bluuebunny/crossref_metadata_2025 huggingface dataset:
Student Satisfaction With Blackboard-Style Videos
Authors: Wolf Andrew B. , Peyre Sarah E.
Published: April 2018

Blackboard-style videos with simple drawings illustrating concepts have become immensely popular in recent years. However, there has been no published research evaluating their efficacy in nursing education. This pilot study evaluates the use of blackboard-style videos in an online pathophysiology course. Quantitative and qualitative evaluation data were analyzed to evaluate student satisfaction. The data indicated that students were highly satisfied with the course and the delivery of content using blackboard-style videos. The qualitative analysis uncovered two key themes explaining the high level of satisfaction: visual plus narrative explanations support learning and student control over pacing enhances learning.
Intracranial Space–occupying Lesion Inducing Intracranial Hypertension Increases the Encephalographic Effects of Isoflurane in a Swine Model
Authors: Kurita Tadayoshi , Kawashima Shingo , Morita Koji , Nakajima Yoshiki
Published: April 2018

Background:

Patients with a brain tumor are susceptible to the hypnotic effect of anesthetics depending on the tumor’s size. We investigated whether intracranial space–occupying lesions (ICSOLs) inducing intracranial hypertension increase isoflurane’s effect on electroencephalographic (EEG) results.

Materials and Methods:

After anesthetic induction with isoflurane, 11 swine were studied with regard to isoflurane’s effect on EEGs at 0.5% to 2.0% inhalational concentration at sequential stages: baseline 1, ICSOL 1, baseline 2, ICSOL 2, baseline 3. At each ICSOL stage, an intracranial epidural balloon catheter was inflated and the intracranial pressure maintained at twice the baseline pressure. The balloon was deflated after each ICSOL stage (baselines 2 and 3). A 95% spectral edge frequency (SEF), which correlates with anesthetic hypnosis, was used to measure isoflurane’s effect. Pharmacodynamics was characterized using a sigmoidal inhibitory maximum effect model for the SEF versus end-tidal concentration.

Results:

ICSOL shifted the relations between SEF and the effect-site concentration (C
e) downward. Baseline and 50% of the maximum spectral edge effect levels significantly decreased during balloon inflation. The C
e that produced SEF=15 was 1.12 (1.04-1.20) (mean [95% confidence interval])% for baseline 1; 0.92 (0.81-1.03) for ICSOL 1; 1.02 (0.94-1.11) for baseline 2; 0.88 (0.82-0.94) for ICSOL 2; 1.05 (0.93-1.17) for baseline 3. Isoflurane’s effect on EEGs increased during balloon inflation, with the alteration tending to recover after balloon deflation.

Conclusions:

ICSOLs inducing intracranial hypertension increase the EEG effect of isoflurane, and external compression from the brain surface enhances the anesthetic hypnosis despite minimum brain injury.
Evolution of Acute Kidney Injury and Its Association With Systemic Hemodynamics in Children With Fluid-Refractory Septic Shock
Authors: Deep Akash , Sagar Hiremath , Goonasekera Chulananda , Karthikeyan Palaniswamy , Brierley Joe , Douiri Abdel
Published: April 2018

Objectives:

There are no studies in pediatrics evaluating the progression of acute kidney injury in septic shock. We investigated the evolution of sepsis-associated acute kidney injury and its association with systemic hemodynamics in children with fluid-refractory septic shock.

Design:

Prospective cohort study.

Setting:

PICU of a tertiary care hospital.

Patients:

All patients with fluid-refractory septic shock (n = 61) between September 2010 and February 2014.

Interventions:

Hemodynamic variables using noninvasive ultrasound cardiac output monitor were measured at admission and 6 hourly thereafter till 48 hours. We used the Kidney Disease: Improving Global Outcomes criteria to define and stage acute kidney injury. Associations between various hemodynamic variables and development of acute kidney injury were evaluated. Severe acute kidney injury was defined as stage 2 or 3 acute kidney injury and was compared with no acute kidney injury or stage 1 acute kidney injury.

Measurements and Main Results:

Severe acute kidney injury developed in 29.5% (n = 18) of the 61 children with fluid-refractory septic shock, whereas 43 patients (70.49%) had either no or stage 1 acute kidney injury. Most patients who developed acute kidney injury did so within the first 48 hours of PICU admission. Severe acute kidney injury conferred a three-fold increased risk of death by day 28 (hazard ratio, 3.23; 95% CI, 1.52–6.67; p = 0.002), longer ICU stay, and increased duration of mechanical ventilation. Central venous pressure at presentation was higher in severe acute kidney injury by 5 cm H2O. Highest lactate in the first 24 hours of PICU admission, low diastolic blood pressure, low systemic vascular resistance index at admission were associated with severe acute kidney injury. This model reliably predicted stage 2/3 acute kidney injury by day 3 with area under the curve equals to 94%; 95% CI, 88.3–99.99. None of the other hemodynamic variables showed any association with severe acute kidney injury.

