Maternal vitamin D status modifies the effects of early life tobacco exposure on child lung function.

BACKGROUND: Prior studies suggest that vitamin D may modify the effects of environmental exposures; however, none have investigated gestational vitamin D and cumulative tobacco smoke exposure (TSE) throughout pregnancy and early life. OBJECTIVES: This study investigated the effects of early life TSE on child lung function and the modulatory effects of gestational vitamin D on this association. METHODS: The VDAART (Vitamin D Antenatal Asthma Reduction Trial) recruited nonsmoking pregnant women and followed the mother-child pairs to age 6 years. TSE was assessed with questionnaires and plasma cotinine measurements in the mothers (10-18 and 32-38 gestational weeks) and children (1, 3, and 6 years). Cumulative TSE was calculated from the repeated cotinine measurements. 25-hydroxyvitamin D (25[OH]D) levels were measured at 10-18 and 32-38 gestational weeks. Lung function was assessed at 6 years with spirometry and impulse oscillometry. RESULTS: Of the 476 mother-child pairs, 205 (43%) had increased cotinine levels at ≥1 time point. Cumulative TSE was associated with decreased FEV1 (ß = -0.043 L, P = .018) and increased respiratory resistance at 5 Hz (R5; ß = 0.060 kPa/L/s, P = .002). This association persisted in subjects with insufficient (<30 ng/mL) 25(OH)D levels throughout pregnancy (ß = 0.077 kPa/L/s, P = .016 for R5) but not among those with sufficient levels throughout pregnancy. CONCLUSIONS: Cumulative TSE from pregnancy to childhood is associated with dose- and duration-dependent decreases in child lung function at 6 years even in the absence of reported maternal smoking. Gestational vitamin D may modulate this effect and have therapeutic potential for minimizing the adverse effect of TSE on lung throughout early life. RANDOMIZED TRIAL: Maternal Vitamin D Supplementation to Prevent Childhood Asthma (VDAART); clinicaltrials.gov identifier: NCT00920621.

Uptake of and Motivational Responses to Mental Health-Promoting Practices: Comparing Relaxation and Mindfulness Interventions.

Background: Comparative analyses of alternative interventions within the same trial enable acceptability and fidelity of each to be investigated more critically. In addition, whereas so far studies have focused on efficacy evaluations, more understanding is needed on motivational factors influencing the uptake of mental health-promoting practices rather than solely their effects. Purpose: This study investigates whether the motivational responses to a mindfulness intervention are different from a relaxation intervention. We compare social cognitions outlined by the reasoned action approach and their roles in practice uptake, self-reported reasons for non-practice, and experienced benefits. Methods: In a cluster-randomized trial (ISRCTN18642659; N = 3134), 12-15-year-old participants were given a 9-week intervention and followed up to 52 weeks. Main statistical analyses included t-tests, mixed ANOVAs, path models, and chi-square tests. Results: Social cognitions in the mindfulness arm were slightly more positive immediately post-intervention, but recipients mostly responded similarly to the two interventions in the longer term. While attitudes, norms, intention, and self-efficacy were relatively high post-intervention, most of them slightly decreased by 26 weeks. Main reasons for non-practice in both arms included not finding the exercises helpful, no felt need, boringness of exercises and forgetting. The most common benefits experienced by practicing respondents were stress management and concentration ability. Better sleep was a more frequently reported benefit in the relaxation arm, but no other major differences emerged. Conclusion: This study offers an example of comparing motivational responses to experimental and active control arm interventions, a potentially helpful approach in improving intervention adherence.

Effects of in ovo injection of nicotinamide riboside on high-yield broiler myogenesis.

