The polymer polydimethylsiloxane (PDMS) is widely used to build microfluidic devices compatible with cell culture. Whilst convenient in manufacture, PDMS has the disadvantage that it can absorb small ...molecules such as drugs. In microfluidic devices like “Organs-on-Chip”, designed to examine cell behavior and test the effects of drugs, this might impact drug bioavailability. Here we developed an assay to compare the absorption of a test set of four cardiac drugs by PDMS based on measuring the residual non-absorbed compound by High Pressure Liquid Chromatography (HPLC). We showed that absorption was variable and time dependent and not determined exclusively by hydrophobicity as claimed previously. We demonstrated that two commercially available lipophilic coatings and the presence of cells affected absorption. The use of lipophilic coatings may be useful in preventing small molecule absorption by PDMS.
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•Binding of different compounds to PDMS varies greatly.•Previous reported correlations of absorption and LogP values could not be repeated.•Topological polar surface area possibly related to compound absorption.•A lipid based coating partially obviates compound absorption.•Presence of cultured cells affects free drug concentration, but less than substrate.
Regular testing for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is an important strategy for controlling virus outbreaks on university campuses during the COVID-19 pandemic but ...testing participation rates can be low. The Residence-Based Testing Participation Pilot (RB-TPP) was a novel intervention implemented at two student residences on a large UK university campus over 4 weeks. The aim of the pilot was to increase the frequency of asymptomatic SARS-CoV-2 saliva testing onsite. This process evaluation aimed to determine whether RB-TPP was implemented as planned and identify implementation barriers and facilitators.
A mixed-methods process evaluation was conducted alongside the RB-TPP. Evaluation participants were students (opting in, or out of RB-TPP) and staff with a role in service provision or student support. Monitoring data were collected from the intervention delivery team and meeting records. Data were collected from students via online survey (n = 152) and seven focus groups (n = 30), and from staff via individual interviews (n = 13). Quantitative data were analysed descriptively and qualitative data thematically. Barriers and facilitators to implementation were mapped to the 'Capability, Opportunity, Motivation-Behaviour' (COM-B) behaviour change framework.
Four hundred sixty-four students opted to participate in RB-TPP (98% of students living onsite). RB-TPP was implemented broadly as planned but relaxed social distancing was terminated early due to concerns relating to national escalation of the COVID-19 Delta variant, albeit testing continued. Most students (97.9%) perceived the period of relaxed social distancing within residences positively. The majority engaged in asymptomatic testing (88%); 46% (52% of testers) were fully compliant with pre-determined testing frequency. Implementation was facilitated by convenience and efficiency of testing, and reduction in the negative impacts of isolation through opportunities for students to socialise. Main barriers to implementation were perceived mixed-messages about the rules, ambivalent attitudes, and lack of adherence to COVID-19 protective measures in the minority.
This process evaluation identifies factors that help or hinder the success of university residence-based outbreak prevention and management strategies. RB-TPP led to increased rates of SARS-CoV-2 testing participation among students in university residences. Perceived normalisation of university life significantly enhanced student mental wellbeing. The complexity and challenge generated by multiple lines of communication and rapid adaptions to a changing pandemic context was evident.
UKAS 307727-02-01; Pre-results.
gov Identifier: NCT05045989 ; post-results (first posted, 16/09/21).
Faculty of Medicine & Health Sciences Research Ethics Committee, University of Nottingham (Ref: FMHS 96-0920).
This study investigated whether perceived physical activity norms moderated the effects of physical activity-related social interactions on intentions to engage in physical activity among ...community-residing older adults (N = 217). Structural equation modeling tested whether two types of social support and social control interacted with personal norms in predicting intentions to be active. Emotional and informational support were associated with higher intentions, and negative social control was associated with lower intentions to engage in activity. Each of these effects was more prominent in the context of weak personal norms, suggesting future research and interventions should consider joint effects of support and norms.
Aims:
Development and rollout of vaccines offers the best opportunity for population protection against the SARS-CoV-2 (COVID-19) virus. However, hesitancy towards the vaccines might impede ...successful uptake in the United Kingdom, particularly in young adults who demonstrate the highest rates of hesitancy. This prospective study explored COVID-19 vaccine hesitancy in young adults and whether the reasons behind these attitudes changed during the initial stages of the United Kingdom’s vaccine rollout.
Method:
Data on vaccination intention were collected from a British university student cohort at three time points: October 2020, February 2021, and March 2021. This online survey included items on intention to receive a vaccine and a free-text response for the reasons behind this intention. Cochran’s Q tests examined changes in rates of hesitancy and acceptance over time and free-text responses were analysed thematically.
Results:
At baseline, 893 students provided data, with 476 participants completing all three time points. Hesitancy declined over time, with 29.4% of participants expressing hesitancy at baseline, reducing to 9.1% at wave 2 and 5.9% at wave 3. The most commonly endorsed themes for those willing to accept a vaccine were self-protection against COVID-19 and pro-social reasons, including protecting the population or unspecific others, and ending the pandemic/returning to normal life. The most commonly endorsed hesitancy themes related to ‘confidence’ in the vaccines and potential personal risk, including insufficient testing/scientific evidence, concern about side effects, and long-term effects. These reasons remained the most commonly endorsed at both waves 2 and 3.
Conclusions:
While a decline in hesitancy was observed over time, the key reasons behind both vaccine acceptance and hesitancy remained consistent. Reasons behind hesitancy aligned with those of the general public, providing support for the use of generalist interventions. Pro-social reasons frequently underpinned vaccine acceptance, so cohort-specific interventions targeting those factors may be of benefit.
