bluuebunny/crossref_metadata_2025 huggingface dataset:
Cell-free hemoglobin: a novel mediator of acute lung injury
Authors: Shaver Ciara M. , Upchurch Cameron P. , Janz David R. , Grove Brandon S. , Putz Nathan D. , Wickersham Nancy E. , Dikalov Sergey I. , Ware Lorraine B. , Bastarache Julie A.
Published: January 2016

Patients with the acute respiratory distress syndrome (ARDS) have elevated levels of cell-free hemoglobin (CFH) in the air space, but the contribution of CFH to the pathogenesis of acute lung injury is unknown. In the present study, we demonstrate that levels of CFH in the air space correlate with measures of alveolar-capillary barrier dysfunction in humans with ARDS ( r = 0.89, P < 0.001) and in mice with ventilator-induced acute lung injury ( r = 0.89, P < 0.001). To investigate the specific contribution of CFH to ARDS, we studied the impact of purified CFH in the mouse lung and on cultured mouse lung epithelial (MLE-12) cells. Intratracheal delivery of CFH in mice causes acute lung injury with air space inflammation and alveolar-capillary barrier disruption. Similarly, in MLE-12 cells, CFH increases proinflammatory cytokine expression and increases paracellular permeability as measured by electrical cell-substrate impedance sensing. Next, to determine whether these effects are mediated by the iron-containing heme moiety of CFH, we treated mice with intratracheal hemin, the chloride salt of heme, and found that hemin was sufficient to increase alveolar permeability but failed to induce proinflammatory cytokine expression or epithelial cell injury. Together, these data identify CFH in the air space as a previously unrecognized driver of lung epithelial injury in human and experimental ARDS and suggest that CFH and hemin may contribute to ARDS through different mechanisms. Interventions targeting CFH and heme in the air space could provide a new therapeutic approach for ARDS.
Caffeine-Induced Suppression of GABAergic Inhibition and Calcium-Independent Metaplasticity
Authors: Isokawa Masako
Published: January 2016

GABAergic inhibition plays a critical role in the regulation of neuron excitability; thus, it is subject to modulations by many factors. Recent evidence suggests the elevation of intracellular calcium ([Ca2+]i) and calcium-dependent signaling molecules underlie the modulations. Caffeine induces a release of calcium from intracellular stores. We tested whether caffeine modulated GABAergic transmission by increasing[Ca2+]i. A brief local puff-application of caffeine to hippocampal CA1 pyramidal cells transiently suppressed GABAergic inhibitory postsynaptic currents (IPSCs) by 73.2 ± 6.98%. Time course of suppression and the subsequent recovery of IPSCs resembled DSI (depolarization-induced suppression of inhibition), mediated by endogenous cannabinoids that require a[Ca2+]irise. However, unlike DSI, caffeine-induced suppression of IPSCs (CSI) persisted in the absence of a[Ca2+]irise. Intracellular applications of BAPTA and ryanodine (which blocks caffeine-induced calcium release from intracellular stores) failed to prevent the generation of CSI. Surprisingly, ruthenium red, an inhibitor of multiple calcium permeable/release channels including those of stores, induced metaplasticity by amplifying the magnitude of CSI independently of calcium. This metaplasticity was accompanied with the generation of a large inward current. Although ionic basis of this inward current is undetermined, the present result demonstrates that caffeine has a robustCa2+-independent inhibitory action on GABAergic inhibition and causes metaplasticity by opening plasma membrane channels.
Chondroitin 6-Sulfation Regulates Perineuronal Net Formation by Controlling the Stability of Aggrecan
Authors: Miyata Shinji , Kitagawa Hiroshi
Published: January 2016

Perineuronal nets (PNNs) are lattice-like extracellular matrix structures composed of chondroitin sulfate proteoglycans (CSPGs). The appearance of PNNs parallels the decline of neural plasticity, and disruption of PNNs reactivates neural plasticity in the adult brain. We previously reported that sulfation patterns of chondroitin sulfate (CS) chains on CSPGs influenced the formation of PNNs and neural plasticity. However, the mechanism of PNN formation regulated by CS sulfation remains unknown. Here we found that overexpression of chondroitin 6-sulfotransferase-1 (C6ST-1), which catalyzes 6-sulfation of CS chains, selectively decreased aggrecan, a major CSPG in PNNs, in the aged brain without affecting other PNN components. Both diffuse and PNN-associated aggrecans were reduced by overexpression of C6ST-1. C6ST-1 increased 6-sulfation in both the repeating disaccharide region and linkage region of CS chains. Overexpression of 6-sulfation primarily impaired accumulation of aggrecan in PNNs, whereas condensation of other PNN components was not affected. Finally, we found that increased 6-sulfation accelerated proteolysis of aggrecan by a disintegrin and metalloproteinase domain with thrombospondin motif (ADAMTS) protease. Taken together, our results indicate that sulfation patterns of CS chains on aggrecan influenced the stability of the CSPG, thereby regulating formation of PNNs and neural plasticity.
Factors Related to Postoperative Pain Trajectories following Total Knee Arthroplasty: A Longitudinal Study of Patients Admitted to a Russian Orthopaedic Clinic
Authors: Kornilov Nikolai , Lindberg Maren Falch , Gay Caryl , Saraev Alexander , Kuliaba Taras , Rosseland Leiv Arne , Muniz Konstantin , Lerdal Anners
Published: January 2016

