UW Neurological Surgery Recent PubMed Publications

Risks for cold frequency vary by sex: role of asthma, age, TLR7 and leukocyte subsets.

Eur Respir J. 2020 Jun 08;:

Authors: Murray LM, Yerkovich ST, Ferreira MA, Upham JW

Abstract
Viral respiratory infections are usually benign but can trigger asthma exacerbations. The factors associated with upper respiratory tract infection (cold) frequency are not fully understood, nor is it clear whether such factors differ between women and men.To determine which immunological and clinical variables associate with the frequency of self-reported respiratory infections (colds), 150 asthma cases and 151 controls were recruited. Associations between antiviral immune response variables - TLR7/8 gene expression, plasmacytoid dendritic cell (pDC) numbers and interferon-alpha, TNF and IL-12 production - and asthma were then examined that might explain cold frequency.People with asthma cases reported more colds per year (median 3 versus 2, p<0.001) and had lower baseline TLR7 gene expression (odds ratio (OR)=0.12, p=0.02) than controls. Associations between many variables and cold frequency differed between women and men. In women, high blood neutrophil counts (beta=0.096, p=0.002), and younger age (beta= -0.017, p<0.001), but not exposure to children, were independently associated with more frequent colds. In men, low TLR7 expression (beta= -0.96, p=0.041) and high CLEC4C gene expression (a marker of pDC; beta=0.88, p=0.008) were independently associated with more frequent colds. Poor asthma symptom control was independently associated with reduced TLR8 gene expression (beta= -1.4, p=0.036) and high BMI (beta=0.041, p=0.004).Asthma, age and markers of inflammation and antiviral immunity in peripheral blood are associated with frequent colds. Interestingly, the variables associated with cold frequency differed between women and men.

PMID: 32513781 [PubMed - as supplied by publisher]

Screening for Drug Use in Primary Care: Practical Implications of the New USPSTF Recommendation.

JAMA Intern Med. 2020 08 01;180(8):1050-1051

Authors: Bradley KA, Lapham GT, Lee AK

PMID: 32515790 [PubMed - indexed for MEDLINE]

Editorial overviews: Editorial matters - point of clarification.

Curr Opin Pharmacol. 2020 02;50:107-108

Authors: Williams M

PMID: 32506004 [PubMed - indexed for MEDLINE]

Antiepileptic Drugs and Bone Health: Current Concepts.

Psychopharmacol Bull. 2020 May 19;50(2):36-44

Authors: Siniscalchi A, Murphy S, Cione E, Piro L, Sarro G, Gallelli L

Abstract
Chronic use of antiepileptic drugs (AEDs) can induce the development of adverse effects on bone metabolism. In epileptic patients treated with AED, the monitoring of biochemical markers of bone turnover, such as the measurement of serum 25 (OH) vitamin D, bone mineral density, before the beginning of the treatment and during the follow-up is not routinely required. In the future, monitoring of biochemical markers in epileptic patients treated with AED may help us for adequate prevention therapy.

PMID: 32508365 [PubMed - in process]

Utilizing Organoid and Air-Liquid Interface Models as a Screening Method in the Development of New Host Defense Peptides.

Front Cell Infect Microbiol. 2020;10:228

Authors: Choi KG, Wu BC, Lee AH, Baquir B, Hancock REW

Abstract
Host defense peptides (HDPs), also known as antimicrobial peptides, are naturally occurring polypeptides (~12-50 residues) composed of cationic and hydrophobic amino acids that adopt an amphipathic conformation upon folding usually after contact with membranes. HDPs have a variety of biological activities including immunomodulatory, anti-inflammatory, anti-bacterial, and anti-biofilm functions. Although HDPs have the potential to address the global threat of antibiotic resistance and to treat immune and inflammatory disorders, they have yet to achieve this promise. Indeed, there are several challenges associated with bringing peptide-based drug candidates from the lab bench to clinical practice, including identifying appropriate indications, stability, toxicity, and cost. These challenges can be addressed in part by the development of innate defense regulator (IDR) peptides and peptidomimetics, which are synthetic derivatives of HDPs with similar or better efficacy, increased stability, and reduced toxicity and cost of the original HDP. However, one of the largest gaps between basic research and clinical application is the validity and translatability of conventional model systems, such as cell lines and animal models, for screening HDPs and their derivatives as potential drug therapies. Indeed, such translation has often relied on animal models, which have only limited validity. Here we discuss the recent development of human organoids for disease modeling and drug screening, assisted by the use of omics analyses. Organoids, developed from primary cells, cell lines, or human pluripotent stem cells, are three-dimensional, self-organizing structures that closely resemble their corresponding in vivo organs with regards to immune responses, tissue organization, and physiological properties; thus, organoids represent a reliable method for studying efficacy, formulation, toxicity and to some extent drug stability and pharmacodynamics. The use of patient-derived organoids enables the study of patient-specific efficacy, toxicogenomics and drug response predictions. We outline how organoids and omics data analysis can be leveraged to aid in the clinical translation of IDR peptides.

