bluuebunny/crossref_metadata_2025 huggingface dataset:
Development and evaluation of a urine protein expert system
Authors: Ivandić M , Hofmann W , Guder W G
Published: January 2020

Based on the quantitative determination of creatinine, total protein, albumin, alpha 1-microglobulin, IgG, alpha 2-macroglobulin, and N-acetyl-beta, D-glucosaminidase in urine in combination with a test strip screening, the findings of hematuria, leukocyturia, and proteinuria can be assigned to prerenal, renal, or postrenal causes. Using this graded diagnostic strategy as a knowledge base, we developed a computerbased expert system for urine protein differentiation ("UPES") as a decision-supporting tool. The knowledge base was implemented as a combination of "if/then" rules and two-step bivariate distance classification of marker proteins. The knowledge for this form of pattern recognition was derived from the results for a set of 267 patients with clinically and histologically documented nephropathies. To determine the diagnostic value of UPES, we tested another set of data: results for 129 urine analyses from 94 patients. Using these data, the system reached 98% concordance with the clinical diagnoses for the patients and was superior to the diagnostic interpretations of four human experts. UPES has been successfully integrated into the laboratory routine process, including automated data import.
Validation protocol of analytical hemostasis systems: measurement of anti-Xa activity of low-molecular-weight heparins
Authors: Houbouyan L , Boutière B , Contant G , Dautzenberg M D , Fievet P , Potron G , Vassault A , Gourmelin Y
Published: January 2020

A standard validation protocol adapted to the chromogenic assay of anti-Xa activity of low-molecular-weight heparins was used in a multicenter study to assess its suitability for comparing and evaluating analytical hemostasis systems. The protocol included: familiarization with the system (repeatability); assessment of limits of linearity, detection limits, and cross-contamination; and validation (reproducibility and accuracy of measurements of treated patients' plasmas). We calibrated the systems with the same range of lyophilized plasmas daily and evaluated repeatability and reproducibility by using a single batch of lyophilized plasmas at three anti-Xa activities. The two automated systems tested [SB 300 (Gilford) and ACL (IL)] and the two semiautomated systems [ST 888 (D. Stago) and Chromotimer (Behring)] gave similar mean values. Dispersion of results was lower with the automated systems than with the semiautomated ones, especially at low anti-Xa activities, a tendency that also was observed for reproducibility. Because each analytical system gave linear results for activities as great as 1000 IU/L, suitable sample dilution is advisable for higher anti-Xa activities. Accuracy was greater in the automated systems. We conclude that this protocol is feasible and is applicable to validation of other analytical hemostasis instruments, in particular the latest generation of fully automated instruments.
Clinical studies of drug effects in humans
Authors: Ray W A
Published: January 2020

Many important drug properties cannot be predicted from in vitro or animal studies but must be quantified from studies of clinically relevant endpoints in humans. Clinical study designs include the randomized controlled trial (RCT) and a variety of observational designs. In RCTs, randomization usually ensures treatment group comparability with respect to other factors, so outcome differences reflect treatment differences per se. Properly conducted RCTs thus are the strongest study design, the mainstay of mandatory premarketing studies, and essential for evaluation of therapeutic efficacy. RCT limitations include frequent use of surrogate endpoints, limited power, short-term follow-up, and cross-contamination of study groups. For ethical reasons, some questions cannot be studied with RCTs. The simplest observational design, the case series, has limited value because it lacks a denominator. Limitations of cohort and case-control studies include misclassification, selection bias, and confounding. Despite their limitations, properly conducted experimental and observational clinical studies provide essential data for clinical practice.
Toxic effects of immunosuppressive drugs: mechanisms and strategies for controlling them
Authors: Shaw L M , Kaplan B , Kaufman D
Published: January 2020

Since cyclosporine (CsA) was introduced into clinical practice in late 1983 to prevent rejection in transplant patients, there has been an almost explosive growth in the number and types of transplants and the number of transplant centers, an increase in the life expectancy of the transplanted organ, and substantial decreases in rates of acute rejection and life-threatening infections. Despite these successes, major improvements in immunosuppressive therapy are needed, especially a reduction in toxic side effects and a rigorous definition of the relation between drug concentration and clinical effects. Such improvements may be achievable with the incorporation of new drugs such as tacrolimus and mycophenolate mofetil into immunosuppression protocols and the development of rigorously defined therapeutic drug-monitoring programs.
Clinical evaluation of the poisoned patient and toxic syndromes
Authors: Liang H K
Published: January 2020

Poisonings and toxic exposures are prominent causes of morbidity and mortality in patients that present to the emergency department. The American Association of Poison Control Centers, in its 1994 annual report, cites a 10% increase in the number of reported cases of poison exposure. The clinical evaluation and management of such patients remain challenging. Few specific antidotes are available for the many potential poisonings that occur annually. Rapid stabilization, resuscitation, and recognition of major toxic syndromes, along with appropriate utilization of laboratory testing, guide the clinician in the treatment of such patients.
Pediatric poisonings
Authors: Goepp J G
Published: January 2020