This study explores sociodemographic, clinical, and surgical factors in relation to pain trajectories during the first 3 days following total knee arthroplasty (TKA). 100 patients (mean age 63.5 ± 7.8 years and 93% female) consecutively admitted for uncomplicated primary TKA were prospectively included. Postoperative pain was assessed using pain diaries. Measures of preoperative pain, symptoms, daily functioning, quality of life, comorbidities, knee function, perioperative characteristics, and physical/biochemical parameters were also evaluated. All pain ratings decreased in the three days following surgery (p<.001) as well as the reported number of daily hours in moderate/severe pain (p<.001). Women reported more pain than men (p=.009). Pain trajectories did not differ by education, employment, cohabitation, or any patient clinical and biochemical characteristics but were significantly related to preoperative anxiety (p=.029). Patients reporting moderate/severe pain prior to surgery also reported more hours in moderate/severe pain on days 0–3 postoperatively (p=.029). Patients with surgeries longer than 90 min reported more hours of moderate/severe pain compared with patients who had shorter surgeries (p=.008), and similar results were observed for ratings of pain with activity (p=.012). In this sample, only female gender, higher levels of preoperative pain and anxiety, and longer surgical duration were associated with increased pain after TKA.
Obesity Severity, Dietary Behaviors, and Lifestyle Risks Vary by Race/Ethnicity and Age in a Northern California Cohort of Children with Obesity
Authors: Ford Margaret C. , Gordon Nancy P. , Howell Amanda , Green Cheryl E. , Greenspan Louise C. , Chandra Malini , Mellor R. Grant , Lo Joan C.
Published: January 2016

Identification of modifiable behaviors is important for pediatric weight management and obesity prevention programs. This study examined obesogenic behaviors in children with obesity in a Northern California obesity intervention program using data from a parent/teen-completed intake questionnaire covering dietary and lifestyle behaviors (frequency of breakfast, family meals, unhealthy snacking and beverages, fruit/vegetable intake, sleep, screen time, and exercise). Among 7956 children with BMI ≥ 95th percentile, 45.5% were females and 14.2% were 3–5, 44.2% were 6–11, and 41.6% were 12–17 years old. One-quarter (24.9%) were non-Hispanic white, 11.3% were black, 43.5% were Hispanic, and 12.0% were Asian/Pacific Islander. Severe obesity was prevalent (37.4%), especially among blacks, Hispanics, and older children, and was associated with less frequent breakfast and exercise and excess screen time, and in young children it was associated with consumption of sweetened beverages or juice. Unhealthy dietary behaviors, screen time, limited exercise, and sleep were more prevalent in older children and in selected black, Hispanic, and Asian subgroups, where consumption of sweetened beverages or juice was especially high. Overall, obesity severity and obesogenic behaviors increased with age and varied by gender and race/ethnicity. We identified several key prevalent modifiable behaviors that can be targeted by healthcare professionals to reduce obesity when counseling children with obesity and their parents.
An Improved Teaching-Learning-Based Optimization with the Social Character of PSO for Global Optimization
Authors: Zou Feng , Chen Debao , Wang Jiangtao
Published: January 2016

An improved teaching-learning-based optimization with combining of the social character of PSO (TLBO-PSO), which is considering the teacher’s behavior influence on the students and the mean grade of the class, is proposed in the paper to find the global solutions of function optimization problems. In this method, the teacher phase of TLBO is modified; the new position of the individual is determined by the old position, the mean position, and the best position of current generation. The method overcomes disadvantage that the evolution of the original TLBO might stop when the mean position of students equals the position of the teacher. To decrease the computation cost of the algorithm, the process of removing the duplicate individual in original TLBO is not adopted in the improved algorithm. Moreover, the probability of local convergence of the improved method is decreased by the mutation operator. The effectiveness of the proposed method is tested on some benchmark functions, and the results are competitive with respect to some other methods.
Vitamin D Deficiency Is Not Associated with Diabetic Retinopathy or Maculopathy
Authors: Alam Uazman , Amjad Yasar , Chan Anges Wan Shan , Asghar Omar , Petropoulos Ioannis N. , Malik Rayaz A.
Published: January 2016

