ActinoBase: tools and protocols for researchers working on Streptomyces and other filamentous actinobacteria.

Actinobacteria is an ancient phylum of Gram-positive bacteria with a characteristic high GC content to their DNA. The ActinoBase Wiki is focused on the filamentous actinobacteria, such as Streptomyces species, and the techniques and growth conditions used to study them. These organisms are studied because of their complex developmental life cycles and diverse specialised metabolism which produces many of the antibiotics currently used in the clinic. ActinoBase is a community effort that provides valuable and freely accessible resources, including protocols and practical information about filamentous actinobacteria. It is aimed at enabling knowledge exchange between members of the international research community working with these fascinating bacteria. ActinoBase is an anchor platform that underpins worldwide efforts to understand the ecology, biology and metabolic potential of these organisms. There are two key differences that set ActinoBase apart from other Wiki-based platforms: [1] ActinoBase is specifically aimed at researchers working on filamentous actinobacteria and is tailored to help users overcome challenges working with these bacteria and [2] it provides a freely accessible resource with global networking opportunities for researchers with a broad range of experience in this field.

The effects of hormonal contraceptive use on sleep patterns in women of reproductive age.

PURPOSE: Hormonal contraceptives alter hormone levels in women and have been linked to alterations in sleep patterns; however, previous studies yielded inconsistent results and lacked generalizability. This study examines hormonal contraceptive use and its impact on sleep outcomes, including sleep duration and sleep disturbances. METHODS: Women self-reported their sleep patterns and use of contraceptives in the 2017 population-based Behavioral Risk Factor Surveillance System Survey (n=1,970). Participants were categorized by use of hormonal or non-hormonal contraceptives for the purpose of pregnancy prevention. Sleep duration was defined as having met the recommended sleep levels of 7-9 hours per 24 hours. Sleep disturbances were defined as trouble falling asleep, staying asleep, or sleeping too much ≥ 6 days within a 14-day period. Prevalence ratios (PRs) and 95% confidence intervals (CIs) were calculated to examine the association between contraceptive use and each sleep outcome. SAS-callable SUDAAN was used for analyses to account for the complex sampling design. RESULTS: Women who used hormonal contraceptives had 6% higher prevalence of sleep disturbances (PR: 1.06, 95% CI: 0.99, 1.14) and 17% lower prevalence of not meeting sleep duration recommendations (PR: 0.83, 95% CI: 0.71, 0.98) compared to those who used non-hormonal contraceptives after adjustment for age. CONCLUSION: These findings suggest the use of hormonal contraceptives may have negative impacts on sleep disturbances, and positive effects on sleep duration among women using contraceptives for preventing pregnancy. Future studies should be conducted in diverse populations utilizing objective measurements of sleep patterns.

Educating pharmacy students through a pandemic: Reflecting on our COVID-19 experience.

The impact of the COVID-19 pandemic on pharmacy education worldwide has been immense, affecting students, educators and regulatory agencies. Pharmacy programmes have had to rapidly adapt in their delivery of education, maintaining standards while also ensuring the safety of all stakeholders. In this commentary, we describe the challenges, compromises and solutions adopted by our institution throughout the pandemic, the lessons learnt, adaptive measures taken, and strategies to develop and future-proof our curricula.

Use of an Electronic Medical Record to Track Adherence to the Mediterranean Diet in a US Neurology Clinical Practice.

OBJECTIVE: We describe our experience with routinely capturing and analyzing Mediterranean diet data via structured clinical documentation support tools built into the electronic medical record and describe adherence to the Mediterranean diet in patients at risk for either stroke or dementia in a US neurology clinical practice. PATIENTS AND METHODS: The Mediterranean diet is associated with a reduced risk of stroke and dementia. The Department of Neurology at NorthShore University HealthSystem routinely evaluates patients at initial and annual outpatient visits using structured clinical documentation support (SCDS) tools built into the electronic medical record (EMR). For patient evaluations in our Vascular Neurology and Brain Health subspecialty clinics, SCDS tools in the EMR include the validated 14-item questionnaire for Mediterranean diet adherence (PREvención con DIeta MEDiterránea [PREDIMED]) that autoscores, auto-interprets, writes to the progress note, and electronically captures data. Our study population includes patients seen at these clinics from July 1, 2015, through November 29, 2017. RESULTS: At their initial office visit, 25.5% (95/373) of Brain Health patients scored 10 or more points ("strongly adherent") on the PREDIMED (median, 8; range, 0-14) whereas 6.7% (55/829) of Vascular Neurology patients achieved a score of 10 or more points (median, 6; range, 0-12). By contrast, 34.7% (2586/7447) of individuals in the original PREDIMED cohort were strongly adherent to the Mediterranean diet. CONCLUSION: PREDIMED scores can be electronically captured to tailor nutrition interventions by assessing baseline adherence at the time of their initial neurology clinic visit. Patients in our Midwestern US clinics were weakly adherent to the Mediterranean diet. This suggests a major opportunity for nutrition intervention and education in US neurology clinical practices, toward preserving and improving brain health.