The objective of this study was to determine the effects of in ovo injection of high-yield broiler embryos with nicotinamide riboside (NR) on pectoralis major muscle (PMM) development, growth, and gene expression. Fertilized Cobb 700 broiler eggs were randomly assigned to one of four treatments within a 2 × 2 factorial design. Factor 1 consisted of NR dose (DOS) with eggs receiving 0 or 2.5 mM NR. Factor 2 consisted of injection location (LOC), with treatments injected into either the yolk sac or albumen. At day 10 of incubation, 100 µL of the assigned NR dose was injected into the yolk sac of the developing embryo and chicks were euthanized within 24 h of hatching. Chick PMM and individual fiber morphometrics, and expression of genes associated with cell cycle progression were analyzed. There were DOS × LOC interactions for hatched chick PM weight and length (P < 0.04). When NR was injected into the albumen, PMM weight decreased (P < 0.05); when NR was injected into the yolk, PMM weight increased (P < 0.05). Pectoralis major length was not affected (P > 0.05) when NR was injected into the albumen but was increased (P < 0.05) when NR was injected into the yolk. There was a DOS × LOC interaction (P = 0.04) for muscle fiber density and tended to be a DOS × LOC interaction (P = 0.07) for muscle fiber CSA. Pectoralis major muscle fiber density was not affected when NR was injected into the albumen (P > 0.05), but density increased when NR was injected into the yolk (P < 0.05). There were DOS × LOC interactions for hatched chick COXII, cyclin D, and SIRT1 expression (P ≤ 0.04), which may indicate NR improves skeletal muscle development and growth by enhancing myoblast proliferation during embryonic development.

Broiler chicken weight gain is a result of genetics and nutrition, with increased muscle mass attributed to accelerated embryonic myogenesis and posthatch muscle growth. During the avian incubation period, in ovo injection may be used as a strategy to deliver exogenous supplements into growing embryos for improving skeletal muscle development and growth. Nicotinamide riboside (NR), a vitamin B3 analog, is a human performance supplement used to stimulate mitochondria biogenesis and elevate tissue NAD+ levels. Research showed injecting NR into the chick embryonic yolk sac increased breast muscle weight and muscle satellite cell numbers and proliferation rate. Therefore, our objective was to determine the effects of in ovo injection of high-yield broilers with NR on broiler breast muscle development and growth. Our study showed in ovo injection of NR into the yolk sac increased hatched chick breast muscle morphometrics, which coincided with an increase in muscle fiber density and tended to decrease fiber cross-sectional area. Increased Sirtuin1 and cyclin D mRNA expression of hatched chicks from eggs injected with 2.5 mM NR into yolk sac indicate a potential NR regulated Sirtuin1/cyclin D molecular mechanism mediating chicken muscle early development.

Virus-Host Interactions and Genetic Diversity of Antarctic Sea Ice Bacteriophages.

Although we know the generally appreciated significant roles of microbes in sea ice and polar waters, detailed studies of virus-host systems from such environments have been so far limited by only a few available isolates. Here, we investigated infectivity under various conditions, infection cycles, and genetic diversity of the following Antarctic sea ice bacteriophages: Paraglaciecola Antarctic GD virus 1 (PANV1), Paraglaciecola Antarctic JLT virus 2 (PANV2), Octadecabacter Antarctic BD virus 1 (OANV1), and Octadecabacter Antarctic DB virus 2 (OANV2). The phages infect common sea ice bacteria belonging to the genera Paraglaciecola or Octadecabacter. Although the phages are marine and cold-active, replicating at 0°C to 5°C, they all survived temporal incubations at ≥30°C and remained infectious without any salts or supplemented only with magnesium, suggesting a robust virion assembly maintaining integrity under a wide range of conditions. Host recognition in the cold proved to be effective, and the release of progeny viruses occurred as a result of cell lysis. The analysis of viral genome sequences showed that nearly one-half of the gene products of each virus are unique, highlighting that sea ice harbors unexplored virus diversity. Based on predicted genes typical for tailed double-stranded DNA phages, we suggest placing the four studied viruses in the class Caudoviricetes. Searching against viral sequences from metagenomic assemblies, we revealed that related viruses are not restricted to Antarctica but are also found in distant marine environments. IMPORTANCE Very little is known about sea ice microbes despite the significant role played by sea ice in the global oceans as well as microbial input into biogeochemical cycling. Studies on the sea ice viruses have been typically limited to -omics-based approaches and microscopic examinations of sea ice samples. To date, only four cultivable viruses have been isolated from Antarctic sea ice. Our study of these unique isolates advances the understanding of the genetic diversity of viruses in sea ice environments, their interactions with host microbes, and possible links to other biomes. Such information contributes to more accurate future sea ice biogeochemical models.

