• A statistical analysis of vaccine-adverse event data

      Ren, J.-J.; Sun, T.; He, Y. (BioMed Central Ltd., 2019)
      Background: Vaccination has been one of the most successful public health interventions to date, and the U.S. FDA/CDC Vaccine Adverse Event Reporting System (VAERS) currently contains more than 500,000 reports for post-vaccination adverse events that occur after the administration of vaccines licensed in the United States. The VAERS dataset is huge, contains very large dimension nominal variables, and is complex due to multiple listing of vaccines and adverse symptoms in a single report. So far there has not been any statistical analysis conducted in attempting to identify the cross-board patterns on how all reported adverse symptoms are related to the vaccines. Methods: For studies of the relationship between vaccines and reported adverse events, we consider a partial VAERS dataset which includes all reports filed over a period of 24 years between 1990-2013. We propose a neighboring method to process this dataset for dealing with the complications caused by multiple listing of vaccines and adverse symptoms in a single report. Then, the combined approaches based on our neighboring method and novel utilization of data visualization techniques are employed to analyze the large dimension dataset for characterization of the cross-board patterns of the relations between all reported vaccines and events. Results: The results of our analysis indicate that those events or symptoms with overall high occurrence frequencies are positively correlated, and those most frequently occurred adverse symptoms are mostly uncorrelated or negatively correlated under different bacteria vaccines, but they are in many cases positively correlated under different virus vaccines, especially under flu vaccines. No particular patterns are shown under live vs. inactive vaccines. Conclusions: This article identifies certain cross-board patterns of the relationship between the vaccines and the reported adverse events or symptoms. This helps for better understanding the VAERS data, and provides a useful starting point for the development of statistical models and procedures to further analyze the VAERS data. Copyright 2019 The Author(s).
    • Protein-based vehicles for biomimetic RNAi delivery

      Pottash, A.E.; Kuffner, C.; Noonan-Shueh, M. (BioMed Central Ltd., 2019)
      Broad translational success of RNA interference (RNAi) technology depends on the development of effective delivery approaches. To that end, researchers have developed a variety of strategies, including chemical modification of RNA, viral and non-viral transfection approaches, and incorporation with delivery vehicles such as polymer- and lipid-based nanoparticles, engineered and native proteins, extracellular vesicles (EVs), and others. Among these, EVs and protein-based vehicles stand out as biomimetically-inspired approaches, as both proteins (e.g. Apolipoprotein A-1, Argonaute 2, and Arc) and EVs mediate intercellular RNA transfer physiologically. Proteins specifically offer significant therapeutic potential due to their biophysical and biochemical properties as well as their ability to facilitate and tolerate manipulation; these characteristics have made proteins highly successful translational therapeutic molecules in the last two decades. This review covers engineered protein vehicles for RNAi delivery along with what is currently known about naturally-occurring extracellular RNA carriers towards uncovering design rules that will inform future engineering of protein-based vehicles. Copyright 2019 The Author(s).
    • 2017 NIH-wide workshop report on "the Human Microbiome: Emerging Themes at the Horizon of the 21st Century"

      Huttenhower, C.; Buck, G.A.; Snyder, M.P. (BioMed Central Ltd., 2019)
      The National Institutes of Health (NIH) organized a three-day human microbiome research workshop, August 16-18, 2017, to highlight the accomplishments of the 10-year Human Microbiome Project program, the outcomes of the investments made by the 21 NIH Institutes and Centers which now fund this area, and the technical challenges and knowledge gaps which will need to be addressed in order for this field to advance over the next 10 years. This report summarizes the key points in the talks, round table discussions, and Joint Agency Panel from this workshop. Copyright 2019 The Author(s).
    • Functional magnetic resonance imaging biomarkers predicting cognitive progression in Parkinson disease: protocol for a prospective longitudinal cohort study