Background. Experimental and clinical studies suggest a possible association between vitamin D deficiency and both diabetic retinopathy and maculopathy.Methods. We have performed a cross-sectional study in adults with types 1 and 2 diabetes mellitus. The relationship between the presence and severity of diabetic retinopathy and maculopathy with serum 25-hydroxyvitamin D concentration was evaluated using logistic regression analyses in the presence of demographic and clinical covariates.Results. 657 adults with diabetes were stratified based on retinopathy grading: No Diabetic Retinopathy (39%), Background Diabetic Retinopathy (37%), Preproliferative Diabetic Retinopathy (21%), and Proliferative Diabetic Retinopathy (3%), respectively. There were no differences in serum 25-hydroxyvitamin D concentrations (25(OH)D) between the groups (15.3±9.0versus16.4±10.5versus15.9±10.4versus15.7±8.5 ng/mL,P=NS). Logistic regression analysis demonstrated no statistically significant relationship between the severity of retinopathy and serum 25(OH)D. Furthermore, there was no difference in serum 25(OH)D between those with (n=94, 14%) and those without (n=563, 86%) Diabetic Maculopathy (16.2±10.0versus15.8±9.8,P=NS) and no relationship was demonstrated by logistic regression analyses between the two variables.Conclusions. This study has found no association between serum 25(OH)D and the presence and severity of diabetic retinopathy or maculopathy.
Wealth, Health, and Inequality: Households Exposure to Environmental Hazards
Authors: Owusu-Sekyere Ebenezer , Attakora-Amaniampong Elvis , Aboagye Dacosta
Published: January 2016

This study examined the geographies of ecological hazards in the “Garden City” of West Africa, Kumasi. The data collection involved questionnaire survey of 300 households using proportional representative sample of residential communities. This was complemented with 6 focus group discussions and 12 in-depth interviews with officers involved in environmental management. The results show that the disparities in household exposure to environmental hazards were not only skewed towards the economically deprived communities but were also disproportionately biased against the indigenous communities. The research views this development as an indication of poor urban environmental management and confirms how lack of holistic environmental planning has led to injustice in the exposure to environmental hazards. We argue that a proper environmental management framework has to be developed to correct the inequalities in order to guarantee social cohesion within the entire urban space.
Vibration Control on Multilayer Cable Moving through the Crossover Zones on Mine Hoist
Authors: Peng Xia , Gong Xian-sheng , Liu Jin-jun
Published: January 2016

Mine hoist is an important piece of equipment in mine hoist systems, and we achieve deep mine hoist through the multilayer winding, but the cable always undergoes severe shock and vibration during the winding process, and the dynamic load and wear would greatly reduce the lifetime of the cable and cause potential safety hazard. In this paper, we start from the course of crossing over of winding cable, use the methods of differential geometry, mechanics, and mathematical analysis, study the movements of the crossover, and derive the important formula that can reduce the vibration of cable during the course of crossover: the formula about central angle of the crossover arc. The results display that four factors contribute to central angle of the crossover arc, that is, the gap of the rope grooves, friction coefficient of the cable, and diameter of the drum and the cable. The result can provide valuable information for designing multilayer winding mine hoist.
Learning-Based Visual Saliency Model for Detecting Diabetic Macular Edema in Retinal Image
Authors: Zou Xiaochun , Zhao Xinbo , Yang Yongjia , Li Na
Published: January 2016

This paper brings forth a learning-based visual saliency model method for detecting diagnostic diabetic macular edema (DME) regions of interest (RoIs) in retinal image. The method introduces the cognitive process of visual selection of relevant regions that arises during an ophthalmologist’s image examination. To record the process, we collected eye-tracking data of 10 ophthalmologists on 100 images and used this database as training and testing examples. Based on analysis, two properties (Feature Property and Position Property) can be derived and combined by a simple intersection operation to obtain a saliency map. The Feature Property is implemented by support vector machine (SVM) technique using the diagnosis as supervisor; Position Property is implemented by statistical analysis of training samples. This technique is able to learn the preferences of ophthalmologist visual behavior while simultaneously considering feature uniqueness. The method was evaluated using three popular saliency model evaluation scores (AUC, EMD, and SS) and three quality measurements (classical sensitivity, specificity, and Youden’sJstatistic). The proposed method outperforms 8 state-of-the-art saliency models and 3 salient region detection approaches devised for natural images. Furthermore, our model successfully detects the DME RoIs in retinal image without sophisticated image processing such as region segmentation.
How Do Nursing Students Perceive the Needs of Older Clients? Addressing a Knowledge Gap
Authors: Hirst Sandra P. , Lane Annette M.
Published: January 2016

Background. Many nurse educators understand that students need to embrace the challenges and rewards of working with older clients. Yet, they might wonder how they can help students to develop and what is the specialized knowledge necessary to care for older clients. Question. How do students perceive the nursing needs of older adults? Method. A qualitative descriptive study was undertaken. Data collection occurred through semistructured interviews (9 students) and one focus group (8 students) using a photoelicitation technique. The researchers used a descriptive approach to analyze the data. Findings. Six themes emerged from the data: ask the older client!; physiology rules; personal, not professional; who can validate?; hierarchy of needs; and help us learn. Conclusion. Participants relied upon previous patterns of learning, primarily experiential, and on the views of health care colleagues in clinical practice to make decisions about the health needs of older clients. Participants clearly recognized the need to and significance of understanding the health care requirements of older clients. Findings have implications for how the care of older clients is introduced into nursing education programs.
Massive Retroperitoneal Hemorrhage as an Initial Presentation of a Rare and Aggressive Form of Multiple Myeloma
Authors: Alawadhi Aydah , Leb Laszlo
Published: January 2016

