Surveying physical therapists' understanding of benign paroxysmal positional vertigo

IntroductionBenign paroxysmal positional vertigo (BPPV) is a common condition with disabling symptoms that is diagnosed and effectively treated at the bedside. Our encounter with patients experiencing prolonged BPPV who may not have received appropriate physical therapy prompted us to explore barriers to the diagnosis and treatment for BPPV among physical therapists, which has not been extensively investigated. We hypothesize that a potential barrier may be a lack of understanding of subtle symptoms of BPPV that deviate from the classical presentation. The gold standard for diagnosing definite BPPV is subjective dizziness or vertigo with nystagmus in response to positional testing. There are variants of BPPV including subjective BPPV (subjective dizziness or vertigo without nystagmus) and vestibular agnosia (nystagmus without subjective dizziness or vertigo) that do not meet the diagnostic criteria for definite BPPV but are equally responsive to the same repositioning maneuvers. The purpose of this project was to survey physical therapists for their understanding of BPPV including subjective BPPV and vestibular agnosia.MethodsA panel of experts created a 16-question survey, designed for physical therapists, with three categories: (1), inquiring if they treat persons with BPPV, (2) three clinical vignettes for definite BPPV, subjective BPPV, and BPPV with vestibular agnosia, and (3) demographic information. Data collection occurred at two large physical therapy meetings, one of which was a national professional meeting and the other was a professional continuing medical education course geared towards advancing vestibular rehabilitation skills.ResultsThere were 426 people who completed the survey, 364 of whom treat BPPV in their practice. In the first clinical vignette created to assess the respondents' understanding of definite BPPV, 229 (62%) of respondents would always assess a patient for BPPV based on complaints of a “room spinning” vertigo from head movement. When asked if the complaint was lingering “lightheadedness or feelings of imbalance” from head movement, only 158 (43%) reported they would perform positional testing to reassess. In the BPPV variant vignettes, 187 (51%) identified the patient with subjective BPPV as having BPPV and 305 (85%) identified the patient with vestibular agnosia as having BPPV.DiscussionThe results of this survey demonstrate gaps in knowledge regarding BPPV across practice settings and experience, with opportunities to bridge these gaps to improve treatment for BPPV

Nalbuphine Tablets for Cough in Patients with Idiopathic Pulmonary Fibrosis

BACKGROUND There are no approved therapies for cough in patients with idiopathic pulmonary fibrosis (IPF). In this small crossover trial we administered nalbuphine extended-release tablets (NAL ER) as a potential cough therapy for such patients. METHODS This randomized, double-blind, placebo-controlled, crossover trial involved two 22-day treatment periods (NAL ER!placebo and placebo!NAL ER) separated by a 2-week washout period. NAL ER was started at a dose of 27 mg once daily and was titrated up to 162 mg twice daily at day 16. The primary end point was percent change from baseline in hourly daytime objective cough frequency as measured by an electronic cough monitor. The daytime period was defined as the patient-reported time of awakening and bedtime. Secondary end points included change in objective 24-hour cough frequency, changes in cough frequency, cough severity, and breathlessness, per patient-reported outcomes. RESULTS A total of 41 patients were randomly assigned and received one or more doses of study medication. There was a 75.1% reduction in daytime objective cough frequency during the NAL ER treatment period versus the placebo treatment period of 22.6%, a 52.5 percentage point placebo-adjusted decrease from baseline (P<0.001) at day 21. There was a 76.1% (95% confidence interval, 83.1 to 69.1) decrease in the 24-hour objective cough frequency with NAL ER, versus a 25.3% (43.9 to 6.7) decrease with placebo, a 50.8 percentage point placebo-adjusted change. Nausea, fatigue, constipation, and dizziness were more common with NAL ER than with placebo. CONCLUSIONS In this short-term crossover trial, NAL ER reduced cough in individuals with IPF. Larger and longer trials are needed to assess the impact on cough versus drug adverse effects. (Funded by Trevi Therapeutics; ClinicalTrials.gov number, NCT04030026.