In a general exposition of clinical and laboratory issues in the emergency management of poisoning in the pediatric patient I briefly discuss the epidemiology of poisonings in the child population, the categories of poisons to which children are exposed most frequently, and clinical and laboratory considerations, focusing on the importance of understanding the pharmacological properties of the compound involved. I review diagnostic and therapeutic decision-making in light of the characteristics of the known or suspected chemical involved. Finally, the information presented is integrated in a discussion of two cases of poisoned patients in a hospital emergency department.
Comparative sensitivities and specificities of the mass measurements of CK-MB2, CK-MB, and myoglobin for diagnosing acute myocardial infarction
Authors: Laurino J P , Bender E W , Kessimian N , Chang J , Pelletier T , Usategui M
Published: January 2020

We evaluated the clinical utility of the mass measurement of the tissue isoform of creatine kinase MB isoenzyme (CK-MB2) in the diagnosis of an acute myocardial infarction (AMI) by determining its sensitivity, specificity, and predictive value relative to those of CK-MB mass and myoglobin. Samples were obtained at 0, 4, 8, and 16 h postpresentation from 100 patients (41% with AMI). The order of sensitivity for the sample proportions taken at 0-2 h from the onset of symptoms was myoglobin > CK-MB2 > CK-MB. At all other time points, the sensitivity of CK-MB2 either equaled or surpassed that of both CK-MB and myoglobin, although the 95% confidence intervals for the population proportions each of these markers overlapped. Of the 41 AMI patients, 31 (76%) exhibited concurrent abnormal increases of CK-MB and %CK-MB2; the other 10 (24%; 8 non-Q wave, 2 Q wave) exhibited abnormal values for %CK-MB2 before their CK-MB exceeded the upper limit of normal. The specificity of myoglobin was statistically lower than that for either CK-MB2 or CK-MB at all time points.
Evaluation of the Du Pont Axial Separation system
Authors: Perkins S L , Adams G A
Published: January 2020

We evaluated the Du Pont Axial Separation Technology (AST) system, which permanently separates a blood specimen into serum or plasma and cells in 1 min. Blood was collected in axial processing containers by standard venipuncture techniques and processed in an Axial Separation Module. Paired patient samples (n = 48 serum pairs, n = 50 plasma pairs) revealed no clinically significant differences in results for common chemistry analytes from samples collected in Becton Dickinson Vacutainer Tubes and centrifuged conventionally vs those from samples collected and processed in the AST system, except for a bias in serum (but not plasma) lactate dehydrogenase activity. This bias was dependent on the extent of stretching of the clot during processing and could be minimized by clotting the blood sample horizontally (axially). We believe the rapid separation of blood by the AST system has the potential to substantially reduce preanalytical specimen handling time.
Using Shewhart p control charts of external quality-assurance program data to monitor analytical performance of a clinical chemistry laboratory
Authors: Chesher D , Burnett L
Published: January 2020

We have investigated the application of Shewhart's p control charts in our external quality-assurance program to monitor the long-term performance of our laboratory's analytical quality. The p control charts have been able to detect long-term changes in our laboratory's analytical performance that would have been difficult to detect by more-conventional techniques. We have explored methods for interpreting these charts as well as some of their limitations, which include minimum subgroup size and dependence on constant specification limits. These charts may be not only a simple method for the long-term monitoring of analytical performance of a laboratory, but also of use to the organizers of external quality-assurance programs.
Towards artificial antibodies prepared by molecular imprinting
Authors: Ansell R J , Ramström O , Mosbach K
Published: January 2020

The new technique of molecular imprinting has increasingly been adopted by research laboratories worldwide during the last few years. We have studied the use of such imprints against drugs as artificial antibody-binding mimics in competitive radioimmuno-style binding assays. The recognition sites "molded" in the polymers mimic the binding sites of natural antibodies in their interactions with the target antigen. Binding constants are as low as 4.0 nmol/L for a small number of well-defined sites, and cross-reactivities are similar to or better than those observed with biological antibodies. In some cases, the polymers have been used to determine drug concentrations in human serum specimens.
Luminescent oxygen channeling assay (LOCI): sensitive, broadly applicable homogeneous immunoassay method
Authors: Ullman E F , Kirakossian H , Switchenko A C , Ishkanian J , Ericson M , Wartchow C A , Pirio M , Pease J , Irvin B R , Singh S , Singh R , Patel R , Dafforn A , Davalian D , Skold C , Kurn N , Wagner D B
Published: January 2020

Luminescent oxygen channeling assay (LOCI) is a homogeneous immunoassay method capable of rapid, quantitative determination of a wide range of analytes--including high and very low concentrations of large and small molecules, free (unbound) drugs, DNA, and specific IgM. Assays have been carried out in serum and in lysed blood. Reliable detection of 1.25 microU/L thyrotropin (TSH) and 5 ng/L hepatitis B surface antigen (HBsAg) corresponds to detection limits approximately 3- and approximately 20-fold lower, respectively, than those of the best commercially available assays. An assay of chorionic gonadotropin is capable of quantification over a 10(6)-fold range of concentrations without a biphasic response. Latex particle pairs are formed in the assay through specific binding interactions by sequentially combining the sample and two reagents. One particle contains a photosensitizer, the other a chemiluminescer. Irradiation causes photosensitized formation of singlet oxygen, which migrates to a bound particle and activates the chemiluminescer, thereby initiating a delayed luminescence emission. Assay times range from 1 to 25 min.
Ultra-specific immunoassays for small molecules: roles of wash steps and multiple binding formats
Authors: Self C H , Dessi J L , Winger L A
Published: January 2020

