Oligonucleotide that binds nuclear factor NF-kappa-B acts as a lymphoid-specific and inducible enhancer element

The immunoglobulin kappa light chain gene contains a lymphoid-specific enhancer that includes several short protein-binding sequences. The sequence that binds the nuclear factor NF-kappa B was tested for its ability to act independently as an enhancer element by inserting it into test plasmids containing the chloramphenicol acetyltransferase gene. When analyzed for activity by transient transfection into lymphoid and nonlymphoid cells, a single copy of the NF-kappa B binding site could act as a tissue-specific upstream activating element. Two copies (dimer) showed 10-fold higher activity than did one copy and could act as an enhancer element 2.5 kilobases downstream of the transcriptional start site. The enhancer activity of this sequence was correlated with the presence of the cognate binding protein, NF-kappa B. This sequence acted as an inducible enhancer under conditions that induce NF-kappa B binding activity. Thus, the NF-kappa B binding site acts by itself as a tissue-specific and inducible enhancer element, and two copies show cooperative interaction

Importance of Employee Engagement during Change

Healthcare is in crisis; nursing is in crisis. Patient acuity is also on the rise (Beaty, 2005). In the United States, hospital and nursing leadership are professionally bound to produce effective clinical patient outcomes. For nursing leaders, producing effective clinical outcomes requires delivering a level of patient care that is appropriate to the individual patient and in direct proportion to his or her needs. If acuity is rising and care needs are expanding, the resulting higher level of nursing care hours affects nursing budgets. If unit budgets do not flex with the patient acuity, nursing leaders are then challenged to provide the higher level-of -care required, and still maintain the budget. Moral fatigue is growing among nurses, as they are continually asked to do more with less. Nursing leaders struggle to address the plethora of related conflicting demands, including clinical excellence in patient outcomes, patient satisfaction, employee satisfaction, budget constraints, compliance with regulatory legislation, fulfillment of accreditation requirements, consumer awareness, and transparency with all interested parties. These unpredictable variables require healthcare leaders to address and effectively manage while revenue and payments continue to be reduced. The question is, “how can our current health care delivery system be revised so that all people in theUnited States have access to affordable quality health care?” The 2008 financial crisis created the need for the hospital to re-organize the entire patient care unit structure resulting in a significant loss to the nurse manager’s patient care unit; major effects were a reduced budget, reduced bed capacity, layoff’s and elimination of shared governance. As a result, patient satisfaction and employee engagement plummeted. All resources were directed toward clinical care, to insure positive patient outcomes. A need to create a manageable nursing work environment was paramount. A systems change project (SCP) was designed that was grounded in ethical, leadership, change and nursing theories. Social justice to address health disparities was fundamental to the researcher’s ethical, professional and moral principles. The forces that influence behavior were the intended object of the work of the initiative. The project objectives were to create an effective and efficient work environment where staff had shared accountability to design system processes and where staff have what they need when they need it. The intended and measurable outcomes were to improve patient satisfaction and employee engagement. The project design used action research methodology within a participation-based framework. A unit champion model was initiated to improve unit work environment by incorporating passion and talents of the PCU staff into a staff-driven project. Each unit staff member assumed responsibility for a self-identified unit task that was over-and-above daily assignments. There were no pre-determined structures or prescribed processes for creation of the individual’s unit task. Deliberate lack of clarity was purposeful; work would evolve as staff became engaged. The logic was simple: if authority was matched with responsibility and employees were empowered to use that authority to meet the needs of their job responsibilities, then employees would demonstrate success through participation. Economic principles were inherent in the project design. For example, return-on-investment was demonstrated by comparing the project costs, mostly in tern of labor, to a reduction in patient days. Data analysis and evaluation included comparison of the hospital’s nationally recognized and well established annual surveys for patient satisfaction and employee engagement. The patient care unit’s 2009 surveys were compared to the respective 2010 surveys. The results were positive in both surveys; patient satisfaction and employee engagement improved statistically. In January 2010, project participation included 63 staff: 49 RNs and 14 Nursing Assistants for 75 unit champion topics compared to six staff in January 2009 when the project was initiated. Conclusions revealed participation and trust that the process would evolve. Authentic leadership and empowerment were critical. We cannot use old methods to address current problems in health care. Recommendations included project scalability to many forums. The clinically doctorally prepared nurse and leader will assist on our journey to improve access to and completion of effective patient care and clinical outcomes for our patients, our organizations, our communities, and our nation

The role of a novel VH sequence (V11) in the formation of anti-phosphocholine antibodies

