COVID-19, Disability, and the International Classification of Functioning, Disability and Health: A Scoping Review of Early-Stage Pandemic Response.

Introduction: This study aimed to systematically identify the environmental factors that impacted people with disability during the COVID-19 pandemic. Methods: A scoping literature review was conducted using LitCOVID (January 1-July 31, 2020). Sixty-six articles met the inclusion criteria that (1) discussed disability and/or health conditions related to functioning and (2) considered environmental factors. A qualitative content analysis was conducted using codes from the WHO International Classification of Functioning, Disability and Health. Results: A total of 212 International Classification of Functioning, Disability and Health codes were used in the coding process. The most frequent codes referred to health services policies and public health guidelines. These policies, although generally considered facilitators for minimizing infection, were frequently identified as barriers to the health, participation, and human rights of people with disability. The lack of disability-specific population data was identified as a key barrier to planning and decision making. Conclusions: The social determinants of health for people with disability were not adequately considered in the acute phase of infection prevention at the population level. Integrating the International Classification of Functioning, Disability and Health in emergency management provides a tool to evaluate functioning and address barriers for those in need.

Diagnostic accuracy of diffusion-weighted imaging in variant Creutzfeldt-Jakob disease.

PURPOSE: This study sought to investigate the diagnostic sensitivity of diffusion-weighted imaging (DWI) in variant Creutzfeldt-Jakob disease (vCJD), a prion disease with significant public health implications on account of its transmissibility. The importance of this research stemmed from the first neuropathologically confirmed vCJD case in a PRNP heterozygous individual in 2016, which displayed DWI features typical of sporadic CJD (sCJD). The case was classified as 'probable' sCJD in life, predominantly based on these imaging findings. While DWI has proven valuable in diagnosing sCJD, its utility in vCJD diagnosis remains unclear. METHODS: DWI and Fluid-attenuated inversion recovery (FLAIR) images from probable and definite vCJD cases referred to the National CJD Research and Surveillance Unit (NCJDRSU) were independently analysed by an expert neuroradiologist. Scans were reviewed within a mixed cohort of CJD cases including definite sCJD and non-CJD controls. RESULTS: FLAIR sequences demonstrated greater sensitivity in identifying the pulvinar sign in vCJD compared to DWI (73% vs 41%, p-value <0.001). Basal ganglia hyperintensities were more prevalent in DWI (84%) than FLAIR (64%), and cortical hyperintensities were exclusive to DWI (24%). The pulvinar sign showed a specificity of 98% for vCJD and was rare in sCJD. CONCLUSION: DWI showed reduced sensitivity compared to FLAIR imaging in detecting the pulvinar sign in vCJD. Conversely, DWI can more distinctively identify basal ganglia and cortical hyperintensities, thus leading to imaging patterns more characteristic of sCJD. Therefore, DWI should be cautiously interpreted in vCJD diagnosis, with axial FLAIR potentially providing a more precise evaluation of the pulvinar sign.

Effects of High-Speed Training on Messenger RNA Expression in Two-Year-Old Thoroughbred Racehorses.

Accumulating high-speed exercise has been identified as a significant risk factor for catastrophic injuries in racing Thoroughbreds. Injuries, regardless of severity, are a main cause of withdrawal from the racing industry, raising animal welfare concerns and resulting in significant economic losses. While most of the current literature focuses on injuries incurred during racing rather than training, the present study aims to help fill this gap. As such, peripheral blood was collected weekly, prior to exercise or administration of medication, from eighteen, two-year-old Thoroughbreds throughout their first season of race training. Messenger RNA (mRNA) was isolated and used to analyze the expression of 34 genes via RT-qPCR. Statistical analysis of the noninjured horses (n = 6) showed that 13 genes were significantly correlated with increasing average weekly high-speed furlong performance. Additionally, there was a negative correlation for CXCL1, IGFBP3, and MPO with both cumulative high-speed furlongs and week of training for all horses. Comparison of both groups showed opposing correlations between the anti-inflammatory index (IL1RN, IL-10, and PTGS1) and average weekly high-speed furlong performance. Furthermore, evaluation of training effects on mRNA expression during the weeks surrounding injury, showed differences between groups in IL-13 and MMP9 at -3 and -2 weeks prior to injury. While some previously reported relationships between exercise adaptation and mRNA expression were not noted in this study, this may have been due to the small sample size. Several novel correlations, however, were identified and warrant further investigation as markers of exercise adaptation or potential risk for injury.