New immunometric forms of immunoassay are much more flexible to use than competitive-format immunoassays for small molecular analytes. An example of the utility of this flexibility is the ability to wash the capture antibody after it has been exposed to analyte but before addition of the labeled reagent. This simple maneuver has a large impact on the specificity obtained from already highly specific assays. We also show that specificity can be further increased by means of our multiple binding assay approach, in which the final reading reflects analyte binding to two different primary capture monoclonal antibodies.
Detection of immobilized amplicons by ELISA-like techniques
Authors: Oroskar A A , Rasmussen S E , Rasmussen H N , Rasmussen S R , Sullivan B M , Johansson A
Published: January 2020

The NucleoLink surface is a physically modified, thermostable, optically clear resin. It allows the covalent binding of 5'-phosphorylated oligonucleotides. Target DNA amplification by polymerase chain reaction (PCR) is accomplished by asymmetric amplification on the covalently immobilized primer that develops into immobilized amplicons. A DNA fragment of bovine leukemia virus is used as a model system for the detection of immobilized amplicons by ELISA-like techniques. Covalently bound oligonucleotides are also utilized as capture probe in the hybridization-based signal amplification for detection of an infectious organism.
Regulatory hurdles in bringing an in vitro diagnostic device to market
Authors: Smith K M , Kates J A
Published: January 2020

We discuss the hurdles that developers and manufacturers of in vitro diagnostic devices face in obtaining regulatory approval to market their products in the US. A thorough understanding of medical device regulation and the early planning of a clinical and regulatory strategy are imperative in assuring successful and timely launches of new products. Finally, it is critical for manufacturers to establish a working partnership with the Food and Drug Administration to expedite their new product applications.
A parallel revolution: payment for new in vitro diagnostic technologies
Authors: Ivor L P
Published: January 2020

To secure a successful product in today's era of cost containment, manufacturers and developers of new in vitro diagnostic technologies must consider payment issues--coverage and reimbursement by healthcare insurers--as critical market forces that must be addressed in the business plan. Similar to the regulatory hurdles involving 510(k)s and premarket applications, the requirements for payment are related to the unique features of the technology, its costs, and its effect on clinical outcomes. Because cost containment continues to be a driving force for change in healthcare, the business plan must not only include strategies for optimal payment at the product's introduction, but also contain provisions for continuous monitoring of the payment environment throughout the product's life cycle.
Intramural coronary pattern in patients with transposition: incidence and impact on follow-up
Authors: Moll Maciej , Moll Jadwiga A , Moll Jacek J , Łubisz Monika , Michalak Krzysztof W
Published: January 2020

OBJECTIVES

Coronary complications are still the main reason for early mortality after an arterial switch operation. The high incidence of coronary anomalies in patients with transposition of the great arteries may increase the difficulty of coronary transfer, and among them, an intramural pattern was shown to be an independent risk factor of early mortality. However, recently published studies have reported that this rare coronary variant has no impact on the survival rate. The aim of this study was to assess the frequency of intramural coronary patterns in patients with transposition and the impact on overall mortality after an arterial switch operation. Additionally, we presented all coronary arrangements associated with intramural patterns in our cohort and the surgical techniques used to manage them successfully.

METHODS

All arterial switch operations were retrospectively reviewed. In each case, the surgical reports contained detailed graphical representations and coronary anatomy patterns. All operatively confirmed intramural patterns were included in the analysis.

RESULTS

Among 806 patients, 271 patients had coronary anomalies (33.62%), and 28 patients had an intramural pattern (3.47%), which was frequently associated with other complex coronary anomalies (P < 0.001). Overall survival was significantly higher in patients with intramural coronary artery patterns than in those with other coronary variants (21.34% vs 8.74%, P = 0.024, log-rank test).

CONCLUSIONS

Intramural patterns associated with transposition remain a surgical challenge and increase overall mortality in our cohort. To reliably confirm or reject the significance of the observed impact of this rare coronary variant, a multicentre data analysis is required.
Astragaloside IV attenuates IL-1β secretion by enhancing autophagy in H1N1 infection
Authors: Zhang Jing , Zhang Wanju , Ren Lehao , He Yanchao , Mei Zhoufang , Feng Jingjing , Shi Tianyun , Zhang Huiying , Song Zhigang , Jie Zhijun
Published: January 2020

Excessive secretion of inflammatory factors (cytokine storm) plays a significant role in H1N1-induced acute pneumonia, and autophagy acts as a cell-intrinsic mechanism to regulate inflammation. Astragaloside IV (AS-IV), originating from the astragalus root, possesses multiple pharmacological activities, such as anti-inflammation. However, the influences of AS-IV on H1N1-induced autophagy and inflammation have remained elusive. It has been reported that H1N1 infection leads to the accumulation of autophagosomes but obstructs autophagosomes incorporating into lysosomes, whereas the present study showed that AS-IV enhanced autophagy activation in H1N1 infection. Furthermore, we found that AS-IV promoted H1N1-triggered formation of autophagosomes and autolysosomes. Additionally, it was noted that AS-IV did not affect viral replication, mRNA level of interleukin-1 beta (IL-1β) and pro-IL-1β protein level, but significantly decreased secretion of IL-1β, and chloroquine (CQ, as an inhibitor of autophagy) increased secretion of IL-1β in H1N1 infection. In conclusion, AS-IV stimulates the formation of autophagosomes and the fusion of autophagosomes and lysosomes in H1N1 infection and may lead to decreased IL-1β secretion.
Occurrence, Identification, and Virulence of Native Fungal Pathogens Isolated From Mexican Fruit Fly (Diptera: Tephritidae) Larvae From Soils of Three Cropping Systems
Authors: Presa-Parra Ehdibaldo , Hernández-Rosas Francisco , Bernal Julio S , Valenzuela-González Jorge E , Altúzar-Molina Alma , Birke Andrea
Published: January 2020