Unexpected induction of arrhythmias in the heart is still one of the major risks of new drugs despite recent improvements in cardiac safety assays. Here we address this in a novel emerging assay ...system. Eleven reference compounds were administrated to spontaneously beating clusters of cardiomyocytes from human pluripotent stem cells (hPSC-CM) and the responses determined using multi-electrode arrays. Nine showed clear dose-dependence effects on field potential (FP) duration. Of these, the Ca2+ channel blockers caused profound shortening of action potentials, whereas the classical hERG blockers, like dofetilide and d,l-sotalol, induced prolongation, as expected.
Unexpectedly, two potent blockers of the slow component of the delayed rectifier potassium current (IKs), HMR1556 and JNJ303, had only minor effects on the extracellular FP of wild-type hPSC-CM despite evidence of functional IKs channels. These compounds were therefore re-evaluated under conditions that mimicked reduced “repolarization reserve,” a parameter reflecting the capacity of cardiomyocytes to repolarize and a strong risk factor for the development of ventricular arrhythmias. Strikingly, in both pharmacological and genetic models of diminished repolarization reserve, HMR1556 and JNJ03 strongly increased the FP duration. These profound effects indicate that IKs plays an important role in limiting action potential prolongation when repolarization reserve is attenuated. The findings have important clinical implications and indicate that enhanced sensitization to repolarization-prolonging compounds through pharmacotherapy or genetic predisposition should be taken into account when assessing drug safety.
► Validation of hPSC-CM for predictive cardiac safety pharmacology. ► IKs plays an important role in limiting action potential prolongation. ► Repolarization reserve determines drug sensitivity. ► Diminished repolarization reserve risk factor for QT prolongation and TdP.
Prophylactic surgical drains are commonly used in Nigeria following intramedullary nailing (IMN) of long bone diaphyseal fractures. However, evidence in the literature suggests that drains do not ...confer any benefit and predispose clean wounds to infection. This study compares outcomes between patients treated with and without prophylactic surgical drainage following diaphyseal long bone fractures treated with IMN.
A prospective cohort study with randomization was conducted at a tertiary referral center in Enugu, Nigeria. Investigators included skeletally mature patients with diaphyseal long bone (femur, tibia, humerus) fractures treated with SIGN IMN. Patients followed-up at 5, 14, and 30 days post-operatively. The primary outcome was surgical site infection (SSI) rate. Secondary outcomes included post-operative pain at 6 and 12 h, need for blood transfusion, wound characteristics (swelling, ecchymosis, and gaping), need for dressing changes, and length of hospital stay.
Of the enrolled patients, 76 (96%) of 79 completed 30-day follow-up. SSI rate was associated with patients who received a prophylactic drain versus those who did not (23.7% vs. 10.5%, p = 0.007). There were no significant differences in transfusion need (p = 0.22), wound swelling (p = 0.74), wound ecchymosis (p = 1.00), wound gaping (p = 1.00), dressing change need (p = 0.31), post-operative pain at 6 h (p = 0.25) or 12 h (p = 0.57), or length of stay (p = 0.95).
Surgical drain placement following IMN of diaphyseal long bone fractures is associated with a significantly higher risk of SSI. Reducing surgical drain use following orthopaedic injuries in lower resource settings may translate to reduced infection rates.
Those new to structural equation modeling (SEM) often encounter problems with convergence, software errors, or poor fitting models. Some basic suggestions are offered to help reduce these problems ...and avoid some common error messages encountered when first testing models. The tips concern initial data management steps, specification of latent variables, avoidance of factor identification problems, special precautions when estimating means, addressing poor measurement model fit, using multistep testing, fitting full structural models, attentiveness to interpretation pitfalls, and troubleshooting software warnings and errors. The advice provided is intended to help save time, effort, and trials and tribulations often encountered by beginner modelers.
Materials discovery provides the opportunity to identify novel materials that are tailored to complex biological environments by using combinatorial mixing of monomers to form large libraries of ...polymers as micro arrays. The materials discovery approach is predicated on the use of the largest chemical diversity possible, yet previous studies into human pluripotent stem cell (hPSC) response to polymer microarrays have been limited to 20 or so different monomer identities in each study. Here we show that it is possible to print and assess cell adhesion of 141 different monomers in a microarray format. This provides access to the largest chemical space to date, allowing us to meet the regenerative medicine challenge to provide scalable synthetic culture ware. This study identifies new materials suitable for hPSC expansion that could not have been predicted from previous knowledge of cell-material interactions.
Objectives
Age-associated accelerated declines in physical health vary across individuals, and researchers have suggested that individual differences in decline may vary as a function of stressors. ...The relation of one such stressor, negative social exchanges, to accelerated declines in self-rated health is investigated.
Method
Participants are from a 2-year, 5-wave, national, longitudinal study of social relationships among older adults. Growth curve analyses are used to examine the relation of negative and positive social exchanges to accelerated changes in self-rated health, controlling for age, sex, race/ethnicity, education, and depressive symptoms.
Results:
Individuals reporting more frequent negative social exchanges showed significantly accelerated declines in physical health. Positive social exchanges were not related to linear or accelerated declines in self-rated health over time.
Discussion:
The association between negative social exchanges and accelerated deterioration in self-rated health provides general support for hypotheses that interpersonal stressors play an important role age-related physical health decline.
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