Cell‐ and Gene‐Based Therapeutic Strategies for Periodontal Regenerative Medicine

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/142086/1/jper1223.pd

The Two-Domain LysX Protein of Mycobacterium tuberculosis Is Required for Production of Lysinylated Phosphatidylglycerol and Resistance to Cationic Antimicrobial Peptides

The well-recognized phospholipids (PLs) of Mycobacterium tuberculosis (Mtb) include several acidic species such as phosphatidylglycerol (PG), cardiolipin, phosphatidylinositol and its mannoside derivatives, in addition to a single basic species, phosphatidylethanolamine. Here we demonstrate that an additional basic PL, lysinylated PG (L-PG), is a component of the PLs of Mtb H37Rv and that the lysX gene encoding the two-domain lysyl-transferase (mprF)-lysyl-tRNA synthetase (lysU) protein is responsible for L-PG production. The Mtb lysX mutant is sensitive to cationic antibiotics and peptides, shows increased association with lysosome-associated membrane protein–positive vesicles, and it exhibits altered membrane potential compared to wild type. A lysX complementing strain expressing the intact lysX gene, but not one expressing mprF alone, restored the production of L-PG and rescued the lysX mutant phenotypes, indicating that the expression of both proteins is required for LysX function. The lysX mutant also showed defective growth in mouse and guinea pig lungs and showed reduced pathology relative to wild type, indicating that LysX activity is required for full virulence. Together, our results suggest that LysX-mediated production of L-PG is necessary for the maintenance of optimal membrane integrity and for survival of the pathogen upon infection

An international consensus definition of thewish to hasten death and Its related factors

Abstract Background The desire for hastened death or wish to hasten death (WTHD) that is experienced by some patients with advanced illness is a complex phenomenon for which no widely accepted definition exists. This lack of a common conceptualization hinders understanding and cooperation between clinicians and researchers. The aim of this study was to develop an internationally agreed definition of the WTHD. Methods Following an exhaustive literature review, a modified nominal group process and an international, modified Delphi process were carried out. The nominal group served to produce a preliminary definition that was then subjected to a Delphi process in which 24 experts from 19 institutions from Europe, Canada and the USA participated. Delphi responses and comments were analysed using a pre-established strategy. Findings All 24 experts completed the three rounds of the Delphi process, and all the proposed statements achieved at least 79% agreement. Key concepts in the final definition include the WTHD as a reaction to suffering, the fact that such a wish is not always expressed spontaneously, and the need to distinguish the WTHD from the acceptance of impending death or from a wish to die naturally, although preferably soon. The proposed definition also makes reference to possible factors related to the WTHD. Conclusions This international consensus definition of the WTHD should make it easier for clinicians and researchers to share their knowledge. This would foster an improved understanding of the phenomenon and help in developing strategies for early therapeutic intervention

Gender and Caregiving

There has also been extremely limited funding available for the essential research that will inform interventions and programs to understand how to best support women and men in their caregiver roles. Hopefully, the changing demographics relating to age and increased budgetary implications for the healthcare system and consumer demand will motivate increases in support for such basic and essential information. Since gender is one of the most basic biological and psychosocial characteristics of individuals, knowledge of caregivers’ gender can be the first step toward understanding the complexities of cancer caregiving. Once intergender variations are more fully and objectively understood, additional components of the caregiver should be studied, such as; intragender differences, culture, age, race/ethnicity, relationship characteristics, stage in life span, and other demographics. Another important factor to be considered is the alignment of expectations and demands of the caregiver and the care recipient. This “fit” is essential for both the caregiver and care recipient's quality of life and can be gained through honest and open communication, education, and a deep understanding of the innate differences between men and women and how these differences are magnified in times of stress. For example, female caregivers report more emotional distress overall; however, male caregivers suffer more physically. In female caregivers, her selfefficacy is highly related to how well she copes as a caregiver. For male caregivers, the emotional state of the care recipient is an important component in how he will cope as a caregiver. The areas of interdependence in the caregiver experience are more common than there are differences. However, to benefit from the unique contributions of women and men, there need to be honest, open, and respectful negotiations over higher levels of reciprocity and conscious choices made about what each individual is capable and willing to provide. The selfawareness afforded to modern women and men through the development of the cerebral frontal cortex, communication skills, education, understanding, social values of equality, and an inherent belief in the worth of all human life creates, an environment where men and women can make conscious decisions about what it means to reach their full potential, independently and interdependently. Never before have women and men been able to use history, science, and technology in a society that increasingly values the equality of the sexes to make conscious and deliberate decisions about how to benefit from our shared values while fully exploiting the synergies of our individual biological, psychological, social, and spiritual inclinations. The caregiver experience is a microcosm of how men and women continue to evolve together and how we are recreating each other through our increasing respect and commitment to enhancing the humanity of both