      Hanna-Pladdy, B.; Gullapalli, R.; Chen, H. (Journal of Medical Internet Research, 2019)
      Background: Cardinal features of Parkinson disease (PD) are motor symptoms, but nonmotor features such as mild cognitive impairment (MCI) are common early in the disease process. MCI can progress and convert to dementia in advanced stages, creating significant disability and reduced quality of life. The primary pathological substrate for cognitive decline in PD is unclear, and there are no reliable biomarkers predicting the risk of conversion to dementia. A subgroup of PD patients with visual hallucinations may display more rapid conversion to dementia, suggesting that regional markers of visuoperceptual dysfunction may be sensitive to pathologic density in posterior cortical regions. Objective: The purpose of this project is to characterize PD-MCI and evaluate the utility of genetic and neuroimaging biomarkers in predicting cognitive outcomes with a prospective longitudinal study. We will evaluate whether accelerated cognitive progression may be reflected in biomarkers of early posterior cortical changes reflective of α-synuclein deposition. Methods: We will evaluate a cohort of early-stage PD patients with the following methods to predict cognitive progression: (1) serial neuropsychological evaluations including detailed visuoperceptual functioning across 4 years; (2) genetic analysis of SNCA (α-synuclein), MAPT (microtubule-associated tau), and APOE (apolipoprotein E); (3) an event-related functional magnetic resonance imaging paradigm of object recognition memory; and (4) anatomical and regional brain activation changes (resting-state functional magnetic resonance imaging) across 4 years. Results: The project received funding from the National Institutes of Health in August 2017, and data collection began in February 2018. Enrollment is ongoing, and subjects will be evaluated annually for 4 years extended across a 5-year project including data analysis and image processing. Conclusions: Cognitive, genetic, and structural and functional magnetic resonance imaging will characterize neural network changes predictive of cognitive progression in PD across 4 years. Identification of biomarkers with sensitivity for early prediction and estimation of risk for conversion to dementia in PD will pave the way for effective intervention with neuroprotective therapies during the critical stage when treatment can have the greatest impact.
    • An atypical pulmonary fibrosis is associated with co-inheritance of mutations in the calcium binding protein genes S100A3 and S100A13

      Al-Mutairy, E.A.; Luzina, I.G.; Al-Mohanna, F. (European Respiratory Society, 2019)
      BACKGROUND: Pulmonary fibrosis is one of the leading indications for lung transplantation. The disease, which is of unknown aetiology, can be progressive, resulting in distortion of the extracellular matrix (ECM), inflammation, fibrosis and eventual death. METHODS: 13 patients born to consanguineous parents from two unrelated families presenting with interstitial lung disease were clinically investigated. Nine patients developed respiratory failure and subsequently died. Molecular genetic investigations were performed on patients' whole blood or archived tissues, and cell biological investigations were performed on patient-derived fibroblasts. RESULTS: The combination of a unique pattern of early-onset lung fibrosis (at 12-15?years old) with distinctive radiological findings, including 1) traction bronchiectasis, 2) intralobular septal thickening, 3) shrinkage of the secondary pulmonary lobules mainly around the bronchovascular bundles and 4) early type 2 respiratory failure (elevated blood carbon dioxide levels), represents a novel clinical subtype of familial pulmonary fibrosis. Molecular genetic investigation of families revealed a hypomorphic variant in S100A3 and a novel truncating mutation in S100A13, both segregating with the disease in an autosomal recessive manner. Family members that were either heterozygous carriers or wild-type normal for both variants were unaffected. Analysis of patient-derived fibroblasts demonstrated significantly reduced S100A3 and S100A13 expression. Further analysis demonstrated aberrant intracellular calcium homeostasis, mitochondrial dysregulation and differential expression of ECM components. CONCLUSION: Our data demonstrate that digenic inheritance of mutations in S100A3 and S100A13 underlie the pathophysiology of pulmonary fibrosis associated with a significant reduction of both proteins, which suggests a calcium-dependent therapeutic approach for management of the disease.
    • Resource utilization in non-academic emergency departments with advanced practice providers