The Mexican fruit fly, Anastrepha ludens Loew, is a significant pest in mango and citrus production areas of Mexico. In this study, we evaluated the effects of some geographic characteristics, rainfall period, soil micro-environmental, and soil coverage variables on the occurrence of entomopathogenic fungi (EPF) associated with A. ludens larvae in soils of mango, grapefruit and mixed crops in central Veracruz state, Mexico. EPF isolates were characterized morphologically and identified by sequence analysis of elongation factor (EF1-1018F, EF1-1620R). We recorded four species of EPF (Metarhizium robertsii J.F. Bisch, S.A. Rehner & Humber [Hypocreales: Cordycipitaceae], M. brunneum Petch [Hypocreales: Cordycipitaceae], M. pinghaense Q.T. Chen & H.L. Guo [Hypocreales: Cordycipitaceae], and Beauveria bassiana (Balsamo) Vuillemin [Hypocreales: Cordycipitaceae]), of which Metarhizium robertsii was the most abundant and the most virulent. Also, we found that rainfall period, organic matter, coverage of herbs and forbs, and calcium levels modulated EPF occurrence. We estimated lethal concentrations for A. ludens larvae of the four most promising isolates, V3-123, V3-160, V1-332, and V3-369. Our results suggest that M. robertsii obtained from agricultural soils holds potential as a biological control agent for A. ludens.
A Political Economy of Global Security Approach
Authors: Cappella Zielinski Rosella , Schilde Kaija , Ripsman Norrin
Published: January 2020

States have historically monopolized the provision of security for their societies. However, recent changes in the global economy combined with new sources of security and insecurity pose new and accelerating challenges that simultaneously hinder and bolster the ability of states to mobilize and extract resources for security provision. In contrast to a traditional political economy of security approach that emphasizes economic inputs shaping state power and economic tools states can use to project power vis-à-vis other states, the approach advanced in this forum stresses both domestic and transnational economic actors and market processes that affect security outcomes in both traditional security spaces and new security domains. The contributions to this forum exemplify the breadth of a political economy of global security approach while revisiting traditional areas of national security and newer security spaces and the application of the approach to both historical and contemporary phenomena.
Ledipasvir/Sofosbuvir in Adolescents With Chronic Hepatitis C Genotype 4 With and Without Hematological Disorders: Virological Efficacy and Impact on Liver Stiffness
Authors: Makhlouf Nahed A , Abdelmalek Mohamed O , Ibrahim Mohamed Eltaher , Abu-Faddan Nagla H , Kheila Abeer E , Mahmoud Amal A
Published: January 2020

Background

Egypt has the highest prevalence of hepatitis C virus (HCV) infection. Anti-HCV antibodies were detectable in 3% of children in Upper Egypt. Our aim was to evaluate the efficacy of ledipasvir/sofosbuvir for chronic HCV genotype 4 in adolescents with/without hematological disorders and to determine the effect of sustained virological response (SVR) on liver stiffness.

Methods

Sixty-five adolescents were recruited. There were 3 patient groups: group 1, 44 treatment-naive without hematological disorders; group 2, 6 previously treated; and group 3, 15 treatment-naive with hematological disorders. All patients received sofosbuvir 400 mg/ledipasvir 90 mg per day for 12 weeks. Serum HCV RNA levels were measured before treatment, at week 12, and at 12 weeks after the end of treatment (SVR12). Liver stiffness and the aspartate aminotransferase–platelet ratio index (APRI) score were estimated at baseline and at SVR12.

Results

SVR12 was 100%. At SVR12, there was a significant improvement in liver stiffness in all groups. The APRI score showed significant improvements in groups 1 and 3 (P < .001 and P = .004, respectively). The treatment was well tolerated, with minimal and self-limited side effects.

Conclusions

Treatment of chronic HCV in adolescents using ledipasvir/sofosbuvir was effective, with a cure rate (at SVR12) of 100%. Significant improvement in liver stiffness was found in all groups.
Plant receptor-like kinase signaling through heterotrimeric G-proteins
Authors: Pandey Sona
Published: January 2020

Heterotrimeric G-proteins regulate multiple aspects of plant growth, development, and response to biotic and abiotic stresses. While the core components of heterotrimeric G-proteins and their basic biochemistry are similar in plants and metazoans, key differences exist in their regulatory mechanisms. In particular, the activation mechanisms of plant G-proteins appear diverse and may include both canonical and novel modes. Classical G-protein-coupled receptor-like proteins exist in plants and interact with Gα proteins, but their ability to activate Gα by facilitating GDP to GTP exchange has not been demonstrated. Conversely, there is genetic and functional evidence that plant G-proteins interact with the highly prevalent receptor-like kinases (RLKs) and are phosphorylated by them. This suggests the exciting scenario that in plants the G-proteins integrate RLK-dependent signal perception at the plasma membrane with downstream effectors. Because RLKs are active kinases, it is also likely that the activity of plant G-proteins is regulated via phosphorylation/dephosphorylation rather than GTP–GDP exchange as in metazoans. This review discusses our current knowledge of the possible RLK-dependent regulatory mechanisms of plant G-protein signaling in the context of several biological systems and outlines the diversity that might exist in such regulation.
Postquantum: A Tale for the Time Being, Atomik Aztex, and Hacking Modern Space-Time
Authors: Lee Derek
Published: January 2020