Conclusions:

Manifestations of sepsis-associated acute kidney injury often occur early after PICU admission and is associated with increased morbidity and mortality. There is a need to develop a predictive model in septic shock which could facilitate early detection of acute kidney injury.
Implication of Highly Cytotoxic Natural Killer Cells for Esophageal Squamous Cell Carcinoma Treatment
Authors: Lim Kee Siang , Mimura Kosaku , Kua Ley-Fang , Shiraishi Kensuke , Kono Koji
Published: April 2018

Esophageal squamous cell carcinoma (ESCC) is an aggressive upper gastrointestinal cancer and effective treatments are limited. Previous studies reported that natural killer (NK) cells expanded by coculturing with K562-mb15-41BBL feeder cells, a genetically modified K562 leukemia cell line that expresses membrane-bound interleukin (IL)-15 and 41BBL ligand, were highly proliferative and highly cytotoxic. Here, we investigated the potential of expanded NK cells for ESCC treatment. We analyzed both genetic and surface expression levels of NKG2D ligands (NKG2DLs) in ESCC using publicly available microarray data sets and ESCC cell lines. The cytotoxicity of resting and of IL-2-activated NK cells against ESCC cell lines was compared with that of expanded NK cells. We then also investigated the effect of epithelial mesenchymal transition (EMT) inducers, GSK3β inhibitor and epidermal growth factor, on NKG2DLs expressions. As a result, MICA and MICB were significantly overexpressed in ESCC compared with adjacent normal tissues and surface NKG2DLs were expressed in ESCC cell lines. Expanded NK cells were much potent than IL-2-activated and resting NK cells against ESCC cell lines. Blocking of NKG2D with anti-NKG2D monoclonal antibody dampened expanded NK cell cytotoxicity, suggesting that the NKG2DLs-NKG2D interaction is crucial for NK cells to eliminate ESCC cells. EMT inducers concurrently induced EMT and NKG2DLs expression in ESCC cell lines rendering transitioned cells more sensitive to expanded NK cells. In conclusion, expanded NK cells were highly cytotoxic against NKG2DLs-expressing ESCC cells, particularly the EMT phenotype. These results provide a strong rationale for clinical use of these NK cells in ESCC patients.
Ultrasonography-guided Cannula Method for Hyaluronic Acid Filler Injection with Evaluation using Laser Speckle Flowgraphy
Authors: Iwayama Takanori , Hashikawa Kazunobu , Osaki Takeo , Yamashiro Kenjiro , Horita Nobuyuki , Fukumoto Takeshi
Published: April 2018

Hyaluronic acid (HA) is present in the connective tissues of the skin and decreases with age. HA fillers are popular as facial rejuvenation treatments. They are generally considered safe; however, complications, such as cutaneous necrosis and blindness due to vascular embolism, sometimes occur. Because vascular embolisms are likely associated with the deep placement of HA fillers, a strategy that involves injection into superficial regions (the conventional method) is commonly used to reduce risks. However, deep injections to achieve revolumization are becoming common, even in high-risk areas for intravascular infusion. We aimed to study the usefulness of the ultrasonography-guided cannula method for preventing intravascular infusion of HA fillers. An HA filler was injected into the region just under the dermis on the left side of the face of a 38-year-old man using the conventional method, and another HA filler was injected into the periosteum on the right side using the ultrasonography-guided cannula method. The skin blood flow on both sides was compared using laser speckle flowgraphy (LSFG). The ultrasonography-guided method was successful in detecting the cannula and the blood vessel, and the HA filler was safely injected into a deep region. Using LSFG, a difference in skin blood flow between the 2 methods was detected. The ultrasonography-guided cannula method was effective in aiding the safe injection of an HA filler in a deep high-risk area and maintained skin blood flow. LSFG may be adopted to evaluate skin blood flow after HA filler injections.
Severe Respiratory Syncytial Virus Infection in Hospitalized Children Less Than 3 Years of Age in a Temperate and Tropical Climate
Authors: Butler Jessica , Gunnarsson Ronny , Traves Aileen , Marshall Helen
Published: April 2018

Background:

Respiratory syncytial virus (RSV) infection is a frequent cause of hospitalization in infants younger than 3 years of age. We aimed to determine the factors associated with severe RSV disease.

Methods:

Retrospective medical review of children up to 3 years of age admitted for laboratory-proven RSV infection between January 1, 2013, and December 31, 2014, was conducted at the Women’s and Children’s Hospital, Adelaide, South Australia, and the Paediatric Department at Cairns Hospital, Cairns, North Queensland. Severity of infection was determined using the validated Brisbane RSV Infection Severity Score.

Results:

Four-hundred ninety-six children (383 at Women’s and Children’s Hospital and 113 at Cairns Hospital) were included in the study, with 76, 323 and 97 patients identified as having mild, moderate or severe disease, respectively. Decreasing age [odds ratio (OR) = 0.95; 95% confidence interval (CI) = 0.90–0.99, P = 0.020), and being Indigenous, increased (OR = 2.6; 95% CI = 1.4–4.9, P = 0.002) the risk of severe RSV infection in hospitalized children. Underlying respiratory (P = 0.029, OR = 2.5; 95% CI = 1.1–5.8) or cardiac (OR = 2.7; 95% CI = 1.1–6.4, P = 0.024) conditions, as well as the presence of tachypnoea on admission (OR = 2.2; 95% CI = 1.2–4.1, P = 0.009), were also independent predictors of severe RSV infection. Seasonal variation in hospitalization was observed between temperate and tropical climates but was not associated with disease severity.

Conclusions:

Young infants, Indigenous patients and children with underlying respiratory and cardiac disease should be observed closely for signs of deterioration. Infants with tachypnoea on admission should be continuously monitored.
Vaccine Impact on Long-term Trends in Invasive Bacterial Disease in New Zealand Children
Authors: Walls Tony , Cho Vicki , Martin Natalie , Williman Jonathan , Brunton Cheryl
Published: April 2018

Background:

Vaccines against Haemophilus influenzae type B (Hib), Neisseria meningitidis and Streptococcus pneumoniae have been serially introduced into the New Zealand national immunization schedule since the 1990s. This study aimed to describe long-term trends in the rates of these invasive bacterial infections in children from New Zealand and compare these to recent UK data.

Methods:

This population-based observational study used 2 national datasets that collect data about hospital discharges (National Minimum Dataset) and notifiable diseases (Epurv). Annual age-specific and age-standardized hospital admission rates and notification rates were analyzed for all children <15 years of age.