Multiple myeloma, a plasma cell neoplasm, presents most commonly with anemia, hypercalcemia, renal failure, and bone pain. Only few cases of clinical aggressive presentation associated with bleeding were reported in the medical literature. The reported cases included gastrointestinal bleeding and cardiac tamponade. Spontaneous retroperitoneal haemorrhage as initial presentation has not been so far reported. We hereby report a case of a 64-year-old female who was found to have catastrophic hemorrhage in the retroperitoneal region that extended into intrathecal space causing cord compression. The case posed a significant diagnostic and management dilemma. This case emphasizes the need to think broadly and include multiple myeloma in the diagnosis of unexplained massive retroperitoneal bleeding.
Effect of Huai Qi Huang on Epithelial‐Mesenchymal Transition of Renal Tubular Epithelial Cells through miR‐200a
Authors: Pu Jinyun , Zhang Yu , Zhou Jianhua
Published: January 2016

Epithelial‐mesenchymal transition (EMT) of renal tubular epithelial cells is a vital mechanism of renal fibrosis. Mounting evidence suggests that miR‐200a expression decreases in tubular epithelial cells in unilateral ureteral obstruction (UUO) rats. Moreover, it has been demonstrated that Huai Qi Huang (HQH) can ameliorate tubulointerstitial damage in adriamycin nephrosis and delay kidney dysfunction in primary glomerular disease. However, the effect of HQH on EMT of tubular epithelial cells in UUO rats and its molecular mechanism is unclear. In order to explore the effect of HQH on EMT and its molecular mechanism in renal fibrosis, in vitro and in vivo experiments were performed in our study. Our results showed that HQH increased miR‐200a expression in UUO rats and in TGF‐β1 stimulated NRK‐52E cells. Meanwhile, HQH decreased ZEB1 and ZEB2 (the transcriptional repressors of E‐cadherin), α‐SMA expression in renal tubular epithelial cells in vitro and in vivo. Furthermore, we found that HQH protected kidney from fibrosis in UUO rats. The results demonstrated that HQH regulated miR‐200a/ZEBs pathway and inhibited EMT process, which may be a mechanism of protecting effect on tubular cells in renal fibrosis.
Geographic Factors and Human Papillomavirus (HPV) Vaccination Initiation among Adolescent Girls in the United States
Authors: Henry Kevin A. , Stroup Antoinette M. , Warner Echo L. , Kepka Deanna
Published: January 2016

Background: This study is among the first to explore geographic factors that may be associated with human papillomavirus (HPV) vaccine uptake in the United States.

Methods: Data from the 2011 and 2012 National Immunization Survey-Teen for 20,565 female adolescents aged 13 to 17 years were analyzed to examine associations of HPV vaccine initiation (receipt of at least one dose) with ZIP code–level geographic factors. Logistic regression including individual and geographic factors was used to estimate the odds of HPV vaccine initiation.

Results: Approximately 53% of girls initiated the HPV vaccine in both years. Girls in high poverty communities had higher HPV vaccine initiation compared with those in low poverty communities [61.1% vs. 52.4%; adjusted OR (AOR), 1.18; 95% confidence intervals (CI), 1.04–1.33]. Initiation was higher among girls in communities where the majority of the population was Hispanic (69.0% vs. 49.9%; AOR, 1.64; 95% CI, 1.43–1.87) or non-Hispanic mixed race (60.4% vs. 49.9%; AOR, 1.30; 95% CI, 1.17–1.44) compared with majority non-Hispanic white communities. Interactions between individual-level race/ethnicity and community racial–ethnic composition indicated significantly higher odds of initiation among Hispanic girls living in Hispanic communities compared with Hispanic girls living in predominantly non-Hispanic White (NHW) (AOR, 2.23; 95% CI, 1.87–2.65) or non-Hispanic Black (NHB) (AOR, 1.90; 95% CI, 1.20–3.04) communities, respectively.

Conclusion: Initiation rates of HPV vaccination among teen girls were highest in the poorest communities and among Hispanics living in communities where the racial–ethnic composition was predominantly Hispanic or mixed race.

Impact: Given low HPV vaccination rates in the United States, these results provide important evidence to inform public health interventions to increase HPV vaccination. Cancer Epidemiol Biomarkers Prev; 25(2); 309–17. ©2016 AACR.
Involvement of Endoplasmic Reticulum Stress in Uremic Cardiomyopathy: Protective Effects of Tauroursodeoxycholic Acid
Authors: Ding Wei , Wang Bin , Zhang Minmin , Gu Yong
Published: January 2016