This study identifies the postquantum novel as an emerging subgenre of speculative ethnic fiction that challenges the prevailing logic of Western space-time in contemporary literature. In contrast with archetypal twentieth-century literary modes such as modernism, postmodernism, and science fiction, postquantum fiction strays from classical and quantum mechanics—and Western science more broadly—as default knowledge systems and instead turns to premodern, indigenous, and non-Western epistemes as equally valid intellectual frameworks for representing reality. Drawing from philosophy of science and postcolonial theory, this study reads Zen Buddhism in Ruth Ozeki’s A Tale for the Time Being (2013) and the Meso-American calendrical sciences in Sesshu Foster’s Atomik Aztex (2005) as alternative logics of space-time and argues that the postquantum novel destabilizes many of the physicalist assumptions undergirding temporality and spatiality in twenty-first-century narrative. Postquantum fiction thus constitutes an original form of epistemological critique that decolonizes Western scientific hegemony in literature via ethnoscientific theory and praxis while also expanding the social justice concerns of ethnofuturism to include traditional and marginalized knowledge.
Evolution of a New Function by Fusion between Phage DNA and a Bacterial Gene
Authors: Warsi Omar , Knopp Michael , Surkov Serhiy , Jerlström Hultqvist Jon , Andersson Dan I
Published: January 2020

Mobile genetic elements, such as plasmids, phages, and transposons, are important sources for evolution of novel functions. In this study, we performed a large-scale screening of metagenomic phage libraries for their ability to suppress temperature-sensitivity in Salmonella enterica serovar Typhimurium strain LT2 mutants to examine how phage DNA could confer evolutionary novelty to bacteria. We identified an insert encoding 23 amino acids from a phage that when fused with a bacterial DNA-binding repressor protein (LacI) resulted in the formation of a chimeric protein that localized to the outer membrane. This relocalization of the chimeric protein resulted in increased membrane vesicle formation and an associated suppression of the temperature sensitivity of the bacterium. Both the host LacI protein and the extracellular 23-amino acid stretch are necessary for the generation of the novel phenotype. Furthermore, mutational analysis of the chimeric protein showed that although the native repressor function of the LacI protein is maintained in this chimeric structure, it is not necessary for the new function. Thus, our study demonstrates how a gene fusion between foreign DNA and bacterial DNA can generate novelty without compromising the native function of a given gene.
Influence of distillers grains with solubles on bull growth and reproductive traits1
Authors: Henley Parker A , Podico Giorgia , Garrett Edgar , Kaplan Claire , Meteer William T , McCann Joshua C , Canisso Igor , Shike Daniel W
Published: January 2020

This study evaluated the effects of offering growing bulls a diet with 40% modified wet distillers grains plus solubles (MWDGS; dry matter [DM] basis) on growth, composition, hoof scores, and reproductive performance. Simmental × Angus bulls (n = 28) were stratified by body weight (BW; 316 ± 29 kg), sire, and day 0 semen production (Y/N) and assigned into one of six pens. Pens were randomly assigned to one of two dietary treatments (n = 3 pens/treatment): 1) offered free-choice access to a corn-based diet with no MWDGS (CON) or 2) offered free-choice access to a diet with 40% MWDGS (DST; DM basis). Bulls were offered treatments for 140 d and, then, switched to a free-choice, common, low-energy diet for an additional 70 d. Bull BW, body condition score (BCS), hip height (HH), ultrasound (rump fat depth [RF], 12th rib fat thickness [BF], marbling score [MS], and longissimus muscle depth [MD]), hoof evaluations, breeding soundness examination (BSE), and semen evaluations were performed on days 0, 28, 56, 84, 112, 140, 175, and 210. There was a tendency (P < 0.09) for a treatment × time effect for BW. Bulls fed DST tended (P ≤ 0.10) to be heavier on days 28 and 56 than CON bulls. A treatment × time effect was detected (P < 0.01) for RF. Bulls fed DST had greater (P = 0.02) RF on day 84 than CON bulls. Treatment × time and treatment effects were detected (P ≤ 0.05) for BF, in which DST bulls had greater (P ≤ 0.05) BF on days 84, 112, and 175 and tended (P ≤ 0.10) to be greater on days 56 and 210 than CON bulls. A treatment × time effect was detected (P < 0.02) for percentage of major sperm defects. Bulls fed DST had a greater (P < 0.01) percentage of major sperm defects on day 140 than control bulls. There was a tendency (P = 0.09) for a treatment × time effect for percentage of sperm with proximal droplets. Bulls fed DST had a greater (P = 0.01) percentage of sperm with proximal droplets on day 140 than CON bulls. In conclusion, offering growing bulls a diet with 40% MWDGS (DM basis) resulted in heavier BW at days 28 and 56, increased RF at day 84, and increased BF and increases in both major sperm defects and sperm with proximal droplets at day 140. However, after 70 d on the common low-energy diet, there were no carryover effects for any growth, composition, hoof, or reproductive measures except for a tendency for BF.
Pediatric Tuberculosis and a Unique Method of Case Finding and Default Prevention: The Case of Baby ‘Lucky’, Moyale Sub-County, Kenya, 2019
Authors: Galgallo Dahabo Adi , Lio Ibrahim , Kochi Adano , Mutiga CCE Dennis Kalikidane , Ransom James
Published: January 2020