      Aledhaim, A.; Walker, A.; Vesselinov, R.; Hirshon, J.M.; Pimentel, L. (eScholarship, 2019)
      Introduction: Advanced practice providers (APP), including physicians' assistants and nurse practitioners, have been increasingly incorporated into emergency department (ED) staffing over the past decade. There is scant literature examining resource utilization and the cost benefit of having APPs in the ED. The objectives of this study were to compare resource utilization in EDs that use APPs in their staffing model with those that do not and to estimate costs associated with the utilized resources. Methods: In this five-year retrospective secondary data analysis of the Emergency Department Benchmarking Alliance (EDBA), we compared resource utilization rates in EDs with and without APPs in non-academic EDs. Primary outcomes were hospital admission and use of computed tomography (CT), radiography, ultrasound, and magnetic resonance imaging (MRI). Costs were estimated using the 2014 physician fee schedule and inpatient payments from the Centers for Medicare and Medicaid Services. We measured outcomes as rates per 100 visits. Data were analyzed using a mixed linear model with repeated measures, adjusted for annual volume, patient acuity, and attending hours. We used the adjusted net difference to project utilization costs between the two groups per 1000 visits. Results: Of the 1054 EDs included in this study, 79% employed APPs. Relative to EDs without APPs, EDs staffing APPs had higher resource utilization rates (use per 100 visits): 3.0 more admissions (95% confidence interval [CI], 2.0�4.1), 1.7 more CTs (95% CI, 0.2�3.1), 4.5 more radiographs (95% CI, 2.2�6.9), and 1.0 more ultrasound (95% CI, 0.3�1.7) but comparable MRI use 0.1 (95% CI, -0.2�0.3). Projected costs of these differences varied among the resource utilized. Compared to EDs without APPs, EDs with APPs were estimated to have 30.4 more admissions per 1000 visits, which could accrue $414,717 in utilization costs. Conclusion: EDs staffing APPs were associated with modest increases in resource utilization as measured by admissions and imaging studies. Copyright 2019 Aledhaim et al.
    • Sexual dimorphism of mitochondrial function in the hypoxic Guinea pig placenta

      Song, H.; Telugu, B.P.; Thompson, L.P. (Oxford University Press, 2019)
      Placental hypoxia can stimulate oxidative stress and mitochondrial dysfunction reducing placental efficiency and inducing fetal growth restriction (FGR). We hypothesized that chronic hypoxia inhibits mitochondrial function in the placenta as an underlying cause of cellular mechanisms contributing to FGR. Pregnant guinea pigs were exposed to either normoxia (NMX) or hypoxia (HPX; 10.5% O2) at 25 day gestation until term (65 day). Guinea pigs were anesthetized, and fetuses and placentas were excised at either mid (40 day) or late gestation (64 day), weighed, and placental tissue stored at −80°C until assayed. Mitochondrial DNA content, protein expression of respiratory Complexes I-V, and nitration and activity rates of Complexes I and IV were measured in NMX and HPX male (N = 6 in each treatment) and female (N = 6 in each treatment) placentas. Mitochondrial density was not altered by HPX in either mid- or late-term placentas. In mid gestation, HPX slightly increased expression of Complexes I-III and V in male placentas only, but had no effect on either Complex I or IV activity rates or nitrotyrosine expression. In late gestation, HPX significantly decreased CI/CIV activity rates and increased CI/CIV nitration in male but not female placentas exhibiting a sexual dimorphism. Complex I-V expression was reduced from mid to late gestation in both male and female placentas regardless of treatment. We conclude that chronic HPX decreases mitochondrial function by inhibiting Complex I/IV activity via increased peroxynitrite in a sex-related manner. Further, there may be a progressive decrease in energy metabolism of placental cell types with gestation that increases the vulnerability of placental function to intrauterine stress. Copyright The Author(s) 2018.
    • Risk of Mortality in Individuals with Hip Fracture and Traumatic Brain Injury