Background/Aims: Uremic cardiomyopathy (UCM) is a complication in chronic kidney disease. We investigated if endoplasmic reticulum stress (ERS) is involved in UCM, and determined the efficacy of tauroursodeoxycholic acid (TUDCA) in UCM prevention. Methods: Mice were divided randomly into three groups: sham (saline, i.p), 5/6 nephrectomized (Nx) (saline, i.p) and Nx+TUDCA (250 mg/kg/day, i.p.). Renal function was assessed by measuring serum creatinine, blood urea nitrogen and by periodic acid-Schiff reagent staining. Histologic examination of cardiac fibrosis and apoptosis was determined by Masson's trichrome and TUNEL assay. Cardiac function was evaluated by echocardiography. Fibrotic factors (transforming growth factor-β, fibronectin, collagen I/IV) were evaluated by real-time PCR. ERS-related proteins were measured by western blotting. Results: Impaired renal function and cardiac dysfunction were shown in 5/6 nephrectomy mice but were improved significantly by TUDCA. 5/6 nephrectomy mice exhibited marked cardiomyocyte apoptosis, cardiac fibrosis and elevated pro-fibrotic factors. ERS markers (GRP78, GRP94, P-PERK, P-eIF2a) and ERS-induced apoptosis pathways (activation of CHOP and caspase-12) were increased significantly in 5/6 nephrectomy mice, and TUDCA treatment blunted these changes. Conclusions: ERS has a key role in UCM, and the cardioprotective role of TUDCA is related to inhibition of ERS-induced apoptosis by inhibition of CHOP and caspase-12 pathways.
Influence of Demographic Variables on Metalinguistic Skills
Authors: Cadório Inês , Lousada Marisa
Published: January 2016

Background/Aims: The existing literature reports no clear patterns for the influence of extralinguistic variables on MSs because they vary across languages. Therefore, the current study addresses this issue by analyzing the development of MSs at the beginning of formal schooling and by determining the extent to which demographic variables affect metalinguistic development in normally developing European-Portuguese (EP) children. Methods: The sample included 80 EP first graders aged 6;00-6;11 years who presented a normal linguistic development. The Language Test - Preschool Language Assessment (TL-ALPE) was used to assess MSs in the domains of semantic, structural, and phonological awareness. Results: At the beginning of formal schooling, only one phonological awareness task involving syllables was considered to be acquired and established among all metalinguistic tasks elicited. Significant group differences were not found for the demographic variables of gender, socioeconomic status, and ecological setting. Conclusion: These findings contribute to the increasing literature on MSs. The reference information provided is important for accurately identifying school-aged children with language impairment.
A Possible New Multiple Endocrine Neoplasia Mutation in a Patient with a Prototypic Multiple Endocrine Neoplasia Presentation
Authors: Buzzola Rino , Kurukulasuriya Lilamani Romayne , Touza Mariana , Litofsky Norman S. , Brietzke Stephen , Sowers James R.
Published: January 2016

Background: Multiple endocrine neoplasia (MEN) type 1 syndrome is an uncommon inherited disorder characterized by the occurrence of tumors involving two or more endocrine glands. These tumors include pheochromocytoma, adrenal cortical and neuroendocrine tumors including (bronchopulmonary, thymic, gastric), lipomas, angiofibromas, collagenomas, and meningiomas. MEN-4 is very rare and has been characterized by the occurrence of parathyroid and anterior pituitary tumors in association with tumors of the adrenals, kidneys, and reproductive organs. Summary: We report the case of a 40-year-old male without significant family history of endocrine disease who was found to have primary hyperparathyroidism, a pituitary tumor causing acromegaly, thyroid cancer, renal cell carcinoma, and pancreatic cysts. We posit that this represents a new version of MEN-4. While renal tumors (angiomyolipoma) have been reported as part of the MEN-4 phenotype, to our knowledge, this is the first case reported of the association of MEN-1 and/or MEN-4 phenotype with this unique constellation of tumors, including renal cell carcinoma. Interestingly, this patient tested negative (DNA sequencing/deletion) for MEN-1 (menin), MEN-4 (CDKN1B) and VHL genes. Key Message: Thus, while this case has clinical characteristics consistent with either MEN-1 or MEN-4, it may represent a unique genetic variant.
Management of Hypertension in Diabetic Nephropathy: How Low Should We Go?
Authors: Sternlicht Hillel , Bakris George L.
Published: January 2016

Hypertension is a frequent comorbidity often following the development of diabetic nephropathy among individuals with type 1 diabetes and affecting most patients with type 2 diabetes at the time of diagnosis. Multiple prospective randomized placebo-controlled trials demonstrate that tight blood pressure control among patients with diabetic nephropathy reduces the rates of macrovascular and microvascular complications. While randomized trials exist and support a blood pressure goal of <140/90 mm Hg for patients with nondiabetic kidney disease, there are no prospective data regarding a specific blood pressure goal on progression of diabetic nephropathy. Retrospective data analyses from trials show a linear relationship between either baseline or achieved study blood pressure and progression of nephropathy. Very high albuminuria is a hallmark of diabetic nephropathy with reductions by either angiotensin converting enzyme inhibitors (ACEi) or angiotensin receptor blocker (ARB) monotherapy associated with slowed nephropathy progression. However, combination antihypertensive therapy, while decreasing proteinuria, augments the risk of hyperkalemia, hypotension, and kidney dysfunction. Given the lack of trial data for a BP goal among patients with diabetic nephropathy, prospective trials are needed to define the optimal blood pressure necessary to preserve kidney function. At present, guideline blood pressure goals of less than 140/90 mm Hg and the use of ACEi or ARB therapy for those with more than 300 mg of albuminuria are mandated.
Nephrotoxicity of Natural Products
Authors: Nauffal Mary , Gabardi Steven
Published: January 2016

