Controlling Anomalous Diffusion in Lipid Membranes

Diffusion in cell membranes is not just simple two-dimensional Brownian motion but typically depends on the timescale of the observation. The physical origins of this anomalous sub-diffusion are unresolved, and model systems capable of quantitative and reproducible control of membrane diffusion have been recognized as a key experimental bottleneck. Here we control anomalous diffusion using supported lipids bilayers containing lipids derivatized with polyethylene glycol (PEG) headgroups. Bilayers with specific excluded area fractions are formed by control of PEG-lipid mole fraction.

http://bit.ly/2Rv17eQ

Research in the Acute Rehabilitation Setting: a Bridge Too Far?

Abstract

Purpose of Review

The goal of this paper is to critically examine the challenges to clinical practice in acute neurorehabilitation settings to provide evidence-based recommendations for conducting research on neurologic recovery.

Recent Findings

Recent changes in health care have dramatically challenged post-acute care by reducing the length of stay and increasing transitions in care with resulting loss of continuity of care and follow-up. These challenges hinder research and undermine progress in neurorehabilitation.

Summary

Based on recent evidence, a hub and spoke model is proposed to bridge and facilitate continuity of care from acute to subacute to community settings to meet these challenges head on and facilitate research on mechanisms of functional recovery from neurologic conditions.

http://bit.ly/2SYsGJV

A single nucleotide polymorphism panel for individual identification and ancestry assignment in Caucasians and four East and Southeast Asian populations using a machine learning classifier

Abstract

Single nucleotide polymorphism (SNP) profiling is an effective means of individual identification and ancestry inferences in forensic genetics. This study established a SNP panel for the simultaneous individual identification and ancestry assignment of Caucasian and four East and Southeast Asian populations. We analyzed 220 SNPs (125 autosomal, 17 X-chromosomal, 30 Y-chromosomal, and 48 mitochondrial SNPs) of the DNA samples from 563 unrelated individuals of five populations (89 Caucasian, 234 Taiwanese Han, 90 Filipino, 79 Indonesian and 71 Vietnamese) and 18 degraded DNA samples. Informativeness for assignment (In) was used to select ancestry informative SNPs (AISNPs). A machine learning classifier, support vector machine (SVM), was used for ancestry assignment. Of the 220 SNPs, 62 were individual identification SNPs (IISNPs) (51 autosomal and 11 X-chromosomal SNPs) and 191 were AISNPs (100 autosomal, 13 X-chromosomal, 30 Y-chromosomal, and 48 mitochondrial SNPs). The 51 autosomal IISNPs offered cumulative random match probabilities (cRMPs) ranging from 1.56 × 10⁻²¹ to 3.16 × 10⁻²² among these five populations. Using AISNPs with the SVM, the overall accuracy rate of ancestry inference achieved in the testing dataset between Caucasian, Taiwanese Han, and Filipino populations was 88.9%, whereas it was 70.0% between Caucasians and each of the four East and Southeast Asian populations. For the 18 degraded DNA samples with incomplete profiling, the accuracy rate of ancestry assignment was 94.4%. We have developed a 220-SNP panel for simultaneous individual identification and ethnic origin differentiation between Caucasian and the four East and Southeast Asian populations. This SNP panel may assist with DNA analysis of forensic casework.

http://bit.ly/2VW67HT

Fatal delayed hemopericardium and hemothorax following blunt chest trauma

Abstract

Cardiac injury following blunt chest trauma is common in motor vehicle accidents due to a crush or blast injury. Severe cardiac trauma is associated with a very high mortality. If a cardiac injury develops several weeks after non-penetrating chest trauma, establishing a causal link between the traumatic event and the cardiac injury becomes complicated. This article reports a case of fatal delayed hemopericardium and hemothorax following a motor vehicle accident including blunt chest trauma 34 days prior to death. The cardiac injury was caused by displacement of a sharp irregular fragment of one of the decedents fractured ribs and the primary defect was sealed by blood clots. Subsequent bleeding occurred when the thrombus was displaced. Since the incidence of blunt high-energy chest injuries is relatively high, heart and large vessel injuries must be taken into account and a comprehensive examination needs to be done in order to prevent the delayed development of fatal complications.

http://bit.ly/2QQimlt

A semi‐active human digital twin model for detecting severity of carotid stenoses from head vibration ‐ a coupled computational mechanics and computer vision method

Summary

In this work we propose a methodology to detect the severity of carotid stenosis from a video of a human face with the help of a coupled blood flow and head vibration model. This semi‐active digital twin model is an attempt to link non‐invasive video of a patient face to the percentage of carotid occlusion. The pulsatile nature of blood flow through the carotid arteries induces a subtle head vibration. This vibration is a potential indicator of carotid stenosis severity and it is exploited in the present study. A head vibration model has been proposed in the present work that is linked to the forces generated by blood flow with or without occlusion. The model is used to generate a large number of virtual head vibration data for different degrees of occlusion. In order to determine the in vivo head vibration, a computer vision algorithm is adopted to use human face videos. The in vivo vibrations are compared against the virtual vibration data generated from the coupled computational blood flow/vibration model. A comparison of the in vivo vibration is made against the virtual data to find the best fit between in vivo and virtual data. The preliminary results on healthy subjects and a patient clearly indicate that the model is accurate and it possesses the potential for detecting approximate severity of carotid artery stenoses.

http://bit.ly/2TQBQIH

Treatment of Peritoneal Surface Malignancies with Cytoreductive Surgery and Hyperthermic Intra-peritoneal Chemotherapy (HIPEC): Experience in Israel

Abstract

The treatment of peritoneal surface malignancies, either primary or secondary (peritoneal metastasis), has evolved over the past two decades. A nihilistic approach of incurable "carcinomatosis" is changing into treatment of peritoneal metastasis with curative intent. The aim of the present study is to review the current practice, past history, and future of peritoneal surface oncology in Israel. A systematic review of all patients treated in institutions performing cytoreductive surgery (CRS) and hyperthermic intra-peritoneal chemotherapy (HIPEC) for the treatment of peritoneal surface malignancies. Each center provided the following data: start year, number of total cases, number of cases performed in 2017, and the method used (open vs. closed technique). Between 1990 and 2018, there were 1462 patients treated by CRS/HIPEC in Israel by eight different surgical groups in six medical centers. Currently, there are seven surgical groups in six medical centers routinely performing CRS/HIPEC. The annual rate of CRS/HIPEC was 171 cases in 2017 with a range of (4–69 cases/center). This is the first step of establishing an Israeli Peritoneal Surface Oncology Group that will have joined database and perform clinical trials in this challenging field of surgical oncology.

http://bit.ly/2Hgaj1X

“Selfie”-related electrocution

Abstract

Electrical injuries contribute a small but significant fraction to all burn trauma cases, and an even smaller proportion to those that are lethal. Accidental death rates among teenagers are the highest of all age-groups, and taking a "selfie" has been a practice that has, on rare occasions, led to such a death, often from electrocution. The case of a young man and his friend, who were electrocuted after climbing onto the roof of a parked railway wagon to take selfies is reported. One died at the scene, while the other survived. This case demonstrates that electrocution may occur with parked railway wagons, and in the young may be associated with selfie taking.

http://bit.ly/2VWmxA0

Unique thermal destruction of the body following suicidal burning

Abstract

The concept of spontaneous combustion has huge appeal as an historical fiction but it has no scientific background. However, in some deaths involving fire, a body can burn away virtually completely with minimal thermal destruction to the neighboring environment. We report an extraordinary case of the self-immolation of an elderly woman who set herself on fire with suicidal intentions. The unusual appearance and location of the body closely resembled the phenomenon of so-called spontaneous human combustion because the upper parts of the body were almost totally destroyed by fire, while the legs and surrounding structures remained almost untouched by flames. The results of all investigations proved that the woman set fire to her body using a box of matches and accelerants (concentrated ethanol and a solid firelighter). Near-total combustion of her body subsequently occurred during the postmortem period. The development of alleged spontaneous human combustion requires the following: ignition (external heat source), fuel (molten human fat), a wick (e.g. charred and porous clothing, bedding, or ground), time, and an optimal microclimate for gradual burning.

http://bit.ly/2QVtpKo

Forensic features of fatal self photography or “selfies”

http://bit.ly/2VVvWrB

Paradoxical Associations of Masculine Ideology and Casual Sex Among Heterosexual Male Geosocial Networking App Users in China

Abstract

Momo, the most popular geosocial networking app in China, is used as a common platform to seek casual sex. The present study, which is based on the social constructionist view of gender, examines how the endorsement of masculinity among heterosexual male Momo users is associated with the number of casual sex partners they meet on the app. The study also explores the mediating role of the sex motive for using Momo. Analyses of survey data from 125 heterosexual male Momo users showed that the endorsement of masculinity had an indirect positive relationship with the number of sex partners mediated by the sex motive; at the same time, it had a direct but negative association with the number of sex partners. These paradoxical associations were explained by different patterns across the individual dimensions of masculinity ideology. Specifically, the dimension of the Importance of Sex was responsible for the positive indirect association whereas the dimension of Avoidance of Femininity was responsible for the negative direct association. These findings are discussed in relation to the wen-wu dyad of Chinese masculinity. Because unsafe sex has been found to be associated with the use of geosocial networking apps, my study also calls for integrating the concept of practicing safer sex with the cultural ideal of masculinity.

http://bit.ly/2Fv1AHd

{-}The Role of UV-B Light on Small RNA Activity During Grapevine Berry Development

We explored the effects of ultraviolet B radiation (UV-B) on the developmental dynamics of microRNAs and phased small-interfering-RNA (phasi-RNAs)-producing loci by sequencing small RNAs in vegetative and reproductive organs of grapevine (Vitis vinifera L.). In particular, we tested different UV-B conditions in in vitro-grown plantlets (high-fluence exposition) and in berries from field-grown (radiation filtering) and greenhouse-grown (low- and high-fluence expositions) adult plants throughout fruit development and ripening. The functional significance of the observed UV-coordinated miRNA responses was supported by degradome evidences of ARGONAUTE (AGO)-programmed slicing of mRNAs. Co-expression patterns of the up-regulated miRNAs miR156, miR482, miR530, and miR828 with cognate target gene expressions in response to high-fluence UV-B was tested by q-RT-PCR. The observed UV-response relationships were also interrogated against two published UV-stress and developmental transcriptome datasets. Together, the dynamics observed between miRNAs and targets suggest that changes in target abundance are mediated transcriptionally and, in some cases, modulated post-transcriptionally by miRNAs. Despite the major changes in target abundance are being controlled primarily by those developmental effects that are similar between treatments, we show evidence for novel miRNA-regulatory networks in grape. A model is proposed where high-fluence UV-B increases miR168 and miR530 that target ARGONAUTE 1 (AGO1) and a Plus-3 domain mRNA, respectively, while decreasing miR403 that targets AGO2, thereby coordinating post-transcriptional gene silencing activities by different AGOs. Up-regulation of miR3627/4376 could facilitate anthocyanin accumulation by antagonizing a calcium effector, whereas miR395 and miR399, induced by micronutrient deficiencies known to trigger anthocyanin accumulation, respond positively to UV-B radiation. Finally, increases in the abundance of an anthocyanin-regulatory MYB-bHLH-WD40 complex elucidated in Arabidopsis, mediated by UV-B-induced changes in miR156/miR535, could contribute to the observed up-regulation of miR828. In turn, miR828 would regulate the AtMYB113-ortologues MYBA5, A6 and A7 (and thereby anthocyanins) via a widely conserved and previously validated auto-regulatory loop involving miR828 and phasi TAS4abc RNAs.

