bluuebunny/crossref_metadata_2025 huggingface dataset:
Virus-inclusive single-cell RNA sequencing reveals the molecular signature of progression to severe dengue
Authors: Zanini Fabio , Robinson Makeda L. , Croote Derek , Sahoo Malaya Kumar , Sanz Ana Maria , Ortiz-Lasso Eliana , Albornoz Ludwig Luis , Rosso Fernando , Montoya Jose G. , Goo Leslie , Pinsky Benjamin A. , Quake Stephen R. , Einav Shirit
Published: December 2018

Dengue virus (DENV) infection can result in severe complications. However, the understanding of the molecular correlates of severity is limited, partly due to difficulties in defining the peripheral blood mononuclear cells (PBMCs) that contain DENV RNA in vivo. Accordingly, there are currently no biomarkers predictive of progression to severe dengue (SD). Bulk transcriptomics data are difficult to interpret because blood consists of multiple cell types that may react differently to infection. Here, we applied virus-inclusive single-cell RNA-seq approach (viscRNA-Seq) to profile transcriptomes of thousands of single PBMCs derived early in the course of disease from six dengue patients and four healthy controls and to characterize distinct leukocyte subtypes that harbor viral RNA (vRNA). Multiple IFN response genes, particularly MX2 in naive B cells and CD163 in CD14
+
CD16
+
monocytes, were up-regulated in a cell-specific manner before progression to SD. The majority of vRNA-containing cells in the blood of two patients who progressed to SD were naive IgM B cells expressing the CD69 and CXCR4 receptors and various antiviral genes, followed by monocytes. Bystander, non-vRNA–containing B cells also demonstrated immune activation, and IgG1 plasmablasts from two patients exhibited clonal expansions. Lastly, assembly of the DENV genome sequence revealed diversity at unexpected sites. This study presents a multifaceted molecular elucidation of natural dengue infection in humans with implications for any tissue and viral infection and proposes candidate biomarkers for prediction of SD.
Combined molecular dynamics and neural network method for predicting protein antifreeze activity
Authors: Kozuch Daniel J. , Stillinger Frank H. , Debenedetti Pablo G.
Published: December 2018

Significance

Antifreeze proteins offer a technologically underutilized approach for controlling the freezing of water, a process intrinsically important in broad areas, such as medicine, agriculture, and food engineering, among others. To harness this capability, a better understanding of the measurable properties involved and their quantitative contribution to the observed antifreeze effect is needed. Here, we present a physically motivated method for the prediction of antifreeze activity purely from simulation, opening routes for the design of computationally optimized antifreeze materials.
MTSS1/Src family kinase dysregulation underlies multiple inherited ataxias
Authors: Brown Alexander S. , Meera Pratap , Altindag Banu , Chopra Ravi , Perkins Emma M. , Paul Sharan , Scoles Daniel R. , Tarapore Eric , Magri Jessica , Huang Haoran , Jackson Mandy , Shakkottai Vikram G. , Otis Thomas S. , Pulst Stefan M. , Atwood Scott X. , Oro Anthony E.
Published: December 2018

Significance

The Src family of nonreceptor tyrosine kinases (SFK) is essential for nervous system function and may contribute to neurodegeneration. Spinocerebellar ataxias (SCAs) are neurodegenerative diseases in which Purkinje neurons fire irregularly and degenerate leading to motor problems. We show that the SFK suppressor Missing-in-metastasis (MTSS1) is an ataxia gene that links multiple SCAs. MTSS1 loss results in increased SFK activity, degenerating Purkinje neurons with low firing rates, and cell death. Surprisingly, mouse models for three different SCAs show elevated SFK activity, with SCA1 and SCA2 models displaying dramatically reduced MTSS1 protein levels. Treatment of each SCA model with an SFK inhibitor corrects Purkinje basal firing and delays ataxia progression in MTSS1 mutants. Our results identify a common link among disparate neurodegenerative diseases.
Fluctuating selection on migrant adaptive sodium transporter alleles in coastal
Arabidopsis thaliana
Authors: Busoms Silvia , Paajanen Pirita , Marburger Sarah , Bray Sian , Huang Xin-Yuan , Poschenrieder Charlotte , Yant Levi , Salt David E.
Published: December 2018

Stressors such as soil salinity and dehydration are major constraints on plant growth, causing worldwide crop losses. Compounding these insults, increasing climate volatility requires adaptation to fluctuating conditions. Salinity stress responses are relatively well understood in
Arabidopsis thaliana
, making this system suited for the rapid molecular dissection of evolutionary mechanisms. In a large-scale genomic analysis of Catalonian
A. thaliana
, we resequenced 77 individuals from multiple salinity gradients along the coast and integrated these data with 1,135 worldwide
A. thaliana
genomes for a detailed understanding of the demographic and evolutionary dynamics of naturally evolved salinity tolerance. This revealed that Catalonian varieties adapted to highly fluctuating soil salinity are not Iberian relicts but instead have immigrated to this region more recently. De novo genome assembly of three allelic variants of the high-affinity K
+
transporter (
HKT1;1
) locus resolved structural variation between functionally distinct alleles undergoing fluctuating selection in response to seasonal changes in soil salinity. Plants harboring alleles responsible for low root expression of
HKT1;1
and consequently high leaf sodium (
HKT1;1

HLS

) were migrants that have moved specifically into areas where soil sodium levels fluctuate widely due to geography and rainfall variation. We demonstrate that the proportion of plants harboring
HKT1;1

