Mapping B-cell epitopes of major and minor peanut allergens and identifying residues contributing to IgE binding.

BACKGROUND: Epitope identification provides valuable information essential for understanding antigen components involved in food allergic reactions. In the present study, an in silico approach is employed to map IgE binding epitopes of major and minor peanut allergens. RESULTS: B-cell epitopes were identified for peanut (Arachis hypogaea) allergens, namely Ara h 5, 6, 7, 8, 9, 10 and 11. A total of 10 web servers were used in the study and 26 linear and 18 conformational epitopes were predicted by a combination of methods. The majority of the predicted B-cell residues were present in the coil regions and the highest percentage of hydrophilic residues were observed for Ara h 6 (70.49%). The absolute solvent accessibility for all the B-cell epitopes was >70%, indicating antibody recognition. The property distance index assessed for the predicted epitopes using SDAP showed that six linear epitopes shared similarity with soybean, hazelnut, tomato, maize, apple and banana allergens. CONCLUSION: These findings suggest that the identified regions may share cross-reactivity with some of the known food allergens or may act as novel antigenic determinants. Further, B-cell epitopes of Ara h 1, 2 and 3 identified by in silico methods correlated well with the experimentally identified regions.

One in four individuals of African-American ancestry harbors a 5.5kb deletion at chromosome 11q13.1.

Cloning and sequencing of 5.5 kb deletion at chromosome 11q13.1 from the HeLa cells, tumorigenic hybrids and two fibroblast cell lines have revealed homologous recombination between AluSx and AluY resulting in the deletion of intervening sequences. Long-range PCR of the 5.5 kb sequence in 494 normal lymphocyte samples showed heterozygous deletion in 28.3% of African-American ancestry samples but only in 4.8% of Caucasian samples (p<0.0001). This observation is strengthened by the copy number variation (CNV) data of the HapMap samples which showed that this deletion occurs in 27% of YRI (Yoruba--West African) population but none in non-African populations. The HapMap analysis further identified strong linkage disequilibrium between 5 single nucleotide polymorphisms and the 5.5 kb deletion in people of African ancestry. Computational analysis of 175 kb sequence surrounding the deletion site revealed enhanced flexibility, low thermodynamic stability, high repetitiveness, and stable stem-loop/hairpin secondary structures that are hallmarks of common fragile sites.

Adolescent health literacy and the Internet: challenges and opportunities.

PURPOSE OF REVIEW: Adolescents have increasingly turned to the Internet as a resource for insight into their health questions and concerns. However, the extent to which adolescents will benefit from using the Internet as a source for health information will be determined in great part by their level of media literacy and health literacy. The purpose of this review is to explore challenges that adolescents face when using the Internet to access health information and opportunities for intervention. RECENT FINDINGS: Adolescents must be able to access, understand, analyze, and evaluate health information on the Internet and then apply this information to make appropriate health decisions. Challenges faced by adolescents fall into the realm of functional literacy (e.g., not being able to spell a medical term needed in a search), critical literacy (e.g., not being able to differentiate accurate from inaccurate online health information), and, lastly, interactive literacy (e.g., translating online health information to appropriate health behaviors). SUMMARY: More research is needed in this field to better understand the challenges and to propose effective solutions. However, a multifaceted approach that engages policymakers, educators, healthcare providers, online health information providers, and parents may be positioned to make the largest impact.

What is appropriate to post on social media? Ratings from students, faculty members and the public.

OBJECTIVES: The purpose of this study was to ascertain what medical students, doctors and the public felt was unprofessional for medical students, as future doctors, to post on a social media site, Facebook(®) . The significance of this is that unprofessional content reflects poorly on a student, which in turn can significantly affect a patient's confidence in that student's clinical abilities. METHODS: An online survey was designed to investigate the perceptions of University of Michigan medical students, attending physicians and non-health care university-wide employees (that serves as a subset of the public) regarding mock medical students' Facebook(®) profile screenshots. For each screenshot, respondents used a 5-point Likert scale to rate 'appropriateness' and whether they would be 'comfortable' having students posting such content as their future doctors. RESULTS: Compared with medical students, faculty members and public groups rated images as significantly less appropriate (p < 0.001) and indicated that they would be less comfortable (p < 0.001) having posting students as future doctors. All three groups rated screenshots containing derogatory or private information about patients, followed by images suggesting marijuana use, as least appropriate. Images conveying intimate heterosexual couples were rated as most appropriate. Overall, the doctor group, females and older individuals were less permissive when compared with employee and student groups, males and younger individuals, respectively. CONCLUSIONS: The most significant conclusion of our study is that faculty members, medical students and the 'public' have different thresholds of what is acceptable on a social networking site. Our findings will prove useful for students to consider the perspectives of patients and faculty members when considering what type of content to post on their social media sites. In this way, we hope that our findings provide insight for discussions, awareness and the development of guidelines related to online professionalism for medical students.