Dietary Habits of Children 0 - 23 Months in Rural Kansas: Early Life Diets of Rural Children.

Introduction: Children in rural areas face increased rates of obesity compared to their urban counterparts, and diet in early childhood may influence the development of diseases related to food intake. This study sought to determine current diet of children 0-23 months of age in rural Kansas. Methods: Medical students participating in 6-week, summer, rural clinical experiences offered the survey to caregivers of children 0-23 months, born at term as singletons without a specialized diet. The survey asked respondents to answer with the child's diet over the last seven days. The survey was in the style of a validated Food Frequency Questionnaire for infants with an image for estimating portion sizes. Diets were compared to guidelines set by the Dietary Guidelines for Americans, 2020-2025. Results: Of 44 responses, 21 children were aged 0-5 months, 7 aged 6-11 months, and 16 aged 12-23 months. Breastfeeding rates were nearly double reported national averages. All children aged 0-5 months met guidelines. None of the children 6-11 months or 12-23 months met guidelines. In the 6-11 month group, four consumed food in addition to breastmilk or formula (complementary foods). In the 12-23 month group, protein and dairy foods were lower than, and whole grains and vegetables were higher than, reported national averages, respectively. Conclusions: Children may fall short of meeting dietary recommendations due to foods consumed in addition to breastmilk. There is a need for improved survey methods to capture the diets of young children in the rural United States.

Shape judgments in natural scenes: Convexity biases versus stereopsis.

Determining the relief of upcoming terrain is critical to locomotion over rough or uneven ground. Given the significant contribution of stereopsis to perceived surface shape, it should play a crucial role in determining the shape of ground surfaces. The aim of this series of experiments was to evaluate the relative contribution of monocular and binocular depth cues to judgments of ground relief. To accomplish this goal, we simulated a depth discrimination task using naturalistic imagery. Stimuli consisted of a stereoscopically rendered grassy terrain with a central mound or a dip with varying height. We measured thresholds for discrimination of the direction of the depth offset. To determine the relationship between relief discrimination and measures of stereopsis, we used two stereoacuity tasks performed under the same viewing conditions. To assess the impact of ambiguous two-dimensional shading cues on depth judgments in our terrain task, we manipulated the intensity of the shading (low and high). Our results show that observers reliably discriminated ground reliefs as small as 20 cm at a viewing distance of 9.1 m. As the shading was intensified, a large proportion of observers (30%) exhibited a strong convexity bias, even when stereopsis indicated a concave depression. This finding suggests that there are significant individual differences in the reliance on assumptions of surface curvature that must be considered in experimental conditions. In impoverished viewing environments with limiting depth cues, these convexity biases could persist in judgments of ground relief, especially when shading cues are highly salient.

Development and Evaluation of a Muscle Atrophy Scoring System (MASS) for Horses.

Loss of skeletal muscle mass likely compromises performance and welfare in horses and thus routine monitoring would be valuable. Currently available methods to assess muscle mass require expert knowledge and are often expensive. To provide a simple method, a muscle atrophy scoring system (MASS) was created and tested by three evaluators (raters) in 38 horses of varying age, breed, and health status. Inter-rater agreement on atrophy scores was in the good-to-excellent range for ratings of the neck (ICC = 0.62), back (ICC = 0.62) and hind (ICC = 0.76) regions but was poor for the abdominal region (ICC = 0.29). Due to this low agreement, the abdominal region was excluded from further analysis. Associations between muscle atrophy scores and age, pituitary pars intermedia dysfunction (PPID) status, and body composition indicators, including weight and estimated fat-free mass (FFM), were examined. Weight was inversely associated with neck, back and hind muscle atrophy scores (ß = -0.008, ß = -0.008, ß = -0.009, respectively; all P <0.001), but estimated FFM was not associated with muscle atrophy scores at any region (P >0.05). Age was positively related to neck (ß = 0.030, P <0.01), back (ß = 0.037, P <0.001) and hind (ß = 0.040, P <0.001) muscle atrophy scores. PPID-positive horses (n = 4) had higher muscle atrophy scores than PPID-negative horses (n = 23), even after adjusting for age (P <0.05). This data suggests that neck, back and hind region evaluations by individual raters likely have acceptable reliability. In addition, these findings support further evaluation of the potential benefits of the MASS to identify and monitor muscle atrophy in horses.

