Effect of Monovalent Cations on the Structure and Dynamics of Multimodal Chromatographic Surfaces.

While multimodal (MM) chromatography is a promising approach for purifying proteins, the lack of a fundamental understanding of how ion-ligand interactions govern selectivity limits its use in the biopharmaceutical industry. This study uses molecular dynamics simulations to study the interactions between simple monovalent cations and two commonly used structurally similar multimodal chromatography ligands, the Capto ligand and Nuvia cPrime, immobilized on the surface. On the Capto ligand surface, ion presence and type play a key role in modulating the formation of phenyl rings and carboxylate clusters. The flexible linkage attaching the Capto ligand to the self-assembled monolayer (SAM) surface allowed multiple ligands to form interactions with the small cations, while large cations interacted less strongly, following the order Li+ > Na+ > K+ > Cs+. Thus, smaller cations resulted in greater ordering on the surface and lower ion diffusivities, while larger cations resulted in less ordering and higher ion diffusivities, following the order Li+ < Na+ < K+ < Cs+. In contrast, due to the rigid attachment of Nuvia cPrime to the SAM surfaces, the cations bound less strongly and had a much smaller effect on ligand clustering or ordering. Additionally, ions in the presence of the Nuvia cPrime surface had generally greater diffusivities than those in the presence of the Capto ligand. Overall, the interaction of cations with the multimodal ligands can lead to unique configurations on the SAM that likely contribute to differential behavior in biological separations.

Appropriate Prescribing for older adults with Multimorbidity (Pro-M): protocol for a feasibility study.

BACKGROUND: Potentially inappropriate prescribing is common among older adults with multimorbidity due to various reasons, from concurrent application of multiple single-disease clinical guidelines to fragmentation of care. Interventions such as medication review have been implemented worldwide to reduce inappropriate prescribing for older adults. However, the implementability of such interventions are underexplored in the outpatient clinics in Singapore's public hospitals. Hence, the Pro-M study aims to assess the feasibility of implementing a physician-pharmacist collaborative care intervention in geriatric medicine outpatient clinics to facilitate appropriate prescribing for older adults in Singapore. METHODS: This is a single-arm, non-randomised feasibility study using a pre-post evaluation design. This study consists of two parts: (1) implementation phase of the intervention (6 months) and an (2) evaluation phase (3 months). Eligible patients will be recruited from geriatric medicine outpatient clinics at two public hospitals in Singapore through convenience sampling. The main components of the Pro-M intervention are: (1) pharmacist-facilitated medication reviews with feedback on any medication issues and potential recommendations to physicians, and (2) physicians communicating changes to other relevant prescribers. The evaluation phase will involve surveying and interviewing physicians and pharmacists involved in the implementation of the intervention. A mixed-method approach will be employed for data collection and analysis. The quantitative and qualitative findings will be triangulated and reported using Proctor's implementation outcomes: appropriateness, penetration, acceptability, fidelity, feasibility, and sustainability. A basic cost analysis will be conducted alongside the study. DISCUSSION: This is a phase 2 study to test the feasibility of implementing an intervention that was co-created with stakeholders during phase 1 development of an intervention to optimise prescribing for older adults with multimorbidity. The implementation will be assessed using Proctor's implementation outcomes to provide insights on the process and the feasibility of implementing medication reviews for older adults with multimorbidity as a routine practice in outpatient clinics. Data collected from this study will inform a subsequent scale-up study. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05756478. Registered on 06 March 2023.

Calf Circumference Measurement Protocols for Sarcopenia Screening: Differences in Agreement, Convergent Validity and Diagnostic Performance.

