Breeding Wheat for Resilience to Increasing Nighttime Temperatures

Increases in global mean temperature since 1960 are largely attributed to the rise in minimum nighttime temperatures thereby decreasing diurnal temperature variation. Increased night temperatures are known to affect crop development. A multi-year study investigating the effects of increased night temperatures on soft red winter wheat (Triticum aestivum L.) varieties was conducted during the 2015-2016 growing seasons at the University of Kentucky Spindletop Research Farm in Lexington, KY. Thirty-six cultivars and breeding lines were chosen based on their genotypes at photoperiod and vernalization loci. This material was planted in a randomized complete block experiment with two replications and two environments, control and passively warmed. To create a passively warmed environment, thermal covers were mounted to frames in plots and connected to a datalogger programmed to cover plants from dusk to dawn based on coordinate location. Night temperature increases ranged from 0.27–0.75 °C above ambient temperature. Grain yield, averaged across genotypes, was significantly reduced in the passively warmed environment by 224 kg ha−1 (p ≤ 0.05) or 6.44%; however, yield response to environment varied among genotypes with several genotypes displaying an increased yield in the warmed environment. Yield reductions may reflect reduced nitrogen utilization (9.4%; p ≤ 0.001) under increased night temperatures

Post-operative atrial fibrillation is influenced by beta-blocker therapy but not by pre-operative atrial cellular electrophysiology

We investigated whether post-cardiac surgery (CS) new-onset atrial fibrillation (AF) is predicted by pre-CS atrial cellular electrophysiology, and whether the antiarrhythmic effect of beta-blocker therapy may involve pre-CS pharmacological remodeling. Atrial myocytes were obtained from consenting patients in sinus rhythm, just prior to CS. Action potentials and ion currents were recorded using whole-cell patch-clamp technique. Post-CS AF occurred in 53 of 212 patients (25%). Those with post-CS AF were older than those without (67 ± 2 vs 62 ± 1 years, P = 0.005). In cells from patients with post-CS AF, the action potential duration at 50% and 90% repolarization, maximum upstroke velocity, and effective refractory period (ERP) were 13 ± 4 ms, 217 ± 16 ms, 185 ± 10 V/s, and 216 ± 14 ms, respectively (n = 30 cells, 11 patients). Peak L-type Ca2+ current, transient outward and inward rectifier K+ currents, and the sustained outward current were −5.0 ± 0.5, 12.9 ± 2.4, −4.1 ± 0.4, and 9.7 ± 1.0 pA/pF, respectively (13-62 cells, 7-19 patients). None of these values were significantly different in cells from patients without post-CS AF (P > 0.05 for each, 60-279 cells, 29-86 patients), confirmed by multiple and logistic regression. In patients treated >7 days with a beta-blocker pre-CS, the incidence of post-CS AF was lower than in non-beta-blocked patients (13% vs 27%, P = 0.038). Pre-CS beta-blockade was associated with a prolonged pre-CS atrial cellular ERP (P = 0.001), by a similar degree (∼20%) in those with and without post-CS AF. Conclusion: Pre-CS human atrial cellular electrophysiology does not predict post-CS AF. Chronic beta-blocker therapy is associated with a reduced incidence of post-CS AF, unrelated to a pre-CS ERP-prolonging effect of this treatment

Seeking help for depression from family and friends: A qualitative analysis of perceived advantages and disadvantages

BACKGROUND People with depression often seek help from family and friends and public health campaigns frequently encourage such help seeking behaviours. However, there has been little systematically collected empirical data concerning the effects of such informal help seeking. The current study sought to investigate the views of consumers about the advantages and disadvantages of seeking support from family and friends for depression. METHODS Participants were the subset of 417 respondents to a survey, sent to 7000 randomly selected members of an Australian electoral community, who indicated that they had sought help for depression from family or friends. One item on the survey asked participants to indicate the advantages or disadvantages of seeking help from family or friends. A coding system was developed based on a content analysis of the responses to the item. Each of the responses was then coded by two raters. RESULTS Respondents identified both advantages and disadvantages of seeking support from friends. The most commonly cited advantage was social support (n = 282) including emotional support (n = 154), informational support (n = 93), companionship support (n = 36) and instrumental support (n = 23). Other advantages related to family's or friend's background knowledge of the person and their circumstances (n = 72), the opportunity to offload the burden associated with depression (n = 62), the personal attributes of family and friends (n = 49), their accessibility (n = 36), and the opportunity to educate family and friends and increase their awareness about the respondent's depression (n = 30). The most commonly cited disadvantages were stigma (n = 53), inappropriate support (n = 45), the family member's lack of knowledge, training and expertise (n = 32) and the adverse impact of the help seeking on the family/friend (n = 20) and the relationship (n = 18). CONCLUSIONS Family and friends are well placed to provide support which consumers perceive to be positive and which can assist them in obtaining formal mental health treatment. However, the input of some family members may be unhelpful or toxic. There may be benefits in undertaking community education and destigmatisation programs which target carers.Kathleen Griffiths is supported by NHMRC Fellowship 525413. Lisa Barney is supported by NHMRC Capacity Building Grant No. 41802

