High-Throughput In-Use and Stress Size Stability Screening of Protein Therapeutics Using Algorithm-Driven Dynamic Light Scattering

Stability of therapeutic proteins (TPs) is a critical quality attribute that impacts both safety and efficacy of the drug. Size stability is routinely performed during and after biomanufacturing. Dynamic light scattering (DLS) is a commonly used technique to characterize hydrodynamic size of the TPs. Herein, we have developed a novel method to evaluate in-use and thermal stress stability of TPs using algorithm-driven high-throughput DLS. Five marketed TPs were tested under the guidance of customized algorithms. The TPs were evaluated at relevant temperature conditions as well as under dilution and thermal stress for size stability. We found that the TPs were stable under the in-use conditions tested; however, sample loss due to evaporation can lead to large protein aggregates. A combined assessment of autocorrelation function and photos of sample well could be useful in formulation screening. Dilution of TPs also has an impact on the hydrodynamic size. Thermal stress experiments showed the importance of using different data processing methods to access size distribution. Polydispersity index was useful in evaluating sample heterogeneity. Herein, we show that algorithm-driven high-throughput DLS can provide additional supportive information during and after biomanufacturing and the potential to be used in a quality control environment.     

Synergistic effects of ischemic preconditioning and immediate post‐conditioning in the protection against ischemia/reperfusion injury in rabbit submandibular glands

Submandibular gland autotransplantation is an effective approach for treating severe keratoconjunctivitis sicca. However, ischemia/reperfusion (I/R) injury, which inevitably occurs during transplantation, is involved in the hypofunction and structural damage that occur early after transplantation. Therefore, it is critical to identify effective strategies to ameliorate I/R injury in submandibular glands. In this study, we investigated the ability of immediate post‐conditioning combined with ischemic preconditioning to attenuate I/R injury. We observed that after I/R injury, the level of reactive oxygen species was increased, inflammatory response was strengthened, and severe apoptosis had occurred. In addition, the salivary flow rate was greatly decreased. However, the pathogenesis of I/R injury was significantly ameliorated by ischemia post‐conditioning or ischemia preconditioning treatments. In addition, the combination of ischemia preconditioning and post‐conditioning achieved synergistic protective effects against I/R injury compared with ischemia preconditioning or ischemia post‐conditioning alone. The secretion function was restored in the combination group. Furthermore, the combination treatment involved the same mechanisms of ischemia preconditioning or ischemia post‐conditioning, including suppression of the inflammatory reaction and neutrophil accumulation, attenuation of oxidation stress, and inhibition of apoptosis. In conclusion, the combination of ischemia preconditioning and ischemia post‐conditioning treatment is a simple and effective approach for treating I/R injury in submandibular glands.     

Adapting the revised prenatal coping inventory (NuPCI) for use in a Spanish population

Objective: To adapt the Revised Prenatal Coping Inventory (NuPCI) for the evaluation of prenatal stress coping strategies utilised by Spanish women.

Methods: A cross-sectional study was performed to evaluate the psychometric properties of NuPCI adapted for a Spanish population. Two hundred and sixty one puerperium women completed the NuPCI at the time of discharge after childbirth. Instrument construct validity was evaluated using subscale item correlations. Internal consistency was assessed using Cronbach’s α test.

Results: Items from each subscale (Preparation, Avoidance and Spiritual – Positive Coping) were significantly correlated with the global result (p?α?>?0.7). The most frequently used coping strategy was Preparation and the least used was Avoidance. Utilisation of the coping strategies with Preparation decreased with increasing parity (p?=?.002) and greater prenatal stress was associated with increased use of the Avoidance coping strategy (p?Conclusions: The NuPCI adapted for Spanish women demonstrates good psychometric properties for evaluating the three types of prenatal stress coping strategies: Preparation, Avoidance and Spiritual – Positive Coping. Results were similar to those presented by the instrument in its English language version.     