HLS

alleles correlates with soil sodium level over time,
HKT1;1

HLS

-harboring plants are better adapted to intermediate levels of salinity, and the
HKT1;1

HLS

allele clusters with high-sodium accumulator accessions worldwide. Together, our evidence suggests that
HKT1;1
is under fluctuating selection in response to climate volatility and is a worldwide determinant in adaptation to saline conditions.
Assessing the discrimination of the Kidney Donor Risk Index/Kidney Donor Profile Index scores for allograft failure and estimated glomerular filtration rate in Ireland’s National Kidney Transplant Programme
Authors: Sexton Donal J , O’Kelly Patrick , Kennedy Claire , Denton Mark , de Freitas Declan G , Magee Colm , O’Seaghdha Conall M , Conlon Peter J
Published: December 2018

Background

The Kidney Donor Risk Index (KDRI)/Kidney Donor Profile Index (KDPI) is relied upon for donor organ allocation in the USA, based on its association with graft failure in time-to-event models. However, the KDRI/KDPI has not been extensively evaluated in terms of predictive metrics for graft failure and allograft estimated glomerular filtration rate (eGFR) outside of the USA.

Methods

We performed a retrospective analysis of outcomes in the Irish National Kidney Transplant Service Registry for the years 2006–13. Associations of the KDRI/KDPI score with eGFR at various time points over the follow-up and ultimate graft failure were modelled.

Results

A total of 772 patients had complete data regarding KDRI/KDPI calculation and 148 of these allografts failed over the follow-up. The median and 25–75th centile for KDRI/KDPI was 51 (26–75). On repeated-measures analysis with linear mixed effects models, the KDRI/KDPI (fixed effect covariate) associated with eGFR over 5 years: eGFR = −0.25 (standard error 0.02; P < 0.001). The variability in eGFR mathematically accounted for by the KDRI/KDPI score was only 21%. The KDRI/KDPI score did not add significantly to graft failure prediction above donor age alone (categorized as > and <50 years of age) when assessed by the categorical net reclassification index.

Conclusions

In this cohort, while the KDRI/KDPI was predictive of eGFR over the follow-up, it did not provide additive discrimination above donor age alone in terms of graft failure prediction. Therefore it is unlikely to help inform decisions regarding kidney organ allocation in Ireland.
Proof of concept for quantitative urine NMR metabolomics pipeline for large-scale epidemiology and genetics
Authors: Tynkkynen Tuulia , Wang Qin , Ekholm Jussi , Anufrieva Olga , Ohukainen Pauli , Vepsäläinen Jouko , Männikkö Minna , Keinänen-Kiukaanniemi Sirkka , Holmes Michael V , Goodwin Matthew , Ring Susan , Chambers John C , Kooner Jaspal , Järvelin Marjo-Riitta , Kettunen Johannes , Hill Michael , Davey Smith George , Ala-Korpela Mika
Published: December 2018

Background

Quantitative molecular data from urine are rare in epidemiology and genetics. NMR spectroscopy could provide these data in high throughput, and it has already been applied in epidemiological settings to analyse urine samples. However, quantitative protocols for large-scale applications are not available.

Methods

We describe in detail how to prepare urine samples and perform NMR experiments to obtain quantitative metabolic information. Semi-automated quantitative line shape fitting analyses were set up for 43 metabolites and applied to data from various analytical test samples and from 1004 individuals from a population-based epidemiological cohort. Novel analyses on how urine metabolites associate with quantitative serum NMR metabolomics data (61 metabolic measures; n = 995) were performed. In addition, confirmatory genome-wide analyses of urine metabolites were conducted (n = 578). The fully automated quantitative regression-based spectral analysis is demonstrated for creatinine and glucose (n = 4548).

Results

Intra-assay metabolite variations were mostly <5%, indicating high robustness and accuracy of urine NMR spectroscopy methodology per se. Intra-individual metabolite variations were large, ranging from 6% to 194%. However, population-based inter-individual metabolite variations were even larger (from 14% to 1655%), providing a sound base for epidemiological applications. Metabolic associations between urine and serum were found to be clearly weaker than those within serum and within urine, indicating that urinary metabolomics data provide independent metabolic information. Two previous genome-wide hits for formate and 2-hydroxyisobutyrate were replicated at genome-wide significance.

Conclusion

Quantitative urine metabolomics data suggest broad novelty for systems epidemiology. A roadmap for an open access methodology is provided.
City Streets in Rural Places: Emerging Cities, Youth Cultures, and the Neoliberalization of Guatemala
Authors: Way J T
Published: December 2018

This article traces the emergence of “agro-urban” cities in rural Guatemala from the genocide of 1981–83 to the end of the millennium, paying special attention to the multilingual Mayan highlands. It weaves together a study of changes in the political economy and the built environment with an examination of the cultural transformations associated with urbanization, ethnic politics, and youth countercultures, including an outbreak of small Maya street gangs in the highlands in the late 1990s. It argues that one of the most “rural” regions on earth became home to a new, agrarian modality of the global city as the result of a stepwise process of neoliberalization and that, as part of this process, youth street cultures moved to the fore as a site of contested cultural production. Behind this surprising urbanization and cultural cosmopolitanism was massive public investment that worked to neoliberalize military structures of counterinsurgency and change the nation’s agricultural portfolio in the midst of a war that lasted until 1996. Organizations such as the World Bank, the Inter-American Development Bank, USAID, scores of NGOs, and the United Nations all played roles in these processes, just as they promoted a burgeoning Mayan Movement and helped to foment “neoliberal multiculturalism” as the politics of race came to overshadow the politics of class. In neoliberalizing Guatemala, the globally inflected city “street,” once a territory almost exclusively restricted to the capital city, took on national dimensions. It became a national commons, a social space in which youth negotiated the terms of their belonging.
High diversity of Candida glabrata in a tertiary hospital—Mwanza, Tanzania
Authors: Mushi Martha F , Gross Uwe , Mshana Stephen E , Bader Oliver
Published: December 2018