Results:

Hospital admissions for Hib reduced by 79% during the 2 years after the introduction of the Hib vaccine (5.94–1.24/100,000). Meningococcal disease notifications fell by 75% over 8 years after the introduction of MeNZB vaccine (26.15–2.48/100,000) and have continued to decline. Meningococcal disease rates were lower than in the United Kingdom despite the absence of an ongoing meningococcal vaccination program in New Zealand (8.16 compared with 10.37/100,000 for 2007–2011). There rates of notifications and hospital admissions for pneumococcal disease were discordant, but both reduced substantially after the introduction of pneumococcal conjugate vaccines. Maori children had the highest rates of disease and the greatest reduction in rates after the introduction of both meningococcal and pneumococcal vaccines.

Conclusions:

Vaccines have had a substantial impact on the rates of invasive bacterial disease in children from New Zealand because of Hib, pneumococcus and meningococcus. Reductions in rates of disease have been greatest in Maori children, improving longstanding disparities in disease burden.
Epidemiology of Meningitis and Encephalitis in Infants and Children in the United States, 2011–2014
Authors: Hasbun Rodrigo , Wootton Susan H. , Rosenthal Ning , Balada-Llasat Joan Miquel , Chung Jessica , Duff Steve , Bozzette Samuel , Zimmer Louise , Ginocchio Christine C.
Published: April 2018

Background:

Large epidemiologic studies evaluating the etiologies, management decisions and outcomes of infants and children with meningitis and encephalitis in the United States are lacking.

Methods:

Children 0–17 years of age with meningitis or encephalitis as assessed by International Classification of Diseases, Ninth Revision, codes available in the Premier Healthcare Database during 2011–2014 were analyzed.

Results:

Six thousand six hundred sixty-five patients with meningitis or encephalitis were identified; 3030 (45.5%) were younger than 1 year of age, 295 (4.4%) were 1–2 years of age, 1460 (21.9%) were 3–9 years of age, and 1880 (28.2%) were 10–17 years of age. Etiologies included enterovirus (58.4%), unknown (23.7%), bacterial (13.0%), noninfectious (3.1%), herpes simplex virus (1.5%), other viruses (0.7%), arboviruses (0.5%) and fungal (0.04%). The majority of patients were male [3847 (57.7%)] and healthy [6094 (91.4%)] with no reported underlying conditions. Most underwent a lumbar puncture in the emergency department [5363 (80%)] and were admitted to the hospital [5363 (83.1%)]. Antibiotic therapy was frequent (92.2%) with children younger than 1 year of age with the highest rates (97.7%). Antiviral therapy was less common (31.1%). Only 539 (8.1%) of 6665 of patients received steroids. Early administration of adjunctive steroids was not associated with a reduction in mortality (P = 0.266). The overall median length of stay was 2 days. Overall mortality rate (0.5%) and readmission rates (<1%) was low for both groups.

Conclusion:

Meningitis and encephalitis in infants and children in the United States are more commonly caused by viruses and are treated empirically with antibiotic therapy and antiviral therapy in a significant proportion of cases. Adjunctive steroids are used infrequently and are not associated with a benefit in mortality.
Mycobacterium abscessus Soft Tissue Disease of the Abdominal Wall
Authors: Rodriguez Vivian Vega , Oehler Richard L.
Published: April 2018

Rapidly growing mycobacteria (RGM) are widely distributed in nature and known to be able to withstand extremes of temperature and nutritionally austere environments. They have been isolated from soil, dust, water, terrestrial and aquatic animals, hospital environments, and contaminated reagents and pharmaceuticals. The Mycobacterium abscessus complex group is considered the most significant set of human pathogens among the RGM. M. abscessus complex includes 3 subspecies: M. abscessus subspecies abscessus, M. abscessus subspecies massiliense, and M. abscessus subspecies bolletii. M. abscessus complex can cause a wide range of clinical manifestations and is responsible for most lung infections associated with the rapid growers. Extrapulmonary manifestations have included infections of the skin and soft tissue, prosthetic devices, surgical site infections, and disseminated disease associated with profound immunosuppression.

In this report, we present a case of intra-abdominal M. abscessus presenting as an enlarging mass in a patient on chronic corticosteroid therapy. Cases of intra-abdominal M. abscessus complex infections are limited in the published literature, and the treatment approach for these infections has not been consistent. Furthermore, M. abscessus complex has acquired the reputation of being the most virulent and chemotherapy-resistant member of the RGM group. As a result, the management of such infections is complicated and lacks specific guidance.
Evaluation of serum procollagen C-proteinase enhancer 1 level as a fibrosis marker in patients with chronic hepatitis B
Authors: Gokce Onur , Ozenirler Seren , Atak Yucel Aysegul , Oruklu Nihan , Yilmaz Esendagli Guldal , Karahan Sevilay
Published: April 2018

Aim

Although liver biopsy has long been considered the gold standard for staging fibrosis, because of the disadvantages and risks of biopsy, several noninvasive processes such as serum biomarkers have been introduced for the assessment of liver fibrosis. The aim of this study was to assess the diagnostic value of serum procollagen C-proteinase enhancer 1 (PCPE-1) as a noninvasive fibrosis marker in treatment-naive chronic hepatitis B patients.

Patients and methods

This study included 126 patients with biopsy-proven hepatitis B and 50 healthy controls. Fibrosis stage was determined using the Ishak scoring system. The PCPE-1 level was measured using the enzyme-linked immunosorbent assay assay, and the aspartate aminotransferase to platelet ratio index and the FIB-4 index were calculated using the formulas described in Appendix 1 (Supplemental digital content 1,
http://links.lww.com/EJGH/A277
).