PMID: 32509598 [PubMed - in process]

Pseudoaneurysm of the Superficial Temporal Artery After Intracranial Pressure Monitoring Device Placement: Case Report of a Rare Complication.

Oper Neurosurg (Hagerstown). 2020 Jun 05;:

Authors: Pan J, Barros G, Greil ME, Meyer RM, Ene CI, Chesnut RM

Abstract
BACKGROUND AND IMPORTANCE: Pseudoaneurysms involving the superficial temporal artery (STA), either iatrogenic or caused by direct trauma, are rare. The STA is prone to injury due to its long course throughout the scalp. Injuries can cause cosmetic defects and/or skin breakdown leading to further complications.
CLINICAL PRESENTATION: We report a case of delayed iatrogenic pseudoaneurysm of the STA after placement of an intracranial pressure monitor in the setting of acute traumatic brain injury. The patient had a delayed development of a pulsatile mass over his right frontal region, with computed tomography angiography concerning for a pseudoaneurysm of the STA. This was managed with surgical resection with complete resolution of symptoms at follow-up.
CONCLUSION: We review the literature regarding the etiology, pathogenesis, and management of these lesions. While iatrogenic injuries to the STA have been previously reported, this is a curious case related to placement of an intracranial pressure monitor. We recommend direct surgical resection of the pseudoaneurysm for cosmetic effect and prevention of further wound breakdown.

PMID: 32503046 [PubMed - as supplied by publisher]

Small Bowel Gastrointestinal Stromal Tumor as a Gateway for Streptococcus anginosus Causing Multiple Liver Abscesses.

World J Oncol. 2020 Jun;11(3):116-121

Authors: Conte GA, Harmon JS, Masia RA, Marchesani D, Sun X, Pichardo EM, Parrilla FB, Levitt MJ, Chinnici AA

Abstract
Gastrointestinal stromal tumors (GISTs) are the most common type of mesenchymal neoplasm of the gastrointestinal tract but consist of only 1% of all primary gastrointestinal neoplasms. Differentiated from other spindle cell tumors, GISTs are uniquely positive for CD117 expression which allows for molecular targeting therapy with imatinib mesylate (Gleevec). Clinical presentations are variable, ranging from asymptomatic to vague symptoms of abdominal pain, early satiety, abdominal distention or gastrointestinal bleeding. Very rarely, patients can present with tumor-bowel fistula and intra-abdominal abscesses. In this article, we discuss a rare presentation of a middle-aged male with multiple liver abscesses found to have a primary small bowel GIST. This patient received prompt intravenous antibiotics; however, hepatic abscesses can be easily misinterpreted as cystic hepatic metastases which can delay appropriate therapy. Streptococcus anginosus was found to be responsible for the formation of the liver abscesses visualized on computed tomography (CT) scan. Similar to Streptococcus bovis, knowledge in the literature is arising about the association between S. anginosus and gastrointestinal malignancies. This case highlights the importance of identifying concomitant primary GISTs with intra-hepatic abscesses, as these lesions can be easily misconstrued as liver metastases and consequently mismanaged. We herein emphasize that hepatic abscesses are a potential sequela of GISTs and should thus prompt further investigation for potential malignancies, if warranted, so that there is no delay in treatment of these gastrointestinal tumors.

PMID: 32494319 [PubMed]

Targeting therapeutic vulnerabilities with PARP inhibition and radiation in IDH-mutant gliomas and cholangiocarcinomas.

