Identification of natural lead molecules as potential Trypanosoma cruzi cruzipain inhibitors and decoding the interaction mechanism for the treatment of Chagas disease: a computational biology analysis.

Chagas disease has grown into a serious public health threat, with a high morbidity rate, major social impact, and global neglect. Therapeutic adhesion, unwanted side-effects, and resistance make its present therapy ineffective. Discovery of more effective drugs is hence needed. Using natural compounds conjointly with computational methods helps better to find promising compounds, speeding up drug discovery process and reducing its cost. In the present study, a docking protocol against cruzipain (PDB: 3l06), an important druggable target, was applied to a library of 50 sorted natural compounds. Compounds were further analysed for binding mode and interactions with cruzipain active site, conformational alignment studies and in-silico pharmacokinetic studies so as to predict their plausible anti-cruzipain mechanism. The results provided computational insights into the molecular interaction of naturals against T. cruzi cruzipain. Study also lead to identification of Hinokiflavone; BA = -10.2 kcal mol-1 as reasonably promising potential natural cruzipain inhibitor.

Factors Influencing Oral Bolus Hold Type: Tipper or Dipper.

Purpose: This retrospective study investigated the impact of age, sex, and swallow task on bolus hold location during cued liquid swallows in healthy, community-dwelling adults. Furthermore, we investigated the association between bolus hold location and Modified Barium Swallow Impairment Profile (MBSImP) Components 2 (bolus hold) and 4 (lingual transport) scores. Method: Cued swallows of standardized barium liquids (thin, nectar-thickened, honey-thickened) observed during videofluoroscopy in 195 participants were judged as either tipper or dipper bolus hold type. Logistic regression was used to determine relationships between bolus hold location and age, sex, and swallow task. Fisher's exact test was used to determine associations between MBSImP scores and bolus hold type. Results: The majority of swallow tasks (95%) were of tipper bolus hold type. A significant relationship was observed between age and bolus hold type for swallows of 5-ml thin liquid and 5-ml honey-thickened liquid, with older individuals more likely to demonstrate a tipper bolus hold type. Sex was observed to be a significant factor for two swallow tasks (cup sip of thin liquid and 5 ml of nectar-thickened liquid), with males being more likely to be dippers. No significant relationships were observed between bolus hold type and MBSImP Component 2 or 4 scores. Conclusions: A tipper bolus hold type was the most common type observed in healthy adults, although the dipper bolus hold type was also observed (albeit at a lower frequency). These study findings further contribute to defining typical swallowing behaviors.

Factors Influencing Initiation of Pharyngeal Swallow in Healthy Adults.

Purpose The purpose of this study was to investigate factors influencing the initiation of pharyngeal swallow (IPS) in healthy, nondysphagic adults. Method A total of 195 healthy participants ranging in age from 21 to 89 years participated in a modified barium swallow study. IPS was quantified using the Modified Barium Swallow Impairment Profile standardized scoring system across nine swallowing tasks observed in the lateral viewing plane for each participant. Results Large variability for bolus head location at time of hyoid burst (IPS) was observed within this healthy cohort, ranging from the ramus of the mandible to the pyriform sinuses. Significant effects of bolus volume, viscosity, sex, and race were also observed. Conclusion Study findings indicate that IPS is variable in healthy adults and influenced by volume, viscosity, sex, and race. Thus, variability in IPS may be considered typical in otherwise nondysphagic adults. The clinical significance of high Modified Barium Swallow Impairment Profile IPS scores in dysphagic patients, therefore, must be considered within the context of other swallowing impairments. Supplemental Material https://doi.org/10.23641/asha.12735935.

Factors Influencing Presence or Absence of Laterality During Pharyngeal Bolus Clearance.