Invasive Haemophilus influenzae Infections after 3 Decades of Hib Protein Conjugate Vaccine Use.

Haemophilus influenzae serotype b (Hib) was previously the most common cause of bacterial meningitis and an important etiologic agent of pneumonia in children aged <5 years. Its major virulence factor is the polyribosyl ribitol phosphate (PRP) polysaccharide capsule. In the 1980s, PRP-protein conjugate Hib vaccines were developed and are now included in almost all national immunization programs, achieving a sustained decline in invasive Hib infections. However, invasive Hib disease has not yet been eliminated in countries with low vaccine coverage, and sporadic outbreaks of Hib infection still occur occasionally in countries with high vaccine coverage. Over the past 2 decades, other capsulated serotypes have been recognized increasingly as causing invasive infections. H. influenzae serotype a (Hia) is now a major cause of invasive infection in Indigenous communities of North America, prompting a possible requirement for an Hia conjugate vaccine. H. influenzae serotypes e and f are now more common than serotype b in Europe. Significant year-to-year increases in nontypeable H. influenzae invasive infections have occurred in many regions of the world. Invasive H. influenzae infections are now seen predominantly in patients at the extremes of life and those with underlying comorbidities. This review provides a comprehensive and critical overview of the current global epidemiology of invasive H. influenzae infections in different geographic regions of the world. It discusses those now at risk of invasive Hib disease, describes the emergence of other severe invasive H. influenzae infections, and emphasizes the importance of long-term, comprehensive, clinical and microbiologic surveillance to monitor a vaccine's impact.

Beyond the hashtag: describing and understanding the full impact of the #BJSConnect tweet chat May 2019.

BACKGROUND: Twitter engagement between surgeons provides opportunities for international discussion of research and clinical practice. Understanding how surgical tweet chats work is important at a time when increasing reliance is being placed on virtual engagement because of the COVID-19 pandemic. METHODS: Individual tweets from the May 2019 #BJSConnect tweet chat were extracted using NodeXL, complemented by Twitter searches in an internet browser to identify responses that had not used the hashtag. Aggregate estimates of tweet views were obtained from a third-party social media tool (Twitonomy) and compared with official Twitter Analytics measurements. RESULTS: In total 37 Twitter accounts posted 248 tweets or replies relating to the tweet chat. A further 110 accounts disseminated the tweets via retweeting. Only 58.5 per cent of these tweets and 35 per cent of the tweeters were identified through a search for the #BJSConnect hashtag. The rest were identified by searching for replies (61), quoting tweets (20), and posts by @BJSurgery that used the hashtag but did not appear in the Twitter search (22). Studying all tweets revealed complex branching discussions that went beyond the discussed paper's findings. Third-party estimates of potential reach of the tweet chat were greatly exaggerated. CONCLUSION: Understanding the extent of the discussion generated by the #BJSConnect tweet chat required looking beyond the hashtag to identify replies and other responses, which was time-consuming. Estimates of reach using a third-party tool were unreliable.

CD137 agonist-based combination immunotherapy enhances activated, effector memory T cells and prolongs survival in pancreatic adenocarcinoma.