Comparisons of self-ratings on managerial competencies,research capability,time management,executive power,workload and work stress among nurse administrators

Aims To assess the level of and the differences in managerial competencies, research capability, time management, executive power, workload and work-stress ratings among nurse administrators (NAs), and to determine the best predictors of managerial competencies for NAs. Background Although NAs require multifaceted managerial competencies, research related to NAs’ managerial competencies is limited. Method A cross-sectional survey was conducted with 330 NAs from 16 acute care hospitals. Managerial competencies were determined through a self-developed questionnaire. Data were collected in 2011. Results All NAs gave themselves the highest rating on integrity and the lowest on both financial/budgeting and business acumen. All scores for managerial competencies, research capability, time management and executive power showed a statistically significant correlation. The stepwise regression analysis revealed that age; having received NA training; having completed a nursing project independently; and scores for research capability, executive power and workload could explain 63.2% of the total variance in managerial competencies. Conclusion The present study provides recommendations for future administrative training programmes to increase NAs’ managerial competency in fulfilling their management roles and functions. Implications for Nursing Management The findings inform leaders of hospitals where NAs need to develop additional competencies concerning the type of training NAs need to function proficiently.     

Decrease in Antioxidant Status of Plasma and Erythrocytes from Geriatric Population

Background: Ageing is associated with an accumulation of free radical damage, which leads to physiological and clinical modifications. The study aims to find out the status of lipid profile, antioxidant enzymes, malondialdehyde in geriatric population. Patients/methods: The study was conducted on 150 subjects (75 healthy control between the ages of 20–30 years and 75 elderly subjects between ages of 50–70 years as cases). The following parameters were analyzed using the standard reference methods: lipid profile, reduced glutathione, glutathione peroxidase, glutathione reductase, catalase, superoxide dismutase and malondialdehyde. Results: The present study was conducted to estimate the oxidative stress parameters in geriatric population. Highly significant increase in total cholesterol (TC), triglyceride (TG), LDL-cholesterol (LDL-C), VLDL-cholesterol (VLDL-C), malondialdehyde, catalase and decrease in high density lipoprotein cholesterol (HDL-C), reduced glutathione, glutathione peroxidase, glutathione reductase, superoxide dismutase was observed in geriatrics when compared with their younger counterparts. Conclusion: This study concluded that there is enhanced oxidative stress and decreased antioxidant defence in geriatrics as compared to younger subjects which could play an important role in ageing. Dyslipidemia has become one of the important risk factors for the increasing prevalence of cardiovascular diseases. There is lack of awareness on the relationship between blood lipids and the risk of cardiovascular diseases in geriatric population. The strategy of early prevention should be adopted against dyslipidemia.     

The time course of psychological stress as revealed by event-related potentials

Psychological stress is common in everyday life and is believed to affect emotion, cognition and health. Previous brain imaging studies have been able to identify the brain regions involved in the stress response. However, our understanding of the temporal neurological response to psychological stress is limited. The present work aims to investigate the time course of psychological stress induced by a mental arithmetic task, utilizing event-related potentials (ERPs). The elicitation of stress was verified by self-reports of stress and increases in salivary cortisol levels. The subjective and physiological data showed that the stress-elicitation paradigm successfully induced a mild-to-moderate level of psychological stress. The electrophysiological data showed that the amplitude of occipital N1 was more negative in the control task than in the stress task, and the latency of frontal P2 was shorter in the stress task than in the control task. Our results provide electrophysiological evidence that psychological stress occurs primarily at the early stage of cognitive processing.     

