PCR-based immunoglobulin (Ig)/T-cell receptor (TCR) clonality testing in suspected lymphoproliferations has largely been standardized and has consequently become technically feasible in a routine ...diagnostic setting. Standardization of the pre-analytical and post-analytical phases is now essential to prevent misinterpretation and incorrect conclusions derived from clonality data. As clonality testing is not a quantitative assay, but rather concerns recognition of molecular patterns, guidelines for reliable interpretation and reporting are mandatory. Here, the EuroClonality (BIOMED-2) consortium summarizes important pre- and post-analytical aspects of clonality testing, provides guidelines for interpretation of clonality testing results, and presents a uniform way to report the results of the Ig/TCR assays. Starting from an immunobiological concept, two levels to report Ig/TCR profiles are discerned: the technical description of individual (multiplex) PCR reactions and the overall molecular conclusion for B and T cells. Collectively, the EuroClonality (BIOMED-2) guidelines and consensus reporting system should help to improve the general performance level of clonality assessment and interpretation, which will directly impact on routine clinical management (standardized best-practice) in patients with suspected lymphoproliferations.
Annual cyanobacterial blooms dominated by Microcystis have occurred in western Lake Erie (U.S./Canada) during summer months since 1995. The production of toxins by bloom-forming cyanobacteria can ...lead to drinking water crises, such as the one experienced by the city of Toledo in August of 2014, when the city was rendered without drinking water for >2 days. It is important to understand the conditions and environmental cues that were driving this specific bloom to provide a scientific framework for management of future bloom events. To this end, samples were collected and metatranscriptomes generated coincident with the collection of environmental metrics for eight sites located in the western basin of Lake Erie, including a station proximal to the water intake for the city of Toledo. These data were used to generate a basin-wide ecophysiological fingerprint of Lake Erie Microcystis populations in August 2014 for comparison to previous bloom communities. Our observations and analyses indicate that, at the time of sample collection, Microcystis populations were under dual nitrogen (N) and phosphorus (P) stress, as genes involved in scavenging of these nutrients were being actively transcribed. Targeted analysis of urea transport and hydrolysis suggests a potentially important role for exogenous urea as a nitrogen source during the 2014 event. Finally, simulation data suggest a wind event caused microcystin-rich water from Maumee Bay to be transported east along the southern shoreline past the Toledo water intake. Coupled with a significant cyanophage infection, these results reveal that a combination of biological and environmental factors led to the disruption of the Toledo water supply. This scenario was not atypical of reoccurring Lake Erie blooms and thus may reoccur in the future.
IntroductionLow and varied quality of care has been demonstrated for childhood illnesses in low-income and middle-income countries. Some quality improvement strategies focus on increasing patient ...engagement; however, evidence suggests that patients demanding medicines can favour the selection of resistant microbial strains in the individual and the community if drugs are inappropriately used. This study examines the effects on quality of care when patients demand different types of inappropriate medicines.MethodsWe conducted an experiment where unannounced standardised patients (SPs), locally recruited individuals trained to simulate a standardised case, present at private clinics. Between 8 March and 28 May 2019, 10 SPs portraying caretakers of a watery diarrhoea childhood case scenario (in absentia) conducted N=200 visits at 200 private, primary care clinics in Kenya. Half of the clinics were randomly assigned to receive an SP demanding amoxicillin (an antibiotic); the other half, an SP demanding albendazole (an antiparasitic drug often used for deworming), with other presenting characteristics the same. We used logistic and linear regression models to assess the effects of demanding these inappropriate medicines on correct and unnecessary case management outcomes.ResultsCompared with 3% among those who did not demand albendazole, the dispensing rate increased significantly to 34% for those who did (adjusted OR 0.06, 95% CI 0.02 to 0.22, p<0.0001). Providers did not give different levels of amoxicillin between those demanding it and those not demanding it (adjusted OR 1.73, 95% CI 0.51 to 5.82). Neither significantly changed any correct management outcomes, such as treatment or referral elsewhere.ConclusionPrivate providers appear to account for both business-driven benefits and individual health impacts when making prescribing decisions. Additional research is needed on provider knowledge and perceptions of profit and individual and community health trade-offs when making prescription decisions after patients demand different types of inappropriate medicines.Trial registration numbersAmerican Economic Association Registry (#AEARCTR-0000217) and Pan African Clinical Trial Registry (#PACTR201502000770329).
The joint impact of sedentary behavior and physical activity on obesity has not been assessed in a large cohort followed from adolescence to adulthood.
Nationally representative longitudinal data ...from Waves II (1995; mean age: 15.9) and III (2001; mean age: 21.4) of the National Longitudinal Study of Adolescent Health (n = 9,155) were collected. Sex-stratified multivariate logistic regression analysis assessed the odds of obesity associated with Wave II MVPA and screen time, controlling for sociodemographic characteristics and change in MVPA and screen time from Wave II to III. Obesity was defined using body mass index (BMI, kg/m2) International Obesity Task Force cut-points at Wave II and adult cut-points at Wave III (BMI >or= 30).