http://bit.ly/2QOiou5

Comparative Genomic Screen in Two Yeasts Reveals Conserved Pathways in the Response Network to Phenol Stress

Living organisms encounter various perturbations, and response mechanisms to such perturbations are vital for species survival. Defective stress responses are implicated in many human diseases including cancer and neurodegenerative disorders. Phenol derivatives, naturally occurring and synthetic, display beneficial as well as detrimental effects. The phenol derivatives in this study, butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), and bisphenol A (BPA), are widely used as food preservatives and industrial chemicals. Conflicting results have been reported regarding their biological activity and correlation with disease development; understanding the molecular basis of phenol action is a key step for addressing issues relevant to human health. This work presents the first comparative genomic analysis of the genetic networks for phenol stress response in an evolutionary context of two divergent yeasts, Schizosaccharomyces pombe and Saccharomyces cerevisiae. Genomic screening of deletion strain libraries of the two yeasts identified genes required for cellular response to phenol stress, which are enriched in human orhtologs. Functional analysis of these genes uncovered the major signaling pathways involved. The results provide a global view of the biological events constituting the defense process, including cell cycle arrest, DNA repair, phenol detoxification by V-ATPases, reactive oxygen species alleviation, and endoplasmic reticulum stress relief through ergosterol and the unfolded protein response, revealing novel roles for these cellular pathways.

http://bit.ly/2VTxv9j

Encapsulation of a new quinoxaline derivative in PLGA alters the pattern of its anticancer potency and induces apoptosis

Abstract

Purpose

Searching for novel anticancer therapeutics which are effective and primarily less toxic is urgently needed. Drug encapsulation provides more protection of drug within the body with more stable drug circulation levels thus avoiding drug peak-related adverse effects. We aimed first to develop and characterize a nano-particulate drug delivery system using poly(lactic-co-glycolic acid) (PLGA) for the new compound N-butylpyridoquinoxaline 1,4-dioxide (NBPQD), and second to investigate its anticancer effect and the probable mechanism.

Methods

NBPQD–PLGA nano-particles were prepared and their shape, size, zeta potential, encapsulation efficiency (EE%), drug loading (DL%), drug release, anticancer activity against six human cancer cell lines, DNA binding ability, and flow cytometric analyses of apoptosis, cell cycle and caspase-3 activity were investigated.

Results and conclusions

NBPQD–PLGA nano-particles were spherical with diameter around 54 nm. Zeta potential, EE%, and DL% values were − 20.4 mV, 88% and 21.8%, respectively. Nano-particles exhibited higher marked anticancer activities (much lower IC₅₀s) and changed the anticancer potency pattern towards all the studied cell lines compared to free NBPQD with superior potency against colorectal carcinoma (HCT-116, IC₅₀ of 12.2 µg/mL). NBPQD–PLGA acts by induction of cancer cell apoptosis through oxidative stress, DNA damage, and activating a caspase-3 signaling pathway.

http://bit.ly/2Hnxmbg

Assessment of Left Ventricular Ejection Fraction by Thallium-201 Myocardial SPECT-CT in Patients with Angina Pectoris: Comparison with 2D Echocardiography

Abstract

Purpose

Left ventricular (LV) ejection fraction (EF) is an important parameter for assessing cardiac systolic function and predicting prognosis in patients with cardiovascular disease. The aim of this study was to evaluate the feasibility of assessing LVEF by Tl-201 hybrid myocardial single-photon emission computed tomography (SPECT)/CT using two attenuation correction methods in patients with angina pectoris.

Methods

A total of 339 patients with angina pectoris (62.8 ± 12.9 years, male:female = 206:133) were analyzed. All patients underwent Tl-201 myocardial SPECT/CT and transthoracic two-dimensional (2D) echocardiograph. We compared LVEF assessed by SPECT/CT using two attenuation correction methods: CT-based attenuation correction (CTAC) and non-attenuation correction (non-AC) methods and 2D echocardiography.

Results

LVEF assessed by either of the two attenuation correction techniques and 2D echocardiography showed moderate correlation in all patients with angina pectoris (r = 0.487 for CTAC and r = 0.473 for non-AC, p < 0.001). Results were similar in the subgroup of patients with perfusion abnormalities on myocardial SPECT/CT images. Overall diagnostic performances were similar for the CTAC and non-AC methods for evaluating normal and decreased LVEF by myocardial SPECT/CT.

Conclusion

LVEF measured by the CTAC method of Tl-201-gated myocardial SPECT/CT was comparable with the conventional non-AC method in patients with angina pectoris and in the subgroup of patients with perfusion abnormality. Tl-201-gated myocardial hybrid SPECT/CT can be a reliable tool in the assessment of LVEF in clinic.

http://bit.ly/2HdVmNH

BCL2/MDM2 Inhibitor Combo Effective in AML [News in Brief]

Venetoclax plus idasanutlin elicited an antileukemic response in older patients with relapsed/refractory disease.

http://bit.ly/2HfNFa1

Breakdown of Blood-Brain Barrier May Drive Dementia

TUESDAY, Jan. 15, 2019 -- Breakdown of the blood-brain barrier (BBB) may be an early biomarker of cognitive dysfunction, independent of amyloid or tau marker status, according to a study published online Jan. 14 in Nature Medicine. Using dynamic...

http://bit.ly/2QNXxqZ

USPSTF Recommends Risk-Reducing Meds for Breast Cancer

TUESDAY, Jan. 15, 2019 -- The U.S. Preventive Services Task Force (USPSTF) recommends risk-reducing medications for women at high risk for breast cancer who are at low risk for adverse events, but medications are not recommended for routine use....

http://bit.ly/2VV93o3

Congo Ebola Outbreak Now Second Worst in History

TUESDAY, Jan. 15, 2019 -- There have been 600 confirmed cases of Ebola and 347 confirmed deaths since early August in the Democratic Republic of the Congo, making this outbreak of the disease the second largest and second deadliest in history. Since...

http://bit.ly/2QQl8Ht

FDA to Resume Inspections of Riskier Foods

TUESDAY, Jan. 15, 2019 -- Routine inspections of riskier foods will resume as early as today, the U.S. Food and Drug Administration says. There was a brief halt in inspections of foods such as produce, infant formula, and cheeses due to the partial...

http://bit.ly/2VYweOz

Stem Cell Transplant Slows Progression of Multiple Sclerosis

TUESDAY, Jan. 15, 2019 -- For patients with relapsing-remitting multiple sclerosis (MS), nonmyeloablative hematopoietic stem cell transplantation (HCST) is associated with prolonged time to disease progression compared with disease-modifying therapy...

http://bit.ly/2QRXkCX

Utility of Diffusion Weighted Imaging to Decrease Unnecessary Biopsies Prompted by Breast MRI: A Trial of the ECOG-ACRIN Cancer Research Group (A6702)

Purpose: Conventional breast MRI is highly sensitive for cancer detection but prompts some false-positives. We performed a prospective, multicenter study to determine whether apparent diffusion coefficients (ADCs) from diffusion weighted imaging (DWI) can decrease MRI false-positives. Experimental Design: 107 women with MRI-detected BI-RADS 3, 4, or 5 lesions were enrolled from March 2014 to April 2015. ADCs were measured both centrally and at participating sites. Receiver operating characteristic (ROC) analysis was employed to assess diagnostic performance of centrally-measured ADCs and identify optimal ADC thresholds to reduce unnecessary biopsies. Lesion reference standard was based on either definitive biopsy result or at least 337 days of follow-up after the initial MRI procedure. Results: Of 107 women enrolled, 67 patients (median age 49, range 24-75 years) with 81 lesions with confirmed reference standard (28 malignant, 53 benign) and evaluable DWI were analyzed. 67/81 lesions were BI-RADS 4 (n=63) or 5 (n=4) and recommended for biopsy. Malignancies exhibited lower mean centrally-measured ADCs (mm²/s) than benign lesions (1.21x10^-3 vs.1.47x10^-3, p<0.0001, area under ROC curve=0.75, 95% confidence interval [CI] 0.65-0.84). In centralized analysis, application of an ADC threshold (1.53x10^-3 mm²/s) lowered the biopsy rate by 20.9% (14/67; 95% CI 11.2-31.2%) without affecting sensitivity. Application of a more conservative threshold (1.68x10^-3mm²/s) to site-derived ADCs reduced the biopsy rate by 26.2%(16/61) but missed three cancers. Conclusion: DWI can re-classify a substantial fraction of suspicious breast MRI findings as benign and thereby decrease unnecessary biopsies. ADC thresholds identified in this trial should be validated in future Phase III studies.

http://bit.ly/2DbFg2Z

Validation of Melanoma Immune Profile (MIP), a Prognostic Immune Gene Prediction Score for Stage II-III Melanoma

Purpose: Biomarkers are needed to stratify patients with stage II-III melanoma for clinical trials of adjuvant therapy because, while immunotherapy is protective, it also confers the risk of severe toxicity. We previously defined and validated a 53-immune gene melanoma immune profile (MIP) predictive both of distant metastatic recurrence (DMR) and of disease-specific survival (DSS). Here, we test MIP on a third independent population. Methods: A retrospective cohort of 78 patients with stage II-III primary melanoma was analyzed using the nanoString assay to measure expression of 53 target genes and MIP score was calculated. Statistical analysis correlating MIP with disease-specific survival, overall survival, distant metastatic recurrence, and distant metastasis-free interval was performed using receiver operating characteristic curves, Kaplan-Meier (KM) curves, and standard univariable and multivariable Cox proportional hazards models. Results: MIP significantly distinguished patients with distant metastatic recurrence from those without distant metastatic recurrence using ROC curve analysis (AUC=0.695, p=0.008). We defined high and low risk groups based on the cutoff defined by this ROC curve and find that MIP correlates with both DSS and OS by ROC curve analysis (AUC=0.719, p=0.004 and AUC=0.698, p=0.004, respectively). Univariable Cox regression reveals that a high-risk MIP score correlates with DSS (p=0.015, HR=3.2). Conclusion: MIP identifies patients with low risk of death from melanoma and may constitute a clinical tool to stratify stage II-III melanoma patients for enrollment in clinical trials.

http://bit.ly/2TTWxn3

The first-week proliferative response of peripheral blood PD-1+CD8+T cells predicts the response to anti-PD-1 therapy in solid tumors