The immune response to phosphocholine (PC) in mice is highly restricted. Most anti-PC antibodies use heavy-chain variable-region (VH) sequences derived from single VH gene segment, V1. In order to investigate whether a highly homologous VH gene segment, V11, could contribute to the formation of PC-binding antibodies, we carried out chain recombination experiments with M47A, a non-PC binding myeloma protein whose H-chain is encoded by the V11 gene segment, and two PC-binding antibodies, HP101.6G6 (HP6G6) and M511. The H-chains from the non-PC-binding myeloma protein, M47A, formed a functional PC-binding site when paired with L-chains from both PC-binding antibodies. These results suggest that a second VH gene segment, V11, could theoretically be used to form PC-binding antibodies. In addition, these results provide direct evidence that a single H-chain can be used in combinatorial association with different L-chains to form antibodies of differing specificities.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/24923/1/0000350.pd

Multi-Center, Single-Blind Randomized Controlled Trial Comparing Functional Electrical Stimulation Therapy to Conventional Therapy in Incomplete Tetraplegia

BACKGROUND: Loss of upper extremity function after tetraplegia results in significant disability. Emerging evidence from pilot studies suggests that functional electrical stimulation (FES) therapy may enhance recovery of upper extremity function after tetraplegia. The aim of this trial was to determine the effectiveness of FES therapy delivered by the Myndmove stimulator in people with tetraplegia. METHODS: A multi-center RESULTS: Between June 2019 to August 2021, 51 participants were randomized to FES ( CONCLUSION: Forty sessions of FES therapy delivered by the MyndMove stimulator are as effective as conventional therapy in producing meaningful functional improvements that persist after therapy is completed. Limitations of this study include the impact of COVID-19 limiting the ability to recruit the target sample size and per-protocol execution of the study in one-third of the participants. REGISTRATION: This trial is registered at www.ClinicalTrials.gov, NCT03439319

Depressed mood predicts pulmonary rehabilitation completion among women, but not men

SummaryBackgroundAs many as 30% of patients who start pulmonary rehabilitation (PR) fail to complete it, and depressed mood has been associated with PR non-completion. Depression is more common in women than men with COPD and historically women with COPD have been under studied. However, no studies to date have investigated gender-specific predictors of PR completion.MethodsThe study included 111 patients with COPD who enrolled in a community based outpatient PR program in Providence, RI. Patients who attended 20 or more sessions were designated “completers”. Depression was measured using the CES-D. Logistic regression models were evaluated to test depressed mood as a predictor of PR completion. Analyses controlled for demographic and health variables found to differ between completers and non-completers.ResultsPatients were 95% white and 49.5% women, and 74% had a GOLD stage ≥3. Sixty-eight percent of patients were PR completers. A logistic regression model, showed that lower depressed mood independently predicted PR completion across all patients (adjusted OR = 0.92, p = .002). In gender-stratified analyses, lower depressed mood was an independent predictor of PR completion for women (adjusted OR = .91, p = .024) but not men (adjusted OR = .97, p = .45). Greater 6-min walk test distance was also an independent predictor of PR completion among women.ConclusionDepressed mood is an important predictor of completion of community based PR among women. Screening and brief treatment of depression should be considered in practice

Who Will Volunteer? Religiosity, Everyday Racism, and Social Participation Among African American Men

This study explores the relative importance of everyday racism, empathic concern, communalism, and religiosity as predictors of pro-social involvement (i.e., volunteerism and membership in political/social justice organizations) among a sample of African American men ( N = 151). Church involvement emerged as a positive predictor of the likelihood that these men were involved in volunteer work as well as the number of hours that men dedicated to volunteer work. Communalism positively predicted the amount of time (in hours per year) that men were involved in volunteer work. Subjective religiosity and the stress of everyday racism were associated with a greater likelihood of being a member of a political–social justice organization. Implications of these findings are discussed.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44632/1/10804_2004_Article_496119.pd

Gross Motor Function in Pediatric Onset TUBB4A-Related Leukodystrophy: GMFM-88 Performance and Validation of GMFC-MLD in TUBB4A

TUBB4A pathogenic variants are associated with a spectrum of neurologic impairments including movement disorders and leukodystrophy. With the development of targeted therapies, there is an urgent unmet need for validated tools to measure mobility impairment. Our aim is to explore gross motor function in a pediatric-onset TUBB4A-related leukodystrophy cohort with existing gross motor outcome tools. Gross Motor Function Measure-88 (GMFM-88), Gross Motor Function Classification System (GMFCS-ER), and Gross Motor Function Classification-Metachromatic Leukodystrophy (GMFC-MLD) were selected through face validity. Subjects with a confirmed clinical and molecular diagnosis of TUBB4A-related leukodystrophy were enrolled. Participants' sex, age, genotype, and age at disease onset were collected, together with GMFM-88 and concurrent GMFCS-ER and GMFC-MLD. Performances on each measure were compared. GMFM-88 floor effect was defined as total score below 20%. A total of 35 subjects participated. Median performance by GMFM-88 was 16.24% (range 0-97.31), with 42.9% (n = 15) of individuals performing above the floor. GMFM-88 Dimension A (Lying and Rolling) was the best-performing dimension in the GMFM-88 (n = 29 above the floor). All levels of the Classification Scales were represented, with the exception of the GMFC-MLD level 0. Evaluation by GMFM-88 was strongly correlated with the Classification Scales (Spearman correlations: GMFCS-ER:GMFM-88 r = 0.90; GMFC-MLD:GMFM-88 r = 0.88; GMFCS-ER:GMFC-MLD: r = 0.92). Despite overall observation of a floor effect, the GMFM-88 is able to accurately capture the performance of individuals with attenuated phenotypes. GMFM-88 Dimension A shows no floor effect. GMFC-MLD shows a strong correlation with GMFCS-ER and GMFM-88, supporting its use as an age-independent functional score in TUBB4A-related leukodystrophy