Sci Adv. 2020 Apr;6(17):eaaz3221

Authors: Wang Y, Wild AT, Turcan S, Wu WH, Sigel C, Klimstra DS, Ma X, Gong Y, Holland EC, Huse JT, Chan TA

Abstract
Mutations in isocitrate dehydrogenase (IDH) genes occur in multiple cancer types, lead to global changes in the epigenome, and drive tumorigenesis. Yet, effective strategies targeting solid tumors harboring IDH mutations remain elusive. Here, we demonstrate that IDH-mutant gliomas and cholangiocarcinomas display elevated DNA damage. Using multiple in vitro and preclinical animal models of glioma and cholangiocarcinoma, we developed treatment strategies that use a synthetic lethality approach targeting the reduced DNA damage repair conferred by mutant IDH using poly(adenosine 5'-diphosphate) ribose polymerase inhibitors (PARPis). The therapeutic effects are markedly enhanced by cotreatment with concurrent, localized radiation therapy. PARPi-buttressed multimodality therapies may represent a readily applicable approach that is selective for IDH-mutant tumor cells and has potential to improve outcomes in multiple cancers.

PMID: 32494639 [PubMed - in process]

Antiviral activity of PLK1-targeting siRNA delivered by lipid nanoparticles in HBV-infected hepatocytes.

Antivir Ther. 2020 Jun 04;:

Authors: Foca A, Dhillon A, Lahlali T, Lucifora J, Salvetti A, Rivoire M, Lee A, Durantel D

Abstract
BACKGROUND: A link between HBV and PLK1 was clearly evidenced in HBV-driven carcinogenesis, and we have also recently shown that PLK1 is a proviral factor in the early phases of HBV infection. Moreover, we have shown that BI-2536, a small molecule PLK1 inhibitor, was very efficient at inhibiting HBV DNA neosynthesis, notably by affecting nucleocapsid assembly as a result of the modulation of HBc phosphorylation. Yet, as small molecule kinase inhibitors often feature poor selectivity, a more specific and safer strategy to target PLK1 would be needed for a potential development against chronic HBV infections.
METHODS: Here, we analysed using both freshly isolated primary human hepatocytes and differentiated HepaRG, the anti-HBV properties of an LNP-encapsulated PLK1-targeting siRNA. Standard assays were used to monitor the effect of LNP siPLK1, or controls (LNP siHBV and LNP siNon-Targeting), on HBV replication and cell viability.
RESULTS: A dose as low as 100ng/mL of LNP-siPLK1 resulted in a >75% decrease in secreted HBV DNA (viral particles), which was comparable to that obtained with LNP siHBV or 10 µM of Tenofovir (TFV), without affecting cell viability. Interestingly, and in contrast to that obtained with TFV, a strong inhibition of viral RNA and HBe/HBsAg secretions was also observed under LNP siPLK1 treatment. This correlated with a significant intracellular decrease of vRNA accumulation, which was independent of any change in cccDNA levels, thus suggesting a transcriptional or post-transcriptional modulation. Such an effect was not obtained with a biochemical approach of PLK1 inhibition, suggesting an enzymatic-independent role of PLK1.
CONCLUSIONS: This study emphasizes that a specific PLK1 inhibition could help achieving an improved HBsAg loss in CHB patients, likely in combination with other HBsAg-targeting strategies.

PMID: 32496211 [PubMed - as supplied by publisher]

The Dancing Cord: Inherent Spinal Cord Motion and Its Effect on Cord Dose in Spine Stereotactic Body Radiation Therapy.

Neurosurgery. 2020 Jun 04;:

Authors: Oztek MA, Mayr NA, Mossa-Basha M, Nyflot M, Sponseller PA, Wu W, Hofstetter CP, Saigal R, Bowen SR, Hippe DS, Yuh WTC, Stewart RD, Lo SS