Purpose: To investigate blood-based dynamic biomarkers that predict responses to anti-PD-1 therapy in solid tumors. Experimental Design: Pre-planned biomarker analysis was performed as part of a phase II clinical trial (NCT02607631)in patients with metastatic or refractory thymic epithelial tumors (TETs; n= 31) who received pembrolizumab. The biomarker was further tested in an independent cohort of prospectively recruited patients with metastatic non-small cell lung cancer (NSCLC) who received pembrolizumab or nivolumab (NSCLC cohort 1; n= 33) and validated in an independent cohort of patients with NSCLC (NSCLC cohort 2; n= 46). Peripheral blood samples were obtained immediately before treatment (D0) and 7 days after the first dose (D7) and analyzed using multi-color flow cytometry. Results: A higher fold-change in the percentage of Ki-67⁺cells among PD-1⁺CD8⁺T cells 7 days after the first dose (Ki-67_D7/D0) significantly predicted durable clinical benefit (DCB;P < 0.001) and prolonged progression-free survival (PFS; P=0.027) in patients with TET. Ki-67_D7/D0≥ 2.8 was also associated with better DCB, PFS, and overall survival (OS) in NSCLC cohort 1 (all P< 0.05). Ki-67_D7/D0was subsequently validated in NSCLC cohort 2, and Ki-67_D7/D0≥ 2.8 significantly predicted better DCB (P=0.001), PFS (P=0.002), and OS (P=0.037). Ki-67_D7/D0had a low correlation with tumor PD-L1 expression and combining both factors did not improve the predictive power of Ki-67_D7/D0. Conclusions: The proliferative response of peripheral blood PD-1⁺CD8⁺T cells, measured as the fold-change in the percentage of Ki-67⁺cells 7 days after treatment (Ki-67_D7/D0), may be a useful surrogate biomarker for predicting the response and prognosis to anti-PD-1 therapy in solid tumors.

http://bit.ly/2Dd8U8a

Fucosylation enhances the efficacy of adoptively transferred antigen-specific cytotoxic T lymphocytes

Purpose: Inefficient homing of adoptively transferred cytotoxic T lymphocytes (CTLs) to tumors is a major limitation to the efficacy of adoptive cellular therapy (ACT) for cancer. However, through fucosylation, a process whereby fucosyltransferases (FTs) add fucose groups to cell surface glycoproteins, this challenge may be overcome. Endogenously fucosylated CTLs and ex vivo fucosylatedcord blood stem cells and regulatory T cells were shown to preferentially home to inflamed tissues and marrow. Here we show a novel approach to enhance CTL homing to leukemic marrow and tumor tissue. Experimental Design: Using the enzyme FT-VII, we fucosylated CTLs that target the HLA-A2-restricted leukemia antigens CG1 and PR1, the HER2-derived breast cancer antigen E75, and the melanoma antigen gp-100. We performed in vitro homing assays to study the effects of fucosylation on CTL homing and target killing. We used in vivo mouse models to demonstrate the effects of ex vivo fucosylation on CTL anti-tumor activities against leukemia, breast cancer and melanoma. Results: Our data show that fucosylation increases in vitro homing and cytotoxicity of antigen specific CTLs. Furthermore, fucosylation enhances in vivo CTL homing to leukemic bone marrow, breast cancer and melanoma tissue in NOD/SCID gamma (NSG) and immunocompetent mice, ultimately boosting the anti-tumor activity of the antigen-specific CTLs. Importantly, our work demonstrates that fucosylation does not interfere with CTL specificity. Conclusions: Together, our data establish ex vivo CTL fucosylation as a novel approach to improving the efficacy of ACT, which may be of great value for the future of ACT for cancer.

http://bit.ly/2TMbt6y

Continued endocrine therapy is associated with improved survival in patients with breast cancer brain metastases

Background: Brain metastases (BM) are a rare but devastating condition in estrogen receptor (ER)- positive metastatic breast cancer (MBC). While endocrine therapy (ET) is the mainstay of treatment in this disease subtype, only case reports have been published concerning the activity of ET in BM henceforth. Therefore, we aimed to systematically investigate the impact of ET after diagnosis of BM on outcome and clinical course of disease in patients with ERpositive MBC. Patients and methods: Patient characteristics, detailed information about BM including diagnosis specific graded prognostic assessment class (DS-GPA) and clinical outcome were obtained by retrospective chart review for all patients treated for ER-positive breast cancer BM between 1990 and 2017 at an academic care center. Overall survival (OS) was measured as the interval from diagnosis of BM until death or last date of follow-up. Results: Overall, 198 patients (female:195/198 (98.5%); male:3/198 (1.5%)) with ER-positive breast cancer BM were available for this analysis. Eighty-eight/198 patients (44.4%) received ET after diagnosis of BM including aromatase inhibitors (AIs; letrozole, anastrozole, exemestane), tamoxifen, and fulvestrant. Median OS was significantly longer in patients receiving ET after diagnosis of BM compared to patients who did not (15 vs 4 months, p<0.001; log-rank-test). No significant difference in terms of OS was observed between patients receiving AIs, tamoxifen or fulvestrant. In patients with concomitant leptomeningeal carcinomatosis (LC) ET prolonged median OS significantly as well (7 vs 3 months,p=0.012; log-rank-test). In a multivariate analysis including DS-GPA and ET, only treatment with ET after diagnosis of BM [hazard ratio(HR) 0.69 (95%CI:0.48-0.99;p=0.046)] was associated with prognosis (Cox regression model). Conclusion: Continuing ET after BM diagnosis was associated with a significantly prolonged OS in this large single-centre cohort. No substantial differences between substances were observed. These findings should be validated in a prospective cohort.

http://bit.ly/2DbeOqu

Brain vital signs detect concussion-related neurophysiological impairments in ice hockey

Abstract

There is a growing demand for objective evaluations of concussion. We developed a portable evoked potential framework to extract 'brain vital signs' using electroencephalography. Brain vital signs were derived from well established evoked responses representing auditory sensation (N100), basic attention (P300), and cognitive processing (N400) amplitudes and latencies, converted to normative metrics (six total). The study evaluated whether concussion-related neurophysiological impairments were detected over the duration of ice hockey seasons using brain vital signs. Forty-seven Tier III, Junior A, male ice hockey players were monitored over two seasons. Twelve sustained concussions after baseline testing then completed post-injury and return-to-play assessments. Twenty-three were not diagnosed with a concussion during the season and completed both baseline and post-season testing. Scores were evaluated using a repeated-measures analysis of variance with post hoc two-tailed paired t-tests. Concussion resulted in significantly increased amplitude and delayed latency scores for all six brain vital signs (P < 0.0001). Importantly, significant changes at return-to-play were also detected in basic attention (P300) amplitude, indicating persistent subclinical impairment. In the non-concussed group, there was also a significant change between baseline and post-season (P = 0.0047), with specific decreases in cognitive processing (N400) speed (P = 0.011) and overall total score (P = 0.002).

http://bit.ly/2srl6vT

Self-assembling vascular endothelial growth factor nanoparticles improve function in spinocerebellar ataxia type 1

Abstract

There is increasing appreciation for the role of the neurovascular unit in neurodegenerative diseases. We showed previously that the angiogenic and neurotrophic cytokine, vascular endothelial growth factor (VEGF), is suppressed to abnormally low levels in spinocerebellar ataxia type 1 (SCA1), and that replenishing VEGF reverses the cerebellar pathology in SCA1 mice. In that study, however, we used a recombinant VEGF, which is extremely costly to manufacture and biologically unstable as well as immunogenic. To develop a more viable therapy, here we test a synthetic VEGF peptide amphiphile that self-assembles into nanoparticles. We show that this nano-VEGF has potent neurotrophic and angiogenic properties, is well-tolerated, and leads to functional improvement in SCA1 mice even when administered at advanced stages of the disease. This approach can be generalized to other neurotrophic factors or molecules that act in a paracrine manner, offering a novel therapeutic strategy for neurodegenerative conditions.

http://bit.ly/2MjvSh3

Chinese translation of a measure of symptom burden, functional limitations, lifestyle, and health care–seeking skills in breast cancer survivors: the Cancer Survivor Profile

Abstract

Purpose

To produce a culturally sensitive Chinese translation of the original version of the Cancer Survivor Profile for breast cancer (CSPro-BC) survivors, which identifies problems in breast cancer patients post-primary treatment for breast cancer.

Methods

Four hundred forty-four female Chinese patients following primary treatment for breast cancer completed a Chinese translation of the CSPro-BC. Participants were randomly divided into two equal groups (n = 222). The two samples were subjected to exploratory and confirmatory factor analysis. Test-retest reliability, internal consistency, and divergent and convergent validities were also determined.

Results

The majority of participants were diagnosed with stage II or III breast cancer (76.1%), with a median of 16 months post-primary treatment, between the ages of 40–59, educated at the junior high school level or below (86.2%), married with children (93.7%), and unemployed (70.7%). Factor analysis generated five factors: symptom burden, function, health behavior, financial strain, and health care–seeking skills. Scales within each domain were similar to the original CSPro-BC. The measurement models for symptom burden (CFI = 0.949, RMSEA = 0.055), function (CFI = 0.925, RMSEA = 0.080), health behavior (CFI = 0.999, RMSEA = 0.015), financial strain (CFI = 0.999, RMSEA = 0.014), and health care–seeking skills (CFI = 0.964, RMSEA = 0.059) were all consistent with the original measure. Test-retest reliability was between 0.80 and 0.92. Internal consistency ranged from 0.65 to 0.95. Discriminant and concurrent validities were consistent to the original.

Conclusions

The translation resulted in a valid and reliable self-assessment tool for identifying common non-medical problems in breast cancer patients' post-cancer treatment.

Implications for Cancer Survivors

A culturally sensitive measure of symptoms, functional limitations, lifestyle, and health care–seeking skills in Chinese-speaking breast cancer survivors is available for further testing.

http://bit.ly/2Dc7jzn

The Influence of Oxidative Stress and Natural Antioxidants on Morphometric Parameters of Red Blood Cells, the Hemoglobin Oxygen Binding Capacity, and the Activity of Antioxidant Enzymes

Using a wide range of different physical and chemical methods, it was found that the oxidative stress caused by addition of hydrogen peroxide to the incubation medium has a significant effect on the conformation of haematoporphyrin, influencing the oxygen-binding properties of haemoglobin in red blood cells. Morphofunctional characteristics of red blood cells change; in particular, we have observed the transformation of erythrocytes, their transition into echinocytes. In erythrocytes, in response to increased lipid peroxidation (LPO) antioxidant enzymes become active. The use of natural antioxidants (-carotene and resveratrol) works towards reducting the level of oxidative processes. Resveratrol has the greatest antioxidant effect.

http://bit.ly/2RMR58e

Acute Effects Using Light-Emitting Diode Therapy (LEDT) for Muscle Function during Isometric Exercise in Asthma Patients: A Pilot Study

The aim of this study was to evaluate the effectiveness of acute application of LEDT in improving peripheral muscle performance during isometric exercise in patients with asthma. Eleven patients, with a mean age 38 ± 10, underwent a single LEDT and sham application in the femoral quadriceps' dominant member (cluster with 50 LED λ = 850 nm, 50 mW, 15 s; 37.5 J), 48 h apart in a randomized crossover design. Before and after LEDT and sham application, the patients were submitted an isometric endurance test (60% of the maximum isometric voluntary contraction), up to the limit of tolerance simultaneous recording of surface electromyography. There were no statistically significant differences between groups at the time of contraction (before 41±14 versus 44±16; after 46±12 versus 45±20 s) during the isometric contraction test and inflammatory markers before and after a single LEDT application. A single application of LEDT in the parameters and dose according to the equipment used in the study were not able to promote differences in the time of contraction and the fatigue response in asthmatic patients. However, the chronic effects of LEDT application for improving muscle performance in these patients are unknown and may present different responses during applications for a long time.

