An assessment of the impact of Raman based glucose feedback control on CHO cell bioreactor process development.

Process analytical technology (PAT) tools such as Raman Spectroscopy have become established tools for real time measurement of CHO cell bioreactor process variables and are aligned with the QbD approach to manufacturing. These tools can have a significant impact on process development if adopted early, creating an end-to-end PAT/QbD focused process. This study assessed the impact of Raman based feedback control on early and late phase development bioreactors by using a Raman based PLS model and PAT management system to control glucose in two CHO cell line bioreactor processes. The impact was then compared to bioreactor processes which used manual bolus fed methods for glucose feed delivery. Process improvements were observed in terms of overall bioreactor health, product output and product quality. Raman controlled batches for Cell Line 1 showed a reduction in glycation of 43.4% and 57.9%, respectively. Cell Line 2 batches with Raman based feedback control showed an improved growth profile with higher VCD and viability and a resulting 25% increase in overall product titer with an improved glycation profile. The results presented here demonstrate that Raman spectroscopy can be used in both early and late-stage process development and design for consistent and controlled glucose feed delivery.

Common genetic variation impacts stress response in the brain.

To explain why individuals exposed to identical stressors experience divergent clinical outcomes, we determine how molecular encoding of stress modifies genetic risk for brain disorders. Analysis of post-mortem brain (n=304) revealed 8557 stress-interactive expression quantitative trait loci (eQTLs) that dysregulate expression of 915 eGenes in response to stress, and lie in stress-related transcription factor binding sites. Response to stress is robust across experimental paradigms: up to 50% of stress-interactive eGenes validate in glucocorticoid treated hiPSC-derived neurons (n=39 donors). Stress-interactive eGenes show brain region- and cell type-specificity, and, in post-mortem brain, implicate glial and endothelial mechanisms. Stress dysregulates long-term expression of disorder risk genes in a genotype-dependent manner; stress-interactive transcriptomic imputation uncovered 139 novel genes conferring brain disorder risk only in the context of traumatic stress. Molecular stress-encoding explains individualized responses to traumatic stress; incorporating trauma into genomic studies of brain disorders is likely to improve diagnosis, prognosis, and drug discovery.

Modeling gene × environment interactions in PTSD using human neurons reveals diagnosis-specific glucocorticoid-induced gene expression.

Post-traumatic stress disorder (PTSD) can develop following severe trauma, but the extent to which genetic and environmental risk factors contribute to individual clinical outcomes is unknown. Here, we compared transcriptional responses to hydrocortisone exposure in human induced pluripotent stem cell (hiPSC)-derived glutamatergic neurons and peripheral blood mononuclear cells (PBMCs) from combat veterans with PTSD (n = 19 hiPSC and n = 20 PBMC donors) and controls (n = 20 hiPSC and n = 20 PBMC donors). In neurons only, we observed diagnosis-specific glucocorticoid-induced changes in gene expression corresponding with PTSD-specific transcriptomic patterns found in human postmortem brains. We observed glucocorticoid hypersensitivity in PTSD neurons, and identified genes that contribute to this PTSD-dependent glucocorticoid response. We find evidence of a coregulated network of transcription factors that mediates glucocorticoid hyper-responsivity in PTSD. These findings suggest that induced neurons represent a platform for examining the molecular mechanisms underlying PTSD, identifying biomarkers of stress response, and conducting drug screening to identify new therapeutics.

Raman based chemometric model development for glycation and glycosylation real time monitoring in a manufacturing scale CHO cell bioreactor process.

The Quality by Design (QbD) approach to the production of therapeutic monoclonal antibodies (mAbs) emphasizes an understanding of the production process ensuring product quality is maintained throughout. Current methods for measuring critical quality attributes (CQAs) such as glycation and glycosylation are time and resource intensive, often, only tested offline once per batch process. Process analytical technology (PAT) tools such as Raman spectroscopy combined with chemometric modeling can provide real time measurements process variables and are aligned with the QbD approach. This study utilizes these tools to build partial least squares (PLS) regression models to provide real time monitoring of glycation and glycosylation profiles. In total, seven cell line specific chemometric PLS models; % mono-glycated, % non-glycated, % G0F-GlcNac, % G0, % G0F, % G1F, and % G2F were considered. PLS models were initially developed using small scale data to verify the capability of Raman to measure these CQAs effectively. Accurate PLS model predictions were observed at small scale (5 L). At manufacturing scale (2000 L) some glycosylation models showed higher error, indicating that scale may be a key consideration in glycosylation profile PLS model development. Model robustness was then considered by supplementing models with a single batch of manufacturing scale data. This data addition had a significant impact on the predictive capability of each model, with an improvement of 77.5% in the case of the G2F. The finalized models show the capability of Raman as a PAT tool to deliver real time monitoring of glycation and glycosylation profiles at manufacturing scale.