Abstract
BACKGROUND: Spinal cord dose limits are critically important for the safe practice of spine stereotactic body radiotherapy (SBRT). However, the effect of inherent spinal cord motion on cord dose in SBRT is unknown.
OBJECTIVE: To assess the effects of cord motion on spinal cord dose in SBRT.
METHODS: Dynamic balanced fast field echo (BFFE) magnetic resonance imaging (MRI) was obtained in 21 spine metastasis patients treated with SBRT. Planning computed tomography (CT), conventional static T2-weighted MRI, BFFE MRI, and dose planning data were coregistered. Spinal cord from the dynamic BFFE images (corddyn) was compared with the T2-weighted MRI (cordstat) to analyze motion of corddyn beyond the cordstat (Dice coefficient, Jaccard index), and beyond cordstat with added planning organ at risk volume (PRV) margins. Cord dose was compared between cordstat, and corddyn (Wilcoxon signed-rank test).
RESULTS: Dice coefficient (0.70-0.95, median 0.87) and Jaccard index (0.54-0.90, median 0.77) demonstrated motion of corddyn beyond cordstat. In 62% of the patients (13/21), the dose to corddyn exceeded that of cordstat by 0.6% to 13.8% (median 4.3%). The corddyn spatially excursed outside the 1-mm PRV margin of cordstat in 9 patients (43%); among these dose to corddyn exceeded dose to cordstat >+ 1-mm PRV margin in 78% of the patients (7/9). Corddyn did not excurse outside the 1.5-mm or 2-mm PRV cord cordstat margin.
CONCLUSION: Spinal cord motion may contribute to increases in radiation dose to the cord from SBRT for spine metastasis. A PRV margin of at least 1.5 to 2 mm surrounding the cord should be strongly considered to account for inherent spinal cord motion.

PMID: 32497210 [PubMed - as supplied by publisher]

Reducing Sitting Time in Obese Older Adults: The I-STAND Randomized Controlled Trial.

J Aging Phys Act. 2020 Jun 04;:1-11

Authors: Rosenberg DE, Anderson ML, Renz A, Matson TE, Lee AK, Greenwood-Hickman MA, Arterburn DE, Gardiner PA, Kerr J, McClure JB

Abstract
BACKGROUND: The authors tested the efficacy of the "I-STAND" intervention for reducing sitting time, a novel and potentially health-promoting approach, in older adults with obesity.
METHODS: The authors recruited 60 people (mean age = 68 ± 4.9 years, 68% female, 86% White; mean body mass index = 35.4). The participants were randomized to receive the I-STAND sitting reduction intervention (n = 29) or healthy living control group (n = 31) for 12 weeks. At baseline and at 12 weeks, the participants wore activPAL devices to assess sitting time (primary outcome). Secondary outcomes included fasting glucose, blood pressure, and weight. Linear regression models assessed between-group differences in the outcomes.
RESULTS: The I-STAND participants significantly reduced their sitting time compared with the controls (-58 min per day; 95% confidence interval [-100.3, -15.6]; p = .007). There were no statistically significant changes in the secondary outcomes.
CONCLUSION: I-STAND was efficacious in reducing sitting time, but not in changing health outcomes in older adults with obesity.

PMID: 32498040 [PubMed - as supplied by publisher]

Lower complication rates associated with transradial versus transfemoral flow diverting stent placement.

J Neurointerv Surg. 2020 Jun 02;:

Authors: Li Y, Chen SH, Spiotta AM, Jabbour P, Levitt MR, Kan P, Griessenauer CJ, Arthur AS, Osbun JW, Park MS, Chalouhi N, Sweid A, Wolfe SQ, Fargen KM, Dumont AS, Dumont TM, Brunet MC, Sur S, Luther E, Strickland A, Yavagal DR, Peterson EC, Schirmer CM, Goren O, Dalal S, Weiner G, Rosengart A, Raper D, Chen CJ, Amenta P, Scullen T, Kelly CM, Young C, Nahhas M, Almallouhi E, Gunasekaran A, Pai S, Lanzino G, Brinjikji W, Abbasi M, Dornbos Iii D, Goyal N, Peterson J, El-Ghanem MH, Starke RM

Abstract
BACKGROUND: Currently, there are no large-scale studies in the neurointerventional literature comparing safety between transradial (TRA) and transfemoral (TFA) approaches for flow diversion procedures. This study aims to assess complication rates in a large multicenter registry for TRA versus TFA flow diversion.
METHODS: We retrospectively analyzed flow diversion cases for cerebral aneurysms from 14 institutions from 2010 to 2019. Pooled analysis of proportions was calculated using weighted analysis with 95% CI to account for results from multiple centers. Access site complication rate and overall complication rate were compared between the two approaches.
RESULTS: A total of 2,285 patients who underwent flow diversion were analyzed, with 134 (5.86%) treated with TRA and 2151 (94.14%) via TFA. The two groups shared similar patient and aneurysm characteristics. Crossover from TRA to TFA was documented in 12 (8.63%) patients. There were no access site complications in the TRA group. There was a significantly higher access site complication rate in the TFA cohort as compared with TRA (2.48%, 95% CI 2.40% to 2.57%, vs 0%; p=0.039). One death resulted from a femoral access site complication. The overall complications rate was also higher in the TFA group (9.02%, 95% CI 8.15% to 9.89%) compared with the TRA group (3.73%, 95% CI 3.13% to 4.28%; p=0.035).
CONCLUSION: TRA may be a safer approach for flow diversion to treat cerebral aneurysms at a wide range of locations. Both access site complication rate and overall complication rate were lower for TRA flow diversion compared with TFA in this large series.