BACKGROUND: Although recommended by the Asian Working Group for Sarcopenia 2019 consensus (AWGS'19) as a screening tool for sarcopenia, there remains no consensus regarding the position (sitting, standing) or laterality (right, left) for the measurement of calf circumference (CC). This study aimed to determine the agreement between CC measurements, correlations with muscle mass and function, and diagnostic performance for sarcopenia screening. METHODS: We studied 176 healthy community-dwelling older adults (mean age, 66.8±7.1 years) from the GERILABS-2 study. CC was measured using non-elastic tape in four ways: left and right sides in the sitting and standing positions. Sarcopenia was diagnosed using the AWGS'19 criteria. We produced Bland-Altman plots to assess the agreement, partial correlations for muscle mass and function to compare convergent validity, and area under the receiver operating characteristic curve (AUC) to compare diagnostic performance. RESULTS: The prevalence rate of sarcopenia was 17.4%. Sitting CC was larger than standing regardless of laterality (right 35.31±2.95 cm vs. 34.61±2.74 cm; left 35.37±2.96 cm vs. 34.70±2.83 cm; both p<0.001), consistent with the systematic bias on Bland-Altman plots showing the overestimation of sitting over standing measurements (right bias=0.70 cm; 95% confidence interval [CI], -0.48-1.88; left bias=0.67 cm, 95% CI, -0.35-1.68). After adjusting for age and sex, CC was significantly correlated with appendicular skeletal mass, hand grip strength, knee extension, gait speed, chair stand, and short physical performance battery. Although right-sided CC measurements had better diagnostic performance (AUC=0.817), the difference was not statistically significant compared to the other positions (p>0.05). The optimal cutoff was <34 cm for all measurements, except for the left standing position (cutoff <35 cm). CONCLUSION: Standing CC measurements are recommended for sarcopenia screening in community-dwelling older adults because of their good agreement without systematic bias, convergent validity, and diagnostic performance.

Barriers to effective prescribing in older adults: applying the theoretical domains framework in the ambulatory setting - a scoping review.

BACKGROUND: As the population ages, potentially inappropriate prescribing (PIP) in the older adults may become increasingly prevalent. This undermines patient safety and creates a potential source of major morbidity and mortality. Understanding the factors that influence prescribing behaviour may allow development of interventions to reduce PIP. The aim of this study is to apply the Theoretical Domains Framework (TDF) to explore barriers to effective prescribing for older adults in the ambulatory setting. METHODS: A scoping review was performed based on the five-stage methodological framework developed by Arksey and O'Malley. From 30 Aug 2018 to 5 Sep 2018, we conducted our search on PubMed, CINAHL, EMBASE, the Cochrane Database of Systematic Reviews, and Web of Science. We also searched five electronic journals, Google and Google Scholar to identify additional sources and grey literature. Two reviewers applied eligibility criteria to the title and abstract screening, followed by full text screening, before systematically charting the data. RESULTS: A total of 5731 articles were screened. Twenty-nine studies met the selection criteria for qualitative analysis. We mapped our results using the 14-domain TDF, eventually identifying 10 domains of interest for barriers to effective prescribing. Of these, significant domains include physician-related factors such as "Knowledge", "Skills", and "Social/Professional Role and Identity"; issues with "Environmental Context and Resources"; and the impact of "Social Influences" and "Emotion" on prescribing behaviour. CONCLUSION: The TDF elicited multiple domains which both independently and collectively lead to barriers to effective prescribing for older adults in the ambulatory setting. Changing the prescribing climate will thus require interventions targeting multiple stakeholders, including physicians, patients and hospital/clinic systems. Further work is needed to explore individual domains and guide development of frameworks to aid guide prescribing for older adults in the ambulatory setting.

The Simplified Nutritional Appetite Questionnaire (SNAQ) as a Screening Tool for Risk of Malnutrition: Optimal Cutoff, Factor Structure, and Validation in Healthy Community-Dwelling Older Adults.