Pancreatic ductal adenocarcinoma(PDAC) is resistant to the PD-1/PD-L1 blockade therapy. Previously, the combination of PD-1 blockade and vaccine therapy was shown to have a modest antitumor activity in murine models of PDAC. We used a murine syngeneic model of metastatic PDAC to identify, among multiple T cell modulators tested, which therapeutic agents in combination with the GVAX cancer vaccine and an anti-PD-1 antagonist antibody(αPD-1) are able to improve the survival. We found that an anti-CD137 agonist antibody(αCD137) most significantly improved survival in the mouse PDAC model. Moreover, αPD-1 and αCD137 together in combination with vaccine therapy more significantly increased the expression of costimulatory molecules CD137 and OX40 on CD4+PD-1+ and CD8+PD-1+ T cells comparing to αPD-1 or αCD137, respectively, suggesting that T cell activation within PDACs were enhanced by a synergy of αCD137 and αPD-1. On another hand, αCD137 treatment led to an increase in effector memory T cells independent of αPD-1. Although αCD137 does not increase the cytotoxic effector T cell function, the addition of αCD137 to GVAX+αPD-1 increased expression of IFNγ in EOMES + exhausted tumor-infiltrating T cells. Taken together, this preclinical study established the mechanism of targeting CD137 to enhance effector memory and activated T cells in PDAC. Immunohistochemistry analysis of resected human PDACs following the neo-adjuvant GVAX treatment showed increased levels of CD8+ T cells in those with high levels of CD137 expression, supporting an ongoing clinical trial of testing CD137 as a potential target in treating PDACs that are inflamed with T cells by vaccine therapy.

A proof-of-concept study on the impact of a chronic pain and physical activity training workshop for exercise professionals.

OBJECTIVES: Physical activity is essential for long-term chronic pain management, yet individuals struggle to participate. Exercise professionals, including fitness instructors, and personal trainers, are preferred delivery agents for education and instruction on chronic pain, physical activity, and strategies to use adherence-promoting behavioral skills. However, exercise professionals receive no relevant training during certification or continuing education opportunities to effectively support their participants living with chronic pain. Based on the ORBIT model for early pre-efficacy phases of development and testing of new behavioral treatments, the present Phase IIa proof-of-concept study was conducted. The purpose was to examine the impacts of a newly developed chronic pain and physical activity training workshop on psychosocial outcomes among exercise professionals. Outcomes included knowledge and attitudes regarding chronic pain, attitudes and beliefs about the relationship between pain and impairment, and self-efficacy to educate and instruct participants with chronic pain. METHODS: Forty-eight exercise professionals (Mage=44.4±11.0 years) participated in a three-hour, in-person workshop that was offered at one of four different locations. Participants completed pre- and post-workshop outcome assessment surveys. RESULTS: Mixed MANOVA results comparing time (pre- versus post-workshop) by workshop location (sites 1 to 4) illustrated a significant within-subjects time effect (p<0.001). All outcomes significantly improved from pre- to post-workshop (p's<0.001), demonstrating large effect sizes (partial eta-squared values ranging from 0.45 to 0.59). CONCLUSIONS: Findings offer early phase preliminary support for the effectiveness of the chronic pain and physical activity training workshop for exercise professionals. Based on ORBIT model recommendations, findings warrant future phased testing via a pilot randomized clinical trial as well as testing for impacts that trained professionals have on activity adherence among their clients living with chronic pain. Eventual workshop adoption by exercise professional certification organizations would ensure widespread and sustainable access to qualified exercise professionals to help individuals engage in physical activity. By increasing the capacity of available exercise professionals to deliver effective support, active individuals could better manage their chronic pain and live well.

Predicting the Farnsworth-Munsell D15 and Holmes-Wright-A lantern outcomes with computer-based color vision tests.

This study determined the AC1 agreement values between computer-based color vision tests and the Farnworth-Munsell D-15 (F-D15) and the Holmes-Wright Type A lantern (HWA). The computer-based tests were the United States Air Force Cone Contrast Test (OCCT), Cambridge Color Test, Innova Rabin Cone Contrast, Konan-Waggoner D15 (KWC-D15), and Color Assessment and Diagnosis (CAD). Sixty-eight color-vision-defective persons participated. The KWC-D15 had the highest AC1 with the F-D15 (${\rm AC1} = {0.88}$AC1=0.88). Both the CAD and OCCT had the highest values with the HWA (${\rm AC1} \gt {0.96}$AC1>0.96). The KWC-D15 would be the best substitute for the F-D15. Either the CAD or OCCT would be appropriate substitutes for the HWA.

Contributions of Stereopsis and Aviation Experience to Simulated Rotary Wing Altitude Estimation.