Candida glabrata is a genetically diverse human pathogenic yeast, whose subpopulations have been documented to vary geographically. Here, we report MLST genotypes and antifungal drug susceptibility of C. glabrata isolates from Africa. Among 47 mostly urogenital isolates, we found 13 sequence types, amounting to a 27% genetic population difference. More than half of the isolates were of novel sequence types. ST18 was most predominant and had reduced susceptibility to fluconazole. There was clear segregation of STs between urine and vaginal specimen. In Tanzania, the C. glabrata population is genetically diverse, and divergent from those seen in other countries.
Flt3 inhibition alleviates chronic kidney disease by suppressing CD103+ dendritic cell-mediated T cell activation
Authors: Wang Ruifeng , Chen Titi , Wang Chengshi , Zhang Zhiqiang , Wang Xin Maggie , Li Qing , Lee Vincent W S , Wang Yuan Min , Zheng Guoping , Alexander Stephen I , Wang Yiping , Harris David C H , Cao Qi
Published: December 2018

Background

Chronic kidney disease (CKD) is a global public health problem, which lacks effective treatment. Previously, we have shown that CD103+ dendritic cells (DCs) are pathogenic in adriamycin nephropathy (AN), a model of human focal segmental glomerulosclerosis (FSGS). Fms-like tyrosine kinase 3 (Flt3) is a receptor that is expressed with high specificity on tissue resident CD103+ DCs.

Methods

To test the effect on CD103+ DCs and kidney injury of inhibition of Flt3, we used a selective Flt3 inhibitor (AC220) to treat mice with AN.

Results

Human CD141+ DCs, homologous to murine CD103+ DCs, were significantly increased in patients with FSGS. The number of kidney CD103+ DCs, but not CD103− DCs or plasmacytoid DCs, was significantly decreased in AN mice after AC220 administration. Treatment with AC220 significantly improved kidney function and reduced kidney injury and fibrosis in AN mice. AC220-treated AN mice had decreased levels of inflammatory cytokines and chemokines, tumor necrosis factor-α, interleukin (IL)-1β, IL-6, CCL2 and CCL5 and reduced kidney infiltration of CD4 T cells and CD8 T cells. The protective effect of AC220 was associated with its suppression of CD103+ DCs-mediated CD8 T cell proliferation and activation in AN mice.

Conclusion

Flt3 inhibitor AC220 effectively reduced kidney injury in AN mice, suggesting that this inhibitor might be a useful pharmaceutical agent to treat CKD.
Repeatable Battery for the Assessment of Neuropsychological Status (RBANS): preliminary utility in adult neuro-oncology
Authors: Loughan Ashlee R , Braun Sarah E , Lanoye Autumn
Published: December 2018

Background

Neurocognitive assessments have become integral to comprehensive neuro-oncology care. Existing screening tools may be insensitive to cognitive changes caused by medical treatments. Research supports the clinical value and psychometric properties of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) in various medical populations; however, there is minimal evidence for its use in neuro-oncology. The purpose of the current study was to further explore the cognitive profile of patients with primary brain tumor (PBT) using the RBANS and to assess rates of below-expectation performance compared to normative data and estimated intellectual functioning.

Methods

Data were collected on 82 PBT patients (54% male; age range, 19-81 years). All patients were administered the RBANS-Update and the Advanced Clinical Solutions–Test of Premorbid Functioning (TOPF) according to standardized instructions. Cognitive strengths and weaknesses were identified for PBT patients. Descriptive analyses, t tests, and chi-squared tests were utilized to identify and compare cognitive profiles.

Results

Overall, cognitive performance was low average for PBT patients. When compared to standardization data, PBT patients performed significantly worse across all 5 RBANS indexes, with Attention and Memory showing the largest discrepancies. Estimated intelligence analyses reflected greater deficits in cognitive functioning than when compared to a normal distribution.

Conclusions

Preliminary research demonstrates the RBANS is an efficient screening tool to assess cognitive deficits in PBT patients. Data also support the importance of comparison to self, rather than normative distribution in ensuring proper identification and classification of patients.
Aberrant Frontostriatal Connectivity in Negative Symptoms of Schizophrenia
Authors: Shukla Dinesh K , Chiappelli Joshua John , Sampath Hemalatha , Kochunov Peter , Hare Stephanie M , Wisner Krista , Rowland Laura M , Hong L Elliot
Published: December 2018

