Examination of Several Physiological and Psychosocial Factors Potentially Associated With Masked Hypertension Among Low-Risk Adults

We examined the association of factors in addition to prehypertensive office blood pressure (BP) level that might improve detection of masked hypertension (MH, defined as non-elevated office BP with elevated out-of-office BP average) among those otherwise at low-risk. This sample of 340 untreated adults 30 years and older with office BP average <140/90 mmHg all had two sets of paired office BP measurements and 24-hour ambulatory BP monitoring (ABPM) sessions one week apart. Other than BP levels, the only factors that were associated (at P<0.10) with MH at both sets were male sex (75% vs 66%) and working outside the home (72% vs 59% first set; 71% vs 45% second set). Adding these variables to BP level in the model did not appreciably improve detection of MH. We found no demographic, clinical, or psychosocial measures that improved upon prehypertension as a potential predictor of MH in this sample

Comparison of patients’ confidence in office, ambulatory, and home blood pressure measurements as methods of assessing for hypertension

Uncertainty exists when relying on office (clinic) blood pressure (BP) measurements to diagnose hypertension. Home BP monitoring and ambulatory BP monitoring (ABPM) provide measurements that are more strongly associated with cardiovascular disease. The degree to which patients exhibit uncertainty about office BP measurements is unknown, as is whether they would have less uncertainty about other BP measurement methods. We therefore assessed people's confidence in methods of BP measurement, comparing perceptions about office BP, home BP, and ABPM techniques

Levels of Office Blood Pressure and Their Operating Characteristics for Detecting Masked Hypertension Based on Ambulatory Blood Pressure Monitoring

BACKGROUND Masked hypertension (MH)—nonelevated office blood pressure (BP) with elevated out-of-office BP average—conveys cardiovascular risk similar to or approaching sustained hypertension, making its detection of potential clinical importance. However, it may not be feasible or cost-effective to perform ambulatory BP monitoring (ABPM) on all patients with a nonelevated office BP. There likely exists a level of office BP below which ABPM is not warranted because the probability of MH is low. METHODS We analyzed data from 294 adults aged ≥30 years not on BP-lowering medication with office BP <140/90mm Hg, all of whom underwent 24-hour ABPM. We calculated sensitivity, false-positive rate, and likelihood ratios (LRs) for the range of office BP cutoffs from 110 to 138mm Hg systolic and from 68 to 88mm Hg diastolic for detecting MH. RESULTS The systolic BP cutoff with the highest +LR for detecting MH (1.8) was 120mm Hg, and the diastolic cutoff with the highest +LR (2.4) was 82mm Hg. However, the systolic level of 120mm Hg had a false-positive rate of 42%, and the diastolic level of 82mm Hg had a sensitivity of only 39%. CONCLUSIONS The cutoff of office BP with the best overall operating characteristics for diagnosing MH is approximately 120/82mm Hg. However, this cutoff may have an unacceptably high false-positive rate. Clinical risk tools to identify patients with nonelevated office BP for whom ABPM should be considered will likely need to include factors in addition to office BP

De Novo Mutations in SIK1 Cause a Spectrum of Developmental Epilepsies

Developmental epilepsies are age-dependent seizure disorders for which genetic causes have been increasingly identified. Here we report six unrelated individuals with mutations in salt-inducible kinase 1 (SIK1) in a series of 101 persons with early myoclonic encephalopathy, Ohtahara syndrome, and infantile spasms. Individuals with SIK1 mutations had short survival in cases with neonatal epilepsy onset, and an autism plus developmental syndrome after infantile spasms in others. All six mutations occurred outside the kinase domain of SIK1 and each of the mutants displayed autophosphorylation and kinase activity toward HDAC5. Three mutations generated truncated forms of SIK1 that were resistant to degradation and also showed changes in sub-cellular localization compared to wild-type SIK1. We also report the human neuropathologic examination of SIK1-related developmental epilepsy, with normal neuronal morphology and lamination but abnormal SIK1 protein cellular localization. Therefore, these results expand the genetic etiologies of developmental epilepsies by demonstrating SIK1 mutations as a cause of severe developmental epilepsy

Reproducibility of masked hypertension among adults 30 years or older

Masked hypertension (MH) refers to non-elevated office blood pressure (BP) with elevated out-of-office BP, but its reproducibility has not been conclusively established. We examined one-week reproducibility of MH by home BP monitoring (HBPM) and ambulatory BP monitoring (ABPM)

Surgical Standards for Management of the Axilla in Breast Cancer Clinical Trials with Pathological Complete Response Endpoint.

Advances in the surgical management of the axilla in patients treated with neoadjuvant chemotherapy, especially those with node positive disease at diagnosis, have led to changes in practice and more judicious use of axillary lymph node dissection that may minimize morbidity from surgery. However, there is still significant confusion about how to optimally manage the axilla, resulting in variation among practices. From the viewpoint of drug development, assessment of response to neoadjuvant chemotherapy remains paramount and appropriate assessment of residual disease-the primary endpoint of many drug therapy trials in the neoadjuvant setting-is critical. Therefore decreasing the variability, especially in a multicenter clinical trial setting, and establishing a minimum standard to ensure consistency in clinical trial data, without mandating axillary lymph node dissection, for all patients is necessary. The key elements which include proper staging and identification of nodal involvement at diagnosis, and appropriately targeted management of the axilla at the time of surgical resection are presented. The following protocols have been adopted as standard procedure by the I-SPY2 trial for management of axilla in patients with node positive disease, and present a framework for prospective clinical trials and practice

Erratum: Author Correction: Surgical Standards for Management of the Axilla in Breast Cancer Clinical Trials with Pathological Complete Response Endpoint.

[This corrects the article DOI: 10.1038/s41523-018-0074-6.]

The impact of oxygen on the transcriptome of recombinant S. cerevisiae and P. pastoris - a comparative analysis

Background: Saccharomyces cerevisiae and Pichia pastoris are two of the most relevant microbial eukaryotic platforms for the production of recombinant proteins. Their known genome sequences enabled several transcriptomic profiling studies under many different environmental conditions, thus mimicking not only perturbations and adaptations which occur in their natural surroundings, but also in industrial processes. Notably, the majority of such transcriptome analyses were performed using non-engineered strains. In this comparative study, the gene expression profiles of S. cerevisiae and P. pastoris, a Crabtree positive and Crabtree negative yeast, respectively, were analyzed for three different oxygenation conditions (normoxic, oxygen-limited and hypoxic) under recombinant protein producing conditions in chemostat cultivations. Results: The major differences in the transcriptomes of S. cerevisiae and P. pastoris were observed between hypoxic and normoxic conditions, where the availability of oxygen strongly affected ergosterol biosynthesis, central carbon metabolism and stress responses, particularly the unfolded protein response. Steady state conditions under low oxygen set-points seemed to perturb the transcriptome of S. cerevisiae to a much lesser extent than the one of P. pastoris, reflecting the major tolerance of the baker's yeast towards oxygen limitation, and a higher fermentative capacity. Further important differences were related to Fab production, which was not significantly affected by oxygen availability in S. cerevisiae, while a clear productivity increase had been previously reported for hypoxically grown P. pastoris. Conclusions: The effect of three different levels of oxygen availability on the physiology of P. pastoris and S. cerevisiae revealed a very distinct remodelling of the transcriptional program, leading to novel insights into the different adaptive responses of Crabtree negative and positive yeasts to oxygen availability. Moreover, the application of such comparative genomic studies to recombinant hosts grown in different environments might lead to the identification of key factors for efficient protein production