A 4-week morning light treatment with stable sleep timing for individuals with fibromyalgia: a randomized controlled trial.

OBJECTIVES: Fibromyalgia is characterized by chronic widespread pain, mood, and sleep disturbance. Pharmacological treatments have modest efficacy and are associated with negative side effects, and alternative approaches are needed. Morning bright light treatment may assist in the management of fibromyalgia as it can reduce depressive symptoms, improve sleep, and advance circadian timing. METHODS: Sixty people with fibromyalgia (58 women, mean age 41.8 ± 13.3 years) were enrolled in a study comparing 4 weeks of a 1-hour daily morning bright light treatment (active treatment) to a morning dim light treatment (comparison treatment). Both light treatments included behavioral procedures to stabilize sleep timing. The morning bright light treatment was expected to produce larger improvements in pain and function than the dim light treatment and larger improvements in potential mediators (mood, sleep, and circadian timing). RESULTS: Both the bright and dim light treatment groups achieved significant but similar levels of improvement in pain intensity, pain interference, physical function, depressive symptoms, and sleep disturbance. Overall, the sample on average displayed a clinically meaningful improvement in the Fibromyalgia Impact Questionnaire-Revised score (mean reduction of 11.2 points), comparable to that reported following physical exercise treatments. Minimal side effects were observed. CONCLUSIONS: Findings indicate that the effects of a morning bright light treatment did not exceed those of a comparison dim light treatment; yet the changes on average in both conditions revealed clinically meaningful improvements. Future research is warranted to identify what elements of this trial may have contributed to the observed effects.

Improvements in cardiovascular health over the perinatal period predicts lower postpartum psychological distress.

Background: Adverse cardiovascular events during pregnancy (e.g., pre-eclampsia) occur at higher rates among individuals with pre-pregnancy overweight or obesity (body mass index [BMI]≥25kg/m2) and have been associated with postpartum depression. However, it is unclear whether cardiovascular health (CVH), defined more holistically than the absence of cardiovascular conditions in pregnancy, relates to postpartum psychological functioning. The present study examined whether changes in CVH during the perinatal period predicted postpartum psychological functioning among individuals with pre-pregnancy BMI≥25kg/m2. Methods: Individuals (N=226; Mage=28.43±5.4 years; MBMI=34.17±7.15kg/m2) were recruited when their pregnancies were 12-20 weeks gestation (M=15.64±2.45 weeks) for a longitudinal study of health and well-being. Participants completed the Center for Epidemiological Studies Depression Scale (CES-D) and Perceived Stress Scale (PSS) and reported on CVH behaviors (dietary intake, physical activity, nicotine exposure, and sleep) at baseline and at 6-months postpartum. BMI and CVH behaviors were coded according to the American Heart Association's Life's Essential 8 to create a CVH score at both timepoints. Linear regression analyses were performed to examine whether change in CVH related to postpartum CES-D and PSS scores. Because sleep was only measured in a subset of participants (n=114), analyses were conducted with and without sleep included. Baseline CVH, CES-D and PSS scores, and demographic factors were included as covariates in all models. Results: Improved CVH was associated with lower postpartum CES-D (ß=-0.18, p<0.01) and PSS (ß=-0.13, p=0.02) scores when excluding sleep. Compared to those whose CVH improved by >1SD from pregnancy to 6-months postpartum, individuals whose CVH worsened by >1SD scored 6.42 points higher on the CESD (MCESD=15.25±10.92 vs. 8.52±6.90) and 6.12 points higher on the PSS (MPSS=24.45±8.29 vs. 17.83±8.70). However, when including sleep, these relationships were no longer significant (ps>0.4). Conclusions: Improvements in CVH from early pregnancy to 6-months postpartum were associated with lower postpartum depressive symptoms and perceived stress. However, these relationships were no longer significant when including sleep in the CVH metric, potentially due to the large reduction in sample size. These data suggest that intervening during pregnancy to promote CVH may improve postpartum psychological functioning among high-risk individuals.