PMID: 32487766 [PubMed - as supplied by publisher]

Want to Work on Asthma Genetics?

Twin Res Hum Genet. 2020 Jun 02;:1

Authors: Ferreira MAR

Abstract
Twins, data and emails. Some of the words that first come to mind when I think of Nick. Lots of twins. With lots of data. And short single-finger-typed emails. And great wine. Well, it works, there is no doubt. That's how I ended up in Australia, working on asthma genetics.

PMID: 32482193 [PubMed - as supplied by publisher]

A replication-competent late liver stage-attenuated human malaria parasite.

JCI Insight. 2020 Jun 02;:

Authors: Goswami D, Betz W, Locham NK, Parthiban C, Brager C, Schäfer C, Camargo N, Nguyen T, Kennedy SY, Murphy SC, Vaughan AM, Kappe SH

Abstract
Whole sporozoite vaccines engender sterilizing immunity against malaria in animal models and importantly, in humans. Gene editing allows for the removal of specific parasite genes, enabling generation of genetically attenuated parasite (GAP) strains for vaccination. Using rodent malaria parasites, we have previously shown that late liver stage-arresting replication-competent (LARC) GAPs confer superior protection when compared to early liver stage-arresting replication-deficient (EARD) GAPs and radiation-attenuated sporozoites. However, generating a LARC GAP in the human malaria parasite Plasmodium falciparum (Pf) has been challenging. Here we report the generation and characterization of an unprecedented Pf LARC GAP generated by targeted gene deletion of the Mei2 gene; Pf mei2-. Robust exoerythrocytic schizogony with extensive cell growth and DNA replication was observed for Pf mei2- liver stages in human liver-chimeric mice. However, Pf mei2- liver stages failed to complete development and did not form infectious exo-erythrocytic merozoites, thereby preventing their transition to asexual blood stage infection. Therefore, Pf mei2- is a replication-competent, attenuated human malaria parasite strain with potentially increased potency, useful for vaccination to protect against Pf malaria infection.

PMID: 32484795 [PubMed - as supplied by publisher]

Whole blood transcriptional responses of very preterm infants during late-onset sepsis.

PLoS One. 2020;15(6):e0233841

Authors: Ng S, Strunk T, Lee AH, Gill EE, Falsafi R, Woodman T, Hibbert J, Hancock REW, Currie A

Abstract
BACKGROUND: Host immune responses during late-onset sepsis (LOS) in very preterm infants are poorly characterised due to a complex and dynamic pathophysiology and challenges in working with small available blood volumes. We present here an unbiased transcriptomic analysis of whole peripheral blood from very preterm infants at the time of LOS.
METHODS: RNA-Seq was performed on peripheral blood samples (6-29 days postnatal age) taken at the time of suspected LOS from very preterm infants <30 weeks gestational age. Infants were classified based on blood culture positivity and elevated C-reactive protein concentrations as having confirmed LOS (n = 5), possible LOS (n = 4) or no LOS (n = 9). Bioinformatics and statistical analyses performed included pathway over-representation and protein-protein interaction network analyses. Plasma cytokine immunoassays were performed to validate differentially expressed cytokine pathways.
RESULTS: The blood leukocyte transcriptional responses of infants with confirmed LOS differed significantly from infants without LOS (1,317 differentially expressed genes). However, infants with possible LOS could not be distinguished from infants with no LOS or confirmed LOS. Transcriptional alterations associated with LOS included genes involved in pathogen recognition (mainly TLR pathways), cytokine signalling (both pro-inflammatory and inhibitory responses), immune and haematological regulation (including cell death pathways), and metabolism (altered cholesterol biosynthesis). At the transcriptional-level cytokine responses during LOS were characterised by over-representation of IFN-α/β, IFN-γ, IL-1 and IL-6 signalling pathways and up-regulation of genes for inflammatory responses. Infants with confirmed LOS had significantly higher levels of IL-1α and IL-6 in their plasma.
CONCLUSIONS: Blood responses in very preterm infants with LOS are characterised by altered host immune responses that appear to reflect unbalanced immuno-metabolic homeostasis.