OBJECTIVE: We examined the contribution of binocular vision and experience to performance on a simulated helicopter flight task. BACKGROUND: Although there is a long history of research on the role of binocular vision and stereopsis in aviation, there is no consensus on its operational relevance. This work addresses this using a naturalistic task in a virtual environment. METHOD: Four high-resolution stereoscopic terrain types were viewed monocularly and binocularly. In separate experiments, we evaluated performance of undergraduate students and military aircrew on a simulated low hover altitude judgment task. Observers were asked to judge the distance between a virtual helicopter skid and the ground plane. RESULTS: Our results show that for both groups, altitude judgments are more accurate in the binocular viewing condition than in the monocular condition. However, in the monocular condition, aircrew were more accurate than undergraduate observers in estimating height of the skid above the ground. CONCLUSION: At simulated altitudes of 5 ft (1.5 m) or less, binocular vision provides a significant advantage for estimation of the depth separation between the landing skid and the ground, regardless of relevant operational experience. However, when binocular cues are unavailable aircrew outperform undergraduate observers, a result that likely reflects the impact of training on the ability to interpret monocular depth cues.

Understanding Physiotherapists' Intention to Counsel Clients with Chronic Pain on Exercise: A Focus on Psychosocial Factors.

Purpose: Twenty percent of Canadians experience chronic pain. Exercise is an effective management strategy, yet participation levels are low. Physiotherapists can be key to counselling clients to engage in long-term unsupervised exercise. Yet, investigations that identify psychosocial factors related to physiotherapists' intention to counsel are lacking. The purpose of this study was to examine whether physiotherapists' knowledge of chronic pain, beliefs about pain, and self-efficacy to counsel on exercise predicted their intention to counsel clients with chronic pain on exercise. Method: Practicing physiotherapists (N = 64) completed an online survey that assessed their knowledge of chronic pain, beliefs about pain, self-efficacy, and intention to counsel. A two-step hierarchical multiple regression predicted intention. Step 1 controlled for years of practice, and Step 2 included study variables significantly correlated with intention. Results: Beliefs about pain (r = -0.35, p < 0.01) and self-efficacy (r = 0.69, p < 0.01) were significantly correlated with intention. The overall regression model was significant, F 3,60 = 18.73; p < 0.001. Self-efficacy was the sole significant predictor, t 60 = 5.71, p < 0.0001, sr 2 = 28%. Conclusions: Self-efficacy may facilitate physiotherapists' intention to counsel on exercise for chronic pain. If shown to be a causal factor, interventions that target a change in physiotherapists' self-efficacy should be pursued.

Objectif : une proportion de 20 % des Canadiens souffre de douleurs chroniques. L'exercice est une stratégie de prise en charge efficace, mais les taux de participation sont faibles. Les physiothérapeutes peuvent jouer un rôle déterminant dans les conseils aux clients afin qu'ils suivent un programme d'exercices non supervisés à long terme. Il n'existe pourtant pas d'études pour déterminer les facteurs psychosociaux liés à l'intention de conseiller des physiothérapeutes. La présente étude visait à examiner si les connaissances des physiothérapeutes à l'égard de la douleur chronique, leurs convictions au sujet de la douleur et leur auto-efficacité à donner des conseils sur l'exercice étaient prédictives de leur intention de donner des conseils sur l'exercice à leurs clients ayant des douleurs chroniques. Méthodologie : des physiothérapeutes en exercice (n = 64) ont rempli un sondage en ligne évaluant leurs connaissances sur la douleur chronique, leurs convictions au sujet de la douleur, leur auto-efficacité et leur intention de conseiller. Une analyse de régression hiérarchique multiple en deux étapes a prédit leur intention. L'étape 1 assurait un contrôle par rapport aux années d'exercice et l'étape 2 incluait des variables ayant une corrélation significative avec l'intention. Résultats : les convictions sur la douleur (r = ­0,35, p < 0,01) et l'auto-efficacité (r = 0,69, p < 0,01) avaient une corrélation significative avec l'intention. Le modèle de régression globale était substantiel : F 3,60 = 18,73; p < 0,001. L'auto-efficacité était le seul prédicteur significatif : t 60 = 5,71, p < 0,0001, sr 2 = 28 %. Conclusion : l'auto-efficacité peut faciliter l'intention des physiothérapeutes de donner des conseils sur l'exercice en cas de douleur chronique. S'il est démontré qu'il s'agit d'un facteur causal, il faudrait prévoir des interventions afin de changer l'auto-efficacité des physiothérapeutes.