Alzheimer's "Prevention" vs. "Risk Reduction": Transcending Semantics for Clinical Practice.

The terms "prevention" and "risk reduction" are often used interchangeably in medicine. There is considerable debate, however, over the use of these terms in describing interventions that aim to preserve cognitive health and/or delay disease progression of Alzheimer's disease (AD) for patients seeking clinical care. Furthermore, it is important to distinguish between Alzheimer's disease prevention and Alzheimer's dementia prevention when using these terms. While prior studies have codified research-based criteria for the progressive stages of AD, there are no clear clinical consensus criteria to guide the use of these terms for physicians in practice. A clear understanding of the implications of each term will help guide clinical practice and clinical research. The authors explore the semantics and appropriate use of the terms "prevention" and "risk reduction" as they relate to AD in clinical practice.

Effect of Mindfulness-Based Stress Reduction Training on Health Care Worker Safety: A Randomized Waitlist Controlled Trial.

OBJECTIVE: The study assessed the impact of mindfulness training on occupational safety of hospital health care workers. METHODS: The study used a randomized waitlist-controlled trial design to test the effect of an 8-week mindfulness-based stress reduction (MBSR) course on self-reported health care worker safety outcomes, measured at baseline, postintervention, and 6 months later. RESULTS: Twenty-three hospital health care workers participated in the study (11 in immediate intervention group; 12 in waitlist control group). The MBSR training decreased workplace cognitive failures (F [1, 20] = 7.44, P = 0.013, (Equation is included in full-text article.)) and increased safety compliance behaviors (F [1, 20] = 7.79, P = 0.011, (Equation is included in full-text article.)) among hospital health care workers. Effects were stable 6 months following the training. The MBSR intervention did not significantly affect participants' promotion of safety in the workplace (F [1, 20] = 0.40, P = 0.54, (Equation is included in full-text article.)). CONCLUSIONS: Mindfulness training may potentially decrease occupational injuries of health care workers.

Comfort over Pain in Pregnancy.

Pregnancy is often a time when chronic pain is exacerbated, or when acute pain appears. Frequently the easiest intervention within reach, for both chronic and acute pain, is a prescription. However, medication cannot correct the cause of the pain; instead it alters the person's experiential perception of the pain. In addition, medication exposes both mother and fetus to risks. To provide simple, evidence-based, holistic/alternative remedies for women who experienced nonemergent pain during pregnancy. Holistic/alternative techniques for increasing comfort were taught to the participants and individualized during three sessions. Levels of pain and comfort were measured before and after the treatment, using the validated General Comfort Questionnaire and Pain Outcomes Profile. Pain scores decreased from an average of 5.8/10 to 3.5/10 (p = .00). Comfort scores increased from an average of 17.5 to 30 (p = .00).

Mutations at several loci cause increased expression of ribonucleotide reductase in Escherichia coli.

Production of deoxyribonucleotides for DNA synthesis is an essential and tightly regulated process. The class Ia ribonucleotide reductase (RNR), the product of the nrdAB genes, is required for aerobic growth of Escherichia coli. In catalyzing the reduction of ribonucleotides, two of the cysteines of RNR become oxidized, forming a disulfide bond. To regenerate active RNR, the cell uses thioredoxins and glutaredoxins to reduce the disulfide bond. Strains that lack thioredoxins 1 and 2 and glutaredoxin 1 do not grow because RNR remains in its oxidized, inactive form. However, suppressor mutations that lead to RNR overproduction allow glutaredoxin 3 to reduce sufficient RNR for growth of these mutant strains. We previously described suppressor mutations in the dnaA and dnaN genes that had such effects. Here we report the isolation of new mutations that lead to increased levels of RNR. These include mutations that were not known to influence production of RNR previously, such as a mutation in the hda gene and insertions in the nrdAB promoter region of insertion elements IS1 and IS5. Bioinformatic analysis raises the possibility that IS element insertion in this region represents an adaptive mechanism in nrdAB regulation in E. coli and closely related species. We also characterize mutations altering different amino acids in DnaA and DnaN from those isolated before.

Repurposing lipoic acid changes electron flow in two important metabolic pathways of Escherichia coli.