Background: The manufacture and sale of natural products constitute a multi-billion dollar industry. Nearly a third of the American population admit to using some form of complementary or alternative medicine, with many using them in addition to prescription medications. Most patients fail to inform their healthcare providers of their natural product use and physicians rarely inquire. Annually, thousands of natural product-induced adverse events are reported to Poison Control Centers nationwide. Natural product manufacturers are not responsible for proving safety and efficacy, as the FDA does not regulate them. However, concerns exist surrounding the safety of natural products. Summary: This review provides details on natural products that have been associated with renal dysfunction. We have focused on products that have been associated with direct renal injury, immune-mediated nephrotoxicity, nephrolithiasis, rhabdomyolysis with acute renal injury, hepatorenal syndrome, and common adulterants or contaminants that are associated with renal dysfunction. Key Messages: The potential for natural products to cause renal dysfunction is justifiable. It is imperative that natural product use be monitored closely in all patients. Healthcare practitioners must play an active role in identifying patients using natural products and provide appropriate patient education.
Acute Kidney Injury: Tubular Markers and Risk for Chronic Kidney Disease and End-Stage Kidney Failure
Authors: Tan Hon Liang , Yap John Q. , Qian Qi
Published: January 2016

Acute kidney injury (AKI) is a common clinical syndrome directly related to patient short-term and long-term morbidity and mortality. Over the last decade, the occurrence rate of AKI has been increasing, and there has also been a growing epidemic of chronic kidney diseases (CKD) and end-stage kidney disease (ESRD) linked to severe and repeated episodes of AKIs. The detection and management of AKI are currently far from satisfactory. A large proportion of AKI patients, especially those with preexisting CKD, are at an increased risk of non-resolving AKI and progressing to CKD and ESRD. Proposed pathological processes that contribute to the transition of AKI to CKD and ESRD include severity and frequency of kidney injury, alterations of tubular cell phenotype with cells predominantly in the G2/M phase, interstitial fibrosis and microvascular rarification related to loss of endothelial-pericyte interactions and pericyte dedifferentiation. Innate immune responses, especially dendritic cell responses related to inadequate adenosine receptor (2a)-mediated signals, autophagic insufficiency and renin-angiotensin system activation have also been implicated in the progression of AKI and transitions from AKI to CKD and ESRD. Although promising advances have been made in understanding the pathophysiology of AKI and AKI consequences, much more work needs to be done in developing biomarkers for detecting early kidney injury, prognosticating kidney disease progression and developing strategies to effectively treat AKI and to minimize AKI progression to CKD and ESRD.
Intradialytic Hypoxemia in Chronic Hemodialysis Patients
Authors: Campos Israel , Chan Lili , Zhang Hanjie , Deziel Sheila , Vaughn Cheryl , Meyring-Wösten Anna , Kotanko Peter
Published: January 2016

When kidney failure occurs, patients are at risk for fluid overload states, which can cause pulmonary edema, pleural effusions, and upper airway obstruction. Kidney disease is also associated with impaired respiratory function, as in central sleep apnea or chronic obstructive pulmonary disease. Hence, respiratory and renal diseases are frequently coexisting. Hypoxemia is the terminal pathway of a multitude of respiratory pathologies. The measurement of oxygen saturation (SO2) is a basic and commonly used tool in clinical practice. Both arterial oxygen saturation (SaO2) and central venous oxygen saturation (ScvO2) can be easily obtained in hemodialysis (HD) patients, SaO2 from an arteriovenous access and ScvO2 from a central catheter. Here, we give a brief overview of the anatomy and physiology of the respiratory system, and the different technologies that are currently available to measure oxygen status in dialysis patients. We then focus on literature regarding intradialytic SaO2 and ScvO2. Lastly, we present clinical vignettes of intradialytic drops in SaO2 and ScvO2 in association with different symptoms and clinical scenarios with an emphasis on the pathophysiology of these cases. Given the fact that in the general population hypoxemia is associated with adverse outcomes, including increased mortality, cardiac arrhythmias and cardiovascular events, we posit that intradialytic SO2 may serve as a potential marker to identify HD patients at increased risk for morbidity and mortality.
Mechanisms and Treatment of Intradialytic Hypertension
Authors: Van Buren Peter Noel , Inrig Jula K.
Published: January 2016