How scientists and physicians use Twitter during a medical congress.

OBJECTIVES: During medical congresses Twitter allows discussions to disseminate beyond the congress hall and reach a wider audience. Insights into the dynamics of social media interactions during congresses, dissemination of scientific information and the determinants of a successful tweet may allow us to better understand social media's role in science communication. METHODS: We retrospectively extracted social media data during the European Congress of Clinical Microbiology and Infectious Diseases (ECCMID) 2017 and 2018 using NodeXL. We compared social media activity during these two congresses. Subsequently, we conducted in-depth analyses to identify the components of a successful tweet and multivariable analysis to assess independent factors associated with retweet activity. RESULTS: In 2018, approximately 13 000 delegates attended ECCMID, but only 591 Twitter accounts actively tweeted about the congress. Although fewer tweets were posted in 2018 compared with 2017 (4213 versus 4657, respectively), ECCMID 2018 generated a 63% increase in the total number of retweets (p < 0.001). According to multivariable logistic regression analysis, using multimedia, URL or hashtags and mentioning other Twitter account(s) were independently associated with retweet success. Mentioning of other users and use of multimedia were the only consistent predictors of retweets irrespective of the number of followers. CONCLUSIONS: A substantial increase in retweet activity and a modest increase in the number of influential Twitter accounts were observed between two successive congresses. Dissemination of scientific messages is more successful when connected accounts are actively involved in social media activity, and social media posts constitute the right combination of components.

Immediate pre-learning stress enhances baseline startle response and fear acquisition in a fear-potentiated startle paradigm.

Extensive work has shown that stress time-dependently influences hippocampus-dependent learning and memory. In particular, stress that is administered immediately before learning enhances long-term memory, while stress that is temporally separated from learning impairs long-term memory. We have extended these findings by examining the impact of immediate, pre-learning stress on an amygdala-dependent fear conditioning task. One hundred and forty-one healthy participants underwent a stress (socially evaluated cold pressor test) or control manipulation immediately before completing differential fear conditioning in a fear-potentiated startle paradigm. Participants then completed extinction and extinction memory testing sessions 24 and 48 h later, respectively. Stress administered immediately before acquisition increased baseline startle responses and enhanced fear learning, as evidenced by greater fear-potentiated startle to the CS + . Although no group differences were observed during extinction training on Day 2, stressed participants exhibited evidence of impaired extinction processes on Day 3, an effect that was driven by group differences in acquisition. Importantly, stressed participants' cortisol responses to the stressor on Day 1 were positively associated with CS discrimination on Days 2 and 3. These findings suggest that stress immediately before fear conditioning strengthens fear memory formation and produces a more enduring fear memory, perhaps via corticosteroid activity. Such a paradigm could be useful for understanding factors that influence traumatic memory formation.

Indirect photopatterning of functionalized organic monolayers via copper-catalyzed "click chemistry".

Solution-based lithographic surface modification of an organic monolayer on a solid substrate is attained based on selective area photo-reduction of copper (II) to copper (I) to catalyze the azide-alkyne dipolar cycloaddition "click" reaction. X-ray photoelectron spectroscopy is used to confirm patterning, and spectroscopic results are analyzed and supplemented with computational models to confirm the surface chemistry. It is determined that this surface modification approach requires irradiation of the solid substrate with all necessary components present in solution. This method requires only minutes of irradiation to result in spatial and temporal control of the covalent surface functionalization of a monolayer and offers the potential for wavelength tunability that may be desirable in many applications utilizing organic monolayers.

Chloride Ion Transport by the E. coli CLC Cl-/H+ Antiporter: A Combined Quantum-Mechanical and Molecular-Mechanical Study.