Are Dietary Bioactives Ready for Recommended Intakes?12

Research has shown that numerous dietary bioactive components that are not considered essential may still be beneficial to health. The dietary reference intake (DRI) process has been applied to nonessential nutrients, such as fiber, yet the majority of bioactive components await a recommended intake. Despite a plethora of new research over the past several years on the health effects of bioactives, it is possible that the field may never reach a point where the current DRI framework is suitable for these food components. If bioactives are to move toward dietary guidance, they will likely require an alternative path to get there

Multidisciplinary Group Clinic Appointments: The Self-Management and Care of Heart Failure (SMAC-HF) Trial

Background—This trial tested the effects of multidisciplinary group clinic appointments on the primary outcome of time to first heart failure (HF) rehospitalization or death. Methods and Results—HF patients (n=198) were randomly assigned to standard care or standard care plus multidisciplinary group clinics. The group intervention consisted of 4 weekly clinic appointments and 1 booster clinic at month 6, where multidisciplinary professionals engaged patients in HF self-management skills. Data were collected prospectively for 12 months beginning after completion of the first 4 group clinic appointments (2 months post randomization). The intervention was associated with greater adherence to recommended vasodilators (P=0.04). The primary outcome (first HF-related hospitalization or death) was experienced by 22 (24%) in the intervention group and 30 (28%) in standard care. The total HF-related hospitalizations, including repeat hospitalizations after the first time, were 28 in the intervention group and 45 among those receiving standard care. The effects of treatment on rehospitalization varied significantly over time. From 2 to 7 months post randomization, there was a significantly longer hospitalization-free time in the intervention group (Cox proportional hazard ratio=0.45 (95% confidence interval, 0.21–0.98; P=0.04). No significant difference between groups was found from month 8 to 12 (hazard ratio=1.7; 95% confidence interval, 0.7–4.1). Conclusions—Multidisciplinary group clinic appointments were associated with greater adherence to selected HF medications and longer hospitalization-free survival during the time that the intervention was underway. Larger studies will be needed to confirm the benefits seen in this trial and identify methods to sustain these benefits

Cluster M Mycobacteriophages Bongo, PegLeg, and Rey with Unusually Large Repertoires of tRNA Isotopes

Genomic analysis of a large set of phages infecting the common hostMycobacterium smegmatis mc2155 shows that they span considerable genetic diversity. There are more than 20 distinct types that lack nucleotide similarity with each other, and there is considerable diversity within most of the groups. Three newly isolated temperate mycobacteriophages, Bongo, PegLeg, and Rey, constitute a new group (cluster M), with the closely related phages Bongo and PegLeg forming subcluster M1 and the more distantly related Rey forming subcluster M2. The cluster M mycobacteriophages have siphoviral morphologies with unusually long tails, are homoimmune, and have larger than average genomes (80.2 to 83.7 kbp). They exhibit a variety of features not previously described in other mycobacteriophages, including noncanonical genome architectures and several unusual sets of conserved repeated sequences suggesting novel regulatory systems for both transcription and translation. In addition to containing transfer-messenger RNA and RtcB-like RNA ligase genes, their genomes encode 21 to 24 tRNA genes encompassing complete or nearly complete sets of isotypes. We predict that these tRNAs are used in late lytic growth, likely compensating for the degradation or inadequacy of host tRNAs. They may represent a complete set of tRNAs necessary for late lytic growth, especially when taken together with the apparent lack of codons in the same late genes that correspond to tRNAs that the genomes of the phages do not obviously encode

Design and rationale of the B-lines lung ultrasound guided emergency department management of acute heart failure (BLUSHED-AHF) pilot trial