Latent profile analysis as a method for process evaluations: Discovering response subgroups in a mindfulness intervention.

RATIONALE: Clustering techniques have been used within intervention studies to locate any distinct subgroups among intervention participants. One way in which they have not yet been utilized, but for which there is potential benefit, is in finding different motivational and behavioral response types to a newly introduced behavior. OBJECTIVE: This study aimed to use latent profile analyses (the same as latent class analyses except with continuous indicator variables) to identify 1) types, or classes, in terms of social cognitive responses to a mindfulness intervention, using The Reasoned Action Approach constructs, and 2) longitudinal/change trajectory classes of the target behavior (i.e., mindfulness practice). METHODS: The data derived from a school-based mindfulness intervention (N = 1646) among 12-15 year-olds, conducted in southern Finland from 2014 to 2016. We explored associations between the identified classes and with gender, linguocultural group, and mental health and practice outcomes. RESULTS: Analyses indicated a solution of five latent classes for both social cognition post-intervention-Uncertain but Positive (40.2%), Acceptable but No (18.8%), Indifferent (16.8), Inclined (15.5%), Disinclined (8.6%)-and practice trajectories-Stable Low (52.1%), Decreased from Seldom (25.8%), Decreased from Sometimes (10.7%), Increased from Zero (6.8%), Increased from Seldom (4.6%). The strongest differentiating theoretical construct among the social cognitive classes was a descriptive norm. The classes were characterized by some associations between each other (e.g., "Acceptable but No" and "Stable Low") and with linguocultural groups (e.g., "Inclined" and small language minorities) and mental health (e.g., "Disinclined" and externalization and depressive symptoms), but no specific associations were found by gender. CONCLUSIONS: This study shows how more person-centered analyses can be utilized in process evaluations, which predominantly only make use of variable-centered analyses. This knowledge could suggest ways to tailor universal interventions for subgroups with different receipt profiles and thereby improve intervention acceptability and engagement.

Fertilizer demand and potential supply through nutrient recovery from organic waste digestate in California.

Diversion of organic waste from landfills offers an opportunity to recover valuable nutrients such as nitrogen and phosphorus that are typically discarded. Although prior research has explored the potential for buildout of anaerobic digestion (AD) infrastructure to treat organic waste and generate energy, a better understanding is needed of the nutrient recovery potential from the solid and liquid byproducts (digestate) resulting from AD of these waste streams. We quantified the system-wide mass of nutrients that can potentially be recovered in California by integrating current and potential future AD facilities with existing nutrient recovery technologies. Based on a profitable build-out scenario for AD, the potential for nitrogen and phosphorus recovery by mass was greatest from municipal sewage sludge. The nutrient recovery (% total mass) was determined for three different end products for the combined organic waste streams: liquid fertilizer [38% of the total recovered nitrogen (TN)], struvite [50% TN, 66% total phosphorous (TP)], and compost (12% TN, 34% TP). Based on the profitable build-out scenario of AD facilities in California, the recovered nutrients would offset an estimated 11% of TN and 29% of TP of in-state synthetic fertilizer demand, whereas a scenario in which all technically recoverable biomass is collected and treated could offset 44% of TN and 97% of TP demand.

Maternal 17q21 genotype influences prenatal vitamin D effects on offspring asthma/recurrent wheeze.

