Using What We Know about Couples in the Context of Chronic Pain to Push for Continued Progress: Commentary on Vivekanantham and Colleagues

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/106957/1/pme12444.pd

Differential transcript expression between the microfilariae of the filarial nematodes, Brugia malayi and B. pahangi

<p>Abstract</p> <p>Background</p> <p><it>Brugia malayi </it>and <it>B. pahangi </it>are two closely related nematodes that cause filariasis in humans and animals. However, <it>B. pahangi </it>microfilariae are able to develop in and be transmitted by the mosquito, <it>Armigeres subalbatus</it>, whereas most <it>B. malayi </it>are rapidly melanized and destroyed within the mosquito hemocoel. A cross-species microarray analysis employing the <it>B. malayi </it>V2 array was carried out to determine the transcriptional differences between <it>B. malayi </it>and <it>B. pahangi </it>microfilariae with similar age distribution.</p> <p>Results</p> <p>Following microarray data analysis, a list of preferentially expressed genes in both microfilariae species was generated with a false discovery rate estimate of 5% and a signal intensity ratio of 2 or higher in either species. A total of 308 probes were preferentially expressed in both species with 149 probes, representing 123 genes, in <it>B. pahangi </it>microfilariae and 159 probes, representing 107 genes, in <it>B. malayi </it>microfilariae. In <it>B. pahangi</it>, there were 76 (62%) up-regulated transcripts that coded for known proteins that mapped into the KEGG pathway compared to 61 (57%) transcripts in <it>B. malayi </it>microfilariae. The remaining 47 (38%) transcripts in <it>B. pahangi </it>and 46 (43%) transcripts in <it>B. malayi </it>microfilariae were comprised almost entirely of hypothetical genes of unknown function. Twenty-seven of the transcripts in <it>B. pahangi </it>microfilariae coded for proteins that associate with the secretory pathway compared to thirty-nine in <it>B. malayi </it>microfilariae. The data obtained from real-time PCR analysis of ten genes selected from the microarray list of preferentially expressed genes showed good concordance with the microarray data, indicating that the microarray data were reproducible.</p> <p>Conclusion</p> <p>In this study, we identified gene transcripts that were preferentially expressed in the microfilariae of <it>B. pahangi </it>and <it>B. malayi</it>, some of which coded for known immunomodulatory proteins. These comparative transcriptome data will be of interest to researchers keen on understanding the inherent differences, at the molecular level, between <it>B. malayi </it>and <it>B. pahangi </it>microfilariae especially because these microfilariae are capable of surviving in the same vertebrate host but elicit different immune response outcomes in the mosquito, <it>Ar. subalbatus</it>.</p

Microarray and EST database estimates of mRNA expression levels differ: The protein length versus expression curve for C. elegans

BACKGROUND: Various methods for estimating protein expression levels are known. The level of correlation between these methods is only fair, and systematic biases in each of the methods cannot be ruled out. We here investigate systematic biases in the estimation of gene expression rates from microarray data and from abundance within the Expressed Sequence Tag (EST) database. We suggest that length is a significant factor in biases to measured gene expression rates. As a specific example of the importance of the bias of expression rate with length, we address the following evolutionary question: Does the average C. elegans protein length increase or decrease with expression level? Two different answers to this question have been reported in the literature, one method using expression levels estimated by abundance within the EST database and another using microarrays. We have investigated this issue by constructing the full protein length versus expression curve for C. elegans, using both methods for estimating expression levels. RESULTS: The microarray data show a monotonic decrease of length with expression level, whereas the abundance within the EST database data show a non-monotonic behavior. Furthermore, the ratio of the expression level estimated by the EST database to that measured by microarrays is not constant, but rather systematically biased with gene length. CONCLUSIONS: It is suggested that the length bias may lie primarily in the abundance within the EST database method, being not ameliorated by internal standards as it is in the microarray data, and that this bias should be removed before data interpretation. When this is done, both the microarray and the abundance within the EST database give a monotonic decrease of spliced length with expression level, and the correlation between the EST and microarray data becomes larger. We suggest that standard RNA controls be used to normalize for length bias in any method that measures expression

Comparison of Four Fitbit and Jawbone Activity Monitors with a Research-Grade ActiGraph Accelerometer for Estimating Physical Activity and Energy Expenditure