Medication adherence and heart failure.

Heart failure remains among the most prevalent and burdensome medical conditions in the United States. With increasing awareness regarding resource use and costs of care, there has been significant interest in the identification of factors that influence rates of hospitalization and readmission in individuals with heart failure. Medication adherence has been identified as one such modifiable factor. Many barriers to medication adherence have been identified and include factors related to the patient, those related to their medical condition, their medical regimen, the healthcare system and others that are social and socioeconomic in nature. Identification of these barriers has led to novel interventions for improving medication adherence with the goal of improving the care of individuals with heart failure.

Tunable Q-factor wavelet transform based identification of diabetic patients using ECG signals.

Diabetes is a chronic health condition that is characterized by increased levels of glucose (sugar) in the blood. It can have harmful effects on different parts of the body, such as the retina of the eyes, skin, nervous system, kidneys, and heart. Diabetes affects the structure of electrocardiogram (ECG) impulses by causing cardiovascular autonomic dysfunction. Multi-resolution analysis of the input ECG signal is utilized in this paper to develop a machine learning-based system for the automated detection of diabetic patients. In the first step, the input ECG signal is decomposed into sub-bands utilizing the tunable Q-factor wavelet transform (TQWT) technique. In the second step, four entropy-based characteristics are evaluated from each SB and elected using the K-W test method. To develop an automatic diabetes detection system, selected features are given as input with 10-fold validation to a SVM classifier using various kernel functions. The 3rd sub-band of TQWT with the Coarse Gaussian kernel function kernel of the SVM classifier yields a classification accuracy of 91.5%. In the same dataset, the comparative analysis demonstrates that the proposed method outperforms other existing methods.

Analysis and Prediction of Pathogen Nucleic Acid Specificity for Toll-like Receptors in Vertebrates.

Identification of key sequence, expression and function related features of nucleic acid-sensing host proteins is of fundamental importance to understand the dynamics of pathogen-specific host responses. To meet this objective, we considered toll-like receptors (TLRs), a representative class of membrane-bound sensor proteins, from 17 vertebrate species covering mammals, birds, reptiles, amphibians, and fishes in this comparative study. We identified the molecular signatures of host TLRs that are responsible for sensing pathogen nucleic acids or other pathogen-associated molecular patterns (PAMPs), and potentially play important roles in host defence mechanism. Interestingly, our findings reveal that such host-specific features are directly related to the strand (single or double) specificity of nucleic acid from pathogens. However, during host-pathogen interactions, such features were unable to explain the pathogenic PAMP (i.e., DNA, RNA or other) selectivity, suggesting a more complex mechanism. Using these features, we developed a number of machine learning models, of which Random Forest achieved a high performance (94.57% accuracy) to predict strand specificity of TLRs from protein-derived features. We applied the trained model to propose strand specificity of some previously uncharacterized distinct fish-specific novel TLRs (TLR18, TLR23, TLR24, TLR25, TLR27).

Internal medicine house officers' attitudes and experience with patients who overstep patient-physician boundaries.

Maintenance of appropriate social boundaries is an essential aspect of patient care. Given limited clinical experience, house officers may be especially vulnerable to such transgressions. We studied the frequency of patients' transgressions of boundaries and house officer responses to these transgressions. An online survey was administered to internal medicine house officers at the University of Michigan Health System that addressed the frequency of patient-physician boundary transgressions, house officer responses to transgressions, and the perceived need for education regarding transgressions. The frequency of reported patient transgressions of various boundaries during the past 6 months ranged from 0 to more than 30. The most common reported incident was being called by their first name, and the least common incidents included patients engaging/attempting to engage in sexual contact and attempting to give expensive gifts. Most respondents denied the need for education regarding appropriate boundaries with patients; however, most perceived a need for training on how to respond to transgressions. Overall, there was a wide range in reported frequencies of transgressions. The frequency of transgressions reported by house officers was greater than what is previously described for attending physicians though their responses to transgressions were similar.

Host-pathogen protein-nucleic acid interactions: A comprehensive review.