http://bit.ly/2Hew0zs

The Pronephros; a fresh perspective

Abstract

Contemporary papers and book chapters on nephrology open with the assumption that human kidney development passes through three morphological stages: pronephros, mesonephros and metanephros. Current knowledge of the human pronephros, however, appears to be based on only a hand full of human specimens. The ongoing use of variations in the definition of a pronephros hamper the interpretation of study results. Because of the increased interest in the anamniote pronephros as a genetic model for kidney organogenesis we aimed to provide an overview of the literature concerning kidney development and to clarify the existence of a pronephros in human embryos.We performed an extensive literature survey regarding vertebrate renal morphology and we investigated histological sections of human embryos between 2 and 8 weeks of development. To facilitate better understanding of the literature about kidney development, a referenced glossary with short definitions was composed.The most striking difference between pronephros versus meso- and metanephros is found in nephron architecture. The pronephros consists exclusively of non-integrated nephrons with external glomeruli, whereas meso- and metanephros are composed of integrated nephrons with internal glomeruli. Animals whose embryos have comparatively little yolk at their disposal and hence have a free-swimming larval stage do develop a pronephros that is dedicated to survival in aquatic environments. Species in which embryos do not have a free-swimming larval stage have embryos that are supplied with a large amount of yolk or that develop within the body of the parent. In those species pronephros is usually absent, incompletely developed, and apparently functionless.Non-integrated nephrons were not identified in histological sections of human embryos. Therefore, we conclude that a true pronephros is not detectable in human embryos although the most cranial part of the amniote excretory organ is often confusingly referred to as pronephros. The term pronephros should be avoided in amniotes unless all elements for a functional pronephros are undeniably present.

http://bit.ly/2sryMqP

Ask good assessment questions to get good answers

Remember that a patient can be your best source in acquiring clinical information. By asking good questions and getting good answers, you can start treatment more quickly than you otherwise would.

http://bit.ly/2Hf6Q3t

Prevalence and trajectories of depressive symptoms among mothers of children with newly diagnosed epilepsy: A longitudinal 10‐year study

Summary

Objective

Parental depression significantly impacts children's health and well‐being. This study aimed to (1) estimate the prevalence of depressive symptoms, at six time points, among mothers over the first 10 years after their child was diagnosed with epilepsy; (2) identify trajectories of maternal depressive symptoms over time; and (3) identify baseline factors associated with each trajectory.

Methods

Data came from the Health‐Related Quality of Life in Children with Epilepsy Study (HERQULES), a Canada‐wide prospective cohort study. Data on child, parent, and family characteristics were collected at the time of diagnosis, and follow‐ups at 0.5, 1, 2, 8, and 10 years. Maternal depressive symptoms were measured using the Center for Epidemiological Studies Depression Scale. Trajectories of depressive symptoms were evaluated using latent class growth modeling, and multinomial logistic regression was used to identify baseline factors associated with each trajectory.

Results

A total of 356 mothers participated in the study, of whom 57% scored in the at‐risk range for major depression disorder (period‐prevalence). Four unique trajectories were identified as follows: "Low‐Stable" (29% of mothers), "Intermediate‐Stable" (46%), "High‐Stable" (20%), and "High‐Decreasing" (5%). Positive family environment was consistently associated with a better trajectory of depressive symptoms over time; other significant factors included type of seizures, child cognitive comorbidity, maternal age, and maternal education.

Significance

A substantial proportion of mothers of children with epilepsy are at risk for depression, and this risk is stable over the long term. Family environment at the time of diagnosis has long‐term and persistent effects and may be an ideal target for interventions.

http://bit.ly/2srvKCX

Researchers Can Predict Childhood Social Transitions

Increasingly, children who identify as the gender "opposite" their sex at birth are changing their names, pronouns and often hairstyle and clothing. But questions remain for doctors, researchers and families: Who is transitioning now, and who is likely to later on? And does the transition itself change a child's sense of their own gender?

A study by a team of researchers at the University of Washington (UW) suggests that the children most apt to socially transition are those who already demonstrate the strongest "cross-gender" identities, and that the transitions don't appear to alter a child's gender identity or preferences.

In other words, said Kristina Olson, a UW associate professor of psychology and the study's senior author, "the new findings suggest that early childhood social transitions are not occurring randomly." The findings are forthcoming in Psychological Science, a journal of the Association for Psychological Science.

For this study, Olson and her team pursued two primary questions: Is it possible to predict who will socially transition to another gender? And are transitions leading children to identify more strongly or behave in more gendered ways?

To answer those questions, the research team recruited three groups of children: 85 who were gender nonconforming; 84 children who had already socially transitioned; and 85 children who were gender conforming (the control group). Each child was asked about the clothes, toys and friends they preferred and answered questions about their gender identity. Researchers contacted the gender nonconforming group again, 2 years after completing the study, to ask if the children had socially transitioned since participating. At that point, 36 children in the gender nonconforming group had transitioned.

The data helped researchers learn two things, Olson said. First, gender nonconforming children who had shown stronger cross-gender interests in their first interview were more likely to have socially transitioned two years later. What's more, the children who later went on to transition showed gender identification and gender preferences comparable to children who had already transitioned and control-group children born with the "opposite" sex.

"Seeing that the two groups do not differ in their identification, we can be less concerned about the impact of social transitions on identities and preferences," Olson said. "One way to think about this is that before or after a transition, a transgender girl feels strongly like a girl and often prefers 'girly' stuff. While the transition itself may impact that child in many ways, identity and preferences do not appear to change."

But there are limits to what can be extrapolated from this data, Olson said. Just because a child transitions socially doesn't mean they will identify as a transgender adult — though this study will follow them over time to see if they do. Also, this study focused on families that were generally supportive of gender diversity; whether these results would generalize to parents with a broader range of views is unknown. The research also should not be used to definitively predict whether an individual child will transition. Tendencies for a group of children, Olson said, may be true of an individual child, but not always.

Olson launched the TransYouth Project at the UW to examine, over the course of 20 years, gender development and well-being among children. To date, more than 300 transgender children between the ages of 3 and 12 have enrolled from more than 40 US states. (Many of their siblings have been recruited, too, as a comparison group.)

In 2018, Olson received a MacArthur Foundation "genius grant," as well as the National Science Foundation's Alan T. Waterman Award, the U.S. government's highest honor for one early career scientist under age 40. With the awards, Olson has said she hopes to expand her research team's study of gender diversity and to continue to support underrepresented students who are interested in her lab's research.

Additional authors on this study were lead author James Rae,  a former UW doctoral student, now a postdoctoral researcher at the University of Massachusetts Amherst; and Selin Gülgöz, Lily Durwood, Madeleine DeMeules, Riley Lowe and Gabrielle Lindquist, all of the University of Washington.

The research was funded by the National Science Foundation, the National Institutes of Health and the Arcus Foundation.

http://bit.ly/2TRivXL

The Current Status of Peritoneal Surface Oncology in Saudi Arabia

Abstract

Peritoneal carcinomatosis (PC) is a common evolution of abdominal cancers. It may arise from the peritoneum itself (primary) or originate from another type of cancer especially those of gastrointestinal or gynecological origin (secondary). Without aggressive multimodal therapeutic approaches, PC is associated with a poor prognosis. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have been used to treat PC since 1990. In Saudi Arabia, the first CRS and HIPEC were done in 2008. In 2018, Saudi Arabia population is 32 millions of people and the demand for such procedures has grown up. This article gives outlines of the current status of peritoneal surface oncology in Saudi Arabia and the future perspective.

http://bit.ly/2ST5z3u

Auricular Plaster Therapy for Comorbid Insomnia: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Background. Although the effectiveness of auricular plaster therapy (APT) on primary insomnia has been systematically reviewed, no systematic review of studies has focused on the effect on comorbid insomnia. Objective. To evaluate the efficacy and safety of APT for comorbid insomnia. Methods. Fifteen databases were searched from inception to July 2018. Randomized controlled trials (RCTs) of APT as an exclusive intervention for comorbid insomnia against Western medications, sham APT or no treatment were identified. Results. Fourteen studies involving 928 participants were identified. The pooled outcomes revealed that APT was superior to control conditions for the global score on PSQI (SMD = -1.13, and 95% CI = -1.48—-0.78) and the effective rate (RR = 1.24, 95% CI = 1.13—1.36, NNT = 5, and 95% CI =4—7). Furthermore, the results of subgroup analyses were similar to the pooled results. Additionally, the pooled results were verified to be stable by sensitivity analyses. Regarding safety, no significant difference was identified between APT and Western medications. Conclusions. APT appears to be an effective and safe treatment for comorbid insomnia. However, the benefits of APT for comorbid insomnia could not be ascertained due to the paucity of the quantity and quality of the included studies. Large-scale studies using proper methodology are needed to yield a firm conclusion.

http://bit.ly/2RrbIr7

Vitamin D Supplementation Can Help Cut COPD Exacerbations

TUESDAY, Jan. 15, 2019 -- Vitamin D supplementation safely and substantially reduces the rate of moderate-to-severe chronic obstructive pulmonary disease (COPD) exacerbations in patients with baseline 25-hydroxyvitamin D levels <25 nmol/L,...

http://bit.ly/2AHe4Yv

American College of Physicians Releases 7th Edition of Ethics Manual

TUESDAY, Jan. 15, 2019 -- Ethical principles are discussed in an updated Ethics Manual, issued by the American College of Physicians (ACP) and published as a supplement to the Jan. 15 issue of the Annals of Internal Medicine. Lois Snyder Sulmasy,...

http://bit.ly/2SRR8wt

Young-Onset Type 2 Diabetes Tied to Increased Hospitalization Risk

TUESDAY, Jan. 15, 2019 -- Adults with young-onset type 2 diabetes (T2D; onset before age 40 years) have an increased hospitalization risk across their life span compared with those with usual-onset T2D, according to a study published online Jan. 15...

http://bit.ly/2AXC8qj

Opioids Now More Deadly for Americans Than Traffic Accidents

TUESDAY, Jan. 15, 2019 -- For the first time in history, Americans' risk for dying from an opioid overdose is higher than their risk for dying in a car accident, the National Safety Council reported Monday. The chances of dying from an accidental...

http://bit.ly/2SX3qUy

Recalling Positive Memories May Cut Depression Risk for Teens

TUESDAY, Jan. 15, 2019 -- Recalling specific positive life experiences may build resilience and help lower vulnerability to depression among adolescents with a history of early-life stress, according to a research letter published online Jan. 14 in...

http://bit.ly/2AXC6Pd

Delayed Contraception Leads to Early Unwanted Pregnancy

TUESDAY, Jan. 15, 2019 -- Delayed contraceptive initiation is associated with unwanted pregnancy within three months of sexual debut, according to a study published online Jan. 15 in Pediatrics. Mara E. Murray Horwitz, M.D., M.P.H., from the Harvard...

http://bit.ly/2SX3p2W

Guideline Issued for Treatment of Mild/Moderate Ulcerative Colitis

TUESDAY, Jan. 15, 2019 -- A new clinical guideline from the American Gastroenterological Association (AGA) published Dec. 18 in Gastroenterology focuses on the medical management of patients with mild-to-moderate ulcerative colitis (UC). To inform...

http://bit.ly/2ANEtUx

Comorbidities Adversely Linked to Cancer Trial Participation

TUESDAY, Jan. 15, 2019 -- For cancer patients, the presence of comorbidities is adversely linked to trial discussions, trial offers, and trial participation, according to a study published online Jan. 10 in JAMA Oncology. Joseph M. Unger, Ph.D.,...

http://bit.ly/2SW5XOR

Cardiometabolic Risk Up With Tourette, Chronic Tic Disorder

TUESDAY, Jan. 15, 2019 -- Patients with Tourette syndrome (TS) or chronic tic disorder (CTD) have an increased risk for developing at least one metabolic or cardiovascular disorder, according to a study published online Jan. 14 in JAMA...

http://bit.ly/2AXC0Hl

Study Explores Influence of Genetics, Environment in Disease

TUESDAY, Jan. 15, 2019 -- The influence of heritability and environmental factors has been identified for a large number of phenotypes, according to a study published online Jan. 14 in Nature Genetics. Chirag M. Lakhani, Ph.D., from Harvard Medical...

http://bit.ly/2SWgM3s

Use of cognitive enhancers: methylphenidate and analogs

OBJECTIVE: In the last decades, several cognitive-enhancing drugs have been sold onto the drug market. Methylphenidate and analogs represent a sub-class of these new psychoactive substances (NPS). We aimed to review the use and misuse of methylphenidate and analogs, and the risk associated. Moreover, we exhaustively reviewed the scientific data on the most recent methylphenidate analogs (methylphenidate and ethylphenidate excluded).