We report the case of a 9-month-old male infant diagnosed in the field with extra-pulmonary tuberculosis (TB). Use of innovative global positioning system tracking of pregnant pastoralist women allowed staff to find the mother, locate the infant and enroll the infant in care and treatment. Due to this innovative intervention of case finding and tracking, the infant was prevented from defaulting and completed his anti-TB regimen.
The health and economic burden of podoconiosis in Ethiopia
Authors: Deribe Kebede , Negussu Nebiyu , Newport Melanie J , Davey Gail , Turner Hugo C
Published: January 2020

Background

Podoconiosis is one of the leading causes of lymphoedema-related morbidity in low-income settings, but little is known about the scale of its health and economic impact. This information is required to inform control programme planning and policy. In this study, we estimated the health and economic burden of podoconiosis in Ethiopia.

Methods

We developed a model to estimate the health burden attributed to podoconiosis in terms of the number of disability-adjusted life years (DALYs) and the economic burden. We estimated the economic burden by quantifying the treatment and morbidity-management costs incurred by the healthcare system in managing clinical cases, patients' out-of-pocket costs and their productivity costs.

Results

In 2017, there were 1.5 million cases of podoconiosis in Ethiopia, which corresponds to 172 073 DALYs or 182 per 100 000 people. The total economic burden of podoconiosis in Ethiopia is estimated to be US$213.2 million annually and 91.1% of this resulted from productivity costs. The average economic burden per podoconiosis case was US$136.9.

Conclusions

The national cost of podoconiosis is formidable. If control measures are scaled up and the morbidity burden reduced, this will lead to Ethiopia saving millions of dollars. Our estimates provide important benchmark economic costs to programme planners, policymakers and donors for resource allocation and priority setting.
Making primary healthcare responsive to non-communicable diseases in sub-Saharan Africa
Authors: Baiden Frank
Published: January 2020

Primary healthcare (PHC) meets the needs of people's health throughout their lives and empowers individuals and communities to oversee their own health. Most of the community-based activities currently undertaken in PHC in sub-Saharan Africa (SSA) address child and maternal health. Non-communicable diseases are now major causes of morbidity and premature mortality in SSA. In this paper, I propose the formal integration of community-based, non-communicable disease prevention and early detection into PHC activities. I offer practical suggestions on how this can be achieved to ensure a continuum of care.
Tissue Engineered Vascularized Patient-Specific Temporomandibular Joint Reconstruction in a Yucatan Pig Model
Authors: Abramowicz Shelly , Crotts Sarah Jo , Hollister Scott J. , Goudy Steve
Published: January 2020

Purpose

Pediatric temporomandibular joint (TMJ) reconstruction occurs as a result of acquired, developmental, and/or congenital conditions. Current pediatric reconstruction options are limited. The aim of this project was to develop a proof of principle porcine model for a load bearing, customized 3-dimensional (3D) printed and BMP2-coated scaffold implanted in a pedicled (temporal) flap as a regenerative approach to pediatric TMJ mandibular condyle reconstruction.

Materials and Methods

Scaffolds were custom designed and 3D printed based on porcine computed tomography and absorbed with BMP2. Two operations occured: (1) implantation of scaffold in temporalis muscle to establish vascularity, and six weeks later, (2) unilateral condylectomy and rotation of the vascularized scaffold (with preservation of superficial temporal artery) onto mandibular ramus defect and secured with titanium screws. At 6 months post-implantation, the pigs were sacrified. The experimental side (muscle-scaffold) and the control side (unoperated condyle) were individually harvested at 6 months and evaluated by clinical, mechanical, radiographic, and qualitative/histologic methods.

Results

Scaffolds maintained physical properties similar in appearance to unoperated condyles. The vascularized scaffolds had bone formation at edges and adjacent to scaffold-bone interface. New bone was visible in scaffold. Condyle height on the reconstructed side was 68% and 78% of the control side. Reconstructed condyle stiffness was between 20% and 45% of the control side.

Conclusion

In our porcine model, customized 3D printed TMJ scaffolds impregnanted with BMP2 and implanted in and pedicled on temporalis muscle has the ability to (1) reconstruct a TMJ defect model, (2) maintain appropriate condylar height and upper airway diameter, and (3) generate new bone, without impacting functional outcomes.
Radius-Optimized Efficient Template Matching for Lesion Detection from Brain Images
Authors: Koley Subhranil , Dutta Pranab K. , Aganj Iman
Published: January 2020

