Raman spectroscopy provides valuable process insights for cell-derived and cellular products.

Two of the big challenges in modern bioprocesses are process economics and in-depth process understanding. Getting access to online process data helps to understand process dynamics and monitor critical process parameters (CPPs). This is an important part of the quality-by- design concept that was introduced to the pharmaceutical industry in the last decade. Raman spectroscopy has proven to be a versatile tool to allow noninvasive measurements and access to a broad spectrum of analytes. This information can then be used for enhanced process control strategies. This review article will focus on the latest applications of Raman spectroscopy in established protein production bioprocesses as well as show its potential for virus, cell therapy, and mRNA processes.

Meta-Analysis of Antidepressant Pharmacotherapy in Patients Eligible for Cardiac Rehabilitation: ANTIDEPRESSANT AMBIVALENCE.

PURPOSE: Many patients exhibit clinically significant depression upon enrollment in cardiac rehabilitation (CR). Antidepressants are a first-line treatment option for depression, but the effectiveness of antidepressants in patients with heart disease is mixed. The purpose of this meta-analysis was to evaluate the efficacy of antidepressants for depression in patients eligible for CR. METHODS: A meta-analysis was conducted including randomized controlled trials of antidepressants from January 1990 to September 2021 that compared antidepressants with placebo. Random-effects models were used between group effect sizes (Hedges' g ). RESULTS: A total of 13 trials with predominately White (68% ± 12; n =7) male (70% ± 11) samples averaging 61 ± 5 yr compared antidepressants (1128 participants) with placebo (1079 participants). Antidepressants reduced depressive symptoms ( g = 0.17: 95% CI, 0.08-0.27), but the effect was small. Heterogeneity among study effects was low ( I2 = 6.42) and nonsignificant ( Q = 10.75, P = .46), although patients with heart failure ( gHF = 0.05: 95% CI, -0.09 to 0.18) demonstrated smaller effects compared with patients with other cardiovascular disease conditions (g non-HF = 0.22: 95% CI, 0.11-0.32) ( QB [1] = 3.97; P < .05). No study reported safety concerns associated with antidepressants. SUMMARY: The effect size of antidepressant pharmacotherapy in this population is small. No trials reported on the combined effects of exercise and pharmacotherapy. If the patient is not suicidal, CR staff may consider patient preference and refer patients for additional treatment as necessary.

Exploring How Trait Mindfulness Relates to Perceived Stress and Cardiovascular Reactivity.

BACKGROUND: Mindfulness interventions have been associated with less global perceived stress as well as attenuated cardiovascular reactivity. The aim of the present study was to evaluate whether high levels of trait mindfulness would also be associated with these benefits. METHODS: Participants were 99 healthy young adults aged 18-25 years. Self-report measures included the Five Facet Mindfulness Questionnaire and the Perceived Stress Scale. Participants completed a laboratory stress protocol comprised of a resting baseline, a mental arithmetic stress task, and a resting recovery period. Blood pressure, heart rate, and heart rate variability were measured throughout the protocol. Regressions were used to analyze whether trait mindfulness predicted global perceived stress, cardiovascular reactivity, and cardiovascular recovery. RESULTS: Two trait mindfulness facets were found to be associated with less global perceived stress, Acting with Awareness (ß = - .306, p = .002) and Nonjudgment (ß = - .342, p < .001). Exploratory analyses also revealed an interaction between the Observe and Nonreactivity facets (p = .002), such that the Observe facet was associated with less stress only when Nonreactivity scores were also high. Although trait mindfulness was not a significant predictor of the physiological variables (p > .05, Cohen's f2 < .060), exploratory analyses revealed an interaction between the Awareness and Nonjudgment facets (p < .001), such that Awareness is associated with lower diastolic blood pressure reactivity only when Nonjudgment scores are also high. CONCLUSIONS: Like mindfulness interventions, trait mindfulness is associated with less global perceived stress. Interactions between trait mindfulness facets that reflect attention monitoring and acceptance might predict physiological reactivity in certain contexts, though a mindful state might be necessary for most real-time cardiovascular benefits.

Sleep quality and daytime sleepiness are not associated with cognition in heart failure.

BACKGROUND: Individuals with heart failure (HF) exhibit comorbid impairments in both sleep and cognitive performance. Sleep quality has been associated with impaired cognitive performance in HF patients, but reports are inconsistent. In this study, we examined associations between sleep quality, daytime sleepiness, and cognitive function in HF. METHODS AND RESULTS: Participants were 267 (age = 69.1 ±â€¯9.3) mostly Caucasian (74.9%), male (59.6%) stable HF patients recruited from outpatient settings. This cross-sectional study was a secondary analysis of a prospective observational study. Cognitive function domains assessed included: global cognitive function, attention, memory, and executive function. Sleep quality and daytime sleepiness were assessed using the Pittsburgh Sleep Quality Index (PSQI) and the Epworth Sleepiness Scale (ESS), respectively. Separate multiple hierarchical linear regressions were conducted to determine associations between cognitive function and sleep quality and daytime sleepiness, after controlling for sex, New York Heart Association (NYHA) class, education, depressive symptoms, and medical comorbidities. Cognitive function was not associated with sleep quality or daytime sleepiness after alpha inflation corrections were applied. CONCLUSIONS: Cognitive function in HF is not associated with sleep quality or daytime sleepiness; other factors may exert greater influence on cognitive performance.