MATERIALS AND METHODS: Literature search was performed on methylphenidate and analogs, using specialized search engines accessing scientific databases. Additional reports were retrieved from international agencies, institutional websites, and drug user forums.

RESULTS: Methylphenidate/Ritalin has been used for decades to treat attention deficit disorders and narcolepsy. More recently, it has been used as a cognitive enhancer and a recreational drug. Acute intoxications and fatalities involving methylphenidate were reported. Methylphenidate was scheduled as an illegal drug in many countries, but NPS circumventing the ban and mimicking the psychostimulant effects of methylphenidate started being available: ethylphenidate, 3,4-dichloromethylphenidate, 3,4-dichloroethylphenidate, 4-fluoromethylphenidate, 4-fluoroethylphenidate, methylnaphthidate, ethylnaphthidate, isopropylphenidate, propylphenidate, 4-methylmethylphenidate, and N-benzylethylphenidate have been available in the past few years. Only little data is currently available for these substances. Many intoxications involving methylphenidate analogs were reported. To date, ethylphenidate was involved in 28 fatalities, although it was reportedly directly related to the cause of death in only 7 cases; 3,4-dichloroethylphenidate was involved in 1 death.

CONCLUSIONS: The rapid expansion of methylphenidate analogs onto the drug market in the past few years makes likely the occurrence of intoxications and fatalities in the next years. Careful monitoring and systematic control of methylphenidate analogs should be undertaken to reduce the uprising threat, and education efforts should be made among high-risk populations.

L'articolo Use of cognitive enhancers: methylphenidate and analogs sembra essere il primo su European Review.

http://bit.ly/2AKMLMV

Investigation of seasonal frequency and pathogens in febrile neutropenia

Summary

Background

In patients with hematological malignancies, febrile neutropenia (FEN) is the most frequent complication and the most important cause of mortality. Various risk factors have been identified for severe infection in neutropenic patients. However, to the best of our knowledge, it is not defined whether there is a change in the risk of febrile neutropenia according to seasons. The first aim of study was to determine the difference in frequency of febrile neutropenic episodes (FNEs) according to months and seasons. The second aim was to document isolated pathogens, as well as demographical and clinical characteristics of patients.

Methods

In the study, 194 FNEs of 105 patients who have been followed with hematological malignancies between June 2013 and May 2014 were evaluated retrospectively.

Results

Although the number of FNEs increased in autumn, there was no significant difference in frequency of FNEs between months (p = 0.564) and seasons (p = 0.345). There was no isolated pathogen in 54.6% of FNEs. In 45.4% of 194 FNEs, pathogens were isolated. Of all pathogens, 50.4% were gram negative bacteria, 29.2% were gram positive bacteria, 13.3% were viruses, 5.3% were fungi, and 1.8% were parasites.

Conclusıons

The frequency of FEN does not change according to months or seasons. Also, the relative proportions of different pathogens in the cause of FEN do not vary according to seasons.

http://bit.ly/2FyYGAE

Issue Information

http://bit.ly/2QR2HT5

Third European Society of Endodontology (ESE) research meeting: ACTA, Amsterdam, The Netherlands, 26th October 2018

http://bit.ly/2VV9eQc

Correction to: Rationale and design of the Caloric Restriction and Exercise protection from Anthracycline Toxic Effects (CREATE) study: a 3-arm parallel group phase II randomized controlled trial in early breast cancer

Following publication of the original article [1], we have been notified that one of the author names was listed incorrectly.

http://bit.ly/2FqC9qB

Brain Tumors Through the Single-Cell RNA Sequencing Lens: Researcher Interview with Mario Suvà

Brain cancers are notoriously hard to study, model, and treat. Dr. Mario Suvà speaks about how single-cell RNA sequencing is helping researchers gain clarity on the origins, development, and response to treatment for these cancers.

http://bit.ly/2Rw6aLK

Dysfunctional Immunity and Microbial Adhesion Molecules in Smoking-induced Pneumonia

American Journal of Respiratory and Critical Care Medicine, Volume 199, Issue 2, Page 250-251, January 15, 2019.


http://bit.ly/2QN88Cl

Supplemental Oxygen for Obstructive Sleep Apnea: Is There a Role After All?

American Journal of Respiratory and Critical Care Medicine, Volume 199, Issue 2, Page 140-141, January 15, 2019.


http://bit.ly/2VV3pm3

Stratification of Pulmonary Nodules Using Quantitative Iodine Maps from Dual-Energy Computed Tomography

American Journal of Respiratory and Critical Care Medicine, Volume 199, Issue 2, Page e3-e4, January 15, 2019.


http://bit.ly/2QN81qp

Dawn of a New Era in the Diagnosis and Treatment of Airway Mucus Dysfunction

American Journal of Respiratory and Critical Care Medicine, Volume 199, Issue 2, Page 133-134, January 15, 2019.


http://bit.ly/2VUKFmB

Dose Optimization of H56:IC31 Vaccine for Tuberculosis-Endemic Populations. A Double-Blind, Placebo-controlled, Dose-Selection Trial

American Journal of Respiratory and Critical Care Medicine, Volume 199, Issue 2, Page 220-231, January 15, 2019.


http://bit.ly/2QN7LYt

Rapid Advances in Primary Ciliary Dyskinesia Research. A Brief Update for Pulmonologists

American Journal of Respiratory and Critical Care Medicine, Volume 199, Issue 2, Page 136-138, January 15, 2019.


http://bit.ly/2W2S9nI

Wildfires Disaster Guidance: Tips for Staying Healthy during Wildfires

American Journal of Respiratory and Critical Care Medicine, Volume 199, Issue 2, Page P3-P4, January 15, 2019.


http://bit.ly/2QSyMtP

Extent of Overuse of Inhaled Corticosteroids in Chronic Obstructive Pulmonary Disease

American Journal of Respiratory and Critical Care Medicine, Volume 199, Issue 2, Page 248-249, January 15, 2019.


http://bit.ly/2W2S97c

Effect of Supplemental Oxygen on Blood Pressure in Obstructive Sleep Apnea (SOX). A Randomized Continuous Positive Airway Pressure Withdrawal Trial

American Journal of Respiratory and Critical Care Medicine, Volume 199, Issue 2, Page 211-219, January 15, 2019.


http://bit.ly/2QSyGlX

Implications of Procalcitonin Testing in Critically Ill Patients with Sepsis

American Journal of Respiratory and Critical Care Medicine, Volume 199, Issue 2, Page 232-234, January 15, 2019.


http://bit.ly/2VTIyiK

An Improved Inhaled Mucolytic to Treat Airway Muco-obstructive Diseases

American Journal of Respiratory and Critical Care Medicine, Volume 199, Issue 2, Page 171-180, January 15, 2019.


http://bit.ly/2QSyAuB

Reply to Eapen et al.: Dysfunctional Immunity and Microbial Adhesion Molecules in Smoking-induced Pneumonia

American Journal of Respiratory and Critical Care Medicine, Volume 199, Issue 2, Page 251-252, January 15, 2019.


http://bit.ly/2VXpTTd

Early Plasma Matrix Metalloproteinase Profiles Offer New Insight into the Biology and Prognosis of Pediatric Acute Respiratory Distress Syndrome

American Journal of Respiratory and Critical Care Medicine, Volume 199, Issue 2, Page 134-136, January 15, 2019.


http://bit.ly/2QMXWdf

Reply to Kardos: Extent of Overuse of Inhaled Corticosteroids in Chronic Obstructive Pulmonary Disease

American Journal of Respiratory and Critical Care Medicine, Volume 199, Issue 2, Page 249-250, January 15, 2019.


http://bit.ly/2VU1Jcw

The Ratio of Peripheral Regulatory T Cells to Lox-1+ Polymorphonuclear Myeloid-derived Suppressor Cells Predicts the Early Response to Anti–PD-1 Therapy in Patients with Non–Small Cell Lung Cancer

American Journal of Respiratory and Critical Care Medicine, Volume 199, Issue 2, Page 243-246, January 15, 2019.


http://bit.ly/2QMXRWZ

Sputum Antineutrophil Cytoplasmic Antibodies in Serum Antineutrophil Cytoplasmic Antibody–Negative Eosinophilic Granulomatosis with Polyangiitis

American Journal of Respiratory and Critical Care Medicine, Volume 199, Issue 2, Page 158-170, January 15, 2019.


http://bit.ly/2VXGDKn

Life-Course Smoking Trajectories and Risk for Emphysema in Middle Age: The CARDIA Lung Study

American Journal of Respiratory and Critical Care Medicine, Volume 199, Issue 2, Page 237-240, January 15, 2019.


http://bit.ly/2QN13lm

Disseminated Cryptococcosis with Bronchiolitis and Cellulitis

American Journal of Respiratory and Critical Care Medicine, Volume 199, Issue 2, Page 235-236, January 15, 2019.


http://bit.ly/2VSyqa1

An RNA Sensor Protects against Pulmonary Hypertension

American Journal of Respiratory and Critical Care Medicine, Volume 199, Issue 2, Page 138-140, January 15, 2019.


http://bit.ly/2QOVdjl

ILD: Upcoming Themed Issue

American Journal of Respiratory and Critical Care Medicine, Volume 199, Issue 2, Page 131-131, January 15, 2019.


http://bit.ly/2VUiuEf

Interaction of bacteria and stem cells in health and disease

Abstract

Adult stem and progenitor cells possess unique qualities of proliferative capacity and phenotypic plasticity making their potential interactions with pathogenic and commensal bacteria a significant factor in health and disease. This interaction may result in the hindrance of regenerative capacity and degenerative disease. In other contexts, bacterial -stem cell cross talk plays an important role in regulating stem cell renewal and maintaining homeostasis. Some stems cells are involved in combating infections and modulating immune responses. The results of these interactions contribute significantly to the outcome of infectious disease. The unique characteristics of stem and progenitor cells also make them attractive targets for bacterial pathogenicity strategies. Several bacterial species have been shown to utilize stem cells as cellular niches or as a means to manipulate host pathogen interactions. In some cases, bacteria can re-program end-differentiated tissue cells towards stem-like cells, taking advantage of their unique properties for dissemination and persistence. The ability of bacteria to interfere in stem cell regulatory pathways can also contribute to hyperplastic growth and the development of cancer. In this review we present current knowledge on the diverse interactions between bacteria and stem cells highlighting the consequences for health and disease.