Systemic and mucosal levels of lactoferrin in very low birth weight infants supplemented with bovine lactoferrin.

Lactoferrin supplementation may help prevent infections in preterm infants, but the efficacy has varied with different doses and products. We assessed the absorption and excretion of bovine lactoferrin (bLF) in 31 infants receiving 100, 200, or 300 mg·kg-1·day-1 of enteral bLF for 30 days. bLF and human lactoferrin (hLF) in infant saliva, blood, urine, and stool, as well as expressed (EBM) or donor breast milk (DBM) that were collected (i) before the treatment was initiated, (ii) at study day 22, and (iii) one week after treatment cessation, were measured using ELISA. During treatment, bLF was absorbed from the gastrointestinal tract and detected in plasma, saliva, and urine, as well as excreted in stool. Levels of bLF in the saliva and stool began to decline within 12 h after dosing, and bLF was undetectable in all samples one week after treatment. The concentrations of hLF exceeded those of bLF across sample types and time-points. Infants receiving EBM demonstrated higher levels of hLF in the saliva and stool than those receiving DBM. Neither bLF nor hLF levels varied by patient characteristics, bLF dosage, or infection status. This is the first study demonstrating bLF absorption into the bloodstream and distribution to saliva and urine in preterm infants. Future studies should further explore LF pharmacokinetics because higher and more frequent dosing may improve the clinical benefit of LF supplementation.

Ergogenic Effect of Nitrate Supplementation: A Systematic Review and Meta-analysis.

Although over 100 studies and reviews have examined the ergogenic effects of dietary nitrate (NO3) supplementation in young, healthy men and women, it is unclear if participant and environmental factors modulate the well-described ergogenic effects-particularly relevant factors include biological sex, aerobic fitness, and fraction of inspired oxygen (FiO2) during exercise. To address this limitation, the literature was systematically reviewed for randomized, crossover, placebo-controlled studies reporting exercise performance outcome metrics with NO3 supplementation in young, healthy adults. Of the 2033 articles identified, 80 were eligible for inclusion in the meta-analysis. Random-effects meta-analysis demonstrated that exercise performance improved with NO3 supplementation compared with placebo (d = 0.174; 95% confidence interval (CI), 0.120-0.229; P < 0.001). Subgroup analyses conducted on biological sex, aerobic fitness, and FiO2 demonstrated that the ergogenic effect of NO3 supplementation was as follows: 1) not observed in studies with only women (n = 6; d = 0.116; 95% CI, -0.126 to 0.358; P = 0.347), 2) not observed in well-trained endurance athletes (≥65 mL·kg·min; n = 26; d = 0.021; 95% CI, -0.103 to 0.144; P = 0.745), and 3) not modulated by FiO2 (hypoxia vs normoxia). Together, the meta-analyses demonstrated a clear ergogenic effect of NO3 supplementation in recreationally active, young, healthy men across different exercise paradigms and NO3 supplementation parameters; however, the effect size of NO3 supplementation was objectively small (d = 0.174). NO3 supplementation has more limited utility as an ergogenic aid in participants with excellent aerobic fitness that have optimized other training parameters. Mechanistic research and studies incorporating a wide variety of subjects (e.g., women) are needed to advance the study of NO3 supplementation; however, additional descriptive studies of young, healthy men may have limited utility.

Enhancing native chemical ligation for challenging chemical protein syntheses.

Native chemical ligation has enabled the chemical synthesis of proteins for a wide variety of applications (e.g., mirror-image proteins). However, inefficiencies of this chemoselective ligation in the context of large or otherwise challenging protein targets can limit the practical scope of chemical protein synthesis. In this review, we focus on recent developments aimed at enhancing and expanding native chemical ligation for challenging protein syntheses. Chemical auxiliaries, use of selenium chemistry, and templating all enable ligations at otherwise suboptimal junctions. The continuing development of these tools is making the chemical synthesis of large proteins increasingly accessible.