Background Medical treatment for acute heart failure (AHF) has not changed substantially over the last four decades. Emergency department (ED)-based evidence for treatment is limited. Outcomes remain poor, with a 25% mortality or re-admission rate within 30 days post discharge. Targeting pulmonary congestion, which can be objectively assessed using lung ultrasound (LUS), may be associated with improved outcomes. Methods BLUSHED-AHF is a multicenter, randomized, pilot trial designed to test whether a strategy of care that utilizes a LUS-driven treatment protocol outperforms usual care for reducing pulmonary congestion in the ED. We will randomize 130 ED patients with AHF across five sites to, a) a structured treatment strategy guided by LUS vs. b) a structured treatment strategy guided by usual care. LUS-guided care will continue until there are ≤15 B-lines on LUS or 6h post enrollment. The primary outcome is the proportion of patients with B-lines ≤ 15 at the conclusion of 6 h of management. Patients will continue to undergo serial LUS exams during hospitalization, to better understand the time course of pulmonary congestion. Follow up will occur through 90 days, exploring days-alive-and-out-of-hospital between the two arms. The study is registered on ClinicalTrials.gov (NCT03136198). Conclusion If successful, this pilot study will inform future, larger trial design on LUS driven therapy aimed at guiding treatment and improving outcomes in patients with AHF

Overlooking Subvisible Particles in Therapeutic Protein Products: Gaps that may Compromise Product Quality

Therapeutic protein products provide unique and effective treatments for numerous human diseases and medical conditions. In many cases, these treatments are used chronically to slow disease progression, reduce morbidity and/or to replace essential proteins that are not produced endogenously in patients. Therefore, any factor that reduces or eliminates the effectiveness of the treatment can lead to patient suffering and even death. One means by which efficacy of therapeutic proteins can be compromised is by an immune response, resulting in antibody-mediated neutralization of the protein’s activity or alterations in bioavailability.1,2 For example, in the case of treatment of hemophilia A, neutralizing antibodies to Factor VIII can cause life-threatening bleeding episodes, resulting in significant morbidity and necessitating treatment with a prolonged course of a tolerance-inducing therapy to reverse immunity.3,4 In other cases, drug-induced antibodies to a therapeutic version of an endogenous protein can cross-react with and neutralize the patient’s endogenous protein. If the endogenous protein serves a non-redundant biological function, such an immune response can have devastating results. For example, pure red cell aplasia can result from neutralizing antibodies to epoetin alpha. 1,2 It is well established that protein aggregates in therapeutic protein products can enhance immunogenicity2, and such an effect is therefore an important risk factor to consider when assessing product quality. The purpose of this commentary is to accomplish the following: i. provide brief summaries on the factors affecting protein aggregation and the key aspects of protein aggregates that are associated with immunogenicity; ii. emphasize the current scientific gaps in understanding and analytical limitations for quantitation of species of large protein aggregates that are referred to as subvisible particles, with specific consideration of those particles 0.1–10 μm in size; iii. offer a rationale for why these gaps may compromise the safety and/or efficacy of a product; iv. provide scientifically sound, risked based recommendations/conclusions for assessment and control of such aggregate species

Remodelling of human atrial K+ currents but not ion channel expression by chronic β-blockade

Chronic β-adrenoceptor antagonist (β-blocker) treatment in patients is associated with a potentially anti-arrhythmic prolongation of the atrial action potential duration (APD), which may involve remodelling of repolarising K+ currents. The aim of this study was to investigate the effects of chronic β-blockade on transient outward, sustained and inward rectifier K+ currents (ITO, IKSUS and IK1) in human atrial myocytes and on the expression of underlying ion channel subunits. Ion currents were recorded from human right atrial isolated myocytes using the whole-cell-patch clamp technique. Tissue mRNA and protein levels were measured using real time RT-PCR and Western blotting. Chronic β-blockade was associated with a 41% reduction in ITO density: 9.3 ± 0.8 (30 myocytes, 15 patients) vs 15.7 ± 1.1 pA/pF (32, 14), p < 0.05; without affecting its voltage-, time- or rate dependence. IK1 was reduced by 34% at −120 mV (p < 0.05). Neither IKSUS, nor its increase by acute β-stimulation with isoprenaline, was affected by chronic β-blockade. Mathematical modelling suggested that the combination of ITO- and IK1-decrease could result in a 28% increase in APD90. Chronic β-blockade did not alter mRNA or protein expression of the ITO pore-forming subunit, Kv4.3, or mRNA expression of the accessory subunits KChIP2, KChAP, Kvβ1, Kvβ2 or frequenin. There was no reduction in mRNA expression of Kir2.1 or TWIK to account for the reduction in IK1. A reduction in atrial ITO and IK1 associated with chronic β-blocker treatment in patients may contribute to the associated action potential prolongation, and this cannot be explained by a reduction in expression of associated ion channel subunits