      Albrecht, J.S.; Al Kibria, G.; Gruber-Baldini, A. (Blackwell Publishing Inc., 2019)
      Objectives: To estimate the prevalence of diagnosed traumatic brain injury (TBI) in individuals hospitalized with hip fracture and examine its association with all-cause mortality. Design: Nested cohort study. Setting: National sample of Medicare beneficiaries from 2006 to 2010. Participants: Beneficiaries aged 65 and older hospitalized with hip fracture. Measurements: TBI at the time of hip fracture was defined using International Classification of Diseases, Ninth Revision, Clinical Modification codes. The main outcome was all-cause mortality during follow-up. Results: Prevalence of TBI in individuals with hip fracture was 2.7%. Absolute risk of mortality attributable to TBI in individuals with hip fracture was 15/100 person-years. TBI was significantly associated with risk of death in multivariable analysis (hazard ratio=1.24, 95% confidence interval=1.14-1.35). Conclusion: TBI was associated with greater risk of mortality in individuals with hip fracture. Practitioners should consider evaluating for presence of TBI in this vulnerable population. J Am Geriatr Soc 67:124-127, 2019. Copyright 2018, the Authors Journal compilation.
    • Ethical considerations in conducting surgical research in severe complicated intra-abdominal sepsis

      Doig, C.J.; Page, S.A.; Diaz, J.J. (BioMed Central Ltd., 2019)
      Background: Severe complicated intra-abdominal sepsis (SCIAS) has high mortality, thought due in part to progressive bio-mediator generation, systemic inflammation, and multiple organ failure. Treatment includes early antibiotics and operative source control. At surgery, open abdomen management with negative-peritoneal-pressure therapy (NPPT) has been hypothesized to mitigate MOF and death, although clinical equipoise for this operative approach exists. The Closed or Open after Laparotomy (COOL) study (https://clinicaltrials.gov/ct2/show/NCT03163095) will prospectively randomize eligible patients intra-operatively to formal abdominal closure or OA with NPTT. We review the ethical basis for conducting research in SCIAS. Main body: Research in critically ill incapacitated patients is important to advance care. Conducting research among SCIAS is complicated due to the severity of illness including delirium, need for emergent interventions, diagnostic criteria confirmed only at laparotomy, and obtundation from anaesthesia. In other circumstances involving critically ill patients, clinical experts have worked closely with ethicists to apply principles that balance the rights of patients whilst simultaneously permitting inclusion in research. In Canada, the Tri-Council Policy Statement-2 (TCPS-2) describes six criteria that permit study enrollment and randomization in such situations: (a) serious threat to the prospective participant requires immediate intervention; (b) either no standard efficacious care exists or the research offers realistic possibility of direct benefit; (c) risks are not greater than that involved in standard care or are clearly justified by prospect for direct benefits; (d) prospective participant is unconscious or lacks capacity to understand the complexities of the research; (e) third-party authorization cannot be secured in sufficient time; and (f) no relevant prior directives are known to exist that preclude participation. TCPS-2 criteria are in principle not dissimilar to other (inter)national criteria. The COOL study will use waiver of consent to initiate enrollment and randomization, followed by surrogate or proxy consent, and finally delayed informed consent in subjects that survive and regain capacity. Conclusions: A delayed consent mechanism is a practical and ethical solution to challenges in research in SCIAS. The ultimate goal of consent is to balance respect for patient participants and to permit participation in new trials with a reasonable opportunity for improved outcome and minimal risk of harm. Copyright 2019 The Author(s).
    • Association of Glucose Concentrations at Hospital Discharge With Readmissions and Mortality: A Nationwide Cohort Study