In bacteria, cysteines of cytoplasmic proteins, including the essential enzyme ribonucleotide reductase (RNR), are maintained in the reduced state by the thioredoxin and glutathione/glutaredoxin pathways. An Escherichia coli mutant lacking both glutathione reductase and thioredoxin reductase cannot grow because RNR is disulfide bonded and nonfunctional. Here we report that suppressor mutations in the lpdA gene, which encodes the oxidative enzyme lipoamide dehydrogenase required for tricarboxylic acid (TCA) cycle functioning, restore growth to this redox-defective mutant. The suppressor mutations reduce LpdA activity, causing the accumulation of dihydrolipoamide, the reduced protein-bound form of lipoic acid. Dihydrolipoamide can then provide electrons for the reactivation of RNR through reduction of glutaredoxins. Dihydrolipoamide is oxidized in the process, restoring function to the TCA cycle. Thus, two electron transfer pathways are rewired to meet both oxidative and reductive needs of the cell: dihydrolipoamide functionally replaces glutathione, and the glutaredoxins replace LpdA. Both lipoic acid and glutaredoxins act in the reverse manner from their normal cellular functions. Bioinformatic analysis suggests that such activities may also function in other bacteria.

Acute effects of fatigue of the plantarflexor muscles on different postural tasks.

Although the effect of muscle fatigue on posture is apparent, results are inconsistent across studies and this may be due to differences in the fatigue protocol, postural stance used and/or amount of visual information provided. The purpose of this study was to test the hypothesis that fatigue would have a more pronounced effect for more difficult compared with less difficult postural tasks. Twenty-three young adults (mean age 22 ± 3 years) were asked to perform three different postural tasks on a force-platform: feet together, semi-tandem and single-leg stance, before and immediately after fatiguing the plantarflexor muscles. Three 30-s trials were performed for each postural task with eyes open and eyes closed. The fatigue protocol consisted of an isometric contraction of the plantarflexor muscles, with subjects instructed to rise on their toes and maintain this position until exhaustion. The 95% ellipse area of the center of pressure (COP), as well as the COP sway amplitudes (standard deviation) and sway velocities in the antero-posterior and medio-lateral directions were calculated. All variables were greater for each postural task performed without vision compared to with vision, with the greatest difference found during the single-leg task. For both visual conditions, all variables increased as the difficulty of the task increased. Fatigue of the plantarflexor muscles mostly affected postural sway variables during single-leg and feet together tasks. In conclusion, the reduction in postural stability with muscle fatigue of the plantarflexors does not depend on the difficulty of the postural task.

Difficulty taking medications, depression, and health status in heart failure patients.

BACKGROUND: Little is known about medication nonadherence in heart failure populations. We evaluated the association between 1 aspect of medication nonadherence, patient-reported difficulty taking medications as directed, and health status among heart failure outpatients, and then examined whether this association was explained by depression. METHODS AND RESULTS: A total of 522 outpatients with left ventricular ejection fraction <0.40 completed clinical evaluation, Kansas City Cardiomyopathy Questionnaire (KCCQ), Medical Outcomes Study-Depression questionnaire, and categorized their difficulty taking medications (5-level Likert-scale question). Multivariable regression was used to evaluate the cross-sectional association between difficulty taking medications and health status, with incremental adjustment for medical history and depressive symptoms. Patients with difficulty taking medications (n = 64; 12.2%) had worse health status (8.2 +/- 2.7 point lower mean KCCQ summary scores; P = .008) and more depressive symptoms (43.8% versus 27.1%; P = .006). Adjusting for demographic and clinical factors had little effect on the association between difficulty taking medications and health status (8.0 +/- 3.2 point lower KCCQ scores; P = .01); however, the relationship was attenuated with adjustment for depressive symptoms (4.7 +/- 2.9 point lower KCCQ scores; P = .11). CONCLUSIONS: Among heart failure outpatients, difficulty taking medications is associated with worse health status. This association appears to be explained, in part, by coexistent depression. Future studies should evaluate interventions such as depression treatment to improve medication adherence and health status.

Costs and effectiveness of pre- and post-operative home physiotherapy for total knee replacement: randomized controlled trial.

AIMS AND OBJECTIVES: To assess the effectiveness of pre- and post-operative physiotherapy at home for unilateral total knee replacement (TKR). METHODS: In this pragmatic randomized controlled trial set in participants' homes (four primary care trust areas) and physiotherapy outpatients in a South Yorkshire teaching hospital trust, 160 osteoarthritis patients waiting for unilateral TKR were randomly allocated to intervention (home) group (n=80) or control (hospital outpatient) group (n=80). The intervention group had pre- and post-operative home visits for assessment and treatment by a community physiotherapist. Outcome measures were health-related quality of life (HRQoL), measured by the Western Ontario McMaster Osteoarthritis index (WOMAC) and the Short Form 36 health survey (SF-36) pre-operatively and at 12 weeks post-TKR operation; patient satisfaction; and NHS resource use. RESULTS: No significant differences were observed between the two treatment groups in the primary outcome measure, the WOMAC pain score, or any other HRQoL score. The home group had a significantly greater mean number of physiotherapy sessions than the hospital group [mean difference 5.2 sessions, 95% confidence interval (CI)=-6.3 to -4.1; P=0.001]. There was no significant difference in the total NHS costs per patient between groups. However, home physiotherapy for TKR was significantly more expensive (mean difference-pound136.5, 95% CI=- pound160 to-pound113; P=0.001). Patients were equally satisfied with physiotherapy at home or in hospital; however, more of the home group would choose their location for physiotherapy again. CONCLUSIONS: Although home physiotherapy was as effective and as acceptable to patients as hospital outpatient physiotherapy for unilateral TKR, it was more expensive. Additional pre-operative home physiotherapy did not improve patient-perceived health outcomes.