Negative symptoms represent a distinct component of psychopathology in schizophrenia (SCZ) and are a stable construct over time. Although impaired frontostriatal connectivity has been frequently described in SCZ, its link with negative symptoms has not been carefully studied. We tested the hypothesis that frontostriatal connectivity at rest may be associated with the severity of negative symptoms in SCZ. Resting state functional connectivity (rsFC) data from 95 mostly medicated patients with SCZ and 139 healthy controls (HCs) were acquired. Negative symptoms were assessed using the Brief Negative Symptom Scale. The study analyzed voxel-wise rsFC between 9 frontal “seed regions” and the entire striatum, with the intention to reduce potential biases introduced by predefining any single frontal or striatal region. SCZ showed significantly reduced rsFC between the striatum and the right medial and lateral orbitofrontal cortex (OFC), lateral prefrontal cortex, and rostral anterior cingulate cortex compared with HCs. Further, rsFC between the striatum and the right medial OFC was significantly associated with negative symptom severity. The involved striatal regions were primarily at the ventral putamen. Our results support reduced frontostriatal functional connectivity in SCZ and implicate striatal connectivity with the right medial OFC in negative symptoms. This task-independent resting functional magnetic resonance imaging study showed that medial OFC–striatum functional connectivity is reduced in SCZ and associated with severity of negative symptoms. This finding supports a significant association between frontostriatal connectivity and negative symptoms and thus may provide a potential circuitry-level biomarker to study the neurobiological mechanisms of negative symptoms.
Christian America in Black and White: Racial Identity, Religious-National Group Boundaries, and Explanations for Racial Inequality
Authors: Perry Samuel L , Whitehead Andrew L
Published: December 2018

Recent research suggests that, for white Americans, conflating national and religious group identities is strongly associated with racism, xenophobia, and Islamophobia, prompting some to argue that claims about Christianity being central to American identity are essentially about reinforcing white supremacy. Prior work has not considered, however, whether such beliefs may influence the racial views of nonwhite Americans differently from white Americans. Drawing on a representative sample of black and white Americans from the 2014 General Social Survey, and focusing on explanations for racial inequality as the outcome, we show that, contrary to white Americans, black Americans who view being a Christian as essential to being an American are actually more likely to attribute black–white inequality to structural issues and less to blacks’ individual shortcomings. Our findings suggest that, for black Americans, connecting being American to being Christian does not necessarily bolster white supremacy, but may instead evoke and sustain ideals of racial justice.
Infrared thermography as a tool to detect hoof lesions in sheep
Authors: Byrne Daire T , Berry Donagh P , Esmonde Harold , McGovern Fiona , Creighton Philip , McHugh Nóirín
Published: December 2018

Lameness has a major negative impact on sheep production. The objective of this study was to 1) quantify the repeatability of sheep hoof temperatures estimated using infrared thermography (IRT); 2) determine the relationship between ambient temperature, sheep hoof temperature, and sheep hoof health status; and 3) validate the use of IRT to detect infection in sheep hooves. Three experiments (a repeatability, exploratory, and validation experiment) were conducted over 10 distinct nonconsecutive days. In the repeatability experiment, 30 replicate thermal images were captured from each of the front and back hooves of nine ewes on a single day. In the exploratory experiment, hoof lesion scores, locomotion scores, and hoof thermal images were recorded every day from the same cohort of 18 healthy ewes in addition to a group of lame ewes, which ranged from one to nine ewes on each day. Hoof lesion and locomotion scores were blindly recorded by three independent operators. In the validation experiment, all of the same procedures from the exploratory experiment were applied to a new cohort of 40 ewes across 2 d. The maximum and average temperature of each hoof was extracted from the thermal images. Repeatability of IRT measurements was assessed by partitioning the variance because of ewe and error using mixed models. The relationship between ambient temperature, hoof temperature, and hoof health status was quantified using mixed models. The percentage of hooves correctly classified as healthy (i.e., specificity) and infected (i.e., sensitivity) was calculated for a range of temperature thresholds. Results showed that a small-to-moderate proportion of the IRT-estimated temperature variability in a given hoof was due to error (1.6% to 20.7%). A large temperature difference (8.5 °C) between healthy and infected hooves was also detected. The maximum temperature of infected hooves was unaffected by ambient temperature (P > 0.05), whereas the temperature of healthy hooves was associated with ambient temperature. The best sensitivity (92%) and specificity (91%) results in the exploratory experiment were observed when infected hooves were defined as having a maximum hoof temperature ≥9 °C above the average of the five coldest hooves in the flock on that day. When the same threshold was applied to the validation dataset, a sensitivity of 77% and specificity of 78% was achieved, indicating that IRT could have the potential to detect infection in sheep hooves.
Influence of therapeutic use of feedgrade tetracyclines in combination with tulathromycin metaphylaxis on animal health and performance of Holstein steer calves1
Authors: Szasz Josh I , McMurphy Casey P , Bryant Tony C , Luque Job , Barcelo Cristobal , Sepulveda Gabriel , Blood K Shawn , Bernhard Bryan C , Hughes Heather D
Published: December 2018