      Spanakis, E.K.; Umpierrez, G.E.; Siddiqui, T.; Zhan, M.; Snitker, S.; Fink, J.C.; Sorkin, J.D. (Oxford Academic, 2019)
      CONTEXT: Low blood glucose concentrations during the discharge day may affect 30-day readmission and posthospital discharge mortality rates. OBJECTIVE: To investigate whether patients with diabetes and low glucose values during the last day of hospitalization are at increased risk of readmission or mortality. DESIGN AND OUTCOMES: Minimum point of care glucose values were collected during the last 24 hours of hospitalization. We used adjusted rates of 30-day readmission rate, 30-, 90-, and 180-day mortality rates, and combined 30-day readmission/mortality rate to identify minimum glucose thresholds above which patients can be safely discharged. PATIENTS AND SETTING: Nationwide cohort study including 843,978 admissions of patients with diabetes at the Veteran Affairs hospitals 14 years. RESULTS: The rate ratios (RRs) increased progressively for all five outcomes as the minimum glucose concentrations progressively decreased below the 90 to 99 mg/dL category, compared with the 100 to 109 mg/dL category: 30-day readmission RR, 1.01 to 1.45; 30-day readmission/mortality RR, 1.01 to 1.71; 30-day mortality RR, 0.99 to 5.82; 90-day mortality RR, 1.01 to 2.40; 180-day mortality RR, 1.03 to 1.91. Patients with diabetes experienced greater 30-day readmission rates, 30-, 90- and 180-day postdischarge mortality rates, and higher combined 30-day readmission/mortality rates, with glucose levels <92.9 mg/dL, <45.2 mg/dL, 65.8 mg/dL, 67.3 mg/dL, and <87.2 mg/dL, respectively. CONCLUSION: Patients with diabetes who had hypoglycemia or near-normal glucose values during the last day of hospitalization had higher rates of 30-day readmission and postdischarge mortality.
    • Clinical Practice Guideline: Sudden Hearing Loss (Update)

      Chandrasekhar, S.S.; Tsai, Do, B.S.; Bontempo, L.J. (SAGE Publications Inc., 2019)
      Objective: Sudden hearing loss is a frightening symptom that often prompts an urgent or emergent visit to a health care provider. It is frequently but not universally accompanied by tinnitus and/or vertigo. Sudden sensorineural hearing loss affects 5 to 27 per 100,000 people annually, with about 66,000 new cases per year in the United States. This guideline update provides evidence-based recommendations for the diagnosis, management, and follow-up of patients who present with sudden hearing loss. It focuses on sudden sensorineural hearing loss in adult patients aged ?18 years and primarily on those with idiopathic sudden sensorineural hearing loss. Prompt recognition and management of sudden sensorineural hearing loss may improve hearing recovery and patient quality of life. The guideline update is intended for all clinicians who diagnose or manage adult patients who present with sudden hearing loss. Purpose: The purpose of this guideline update is to provide clinicians with evidence-based recommendations in evaluating patients with sudden hearing loss and sudden sensorineural hearing loss, with particular emphasis on managing idiopathic sudden sensorineural hearing loss. The guideline update group recognized that patients enter the health care system with sudden hearing loss as a nonspecific primary complaint. Therefore, the initial recommendations of this guideline update address distinguishing sensorineural hearing loss from conductive hearing loss at the time of presentation with hearing loss. They also clarify the need to identify rare, nonidiopathic sudden sensorineural hearing loss to help separate those patients from those with idiopathic sudden sensorineural hearing loss, who are the target population for the therapeutic interventions that make up the bulk of the guideline update. By focusing on opportunities for quality improvement, this guideline should improve diagnostic accuracy, facilitate prompt intervention, decrease variations in management, reduce unnecessary tests and imaging procedures, and improve hearing and rehabilitative outcomes for affected patients. Methods: Consistent with the American Academy of Otolaryngology�Head and Neck Surgery Foundation�s �Clinical Practice Guideline Development Manual, Third Edition� (Rosenfeld et al. Otolaryngol Head Neck Surg. 2013;148[1]:S1-S55), the guideline update group was convened with representation from the disciplines of otolaryngology�head and neck surgery, otology, neurotology, family medicine, audiology, emergency medicine, neurology, radiology, advanced practice nursing, and consumer advocacy. A systematic review of the literature was performed, and the prior clinical practice guideline on sudden hearing loss was reviewed in detail. Key Action Statements (KASs) were updated with new literature, and evidence profiles were brought up to the current standard. Research needs identified in the original clinical practice guideline and data addressing them were reviewed. Current research needs were identified and delineated. Results: The guideline update group made strong recommendations for the following: (KAS 1) Clinicians should distinguish sensorineural hearing loss from conductive hearing loss when a patient first presents with sudden hearing loss.
    • Characterization of CD44 intracellular domain interaction with RUNX2 in PC3 human prostate cancer cells