Background/aim Consumer-based physical activity (PA) monitors have become popular tools to track PA behaviours. Currently, little is known about the validity of the measurements provided by consumer monitors. We aimed to compare measures of steps, energy expenditure (EE) and active minutes of four consumer monitors with one research-grade accelerometer within a semistructured protocol. Methods Thirty men and women (18–80 years old) wore Fitbit One (worn at the waist), Fitbit Zip (waist), Fitbit Flex (wrist), Jawbone UP24 (wrist) and one waist-worn research-grade accelerometer (ActiGraph) while participating in an 80 min protocol. A validated EE prediction equation and active minute cut-points were applied to ActiGraph data. Criterion measures were assessed using direct observation (step count) and portable metabolic analyser (EE, active minutes). A repeated measures analysis of variance (ANOVA) was used to compare differences between consumer monitors, ActiGraph, and criterion measures. Similarly, a repeated measures ANOVA was applied to a subgroup of subjects who didn’t cycle. Results Participants took 3321±571 steps, had 28±6 active min and expended 294±56 kcal based on criterion measures. Comparatively, all monitors underestimated steps and EE by 13%–32% (p\u3c0.01); additionally the Fitbit Flex, UP24, and ActiGraph underestimated active minutes by 35%–65% (p\u3c0.05). Underestimations of PA and EE variables were found to be similar in the subgroup analysis. Conclusion Consumer monitors had similar accuracy for PA assessment as the ActiGraph, which suggests that consumer monitors may serve to track personal PA behaviours and EE. However, due to discrepancies among monitors, individuals should be cautious when comparing relative and absolute differences in PA values obtained using different monitors

Complete genome sequence of Liberibacter crescens BT-1

Liberibacter crescens BT-1, a Gram-negative, rod-shaped bacterial isolate, was previously recovered from mountain papaya to gain insight on Huanglongbing (HLB) and Zebra Chip (ZC) diseases. The genome of BT-1 was sequenced at the Interdisciplinary Center for Biotechnology Research (ICBR) at the University of Florida. A finished assembly and annotation yielded one chromosome with a length of 1,504,659 bp and a G+C content of 35.4%. Comparison to other species in the Liberibacter genus, L. crescens has many more genes in thiamine and essential amino acid biosynthesis. This likely explains why L. crescens BT-1 is culturable while the known Liberibacter strains have not yet been cultured. Similar to Candidatus L. asiaticus psy62, the L. crescens BT-1 genome contains two prophage regions

MicroRNA-203 predicts human survival after resection of colorectal liver metastasis.

BackgroundResection of colorectal liver metastasis (CRLM) can be curative. Predicting which patients may benefit from resection, however, remains challenging. Some microRNAs (miRNAs) become deregulated in cancers and contribute to cancer progression. We hypothesized that miRNA expression can serve as a prognostic marker of survival after CRLM resection.ResultsMiR-203 was significantly overexpressed in tumors of short-term survivors compared to long-term survivors. R1/R2 margin status and high clinical risk score (CRS) were also significantly associated with short-term survival (both p = 0.001). After adjusting for these variables, higher miR-203 expression remained an independent predictor of shorter survival (p = 0.010). In the serum cohort, high CRS and KRAS mutation were significantly associated with short-term survival (p = 0.005 and p = 0.026, respectively). After adjusting for CRS and KRAS status, short-term survivors were found to have significantly higher miR-203 levels (p = 0.016 and p = 0.033, respectively).Materials and methodsWe employed next-generation sequencing of small-RNAs to profile miRNAs in solid tumors obtained from 38 patients who underwent hepatectomy for CRLM. To validate, quantitative reverse-transcription polymerase chain reaction (qRT-PCR) was performed on 91 tumor samples and 46 preoperative serum samples.ConclusionsAfter CRLM resection, short-term survivors exhibited significantly higher miR-203 levels relative to long-term survivors. MiR-203 may serve as a prognostic biomarker and its prognostic capacity warrants further investigation

Safety of Same and Next Day Discharge Following Revision Hip and Knee Arthroplasty Using Modern Perioperative Protocols

Introduction: Advances in perioperative care have enabled early discharge and outpatient primary total joint arthroplasty (TJA). However, the safety of early discharge after revision TJA (rTJA) remains unknown and the COVID-19 pandemic will force decreased hospitalization. This study compared 90-day outcomes in patients undergoing aseptic rTJA discharged the same or next day (early) to those discharged two or three days postoperatively (later). Methods: 530 aseptic rTJAs performed at a single tertiary referral center (12/5/2011-12/30/2019) were identified. Early and later discharge patients were matched as closely as possible on procedure type, sex, ASA-PS classification, age, and BMI. All patients were optimized using modern perioperative protocols. The rate of 90-day ED visits and hospital admissions was compared between groups. Results: 183 early discharge rTJAs (54 hips, 129 knees) in 178 patients were matched to 183 later discharge rTJAs (71 hips, 112 knees) in 165 patients. 62% of the sample was female, with an overall average age and BMI of 63±9.9 (range: 18-92) years and 32±6.9 (range: 18-58) kg/m2. There was no statistical difference in 90-day ED visit rates between early (6/178, 3.4%) and later (11/165, 6.7%) discharge patients (p=0.214). 90-day hospital admission rates for early (7/178, 3.9%) and later (4/165, 2.4%) did not differ (p=0.545) Conclusions: Using modern perioperative protocols and with appropriate patient selection, early discharge following aseptic rTJA does not increase 90-day readmissions or ED visits. As hospital inpatient capacity remains limited due to COVID-19, select rTJA patients may discharge home the same or next day to preserve hospital beds and resources for more critical medically related illness

Is There Benefit in Keeping Early Discharge Patients Overnight After Total Joint Arthroplasty?