http://bit.ly/2SW02JJ

Lipopolysaccharide structures of Gram-negative populations in the Gut Microbiota and effects on host interactions

Abstract

The human gastrointestinal tract harbors a heterogeneous and complex microbial community which plays a key role in human health. The gut microbiota controls the development of the immune system by setting systemic threshold for immune activation. Glycoconjugates, such as lipopolysaccharides, from gut bacteria have been shown to be able to elicit both systemic proinflammatory and immunomodulatory responses. This phenomenon is particularly intriguing considering that the immune system is charged with the task to distinguish the beneficial microbes from the pathogens, even if the commensal bacteria have molecular patterns resembling those of the pathogenic counterparts. Therefore, the importance of the chemical structure of these macromolecules in the fine tuning this delicate equilibrium is beyond question. This review offers an overview of the current understanding of chemical peculiarities of the lipopolysaccharides isolated from the gut microbiota, and their relationships to their biological activity in terms of immune system maturation and development.

http://bit.ly/2AXnoHZ

Immunodeficiencies that predispose to pathologies by human oncogenic γ-herpesviruses

Abstract

Human γ-herpesviruses include the closely related tumor viruses Epstein Barr virus (EBV) and Kaposi Sarcoma-associated herpesvirus (KSHV). EBV is the most growth transforming pathogen known and linked to at least seven human malignancies. KSHV is also associated with three human cancers. Most EBV and KSHV infected individuals fortunately remain disease free despite persistent infection and this is likely due to the robustness of the immune control that they mount against these tumor viruses. However, upon immune suppression EBV and KSHV associated malignancies emerge at increased frequencies. Moreover, primary immunodeficiencies with individual mutations that predispose to EBV or KSHV disease allow us to gain insights into a catalogue of molecules that are required for the immune control of these tumor viruses. Curiously, there is little overlap between the mutation targets that predispose individuals to EBV versus KSHV disease, even so both viruses can infect the same host cell, human B cells. These differences will be discussed in this review. A better understanding of the crucial components in the near perfect life-long immune control of EBV and KSHV should allow us to target malignancies that are associated with these viruses, but also induce similar immune responses against other tumors.

http://bit.ly/2T3n6pC

Cancers, Vol. 11, Pages 98: Overcoming Intrinsic and Acquired Cetuximab Resistance in RAS Wild-Type Colorectal Cancer: An In Vitro Study on the Expression of HER Receptors and the Potential of Afatinib

Cancers, Vol. 11, Pages 98: Overcoming Intrinsic and Acquired Cetuximab Resistance in RAS Wild-Type Colorectal Cancer: An In Vitro Study on the Expression of HER Receptors and the Potential of Afatinib

Cancers doi: 10.3390/cancers11010098

Authors: Ines De Pauw Filip Lardon Jolien Van den Bossche Hasan Baysal Patrick Pauwels Marc Peeters Jan Baptist Vermorken An Wouters

The epidermal growth factor receptor (EGFR) is an important therapeutic target in colorectal cancer (CRC). After the initial promising results of EGFR-targeted therapies such as cetuximab, therapeutic resistance poses a challenging problem and limits the success of effective anti-EGFR cancer therapies in the clinic. In order to overcome resistance to these EGFR-targeted therapies, new treatment options are necessary. The objective of this study was to investigate the expression of human epidermal growth factor (HER) receptors and the efficacy of afatinib, a second-generation irreversible EGFR-tyrosine kinase inhibitor, in RAS wild-type CRC cell lines with different cetuximab sensitivities. CRC cell lines with different sensitivities to cetuximab showed rather low EGFR expression but high HER2 and HER3 expression. These results were in line with the The Cancer Genome Atlas (TCGA) data from CRC patients, where higher mRNA levels of HER2 and HER3 were also detected compared to EGFR. Therefore, the targets of afatinib were indeed expressed on the CRC cell lines used in this study and in CRC patients. Furthermore, cetuximab resistance had no significant influence on the expression levels of HER receptors in CRC cell lines (p ≥ 0.652). This study also demonstrated that afatinib was able to induce a concentration-dependent cytotoxic effect in RAS wild-type CRC cell lines with different cetuximab sensitivities. Neither cetuximab resistance (p = 0.233) nor hypoxia (p = 0.157) significantly influenced afatinib's cytotoxic effect. In conclusion, our preclinical data support the hypothesis that treatment with afatinib might be a promising novel therapeutic strategy for CRC patients experiencing intrinsic and acquired cetuximab resistance.

http://bit.ly/2CscVnw

Cancers, Vol. 11, Pages 99: Opposing Regulation of Cancer Properties via KRT19-Mediated Differential Modulation of Wnt/β-Catenin/Notch Signaling in Breast and Colon Cancers

Cancers, Vol. 11, Pages 99: Opposing Regulation of Cancer Properties via KRT19-Mediated Differential Modulation of Wnt/β-Catenin/Notch Signaling in Breast and Colon Cancers

Cancers doi: 10.3390/cancers11010099

Authors: Subbroto Kumar Saha Yingfu Yin Hee Sung Chae Ssang-Goo Cho

Although Keratin 19 (KRT19) has been reported as a tumor cell marker and found to interact with other proteins that modulate cancer properties, its role in cancer prognosis remains to be fully elucidated. We found that KRT19 expression was increased in both colon and breast cancer, but that knockdown of KRT19 showed opposing effects on cancer properties. In colon cancer, KRT19 knockdown resulted in suppression of cancer via downregulation of Wnt/Notch signaling without altering NUMB transcription. In breast cancer, KRT19 knockdown led to an increase in cancer properties because of attenuated Wnt and enhanced Notch signaling. In colon cancer, KRT19 interacted with β-catenin but not with RAC1, allowing the LEF/TCF transcription factor to bind primarily to the LEF1 and TCF7 promoter regions, whereas in breast cancer, KRT19 interacted with the β-catenin/RAC1 complex and led to apparent upregulation of NUMB expression and NUMB-mediated suppression of Notch signaling. These results reveal a novel differential role of KRT19 in carcinogenesis, due to differential modulation of Wnt/β-catenin/Notch signaling crosstalk through various interactions of KRT19 with only β-catenin or with the β-catenin/RAC1 complex, which might have implications for clinical cancer research.

http://bit.ly/2Rsotl7

Creatine and pregnancy outcomes, a prospective cohort study in low-risk pregnant women: study protocol

Introduction

The creatine kinase circuit is central to the regulation of high-energy phosphate metabolism and the maintenance of cellular energy turnover. This circuit is fuelled by creatine, an amino acid derivative that can be obtained from a diet containing animal products, and by synthesis in the body de novo. A recent retrospective study conducted in a cohort of 287 pregnant women determined that maternal excreted levels of creatine may be associated with fetal growth. This prospective study aims to overcome some of the limitations associated with the previous study and thoroughly characterise creatine homeostasis throughout gestation in a low-risk pregnant population.

Methods and analysis

This study is recruiting women with a singleton low-risk pregnancy who are attending Monash Health, in Melbourne, Australia. Maternal blood and urine samples, along with dietary surveys, are collected at five time points during pregnancy and then at delivery. Cord blood and placenta (including membranes and cord) are collected at birth. A biobank of tissue samples for future research is being established. Primary outcome measures will include creatine, creatine kinase and associated metabolites in antenatal bloods and urine, cord bloods and placenta, along with molecular analysis of the creatine transporter (SLC6A8) and synthesising enzymes L - arginine:glycine amidinotransferase (AGAT) and guanidinoacetate methyltransferase (GAMT) in placental tissues. Secondary outcome measures include dietary protein intake over pregnancy and any associations with maternal creatine, pregnancy events and birth outcomes.

Ethics and dissemination

Ethical approval was granted in August 2015 from Monash Health (Ref: 14140B) and Monash University (Ref: 7785). Study outcomes will be disseminated at international conferences and published in peer-reviewed scientific journals.

Trial registration number

ACTRN12618001558213; Pre-results.

http://bit.ly/2DbojpG

Comorbidity and healthcare use for individuals with CVD in the Ireland: a cross-sectional, population-based study

Objective

This study explores the factors associated with health service use for individuals with cardiovascular disease (CVD) and comorbidity in the Ireland.

Design

Population-based cross-sectional survey.

Setting

Nationally representative health and health service use survey from the 2010 Quarterly National Household Survey was analysed.

Primary outcome measures

Four outcome variables were examined: no CVD, CVD only, CVD with CVD-related comorbidities and CVD with non-CVD-related comorbidity.

Results

Of the 791 individuals reporting doctor-diagnosed CVD, 77% had a second morbidity. Using type of healthcare coverage as a proxy for socioeconomic status, both CVD-related and non CVD-related comorbidity increases the use of health service usage substantially for individuals with CVD, particularly general practitioner services (8.47, CI 4.49 to 15.96 and 5.20, CI 2.10 to 12.84) and inpatient public hospital care (3.64, CI 2.93 to 4.51 and 3.00, CI 2.11 to 4.26).

Conclusion

This study indicated that even when demographic and socioeconomic factors are controlled for, comorbidity significantly increases the risk of accessing health services for individuals with CVD.

http://bit.ly/2Fqrg8d

Long-term outcome of therapist-guided internet-based cognitive behavioural therapy for body dysmorphic disorder (BDD-NET): a naturalistic 2-year follow-up after a randomised controlled trial

Objectives

Most patients with body dysmorphic disorder (BDD) do not receive evidence-based treatment. A randomised controlled trial (RCT) has found that a therapist-guided internet-based cognitive–behavioural therapy (CBT) programme for BDD (BDD-NET) can be delivered safely via the internet with significant improvements in BDD symptom severity in the short term. The purpose of this study was to evaluate if the therapeutic gains of BDD-NET are maintained 2 years after treatment.

Setting

Academic medical centre.

Participants

A naturalistic 2-year follow-up study of the 88 self-referred adult outpatients with a diagnosis of BDD that had received BDD-NET within the context of the RCT.

Primary and secondary outcomes

The primary outcome was the BDD-Yale-Brown Obsessive-Compulsive Scale (YBOCS). Responder status was defined as a ≥30% reduction in symptoms. Remission was defined as no longer meeting Diagnostic and Statistical Manual of Mental Disorders 5th edition criteria for BDD. Secondary outcomes included measures of depression, global functioning and quality of life.

Results

The efficacy of BDD-NET was sustained long- term, with further improvements observed on the BDD-YBOCS during the follow-up period. At follow-up, 69% (95% CI 57% to 80%) were classified as responders and 56% (95% CI 43% to 69%) were in remission. Gains on depressive symptoms and global functioning were also sustained but not quality of life. A majority of participants reported that the main reason for seeking help for their BDD was the possibility to access the treatment from home.

Conclusion

BDD-NET is an effective treatment for BDD, and the patients' gains are maintained in the long term. BDD-NET has the potential to increase access to CBT and may lower the threshold for BDD sufferers to seek help in the first place.