Screening, assessment, and management of fatigue in adult survivors of cancer: an American Society of Clinical oncology clinical practice guideline adaptation.

PurposeThis guideline presents screening, assessment, and treatment approaches for the management of adult cancer survivors who are experiencing symptoms of fatigue after completion of primary treatment.MethodsA systematic search of clinical practice guideline databases, guideline developer Web sites, and published health literature identified the pan-Canadian guideline on screening, assessment, and care of cancer-related fatigue in adults with cancer, the National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines In Oncology (NCCN Guidelines) for Cancer-Related Fatigue and the NCCN Guidelines for Survivorship. These three guidelines were appraised and selected for adaptation.ResultsIt is recommended that all patients with cancer be evaluated for the presence of fatigue after completion of primary treatment and be offered specific information and strategies for fatigue management. For those who report moderate to severe fatigue, comprehensive assessment should be conducted, and medical and treatable contributing factors should be addressed. In terms of treatment strategies, evidence indicates that physical activity interventions, psychosocial interventions, and mind-body interventions may reduce cancer-related fatigue in post-treatment patients. There is limited evidence for use of psychostimulants in the management of fatigue in patients who are disease free after active treatment.ConclusionFatigue is prevalent in cancer survivors and often causes significant disruption in functioning and quality of life. Regular screening, assessment, and education and appropriate treatment of fatigue are important in managing this distressing symptom. Given the multiple factors contributing to post-treatment fatigue, interventions should be tailored to each patient's specific needs. In particular, a number of nonpharmacologic treatment approaches have demonstrated efficacy in cancer survivors

Screening, assessment, and management of fatigue in adult survivors of cancer: an American Society of Clinical oncology clinical practice guideline adaptation.

PurposeThis guideline presents screening, assessment, and treatment approaches for the management of adult cancer survivors who are experiencing symptoms of fatigue after completion of primary treatment.MethodsA systematic search of clinical practice guideline databases, guideline developer Web sites, and published health literature identified the pan-Canadian guideline on screening, assessment, and care of cancer-related fatigue in adults with cancer, the National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines In Oncology (NCCN Guidelines) for Cancer-Related Fatigue and the NCCN Guidelines for Survivorship. These three guidelines were appraised and selected for adaptation.ResultsIt is recommended that all patients with cancer be evaluated for the presence of fatigue after completion of primary treatment and be offered specific information and strategies for fatigue management. For those who report moderate to severe fatigue, comprehensive assessment should be conducted, and medical and treatable contributing factors should be addressed. In terms of treatment strategies, evidence indicates that physical activity interventions, psychosocial interventions, and mind-body interventions may reduce cancer-related fatigue in post-treatment patients. There is limited evidence for use of psychostimulants in the management of fatigue in patients who are disease free after active treatment.ConclusionFatigue is prevalent in cancer survivors and often causes significant disruption in functioning and quality of life. Regular screening, assessment, and education and appropriate treatment of fatigue are important in managing this distressing symptom. Given the multiple factors contributing to post-treatment fatigue, interventions should be tailored to each patient's specific needs. In particular, a number of nonpharmacologic treatment approaches have demonstrated efficacy in cancer survivors