Feedgrade chlortetracycline (CTC) and oxytetracycline (OTC) are approved for use in beef cattle diets for the control of bovine respiratory disease (BRD). The objectives of this experiment were to compare CTC and OTC, administered according to label, for the treatment of BRD in Holstein calves and to characterize the influence of tulathromycin metaphylaxis in combination with tetracycline treatment. Summer-placed Holstein steer calves (n = 6,800) were randomly assigned to one of four treatments (11 blocks; initial BW = 140 ± 18 kg) as they passed through the squeeze chute at initial processing in a commercial feedlot. Treatments consisted of: (i) CTC and tulathromycin metaphylaxis (CTC+TUL), (ii) OTC and tulathromycin metaphylaxis (OTC+TUL), (iii) tulathromycin metaphylaxis only (TUL), or (iv) CTC only (CTC). Cattle were fed for an average of 118 d. Tetracycline feeding was instituted based on visual assessment of the attending veterinarian in accordance with the veterinary feed directive. When applicable, CTC was fed as a top-dress at a rate of 4 g CTC·steer−1·d−1 for 5 consecutive days, beginning on 6 d on feed (DOF). Three 5-d pulses were delivered to CTC+TUL and CTC cattle, with a 48-h time lapse between pulses. Cattle on OTC+TUL were administered 4 g OTC·steer−1·d−1 as part of a complete diet for 14 consecutive days beginning on 10 DOF. Within the first 30 d of the feeding period, BRD first pulls were reduced (P = 0.001) for CTC+TUL, OTC+TUL, and TUL relative to CTC alone. Percentage of BRD first pulls and total morbidity were lowest (P = 0.001) for CTC+TUL across the feeding period, with OTC+TUL and TUL being intermediate, and CTC alone exhibiting the highest percentage. Death loss and railers were not influenced (P ≥ 0.58) by treatment. Dry matter intake was greater (P = 0.001) for CTC+TUL than all other treatments. Final BW and ADG were greatest for CTC+TUL, lowest for TUL alone, and intermediate for the remaining treatments (P < 0.05) on a deads-and-railers-out basis. Deads-and-railers-in ADG was greatest (P < 0.05) for CTC+TUL compared to all other treatments. Feed conversion was not influenced (P ≥ 0.22) by treatment. In the current study, supplementation of OTC in combination with tulathromycin metaphylaxis did not benefit health over tulathromycin alone. Results suggest that CTC in combination with tulathromycin metaphylaxis reduces morbidity in Holstein steers calves, which may lead to improved performance.
Correction of complex lower limb angular deformities with or without length discrepancy in children using the TL-HEX hexapod system: comparison of clinical and radiographical results
Authors: Riganti Simone , Nasto Luigi A. , Mannino Salvatore , Marrè Brunenghi Giorgio , Boero Silvio
Published: December 2018

The aim of this study was to compare clinical and radiographical results for treatment of lower limb multiaxial deformities±limb length discrepancy (LLD) of at least 2 cm with the Truelok hexapod fixator system (TL-HEX). All consecutive cases of lower limb multiaxial deformities were included. Patients were divided in two groups: group 1, lower limb angular deformity+LLD less than 2 cm, and group 2, lower limb angular deformity+LLD of at least 2 cm. Only patients with age younger than or equal to 20 years and follow-up of 6 months after removal of the external fixator were included. A total of 27 (six femur and 39 tibia treated) and 20 patients (12 femur and 19 tibia) were enrolled in groups 1 and 2, respectively. Complete correction of the deformity was achieved in 90 and 96% of the patients in groups 1 and 2, respectively. There were no differences in terms of external fixator, maturation, and distraction indexes between the two groups and between different anatomical sites. Good to excellent functional results (ASAMI score) were obtained in 93% of patients in group 1 and 75% in group 2 (P=0.01). Complication rate was similar between the two groups (7.4 vs. 10%, respectively). Average follow-up after removal of the external fixator was 25.6 (range: 7.0–54.0) months. The TL-HEX external fixator system allows a predictable correction of complex lower limb deformities regardless of the presence of LLD. Although complication rate is similar between the two groups, lower functional outcomes can be expected in patients with significant preoperative LLD.
Cardiovascular Effects of Drugs Used to Treat Attention-Deficit/Hyperactivity Disorder Part 2
Authors: Fay Thomas B. , Alpert Martin A.
Published: December 2018

A variety of psychostimulant and nonpsychostimulant medications have proven to be successful in reducing inattention, impulsivity, and hyperactivity in individuals with attention-deficit/hyperactivity disorder (ADHD). Psychostimulants used to treat ADHD include methylphenidate and related drugs and various amphetamine preparations. Nonpsychostimulant medications used to treat ADHD include atomoxetine and 2 α-2 adrenergic agonists: guanfacine extended-release and clonidine extended-release. The psychostimulants and atomoxetine have been shown, on average, to increase heart rate by 3–10 beats/min, systolic blood pressure by 3–8 mm Hg, and diastolic BP by 2–14 mm Hg. These drugs may also delay ventricular repolarization. The α-2 adrenergic agonists may reduce heart rate and BP. For these reasons, there is concern about the safety of psychostimulant and nonpsychostimulant medications in patients with ADHD. Studies in healthy children adolescents and adults have not consistently shown a disproportionately high risk of major adverse cardiovascular (CV) outcomes, including sudden unexpected death. Those with underlying CV disease have, in general, tolerated these drugs well. Certain high-risk groups have been identified who may benefit from cardiology consultation prior to drug initiation. Several American and Canadian professional societies have published guidelines for CV evaluation, management, and monitoring of patients with ADHD who are candidates for pharmacotherapy.
Cardiac Applications of Dual-Energy Computed Tomography
Authors: Lempel Matthew , Frishman William H.
Published: December 2018

Computed tomography is an established tool in the assessment of cardiac anatomy and function. As demonstrated by single photon emission computed tomography, positron emission tomography, and magnetic resonance, the noninvasive evaluation of coronary hemodynamics is an important step in guiding clinical management. Nevertheless, no single modality has been shown to accurately quantify coronary artery stenosis, evaluate an atherosclerotic plaque’s composition for embolic risk stratification, and assess myocardial perfusion. Although not a novel technology, dual-energy computed tomography has undergone significant advancements that have increased interest in this modality’s potential clinical cardiac applications. Albeit still in the early stages of development, one can expect additional clinical studies to further develop this important tool for cardiac imaging as more institutions acquire dual-energy compatible scanners.
Femtosecond Laser-Assisted Deep Lamellar Descemet Membrane Endothelial Keratoplasty for the Treatment of Endothelial Dysfunction Associated With Posterior Stromal Scarring
Authors: Alió del Barrio Jorge L. , Vargas Verónica
Published: December 2018

Purpose:

To describe an alternative surgical approach, femtosecond laser-assisted deep lamellar Descemet membrane endothelial keratoplasty (Femto-DL-DMEK), for the treatment of corneal endothelial diseases associated with posterior stromal scarring.