Trial registration number

NCT02010619.

http://bit.ly/2DbQvZu

Lunar cycle in homicides: a population-based time series study in Finland

Objective

To test whether homicides in Finland vary according to moon phases.

Design

A time series study.

Setting

Finland.

Participants

6808 homicides committed in 1961–2014.

Outcome

Daily numbers of homicides.

Method

The daily numbers of homicides were related to eight moon phases and the illuminated percentage of the moon disc using negative binomial regression. To identify lunar patterns, piecewise linear terms of lunar days were used, together with changes from one moon phase to another. Homicides were similarly regressed on quintiles of the illuminated percentage of the moon disc. A periodic term of length 29.53 days was included to detect cyclic patterns. The results were adjusted for sex, age, secular trend, distance from the moon, seasons, weekday, major holidays and temperature.

Results

During the full moon, 15% less homicides were committed than during the new moon (RR 0.85; 95% CI 0.77 to 0.94) and 86% less during the lightest quintile of illumination compared with the darkest quintile (RR 0.14; 95% CI 0.04 to 0.50). Adjustments did not change the results. Piecewise linear regressions showed a significant decline in homicides at the full moon and a rise thereafter. The full moon drop in homicides was directionally similar for seasons, weekdays, sex, age and time periods, and it was particularly pronounced in the early part of period studied (1961–1974). Periodic regression showed a regular cyclic pattern of length 29.53 days (p~0.035).

Conclusions

Contrary to current scientific opinion, an association exists between moon phases and homicides, and contrary to what has been previously assumed, homicides declined during the full moon, especially in earlier decades. However, the causality of the association remains elusive.

http://bit.ly/2TQUTT7

Qualitative study investigating the underlying motivations of healthy participants in phase I clinical trials

Objectives

If patients are to reap the benefits of continued drug development, an understanding of why healthy participants take part in phase I clinical trials is imperative. The current study aimed to explore the nature of these underlying motivations which may, in turn, improve the overall participant experience and assist in the development of more effective recruitment and retention strategies.

Design

This study used a qualitative design based on the theory of planned behaviour. Specifically, it explored healthy participants' underlying behavioural, control and normative beliefs which influence their participation in phase I clinical trials.

Setting

This study took place at a company that specialises in conducting phase I and phase II clinical trials in the Australian state of Queensland.

Participants

Participants (n=31) were either currently undergoing a phase I clinical trial or had previously taken part in a phase I clinical trial.

Results

Results showed that the motivations were varied and not solely centred on financial gains. Reported advantages of participation included altruism, while inconvenience was most often reported as a disadvantage. Friends were reported as those most likely to approve, while one's mother was reported as most likely to disapprove. Having a suitable time frame/flexible scheduling and feeling comfortable taking part in the trial were both the most commonly reported facilitators, while inflexible scheduling/time commitment was the most commonly reported barrier.

Conclusions

Practical implications included the need for organisations involved in clinical trials to be mindful of inflexible scheduling and exploring the possibility of making educational materials available to family members who may be concerned about the risks associated with participation. Overall, it is anticipated that the results of this study will improve the understanding of factors that influence phase I clinical trial participation which may, ultimately, help develop new therapeutics to improve patient health.

http://bit.ly/2DbRbhq

Clinical and pathological factors of renal anaemia in patients with IgA nephropathy in Chinese adults: a cross-sectional study

Objective

Few studies with large sample populations concerning renal anaemia and IgA nephropathy have been reported worldwide. The purpose of this cross-sectional study was to examine the clinical and pathological characteristics and influencing factors associated with renal anaemia in patients with IgA nephropathy, which is the most common aetiology of chronic kidney disease.

Methods

A total of 462 hospitalised patients with IgA nephropathy confirmed by renal biopsy who met the inclusion criteria were consecutively recruited from January 2014 to January 2016. Their general information, routine blood test results, blood chemistries, estimated glomerular filtration rates (eGFRs) and renal pathologies were collected. The Oxford classification was used to characterise the renal pathologies. Univariable and multivariate logistic regression models were used to analyse the influencing factors of anaemia associated with IgA nephropathy.

Results

The incidence of renal anaemia was 28.5% (132/462 patients) in our study (21.3% in males and 38.9% in females). The anaemia type was primarily normocytic and normochromic. The rate of anaemia in patients with eGFR values of 30–59 mL/min/1.73 m² was higher than that in patients with an eGFR >60 mL/min/1.73 m² (42.9% vs 17.8%, p<0.001). Notably, in the group with eGFR values <15 mL/min/1.73 m², the anaemia rate was 100%. Logistic regression analysis showed that factors affecting anaemia in patients with IgA nephropathy included being female (OR 3.02, 95% CI 1.76 to 5.17), low albumin levels (OR 0.87, 95% CI 0.82 to 0.93), reduced eGFR values (OR 0.98, 95% CI 0.97 to 0.99) and renal tubulointerstitial lesions >50% (OR 2.57, 95% CI 1.22 to 5.40).

Conclusions

The female sex, hypoalbuminaemia, reduced eGFR levels and severe renal tubulointerstitial lesions were correlated with renal anaemia in patients with IgA nephropathy. These results provide new insight into our understanding of anaemia in IgA nephropathy and may improve the management and treatment of clinical renal anaemia.

http://bit.ly/2TV5SLv

Screening strategies for hypertension: a systematic review protocol

Introduction

It is unclear whether early detection of hypertension, through screening, leads to healthier behaviours and better control of blood pressure levels. There is a need to learn from studies that have assessed the impact of different screening approaches on patient important outcomes. This systematic review protocol outlines the methods that will be used to assess the comparative effectiveness of different screening strategies (mass, targeted or opportunistic) for hypertension to reduce morbidity and mortality associated with hypertension.

Methods and analysis

We will primarily search Cochrane Central Register of Controlled Trials, Medline, Embase and Latin American and Caribbean Health Sciences Literature (LILACS). Relevant randomised controlled trials, controlled before and after, interrupted time series and prospective analytic cohort studies regardless of publication date, language and geographic location, will be included. We are interested in clinical, adverse event and health system outcomes. Two reviewers will independently screen titles, abstracts and full-text articles against inclusion criteria; perform data extraction and assess risk of bias in included studies. We will assess the certainty of the overall evidence using the Grading of Recommendations Assessment, Development and Evaluation approach and report findings accordingly.

Ethics and dissemination

No ethics approval will be sought, as only secondary studies will be used. Findings will be disseminated through peer-reviewed publication and conference presentations.

PROSPERO registration number

CRD42018093046.

http://bit.ly/2DcYGox

Protocol for a scoping review to understand how interorganisational electronic health records affect hospital physician and pharmacist decisions

Introduction

Patient records are often fragmented across organisations and departments in UK health and care services, often due to substandard information technology. However, although government policy in the UK and internationally is strongly pushing 'digital transformation', the evidence for the positive impact of electronic information systems on cost, quality and safety of healthcare is far from clear. In particular, the mechanisms by which information availability is translated into better decision-making are not well understood. We do not know when a full interorganisational record is more useful than a key information summary or an institutional record. In this paper, we describe our scoping review of how interorganisational electronic health records affect decision-making by hospital physicians and pharmacists.

Methods and analysis

This scoping review will follow the Arksey and O'Malley (2005) methodology. The review has adopted sociotechnical systems thinking and the notion of distributed cognition as its guiding conceptual models. The UK National Institute for Health and Care Excellence Healthcare Databases Advanced Search will be used, as it incorporates key sources including PubMed, Medline, Embase, HMIC and Health Business Elite. A hand search will be conducted using the reference lists of included studies to identify additional relevant articles. A two-part study selection process will be used: (1) a title and abstract review and (2) full text review. During the first step, two researchers separately will review the citations yielded from the search to determine eligibility based on the defined inclusion and exclusion criteria. Related articles will be included if they are empirical studies that address how interorganisational records affect decision-making by hospital physicians and pharmacists.

Ethics and dissemination

The results will be disseminated through stakeholder meetings, conference presentations and peer-reviewed publication. The data used are from publicly available secondary sources, so this study does not require ethical review.

http://bit.ly/2TTWS9n

Efficacy and safety of different drug monotherapies for tension-type headache in adults: study protocol for a Bayesian network meta-analysis

Introduction

Tension-type headache (TTH) is the most prevalent neurological disease, with an estimated 1.5 billion cases worldwide. Pharmacotherapy should be considered by patients with TTH who have a limited response to non-pharmacological treatment. However, recommendations for the vast array of therapeutic drugs for TTH partially overlap, with conflicting recommendations for strength in different guidelines; these may confuse the decision-making process of clinicians. Hence, the aims of this study are to analyse the available direct and indirect evidence on different drug monotherapies for TTH in adults, and to generate a treatment ranking according to their efficacy and safety outcomes by using a Bayesian network meta-analysis (NMA).

Methods and analysis

We will systematically search the Cochrane Library, PubMed, Web of Science, Embase, China Biomedical Literature Database, International Clinical Trials Registry Platform and other resources for eligible studies. Randomised controlled trials on different drug monotherapies for TTH will be included. Two review authors (RX and YW) will independently search and select the studies, extract the data and assess the risk of bias. A Bayesian NMA will afterwards be conducted to pool the effect measures across all types of monotherapy drugs. The ranking probabilities of the efficacy and safety of different drug monotherapies will be estimated. Heterogeneity will be quantified using the Q statistic and the I² index. Inconsistency between direct and indirect evidence will be assessed by the node-splitting model. In addition, the overall quality of evidence will be assessed using the Grading of Recommendations Assessment, Development and Evaluation approach.

Ethics and dissemination

No ethical issues are foreseen. The results will be published in a peer-reviewed journal, which will be disseminated electronically and in print.

PROSPERO registration number

CRD42018090554.

http://bit.ly/2TUqLq7

Community health worker-delivered counselling for common mental disorders among chronic disease patients in South Africa: a feasibility study

Objectives

To examine the feasibility and acceptability of integrating a 'designated' approach to community health worker (CHW)-delivered mental health counselling (where existing CHWs deliver counselling in addition to usual duties) and a 'dedicated' approach (where additional CHWs have the sole responsibility of delivering mental health counselling) into chronic disease care.

Design

A feasibility test of a designated and dedicated approach to CHW-delivered counselling and qualitative interviews of CHWs delivering the counselling.

Setting

Four primary healthcare clinics in the Western Cape, South Africa allocated to either a designated or dedicated approach and stratified by urban/rural status.

Participants

Forty chronic disease patients (20 with HIV, 20 with diabetes) reporting hazardous alcohol use or depression. Interviews with seven CHWs.

Intervention

Three sessions of structured mental health counselling.

Main outcome measures

We assessed feasibility by examining the proportion of patients who were willing to be screened, met inclusion criteria, provided consent, completed counselling and were retained in the study. Acceptability of these delivery approaches was assessed through qualitative interviews of CHWs.

Results

Regardless of approach, a fair proportion (67%) of eligible patients were willing to receive mental health counselling. Patients who screened positive for depression were more likely to be interested in counselling than those with hazardous alcohol only. Retention in counselling (85%) and the study (90%) was good and did not differ by approach. Both dedicated and designated CHWs viewed the counselling package as highly acceptable but requested additional training and support to facilitate implementation.