Introduction: In recent years, cost containment relative to patent safety and quality of care for total joint arthroplasty (TJA) has been a key focus for the Centers for Medicare and Medicaid Services (CMS) spawning significant research and programmatic change, including a move toward early discharge and outpatient TJA. TJA outpatients receive few, if any, medical interventions prior to discharge, but the type and quantity of medical interventions provided for TJA patients who stay overnight in the hospital is unknown. This study quantified the nature, frequency, and outcome of interventions occurring overnight after primary TJA. Methods: 1,725 consecutive primary unilateral TJAs performed between 2012 and 2017 by a single surgeon in a rapid-discharge program, managed by a perioperative internal medicine specialist, were reviewed. Medical records were examined for diagnostic tests, treatments, and procedures performed, results of interventions, and all-cause readmissions. Recorded interventions included any that varied from the preoperative treatment plan, were beyond standard-of-care, and could not be completed at home. Results: 759 patients were discharged on postoperative day one. 84% (641/759) received no medical interventions during their overnight hospital stay. Twelve (1.6%) received diagnostic tests, 90 (11.9%) received treatments, and 29 (3.8%) received procedures. 92% (11/12) of diagnostic tests were negative, 66% of 100 treatments in 90 patients were intravenous fluids for oliguria or hypotension, and all procedures were in/out catheterizations for urinary retention. 90-day all cause readmission rates were similar in patients who received (2.5%) and did not receive (3.3%) a clinical intervention. Conclusion: The majority of patients received no overnight interventions, suggesting unnecessary costly hospitalization. The most common issues addressed were oliguria, urinary retention, and hypotension. Protocols to prevent these conditions would facilitate outpatient TJA, improve patient safety, and reduce costs.This research was supported by the Indiana University Health – Indiana School of Medicine Strategic Research Initiative

T Cell Receptor Immunotherapy Drives Human Immunodeficiency Virus Evolution in Humanized Mice

Effective CD8+ T cell responses targeted to the KK10 epitope of HIV presented by HLA-B*27:05, a protective HLA allele, correlate with the ability to control infection without antiretroviral therapy (ART). Here, we report an immunotherapy approach using two B*27:05-KK10-specific T Cell Receptors (TCRs) isolated from HIV controllers. Immunocompromised mice engrafted with human Hematopoietic Stem/Progenitor Cells (HSPCs) encoding for the TCRs showed differentiation into functionally active engineered T cells. Following infection with HIV, both TCRs showed sustained, albeit modest, viral suppression over 32 weeks, accompanied by a concomitant increase in CD4+ T cells. Sequencing of viral quasi-species from the plasma of infected mice demonstrated clear evidence for viral evolution under selection pressure from the TCRs. The most commonly observed mutation in the KK10 epitope was L6M, which preserved viral fitness but showed attenuated recognition by the TCRs. These studies show that TCR-immunotherapy was able to suppress HIV infection long-term while driving HIV evolution in humanized mice

Assessing awareness and attitudes of healthcare professionals on the use of biosimilar medicines: A survey of physicians and pharmacists in Ireland

Increasing numbers of biosimilar medicines are becoming available. The objective of this survey was to assess awareness of and attitudes to biosimilars amongst physicians (medical specialists and General Practitioners (GPs)) and community pharmacists in Ireland. Physicians were invited to complete an online questionnaire during April and May 2016. Community pharmacists received a postal questionnaire in August 2015. Responses from 102 medical specialists, 253 GPs and 125 community pharmacists were analysed. The majority of medical specialists (85%) and pharmacists (77%) claimed to be either very familiar or familiar with the term biosimilar, whereas many GPs (60%) were unable to define or had never heard of the term. One in five (21%) healthcare professionals responded that biosimilars were the same as generic medicines. The majority of medical specialists opposed pharmacist-led substitution of biological medicines but some thought it could be appropriate if agreed with the clinician in advance. Medical specialists who prescribe biosimilars (n = 43) were more likely to do so on treatment initiation (67%), than switch a patient from an originator medicine to a biosimilar (28%). The findings will aid the design of educational initiatives for healthcare professionals and highlight attitudes of healthcare professionals to biosimilars, so informing regulators, policy makers and industry