Methods:

Case report of a 52-year-old man with pseudophakic bullous keratopathy and posterior corneal scarring secondary to viral endotheliitis who underwent Femto-DL-DMEK. The surgical technique was as follows: First, a manual lamellar dissection plane was created at approximately 75% to 85% depth through a 5.0-mm superior scleral incision. One week later, using a femtosecond laser, an intersecting posterior side cut of 8.2 mm diameter was created. Subsequently, the dissected posterior recipient disk was removed from the anterior chamber through a 3.2-mm limbal incision. Finally, an 8.0-mm DMEK graft was placed.

Results:

The patient's uncorrected distance visual acuity improved from 20/200 (0.15; decimal) preoperatively to 15/25 (0.6) after surgery; corrected distance visual acuity improved from 20/200 (0.15) to 20/25 (0.9) with a residual refraction of +1.0–0.50 at 140 degrees. Endothelial cell count was 2062 cell/mm2 6 months after surgery. No intra- or postoperative complications were noted.

Conclusions:

As long as the anterior and mid-stroma are unaffected, those with endothelial diseases associated with opacification of the posterior stroma can benefit from endothelial keratoplasty through a Femto-DL-DMEK procedure, avoiding all well-known drawbacks of penetrating keratoplasty.
Primary Endovascular Repair of the Ascending Aorta
Authors: Borrello Bruno , Carino Davide , Agostinelli Andrea , Budillon Alessandro Maria , Nicolini Francesco
Published: December 2018

Different case series have been published demonstrating the feasibility of endovascular repair of the ascending aorta in selected patients deemed unfit for open surgery. However, the use of commercially available stent graft in the ascending aorta remains off-label, and their excessive length often prevents their deployment in the ascending aorta. Here we report a case of successful primary endovascular repair of the ascending aorta using a physician modified off-the-shelf device.
Reason and Timing for Conversion to Sternotomy in Robotic-Assisted Coronary Artery Bypass Grafting and Patient Outcomes
Authors: Christidis Nickolas K. , Fox Stephanie A. , Swinamer Stuart A. , Bagur Rodrigo , Sridhar Kumar , Lavi Shahar , Iglesias Ivan , Bainbridge Daniel , Jones Philip M. , Harle Christopher C. , Chu Michael W. A. , Teefy Patrick , Kiaii Bob B.
Published: December 2018

Objective

Conversion to sternotomy is a primary bailout method for robotically assisted coronary artery bypass grafting procedures. The aims of this study were to identify the primary reasons for conversion from robotically assisted coronary artery bypass grafting to sternotomy and to evaluate the in-hospital outcomes in such patients.

Methods

Prospectively collected data from February 2004 to April 2017 were reviewed for 72 patients (56 men; mean age = 63.8 years) who required conversion to sternotomy during a robotically assisted coronary artery bypass grafting procedure with planned endoscopic left internal thoracic artery harvest and anastomosis to the left anterior descending on the beating heart.

Results

The overall rate of conversion was 12.4% (72/581). Conversions occurred either during attempted endoscopic left internal thoracic artery harvest (31.9%), during endoscopic left anterior descending isolation (40.3%), during manual isolation and anastomosis of the left anterior descending (19.4%), or after anastomosis due to unsatisfactory flow (8.3%). Overall, the most common reason for conversion was an intramyocardial left anterior descending (43.1%). The median stay in the intensive care unit was 1 day (range = 0–20) and the median hospital length of stay was 5 days (range = 3–43). In-hospital complications included new atrial fibrillation (16.7%), need for blood transfusion (20.8%), mediastinitis (4.2%), postoperative myocardial infarction (2.8%), exploration for bleeding (2.8%), and 1 in-hospital death.

Conclusions

The reasons for conversion were primarily related to anatomical factors that created difficulties for endoscopic left internal thoracic artery harvesting and left anterior descending identification. Patients who required conversion to sternotomy from robotically assisted coronary artery bypass grafting demonstrated acceptable outcomes and low complication rates.
A Minimally Invasive Approach for Placing Sew-On Epicardial Leads in the Child
Authors: Nellis Joseph R. , Fitch Zachary W. , Choi Ashley Y. , Meza James M. , Spector Zebulon Z. , Von Bergen Nicholas H. , Torres Jose E. , Klapper Jacob A. , Sauer Jude S. , Turek Joseph W.
Published: December 2018

Traditionally, pacing leads are placed transvenously, although smaller pediatric patients who require permanent pacemakers may benefit from delaying tranvenous lead placement until they are larger. Alternative, minimally invasive atrioventricular pacing options have not previously existed for this patient population, leaving many of these children with large sternotomies or thoracotomies. Using three port sites and an adjustable shaft dual-needle suturing device, we placed a steroid-eluting, sew-on epicardial lead on the right atrium of a 9-year-old patient. This is one of the earliest reported cases of a minimally invasive technique for sew-on epicardial lead placement on the atrium of a child. Although based on a single case, we believe that this approach is safe, reliable, and reproducible and that it can be used to place leads on any aspect of the heart. Adoption of this technique will allow for earlier atrioventricular pacing, which may decrease the incidence of pacemaker syndrome, and thus improve overall outcomes in this patient population.
Medicine use during acute and chronic postinjury periods in whiplash-injured individuals
Authors: Ritchie Carrie , Hollingworth Samantha A. , Warren Jacelle , Sterling Michele
Published: December 2018