Validation of a breast cancer assay for radiotherapy omission: an individual participant data meta-analysis

Background: There are currently no molecular tests to identify individual breast cancers where radiotherapy (RT) offers no benefit. Profile for the Omission of Local Adjuvant Radiotherapy (POLAR) is a 16-gene molecular signature developed to identify low risk cancers where RT will not further reduce recurrence rates. Methods: An individual participant data meta-analysis was performed in 623 cases of node-negative ER+/HER2-negative early breast cancer enrolled in three RT randomized trials for whom primary tumor material was available for analysis. A Cox proportional hazards model on time to locoregional recurrence (LRR) was used to test the interaction between POLAR score and RT.Results: 429 (69%) patients’ tumors had a high POLAR score and 194 (31%) had a low score. Patients with high POLAR score had, in the absence of RT, a 10-year cumulative incidence of LRR: 20% (15%-26%) vs 5% (2%-11%) for those with a low score. Patients with a high POLAR score had a large benefit from RT (hazard ratio [HR] for RT vs no RT: 0.37 [0.23-0.60], p&lt;0.001). In contrast, there was no evidence of benefit from RT for patients with a low POLAR score (HR: 0.92 [0.42-2.02], p = 0.832). The test for interaction between RT and POLAR was statistically significant (p = 0.022).Conclusions: POLAR is not only prognostic for locoregional recurrence but also predictive of benefit from radiotherapy in selected patients. Patients ≥ 50 years with ER+/HER2-negative disease and a low POLAR score could consider omitting adjuvant RT. Further validation in contemporary clinical cohorts is required.<br/

eHealth interventions for family carers of people with long term illness: A promising approach?

Family carers of people who have long term illness often experience physical and mental health morbidities, and burden. While there is good evidence to suggest that carers benefit from psychosocial interventions, these have primarily been delivered via face-to-face individual or group-formats. eHealth interventions offer a novel, accessible and self-paced approach to care delivery. Whether these are effective for carers' wellbeing has been little explored. This paper reports the first comprehensive systematic review in this area. A total of 78 studies, describing 62 discrete interventions, were identified. Interventions commonly aimed to promote carers' knowledge, self-efficacy, caregiving appraisal, and reduce global health morbidities. Interventions were offered to carers of people with a wide range of long term illness; dementia has been the most researched area, as reported in 40% of studies. Clinical and methodological heterogeneity in interventions precluded meta-analyses, and so data were analysed narratively. The most popular approach has comprised psychoeducational interventions delivered via an enriched online environment with supplementary modes of communication, such as network support with professionals and peers. Overall, carers appreciate the flexibility and self-paced nature of eHealth interventions, with high rates of satisfaction and acceptability. More studies using robust designs are needed to extend the evidence base

Prostate Cancer Postoperative Nomogram Scores and Obesity

Nomograms are tools used in clinical practice to predict cancer outcomes and to help make decisions regarding management of disease. Since its conception, utility of the prostate cancer nomogram has more than tripled. Limited information is available on the relation between the nomograms' predicted probabilities and obesity. The purpose of this study was to examine whether the predictions from a validated postoperative prostate cancer nomogram were associated with obesity.We carried out a cross-sectional analysis of 1220 patients who underwent radical prostatectomy (RP) in southern California from 2000 to 2008. Progression-free probabilities (PFPs) were ascertained from the 10-year Kattan postoperative nomogram. Multivariable logistic regression models estimated odds ratios (ORs) and 95% confidence intervals (CIs).In the present study, aggressive prostate cancer (Gleason ≥7), but not advanced stage, was associated with obesity (p = 0.01). After adjusting for age, black race, family history of prostate cancer and current smoking, an inverse association was observed for 10-year progression-free predictions (OR = 0.50; 95% CI = 0.28–0.90) and positive associations were observed for preoperative PSA levels (OR = 1.23; 95% CI = 1.01–1.50) and Gleason >7 (OR = 1.45; 95% CI = 1.11–1.90).Obese RP patients were more likely to have lower PFP values than non-obese patients, suggesting a higher risk of experiencing prostate cancer progression. Identifying men with potentially higher risks due to obesity may improve disease prognosis and treatment decision-making