Malnutrition is an independent marker of adverse outcomes in older adults. While the Simplified Nutritional Appetite Questionnaire (SNAQ) for anorexia has been validated as a nutritional screening tool, its optimal cutoff and validity in healthy older adults is unclear. This study aims to determine the optimal cutoff for SNAQ in healthy community-dwelling older adults, and to examine its factor structure and validity. We studied 230 community-dwelling older adults (mean age 67.2 years) who were nonfrail (defined by Fatigue, Resistance, Ambulation, Illnesses & Loss (FRAIL) criteria). When compared against the risk of malnutrition using the Mini Nutritional Assessment (MNA), the optimal cutoff for SNAQ was ≤15 (area under receiver operating characteristic (ROC) curve: 0.706, sensitivity: 69.2%, specificity: 61.3%). Using exploratory factor analysis, we found a two-factor structure (Factor 1: Appetite Perception; Factor 2: Satiety and Intake) which accounted for 61.5% variance. SNAQ showed good convergent, discriminant and concurrent validity. In logistic regression adjusted for age, gender, education and MNA, SNAQ ≤15 was significantly associated with social frailty, unlike SNAQ ≤4 (odds ratio (OR) 1.99, p = 0.025 vs. OR 1.05, p = 0.890). Our study validates a higher cutoff of ≤15 to increase sensitivity of SNAQ for anorexia detection as a marker of malnutrition risk in healthy community-dwelling older adults, and explicates a novel two-factor structure which warrants further research.

Caregiver Burden: Looking Beyond the Unidimensional Total Score.

The Zarit Burden Interview allows caregiver burden to be interpreted from a total score. However, recent studies propose a multidimensional Zarit Burden Interview model. This study aims to determine the agreement between unidimensional (UD) and multidimensional (MD) classification of burden, and differences in predictors among identified groups. We studied 165 dyads of dementia patients and primary caregivers. Caregivers were dichotomized into low-burden and high-burden groups based upon: (1) UD score using quartile cutoffs; and (2) MD model via exploratory cluster analysis. We compared UD versus MD 2×2 classification of burden using κ statistics. Caregivers not showing agreement by either definition were classified as "intermediate" burden. We performed binary logistic regression to ascertain differences in predictive factors. The 2 models showed moderate agreement (κ=0.72, P<0.01), yielding 104 low, 20 intermediate (UD "low burden"/MD "high burden"), and 41 high-burden caregivers. Neuropsychiatric symptoms [odds ratio (OR)=1.27, P=0.003], coresidence (OR=6.32, P=0.040), and decreased caregiving hours (OR=0.99, P=0.018) were associated with intermediate burden, whereas neuropsychiatric symptoms (OR=1.21, P=0.001) and adult children caregivers (OR=2.80, P=0.055) were associated with high burden. Our results highlight the differences between UD and MD classification of caregiver burden. Future studies should explore the significance of the noncongruent intermediate group and its predictors.

Subconjunctival haemorrhage from bronchoscopy: A case report.

Flexible bronchoscopy has been available for almost five decades. It has evolved as one of the most commonly used invasive diagnostic and therapeutic procedure in pulmonology, and its scope of applications is progressively expanding with the addition of new adjunct technologies such as endobronchial ultrasound, bronchial Thermoplasty, and navigational bronchoscopy. It is a safe procedure with complications ranging from fever, infiltrates, hypoxemia, bleeding, pneumothoraces and death, with most significant complications being bleeding and pneumothorax. We report a case of subconjuctival haemorrhage as an immediate complication of bronchoscopy. To our knowledge this is the first report documenting this rare complication.

Biomechanical response targets for physical and computational models of the pediatric trunk.

OBJECTIVES: This paper quantifies pediatric thoracoabdominal response to belt loading to guide the scaling of existing adult response data and to assess the validity of a juvenile porcine abdominal model for application to the development of physical and computational models of the human child. METHODS: Table-top belt-loading experiments were performed on 6, 7, and 15 year-old pediatric post-mortem human subjects (PMHS). Response targets are reported for diagonal belt and distributed loading of the anterior thorax and for horizontal belt loading of the abdomen. RESULTS: The pediatric PMHS exhibited abdominal response similar to the swine, including the degree of rate sensitivity. The thoraces of the PMHS were as stiff as, or slightly more stiff than, published adult corridors. CONCLUSIONS: An assessment of age-related changes in thoracic stiffness suggests that the effective stiffness of the chest increases through the fourth decade of life and then decreases, resulting in stiffness values similar for children and elderly adults.