Medicine use as part of multimodal management for whiplash-associated disorders (WAD) is common: neck pain is the cardinal symptom, mental health conditions are common, and some individuals may have neurological signs and symptoms. Almost half of the individuals with WAD have ongoing pain and disability. However, medicine use during acute and chronic recovery periods for WAD management is unknown. We analysed medicine use during acute (<12 weeks) and chronic (12 weeks to 2 years) postinjury periods in adults claiming compensation for WAD in the no-fault jurisdiction of Victoria, Australia (n = 2871). Compared with males, females were more likely to have only nonopioid analgesic and/or NSAID claims during the acute postinjury period (odds ratio = 1.35 [95% confidence interval: 1.08-1.68]). However, high medicine use was more likely in males (1.39 [1.16-1.67]), middle-aged claimants (35-44 years) (1.74 [1.12-2.56]), and claimants with a common law claim (2.96 [2.38-3.68]). During both acute and chronic postinjury periods, over half of the pharmaceutical claimants were prescribed NSAIDs and weak opioid medicines, and over one quarter were prescribed benzodiazepines. Antidepressant use was high during the chronic period. The proportion of strong opioid claimants quadrupled between 2000/2001 (5.5%) and 2012/2013 (23.4%). Opioid consumption, expressed as oral morphine equivalent, was double in males than in females (z = −5.4, P < 0.001), and higher in middle-aged than in younger or older claimants (χ2 = 13.9, P < 0.001). The high opioid, benzodiazepine, and antidepressant medicine use in this study is concerning and highlights the need for pharmaceutical approaches that balance pain management while minimising risk.
The clinical outcomes of S-1 plus cisplatin for patients with advanced gastric cancer
Authors: Yang Lei , Wang Xingcheng , Wang Binsheng , Chao Peng , Li Debang , Chai Chen
Published: December 2018

Background:

To evaluate the clinical outcomes of S-1 plus cisplatin (SC) for the treatment of patients with advanced gastric cancer (AGC).

Methods:

A systematic literature search was conducted by searching PubMed, the Cochrane Library, Embase, China Biology Medicine disc (CBMdisc), China National Knowledge Infrastructure (CNKI), and WanFang Database, for all year up to January 2017. Pooled analyses of overall survival (OS), progress-free survival rates, and adverse events were performed.

Results:

A total of 8 random controlled trails (RCTs) consisting of 2699 patients with AGC were selected and included in this meta-analysis. The results of our meta-analysis showed that AGC patients who treated with SC regimen receive a similar OS (HR = 1.01, 95%CI: 0.86–1.18, P = .928), PFS (HR = 0.89, 95%CI: 0.72–1.09, P = .263), and overall response rate (HR = 0.88, 95%CI: 0.70–1.11, P = .283). However, SC regimen may increase the risk of 1 to 2 grade (OR = 1.128, 95%CI: 1.075–1.184, P = .000) and 3 to 4 grade (OR = 1.24, 95%CI: 1.01–1.52, P = .039) adverse events.

Conclusion:

SC chemotherapy showed no difference in survival compared with 5-FU- and S-1-based other therapy, but has a higher rate of adverse events compared with other chemotherapy regimens.
A pilot study of limb stimulation for the treatment of neonatal apnea
Authors: Dong Li-bin , Li Yu-fen , Zhang Yu , Qiao Shuang
Published: December 2018

This study explored the feasibility effect and safety of the limb stimulation (LS) for the treatment of neonatal apnea (NAP).

The cases of 30 eligible premature infants with NAP were included in this retrospective study. These cases were equally divided into an intervention group (n = 15) and a control group (n = 15). The infants in both groups received caffeine treatment. Moreover, cases in the intervention group also received LS for a total 30 hours, while the subjects in the control group did not receive LS during this period. The primary outcome included apnea frequency (number of episodes per 24 hours), and apnea rate. The secondary outcomes consisted of desaturation (number of episodes per 24 hours), and heart rate (beats per minute). Additionally, adverse events were also documented during the treatment period.

After treatment, LS did not show better outcomes in apnea frequency (P = .48), apnea rate (P = .33), desaturation (P = .55), and heart rate (P = .41). Furthermore, no significant differences of all adverse events were found between 2 groups.

The results of this pilot study demonstrated that LS might be not efficacious for premature infants with NAP.
Identification of multiple cardiac metastases from nonsmall-cell lung cancer by 18F-FDG PET/CT
Authors: Deng Shengming , Zhang Bin , Li Jihui , Sang Shibiao , Zhang Wei
Published: December 2018

Introduction:

Multiple cardiac metastases from nonsmall-cell lung cancer are extremely rare. Multiple cardiac metastases detected by 18F-fluorodeoxyglucose positron-emission tomography/computed tomography (18F-FDG PET/CT) have not been previously reported.

Patient concerns:

A 53-year-old man was admitted to the hospital with left back pain for 1 month.

