The effect of mobilizing large numbers of CD34 + cells (super-mobilizers) on the engraftment and survival in patients undergoing autologous stem cell transplantation.

With the use of plerixafor in addition to growth factor for peripheral blood stem cell mobilization, the yield of autologous stem cell harvest has been higher while the length of apheresis days has become shorter. There is still debate whether higher cell collection efficacy in autologous stem cell transplant (ASCT) affect outcomes. In this retrospective study, we defined two groups of patients, group 1, super-mobilizers, with more than double the target cell dose collected (n = 15), while group 2 included all other patients (n = 75). Multiple myeloma (MM) and lymphoma patients were combined. Patients with chemo-mobilization, those needed more than one day apheresis, or with less than 100 days after ASCT were excluded. Correlations were performed between cell collection efficacy and post thaw CD34 cell viability (by 7AAD flow cytometry method), product HCT, and engraftment of neutrophils and platelets. We performed multiple linear regression using the above variables in addition to age, sex and disease type. We used Kaplan Meier's curves to show effect of cell collection efficacy on 1-year overall survival (OS). Our results show that all super-mobilizers received plerixafor in addition to G-CSF, while 83% did in group 2. Correlations between cell collection efficacy and neutrophil and platelet engraftment in group 1 and 2 was modest and better in group 1 (R=0.449 Vs 0.233 for neutrophils; R=0.464 Vs 0.110 for platelets, respectively). However, multiple linear regression showed statistically significant association between cell collection, as a continuous variable, with disease type (P < 0.001), product HCT (P < 0.001), post thaw viability (P = 0.003), and age (P = 0.013). MM patients were more likely to be super-mobilizers, while the product HCT was higher in the super-mobilizers. No significant effect of cell collection efficacy was found on engraftment of neutrophils or platelets. With relatively short post ASCT follow up, 6 patients in group 2 died of any cause while no deaths were recorded in the super-mobilizers group (P = 0.1892 by log-rank test). In conclusion, stem cell collection efficacy in ASCT is more frequent in MM than lymphoma patients, but is not predictive of faster engraftment. On the other hand, 1-year OS was 100% in the super-mobilizers group versus 93% in the other group.

Microfilariae of Brugia malayi Inhibit the mTOR Pathway and Induce Autophagy in Human Dendritic Cells.

Immune modulation is a hallmark of patent filarial infection, including suppression of antigen-presenting cell function and downmodulation of filarial antigen-specific T cell responses. The mammalian target of rapamycin (mTOR) signaling pathway has been implicated in immune regulation, not only by suppressing T cell responses but also by regulating autophagy (through mTOR sensing amino acid availability). Global proteomic analysis (liquid chromatography-tandem mass spectrometry) of microfilaria (mf)-exposed monocyte-derived dendritic cells (DC) indicated that multiple components of the mTOR signaling pathway, including mTOR, eIF4A, and eIF4E, are downregulated by mf, suggesting that mf target this pathway for immune modulation in DC. Utilizing Western blot analysis, we demonstrate that similar to rapamycin (a known mTOR inhibitor), mf downregulate the phosphorylation of mTOR and its regulatory proteins, p70S6K1 and 4E-BP1, a process essential for DC protein synthesis. As active mTOR signaling regulates autophagy, we examined whether mf exposure alters autophagy-associated processes. mf-induced autophagy was reflected in marked upregulation of phosphorylated Beclin 1, known to play an important role in both autophagosome formation and autolysosome fusion, in induction of LC3II, a marker of autophagosome formation, and in induced degradation of p62, a ubiquitin-binding protein that aggregates protein in autophagosomes and is degraded upon autophagy that was reduced significantly by mf exposure and by rapamycin. Together, these results suggest that Brugia malayi mf employ mechanisms of metabolic modulation in DC to influence the regulation of the host immune response by downregulating mTOR signaling, resulting in increased autophagy. Whether this is a result of the parasite-secreted rapamycin homolog is currently under study.

Predicting COVID-19 and respiratory illness: results of the 2022-2023 Armed Forces Health Surveillance Division forecasting challenge.