A propensity score-matched analysis of the impact of minimum inhibitory concentration on mortality in patients with Pseudomonas aeruginosa bacteremia treated with cefepime or ceftazidime.

The United States Clinical and Laboratory Standards Institute recently elected not to revise ceftazidime and cefepime Pseudomonas aeruginosa minimum inhibitory concentration (MIC) susceptibility breakpoints but rather recommended specific dosage regimens to correspond to breakpoints. This study's objective was to examine mortality of low and high MIC P. aeruginosa isolates in bacteremic patients treated with cefepime or ceftazidime. Data were gathered through a Veterans Health Administration national administrative database for veterans with P. aeruginosa blood cultures who received cefepime or ceftazidime. Seventy-four patients in the low MIC (≤2 µg/mL) group and 29 patients in the high (4-8 µg/mL) MIC group were included. Independent baseline variables associated with 30-day all-cause mortality were determined through multivariate analysis to calculate propensity scores and perform matching. All-cause 30-day mortality was not statistically significant between the 2 resultant propensity score-matched groups (17.2% mortality in the low MIC group versus 27.6% in the high MIC group; P=0.34). Data suggested that P. aeruginosa bacteremia episodes where the cephalosporin MIC = 8 µg/mL may have higher mortality, however this may be reflective of higher propensity scores. Our study suggests that it is reasonable to designate a cefepime or ceftazidime MIC ≤8 µg/mL as susceptible for P. aeruginosa bacteremia infections, but potential suboptimal outcomes in episodes for which the P. aeruginosa MIC is 8 µg/mL may need further investigation.

Enhancing HIV/AIDS, viral hepatitis, sexually transmitted disease, and tuberculosis prevention in the United States through program collaboration and service integration: the case for broader implementation.

HIV infection, viral hepatitis, sexually transmitted diseases, and tuberculosis in the United States remain major public health concerns. The current disease-specific prevention approach oftentimes has led to narrow success and missed opportunities for increasing program capacity, leveraging resources, addressing social and structural determinants, and accelerating health impact-suggesting a need for greater innovation to prevent related diseases. The National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention's Program Collaboration and Service Integration (PCSI) strategic priority aims to strengthen collaborative engagement across these disease areas and to integrate services at the client level. In this review, we articulate the 5 principles of PCSI-appropriateness, effectiveness, flexibility, accountability, and acceptability. Drawing upon these principles and published literature, we discuss the case for change that underlies PCSI, summarize advances in the field since 2007, and articulate key next steps. Although formal evaluation is needed to fully assess the health impact of PCSI, available evidence suggests that this approach is a promising tool to advance prevention goals.

Managed behavioral healthcare in the private sector.

Employers, in their search for cost containment and quality improvement, have driven the development of the behavioral health managed care vendor. More specifically, the behavioral health carve-out is an innovation that was developed to respond to employer and, more recently, health plan needs. Now that the product has matured, it is increasingly being asked to justify its existence. Costs have certainly been maintained, but improvements in quality have not always been evident. The issues the authors address include, as cost pressures continue, can the industry deliver on its promise to improve care? Will it need to evolve to yet another level, with new or different features?

Development of an animal model for autotransfusion therapy: in vitro characterization and analysis of anti-CD3/CD28 expanded cells.

Previous studies have shown that in vitro culture of human CD4+ T cells with antibodies to CD3 and CD28 immobilized on beads induced an antiviral effect to HIV-1 infection. Herein, we have used CD4+ T cells from nonhuman primates to address issues critical for use of such cells for therapy and immune reconstitution of humans and nonhuman primates infected with HIV and simian immunovirus (SIV). These studies include definition of the kinetics of the antiviral effect, the relative stability of the acquired phenotype, and whether such activated and expanded CD4+ T cells retain their immune function. Results of our studies show that antiviral effect is induced rapidly following activation with anti-CD3/CD28-coated beads. Additionally, the antiviral effect is not stable in these cells and requires continuous culture with anti-CD3/CD28 beads. Removal of CD4+ T cells from anti-CD3/CD28 stimulation renders these cells susceptible to infection, demonstrating that the resistant phenotype is not stable in these cultures. However, anti-CD3/CD28 expanded CD4+ T cells do retain immune function. Thus, although these findings imply a note of caution for therapeutic strategies aimed at providing patients with virus-resistant CD4+ T cells, the present study suggests that transfusion of such cells with retained immune function may have immune restoration capability.