      Senbanjo, L.T.; Aljohani, H.; Majumdar, S.; Chellaiah, M.A. (BioMed Central Ltd., 2019)
      Background: Expression of CD44 receptor is associated with the onset of several tumors. The intracellular domain of CD44 (CD44-ICD) has been implicated as a co-transcription factor for RUNX2 in the regulation of expression of MMP-9 in breast carcinoma cells. Previous studies from our laboratory demonstrated the role of CD44 in migration and invasion of PC3 prostate cells through activation of MMP-9. CD44 signaling regulates the phosphorylation and hence the localization of RUNX2 in the nucleus. The role of CD44-ICD has not been studied in prostate cancer cells. This study aimed to explore the role of CD44-ICD and RUNX2 in the regulation of expression of metastasis-related genes. Methods: PC3 and PC3 cells overexpressing RUNX2 protein were analyzed for RUNX2/CD44-ICD interaction by immunoprecipitation, immunoblotting, and Immunofluorescence analyses. Wound healing and tumorsphere formation analyses were also done in these cells. The real-time PCR analysis was used to detect the expression levels of different genes. Results: Expression of CD44 and RUNX2 was observed only in PC3 cells (androgen receptor positive) and not in LNCaP or PCa2b cells (androgen receptor negative). Therefore, CD44-ICD fragment (~ 15-16 kDa) was observed in PC3 cells. Moreover, localization of CD44-ICD was more in the nucleus than in the cytoplasm of PC3 cells. Inhibition of cleavage of CD44 with a γ-secretase inhibitor, DAPT reduced the formation of CD44-ICD; however, accumulation of CD44-external truncation fragments (~ 20 and ~ 25 kDa) was detected. RUNX2 and CD44-ICD interact in the nucleus of PC3 cells, and this interaction was more in PC3 cells transfected with RUNX2 cDNA. Overexpression of RUNX2 augments the expression of metastasis-related genes (e.g., MMP-9 and osteopontin) which resulted in increased migration and tumorsphere formation. Conclusions: We have shown here a strong functional relationship between CD44-ICD and RUNX2 in PC3 cells. RUNX2 forms a complex with CD44-ICD as a co-transcriptional factor, and this complex formation not only activates the expression of metastasis-related genes but also contributes to migration and tumorsphere formation. Therefore, RUNX2 and CD44-ICD are potential targets for anti-cancer therapy, and attenuation of their interaction may validate the regulatory effects of these proteins on cancer migration and progression. Copyright 2019 The Author(s).
    • A Novel Dental Sealant Containing Dimethylaminohexadecyl Methacrylate Suppresses the Cariogenic Pathogenicity of Streptococcus mutans Biofilms