In males, adjusted odds of prevalent obesity was strongly predicted by MVPA bouts OR (95% CI): OR6 vs. 1 MVPA bouts = 0.50 (0.40, 0.62); OR4 vs. 40 hrs screen time = 0.83 (0.69, 1.00). In females, greater MVPA bouts and lower screen time correlated with lower prevalent obesity OR (95% CI): OR6 vs. 1 MVPA bouts = 0.67 (0.49, 0.91); OR4 vs. 40 hrs screen time = 0.67 (0.53, 0.85). Longitudinally, adolescent screen time hours had a stronger influence on incident obesity in females OR (95% CI): OR4 vs. 40 hrs = 0.58 (0.43, 0.80) than males OR (95% CI): OR4 vs. 40 hrs = 0.78 (0.61, 0.99). Longitudinal activity patterns were not predictive of incident obesity.
Reducing screen time during adolescence and into adulthood may be a promising strategy for reducing obesity incidence, especially in females.
Keloids are benign tumors of the dermis that form during a protracted wound healing process. Susceptibility to keloid formation occurs predominantly in people of African and Asian descent. The key ...alteration(s) responsible for keloid formation has not been identified and there is no satisfactory treatment for this disorder. The altered regulatory mechanism is limited to dermal wound healing, although several diseases characterized by an exaggerated response to injury are prevalent in individuals of African ancestry. We have observed a complex pattern of phenotypic differences in keloid fibroblasts grown in standard culture medium or induced by hydrocortisone (HC). In this study Affymetrix-based microarray was performed on RNA obtained from fibroblasts cultured from normal scars and keloids grown in the absence and presence of HC. We observed differential regulation of approximately 500 genes of the 38,000 represented on the Affymetrix chip. Of particular interest was increased expression of several IGF-binding and IGF-binding-related proteins and decreased expression of a subset of Wnt pathway inhibitors and multiple IL-1-inducible genes. Increased expression of connective tissue growth factor and insulin-like growth factor binding protein-3 was observed in keloid fibroblasts only in the presence of HC. These findings support a role for multiple fibrosis-related pathways in the pathogenesis of keloids.
Rapid spread of the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) and concern for viral transmission by ambulatory patients with minimal to no symptoms underline the importance of ...identifying early or subclinical symptoms of coronavirus disease 2019 (COVID-19) infection. Two such candidate symptoms include anecdotally reported loss of smell and taste. Understanding the timing and association of smell/taste loss in COVID-19 may help facilitate screening and early isolation of cases.
A single-institution, cross-sectional study evaluating patient-reported symptoms with a focus on smell and taste was conducted using an internet-based platform on adult subjects who underwent testing for COVID-19. Logistic regression was employed to identify symptoms associated with COVID-19 positivity.
A total of 1480 patients with influenza-like symptoms underwent COVID-19 testing between March 3, 2020, and March 29, 2020. Our study captured 59 of 102 (58%) COVID-19-positive patients and 203 of 1378 (15%) COVID-19-negative patients. Smell and taste loss were reported in 68% (40/59) and 71% (42/59) of COVID-19-positive subjects, respectively, compared to 16% (33/203) and 17% (35/203) of COVID-19-negative patients (p < 0.001). Smell and taste impairment were independently and strongly associated with COVID-19 positivity (anosmia: adjusted odds ratio aOR 10.9; 95% CI, 5.08-23.5; ageusia: aOR 10.2; 95% CI, 4.74-22.1), whereas sore throat was associated with COVID-19 negativity (aOR 0.23; 95% CI, 0.11-0.50). Of patients who reported COVID-19-associated loss of smell, 74% (28/38) reported resolution of anosmia with clinical resolution of illness.
In ambulatory individuals with influenza-like symptoms, chemosensory dysfunction was strongly associated with COVID-19 infection and should be considered when screening symptoms. Most will recover chemosensory function within weeks, paralleling resolution of other disease-related symptoms.
Polymerase chain reaction (PCR) assessment of clonal immunoglobulin (Ig) and T-cell receptor (TCR) gene rearrangements is an important diagnostic tool in mature B-cell neoplasms. However, lack of ...standardized PCR protocols resulting in a high level of false negativity has hampered comparability of data in previous clonality studies. In order to address these problems, 22 European laboratories investigated the Ig/TCR rearrangement patterns as well as t(14;18) and t(11;14) translocations of 369 B-cell malignancies belonging to five WHO-defined entities using the standardized BIOMED-2 multiplex PCR tubes accompanied by international pathology panel review. B-cell clonality was detected by combined use of the IGH and IGK multiplex PCR assays in all 260 definitive cases of B-cell chronic lymphocytic leukemia (n=56), mantle cell lymphoma (n=54), marginal zone lymphoma (n=41) and follicular lymphoma (n=109). Two of 109 cases of diffuse large B-cell lymphoma showed no detectable clonal marker. The use of these techniques to assign cell lineage should be treated with caution as additional clonal TCR gene rearrangements were frequently detected in all disease categories. Our study indicates that the BIOMED-2 multiplex PCR assays provide a powerful strategy for clonality assessment in B-cell malignancies resulting in high Ig clonality detection rates particularly when IGH and IGK strategies are combined.