Since 2019, the Integrated Biosurveillance Branch of the Armed Forces Health Surveillance Division has conducted an annual forecasting challenge during influenza season to predict short-term respiratory disease activity among Military Health System beneficiaries. Weekly case and encounter observed data were used to generate 1- through 4-week advanced forecasts of disease activity. To create unified combinations of model inputs for evaluation across multiple spatial resolutions, 8 individual models were used to calculate 3 ensemble models. Forecast accuracy compared to the observed activity for each model was evaluated by calculating a weighted interval score. Weekly 1- through 4-week ahead forecasts for each ensemble model were generally higher than observed data, especially during periods of peak activity, with peaks in forecasted activity occurring later than observed peaks. The larger the forecasting horizon, the more pronounced the gap between forecasted peak and observed peak. The results showed that several models accurately predicted COVID-19 cases and respiratory encounters with enough lead time for public health response by senior leaders.

Correlation of health literacy and learning style preference in persons with heart failure.

OBJECTIVE: The purpose of the study was to describe demographic and health literacy correlates of learning style in older adults with heart failure (HF). METHODS: Cross sectional data on learning styles (VARK Questionnaire, 16 items) and health literacy (S-TOFHLA, 36 items) were collected. Preferred learning style was determined and correlated to health literacy and demographic measures. RESULTS: 116 participants with heart failure (M age = 75.1 (SD 12.5) years, M health literacy of 19 (SD 11.5). Most identified as male (59 %); with inadequate health literacy (67 %). Thirty percent reported a multimodal learning style preference with a kinesthetic (r = .33, p = .03) and not a visual preference (r = -.49, p < .001). Among unimodal learning styles, the most frequent was kinesthetic (26.7 %). Those with lower literacy levels were older (r = -.44, p = <.001), had less education (r = .48, p < .001) and reported a kinesthetic learning preference (r = .37, p = .001). CONCLUSION: Older individuals identifying as male, with low health literacy, preferred a kinesthetic approach to HF education. Future research should consider the linkage between education tailored to learning style, health literacy and outcomes. PRACTICE IMPLICATIONS: Assessment of learning style should be completed prior to an educational encounter.

Improving Nurses' Attitudes Toward Substance Use Disorder: Screening, Brief Intervention, and Referral to Treatment.

ABSTRACT: Patients with substance use disorder (SUD) encounter many barriers to healthcare, including negative attitudes of healthcare personnel. Compared with other healthcare professions, nurses have been reported as having less tolerant attitudes toward patients with SUD. Knowledge acquisition combined with role support has been shown to improve therapeutic attitudes of nurses toward patients with SUD. Screening, Brief Intervention, and Referral to Treatment (SBIRT) is an evidence-based educational intervention aimed to improve the outcomes of patients at risk and with SUD. SBIRT education has been shown as an effective educational tool with licensed nurses. Therefore, the aim of this study was to evaluate whether a 2-hour educational session on SBIRT (Mitchell et al., 2013) improved the therapeutic attitudes of nurses toward patients with SUD. Peplau's theory of interpersonal relations guided this study with an emphasis on the nurse-patient relationship. A quasi-experimental pretest/posttest design was used to evaluate nurses' attitudes pre and post a 2-hour educational session. Participants included 65 registered nurses employed in a 247-bed teaching hospital in New England. Attitudes were measured before and after the educational session using the 20-item, five-subscale Drug and Drug Problems Perceptions Questionnaire. A paired t test was performed, showing statistically significant improvements in attitudes postintervention. Prior education on SUD significantly correlated with baseline attitudes. A standard regression model, with practice setting, family history of SUD, and prior education as dependent variables, was not predictive of baseline attitudes. The results suggest conducting SBIRT should be considered a mandatory nursing competency, both in undergraduate curriculum and among licensed nurses.

Perceived Stressors and Support in Family Caregivers of Individuals With Opioid Use Disorder.

ABSTRACT: Stress experienced by family caregivers of individuals with opioid use disorder (OUD) contributes to caregiver burden. To understand the stressors experienced by family caregivers of individuals with OUD and the factors that influence their personal resiliency, data were collected from a convenience sample of family caregivers who answered two open-ended questions about sources of stress and factors that affect their personal resilience as part of an online survey. Yin's thematic analysis revealed five objective and two subjective burden themes and four resilience themes. Results indicate OUD places significant burden on families and may contribute to decreased physical and mental well-being in caregivers. Caregivers who perceived adequate support were able to use their experience and innate knowledge to cope and emerge with more resilience. Results of this study support the need for translational research to increase resilience and coping in this population of caregivers.

Predictors of Burden and Resilience in Family Caregivers of Individuals With Opioid Use Disorder.