Results

Serum PCPE-1 levels of chronic hepatitis B patients were found to be significantly lower than those of the healthy control group (4.49±2.74 vs. 42.9±59.6 pg/ml, respectively, P<0.001). There was a statistically significant negative correlation between serum PCPE-1 level and fibrosis stage (P=0.011; r=−0.226). A statistically significant negative correlation was found between serum PCPE-1 level and necroinflammatory activity (P=0.030; r=−0.194). PCPE-1 levels of patients with liver fibrosis scores of F1–2 were statistically significantly lower than those of the healthy control group (P<0.001) (area under the receiver operating characteristic: 0.955). The area under the receiver operating characteristic of the PCPE-1 level was 0.615 for the prediction of fibrosis (F0 vs. F1–6) (P=0.039).

Conclusion

Serum PCPE-1 might be used as a noninvasive marker of liver fibrosis. Further animal and human studies are needed to assess the utility of this marker.
Chronic liver diseases and the potential use of S-adenosyl-l-methionine as a hepatoprotector
Authors: Mora Silvia I. , García-Román Jonathan , Gómez-Ñañez Iván , García-Román Rebeca
Published: April 2018

Chronic liver diseases result in overall deterioration of health status and changes in metabolism. The search for strategies to control and combat these hepatic diseases has witnessed a great boom in the last decades. Nutritional therapy for controlling and managing liver diseases may be a positive influence as it improves the function of the liver. In this review, we focus mainly on describing liver conditions such as nonalcoholic fatty liver disease, and intrahepatic cholestasis as well as using S-adenosyl-l-methionine as a dietary supplement and its potential alternative therapeutic effect to correct the hepatic dysfunction associated with these conditions.
Diagnostic Accuracy of Preoperative Imaging for Differentiation of Branch Duct Versus Mixed Duct Intraductal Papillary Mucinous Neoplasms
Authors: Ugbarugba Emmanuel E. , Grieco Carmen , Hart Phil A. , Li Feng , Sklaw Brett , Cronley Kevin , Oza Veeral M. , Swanson Benjamin J. , Walker Jon P. , El-dika Samer , Conwell Darwin L. , Krishna Somashekar G.
Published: April 2018

Objective

The aim of this study is to determine the diagnostic accuracy of preoperative evaluation to detect main pancreatic duct involvement in pancreatic cystic lesions thus differentiating mixed intraductal papillary mucinous neoplasm (IPMN) from branch duct (BD)–IPMN.

Methods

The pathology database of pancreatic resections from 2000 to 2014 was reviewed. Main pancreatic duct-IPMNs and IPMNs with intracystic mass/nodules were excluded. The preoperative test characteristics were analyzed using surgical histopathology as the “gold standard.”

Results

Sixty BD-IPMNs and 23 mixed-IPMNs were identified. Mixed-IPMNs were larger (mean [standard deviation], 4.14 [2.9] vs 2.74 [1.9] mm; P = 0.03) and demonstrated frequent high-grade dysplasia/adenocarcinoma (43% vs 12%, P = 0.004) than BD-IPMNs. Endoscopic ultrasound (EUS) (sensitivity, 80%; specificity, 78%; accuracy, 79%) had the best diagnostic accuracy, whereas magnetic resonance imaging (MRI) (sensitivity, 83%; specificity, 63%; accuracy, 68%) had the highest sensitivity for the diagnosis of mixed-IPMN. A combination of EUS and MRI reached maximum sensitivity but with decreased accuracy (sensitivity, 100%; specificity, 64%; accuracy, 67%). The area under the curve for receiver operation curve was 0.71 whereas the optimal cyst size to detect main duct involvement was 3 cm.

Conclusions

For preoperative evaluation of pancreatic cystic lesions without evidence of intracystic nodules, a combination of MRI and EUS should be considered for improved detection of main duct involvement.
Hematopoietic Stem Cell Transplantation From Unrelated Donors in 2 Cases of Interleukin-10 Receptor Deficiency: Is Surgery Not a Requirement?
Authors: Kocacik Uygun Dilara F. , Uygun Vedat , Daloğlu Hayriye , Öztürkmen Seda , Karasu Gülsün , Reisli İsmail , Sayar Ersin , Yüksekkaya Hasan A. , Glocker Erik-Oliver , Boztuğ Kaan , Yeşilipek Akif
Published: April 2018

Mutations in interleukin-10 and its receptors cause infantile inflammatory bowel disease (IBD), a hyperinflammatory disorder characterized by severe, treatment-refractory colitis, multiple abscesses, and enterocutaneous fistulas. Patients with infantile IBD often require several surgical interventions, including complete colectomy, and hematopoietic stem cell transplantation is currently the only known medical therapy. Traditionally, operative management has been preferred before stem cell transplantation because of the latter’s increased susceptibility to procedural complications; however, surgical intervention could be delayed, and possibly reconsidered, because our 2 patients with infantile IBD demonstrated a rapid response to treatment via engraftment.
Atypical Autoimmune Hematologic Disorders in a Patient With Kabuki Syndrome
Authors: Almécija Ara C. , Pérez Vanesa , Baro María , Guerra-García Pilar , Vivanco Jose L.
Published: April 2018

Kabuki syndrome is a rare genetic disorder characterized by congenital anomalies and developmental delay. It is often associated with impaired immune response and autoimmune abnormalities. We report the clinical case of a girl with Kabuki syndrome who developed autoimmune neutropenia, not previously reported, followed by hemolytic anemia and autoimmune thrombocytopenia.
EBV-related Cold Agglutinin Disease Presenting With Conjugated Hyperbilirubinemia: A Pediatric Case Report and Mini Review
Authors: Mantadakis Elpis , Chatzimichael Eleftherios , Kontekaki Eftychia , Panopoulou Maria , Martinis Georges , Tsalkidis Aggelos
Published: April 2018