Vocally disruptive behavior: A case report and literature review.

Vocally disruptive behavior (VDB) is a common and particularly difficult symptom to manage in dementia. VDB is usually considered collectively with agitation and aggression as a component of behavioral and psychological symptoms in dementia and is therefore poorly understood as an individual symptom. A review of the literature is described where VDB as a challenging behavior has been individually examined as a symptom. A case of VDB occurring in patient with dementia is described where the patient's repetitive vocalizations responded to treatment with pregabalin. This has not been previously reported in the literature. The prevalence of VDB, the factors associated with it and the current management guidelines for clinicians are outlined with a review of the drug treatment strategies for VDB. Pregabalin with its unique pharmacological profile and excellent tolerability should be considered as a possible treatment for VDB where drug treatment is indicated.

Old age psychiatry in the house: assessing the impact of a service transition from consultation to liaison old age psychiatry.

OBJECTIVE: The impact of a change in service delivery in a psychogeriatric service, moving from a consultation model to liaison model of care, was examined in a naturalistic study. METHODS: The study period was divided into two phases, defined by the change in service delivery. The impact of the change on (1) referral rate, (2) referrals seen, (3) extent of intervention and (4) clinical characteristics was examined. RESULTS: While we did not see a dramatic improvement in time waiting for assessment (2.9 vs. 2.4 days), the enhanced team provided significantly more clinical input. The number of assessments completed increased by 60% (39 vs. 66). Most significantly, during phase I, more than half of all referrals were not seen (54%), while during phase II only one patient referred was not assessed (1%). The number of reviews undertaken also increased significantly. CONCLUSIONS: The results of the present study suggest improved outcomes for patients and improved satisfaction in the clinical teams. Further clinical effectiveness and cost-effectiveness studies are needed.

Treatment of Desire Discrepancy: One Clinician's Approach.

For couples, the most common sexual problems that arise in therapy are low desire and desire discrepancy. The complex and challenging nature of desire discrepancy is addressed, along with core therapeutic interventions to confront the traditional power struggle over defining sex as intercourse only. The importance of desire is recognized in understanding that sexual satisfaction means feeling good about oneself as a sexual person and energized as a sexual couple. Intimacy and eroticism are explored, assisting the couple in understanding the value of both security and warmth, but also sensuality and arousal. The individual sex performance is replaced with a focus on intimacy, non-demanding pleasure, and the inclusion of erotic scenarios to enhance the couples' mutual sharing of sexual desire and pleasure and turn toward one another as sexual friends.

Expanding the Types of Clients Receiving Sex Therapy and Sexual Health Services.

The provision of sex therapy primarily occurs for middle-class couples by middle-class clinicians. This conceptual/clinical article advocates for sex therapy approaches that better meet the needs of individuals and couples within a broader socioeconomic range, and includes two case studies as examples. Every couple, regardless of socioeconomic status, deserves first-class sex therapy that helps establish a satisfying, secure, and sexual relationship from an empathic, respectful clinician who remains sensitive to specific vulnerabilities and challenges related to economic and social class factors.

Factors Associated With Marital Satisfaction in Infertile Couple: A Comprehensive Literature Review.

BACKGROUND: Many factors impact on marital satisfaction. Related factors include demographic factors, assisted reproductive techniques, psychological health, quality of life, psychological, socioeconomic and family support, and sexual function. METHODS: This study is a literature review of research studies conducted on factors associated with marital satisfaction in infertile couples. The current literature review search was undertaken using multiple databases selected from articles pertinent to the study. The selection of subjects was undertaken from1990 through 2015. The methodological quality was analyzed based on a checklist adopted from a systematic review. Quality assessment of full text studies was finally carried out by two reviewers. RESULTS: The initial search yielded a list of 445 papers, and then reviewers studied titles and abstracts. Thereafter, 69 papers were incorporated, and researchers reviewed summaries of all of the searched articles. Finally, the researchers utilized the data gained from 64 full articles so as to compile this review paper. Reviewing the studies conducted on marital satisfaction, they classified related findings into 6 categories: demographic factors, using fertility assisting methods, psychological health, life quality, economic, social, and family support, and sexual function. CONCLUSION: The results of this review article depicted that various factors play role in creating marriage life satisfaction in an infertile couple, so that paying attention to them can play an important role in continuing their treatment. Thus, to identify such factors is considered essential in their treatment protocol highly based on culture. Of the drawbacks of this research is that it has tried at best to employ the studies belonging to diverse countries with different cultures. Also, the number of the papers was considerably limited.