      Ibrahim, M.S.; Balhaddad, A.A.; Weir, M.D.; Oates, T.W.; Xu, H.H.K.; Melo, M.A.S. (MDPI, 2019)
      Cariogenic oral biofilms are strongly linked to dental caries around dental sealants. Quaternary ammonium monomers copolymerized with dental resin systems have been increasingly explored for modulation of biofilm growth. Here, we investigated the effect of dimethylaminohexadecyl methacrylate (DMAHDM) on the cariogenic pathogenicity of Streptococcus mutans (S. mutans) biofilms. DMAHDM at 5 mass% was incorporated into a parental formulation containing 20 mass% nanoparticles of amorphous calcium phosphate (NACP). S. mutans biofilms were grown on the formulations, and biofilm inhibition and virulence properties were assessed. The tolerances to acid stress and hydrogen peroxide stress were also evaluated. Our findings suggest that incorporating 5% DMAHDM into 20% NACP-containing sealants (1) imparts a detrimental biological effect on S. mutans by reducing colony-forming unit counts, metabolic activity and exopolysaccharide synthesis; and (2) reduces overall acid production and tolerance to oxygen stress, two major virulence factors of this microorganism. These results provide a perspective on the value of integrating bioactive restorative materials with traditional caries management approaches in clinical practice. Contact-killing strategies via dental materials aiming to prevent or at least reduce high numbers of cariogenic bacteria may be a promising approach to decrease caries in patients at high risk.
    • Crypt- and Mucosa-Associated Core Microbiotas in Humans and Their Alteration in Colon Cancer Patients

      Saffarian, A.; Ravel, J.; Pedron, T. (American Society for Microbiology, 2019)
      We have previously identified a crypt-specific core microbiota (CSCM) in the colons of healthy laboratory mice and related wild rodents. Here, we confirm that a CSCM also exists in the human colon and appears to be altered during colon cancer. The colonic microbiota is suggested to be involved in the development of colorectal cancer (CRC). Because the microbiota identified in fecal samples from CRC patients does not directly reflect the microbiota associated with tumor tissues themselves, we sought to characterize the bacterial communities from the crypts and associated adjacent mucosal surfaces of 58 patients (tumor and normal homologous tissue) and 9 controls with normal colonoscopy results. Here, we confirm that bacteria colonize human colonic crypts in both control and CRC tissues, and using laser-microdissected tissues and 16S rRNA gene sequencing, we further show that right and left crypt- and mucosa-associated bacterial communities are significantly different. In addition to Bacteroidetes and Firmicutes, and as with murine proximal colon crypts, environmental nonfermentative Proteobacteria are found in human colonic crypts. Fusobacterium and Bacteroides fragilis are more abundant in right-side tumors, whereas Parvimonas micra is more prevalent in left-side tumors. More precisely, Fusobacterium periodonticum is more abundant in crypts from cancerous samples in the right colon than in associated nontumoral samples from adjacent areas but not in left-side colonic samples. Future analysis of the interaction between these bacteria and the crypt epithelium, particularly intestinal stem cells, will allow deciphering of their possible oncogenic potential.IMPORTANCE Due to the huge number of bacteria constituting the human colon microbiota, alteration in the balance of its constitutive taxa (i.e., dysbiosis) is highly suspected of being involved in colorectal oncogenesis. Indeed, bacterial signatures in association with CRC have been described. These signatures may vary if bacteria are identified in feces or in association with tumor tissues. Here, we show that bacteria colonize human colonic crypts in tissues obtained from patients with CRC and with normal colonoscopy results. Aerobic nonfermentative Proteobacteria previously identified as constitutive of the crypt-specific core microbiota in murine colonic samples are similarly prevalent in human colonic crypts in combination with other anaerobic taxa. We also show that bacterial signatures characterizing the crypts of colonic tumors vary depending whether right-side or left-side tumors are analyzed. Copyright 2019 Saffarian et al.
    • Comment on "pP2A inhibition sensitizes cancer stem cells to ABL tyrosine kinase inhibitors in BCR-ABL human leukemia"

      Perrotti, D.; Agarwal, A.; Lucas, C.M. (American Association for the Advancement of Science, 2019)
      LB100 does not sensitize CML stem cells to tyrosine kinase inhibitor-induced apoptosis. Copyright 2019 The Authors.
    • Plasma for burn shock resuscitation: is it time to go back to the future?