The biomechanics of the pediatric and adult human thoracic spine.

A growing body of literature points out the relevance of the thoracic spine dynamics in understanding the thorax-restraint interaction as well as in determining the kinematics of the head and cervical spine. This study characterizes the dynamic response in bending of eight human spinal specimens (4 pediatric: ages 7 and 15 years, 4 adult: ages 48 and 52 years) from two sections along the thoracic spine (T2-T4 and T7-T9). Each specimen consisted of three vertebral bodies connected by the corresponding intervertebral discs. All ligaments were preserved in the preparation with the exception of the inter-transverse ligament. Specimens were exposed to a series of five dynamic bending ramp-and-hold tests with varying amplitudes at a nominal rate of 2 rad/s. After this battery of tests, failure experiments were conducted. The 7-year-old specimen showed the lowest tolerance to a moment (T2-T4: 12.1 Nm; T7-T9: 11.6 Nm) with no significant reduction of the relative rotation between the vertebrae. The 15-year-old failure tolerance was comparable to that of the adult specimens. Failure of the adult specimens occurred within a wide range at the T2-T4 thoracic section (23.3 Nm- 53.0 Nm) while it was circumscribed to the interval 48.3 Nm-52.5 Nm for the T7-T9 section. The series of dynamic ramp-and-hold were used to assess two different scaling methods (mass scaling and SAE scaling). Neither method was able to capture the stiffness, peak moment and relaxation characteristics exhibited by the pediatric specimens.

Response of the human torso to lateral and oblique constant-velocity impacts.

The objective of this study was to provide new biomechanical response data for the thorax with lateral and oblique loading, so as to support the development of safety systems for side impact protection that would offer the level of protection that has been achieved in frontal impact. Three male human cadavers were successively impacted by an impactor system delivering a constant velocity impact from the left and the right sides at three levels (shoulder, upper chest and mid-chest). Different impact directions were also chosen for each side: lateral, +15° posterolateral, -15° anterolateral. One subject was impacted at 1, 3 and 6 m/s whereas the other two subjects were impacted at 3 m/s only. A total of nineteen tests was performed. The impact force and the chest lateral deflection were measured using respectively a standard data acquisition system and also an optoelectronic stereophotogrammetric system (OSS). After each test, attempts were made to detect rib fractures by palpation, and a necropsy of the torso was performed after the tests series to document the injuries produced by all the tests. Overall, the peak impact force increased from the lowest impact level (mid-chest) to the highest (shoulder) and was found to be rate-sensitive. The force-deflection relationship was non linear for the shoulder impacts (stiffness increased with increasing deflection) whereas stiffness was nearly constant for the mid- and upper-chest impacts. The anterolateral impacts to the mid- and upper-chest generated more rib fractures than the other impact directions.

Expansion and evaluation of data characterizing the structural behavior of the pediatric abdomen.

Despite the importance of abdominal injuries in children involved in motor vehicle collisions, only two papers have reported experimental data quantifying the pediatric abdominal response to belt loading. One developed and characterized a porcine model of the pediatric abdomen and the other presented a series of tests performed on a single pediatric (7-year-old female) post-mortem human subject (PMHS) and used the data to evaluate the efficacy of the porcine model. The current paper presents the results from an additional pediatric (6-year-old female) PMHS test series and an expanded evaluation of the porcine model using the combined PMHS data. The two PMHS exhibited remarkably similar abdominal stiffness, both by level (upper and lower) and by rate (quasi-static and ∼2 m/s dynamic). Both PMHS and swine exhibited the same stiffness trend by abdominal level (lower stiffer than upper: 3444 N reaction force at 30.5 mm of displacement compared to 1756 N in the 6-year-old dynamic tests). The magnitude of lower abdomen stiffness was slightly less in the swine than in the PMHS (the average dynamic PMHS response was 1086 N greater than the porcine envelopes at 30.5 mm displacement) while the upper abdomen PMHS responses fit within the porcine response envelope.