Hemolytic anemia occurs in only 1% to 3% of hospitalized patients with infectious mononucleosis. The authors describe an 8-year-old girl without cervical lymphadenopathy or splenomegaly, who presented with conjugated hyperbilirubinemia and was diagnosed with cold agglutinin disease caused by an immunoglobulin M autoantibody with anti-i specificity. Acute Epstein-Barr virus infection was confirmed by serologic and molecular methods. She recovered uneventfully after a 3-week course of methylprednisolone. Epstein-Barr virus infection should be considered in any case of hemolytic anemia associated with hepatic dysfunction, especially when direct antiglobulin test is positive for C3d. In these cases, a course of corticosteroids seems safe and may be beneficial.
Impact of Improved HIV Care and Treatment on PrEP Effectiveness in the United States, 2016–2020
Authors: Khurana Nidhi , Yaylali Emine , Farnham Paul G. , Hicks Katherine A. , Allaire Benjamin T. , Jacobson Evin , Sansom Stephanie L.
Published: April 2018

Background:

The effect of improving diagnosis, care, and treatment of persons living with HIV (PLWH) on pre-exposure prophylaxis (PrEP) effectiveness in the United States has not been well established.

Methods:

We used a dynamic, compartmental model that simulates the sexually active US population. We investigated the change in cumulative HIV incidence from 2016 to 2020 for 3 HIV care-continuum levels and the marginal benefit of PrEP compared with each. We also explored the marginal benefit of PrEP for individual risk groups, and as PrEP adherence, coverage and dropout rates varied.

Results:

Delivering PrEP in 2016 to persons at high risk of acquiring HIV resulted in an 18.1% reduction in new HIV infections from 2016 to 2020 under current care-continuum levels. Achieving HIV national goals of 90% of PLWH with diagnosed infection, 85% of newly diagnosed PLWH linked to care at diagnosis, and 80% of diagnosed PLWH virally suppressed reduced cumulative incidence by 34.4%. Delivery of PrEP in addition to this scenario resulted in a marginal benefit of 11.1% additional infections prevented. When national goals were reached, PrEP prevented an additional 15.2% cases among men who have sex with men, 3.9% among heterosexuals, and 3.8% among persons who inject drugs.

Conclusions:

The marginal benefit of PrEP was larger when current HIV-care-continuum percentages were maintained but continued to be substantial even when national care goals were met. The high-risk men who have sex with men population was the chief beneficiary of PrEP.
A Spatiotemporal Analysis of HIV-Associated Mortality in Rural Western Kenya 2011–2015
Authors: Sifuna Peter , Otieno Lucas , Andagalu Ben , Oyieko Janet , Ogutu Bernhards , Singoei Valentine , Owuoth John , Ogwang Sheila , Cowden Jessica , Otieno Walter
Published: April 2018

Background:

Reliable data on the HIV epidemic is critical for the measurement of the impact of HIV response and for the implementation of further interventions.

Methods:

We used mortality data from the Kombewa health and demographic surveillance systems (HDSS) from January 1, 2011 to December 31, 2015 to examine the space–time pattern of HIV-associated mortality. HIV mortality rate was calculated per 1000 persons living with HIV (for comparison with regional and national averages) and per 1000 person-years (p-y) for comparison with data from other HDSS sites. We used the Optimized Hot Spot Analysis to examine whether HIV-associated deaths would form statistically significant local aggregation in the 5-year period. P-value of <0.05 and <0.01 was considered significant.

Results:

The HIV-associated mortality rate over the 5-year period was 9.8 per 1000 persons living with HIV (PLHIV). Mortality declined from 11.6 per 1000 PLHIV in 2011 to 7.3 per 1000 PLHIV by the end of 2015. The rates of HIV were highest among infants [hazard ratio (HR) = 2.39 (<0.001)]. Tuberculosis mortality rates were highest in the age group 5–14 years [HR = 2.29 (0.002)] and the age group 50–64 years [HR = 1.18 (0.531)]. The overall trend in HIV-associated mortality showed a decline from 1.8 per 1000 p-y in 2011 to 1.3 per 1000 p-y by the end of 2015. The hotspot analysis showed that 20.0% of the study area (72 km2) was detected as hotspots (Z = 2.382–3.143, P ≤ 0.001) and 4.2% of the study area as cold spots (15 km2).

Conclusions:

HIV attributable death in the HDSS population is substantial, although it is lower than both the national and the regional estimates.
Pulmonary Ultrasound
Authors: Ñamendys-Silva Silvio A. , Garrido-Aguirre Eduardo , Romero-González Juan P. , Mena-Arceo Roger G. , Rojo del Moral Oscar , González-Chon Octavio
Published: April 2018

Pulmonary ultrasonography is a complementary study that is easy to perform at the patient bedside with no need to transfer the patient to special areas. The technique provides information with high sensitivity and specificity for different pathologies. Pulmonary ultrasonography is a very important diagnostic tool in the assessment of lung, pleural, and chest wall diseases. Pulmonary ultrasound provides low-cost analysis, easy real-time reproduction, and safety, all of which have made it a beneficial tool in the diagnostic arsenal available to medical personnel. The purpose of this review was to describe the usefulness of pulmonary ultrasound in critical areas.
Alterations of Vascular Endothelial Growth Factor A Expression and Microvessel Density Associated With Polypropylene Vaginal Mesh
Authors: Kowalski Joseph T. , Goodheart Michael J. , Genadry Rene , Bhattarai Ava , Bradley Catherine S.
Published: April 2018

Objective

Vaginal mesh exposure is the most common complication from mesh use in prolapse and incontinence surgery. Angiogenesis is an essential component of tissue healing, and defective angiogenesis plays a role in chronic wounds. We hypothesized that patients with exposures will have impaired angiogenesis as evidenced by altered tissue vascular endothelial growth factor A (VEGFA) expression and microvessel density. The study objective was to compare angiogenesis in women with vaginal mesh exposures, those with vaginal mesh without exposures, and in women who were mesh-naive.