The manufacture of insulin analogs requires sophisticated production procedures which can lead to differences in the structure, purity, and/or other physiochemical properties of resultant products ...that can affect their biologic activity. Here, we sought to compare originator and non-originator copies of insulin glargine for innate immune activity and mechanisms leading to differences in these response profiles in an in vitro model of human immunity.
An endothelial/dendritic cell-based innate immune model was used to study antigen-presenting cell activation, cytokine secretion, and insulin receptor signalling pathways induced by originator and non-originator insulin glargine products. Mechanistic studies included signalling pathway blockade with specific inhibitors, analysis of the products in a Toll-like receptor reporter cell line assay, and natural insulin removal from the products by immunopurification.
All insulin glargine products elicited at least a minor innate immune response comparable to natural human insulin, but some lots of a non-originator copy product induced the elevated secretion of the cytokines, IL-8 and IL-6. In studies aimed at addressing the mechanisms leading to differential cytokine production by these products, we found (1) the inflammatory response was not mediated by bacterial contaminants, (2) the innate response was driven by the native insulin receptor through the MAPK pathway, and (3) the removal of insulin glargine significantly reduced their capacity to induce innate activity. No evidence of product aggregates was detected, though the presence of some high molecular weight proteins argues for the presence of insulin glargine dimers or others contaminants in these products.
The data presented here suggests some non-originator insulin glargine product lots drive heightened in vitro human innate activity and provides preliminary evidence that changes in the biochemical composition of non-originator insulin glargine products (dimers, impurities) might be responsible for their greater immunostimulatory potential.
Zika: A scourge in urban slums Snyder, Robert E; Boone, Claire E; Cardoso, Claudete A Araújo ...
PLoS neglected tropical diseases,
03/2017, Letnik:
11, Številka:
3
Journal Article
Recenzirano
Odprti dostop
In December 2014, during the height of the Ebola virus disease (EVD) epidemic in West Africa, we wrote, “EVD is only the beginning and only one disease; even if we are to control the current ...epidemic, the future introduction of this and other highly contagious and virulent microbes to and from global slums is inevitable” 1.Fast forward to late 2015: another epidemic of another virus-Zika-together with its major neurological complication-microcephaly-explodes in Brazil. Again, as with the EVD epidemic, the world’s attention is focused on issues such as where the virus originated, the need to control vectors, how quickly we can develop a vaccine, and how long the epidemic will continue. While these are important discussions to have, they are irrelevant if the world does not recognize and address a crucial reason why these explosive epidemics continue to occur in the first place: the world must talk about urban slums.Zika is, and will continue to be, a disease of the urban poor. Slum-defining characteristics-poor water and sanitation infrastructure, crowding, and poor structural quality of housing-offer ample opportunities for mosquitoes to breed and spread the Zika virus. It was recently estimated that 1.6 million childbearing women and 93 million people will be infected in the Americas’ first epidemic wave 2. From this reservoir of infections, the world is witnessing the largest epidemic ever of a congenital complication-microcephaly. Except for sporadic reports, largely absent from discussion is the fact that the greatest proportion of Zika infections and its complications have occurred, and will continue to occur, among residents of the large, densely packed informal human settlements of Latin America and the Caribbean.
To determine if a community pharmacy-based transition of care (TOC) program that included the full scope of medication therapy management (MTM) services (TransitionRx) decreased hospital ...readmissions, resolved medication-related problems, and increased patient satisfaction.
Prospective, quasi-experimental study.
Nine Kroger Pharmacies located in Western Cincinnati.
Patients older than 18 years of age and discharged from two local hospitals with a diagnosis of congestive heart failure, chronic obstructive pulmonary disease, or pneumonia. Patients were recruited from two local hospitals and referred to the community pharmacy for MTM services with the pharmacist within 1 week of discharge.
Pharmacists reconciled the patients' medications, identified drug therapy problems, recommended changes to therapy, and provided self-management education. At 30 days after discharge, research personnel conducted telephone surveys, using a previously validated survey instrument, to assess hospital readmissions and patient satisfaction. Pharmacist interventions and medication-related problems were documented.
A total of 90 patients completed the study. Of these, 20% of patients in the usual care group were admitted to the hospital within 30 days compared with 6.9% of patients in the intervention group (P = 0.019). In the 30 patients who received MTM services from the pharmacist, 210 interventions were made. The overall mean patient satisfaction with the TOC process was not significantly different between patients who were seen by the pharmacist and those who were not seen by the pharmacist.
Community pharmacies successfully collaborated with hospitals to develop a referral process for TOC interventions. Patients who received MTM services from the pharmacist experienced significantly fewer readmissions than patients who received usual care.
PDF