PMID: 32479514 [PubMed - indexed for MEDLINE]

Delayed presentation of acute ischemic strokes during the COVID-19 crisis.

J Neurointerv Surg. 2020 Jul;12(7):639-642

Authors: Schirmer CM, Ringer AJ, Arthur AS, Binning MJ, Fox WC, James RF, Levitt MR, Tawk RG, Veznedaroglu E, Walker M, Spiotta AM, Endovascular Research Group (ENRG)

Abstract
BACKGROUND: The COVID-19 pandemic has disrupted established care paths worldwide. Patient awareness of the pandemic and executive limitations imposed on public life have changed the perception of when to seek care for acute conditions in some cases. We sought to study whether there is a delay in presentation for acute ischemic stroke patients in the first month of the pandemic in the US.
METHODS: The interval between last-known-well (LKW) time and presentation of 710 consecutive patients presenting with acute ischemic strokes to 12 stroke centers across the US were extracted from a prospectively maintained quality database. We analyzed the timing and severity of the presentation in the baseline period from February to March 2019 and compared results with the timeframe of February and March 2020.
RESULTS: There were 320 patients in the 2-month baseline period in 2019, there was a marked decrease in patients from February to March of 2020 (227 patients in February, and 163 patients in March). There was no difference in the severity of the presentation between groups and no difference in age between the baseline and the COVID period. The mean interval from LKW to the presentation was significantly longer in the COVID period (603±1035 min) compared with the baseline period (442±435 min, P<0.02).
CONCLUSION: We present data supporting an association between public awareness and limitations imposed on public life during the COVID-19 pandemic in the US and a delay in presentation for acute ischemic stroke patients to a stroke center.

PMID: 32467244 [PubMed - indexed for MEDLINE]

Pain Anxiety Symptoms Scale-20: An empirical evaluation of measurement invariance across race/ethnicity, sex, and pain.

Psychol Assess. 2020 Sep;32(9):818-828

Authors: Rogers AH, Gallagher MW, Garey L, Ditre JW, Williams MW, Zvolensky MJ

Abstract
Pain-related anxiety, defined as fear of pain and pain-related sensations, is a transdiagnostic individual difference factor associated with pain-related problems, addictive disorders, and physical impairment among nonclinical and clinical populations. Pain-related anxiety is most commonly measured using the Pain Anxiety Symptoms Scale-20 (PASS-20). It was hypothesized that the data would provide evidence for a higher order PASS-20 factor structure and this structure would be invariant across race/ethnicity and sex. Therefore, the current study examined measurement invariance of the PASS-20 across a large (n = 3,455) diverse sample (Mage = 21.49, SD = 4.24, 73.7% female, 33.5% Hispanic, 29.3% Asian/Pacific Islander, 22.4% White, and 14.8% Black/African American) of young adults. Results supported measurement invariance across all race/ethnicity and sex groups for the PASS-20 total score, but results were inconsistent for the lower order factors. The PASS-20 total score showed good internal consistency and evidence of convergent and divergent validity with established constructs. These results provide empirical support only for the higher order factor structure of the PASS-20 and support its use across race/ethnicity and sex. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

PMID: 32463267 [PubMed - indexed for MEDLINE]

Pay-it-forward strategy to enhance uptake of dual gonorrhea and chlamydia testing among men who have sex with men in China: a pragmatic, quasi-experimental study.

Lancet Infect Dis. 2019 01;19(1):76-82

Authors: Li KT, Tang W, Wu D, Huang W, Wu F, Lee A, Feng H, Pan SW, Han L, Mak V, Yang L, Tucker JD