Methods

Patients undergoing polypropylene mesh removal and patients without mesh undergoing urinary incontinence or prolapse surgery were recruited. Full-thickness vaginal epithelial biopsies were obtained. The relative abundance of VEGFA RNA was measured with reverse transcription-polymerase chain reaction. The VEGFA and CD31 immunohistochemistry were also performed.

Results

Ninety-two subjects were enrolled and biopsied. Mean age (SD) was 57.2 (12.8) years, 16 (17.4%) were smokers, and 68 (73.9%) were postmenopausal.

The VEGFA RNA expression did not differ between subjects with mesh exposure and with mesh but no exposure (P = 0.89). However, compared with subjects with no mesh, vaginal VEGFA expression was decreased in subjects with any implanted mesh (relative expression, 0.72; P = 0.02). Microvessel density was increased in subjects with mesh exposure compared with subjects with no mesh (P < 0.01). The VEGFA expression by immunohistochemistry was significantly lower in postmenopausal subjects without estrogen treatment compared with premenopausal and postmenopausal subjects being treated with estrogen (P = 0.02).

Conclusions

The presence of polypropylene mesh and hormonal status are associated with evidence of altered angiogenesis.
Renewing Our Cultural Borderlands
Authors: Pillay Mershen , Kathard Harsha
Published: April 2018

The professions of speech–language pathology and audiology provide valuable services for persons with communication, hearing, and feeding/swallowing disabilities. However, from a global perspective, mainstream practice discourses represent values from colonial perspectives (called Northern here). As such, they remain largely inaccessible to most people in the world. We argue, from a South African perspective, for a postcolonial or Southern discourse in alignment with other Africans, Latin Americans, and Asians who historically have had limited opportunities to shape professional practices. We use ideology critique (a disruptive tool) to reflect and make visible hegemonic Northern practices. Critical science and decoloniality are offered as pivotal axes for transformation. Decoloniality is discussed in relation to (i) Equitable (ii) Population-based (iii) Innovations for (iv) Communication (EPIC) using illustrative examples of emerging South African practices. We argue for redefining communication disorder professions' cultural borderlands to engage Northern with Southern ideologies critically to strengthen professional practice transformation.
Changes in Pediatric Heart Transplant Hospitalization Costs Over Time
Authors: Godown Justin , Thurm Cary , Hall Matt , Soslow Jonathan H. , Feingold Brian , Mettler Bret A. , Smith Andrew H. , Bearl David W. , Dodd Debra A.
Published: April 2018

Background

Despite significant changes in the past decade for children undergoing heart transplantation, including the evolution of mechanical circulatory support and increasing patient complexity, costs and resource utilization have not been reassessed. We sought to use a novel linkage of clinical-registry and administrative data to examine changes in hospitalization costs over time in this population.

Methods

We identified all pediatric heart transplant recipients in a unique linked Pediatric Health Information System/Scientific Registry of Transplant Recipients data set (2002-2016). Hospital costs were estimated from charges using cost-to-charge ratios, inflated to 2016 dollars. Severity-adjusted costs were calculated using generalized linear mixed-effects models. Costs were compared across 3 eras (era 1, 2002-2006; era 2, 2007-2011; and era 3, 2012-2016).

Results

A total of 2896 pediatric heart transplant recipients were included: era 1, 649 (22.4%); era 2, 1028 (35.5%); and era 3, 1219 (42.1%). Extracorporeal membrane oxygenation support at transplant decreased over time, concurrent with an increase in ventricular assist device–supported patients. Between era 1 and era 2, there was an increase in pretransplant hospitalization costs (US $343 692 vs US $435 554; P < 0.001). However, between era 2 and era 3, there was a decline in total (US $906 454 vs US $767 221; P < 0.001), pretransplant (US $435 554 vs US $353 364; P < 0.001), and posttransplant (US $586 133 vs US $508 719; P = 0.002) hospitalization costs.

Conclusions

Concurrent with the increase in utilization of ventricular assist device support, there has been an increase in pretransplant costs associated with pediatric heart transplantation. However, in the most recent era, costs have declined. These findings suggest the evolution of more cost-effective management strategies, which may be related to shifts in the approach to pediatric mechanical circulatory support.
Frailty, Inflammatory Markers, and Waitlist Mortality Among Patients With End-stage Renal Disease in a Prospective Cohort Study
Authors: McAdams-DeMarco Mara A. , Ying Hao , Thomas Alvin G. , Warsame Fatima , Shaffer Ashton A. , Haugen Christine E. , Garonzik-Wang Jacqueline M. , Desai Niraj M. , Varadhan Ravi , Walston Jeremy , Norman Silas P. , Segev Dorry L.
Published: April 2018

Background

Among community-dwelling older adults, frailty is associated with heightened markers of inflammation and subsequent mortality. Although frailty is common among end-stage renal disease (ESRD) patients, the role of frailty and markers of inflammation in this population remains unclear. We quantified these associations in patients on the kidney transplant waitlist and tested whether frailty and/or markers of inflammation improve waitlist mortality risk prediction.