Conclusions

Dedicated and designated approaches to CHW-delivered mental health counselling were matched in terms of their feasibility and acceptability. A comparative efficacy trial of these approaches is justified, with some adjustments to the training and implementation protocols to provide further support to CHWs.

http://bit.ly/2DaPLUv

Global certification of wild poliovirus eradication: insights from modelling hard-to-reach subpopulations and confidence about the absence of transmission

Objective

To explore the extent to which undervaccinated subpopulations may influence the confidence about no circulation of wild poliovirus (WPV) after the last detected case.

Design and participants

We used a hypothetical model to examine the extent to which the existence of an undervaccinated subpopulation influences the confidence about no WPV circulation after the last detected case as a function of different characteristics of the subpopulation (eg, size, extent of isolation). We also used the hypothetical population model to inform the bounds on the maximum possible time required to reach high confidence about no circulation in a completely isolated and unvaccinated subpopulation starting either at the endemic equilibrium or with a single infection in an entirely susceptible population.

Results

It may take over 3 years to reach 95% confidence about no circulation for this hypothetical population despite high surveillance sensitivity and high vaccination coverage in the surrounding general population if: (1) ability to detect cases in the undervaccinated subpopulation remains exceedingly small, (2) the undervaccinated subpopulation remains small and highly isolated from the general population and (3) the coverage in the undervaccinated subpopulation remains very close to the minimum needed to eradicate. Fully-isolated hypothetical populations of 4000 people or less cannot sustain endemic transmission for more than 5 years, with at least 20 000 people required for a 50% chance of at least 5 years of sustained transmission in a population without seasonality that starts at the endemic equilibrium. Notably, however, the population size required for persistent transmission increases significantly for realistic populations that include some vaccination and seasonality and/or that do not begin at the endemic equilibrium.

Conclusions

Significant trade-offs remain inherent in global polio certification decisions, which underscore the need for making and valuing investments to maximise population immunity and surveillance quality in all remaining possible WPV reservoirs.

http://bit.ly/2TSTwU4

Utilizing a 3S (strategies, source and setting) approach to understand the patients preferences when addressing medication non-adherence in patients with diabetes: a focus group study in a primary outpatient clinic

Objective

Non-adherence with diabetes medicines is a challenge. Approximately 54% of patients are non-adherent with their diabetes medicines. The objective of this study was to understand patients' preferences when addressing non-adherence based on the 3S approach—strategies (what approaches can be used in addressing non-adherence), settings (when and where should the intervention happen) and sources (who should provide the intervention).

Design

A focus group research design was used.

Setting

A primary outpatient clinic from an integrated healthcare system in the USA.

Participants

Patients who were non-adherent with diabetes medicines.

Data collection

The focus group guide was based on the Medication Adherence Reasons Scale, which has 19 reasons identified for non-adherence. For each item in the scale, patients were asked for strategies that can be used in addressing that issue, the setting in which the interventions should be provided and the source to provide the interventions.

Data analysis

Open coding and content analysis.

Results

Two focus groups, each group having seven patients, were conducted. The major strategies identified were patient education, self-responsibility of patients, family support, reminders and societal support. The key educational needs were dealing with side effects and learning to use insulin properly, and a need for different learning styles when offering education. For the source, the major ones were physicians and pharmacists, having a continuous dialogue about the disease and medicines, and individuality in managing the disease. Respondents also recommended using a peer support group. For the setting, the patients preferred continuity of patient education throughout the disease.

Conclusion

The 3S approach was able to elicit several recommendations from patients to improve their adherence with diabetes medicines. Educational strategies were identified as the foremost approach coming from physicians and pharmacists throughout their disease journey, in addition to peer support.

http://bit.ly/2DaPAZl

Chinese herbal medicine for postpartum constipation: a protocol of systematic review and meta-analysis

Introduction

Constipation is one of the most common gastrointestinal symptoms in postpartum mothers. The choice of treatments for postpartum constipation remains a challenging clinical problem. Chinese herbal medicine has become increasingly popular as an alternative therapy for constipation. This systematic review aims to evaluate the efficacy and safety of Chinese herbal medicine for postpartum constipation.

Methods and analysis

We will search PubMed (1946 to present), EMBASE (1974 to present), Cochrane Central Register of Controlled Trials (all years), Web of Science (1900 to present), Chinese Biomedical Literatures Database (1978 to present), China National Knowledge Infrastructure (1979 to present) and WANFANG data (1998 to present) to identify any eligible study. No restriction will be put on the language, publication date or status of the study. The primary outcome will be the spontaneous bowel movement. Secondary outcomes will be stool consistency, quality of life, transit time, relief of constipation symptoms and adverse events. We will perform the meta-analysis when more than one trial examines the same intervention and outcomes with comparable methods in similar populations. If the heterogeneity is not significant statistically (p>0.10 or I²<50%), the fixed-effect model will be built to estimate the overall intervention effects. Otherwise, the random-effect model will be used to provide more conservative results.

Ethics and dissemination

No ethical issues are foreseen because no primary data will be collected. The results will be published in a peer-reviewed scientific journal.

PROSPERO registration number

CRD42018093741

http://bit.ly/2TOtHo0

Prevalence and correlates of advance care directives among older Australians accessing health and residential aged care services: multicentre audit study

Objectives

It is important that the outcomes of advance care planning (ACP) conversations are documented and available at the point of care. Advance care directives (ACDs) are a subset of ACP documentation and refer to structured documents that are completed and signed by competent adults. Other ACP documentation includes informal documentation by the person or on behalf of the person by someone else (eg, clinician, family). The primary objectives were to describe the prevalence and correlates of ACDs among Australians aged 65 and over accessing health and residential aged care services. The secondary aim was to describe the prevalence of other ACP documentation.

Design and setting

A prospective multicentre health record audit in general practices (n=13), hospitals (n=12) and residential aged care facilities (RACFs; n=26).

Participants

503 people attending general practice, 574 people admitted to hospitals and 1208 people in RACFs.

Primary and secondary outcome measures

Prevalence of one or more ACDs; prevalence of other ACP documentation.

Results

29.8% of people had at least one ACD on file. The majority were non-statutory documents (20.9%). ACD prevalence was significantly higher in RACFs (47.7%) than hospitals (15.7%) and general practices (3.2%) (p<0.001), and varied across jurisdictions. Multivariate logistic regression showed that the odds of having an ACD were positively associated with greater functional impairment and being in an RACF or hospital compared with general practice. 21.6% of people had other ACP documentation.

Conclusions

In this study, 30% of people had ACDs accessible and a further 20% had other ACP documentation, suggesting that approximately half of participants had some form of ACP. Correlates of ACD completion were greater impairment and being in an RACF or hospital. Greater efforts to promote and standardise ACDs across jurisdictions may help to assist older people to navigate and complete ACDs and to receive care consistent with their preferences.

Trial registration number

ACTRN12617000743369.

http://bit.ly/2DaPsJl

Treatment outcomes for eating disorders in Sweden: data from the national quality registry

Objective

To report the outcomes of eating disorders treatment in Sweden in 2012–2016.

Design

The number of patients treated and the number of patients not fulfilling an eating disorders diagnosis (remission) at 1 year of follow-up at the clinics listed in the National Quality Registry for Eating Disorders Treatment were analysed. The published outcomes at three clinics, which used survival analysis to estimate outcomes, were compared with their outcomes in the registry. Outcomes at the three biggest clinics were compared.

Setting

All eating disorders clinics.

Participants

All patients treated at eating disorders clinics.

Intervention

Cognitive–behavioural therapy at most clinics and normalisation of eating behaviour at the three clinics with published outcomes.

Outcome measure

Proportion of patients in remission.

Results

About 2600 patients were treated annually, fewer than half were followed up and remission rates decreased from 21% in 2014 to 14% in 2016. Outcomes, which differed among clinics and within clinics over time, have been publicly overestimated by excluding patients lost to follow-up. The published estimated rate of remission at three clinics that treated 1200 patients in 1993–2011 was 27%, 28% and 40% at 1 year of follow-up. The average rate of remission over the three last years at the biggest of these clinics was 36% but decreased from 29% and 30% to 16 and 14% at the two other of the biggest clinics.

Conclusions

With more than half the patients lost to follow-up and no data on relapse in the National Quality Registry, it is difficult to estimate the effects of eating disorders treatment in Sweden. Analysis of time to clinically significant events, including an extended period of follow-up, has improved the quality of the estimates at three clinics. Overestimation of remission rates has misled healthcare policies. The effect of eating disorders treatment has also been overestimated internationally.

http://bit.ly/2TOtuBe

Evaluation of instructions in patient information leaflets for the use of intranasal corticosteroid sprays: an observational study

Objectives

In this study, we analysed patient information leaflets (PILs) of intranasal corticosteroid sprays (INCS) of different manufacturers in the UK to determine if instructions for the use of INCS are complete and uniform.

Setting

PILs of all INCS of all manufacturers, available for patients in the UK, were collected from the British National Formulary website and the Medicines and Healthcare products Regulatory Agency website. All instructions in these PILs were analysed.

Participants

We identified PILs of INCS from 21 different manufacturers, available for patients in the UK.

Results

We analysed the instructions for the use of INCS in 21 different PILs and there is large variation in the PIL instructions for the technique of using INCS across PILs.

Conclusion

Complete and uniform instructions for the use of INCS are lacking in PILs for registered preparations in the UK. Structured and standardised instructions to be used by both professionals and patients are essential in order to optimise daily use of INCS.

http://bit.ly/2DbURQs

Validation of the hospital frailty risk score in a tertiary care hospital in Switzerland: results of a prospective, observational study

Objectives

Recently, the Hospital Frailty Risk Score based on a derivation and validation study in the UK has been proposed as a low-cost, systematic screening tool to identify older, frail patients who are at a greater risk of adverse outcomes and for whom a frailty-attuned approach might be useful. We aimed to validate this Score in an independent cohort in Switzerland.

Design

Secondary analysis of a prospective, observational study (TRIAGE study).

Setting

One 600-bed tertiary care hospital in Aarau, Switzerland.

Participants

Consecutive medical inpatients aged ≥75 years that presented to the emergency department or were electively admitted between October 2015 and April 2018.

Primary and secondary outcome measures

The primary endpoint was all-cause 30-day mortality. Secondary endpoints were length of hospital stay, hospital readmission, functional impairment and quality of life measures. We used multivariate regression analyses.

Results

Of 4957 included patients, 3150 (63.5%) were classified as low risk, 1663 (33.5%) intermediate risk, and 144 (2.9%) high risk for frailty. Compared with the low-risk group, patients in the moderate risk and high-risk groups had increased risk for 30-day mortality (OR (OR) 2.53, 95% CI 2.09 to 3.06, p<0.001 and OR 4.40, 95% CI 2.94 to 6.57, p<0.001) with overall moderate discrimination (area under the ROC curve 0.66). The results remained robust after adjustment for important confounders. Similarly, we found longer length of hospital stay, more severe functional impairment and a lower quality of life in higher risk group patients.

Conclusion

Our data confirm the prognostic value of the Hospital Frailty Risk Score to identify older, frail people at risk for mortality and adverse outcomes in an independent patient population.

Trial registration number

NCT01768494; Post-results.

http://bit.ly/2TLjOHM