Participating together: dialogic space for children and architects in the design process

© 2016 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis GroupTypically enmeshed in the ‘voice’ perspective within children’s participation debates, there are currently sporadic insights into designer–child creative dialogue. Drawing on the findings of a Leverhulme Trust-funded research project, this paper articulates moments of dialogue between architects and children in spatial design processes, whose spatial and symbolic qualities help to understand the interactions and meeting of cultures. Several authors have discussed the transformational potential for adults and children to ‘co-author’ identities in dialogical contexts. The paper builds on this body of research to suggest that design dialogue offers the space, literally and metaphorically, for children and architects to participate together. Identifying the qualities of the dialogic design space as potentially present in children’s and adults’ everyday cultures and interdependent relations, it is proposed that this dialogical framework might diversify architects’ and children’s roles in the design process and enrich practices and perceptions of design participation

British Lung Foundation/United Kingdom primary immunodeficiency network consensus statement on the definition, diagnosis, and management of granulomatous-lymphocytic interstitial lung disease in common variable immunodeficiency disorders

A proportion of people living with common variable immunodeficiency disorders develop granulomatous-lymphocytic interstitial lung disease (GLILD). We aimed to develop a consensus statement on the definition, diagnosis, and management of GLILD. All UK specialist centers were contacted and relevant physicians were invited to take part in a 3-round online Delphi process. Responses were graded as Strongly Agree, Tend to Agree, Neither Agree nor Disagree, Tend to Disagree, and Strongly Disagree, scored +1, +0.5, 0, −0.5, and −1, respectively. Agreement was defined as greater than or equal to 80% consensus. Scores are reported as mean ± SD. There was 100% agreement (score, 0.92 ± 0.19) for the following definition: “GLILD is a distinct clinico-radio-pathological ILD occurring in patients with [common variable immunodeficiency disorders], associated with a lymphocytic infiltrate and/or granuloma in the lung, and in whom other conditions have been considered and where possible excluded.” There was consensus that the workup of suspected GLILD requires chest computed tomography (CT) (0.98 ± 0.01), lung function tests (eg, gas transfer, 0.94 ± 0.17), bronchoscopy to exclude infection (0.63 ± 0.50), and lung biopsy (0.58 ± 0.40). There was no consensus on whether expectant management following optimization of immunoglobulin therapy was acceptable: 67% agreed, 25% disagreed, score 0.38 ± 0.59; 90% agreed that when treatment was required, first-line treatment should be with corticosteroids alone (score, 0.55 ± 0.51)

MicroRNA-135b promotes cancer progression by acting as a downstream effector of oncogenic pathways in colon cancer

MicroRNA deregulation is frequent in human colorectal cancers (CRCs), but little is known as to whether it represents a bystander event or actually drives tumor progression in vivo. We show that miR-135b overexpression is triggered in mice and humans by APC loss, PTEN/PI3K pathway deregulation, and SRC overexpression and promotes tumor transformation and progression. We show that miR-135b upregulation is common in sporadic and inflammatory bowel disease-associated human CRCs and correlates with tumor stage and poor clinical outcome. Inhibition of miR-135b in CRC mouse models reduces tumor growth by controlling genes involved in proliferation, invasion, and apoptosis. We identify miR-135b as a key downsteam effector of oncogenic pathways and a potential target for CRC treatment

Biannual Administrations of Azithromycin and the Gastrointestinal Microbiome of Malawian Children: A Nested Cohort Study Within a Randomized Controlled Trial.

Community-level mass treatment with azithromycin has been associated with a mortality benefit in children. However, antibiotic exposures result in disruption of the gut microbiota and repeated exposures may reduce recovery of the gut flora. We conducted a nested cohort study within the framework of a randomized controlled trial to examine associations between mass drug administration (MDA) with azithromycin and the gut microbiota of rural Malawian children aged between 1 and 59 months. Fecal samples were collected from the children at baseline and 6 months after two or four biannual rounds of azithromycin treatment. DNA was extracted from fecal samples and V4-16S rRNA sequencing used to characterize the gut microbiota. Firmicutes, Bacteroidetes, Proteobacteria and Actinobacteria were the dominant phyla while Faecalibacterium and Bifidobacterium were the most prevalent genera. There were no associations between azithromycin treatment and changes in alpha diversity, however, four biannual rounds of treatment were associated with increased abundance of Prevotella. The lack of significant changes in gut microbiota after four biannual treatments supports the use of mass azithromycin treatment to reduce mortality in children living in low- and middle-income settings