Diagnoses:

A contrast-enhanced computed tomography (CECT) scan showed a moderately enhancing mass with a necrotic area in the upper left lobe of the lung and a filling defect in the interventricular septum. Two-dimensional transthoracic echocardiography identified a mass attaching to the endocardial surface of interventricular septum. 18F-FDG PET/CT showed multiple intense 18F-FDG uptakes in the cardiac region. Nonsmall-cell lung cancer was confirmed by histopathologic examination of the mass in the upper left lobe of the lung.

Intervention:

The patient was treated with Gemcitabine chemotherapy.

Outcomes:

After 18 months of follow-up, the patient achieved stable disease status according to the Response Evaluation Criteria In Solid Tumors guidelines.

Lessons:

Our case demonstrates that 18F-FDG PET/CT is a sensitive and feasible imaging modality to diagnosis multiple cardiac metastases.
Obesity and risk of urinary tract infection in young children presenting with fever
Authors: Hsu Po-Chang , Chen Shyi-Jou
Published: December 2018

Obesity may increase the risk of infection, but the association between obesity and febrile urinary tract infection (fUTI) is controversial. Although the prevalence of infant and childhood obesity has been increasing worldwide, the results of previous investigations on the association with urinary tract infection (UTI) are conflicting. The purpose of this study was to evaluate the relationship between overweight and obesity and UTI in febrile children.

The study reviewed medical records of a consecutive series of 472 children <2 years of age presenting with fever ≥ 38°C were retrospectively evaluated and stratified by the presence or absence of a UTI. The proportions of underweight, healthy weight, overweight, and obese children in the 2 groups were compared following calculation of individual weight-for-length percentiles. The effect of obesity on UTI risk was evaluated, and odds ratios (ORs) were calculated.

A total of 212 patients with and 260 controls without UTI were included. There were more overweight and obese children with (71/212, 33.5%) than without UTIs (45/260, 17.3%; P < .001). The OR of UTI in overweight relative to healthy-weight children was 1.92 [95% confidence interval (95% CI):1.15–3.21]. The OR of UTI in obese relative to healthy weight children was 2.46 (95% CI: 1.54–3.93).

Compared with previous studies that made comparison between UTI and healthy children, this is the first study to demonstrate an association of obesity and fUTI in febrile children <2 years of age. In this series of pediatric patients, obesity was strongly associated with the presence of fUTI and obese children had a higher risk of developing an UTI than nonobese children.

The incidence of UTI was higher in young, overweight, and obese children presenting with fever than in normal-weight, febrile children. Control of excess body weight should be considered as early as possible. Urinalysis should be considered for obese children <2 years of age who present with fever, especially those with mild respiratory or gastrointestinal symptoms.
Risk factor of benign paroxysmal positional vertigo in trauma patients
Authors: Kim Maru , Lee Dae-Sang , Hong Tae Hwa , Joo Cho Hang
Published: December 2018

Benign paroxysmal positional vertigo (BPPV) is a comorbid condition prevalent in patients recovering from trauma. Due to the paucity of studies investigating the etiology of this condition, the present study sought to analyze the high-risk group of BPPV patients following trauma.

Trauma patients visiting the emergency department from January to December 2016 were enrolled. The study excluded patients with minor superficial injuries, those who were dead, and those discharged within 2 days after their visit. The medical records were reviewed, and every abbreviated injury score, injury severity score, and other clinical characteristics, such as age and sex, were gathered. A diagnosis of BPPV was reached only after a provocation test was administered by an otolaryngologist. The correlation was statistically analyzed.

A total of 2219 trauma patients were analyzed. The mean age of the patients was 52.6 years, and the mean injury severity score (ISS) was 7.9. About 70% of the patients were men. Additional BPPV patients were identified among patients with injuries to head and neck, chest, and abdomen, and those with external injuries. However, patients with head and neck (odds ratio [OR] (95% confidence interval [CI]) = 10.556 (1.029–108.262), and abdominal injury (OR [95% CI] = 78.576 [1.263–4888.523]) showed statistically significant correlation with BPPV in the logistic regression analysis. Patients—not only those with head and neck injuries but those with abdominal injuries—who complain of dizziness need to be evaluated for BPPV using provocation tests. Further studies investigating traumatic BPPV are needed.
Transition of a Mallory-Weiss syndrome to a Boerhaave syndrome confirmed by anamnestic, necroscopic, and autopsy data
Authors: Cuccì Maria , Caputo Fiorella , Fraternali Orcioni Giulio , Roncallo Anna , Ventura Francesco
Published: December 2018

Rationale:

Spontaneous esophageal rupture (Boerhaave syndrome) is a rare, though frequently fatal, event. It is generally caused by a sudden increase in pressure inside the esophagus. In some cases, full-thickness perforations of the esophagus may develop from previous lesions that initially involve only the esophageal mucosa (Mallory-Weiss syndrome) and which, following further triggering events, give rise to a transmural lesion.

Patient concerns:

Here, we present the case of a 45-year-old subject who suddenly died of acute cardio-respiratory failure, an autopsy was performed to identify the cause of death.

Diagnosis, interventions, and outcomes:

The autopsy examination revealed a full-thickness rupture of the esophageal wall. Through the integration of necroscopy findings, anamnestic data, and histopathological examination, it has been possible to establish that complete esophageal rupture resulted from the evolution of a previous partial lesion of the esophageal wall, and that an untreated Mallory-Weiss syndrome evolved into a rapidly fatal Boerhaave syndrome.

Lessons:

This case shows that distal esophageal tears, rather than constituting a distinct entity, may be part of a spectrum of diseases and that a partial lesion of the esophageal wall caused by barogenic injury may evolve into a full-thickness rupture following further barotraumas.