Methods

We studied 1975 ESRD patients on the kidney transplant waitlist (November 1, 2009, to February 28, 2017) in a multi-center cohort study of frailty. Serum inflammatory markers (interleukin-6 [IL-6], soluble tumor necrosis factor-α receptor-1 [sTNFR1], and C-reactive protein [CRP]) were analyzed in 605 of these participants; we calculated the inflammatory index score using IL-6 and sTNFR1. We compared the C-statistic of an established registry-based prediction model for waitlist mortality adding frailty and/or inflammatory markers (1 SD change in log IL-6, sTNFR1, CRP, or inflammatory index).

Results

The registry-based model had moderate predictive ability (c-statistic = 0.655). Frailty was associated with increased mortality (2.19; 95% confidence interval [CI], 1.26-3.79) but did not improve risk prediction (c-statistic = 0.646; P = 0.65). Like frailty, IL-6 (2.13; 95% CI, 1.41-3.22), sTNFR1 (1.70; 95% CI, 1.12-2.59), CRP (1.68; 95% CI, 1.06-2.67), and the inflammatory index (2.09; 95% CI, 1.38-3.16) were associated with increased mortality risk; unlike frailty, adding IL-6 (c-statistic = 0.777; P = 0.02), CRP (c-statistic = 0.728; P = 0.02), or inflammatory index (c-statistic = 0.777; P = 0.02) substantially improved mortality risk prediction.

Conclusions

Frailty and markers of inflammation were associated with increased waitlist mortality risk, but only markers of inflammation significantly improved ESRD risk prediction. These findings help clarify the accelerated aging physiology of ESRD and highlight easy-to-measure markers of increased waitlist mortality risk.
Graphene and its derivatives as biomedical materials: future prospects and challenges
Authors: Banerjee Arghya Narayan
Published: April 2018

Graphene and its derivatives possess some intriguing properties, which generates tremendous interests in various fields, including biomedicine. The biomedical applications of graphene-based nanomaterials have attracted great interests over the last decade, and several groups have started working on this field around the globe. Because of the excellent biocompatibility, solubility and selectivity, graphene and its derivatives have shown great potential as biosensing and bio-imaging materials. Also, due to some unique physico-chemical properties of graphene and its derivatives, such as large surface area, high purity, good bio-functionalizability, easy solubility, high drug loading capacity, capability of easy cell membrane penetration, etc., graphene-based nanomaterials become promising candidates for bio-delivery carriers. Besides, graphene and its derivatives have also shown interesting applications in the fields of cell-culture, cell-growth and tissue engineering. In this article, a comprehensive review on the applications of graphene and its derivatives as biomedical materials has been presented. The unique properties of graphene and its derivatives (such as graphene oxide, reduced graphene oxide, graphane, graphone, graphyne, graphdiyne, fluorographene and their doped versions) have been discussed, followed by discussions on the recent efforts on the applications of graphene and its derivatives in biosensing, bio-imaging, drug delivery and therapy, cell culture, tissue engineering and cell growth. Also, the challenges involved in the use of graphene and its derivatives as biomedical materials are discussed briefly, followed by the future perspectives of the use of graphene-based nanomaterials in bio-applications. The review will provide an outlook to the applications of graphene and its derivatives, and may open up new horizons to inspire broader interests across various disciplines.
Yap regulates glucose utilization and sustains nucleotide synthesis to enable organ growth
Authors: Cox Andrew G. , Tsomides Allison , Yimlamai Dean , Hwang Katie L. , Miesfeld Joel , Galli Giorgio G. , Fowl Brendan H. , Fort Michael , Ma Kimberly Y. , Sullivan Mark R. , Hosios Aaron M. , Snay Erin , Yuan Min , Brown Kristin K. , Lien Evan C. , Chhangawala Sagar , Steinhauser Matthew L. , Asara John M. , Houvras Yariv , Link Brian , Heiden Matthew G. Vander , Camargo Fernando D. , Goessling Wolfram
Published: April 2018

The Hippo pathway and its nuclear effector Yap regulate organ size and cancer formation. While many modulators of Hippo activity have been identified, little is known about the Yap target genes that mediate these growth effects. Here, we show that yap-/- mutant zebrafish exhibit defects in hepatic progenitor potential and liver growth due to impaired glucose transport and nucleotide biosynthesis: transcriptomic and metabolomic analyses reveal that Yap regulates expression of glucose transporter glut1, causing decreased glucose uptake and use for nucleotide biosynthesis in yap-/- mutants, and impaired glucose tolerance in adults. Nucleotide supplementation improved Yap-deficiency phenotypes, indicating functional importance of glucose-fuelled nucleotide biosynthesis. Yap-regulated Glut1 expression and glucose uptake are conserved in mammals, suggesting that stimulation of anabolic glucose metabolism is an evolutionarily conserved mechanism by which the Hippo pathway controls organ growth. Together, our results reveal a central role for Hippo signalling in metabolic homeostasis.
Predicting the time needed to conduct an environmental systematic review or systematic map: analysis and decision support tool
Authors: Haddaway Neal R , Westgate Martin J
Published: April 2018

