0.40 (95% CI: -0.68, -0.12). In the REDUCE cohort study, E. coli in child play spaces, on children's hands, and in stored drinking water was associated with lower developmental outcome scores (communication, gross motor, fine motor, and problem-solving skills). These results suggest the need for interventions to reduce fecal contamination in the household environment to protect the cognitive development of susceptible pediatric populations in rural DRC.

Application of phage display for T-cell receptor discovery.

The immune system is tasked to keep our body unharmed and healthy. In the immune system, B- and T-lymphocytes are the two main components working together to stop and eliminate invading threats like virus particles, bacteria, fungi and parasite from attacking our healthy cells. The function of antibodies is relatively more direct in target recognition as compared to T-cell receptors (TCR) which recognizes antigenic peptides being presented on the major histocompatibility complex (MHC). Although phage display has been widely applied for antibody presentation, this is the opposite in the case of TCR. The cell surface TCR is a relatively large and complex molecule, making presentation on phage surfaces challenging. Even so, recombinant versions and modifications have been introduced to allow the growing development of TCR in phage display. In addition, the increasing application of TCR for immunotherapy has made it an important binding motif to be developed by phage display. This review will emphasize on the application of phage display for TCR discovery as well as the engineering aspect of TCR for improved characteristics.