Evaluation of stress and pain during rapid maxillary expansion treatments

Summary The purpose of this study was to use salivary cortisol levels, pressure pain threshold (PPT) and Spielberger’s State‐Trait Anxiety Inventory for Children (STAIC) to assess stress, anxiety and pain during the expansion and retention phase of rapid maxillary expansion (RME) in children and investigate to whether this parameters are associated with gender or skeletal maturity stages. STAIC was used to assess the anxiety levels of the children. Salivary samples were collected for stress hormone determination. Visual Analog Scale was used for pain determination. Pressure pain threshold (PPT) was measured by using algometer. Data collection was performed a week before RME treatment (T0), at the day of the expansion appliance was bonded (T1), at the days of 1st, 4th, 7th, 14th, 25th, 36th activations of expansion screw (T2, T3, T4, T5, T6, T7) and after the retention period of 3 months (T8). The results of this study showed that the differences were statistically significant within‐day (P < 0·001) and within‐hours (P < 0·001) in cortisol levels during treatment. PPT levels were statistically significant within sex differences and skeletal maturity stages (P < 0·05). State‐trait anxiety scale scores were similar with respect to gender (P > 0·05). There were statistically significant differences of state‐trait anxiety levels between pre and post‐treatment stages (P < 0·05). The maximum number of patients reporting pain were days at T3 and T4. From day T5 the percentage of patients reporting pain then gradually reduced. Based on the findings of this study, it has been shown that RME leads to changes in patients’ state‐trait anxiety and cortisol levels.     

Type a Behavior and Cardiovascular Recovery from a Psychosocial Stressor

Abstract

The present study examined heart rate responses of Type A and Type B individuals during and after performance on the Stroop perceptual conflict task. The student version of the Jenkins Activity Survey was administered to thirty-two male Caucasians, who then performed the Stroop task for six minutes under conditions that emphasized time urgency and competition. Results showed that Type A's recovered significantly slower than Type B's after task completion. Type A's, compared to Type B's reported feeling more angry, time pressured, and impatient. The notion that Type A individuals may be at higher risk for coronary heart disease because of maladaptively prolonged cardiovascular arousal was discussed.     

The stress response resolution assay. II. Quantitative assessment of environmental agent/condition effects on cellular stress resolution outcomes in epithelium

Cellular stress responses consist of a complex network of pathways and linked processes that, when perturbed, are postulated to have roles in the pathogenesis of various human diseases. To assess the impact of environmental insults upon this network, we developed a novel stress response resolution (SRR) assay for investigation of cellular stress resolution outcomes and the effects of environmental agents and conditions thereupon. SRR assay‐based criteria identified three distinct groups of surviving cell clones, including those resembling parental cells, those showing Hprt/HPRT mutations, and a third type, “Phenotype‐altered” clones, that occurred predominantly in cells pretreated with a chemical mutagen, was heterogeneous in nature, and expressed significant alterations in cell morphology and/or function compared with parental cells. Further evaluation of Phenotype‐altered clones found evidence of various alterations that resembled epithelial‐to‐mesenchymal transition, phenotype switching, checkpoint dysfunction, senescence barrier bypass, and/or epigenetic reprogramming. Phenotype‐altered clones were found to occur spontaneously in a cell line with a mutator phenotype, to represent the major surviving clone type in a variation of the SRR assay, and to be tumorigenic in nude mice. Assessment of SRR assay final results showed that pretreatment with a chemical mutagen induced significant changes in cellular stress response prosurvival capacity, in damage avoidance versus damage tolerance stress resolution outcomes, and in the damage burden in the final surviving cell populations. Taken together, these results support the conclusion that use of the SRR assay can provide novel insights into the role of environmental insults in the pathogenesis of cancer and other human diseases. Environ. Mol. Mutagen. 54:281–293, 2013. © 2013 Wiley Periodicals, Inc.     

Stressful Life Events and Perimenstrual Symptoms

Abstract

The purpose of this study was to determine whether the effects of stressful life events on perimenstrual symptoms were due to operational confounding of the instruments used to measure the independent and dependent variables. Women aged 18 to 35 (n = 179) completed the Schedule of Recent Events (SRE) and the Moos Menstrual Distress Questionnaire during a home interview. When variance in PMS scores attributable to age, parity, education, and contraceptive method was controlled using hierarchical multiple regression, total SRE scores were correlated with premenstrual and menstrual negative affect, menstrual water retention, and menstrual performance impairment. When health-related components of the SRE score were controlled in a similar manner, however, the residual SRE scores explain a diminished amount of the variance in premenstrual and menstrual negative affect and menstrual performance impairment. Future investigations are needed to clarify whether the effects of health-related life events on perimenstrual symptoms are simply a matter of operational confounding of measures of the independent and dependent variables, or whether women who recently have experienced personal illness or injury are at greater risk of developing perimenstrual symptoms.