Recognition of pathogen-derived nucleic acids by host cells is an effective host strategy to detect pathogenic invasion and trigger immune responses. In the context of pathogen-specific pharmacology, there is a growing interest in mapping the interactions between pathogen-derived nucleic acids and host proteins. Insight into the principles of the structural and immunological mechanisms underlying such interactions and their roles in host defense is necessary to guide therapeutic intervention. Here, we discuss the newest advances in studies of molecular interactions involving pathogen nucleic acids and host factors, including their drug design, molecular structure and specific patterns. We observed that two groups of nucleic acid recognizing molecules, Toll-like receptors (TLRs) and the cytoplasmic retinoic acid-inducible gene (RIG)-I-like receptors (RLRs) form the backbone of host responses to pathogen nucleic acids, with additional support provided by absent in melanoma 2 (AIM2) and DNA-dependent activator of Interferons (IFNs)-regulatory factors (DAI) like cytosolic activity. We review the structural, immunological, and other biological aspects of these representative groups of molecules, especially in terms of their target specificity and affinity and challenges in leveraging host-pathogen protein-nucleic acid interactions (HP-PNI) in drug discovery.

Unraveling molecular mechanisms of head and neck cancer.

Malignancies that develop from mucosal epithelium of the upper aerodigestive tract are known as head and neck squamous cell carcinomas (HNSCC). Heterogeneity, late stage diagnosis and high recurrence rate are big hurdles in head and neck treatment regimen. Presently, the biomarkers available for diagnosis and prognosis of HNSCC are based on smoking as the major risk habit. This review shed light on the differential environment of HNSCC in smokeless tobacco consuming Indian patients. Frequent mutation in genes involved in DNA repair pathway (p53), cell proliferation (PIK3CA, HRAS) and cell death (CASP8, FADD) are common in western population. On the contrary, the genes involved in metastasis (MMPs, YAP1), lymphocyte proliferation (TNFRSF4, CD80), cell-cell adhesion (DCC, EDNRB), miRNA processing (DROSHA) and inflammatory responses (TLR9, IL-9) are mutated in Indian HNSCC patients. Gene ontology enrichment analysis highlighted that responses to chemical stimulus, immune pathways and stress pathways are highly enriched in Indian patients.

MycoVarP: Mycobacterium Variant and Drug Resistance Prediction Pipeline for Whole-Genome Sequence Data Analysis.

Whole-genome sequencing (WGS) provides a comprehensive tool to analyze the bacterial genomes for genotype-phenotype correlations, diversity of single-nucleotide variant (SNV), and their evolution and transmission. Several online pipelines and standalone tools are available for WGS analysis of Mycobacterium tuberculosis (Mtb) complex (MTBC). While they facilitate the processing of WGS data with minimal user expertise, they are either too general, providing little insights into bacterium-specific issues such as gene variations, INDEL/synonymous/PE-PPE (IDP family), and drug resistance from sample data, or are limited to specific objectives, such as drug resistance. It is understood that drug resistance and lineage-specific issues require an elaborate prioritization of identified variants to choose the best target for subsequent therapeutic intervention. Mycobacterium variant pipeline (MycoVarP) addresses these specific issues with a flexible battery of user-defined and default filters. It provides an end-to-end solution for WGS analysis of Mtb variants from the raw reads and performs two quality checks, viz, before trimming and after alignments of reads to the reference genome. MycoVarP maps the annotated variants to the drug-susceptible (DS) database and removes the false-positive variants, provides lineage identification, and predicts potential drug resistance. We have re-analyzed the WGS data reported by Advani et al. (2019) using MycoVarP and identified some additional variants not reported so far. We conclude that MycoVarP will help in identifying nonsynonymous, true-positive, drug resistance-associated variants more effectively and comprehensively, including those within the IDP of the PE-PPE/PGRS family, than possible from the currently available pipelines.

Comparison of Continuous Epidural Analgesia and Intravenous Patient-Controlled Analgesia with Opioids in Terms of Postoperative Pain and Their Complications in Mega-Prosthesis Total Knee Arthroplasty for Bone Cancers.