BRCA2 polymorphic stop codon K3326X and the risk of breast, prostate, and ovarian cancers

Background: The K3326X variant in BRCA2 (BRCA2*c.9976A&gt;T; p.Lys3326*; rs11571833) has been found to be associated with small increased risks of breast cancer. However, it is not clear to what extent linkage disequilibrium with fully pathogenic mutations might account for this association. There is scant information about the effect of K3326X in other hormone-related cancers. Methods: Using weighted logistic regression, we analyzed data from the large iCOGS study including 76 637 cancer case patients and 83 796 control patients to estimate odds ratios (ORw) and 95% confidence intervals (CIs) for K3326X variant carriers in relation to breast, ovarian, and prostate cancer risks, with weights defined as probability of not having a pathogenic BRCA2 variant. Using Cox proportional hazards modeling, we also examined the associations of K3326X with breast and ovarian cancer risks among 7183 BRCA1 variant carriers. All statistical tests were two-sided. Results: The K3326X variant was associated with breast (ORw = 1.28, 95% CI = 1.17 to 1.40, P = 5.9x10- 6) and invasive ovarian cancer (ORw = 1.26, 95% CI = 1.10 to 1.43, P = 3.8x10-3). These associations were stronger for serous ovarian cancer and for estrogen receptor–negative breast cancer (ORw = 1.46, 95% CI = 1.2 to 1.70, P = 3.4x10-5 and ORw = 1.50, 95% CI = 1.28 to 1.76, P = 4.1x10-5, respectively). For BRCA1 mutation carriers, there was a statistically significant inverse association of the K3326X variant with risk of ovarian cancer (HR = 0.43, 95% CI = 0.22 to 0.84, P = .013) but no association with breast cancer. No association with prostate cancer was observed. Conclusions: Our study provides evidence that the K3326X variant is associated with risk of developing breast and ovarian cancers independent of other pathogenic variants in BRCA2. Further studies are needed to determine the biological mechanism of action responsible for these associations

A Novel SALL4/OCT4 Transcriptional Feedback Network for Pluripotency of Embryonic Stem Cells

Background: SALL4 is a member of the SALL gene family that encodes a group of putative developmental transcription factors. Murine Sall4 plays a critical role in maintaining embryonic stem cell (ES cell) pluripotency and self-renewal. We have shown that Sall4 activates Oct4 and is a master regulator in murine ES cells. Other SALL gene members, especially Sall1 and Sall3 are expressed in both murine and human ES cells, and deletions of these two genes in mice lead to perinatal death due to developmental defects. To date, little is known about the molecular mechanisms controlling the regulation of expressions of SALL4 or other SALL gene family members. Methodology/Principal Findings: This report describes a novel SALL4/OCT4 regulator feedback loop in ES cells in balancing the proper expression dosage of SALL4 and OCT4 for the maintenance of ESC stem cell properties. While we have observed that a positive feedback relationship is present between SALL4 and OCT4, the strong self-repression of SALL4 seems to be the “break” for this loop. In addition, we have shown that SALL4 can repress the promoters of other SALL family members, such as SALL1 and SALL3, which competes with the activation of these two genes by OCT4. Conclusions/Significance: Our findings, when taken together, indicate that SALL4 is a master regulator that controls its own expression and the expression of OCT4. SALL4 and OCT4 work antagonistically to balance the expressions of other SALL gene family members. This novel SALL4/OCT4 transcription regulation feedback loop should provide more insight into the mechanism of governing the “stemness” of ES cells

Spindle rotation in human cells is reliant on a MARK2-mediated equatorial spindle-centering mechanism

This work was supported by a Cancer Research UK Career Development Award (C28598/A9787), Biotechnology and Biological Sciences Research Council Project grant (BB/R01003X/1), and a Queen Mary University of London Laboratory startup grant to V.M. Draviam, a Universiti Brunei Darussalam PhD studentship to I. Zulkipli, a Queen Mary University of London PhD studentship to M. Hart, a London Interdisciplinary Biosciences Consortium Biotechnology and Biological Sciences Research Council–Doctoral Training Partnerships PhD studentship to D. Dang (cosupervised by V.M. Draviam and N. Sastry; BB/M009513/1), and an Islamic Development Bank PhD studentship to P. Gul