Background: Intradialytic hypertension is a condition where there is an increase in blood pressure (BP) from pre- to post-hemodialysis; this condition has been recently identified as an independent mortality risk factor in hypertensive hemodialysis patients. The mechanisms and management of intradialytic hypertension have been explored in numerous research studies over the past few years. Summary: Patients with intradialytic hypertension have been found to be more chronically volume overloaded compared to other hemodialysis patients, although no causal role has been established. Patients with intradialytic hypertension have intradialytic vascular resistance surges that likely explain the BP increase during dialysis. Acute intradialytic changes in endothelial cell function have been proposed as etiologies for the increase in vascular resistance, although it is unclear if endothelin-1 or some other vasoconstrictive peptide is responsible. There is an association between dialysate to serum sodium gradients and BP increase during dialysis in patients with intradialytic hypertension, although it is unclear if this is related to endothelial cell activity or acute osmolar changes. In addition to probing the dry weight of patients with intradialytic hypertension, other management strategies include lowering dialysate sodium and changing antihypertensives to include carvedilol or other poorly dialyzed antihypertensives. Key Messages: Hemodialysis patients with intradialytic hypertension have an increased mortality risk compared to patients with modest decreases in BP during dialysis. Intradialytic hypertension is associated with extracellular volume overload in addition to acute increases in vascular resistance during dialysis. Management strategies should include reevaluation of dry weight and modification of both the dialysate prescription and medication prescription.
Quantifying Physical Activity Levels and Sleep in Hemodialysis Patients Using a Commercially Available Activity Tracker
Authors: Han Maggie , Williams Schantel , Mendoza Melissa , Ye Xiaoling , Zhang Hanjie , Calice-Silva Viviane , Thijssen Stephan , Kotanko Peter , Meyring-Wösten Anna
Published: January 2016

Background/Aims: Hemodialysis (HD) patients are less active than their healthy counterparts and frequently experience poor sleep. Our aims were to objectively quantify activity and sleep quality in HD patients of an urban population and to determine the effect of providing feedback on activity. Methods: Activity parameters and sleep parameters were collected by a commercially available activity tracker in 29 chronic HD patients. Patients in the feedback group were provided with their activity and sleep data during each HD treatment. Questionnaires were administered at the beginning and at the end of the study. Results: On average, patients walked 8,454 steps/day and slept 349 min/night. Only 28% of the patients were sedentary, defined as walking <5,000 steps/day. Providing feedback did not increase the activity in this urban population. Patients walked significantly less on Sundays compared to other days of the week: 7,024 steps on Sundays vs. 8,633 steps on HD days and 8,732 on non-HD days. It was also found that patients experienced poor sleep quality. HD treatments during shift 1 (6 a.m. to 10 a.m.) interfered with sleep patterns. Most patients reported that physical activity became more important to them after the 5-week period. The tracking device was very well accepted. Conclusion: Interventions to increase physical activity on Sundays could improve physical activity levels overall. Prospective studies are necessary to further explore the use of tracking devices to identify patients at risk and to implement targeted interventions.
Adolescents and Young Adults with Chronic or End-Stage Kidney Disease
Authors: Ferris Maria E. , Miles J. Alexander , Seamon Meredith L.
Published: January 2016

Background: Adolescents and young adults face unique and complex physical, psychological, and family challenges. Despite improvements in care for chronic kidney disease (CKD) and end-stage kidney disease (ESKD), long-term mortality for children, adolescents, and young adults with CKD remains substantially higher than their healthy counterparts. Summary: In this article, we discuss the complex challenges that adolescent and young adult CKD/ESKD patients face. Adolescents have different CKD etiologies and progress along a course dissimilar to the adult population, but have similar multifarious comorbidities. In the setting of puberty and learning to become self-sufficient, adolescence is a critical time for growth and psychosocial development. Physiological complications of CKD underlie many of the long-term outcomes. CKD-mineral and bone disorder and anemia are particularly challenging given that they are exacerbated by the rapid growth of adolescents. Endocrine imbalances and malnutrition can delay and limit growth. All of these factors, together with family dynamics and socioeconomic status, contribute to the poor long-term outcomes and decreased quality of life (QoL) for these patients and their families. Key Messages: Care for the adolescent CKD/ESKD population is uniquely challenging, but research has identified ways in which we can continue to improve long-term outcomes and QoL for adolescents with CKD/ESKD.
Health-Related Quality of Life in End-Stage Renal Disease Patients: How Often Should We Ask and What Do We Do with the Answer?
Authors: Chen Shan Shan , Al Mawed Saleem , Unruh Mark
Published: January 2016

Background: End-stage renal disease (ESRD) patients have poor health-related quality of life (HRQOL) comparing to general population and comparable HRQOL to patients with other major chronic diseases. Poor HRQOL is associated with shorter survival. There is a limited threshold to which dialysis dose and parameters management can improve HRQOL in ESRD patients. Numerous studies have sought to find interventions to improve HRQOL. This article is to review the symptoms associated with poor HRQOL and how frequent the quality of life (QOL) should be evaluated to improve the outcome. Summary: It is required by the Center for Medicare and Medicaid Services to evaluate HRQOL of dialysis patients annually. KDIGO recommends the symptoms to be assessed regularly and the treatment is redirected toward a patient-centered care model. Studies have shown that measuring patient-reported outcomes frequently, from 4 times a day to every 3-6 months, without intervention did not improve the HRQOL significantly. Appropriate intervention of the symptoms may improve the quality of life (QOL). Studies in oncology have also showed a similar result. The commonly used tools to evaluate the HRQOL in dialysis patients take up to 30 min for completion. Therefore, frequent assessment of all the symptoms can provide more burden than benefit to the patients. In addition to the annual HRQOL measurements, more frequent evaluation of targeted symptoms can be helpful. For appropriate intervention of the symptoms, effective communication between providers, as well as a multidisciplinary approach, is essential to improve HRQOL and outcomes in dialysis patients. Key Messages: Measurement of patient-reported outcomes may provide an opportunity to improve outcomes in ESRD. The frequent measurement of symptoms and QOL may be burdensome. Consider targeted measurement of symptoms to complement HRQOL measurement. Improved communication and the use of a multidisciplinary team provide mechanisms to improve HRQOL in ESRD.
Reading in Autism Spectrum Disorders: A Literature Review
Authors: Fernandes Fernanda Dreux Miranda , de La Higuera Amato Cibelle Albuquerque , Cardoso Carla , Navas Ana Luiza Gomes Pinto , Molini-Avejonas Daniela Regina
Published: January 2016