PURPOSE: The aim of this study was to identify factors influencing pharyngeal laterality of bolus clearance through the pharyngoesophageal segment. METHOD: Two swallowing trials (5-ml nectar-thickened liquid and 5-ml pudding) administered in the anteroposterior viewing plane during videofluoroscopy were extracted from a normative database of 195 healthy adult participants. Each swallow was determined as either having no laterality, right dominance/right side only, or left dominance/left side only. Descriptive measures were performed on all data variables. Chi-square tests were performed to determine the relationship between laterality and several factors, including age category, sex, race, and swallow task. RESULTS: The majority of swallows demonstrated no laterality. No significant associations were observed between laterality and the following factors: age category, race, or swallow task. Significant differences in laterality were observed between males and females, with females more likely to demonstrate no laterality. CONCLUSIONS: Majority of swallows in the current healthy sample demonstrated no laterality preference. If present, males were more likely to demonstrate laterality compared to females. Laterality observed during videofluoroscopy does not imply impairment if there are no other factors present influencing bolus flow into the esophagus (e.g., mass). Study findings further define typical swallowing behaviors, allowing clinicians to better delineate normal variations from true impairment. Further research should include a larger sample of individuals aged 80 years and older, as well as additional swallowing tasks, to further investigate patient- and bolus-related factors on laterality.

Assessment of weight status, dietary habits and beliefs, physical activity, and nutritional knowledge among university students.

AIMS: The purpose of this study was to assess weight status, dietary habits, physical activity, dietary beliefs, and nutrition knowledge among a sample of students from Central Michigan University. METHODS: A cross-sectional survey was conducted among a sample of undergraduate students in Fall 2011 and Spring 2012 at Central Michigan University. Participating students completed an online questionnaire that included questions related to their eating habits, physical activity and lifestyle, dietary beliefs, and nutritional knowledge. Weight, height, and waist circumference were measured. Percentage body fat and visceral fat score were determined using a Tanita body composition analyser (SC-331S). RESULTS: Outcomes of this study indicated that 78% of female students were within the healthy weight range compared to 52% of male students. Visceral body fat and waist circumference scores were higher in males than in females. Most students showed 'satisfactory' dietary habits. Almost half of the students reported drinking two glasses of milk and consuming two cups of fruits and vegetables daily. Physical activity and lifestyle score indicated that most of the students were not physically active. Only 7% of students reported having a very active lifestyle, and 4% had quite good nutritional knowledge. CONCLUSION: The majority of students, particularly females, were within the healthy body weight range. Students' dietary habits were satisfactory. However, physical activity, students' knowledge of healthy and unhealthy diet habits, and nutritional knowledge needed improvement. Developing gender-specific programmes for promoting healthy lifestyle behaviours among students is recommended.

Residential tap water contamination following the Freedom Industries chemical spill: perceptions, water quality, and health impacts.

During January 2014, an industrial solvent contaminated West Virginia's Elk River and 15% of the state population's tap water. A rapid in-home survey and water testing was conducted 2 weeks following the spill to understand resident perceptions, tap water chemical levels, and premise plumbing flushing effectiveness. Water odors were detected in all 10 homes sampled before and after premise plumbing flushing. Survey and medical data indicated flushing caused adverse health impacts. Bench-scale experiments and physiochemical property predictions showed flushing promoted chemical volatilization, and contaminants did not appreciably sorb into cross-linked polyethylene (PEX) pipe. Flushing reduced tap water 4-methylcyclohexanemethanol (4-MCHM) concentrations within some but not all homes. 4-MCHM was detected at unflushed (<10 to 420 µg/L) and flushed plumbing systems (<10 to 96 µg/L) and sometimes concentrations differed among faucets within each home. All waters contained less 4-MCHM than the 1000 µg/L Centers for Disease Control drinking water limit, but one home exceeded the 120 µg/L drinking water limit established by independent toxicologists. Nearly all households refused to resume water use activities after flushing because of water safety concerns. Science based flushing protocols should be developed to expedite recovery, minimize health impacts, and reduce concentrations in homes when future events occur.