Abstract
BACKGROUND: Chinese men who have sex with men (MSM) rarely receive gonorrhoea and chlamydia testing. The purpose of this pilot study was to evaluate a pay-it-forward strategy to increase uptake of gonorrhoea and chlamydia testing among MSM.
METHODS: We performed a quasi-experimental pragmatic study to compare a pay-it-forward model with standard of care at two HIV testing sites for MSM in Guangzhou, China: an STD clinic for MSM and a local MSM community-based organisation. All men who arrived at the STD clinic or the community-based organisation were invited to participate. In the pay-it-forward programme, men were offered free gonorrhoea and chlamydia testing and given the option of donating money toward testing for future participants. In the standard-of-care group, men were offered gonorrhoea and chlamydia testing at the standard patient price of ¥150 (about US$21·50). The pay-it-forward programme was implemented for 3 months, after which both sites switched to standard of care offering dual testing for 3 months. The primary outcome for this study was uptake of dual gonorrhoea and chlamydia testing, which we compared using χ2 test and logistic regression, reported as crude odds ratios (cOR) and adjusted odds ratios (aOR), by adjusting for nationality, marital status, income, and site of testing.
FINDINGS: The pay-it-forward programme took place from Dec 2, 2017, to Feb 3, 2018, and the standard-of-care control took place from March 11, 2018, to May 1, 2018. 408 men were included in this study. 203 men were offered pay-it-forward, and 205 were offered standard of care. Overall, 109 (54%) of 203 men in the pay-it-forward group and 12 (6%) of 205 men in the standard-of-care group received gonorrhoea and chlamydia testing (cOR 18·65, 9·78-35·54; p<0·0001; aOR 19·73, 95% CI 10·02-38·85; p<0·0001). Of all 121 men who tested, this was the first gonorrhoea test for 97 (80%) men and the first chlamydia test for 104 (86%) men. Five (4%) of these 121 men were diagnosed with gonorrhoea and 15 (12%) were diagnosed with chlamydia. 97 (89%) of 109 men who received testing in the pay-it-forward group donated some money toward testing for future participants.
INTERPRETATION: Pay-it-forward might be a sustainable model for expanding integrated HIV testing services among MSM in China.
FUNDING: National Institutes of Health, Southern Medical University Dermatology Hospital, Doris Duke Charitable Foundation.

PMID: 30587296 [PubMed - indexed for MEDLINE]

Ovarian Cancer Exosomes Trigger Differential Biophysical Response in Tumor-Derived Fibroblasts.

Sci Rep. 2020 05 26;10(1):8686

Authors: Lee AH, Ghosh D, Quach N, Schroeder D, Dawson MR

Abstract
Exosomes are cell-secreted microvesicles that play important roles in epithelial ovarian cancer (EOC) progression, as they are constantly secreted into ascites fluids. While cells spontaneously release exosomes, alterations in intracellular calcium or extracellular pH can release additional exosomes. Yet, little is known about how these exosomes compare to those that are continuously released without stimulation and how they mediate cellular activities important in cancer progression. Here, we demonstrate that chelation of extracellular calcium leads to release of chelation-induced exosomes (CI-exosomes) from OVCAR-3 EOC cells. CI-exosomes display a unique miRNA profile compared to naturally secreted exosomes (SEC-exosomes). Furthermore, treatment with CI- and SEC-exosomes leads to differential biophysical and functional changes including, adhesion and migration in EOC-derived fibroblasts that suggest the development of a malignant tumor microenvironment. This result highlights how tumor environmental factors contribute to heterogeneity in exosome populations and how different exosome populations mediate diversity in stromal cell behavior.

PMID: 32457479 [PubMed - indexed for MEDLINE]

Loneliness and its Association with Health Behaviors in People with a Lived Experience of a Serious Mental Illness.

Psychiatr Q. 2020 May 26;:

Authors: Fortuna KL, Ferron J, Bianco CL, Santos MM, Williams A, Williams M, Mois G, Pratt SI

Abstract
To explore the association between loneliness and efficacy to engage in health behaviors that are known to reduce the risk of early mortality in people with serious mental illness (SMI). This secondary data analysis was based on a cross-sectional study of 113 participants with SMI residing in New Hampshire. Ordinary Least Squares regressions were used to examine bivariate relationships between variables of interest. Participants had a primary mental health diagnosis of major depressive disorder (37.2%), schizophrenia spectrum disorder (28.3%), bipolar disorder (29.2%), or posttraumatic stress disorder (5.3%). High levels of loneliness were associated with low levels of self-efficacy to manage chronic diseases (p = 0.0001), as well as low levels of self-efficacy to manage psychological well-being (R2 = .31; F = 9.49, p = 0.0001; RMSE = 1.66). Loneliness may serve as a barrier to healthy behaviors, and thus, contribute to early mortality among people with SMI. The growing body of literature that demonstrates the importance of addressing loneliness in people with SMI should stimulate policymakers and researchers to target loneliness as a mechanism to address early mortality in people with SMI.

PMID: 32458342 [PubMed - as supplied by publisher]