      Gurney, J.M.; Kozar, R.A.; Cancio, L.C. (Blackwell Publishing Inc., 2019)
      Patients with burn shock can be challenging to resuscitate. Burn shock produces a variety of physiologic derangements: Patients are hypovolemic from volume loss, have a increased systemic vascular resistance, and may have a depressed cardiac output depending on the extent of the thermal injury. Additionally, the burn wound produces a significant inflammatory cascade of events that contributes to the shock state. Fluid resuscitation is foundational for the initial treatment of burn shock. Typical resuscitation is with intravenous lactated Ringer's in accordance with well-established formulas based on burn wound size. In the past century, as therapies to treat thermal injuries were being developed, plasma was the fluid used for burn resuscitation; in fact, plasma was used in World War II and throughout the 1950s and 1960s. Plasma was abandoned because of infectious risks and complications. Despite huge strides in transfusion medicine and the increased safety of blood products, plasma has never been readopted for burn resuscitation. Over the past 15 years, there has been a paradigm shift in trauma resuscitation: Less crystalloid and more blood products are used; this strategy has demonstrated improved outcomes. Plasma is a physiologic fluid that stabilizes the endothelium. The endotheliopathy of trauma has been described and is mitigated by transfusion strategies with a 1:1 ratio of RBCs to plasma. Thermal injury also results in endothelial dysfunction: the endotheliopathy of burns. Plasma is likely a better resuscitation fluid for patients with significant burn wounds because of its capability to restore intravascular volume status and treat the endotheliopathy of burns.
    • HAS-BLED - A Canary in Cardiac Surgery Bleeding?

      Strauss, E.; Tanaka, K.; Mazzeffi, M. (W.B. Saunders, 2019)
    • Preventing Suicide Among Working-Age Adults: The Correlates of Help-Seeking Behavior

      Ko, J.; Frey, J.J.; Harrington, D. (SAGE Publications Inc., 2019)
      We aimed to identify the correlates with not seeking help among working-age adults with suicidal ideation. By adapting the integrated model of suicide help-seeking, we examined help-seeking behavior in the following 3 stages: problem recognition, decision to seek help, and sources of help. We used a sample of working-age adults between 26 and 64 years old, who reported suicidal ideation in the past year (N = 1414). Data were drawn from the 2011 and 2012 National Survey on Drug Use and Health, and multinomial logistic regression analyses were applied. Findings suggested that being male, being nonwhite, being employed full-time, having lower levels of general mental health needs, and not having health insurance were associated with not seeking help. Results also indicated how each factor was related in the help-seeking pathway. Strategies to help problem recognition can be effective in enhancing help-seeking behavior among men, racial/ethnic minorities, and those without serious clinical conditions. Help-seeking interventions for working-age adults with suicidal ideation should also consider that race/ethnic minorities and those with lower levels of functional impairment might rely on alternative sources of help, such as family, friends, and religious advisors. Copyright The Author(s) 2019.
    • Robot-assisted therapy in upper extremity hemiparesis: Overview of an evidence-based approach

      Duret, C.; Grosmaire, A.-G.; Krebs, H.I. (Frontiers Media S.A., 2019)
      Robot-mediated therapy is an innovative form of rehabilitation that enables highly repetitive, intensive, adaptive, and quantifiable physical training. It has been increasingly used to restore loss of motor function, mainly in stroke survivors suffering from an upper limb paresis. Multiple studies collated in a growing number of review articles showed the positive effects on motor impairment, less clearly on functional limitations. After describing the current status of robotic therapy after upper limb paresis due to stroke, this overview addresses basic principles related to robotic therapy applied to upper limb paresis. We demonstrate how this innovation is an evidence-based approach in that it meets both the improved clinical and more fundamental knowledge-base about regaining effective motor function after stroke and the need of more objective, flexible and controlled therapeutic paradigms.