Sexual challenges with aging: integrating the GES approach in an elderly couple.

An advantage of sexuality after 60 years of age is the increased need for couple involvement to promote desire, pleasure, eroticism, and satisfaction inherent to the healthy aging process. This case study clinically explores the complex psychobiosocial interactions for understanding, assessing, and treating sexual problems for couples age 60 years and older, emphasizing the Good Enough Sex approach of variable, flexible, and shared sexual pleasure. Aging couples are discouraged from appraising their sexual experiences within the parameters of the pass/fail binary of the traditional individual performance model and are instead encouraged to embrace the evolving elasticity of their sexual experiences. The Good Enough Sex model espouses an approachable and satisfying alternative for the promotion of sexual function and satisfaction throughout the life span, with particular interest in late adulthood sexual health.

New strategies in assessing, treating, and relapse prevention of extramarital affairs.

Understanding, assessing, treating, and preventing relapse of extra-marital affairs has involved significant changes in the past 10 years. This conceptual/clinical article expands on the groundbreaking work of Snyder, Gordon, and Baucom (2007), and has a special focus placed on the process of sexual recovery from an extra-marital affair. Secondly, this article focuses on the importance of creating a relapse prevention agreement. Both traditional and non-traditional agreements with regard to monogamy are described. Recognizing individual, couple, cultural, and value differences in norms and expectations exhibits a particular challenge in the study and treatment of extra-marital affairs. The clinician honors these complexities and differences by designing a treatment program that meets the needs of each couple.

The impact of sexual trauma on sexual desire and function.

The field of sexual trauma is one of the most controversial and value-laden in mental health. The three factors which most affect adult sexual desire and function are the type of sexual trauma, how the sexual incidents were dealt with at the time and, most important, whether the person views her/himself as a survivor or victim. The assessment and treatment program described focuses on couple sex therapy with a special focus on processing the sexual trauma, honoring the person's veto and being 'partners in healing'. The core therapeutic theme is valuing intimate, erotic sexuality, which reinforces being a proud survivor rather than a shameful, anxious or angry victim. It is crucial to create a relapse prevention program to ensure that the person with the sexual trauma history continues to experience the positive roles of adult couple sexuality.

Sex therapy failures: a crucial, yet ignored, issue.

There are a range of factors that can cause sex therapy failure including biological/medical, psychological, relational, and relapse prevention issues. The goal of this article is to generate conceptual, empirical, and clinical interest in the crucial, yet ignored, problem of sex therapy failure.

Men, intimacy, and eroticism.

INTRODUCTION: We present a conceptual/clinical article focused on the Good-Enough Sex model of male and couple sexuality. This offers a comprehensive, integrative couple approach to understanding and treating male sexual dysfunction. AIM: To examine the couple biopsychosocial approach to assessing and treating male sexual dysfunction. The focus is integrating intimacy and eroticism as the man and the relationship age. METHODS: The clinical case example examines the role of integrating intimacy and eroticism as the man and the relationship mature. The role of the clinician in helping the man and couple develop positive, realistic sexual expectations is crucial in both the change process and relapse prevention. MAIN OUTCOME MEASURES: The clinical assessment of the man and couple focuses specifically on the interplay of desire, erection, intercourse, and orgasm. RESULTS: The man and couple valuing each other as intimate, erotic partners, and adopting the Good-Enough Sex model rather than clinging to the pass-fail perfect intercourse performance criterion are crucial for therapeutic success. CONCLUSIONS: When couples stop being sexual, it is almost always the man's decision-he has lost confidence with arousal, intercourse, and orgasm. Men and couples who adopt the Good-Enough Sex model are well positioned to ensure pleasurable, satisfying sexuality into their 60s, 70s, and 80s.

Integrating medication, realistic expectations, and therapeutic interventions in the treatment of male sexual dysfunction.

Male sexuality in adolescence and early adulthood is characterized by autonomous, predictable erections. As males age, however, their arousal becomes less predictable and more dependent on partner interaction. This transition can produce anxiety. Many males view this change as a medical dysfunction requiring pharmacologic treatment or specialist intervention. New medical interventions, including Viagra, have been developed promising to return males to their automatic erections. A medical approach, however, fails to address the multidimensional nature of male sexuality and reinforces sex as intercourse performance. This article outlines a biopsychosocial approach to the assessment, treatment, and relapse prevention of male sexual dysfunction.

Sexual secrets, trauma, and dysfunction.

The majority of people who present for couple sex therapy have sexual secrets, often involving both past and present experiences. This article explores the most-common sexual secrets, the ways that secrets can subvert treatment, the decision whether to share secrets, techniques for sharing secrets, and the motivating impact on marital trust and sexuality of confronting secrets.