Total knee arthroplasty with mega-prosthesis in oncologic patients is a painful surgery and may be associated with nerve injury. Epidural analgesia (EA) with local anaesthetics (LA) is routinely used for pain relief in these patients. At our institute, we came across a high incidence of motor weakness in these patients compelling to shift to patient-controlled analgesia (PCA) with intravenous opioids. We retrospectively analysed our data to find the incidence and reasons for motor weakness and also to compare the efficacy of EA and PCA as analgesics. Over a period of 15 months, 68 patients were operated; out of these, 41 were in EA and 27 in PCA. Demographic details, level of epidural placement, drug used, pain scores, degree of motor weakness, measures taken to relieve the motor weakness and the improvement in symptoms after treatment were recorded. In the IV PCA group, details of drug used, dose of bolus, pain and sedation scores were analysed. Groups were comparable demographically. Motor weaknesses were present in 9 (22%) and 0 patients in EA and IV PCA groups respectively (p = 0.009). Average and maximum pain scores were significantly higher on day 1 in the IV PCA group (p of 0.00 and 0.001 respectively). Maximum pain scores were also significantly higher in the IV PCA group on day 2 (p = 0.010). Two patients out of 27 in IV PCA were found drowsy. Motor weakness is known with EA but can be managed effectively using a lower concentration of LA or by stopping the infusion of LA.

Ultrasonographic assessment of internal jugular vein diameter and its relationship with the carotid artery at the apex, middle, and base of the triangle formed by two heads of sternocleidomastoid muscle: A pilot study in healthy volunteers.

BACKGROUND: Anteroposterior (AP) diameter of internal jugular vein (IJV) and its relative position with carotid artery (CA) varies in the triangle formed by two heads of sternocleidomastoid muscle, which is the site of insertion of needle for IJV cannulation. This study assessed the maximum AP diameter of the IJV in supine and Trendelenburg positions and during Valsalva maneuver (supine position) at the apex, middle, and base of the triangle and to study the relationship of the IJV with the CA. MATERIALS AND METHODS: Twenty-five healthy volunteers were included and ultrasonography of IJV was performed in supine and Trendelenburg positions and during Valsalva maneuver (supine position) at the apex, middle, and base of the triangle bilaterally. The AP diameter of IJV was measured. The relative anatomical position of IJV was assessed as anterior (A), anterolateral (AL), or lateral (L) to CA in neutral head position and 30°, 45°, and 90° head rotation to the contralateral side in supine position. RESULTS: The difference in right IJV diameter was significant (P = 0.001) between supine vs. Trendelenburg position at the base of the triangle. Within one position there was significant difference between apex and base of the triangle. The left IJV diameter was significantly different between supine vs. Trendelenburg position at the apex (P = 0.004), middle (P = 0.003), and base of the triangle (P-value = 0.001). There was significant difference between supine vs. Valsalva maneuver at the middle (P = 0.011) and base (P = 0.014) of the triangle. The right IJV was more L or AL to the CA in apex with head in neutral or 30° rotation. The left IJV was more L or AL to the CA in middle with head in neutral position. CONCLUSION: Trendelenburg and Valsalva increase diameter of IJV on both right and left side. Diameter of IJV is greater at the base of the triangle. IJV is lateral or anterolateral when the head is either neutral or turned 30° to the contralateral side.

The 2011 ACGME standards: impact reported by graduating residents on the working and learning environment.

OBJECTIVE: Changes in Accreditation Council for Graduate Medical Education (ACGME) requirements, including duty hours, were implemented in July 2011. This study examines graduating pediatrics residents' perception of the impact of these standards. METHODS: A national, random sample survey of 1000 graduating pediatrics residents was performed in 2012; a total of 634 responded. Residents were asked whether 9 areas of their working and learning environments had changed with the 2011 standards. Three combined change scores were created for: 1) patient care, 2) senior residents, and 3) program effects, with scores ranging from -1 (worse) to 1 (improved). Respondents were also asked about hours slept and perceived change in hours slept. RESULTS: Most respondents felt that several areas had worsened, including continuity of care and senior resident workload, or not changed, including supervision and sleep. Mean change scores that included all study variables except those related to sleep all showed worsening: patient care (mean -0.37); senior residents (mean -0.36), and program effects (mean -0.06) (P < .01). Respondents reported a mean of 6.7 hours of sleep in a 24-hour period, with the majority (71%) reporting this amount of sleep has not changed with the 2011 standards. CONCLUSIONS: In the year after implementation of the 2011 ACGME standards, graduating pediatrics residents report no changes or a worsening in multiple components of their working and learning environments, as well as no changes in the amount of sleep they receive each day.

Global QSAR modeling of logP values of phenethylamines acting as adrenergic alpha-1 receptor agonists.