BACKGROUND: Prenatal vitamin D3 supplementation has been linked to reduced risk of early-life asthma/recurrent wheeze. This protective effect appears to be influenced by variations in the 17q21 functional single nucleotide polymorphism rs12936231 of the child, which regulates the expression of ORMDL3 (ORM1-like 3) and for which the high-risk CC genotype is associated with early-onset asthma. However, this does not fully explain the differential effects of supplementation. We investigated the influence of maternal rs12936231 genotype variation on the protective effect of prenatal vitamin D3 supplementation against offspring asthma/recurrent wheeze. METHODS: We determined the rs12936231 genotype of mother-child pairs from two randomised controlled trials: the Vitamin D Antenatal Asthma Reduction Trial (VDAART, n=613) and the Copenhagen Prospective Studies on Asthma in Childhood 2010 (COPSAC2010, n=563), to examine the effect of maternal genotype variation on offspring asthma/recurrent wheeze at age 0-3 years between groups who received high-dose prenatal vitamin D3 supplementation versus placebo. RESULTS: Offspring of mothers with the low-risk GG or GC genotype who received high-dose vitamin D3 supplementation had a significantly reduced risk of asthma/recurrent wheeze when compared with the placebo group (hazard ratio (HR) 0.54, 95% CI 0.37-0.77; p<0.001 for VDAART and HR 0.56, 95% CI 0.35-0.92; p=0.021 for COPSAC2010), whereas no difference was observed among the offspring of mothers with the high-risk CC genotype (HR 1.05, 95% CI 0.61-1.84; p=0.853 for VDAART and HR 1.11, 95% CI 0.54-2.28; p=0.785 for COPSAC2010). CONCLUSION: Maternal 17q21 genotype has an important influence on the protective effects of prenatal vitamin D3 supplementation against offspring asthma/recurrent wheeze.

Effect of pulse waveforms on movement amplitudes and perceived discomfort in electric muscle stimulation in unresolved facial nerve palsy.

Studies on the effects of the pulse waveform used in electrical muscle stimulation on the activations and perceived discomfort of the waveform have been mainly executed on limb muscles with variable results, however, knowledge of these effects on facial muscles is currently lacking. We studied two waveforms, square wave and sinusoidal wavelet, for the activation of the frontalis muscle in 9 individuals with unresolved facial nerve palsy. Both waveforms produced a movement that was greater in amplitude compared with the maximal voluntary movement of the affected side in 8 participants and at least as great as the healthy side's maximal voluntary movement in 4 participants. Both waveforms were equally successful in producing movements, and there was no significant difference in perceived discomfort ratings between the two waveforms. These findings will be useful for the future development of neuroprosthetic applications for reanimating facial muscles using electrical stimulation. Trial registration: ClinicalTrials.gov NCT03496025, registration date March 19, 2018.

Views of professionals and volunteers in palliative care on patient-centred care: a Q-methodology study in the Netherlands.

BACKGROUND: Patients with palliative care needs, require support with their physical needs, but also with their emotional, spiritual and social needs. Patient-Centred Care (PCC) may help organizations to support these patients according to their needs and so improve the quality of care. PCC has been shown to consist of eight dimensions, including for instance access to care and continuity of care, but these eight dimensions may not be equally important in all care settings and to all patients. Furthermore, the views of those involved in care provision may affect the choices they make concerning care and support to patients. Therefore, insight into how professionals and volunteers involved in palliative care delivery view PCC is important for understanding and improving the quality of care in the palliative sector. METHODS: This study was conducted in the palliative care setting (hospices and hospitals) in the Netherlands. Views on palliative care were investigated using the Q-methodology. Participants were asked to rank 35 statements that represented the eight dimensions of PCC in palliative care settings, and to explain their ranking during a follow-up interview. Ranking data were analysed using by-person factor analysis. Interview materials were used to help interpret the resulting factors. RESULTS: The analysis revealed two distinct viewpoints on PCC in palliative care: 'The patient in the driver seat', particularly emphasizing the importance of patient autonomy during the last phase of life, and 'The patient in the passenger seat', focussed on the value of coordination between professionals, volunteers and patients. CONCLUSIONS: The most distinguishing aspect between views on PCC in palliative care concerned control; a preference for the patient in the driver's seat versus shared decision-making by a team consisting of patient, professionals and volunteers. Different types of care and support may be most adequate to satisfy the different needs and preferences of patients with either of these views.