BACKGROUND: Family caregivers are an essential resource for individuals with opioid use disorder (OUD). Overburdened caregivers often experience detrimental effects to their emotional and physical well-being. METHOD: A cross-sectional, nonexperimental, correlational study was used to identify correlates and predictors of burden and resilience in caregivers of care recipients with OUD. Pearson product-moment correlation and multiple regression analysis were used to explore the relationships between caregiver characteristics, care recipient characteristics, the caregiver-care-recipient dyad characteristics, and burden and resilience among caregivers of individuals with OUD and to determine the best predictive model. Participants ( N = 152) completed the study using an online electronic survey. RESULTS: The standardized regression coefficients indicated that supervision of care recipient behavioral problems (ß = .29), dyadic interaction (ß = .29), caregiver stress (ß = .28), and care recipient opioid use (ß = .12) were the strongest predictors of caregiver burden, whereas caregiver mental health (ß = -.31) and physical health (ß = .30) were the strongest predictors of caregiver resilience. CONCLUSIONS: Caregiver and care recipient characteristics, and their dyadic interaction, directly influence the degree of burden and resilience reported by family caregivers. Caregivers experiencing increased stress who are tasked with supervising problematic care recipient behaviors are more likely to experience higher levels of burden. In contrast, caregivers with good physical and mental health and adequate resources showed higher levels of resilience.

Changing Nurse Practitioner Students' Attitudes and Beliefs About Caring for Those With Opioid Use Disorders.

PURPOSE: Nurse practitioners (NPs) are in a unique position to address the problem of opioid use disorders (OUDs) because they provide a large percentage of primary care services (Agency for Healthcare Research and Quality, 2014). This study aimed to increase doctoral NP students' beliefs/attitudes about their ability to care for and about individuals with OUDs through a multifaceted educational approach, guided by social cognitive theory. METHODS: Researchers used a quasi-experimental pre/post design. Five doctoral students attended lectures and 16 hours of direct clinical exposure to individuals with OUDs at a medication-assisted treatment center. The 22-item Drug and Drug Problems Perception Questionnaire examined students' attitudes toward individuals with OUDs before and after receiving this multifaceted education. Students completed reflective writings. Descriptive statistics and effect sizes were computed, and reflective writings were reviewed. RESULTS: Changes in Drug and Drug Problems Perception Questionnaire scores before and after intervention showed a fairly large effect size. This suggests that the intervention may have clinical significance for practice and is likely to attain statistical significance with a larger sample size. Greatest changes occurred in students' perceptions of role adequacy and self-esteem scores, indicative of higher self-efficacy. Measured score increases correspond to increases in confidence, knowledge, and skills to therapeutically engage with this population. CONCLUSION: Doctoral NP students had more positive attitudes and beliefs about individuals with OUDs after the multifaceted intervention. Enhancement of self-esteem and adequacy in the caregiver role for this population were promising signals that education can reduce stigma. Further study is warranted with a larger and more diverse sample.

The association between frequency of opioid misuse and opioid use disorder among youth and adults in the United States.

BACKGROUND: Studies have shown the frequency of drug misuse is important in the development of a substance use disorder, but little is known about this relationship in the context of opioid misuse and opioid use disorder and withdrawal symptoms. METHODS: Our study included 2694 civilian respondents from the United States 12 years and older who had misused prescription opioids in the past year from the 2014 National Survey on Drug Use and Health. Logistic regression was used to model the association between frequency of prescription opioid misuse and opioid use disorder and withdrawal symptoms, adjusting for age, sex, race/ethnicity, and income level. RESULTS: Misusing prescription opioids more frequently was significantly associated with opioid use disorder in a dose-dependent manner (daily misuse: OR = 14.92, 95% confidence interval (CI) 9.29, 23.95; 1-2 days/week: OR = 4.46 95% CI: 2.52, 7.89}; 1-4 times/month: OR = 2.40, 95% CI: 1.37, 4.18) compared to use less than 1 time a month. OR = 2.89, 95% CI 1.90, 4.40, respectively) after controlling for sex, age, race/ethnicity, and income. A dose-dependent relationship was found between frequency of opioid misuse and withdrawal symptoms (daily misuse: OR = 2.89, 95% CI: 1.90, 4.40; 1-2 times/week: OR = 1.91, 95% CI: 1.05, 3.45; and 1-4 times/month: 1.74, 95% CI: 1.90, 4.40) after controlling for all covariates mentioned above. CONCLUSIONS: Our results provide evidence that higher frequency of opioid misuse is associated with both opioid use disorder and withdrawal symptoms. Frequency of use should be considered in the development of more effective opioid use disorder prevention strategies.

Novel CARM1-Interacting Protein, DZIP3, Is a Transcriptional Coactivator of Estrogen Receptor-α.