Computer-aided detection of brain lesions from volumetric magnetic resonance imaging (MRI) is in demand for fast and automatic diagnosis of neural diseases. The template-matching technique can provide satisfactory outcome for automatic localization of brain lesions; however, finding the optimal template size that maximizes similarity of the template and the lesion remains challenging. This increases the complexity of the algorithm and the requirement for computational resources, while processing large MRI volumes with three-dimensional (3D) templates. Hence, reducing the computational complexity of template matching is needed. In this paper, we first propose a mathematical framework for computing the normalized cross-correlation coefficient (NCCC) as the similarity measure between the MRI volume and approximated 3D Gaussian template with linear time complexity,, as opposed to the conventional fast Fourier transform (FFT) based approach with the complexity, whereNis the number of voxels in the image andamaxis the number of tried template radii. We then propose a mathematical formulation to analytically estimate the optimal template radius for each voxel in the image and compute the NCCC with the location-dependent optimal radius, reducing the complexity to. We test our methods on one synthetic and two real multiple-sclerosis databases, and compare their performances in lesion detection with FFT and a state-of-the-art lesion prediction algorithm. We demonstrate through our experiments the efficiency of the proposed methods for brain lesion detection and their comparable performance with existing techniques.
Amphetamine Maintenance Therapy During Intermittent Cocaine Self-Administration in Rats: Reduction of Addiction-like Behavior is Associated with Attenuation of Psychomotor and Dopamine Sensitization
Authors: Allain Florence , Delignat-Lavaud Benoît , Beaudoin Marie-Pierre , Jacquemet Vincent , Robinson Terry E. , Trudeau Louis-Eric , Samaha Anne-Noël
Published: January 2020

Background

D-amphetamine maintenance therapy shows promise as a treatment for people with cocaine addiction. Preclinical studies using Long Access (LgA) cocaine self-administration procedures suggest D-amphetamine may act by preventing tolerance to cocaine’s effects at the dopamine transporter (DAT). However, Intermittent Access (IntA) cocaine self-administration better reflects human patterns of use, is especially effective in promoting addiction-relevant behaviors, and instead of tolerance, produces psychomotor, incentive, and neural sensitization. We asked, therefore, how D-amphetamine maintenance during IntA influences cocaine use and cocaine’s potency at the DAT.

Methods

Male rats self-administered cocaine intermittently (5 minutes ON, 25 minutes OFF x 10) for 14 sessions, with or without concomitant D-amphetamine (5 mg/kg/day via s.c. osmotic minipump). In Experiment 1, psychomotor sensitization, responding for cocaine under a progressive ratio schedule, responding under extinction and cocaine-primed relapse were assessed. In Experiment 2, rats self-administered cocaine or saline intermittently, with or without D-amphetamine, and the ability of cocaine to inhibit dopamine uptake in the nucleus accumbens core was assessed using fast scan cyclic voltammetryex vivo.

Results

IntA cocaine self-administration produced psychomotor sensitization, strong motivation to take and seek cocaine, and it increased cocaine’s potency at the DAT. The co-administration of D-amphetamine suppressed both the psychomotor sensitization and high motivation for cocaine produced by IntA experience, and also reversed sensitization of cocaine’s actions at the DAT, leaving baseline DAT function unchanged.

Conclusions

Treatment with D-amphetamine might reduce cocaine use by preventing sensitization-related changes in cocaine potency at the DAT, consistent with an incentive-sensitization view of addiction.
Endemic and epidemic human alphavirus infections in Eastern Panama; An Analysis of Population-based Cross-Sectional Surveys
Authors: Carrera Jean-Paul , Cucunubá Zulma M. , Neira Karen , Lambert Ben , Pittí Yaneth , Jackman Carmela , Liscano Jesus , Garzón Jorge L. , Beltran Davis , Collado-Mariscal Luisa , Saenz Lisseth , Sosa Néstor , Rodriguez-Guzman Luis D. , González Publio , Lezcano Andrés G. , Pereyra-Elías Reneé , Valderrama Anayansi , Weaver Scott C. , Vittor Amy Y. , Armién Blas , Pascale Juan-Miguel , Donnelly Christl A.
Published: January 2020

Background

Madariaga virus (MADV), has recently been associated with severe human disease in Panama, where the closely related Venezuelan equine encephalitis virus (VEEV) also circulates. In June, 2017, a fatal MADV infection was confirmed in a community of Darien province.

Methods

We conducted a cross-sectional outbreak investigation with human and mosquito collections in July 2017, where sera were tested for alphavirus antibodies and viral RNA. Additionally, by applying a catalytic, force-of-infection statistical model to two serosurveys from Darien province in 2012 and 2017, we investigated whether endemic or epidemic alphavirus transmission occurred historically.

Results

In 2017, MADV and VEEV IgM seroprevalence was 1.6% and 4.4%, respectively; IgG antibody prevalences were MADV: 13.2%; VEEV: 16.8%; Una virus (UNAV): 16.0%; and Mayaro virus (MAYV): 1.1%. Active viral circulation was not detected. Evidence of MADV and UNAV infection was found near households — raising questions about its vectors and enzootic transmission cycles. Insomnia was associated with MADV and VEEV infection, depression symptoms were associated with MADV, and dizziness with VEEV and UNAV. Force-of-infection analyses suggest endemic alphavirus transmission historically, with recent increased human exposure to MADV and VEEV in some regions.

Conclusions

The lack of additional neurological cases suggest that severe MADV and VEEV infections occur only rarely. Our results indicate that, over the past five decades, alphavirus infections have occurred at low levels in eastern Panama, but that MADV and VEEV infections have recently increased — potentially during the past decade. Endemic infections and outbreaks of MADV and VEEV appear to differ spatially.