Beyond Iron: Iridium-Containing P450 Enzymes for Selective Cyclopropanations of Structurally Diverse Alkenes.

Enzymes catalyze organic transformations with exquisite levels of selectivity, including chemoselectivity, stereoselectivity, and substrate selectivity, but the types of reactions catalyzed by enzymes are more limited than those of chemical catalysts. Thus, the convergence of chemical catalysis and biocatalysis can enable enzymatic systems to catalyze abiological reactions with high selectivity. Recently, we disclosed artificial enzymes constructed from the apo form of heme proteins and iridium porphyrins that catalyze the insertion of carbenes into a C-H bond. We postulated that the same type of Ir(Me)-PIX enzymes could catalyze the cyclopropanation of a broad range of alkenes with control of multiple modes of selectivity. Here, we report the evolution of artificial enzymes that are highly active and highly stereoselective for the addition of carbenes to a wide range of alkenes. These enzymes catalyze the cyclopropanation of terminal and internal, activated and unactivated, electron-rich and electron-deficient, conjugated and nonconjugated alkenes. In particular, Ir(Me)-PIX enzymes derived from CYP119 catalyze highly enantio- and diastereoselective cyclopropanations of styrene with ±98% ee, >70:1 dr, >75% yield, and ∼10,000 turnovers (TON), as well as 1,2-disubstituted styrenes with up to 99% ee, 35:1 dr, and 54% yield. Moreover, Ir(Me)-PIX enzymes catalyze cyclopropanation of internal, unactivated alkenes with up to 99% stereoselectivity, 76% yield, and 1300 TON. They also catalyze cyclopropanation of natural products with diastereoselectivities that are complementary to those attained with standard transition metal catalysts. Finally, Ir(Me)-PIX P450 variants react with substrate selectivity that is reminiscent of natural enzymes; they react preferentially with less reactive internal alkenes in the presence of more reactive terminal alkenes. Together, the studies reveal the suitability of Ir-containing P450s to combine the broad reactivity and substrate scope of transition metal catalysts with the exquisite selectivity of enzymes, generating catalysts that enable reactions to occur with levels and modes of activity and selectivity previously unattainable with natural enzymes or transition metal complexes alone.

Using low level laser therapy to reduce early postoperative airway obstruction following modified Hogan’s flap / El uso de la terapia con láser de baja intensidad para reducir la obstrucción de la vía aérea postoperatoria temprana después del colgajo de Hogan modificado

Introduction and objective: The most common postoperative complications of velopharyngeal insufficiency surgery are postoperative bleeding and airway obstruction or obstructive sleep apnoea. Consequently, the aim of this study was to evaluate the effect of low level laser therapy (LLLT) during the first postoperative days in children undergoing superiorly based pharyngeal flap (SBF) surgery. Materials and methods: A randomized double blind clinical study on 30 children divided on two groups 15 patients each, who underwent SBF. LLLT was used in a group and the other was a control group. The study was conducted in academic tertiary care medical centres between 2013 and 2015. The degree of edema, oxygen saturation, occurrence of obstructive sleep apnoea (OSA) and steroid administration were recorded. Results: The mean of the average oxygen saturation was significantly less in the control group in the 1st and 2nd day as compared to the laser group. The need for oxygen and the incidence of OSA in the first 3 days were significantly higher in the control group as compared to the laser group. The degree of edema showed no significant difference in the first day but was significantly higher in the control group in the 2nd and 3rd days. Hence, the need of steroids was significantly higher in the control group in the first 3 days. Conclusions: Preliminary results showed that low level laser therapy is effective in reducing the incidence of early postoperative airway obstruction after SBF operations (AU)