Coactivator-associated arginine methyltransferase 1 (CARM1) is known to promote estrogen receptor (ER)α-mediated transcription in breast cancer cells. To further characterize the regulation of ERα-mediated transcription by CARM1, we screened CARM1-interacting proteins by yeast two-hybrid. Here, we have identified an E3 ubiquitin ligase, DAZ (deleted in azoospermia)-interacting protein 3 (DZIP3), as a novel CARM1-binding protein. DZIP3-dependent ubiquitination of histone H2A has been associated with repression of transcription. However, ERα reporter gene assays demonstrated that DZIP3 enhanced ERα-mediated transcription and cooperated synergistically with CARM1. Interaction with CARM1 was observed with the E3 ligase RING domain of DZIP3. The methyltransferase activity of CARM1 partially contributed to the synergy with DZIP3 for transcription activation, but the E3 ubiquitin ligase activity of DZIP3 was dispensable. DZIP3 also interacted with the C-terminal activation domain 2 of glucocorticoid receptor-interacting protein 1 (GRIP1) and enhanced the interaction between GRIP1 and CARM1. Depletion of DZIP3 by small interfering RNA in MCF7 cells reduced estradiol-induced gene expression of ERα target genes, GREB1 and pS2, and DZIP3 was recruited to the estrogen response elements of the same ERα target genes. These results indicate that DZIP3 is a novel coactivator of ERα target gene expression.

The effects of a pre-movement delay on the kinematics of prehension in middle childhood.

The present study examined the effects of a pre-movement delay on the kinematics of prehension in middle childhood. Twenty-five children between the ages of 5 and 11 years made visually open-loop reaches to two different sized objects at two different distances along the midline. Reaches took place either (i) immediately, or (ii) 2 s after the occlusion of the stimulus. In all age groups, reaches following the pre-movement delay were characterised by longer movement durations, lower peak velocities, larger peak grip apertures and longer time spent in the final slow phase of the movement. This pattern of results suggests that the representations that control the transport and grasp component are affected similarly by delay, and is consistent with the results previously reported for adults. Such representations therefore appear to develop before the age of 5.

The effect of a tailored message intervention on heart failure readmission rates, quality of life, and benefit and barrier beliefs in persons with heart failure.

OBJECTIVE: The purpose of this study was to determine the effect of a tailored message intervention on heart failure readmission rates, quality of life, and health beliefs in persons with heart failure (HF). DESIGN: This randomized control trial provided a tailored message intervention during hospitalization and 1 week and 1 month after discharge.Theoretic framework The organizing framework was the Health Belief Model. SUBJECTS: Seventy persons with a primary diagnosis of chronic HF were included in the study. RESULTS: HF readmission rates and quality of life did not significantly differ between the treatment and control groups. Health beliefs, except for benefits of medications, significantly changed from baseline in the treatment group in directions posited by the Health Belief Model. CONCLUSIONS: A tailored message intervention changed the beliefs of the person with HF in regard to the benefits and barriers of taking medications, following a sodium-restricted diet, and self-monitoring for signs of fluid overload. Future research is needed to explore the effect of health belief changes on actual self-care behaviors.

Perceived benefits and barriers of heart failure self-care during and after hospitalization.

This longitudinal study describes the heart failure (HF) patient's perceived benefits and barriers to self-care during hospitalization, 1 week, and 1 month after hospitalization. Seventy-eight patients with acute HF completed the Health Belief Scales to determine the greatest benefits and barriers to self-care at each time point. Findings suggest that early benefits to performing self-care include reducing symptoms and improving quality of life. Later benefits focus more on promoting health. Barriers to self-care include forgetfulness and knowledge deficits about self-care behaviors. At 1 month, 15.1% to 48.5% patients reported that monitoring increases worry about HF. Home care clinicians can promote self-care through education and skills training.

Early versus delayed operative intervention in displaced clavicle fractures.