Factors associated with cytoreducibility among women with ovarian carcinoma.

OBJECTIVES: The aim of the current study is to investigate the clinical and molecular factors associated with cytoreduction among women with advanced stage epithelial ovarian carcinoma EOC. METHODS: Seventy-two women with FIGO stage III and IV EOC or primary peritoneal carcinoma (PPC) underwent similar attempt at surgical cytoreduction, mostly by the same surgeon. The histologic material of these patients was reviewed and the histologic subtype and grade were assigned. Immunohistochemical tests were performed for expression of molecular regulators of apoptosis (p53, p21, Bcl(2), Bcl(x), Bax) and chemoresistance (PGP, MRP, LRP, GST). The following factors were assessed for their association with complete (no residual tumor) and optimal (residual tumor < 1 cm) cytoreduction: type of carcinoma (EOC versus PPC), stage, CA-125 values, ascites, histology, tumor grade, and p53, p21, Bcl(2), Bcl(x), Bax, PGP, MRP, LRP, GST expression using the odds ratio and associated 95% confidence intervals. Significant univariate odds ratios were assessed jointly in a multivariate logistic regression model. Receiver operating characteristic curve analysis was performed to determine the CA-125 level with the maximal cytoreduction prognostic power. RESULTS: Twenty-three (31.9%) women had no residual tumor, 35 (48.6%) had 1 cm. Factors with significant univariate associations with complete cytoreduction included stage, CA-125 level, ascites, histology, and p53. p53 expression was the only factor which remained significant in the multivariate analysis (odds ratio 7.2, 95% CI 1.5, 34.9). A preoperative CA-125 value of

Purification of anthocyanins from species of Banksia and Acacia using high-voltage paper electrophoresis.

A new method has been developed for the isolation and rapid identification of anthocyanins from two floricultural crops based on the use of high-voltage paper electrophoresis with bisulphite buffer. Using this method, anthocyanin pigments were successfully purified as their negatively charged bisulphite-addition compounds from crude extracts of plant tissue. In conjunction with liquid chromatography-electrospray mass spectrometry, the method enabled the anthocyanins from the flowers of two Banksia species and the leaves of two Acacia species to be identified. The Banksia flowers contained both cyanidin and peonidin-based pigments, while the Acacia leaves contained cyanidin and delphinidin derivatives.

Health-related quality of life and cost impact of irritable bowel syndrome in a UK primary care setting.

OBJECTIVES: To identify the impact of irritable bowel syndrome (IBS) on health-related quality of life (HR-QOL), time off work and the utilisation and cost of health services. DESIGN: A case-control study was undertaken matching patients with IBS and controls. Quality-of-life information was collected using the Medical Outcomes Study 36-item Short Form (SF-36) health survey, EuroQOL instrument (EQ-5D) and IBS Quality-of-Life (IBS-QOL) instruments. Data on time off work was also collected. National Health Service (NHS) resource use in primary and secondary care was estimated by review of general practitioner (GP) and hospital records over a 12-month period. SETTING: Recruitment was from six GPs' surgeries in the Trent Region of the United Kingdom. PARTICIPANTS: 161 patients with IBS, as defined by the Rome Criteria I were recruited. These were compared with 213 controls matched for age, sex and social characteristics. MAIN OUTCOME MEASURES: SF-36 and EQ-5D scores; mean number of days off work; mean NHS costs per person during the 12-month study period. RESULTS: Patients with IBS had considerably lower HR-QOL than controls. They scored worse in all dimensions of the SF-36 and the EQ-5D and they had more time off work. On average patients with IBS cost the NHS 123 UK pounds (95% confidence interval: 35 UK pounds to 221 UK pounds, 1999 values) more per year than individuals in the control group (p = 0.04). CONCLUSIONS: IBS affects patients through reduced quality of life, more time off work and greater healthcare utilisation than a control group of patients without IBS. The difference in quality of life was pronounced and unusual in that it was influential in every dimension of both the SF-36 and the EQ-5D.