Construction of a transcription map around the gene for ataxia telangiectasia: identification of at least four novel genes.

We have constructed YAC, PAC, and cosmid contigs in the ataxia-telangiectasia gene region and used the assembled clones to isolate expressed sequences by exon trapping and hybridization selection. In the interval between D11S1819 and D11S2029, exons and cDNAs for potentially 13 different genes were identified. Three of these genes, F37, K28, and 6.82, are large novel genes expressed in a variety of different tissues. K28 shows sequence homology to the Rab GTP binding protein family and gene 6.82 homology to the rabbit vasopressin activated calcium mobilizing receptor, while gene F37 has no homology to any known sequence in the database. Three further clones, exon 6.41 and cDNAs K22 and E74, from the interval between D11S1819 and D11S2029, appear to be expressed endogenous retrovirus sequences. The fourth large novel genes, E14, together with two further possible novel genes, E13 and E3, was identified from exons and cDNAs in the more telomeric 300-kb interval between markers D11S2029 and D11S2179. These are in addition to the genes for mitochondrial acetoacetyl-CoA-acetyltransferase (ACAT) and the ATM gene in the same region. Genes E3, E13, and E14 do not show homology to any known genes. K28, 6.82, ACAT, and ATM all appear to have the same transcriptional orientation toward the telomere.

The scholarship of a practice discipline.

The article proposes that all nurses, as members of a discipline that is embedded in practice, share in the obligation to take part, in different capacities, in the generation of nursing scholarship. A model of scholarly inquiry that connects knowledge development and professional values to gather wisdom that benefits the health and well-being of society is advanced. Opportunity for all nurses to engage in a dialogue to create ownership of their scholarship is pivotal to its revisioning.

Dual diagnosis. Comorbid substance abuse or dependency and mental illness.

The existence of comorbid substance abuse or dependency and psychiatric impairment presents complex challenges for the mental health care provider. Because of the holistic approaches to assessment and intervention practiced by psychiatric/mental health nurses, they are in a unique position to contribute to the design and delivery of efficacious treatment strategies for such individuals.

Sulfasalazine-induced fulminant hepatic failure.

We report two cases of massive hepatic necrosis associated with sulfasalazine. Both patients had underlying inflammatory bowel disease. One of the patients had a history of an ill-defined autoimmune disorder (Sjögren's syndrome). Symptoms and signs of a generalized hypersensitivity reaction were present in both patients. One patient died of a subarachnoid hemorrhage while awaiting transplant, the second died 2 weeks after transplant from disseminated aspergillosis. These two cases remind us of one of the potential hazards of sulfasalazine at a time when alternative therapies are now available.

The impact of transcutaneous electrical nerve stimulation on the postcesarean patient.

Nurses need to be actively involved in current research on TENS therapy. A thorough in-service training program for all nurses involved in the TENS program must be developed in order for nurses to knowledgeably assist their patients in maximal adaptation to TENS therapy. Transcutaneous electrical nerve stimulation therapy is not a panacea in postpartal pain management. It can be argued that TENS is another extension of technology interfering with the original natural simplicity of the birthing process; however, further research in the technique needs to be conducted before TENS can be rejected as such. Ultimately, the goal of postpartal care for the cesarean-birth family is to allow the parents to enjoy the birth experience without the dangers of the past and the, at times, unnecessary interference of the present. TENS therapy may be a means toward that end.