OBJECTIVES: Recent evidence to suggest that fixation of clavicle fractures yields better outcomes than conservative treatments has led to an increasing trend toward operative management. There is no evidence, however, to compare early fixation with delayed fixation for symptomatic patients before union. DESIGN: Prospective comparative case series. SETTING: Level 1 regional trauma center. PATIENTS: Displaced clavicle fractures treated operatively in our institution during a 4-year period. Ninety-seven patients were included: 68 with early fixation and 29 delayed. Radiographic and clinical outcomes were available for all patients and scores were available for 62. INTERVENTION: Early plate fixation (within 3 weeks) of displaced clavicle fractures compared with delayed (3-12 weeks) fixation of displaced clavicle fractures. OUTCOMES: Radiographic union, Oxford Shoulder Score, QuickDASH, EQ5D, and a patient interview. Mean follow-up was to 30 months. RESULTS: There were no statistically significant differences in age (P > 0.05), sex (P > 0.05), and energy of injury (P > 0.05) between the 2 groups. The mean QuickDASH was 8.9 early and 9.1 delayed (P < 0.05) and the Oxford Shoulder Score was 44.2 early and 43.9 delayed (P < 0.05). In the early fixation group, there were 5 wound healing complications, and 8 went on subsequently to have removal of prominent metalwork. In the delayed fixation group, 2 had wound healing complications and 4 required removal of prominent metalwork. There were no statistically significant differences in the EQ5D scores. CONCLUSION: Our series supports delayed fixation of symptomatic clavicle fractures as results do not differ from early fixation. LEVEL OF EVIDENCE: Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.

Attitudes and experiences of community pharmacists towards paediatric off-label prescribing: a prospective survey.

AIM: To identify community pharmacist experiences of, and attitudes towards paediatric off-label prescribing. METHODS: A prospective questionnaire-based study, with a 21-item questionnaire issued to 1500 randomly selected community pharmacies throughout the UK during 2005 on three separate occasions. RESULTS: Four hundred and eighty-two (32.1%) completed questionnaires were returned. Over 70% of respondents were familiar with the concept of off-label prescribing, primarily through dispensing experience rather than education, although only 40% were aware of having dispensed a paediatric off-label prescription within the previous month. The reasons given for a prescription being off label were younger age than recommended (84.6%, 297/351), primarily for antihistamines, analgesics and beta(2)-agonists, and higher (73.9%, 229/310) or lower than (41%, 103/258) recommended dose, primarily antibiotics and analgesics. Over 60% of respondents had been asked by the public to sell paediatric over-the-counter medicines, such as antihistamines, analgesics and steroid preparations for off-label use. The majority of respondents used the British National Formulary or the Pack Insert rather than specialist formularies or guidelines as a source of specialist paediatric information. Although 78% of respondents believed they had a responsibility to inform the prescriber that a medicine was off label, only 66% believed that they had a similar responsibility to inform parents. CONCLUSION: The community pharmacists who responded to this questionnaire appear to be aware of and concerned by the issues which surround paediatric off-label prescribing. Despite this, most gained relevant knowledge through work experience rather than undergraduate or postgraduate training or professional development.

The role of binocular information in the 'on-line' control of prehension.

Binocular visual information may be involved in the selection of appropriate motor programs before a reach is executed or it may be involved during the movement-execution phase in order to monitor and guide the hand to the target object. Here we introduced binocular information after 0%, 25%, 50% or 75% of the movement-execution phase and determined its effects on the kinematic indices of prehensile movements made to objects of different sizes placed at different distances. Kinematic indices linked to the transport component, such as peak velocity and time-to-peak velocity, were unaffected by the presence of binocular cues whereas later occurring indices, such as peak grip aperture and time in the slow phase, were significantly affected. Although the magnitude of the peak grip was affected by the presence of binocular cues, the time at which it occurred did not change. This pattern of results suggest that the visuo-motor control of prehensile movements utilises both feedforward and feedback strategies and that binocular cues are particularly important for the fine manual adjustments typical of the latter.

Binocular cues and the control of prehension.

The present study was designed to assess the importance of binocular information (i.e. binocular disparity and angle of convergence) in the control of prehension. Previous studies which have addressed this question have typically used the same experimental manipulation: comparing prehensile movements executed either under binocular conditions to those executed when one eye was occluded (monocular). However this may not be the correct comparison as in addition to depriving the subject of binocular depth cues. it also deprives the subject of any visual information in one eye. Therefore we determined the prehensile performance when the subject viewed the target object and scene with either (i) two different views (binocular), (ii) two identical views (bi-ocular), or (iii) one view only (monocular). Overall, the qualitative and quantitative performance in the bi-ocular and monocular control conditions was very similar on all the main measures (and different from the performance in the binocular condition). We conclude that the deficits in performance observed found for 'monocular' reaches should be attributed to the lack of local depth information specified by the binocular cues. In addition we speculate that convergence angle and binocular disparity, although involved in both the pre-movement and movement-execution phases of the reach, the cues may be weighted differently in both phases of a prehension movement depending on the behavioural strategy involved.