We performed steered molecular dynamics (SMD) and umbrella sampling simulations of Cl- ion migration through the transmembrane domain of a prototypical E. coli CLC Cl-/H+ antiporter by employing combined quantum-mechanical (QM) and molecular-mechanical (MM) calculations. The SMD simulations revealed interesting conformational changes of the protein. While no large-amplitude motions of the protein were observed during pore opening, the side chain rotation of the protonated external gating residue Glu148 was found to be critical for full access of the channel entrance by Cl-. Moving the anion into the external binding site (Sext) induced small-amplitude shifting of the protein backbone at the N-terminal end of helix F. As Cl- traveled through the pore, rigid-body swinging motions of helix R separated it from helix D. Helix R returned to its original position once Cl- exited the channel. Population analysis based on polarized wavefunction from QM/MM calculations discovered significant (up to 20%) charge loss for Cl- along the ion translocation pathway inside the pore. The delocalized charge was redistributed onto the pore residues, especially the functional groups containing π bonds (e.g., the Tyr445 side chain), while the charges of the H atoms coordinating Cl- changed almost negligibly. Potentials of mean force computed from umbrella sampling at the QM/MM and MM levels both displayed barriers at the same locations near the pore entrance and exit. However, the QM/MM PMF showed higher barriers (~10 kcal/mol) than the MM PMF (~2 kcal/mol). Binding energy calculations indicated that the interactions between Cl- and certain pore residues were overestimated by the semi-empirical PM3 Hamiltonian and underestimated by the CHARMM36 force fields, both of which were employed in the umbrella sampling simulations. In particular, CHARMM36 underestimated binding interactions for the functional groups containing π bonds, missing the stabilizations of the Cl- ion due to electron delocalization. The results suggested that it is important to explore these quantum effects for accurate descriptions of the Cl- transport.

Carbon Nanotubes Covalently Attached to Functionalized Surfaces Directly through the Carbon Cage.

The covalent attachment of nonfunctionalized and carboxylic acid-functionalized carbon nanotubes to amine-terminated organic monolayers on gold and silicon surfaces is investigated. It is well established that the condensation reaction between a carboxylic acid and an amine is a viable method to anchor carbon nanotubes to solid substrates. The work presented here shows that the presence of the carboxylic group on the nanotube is not required for attachment to occur, as direct attachment via the substrate amine and the nanotube cage can take place. Scanning and transmission electron microscopy and atomic force microscopy confirm the presence of carbon nanotubes in intimate contact with the surface. X-ray photoelectron spectroscopy is utilized to compare the surface chemistry of the functionalized and nonfunctionalized carbon nanotubes and is supported by a computational investigation. Ion fragments attributed to the direct attachment between the surface and carbon nanotube cage are detected by time-of-flight secondary ion mass spectrometry. The overall attachment scheme is evaluated and can be further used on multiple carbonaceous materials attached to solid substrates.

Zinc deficiency affects the STAT1/3 signaling pathways in part through redox-mediated mechanisms.

Zinc deficiency affects the development of the central nervous system (CNS) through mechanisms only partially understood. We previously showed that zinc deficiency causes CNS oxidative stress, damaging microtubules and impairing protein nuclear shuttling. STAT1 and STAT3 transcription factors, which require nuclear import for their functions, play major roles in CNS development. Thus, we investigated whether zinc deficiency disrupts STAT1 and STAT3 signaling pathways in the developing fetal CNS, characterizing the involvement of oxidative stress and the cytoskeleton in the adverse effects. Maternal (gestation day 0-19) marginal zinc deficiency (MZD) reduced STAT1 and STAT3 tyrosine phosphorylation and their nuclear translocation in the embryonic day 19 (E19) rat brain. Similar effects were observed in zinc depleted IMR-32 neuroblastoma cells, with an associated decrease in STAT1- and STAT3-dependent gene transactivation. Zinc deficiency caused oxidative stress (increased 4-hydroxynonenal-protein adducts) in E19 brain and IMR-32 cells, which was prevented in cells by supplementation with 0.5mM α-lipoic acid (LA). In zinc depleted IMR-32 cells, the low tyrosine phosphorylation of STAT1, but not that of STAT3, recovered upon incubation with LA. STAT1 and STAT3 nuclear transports were also restored by LA. Accordingly, chemical disruption of the cytoskeleton partially reduced STAT1 and STAT3 nuclear levels. In summary, the redox-dependent tyrosine phosphorylation, and oxidant-mediated disruption of the cytoskeleton are involved in the deleterious effects of zinc deficit on STAT1 and STAT3 activation and nuclear translocation. Therefore, disruption of the STAT1 and STAT3 signaling pathways may in part explain the deleterious effects of maternal MZD on fetal brain development.