Global QSAR models predict biological response of molecular structures which are generic in particular class. A global QSAR dataset admits structural features derived from larger chemical space, intricate to model but more applicable in medicinal chemistry. The present work is global in either sense of structural diversity in QSAR dataset or large number of descriptor input. Forty phenethylamine structure derivatives were selected from a large pool (904) of similar phenethylamines available in Pubchem database. LogP values of selected candidates were collected from physical properties database (PHYSPROP) determined in identical set of conditions. Attempts to model logP value have produced significant QSAR models. MLR aided linear one-variable and two-variable QSAR models with their respective R(2) (0.866, 0.937), R(2)A (0.862, 0.932), F-stat (181.936, 199.812) and Standard Error (0.365, 0.255) are statistically fit and found predictive after internal validation and external validation. The descriptors chosen after improvisation and optimization reveal mechanistic part of work in terms of Verhaar model of Fish base-line toxicity from MLOGP, i.e. (BLTF96) and 3D-MoRSE -signal 15 /unweighted molecular descriptor calculated by summing atom weights viewed by a different angular scattering function (Mor15u) are crucial in regulation of logP values of phenethylamines.

Implementing a nurse-shadowing program for first-year medical students to improve interprofessional collaborations on health care teams.

Although physicians and nurses play critical roles in providing team-based collaborative care, the literature on current relationships between physicians and nurses in typical health care settings reveals troublesome characteristics that affect the quality of the patient care that they provide. Studies report communication failures, poor coordination, and fragmented care within and across organizations, which then have been associated with medication errors, patient safety issues, and patient deaths. Because the physician-nurse relationship is a critical component of a high-functioning patient care team, curricular interventions are needed to improve communication between physicians and nurses and to avoid professional conflict that can potentially compromise the quality of the patient care they offer.Currently, medical schools provide students with limited education and training on the roles of other health care professionals. In 2009, to begin addressing this need in the curriculum, the authors implemented a nurse-shadowing program at the University of Michigan Medical School. They set out to help first-year medical students learn more about the role of nurses in health care to positively influence their attitudes toward nurses and improve their understanding of nurses' roles in health care teams. Pre- and postprogram survey results revealed that medical students' attitudes toward nurses improved and their knowledge of the profession increased as a result of this intervention. In this article, the authors provide a description of the half-day program, evidence of its effectiveness, the implications of those findings, and future directions for teaching medical students about effectively working on interprofessional teams.

The effect of stress on craving for methadone depends on the timing of last methadone dose.

BACKGROUND: This study examined the extent to which the timing of last methadone dose moderates the influence of a laboratory stressor on craving for methadone in a sample of methadone maintenance patients. METHODS: Methadone maintenance patients (N=41) completed a computerized stress manipulation with two levels (low and high stress) on two separate days: (1) immediately following the administration of their standard daily methadone dose and (2) immediately prior to receiving their standard daily dose. The impact of stress, timing of methadone dose and their interaction were examined on self-report measures of stress and craving for methadone. RESULTS: Craving ratings varied according to the timing of last methadone dose. Immediately following methadone dose (i.e., day 1), there was no effect for stress on craving (0.12; p=0.30). However, prior to receiving methadone dose (i.e., day 2), the high stress effect on craving was significant (1.51; p<0.001). DISCUSSION: The present findings indicate that patients currently receiving methadone maintenance treatment may be particularly vulnerable to stress-related relapse immediately prior to daily methadone dosing.

Substance use-disorder treatment and a decline in attempted suicide during and after treatment.

OBJECTIVE: Suicide attempts are common in patients being treated for substance-use disorders (SUDs). However, little is known about the frequency of suicidal behavior during and after SUD treatment or about aspects of treatment that predict subsequent suicidal behavior. The present study examines whether treatment setting, length of treatment, and availability/use of psychiatric services are associated with a reduced likelihood of a suicide attempt during and 1 year after treatment. METHOD: A national sample of 3,733 patients was assessed at the start of an episode of SUD treatment and again at discharge and/or 1 year after treatment. Mixed-model logistic regression analyses examined treatment-related predictors of in-treatment and posttreatment suicide attempts. RESULTS: The rate of suicide attempts was significantly lower in the year following treatment (4%) than in the year before treatment (9%). Additionally, a total of 2% of patients reported a suicide attempt during treatment. Suicide attempts made during treatment were less likely in patients treated in residential as compared with outpatient settings. A longer course of treatment was associated with a lower likelihood of a posttreatment suicide attempt. CONCLUSIONS: A sizable minority of patients report a suicide attempt either during or within 1 year after completion of SUD treatment. Even after controlling for baseline suicidality, aspects of the SUD treatment episode are associated with a lower risk of a future suicide attempt. Treatment providers should consider placing patients in residential settings to reduce suicide attempts made during treatment and providing a longer course of treatment to reduce the likelihood of suicide following treatment.