Microfluidic Flow Cell Array for Controlled Cell Deposition in Engineered Musculoskeletal Tissues.

Musculoskeletal tissues contain critical gradients in extracellular matrix (ECM) composition and cell types that allow for proper mechanical function of tissues and integration between adjacent tissues. However, properly controlling these patterns in engineered tissues is difficult and tissue engineering (TE) is presently in need of methods to generate integration zones for tissue anchoring, transition zones between tissues, and controlled ECM gradients for proper mechanical function. In this study, we present a novel method of using a microfluidic flow cell array (MFCA) to precisely control cell deposition onto TE constructs to produce tunable cell patterns on engineered constructs. In this study, we characterized MFCA cell deposition to efficiently and reliably deposit cells in controllable patterns and densities. We developed methods for deposition of human adipose-derived stem cells and human osteoblasts using a 12-channel pilot printhead. We mimicked key gradients and transitions by creating two-cell and three-cell-type transitions characteristic of the integration zones of musculoskeletal tissues. Overall, we demonstrate the ability to precisely and reproducibly control cell deposition on engineered constructs using this method and control cell population gradients. We establish the production of multicell transitions and multicell interfaces utilizing MFCA cell deposition, to demonstrate the potential of the method to create an extensive variety of engineered musculoskeletal tissues. Furthermore, customization of the printhead design can accommodate various structures, sizes, shapes, and number of flow cell channels to meet specific requirements for a broad range of musculoskeletal tissues.

A soft patellar tendon on ultrasound elastography is associated with pain and functional deficit in volleyball players.

OBJECTIVES: To investigate the diagnostic performance of grey scale Ultrasound (US), power Doppler (PD) and US elastography for diagnosing painful patellar tendinopathy, and to establish their relationship with Victorian Institute of Sport Assessment-Patella (VISA-P) scores in a group of volleyball players with and without symptoms of patellar tendinopathy. DESIGN: Cross-sectional study. METHODS: Thirty-five volleyball players (70 patellar tendons) were recruited during a national university volleyball competition. Players were imaged with conventional US followed by elastography. The clinical findings of painful patellar tendons were used as the reference standard for diagnosing patellar tendinopathy. In addition, all participants completed the VISA-P questionnaires. RESULTS: Of the 70 patellar tendons, 40 (57.1%) were clinically painful. The diagnostic accuracy of grey scale US, PD and elastography were 60%, 50%, 62.9%, respectively, with sensitivity/specificity of 72.5%/43.3%, 12.5%/100%, and 70%/53.3%, respectively. Combined US elastography and grey scale imaging achieved 82.5% sensitivity, 33.3% specificity and 61.4% accuracy while routine combination technique of PD and grey scale imaging revealed 72.5% sensitivity, 43.3% specificity and 60.0% accuracy. Tendons in players categorized as soft on elastography had statistically significantly greater AP thickness (p<0.001) and lower VISA-P scores (p=0.004) than those categorized as hard. There was no significant association between grey scale US abnormalities (hypoechogenicities and/or fusiform swelling) and VISA-P scores (p=0.098). CONCLUSIONS: Soft tendon properties depicted by US elastography may be more related to patellar tendon symptoms compared to grey scale US abnormalities. The supplementation of US elastography to conventional US may enhance the sensitivity for diagnosing patellar tendinopathy in routine clinical practice.

Fractures of the olecranon: an in vitro study of elbow joint stresses after tension-band wire fixation versus proximal fracture fragment excision.

BACKGROUND: Displaced fractures of the olecranon usually require operative treatment, by either open reduction with internal fixation (ORIF) or excision of the proximal fragment. However, the relative merits of these treatment options have not been fully delineated. One treatment outcome measure of joint function is residual intra-articular stress. The purpose of this study was to evaluate the effect of these two types of olecranon fracture treatment on humeroulnar joint stress. METHODS: Eight matched pairs of fresh frozen cadaveric upper extremities were thawed; stripped of skin, muscular, and neurovascular tissue; and potted in polymethylmethacrylate. The intra-articular humeroulnar joint peak pressures were measured at 90 degrees of elbow flexion using pressure-sensitive film after application of a 0.15 kg-m torque through the remaining triceps muscle attachment. First, pretreatment (normal) pressures were obtained from the major contact regions of the humeroulnar joint. A 50% olecranon osteotomy was then performed simulating a fracture, and the elbows from each of the paired specimens were randomly assigned to one or the other of two treatment groups: ORIF (using a tension-band wiring technique) and proximal fragment excision. Joint pressures were remeasured. A two-tailed paired t test was used for statistical analysis. RESULTS: After osteotomy, the peak pressures were higher, overall, in the excision group. Comparing each posttreatment experimental group to its pretreatment (normal) counterpart revealed that the peak pressures in the distal medial and distal lateral articular subzones were significantly higher for the fragment excision group (p = 0.005 and p= 0.0008, respectively), but were not significantly different in the ORIF group (p = 0.545 and p= 0.153, respectively). CONCLUSION: The findings of this study indicate that ORIF restores the normal biomechanics of the elbow joint and proximal fragment excision results in abnormally elevated joint stresses. These elevated joint stresses may, over time, contribute to the development of elbow pain and osteoarthrosis. Therefore, ORIF should continue to be regarded as the treatment of choice for displaced fractures of the olecranon involving large proximal fracture fragments similar in size to those in this study.