Systematic reviews aim to maximise transparency and comprehensiveness, whilst also minimising subjectivity and sources of bias. Because of these time-consuming and complex tasks, systematic reviews are perceived as being resource-intensive. To date, published estimates of systematic review resource requirements have been largely anecdotal, being imprecise and not based on evidence. However, it is valuable to provide reliable means of estimating the resource and time requirements of systematic reviews and maps. We analysed all CEE systematic reviews (n=66) and maps (n=20) published or registered between 2012 and 2017 to estimate the average time needed to complete a systematic review and map. We then surveyed 33 experienced systematic reviewers to collate information on time needed for each stage of the review process. Our results show that the average CEE systematic review takes 157 days (SD; ±22), whilst the average CEE systematic map takes 209 days (SD; ±53). While screening of titles and abstracts is widely accepted to be time-consuming, in practice meta-data extraction and critical appraisal can take as long (or even longer) to complete, especially when producing systematic maps. Finally, we present a tool that allows the user to predict the time requirements of a review or map given information known about the planned methods and evidence base likely to be identified. Our tool uses evidence-based defaults as a useful starting point for those wishing to predict the time requirements for a particular review. Our analyses shed light on the most time-consuming stages of the systematic review and map process, and highlight key bottlenecks from the perspective of time requirements, helping future reviewers to plan their time accordingly. Future predictions of effort required to complete systematic reviews and maps could be improved if CEE and CEE review authors provided more detailed reporting of the methods and results of their reviewing processes.
Characterisation and functional predictions of canine long non-coding RNAs
Authors: Le Béguec Céline , Wucher Valentin , Lagoutte Lætitia , Cadieu Edouard , Botherel Nadine , Hédan Benoît , De Brito Clotilde , Anne-Sophie Guillory , André Catherine , Derrien Thomas , Hitte Christophe
Published: April 2018

Long non-coding RNAs (lncRNAs) are a family of heterogeneous RNAs that play major roles in multiple biological processes. We recently identified an extended repertoire of more than 10,000 lncRNAs of the domestic dog however, predicting their biological functionality remains challenging. In this study, we have characterised the expression profiles of 10,444 canine lncRNAs in 26 distinct tissue types, representing various anatomical systems. We showed that lncRNA expressions are mainly clustered by tissue type and we highlighted that 44% of canine lncRNAs are expressed in a tissue-specific manner. We further demonstrated that tissue-specificity correlates with specific families of canine transposable elements. In addition, we identified more than 900 conserved dog-human lncRNAs for which we show their overall reproducible expression patterns between dog and humans through comparative transcriptomics. Finally, co-expression analyses of lncRNA and neighbouring protein-coding genes identified more than 3,400 canine lncRNAs, suggesting that functional roles of these lncRNAs act as regulatory elements. Altogether, this genomic and transcriptomic integrative study of lncRNAs constitutes a major resource to investigate genotype to phenotype relationships and biomedical research in the dog species.
Unifying mutualism diversity for interpretation and prediction
Authors: Wu Feilun , Lopatkin Allison J. , Needs Daniel A. , Lee Charlotte T. , Mukherjee Sayan , You Lingchong
Published: April 2018

Coarse-grained rules are widely used in chemistry, physics and engineering. In biology, however, such rules are less common and under-appreciated. This gap can be attributed to the difficulty in establishing general rules to encompass the immense diversity and complexity of biological systems. Even when a rule is established, it is often challenging to map it to mechanistic details and to quantify these details. We here address these challenges on a study of mutualism, an essential type of ecological interaction in nature. Using an appropriate level of abstraction, we deduced a general rule that predicts the outcomes of mutualistic systems, including coexistence and productivity. We further developed a standardized calibration procedure to apply the rule to mutualistic systems without the need to fully elucidate or characterize their mechanistic underpinnings. Our approach consistently provides explanatory and predictive power with various simulated and experimental mutualistic systems. Our strategy can pave the way for establishing and implementing other simple rules for biological systems.
Nuclear import ofArabidopsisPOLY(ADP-RIBOSE) POLYMERASE 2 is mediated by importin-α and a nuclear localization sequence located between the predicted SAP domains
Authors: Chen Chao , Lintermann Ruth , Wirthmueller Lennart
Published: April 2018

Proteins of the poly(ADP-ribose) polymerase (PARP) family modify target proteins by covalent attachment of ADP-ribose moieties onto amino acid side chains. InArabidopsis, PARP proteins contribute to repair of DNA lesions and modulate plant responses to various abiotic and biotic stressors.ArabidopsisPARP1 and PARP2 are nuclear proteins and given that their molecular weights exceed the diffusion limit of nuclear pore complexes, an active import mechanism into the nucleus is likely. Here we use confocal microscopy of fluorescent protein-taggedArabidopsisPARP2 and PARP2 deletion constructs in combination with site-directed mutagenesis to identify a nuclear localization sequence in PARP2 that is required for nuclear import. We report that in co-immunoprecipitation assays PARP2 interacts with several isoforms of the importin-α group of nuclear transport adapters and that PARP2 binding to IMPORTIN-α2 is mediated by the identified nuclear localization sequence. Our results demonstrate that PARP2 is a cargo protein of the canonical importin-α/β nuclear import pathway.
Neuromesodermal Progenitors are a Conserved Source of Spinal Cord with Divergent Growth Dynamics
Authors: Attardi Andrea , Fulton Timothy , Florescu Maria , Shah Gopi , Muresan Leila , Huisken Jan , van Oudenaarden Alexander , Steventon Benjamin
Published: April 2018

During gastrulation, embryonic cells become specified into distinct germ layers. In mouse, this continues throughout somitogenesis from a population of bipotent stem cells called neuromesodermal progenitors (NMps). However, the degree self-renewal is associated with NMps in the fast-developing zebrafish embryo is unclear. With a genetic clone tracing method, we labelled early embryonic progenitors and find a strong clonal similarity between spinal cord and mesoderm tissues. We then followed individual cell lineages by light-sheet imaging and reveal a common neuromesodermal lineage contribution to a subset of spinal cord tissue across the anterior-posterior body axis. An initial population subdivides at mid gastrula stages and is directly allocated to neural and mesodermal compartments during gastrulation. A second population in the tailbud undergoes delayed allocation to contribute to the neural and mesodermal compartment only at late somitogenesis. We suggest that NMps undergo vastly different rates of differentiation and growth in a species-specific manner.