Author summary

Prior to 2010, it was believed that the Madariaga virus (MADV) was primarily associated with equine disease. However, an outbreak reported in Panama, in an endemic area where Venezuelan equine encephalitis virus (VEEV) also circulates, suggested a change in its epidemiological profile. We aimed to reconstruct the epidemiological dynamics of MADV and VEEV, as well as additional alphaviruses known to circulate in the region in order to understand MADV emergence. For this, cross-sectional serosurveys were used to demonstrate that the Alphaviruses MADV, VEEV and Una virus have repeatedly infected humans in eastern Panama over the past five decades. Whilst their historical transmission has been low, we confirm that the transmission has recently increased for both MADV and VEEV.
Fertility factors affect the vaginal microbiome in women of reproductive age
Authors: Xu Jieying , Bian Gaorui , Zheng Min , Lu Gang , Chan Wai‐Yee , Li Weiping , Yang Kaiping , Chen Zi‐Jiang , Du Yanzhi
Published: January 2020

Problem

For women of reproductive age, achieving a successful pregnancy requires both the normal functioning of reproductive endocrine and the health of the reproductive tract environment. We aimed to study how these fertility factors, such as female age, baseline sexual hormone levels, tubal patency, and vaginal pH, affect the composition of vaginal microbiome.

Method of study

The 16S rRNA sequencing was carried on vaginal microbiome samples from 85 women of reproductive age without vaginal infections or reproductive endocrine diseases. The detailed correlations between fertility factors and vaginal microbiome were quantified by Spearman's rank tests. A linear discriminant analysis was carried out to explore the effects of fertility factors on the relative abundances of vaginal bacterial species.

Results

The vaginal pH, levels of basal E2, LH, and FSH all had significant effects on the distribution of vaginal microbiome. The relative abundances of vaginal bacterial species, includingEscherichia coli,Streptococcus agalactiae, andPrevotella intermedia, were significantly different due to the host's state of reproductive endocrine and tubal patency. It was worth noting that women with tubal obstruction, or prolonged menstrual cycle, or antral follicle count >15, or vaginal pH > 4.5 all had a higher abundance ofEscherichia coliin vagina.

Conclusion

The fertility factors associated with the reproductive endocrine and the genital tract environment affected vaginal microbiome in women of reproductive age. The speciesEscherichia coli,Streptococcus agalactiae,Prevotella intermedia, etc could be used as biomarkers to reflect the pathological state of reproductive endocrine and genital tract.
Understanding children with cerebral palsy and bullying: A mixed methods approach
Authors: Stang Kristina , Frainey Brendan , Tann Beverley , Ehrlich‐Jones Linda , Deike Dawn , Gaebler‐Spira Deborah
Published: January 2020

Aim

The study aims to explore the views of children with cerebral palsy (CP) regarding their experiences being bullied and their perceptions of their primary bully.

Method

Forty‐three children aged 10–18 with CP were given the California Bullying Victimization Scale. Fourteen of the children shared a bullying experience orally or written after the survey. Using a mixed methods analysis, the survey answers were tabulated with descriptive statistics and analysed by Gross Motor Function Classification System (GMFCS) level. The comments were coded to determine qualitative responses.

Results

Most bullied children viewed the bully as less than or at least equal to them regarding popularity (73%), performance in schoolwork (85%), and physical strength (56%). Bullied children preferentially told an adult at home. Code words and common categories of bullying were determined from their experiences.

Interpretation

Children with CP experience bullying but do not view themselves as inferior to their bully in popularity, intelligence, or physical strength. Most bullied participants confided in an adult at home. Children with GMFCS Levels 1, 2, and 3 seem to be at greater risk for bullying than children with GMFCS Levels 4 and 5. Children with CP demonstrate individualized strategies for resilience with reliance on adults for resources.
Estimated prevalence of disability and developmental delay among preschool children in rural Malawi: Findings from “Tikule Limodzi,” a cross‐sectional survey
Authors: Murphy Rachel , Jolley Emma , Lynch Paul , Mankhwazi Mika , Mbukwa Jenipher , Bechange Stevens , Gladstone Melissa J. , Schmidt Elena
Published: January 2020

Background

Early childhood development (ECD) is a critical stage in children's lives, influencing future development and social integration. ECD research among children with disability and developmental delay in low‐ and middle‐income countries is limited but crucial to inform planning and delivery of inclusive services. This study is the first to measure and compare the prevalence of disability and developmental delay among children attending preschool centres in rural Malawi.

Methods

A cross‐sectional survey was conducted in 48 preschool centres in Thyolo district, Malawi. Data were collected from parents or guardians of 20 children per centre. Disability was ascertained using the Washington Group/UNICEF Child Functioning Module. Child development was measured using the language and social domains of the Malawi Development Assessment Tool.

Results

A total of 960 children were enrolled; 935 (97.4%) children were assessed for disability and 933 (97.2%) for developmental delay; 100 (10.7%) children were identified as having a disability. The prevalence of disability was higher among children 5+ years (n = 60; 29.3%) than children 2–4 years (n = 40; 5.5%); 109 of 933 (11.7%) children were classified as having developmental delay, 41 (4.4%) in “language” and 77 (8·3%) in “social” domains.

Conclusions

This study found that disability and developmental delays are common among preschool children in Malawi. It is one of the first to measure disability and delay among children in a preschool setting in Africa.