Introducción y objetivo: La más común de las complicaciones postoperatorias tras la cirugía de la insuficiencia velofaríngea son el sangrado y la obstrucción postoperatoria de las vías respiratorias, o la apnea obstructiva del sueño. Por lo tanto, el objetivo de este estudio fue evaluar el efecto de la terapia láser de baja intensidad durante los primeros días del postoperatorio en niños sometidos a colgajo faríngeo de base superior (SBF). Métodos: Estudio clínico aleatorizado doble ciego en 30 niños, entre el grupo de láser y el grupo control, que fueron sometidos a SBF. El estudio se llevó a cabo en dos centros médicos académicos de atención terciaria, entre 2013 y 2015. Se registró grado de edema, la saturación de oxígeno, la aparición de apnea obstructiva del sueño y la necesidad de esteroides. Resultados: Durante los 3 primeros días, la media de la saturación de oxígeno muestra cambios significativos entre los dos grupos. Por otra parte, la necesidad de oxígeno en los primeros 3 días muestra también cambios significativos entre los dos grupos. Así como la incidencia de apnea obstructiva del sueño. El grado de edema no muestra ningún cambio significativo en el primer día, pero sí en los 2 días siguientes. Por lo tanto, la necesidad de esteroides en los primeros 3 días también muestra cambios significativos entre los dos grupos. Conclusiones: Los resultados preliminares mostraron que la terapia con láser de baja intensidad es eficaz en la reducción de la incidencia de obstrucción de vía aérea en el postoperatorio temprano después de las operaciones SBF (AU)

Extracorporeal shockwave therapy in the treatment of chronic diabetic foot ulcers: a prospective randomised trial.

OBJECTIVE: To investigate the efficacy of extracorporeal shockwave therapy (ESWT) on healing chronic diabetic foot ulcers (DFU). METHOD: Patients with chronic DFUs were randomised (1:1) to receive a series of six ESWT treatments over 3 weeks in combination with standard care or standard care alone. ESWT was performed on DFUs using 250 shocks/cm2 and 500 shocks on arterial beds supplying the ulcer location. RESULTS: We recruited 23 patients, 11 in the intervention group and 12 in the control. Transcutaneous oxygen tension was significantly increased in patients treated with ESWT compared with those receiving standard care alone at 3 weeks (p=0.044). Ulcer area reduction was 34.5% in the intervention group versus 5.6% in the control group at 7 weeks (p=0.387). Within-group analysis revealed a significant reduction of ulcer area in the intervention group (p<0.01), while healing was not demonstrated in the control group (p>0.05) (data tested for trend). CONCLUSION: This randomised study indicates a potential beneficial effect of ESWT on ulcer healing as well as tissue oxygenation. Owing to weaknesses of the study and the fact that ulcer healing was not significantly improved in the intervention group compared with the control group, a larger randomised trial with blinded design is suggested.

The effectiveness of low-level laser on postoperative pain and edema in secondary palatal operation.

OBJECTIVE: The postoperative period after palatal surgery is usually very painful, requiring the use of pain-relieving drugs. Hence, the aim of this study was to evaluate the efficacy of Low-level laser therapy (LLLT) in post-operative pain control and edema after secondary palatal operations. METHODS: A randomized double blinded clinical study on 20 children undergoing secondary palatal operations between 2013 and 2015 was done. Patients were randomly divided on two groups 10 patients each. In one group patients received local application of therapeutic laser immediately after surgery while patients received nothing in the control group. The mean age was 5.22 years ± 2.53 SD in the laser group and 6.42 years ± 0.76 in the control group. Postoperative pain was assessed by using visual analog scale scores and by recording the need of analgesics. The degree of postoperative edema was also recorded. RESULTS: The pain scale showed significantly less postoperative pain in the laser group than in the control group from the first day (P-value = 0.006) to the 6th day (P-value = 0.014). The number of postoperative analgesic doses needed were significantly less in the laser group in the second and third days (P-value = 0.014). The postoperative edema was significantly higher in the control group from the 2nd (P-value = 0.004) to the 7th (P-value = 0.014) postoperative days. CONCLUSIONS: Preliminary results showed that low-level laser therapy is effective in the reduction of postoperative pain and edema, and minimizing the need of analgesic medication after secondary palatal operations.

Using low level laser therapy to reduce early postoperative airway obstruction following modified Hogan's flap.

INTRODUCTION AND OBJECTIVE: The most common postoperative complications of velopharyngeal insufficiency surgery are postoperative bleeding and airway obstruction or obstructive sleep apnoea. Consequently, the aim of this study was to evaluate the effect of low level laser therapy (LLLT) during the first postoperative days in children undergoing superiorly based pharyngeal flap (SBF) surgery. MATERIALS AND METHODS: A randomized double blind clinical study on 30 children divided on two groups 15 patients each, who underwent SBF. LLLT was used in a group and the other was a control group. The study was conducted in academic tertiary care medical centres between 2013 and 2015. The degree of edema, oxygen saturation, occurrence of obstructive sleep apnoea (OSA) and steroid administration were recorded. RESULTS: The mean of the average oxygen saturation was significantly less in the control group in the 1st and 2nd day as compared to the laser group. The need for oxygen and the incidence of OSA in the first 3 days were significantly higher in the control group as compared to the laser group. The degree of edema showed no significant difference in the first day but was significantly higher in the control group in the 2nd and 3rd days. Hence, the need of steroids was significantly higher in the control group in the first 3 days. CONCLUSIONS: Preliminary results showed that low level laser therapy is effective in reducing the incidence of early postoperative airway obstruction after SBF operations.

[Good prescribing practice]. / Gute Verordnungspraxis.

Drug prescription is the very first step initiating a cascade of events in the medication process. It is, hence, decisive for success or failure of any pharmacologic treatment. A good prescription must therefore consider (1) relevant patient factors and co-morbidities, (2) evidence-based knowledge on medically sound prescribing practices, and (3) the setting in which a prescription is issued. The setting will determine which partners will participate, contribute, and safeguard the ongoing medication process and how much responsibility can be shared. Partners in the medication process refer to other healthcare professionals dispensing the drug, teaching the patient, or administering the medicines. It also involves the patients or their relatives with their information needs and often variable motivation and conviction to use a drug. By issuing a prescription, the physician must provide the partners with sufficient and appropriate information, must ensure that they understand the meaning of the prescription and are able to perform their assigned tasks during the medication process. Lastly, medication prescription is also subject to formal constraints and must meet legal criteria that are relevant for reimbursement by health insurance companies.

[Good prescription practice for out-patients-quality requirements of prescriptions in Germany]. / Gute Verordnungspraxis im ambulanten Sektor - Qualitätsanforderungen an die Rezeptschreibung in Deutschland.

Because the written prescription is a central communication medium between the prescribing physician and the dispensing pharmacist measures to improve the prescription quality are top priorities. While most primary care physicians in Germany use electronic systems, in outpatient clinics and nursing homes and on special occasions such as emergency services and home visits, many prescriptions are still handwritten. Incorrectly and illegibly issued prescriptions impair the physician-pharmacist-patient relationship and thus represent a risk factor in the context of medication safety. Well issued prescriptions expedite the dispensing and thus the continuity of treatment of the patients and spare human resources by avoiding queries and unnecessary steps in the care process. At the same time, legible and unequivocal prescriptions facilitate measures for quality assurance by the dispensing pharmacists and are essential preconditions needed for insurance reimbursement. Probably the most important step to high quality prescriptions is the consistent use of suitable electronic prescription software. This is only possible if physicians are willing to cooperate and understand the significance and benefits of an electronic prescription system.

A generic, whole-cell-based screening method for Baeyer-Villiger monooxygenases.

Baeyer-Villiger monooxygenases (BVMOs) have been receiving increasing attention as enzymes useful for biocatalytic applications. Industrial requirements call for rapid and extensive redesign of these enzymes. In response to the need for screening large libraries of BVMO mutants, we established a generic screening method that allows screening of Escherichia coli cells expressing active BVMOs in 96-well plate format. For this, we first developed an expression system for production of phenylacetone monooxygenase (PAMO) in the periplasm of E. coli. This allows probing the enzyme for any target substrate while it is also compatible with extracellular coenzyme regeneration. For coenzyme regeneration, we used phosphite dehydrogenase, which forms phosphate upon NADPH recycling. This allowed the use of a chromogenic molybdate-based phosphate determination assay. The screening procedure was supplemented with a detection method for identification of mutant enzymes that act as NADPH oxidases, thereby excluding false-positives. The whole-cell-based screening method was validated by screening site-saturation libraries of PAMO and resulted in the identification of PAMO mutants with altered catalytic properties. This new method can be used for screening libraries of BVMOs for activity with any desired substrate and therefore is a powerful tool for engineering of these enzymes.

Randomised, double blind, placebo-controlled trial of echinacea supplementation in air travellers.

Objective. To identify whether a standardised Echinacea formulation is effective in the prevention of respiratory and other symptoms associated with long-haul flights. Methods. 175 adults participated in a randomised, double-blind placebo-controlled trial travelling back from Australia to America, Europe, or Africa for a period of 1-5 weeks on commercial flights via economy class. Participants took Echinacea (root extract, standardised to 4.4 mg alkylamides) or placebo tablets. Participants were surveyed before, immediately after travel, and at 4 weeks after travel regarding upper respiratory symptoms and travel-related quality of life. Results. Respiratory symptoms for both groups increased significantly during travel (P < 0.0005). However, the Echinacea group had borderline significantly lower respiratory symptom scores compared to placebo (P = 0.05) during travel. Conclusions. Supplementation with standardised Echinacea tablets, if taken before and during travel, may have preventive effects against the development of respiratory symptoms during travel involving long-haul flights.

Acetazolamide efficacy in hypokalemic periodic paralysis and the predictive role of genotype.

OBJECTIVES: Acetazolamide has been the most commonly used treatment for hypokalemic periodic paralysis since 1968. However, its mechanism of efficacy is not fully understood, and it is not known whether therapy response relates to genotype. We undertook a clinical and genetic study to evaluate the response rate of patients treated with acetazolamide and to investigate possible correlations between response and genotype. METHODS: We identified a total of 74 genotyped patients for this study. These included patients who were referred over a 15-year period to the only U.K. referral center or to a Chinese center and who underwent extensive clinical evaluation. For all genotyped patients, the response to acetazolamide therapy in terms of attack frequency and severity was documented. Direct DNA sequencing of CACNA1S and SCN4A was performed. RESULTS: Only 46% of the total patient cohort (34 of 74) reported benefit from acetazolamide. There was a greater chance of benefit in patients with mutations in CACNA1S (31 responded of 55 total) than in those with mutations in SCN4A (3 responded of 19 total). Patients with mutations that resulted in amino acids being substituted by glycine in either gene were the least likely to report benefit. CONCLUSIONS: This retrospective study indicates that only approximately 50% of genotyped patients with hypokalemic periodic paralysis respond to acetazolamide. We found evidence supporting a relationship between genotype and treatment response. Prospective randomized controlled trials are required to further evaluate this relationship. Development of alternative therapies is required.