Objective: To review what the literature says about reading abilities of children on the autism spectrum (autism spectrum disorders, ASD) as well as to assess the results of intervention proposals. The broad ASD diagnosis used in the last decades and the resulting changes in the prevalence of these disorders have led to a relevant increase in the number of children diagnosed with ASD in the school system. The purpose of this review is to identify the different profiles of reading abilities shown by children with ASD described in the recent literature and the results of reported intervention methods. Methods: A review of the literature was conducted in the Web of Sciences and PubMed databases with the keywords ‘autism' AND ‘read*' and the filter 2010-2015. All articles published in the last 5 years focusing on description of and intervention for reading abilities in individuals with ASD were included. Review articles were excluded. Results: The selected 58 articles were divided into those that described reading abilities in individuals with ASD (n = 27) and those that reported intervention procedures for reading development (n = 31). Conclusions: Direct comparisons and associations were prevented due to different inclusion criteria and lack of detailed information about intervention processes. We propose tentative conclusions that should be confirmed by further studies.
Clinical Outcome and Predictive Factors in the Response to Splenectomy in Elderly Patients with Primary Immune Thrombocytopenia: A Multicenter Retrospective Study
Authors: Park Young Hoon , Yi Hyeon Gyu , Kim Chul Soo , Hong Junshik , Park Jinny , Lee Jae Hoon , Kim Ho Young , Kim Hyo Jung , Zang Dae Young , Kim Se Hyung , Park Seong Kyu , Hong Dae Sik , Lee Guk Jin , Jin Jong-Youl ,   on behalf of Gyeonggi/Incheon Branch, The Korean Society of Hematology
Published: January 2016

Background: Because many physicians seem reluctant to recommend splenectomy for elderly patients with immune thrombocytopenia (ITP), we investigated the safety and efficacy of splenectomy and the predictive factors for response in these patients. Methods: 184 patients with primary ITP were retrospectively analyzed based on age at splenectomy: an elderly group (≥60 years, n = 52) and a younger group (<60 years, n = 132). Results: There was no difference in the response rate of elderly versus younger patients (80.7 vs. 80.3%, p = 0.466). Relapse (45.2 vs. 22.6%, p = 0.006), complications, and median postoperative stay (9.5 vs. 7 days, p = 0.019) were significantly higher in the elderly group. The 5-year relapse-free survival of responders was 51.8% in the elderly group and 76.3% in the younger group (p = 0.002). Response to any treatment before splenectomy (HR 2.9, 95% CI: 1.24-6.80, p = 0.014) and platelet count on postoperative day 14 ≥200 × 109/l (HR 31.43, 95% CI: 4.15-238.28, p = 0.001) were independent factors for a favorable response. Conclusions: Age ≥60 years did not influence the response to splenectomy but was associated with increased relapse and postoperative complications. Splenectomy could provide a durable long-term response for elderly ITP patients.
Immunoglobulin Light-Chain Amyloidosis: From Basics to New Developments in Diagnosis, Prognosis and Therapy
Authors: Muchtar Eli , Buadi Francis K. , Dispenzieri Angela , Gertz Morie A.
Published: January 2016

Immunoglobulin amyloid light-chain (AL) amyloidosis is the most common form of systemic amyloidosis, where the culprit amyloidogenic protein is immunoglobulin light chains produced by marrow clonal plasma cells. AL amyloidosis is an infrequent disease, and since presentation is variable and often nonspecific, diagnosis is often delayed. This results in cumulative organ damage and has a negative prognostic effect. AL amyloidosis can also be challenging on the diagnostic level, especially when demonstration of Congo red-positive tissue is not readily obtained. Since as many as 31 known amyloidogenic proteins have been identified to date, determination of the amyloid type is required. While several typing methods are available, mass spectrometry has become the gold standard for amyloid typing. Upon confirming the diagnosis of amyloidosis, a pursuit for organ involvement is essential, with a focus on heart involvement, even in the absence of suggestive symptoms for involvement, as this has both prognostic and treatment implications. Details regarding initial treatment options, including stem cell transplantation, are provided in this review. AL amyloidosis management requires a multidisciplinary approach with careful patient monitoring, as organ impairment has a major effect on morbidity and treatment tolerability until a response to treatment is achieved and recovery emerges.
Non-Steroidal Anti-Inflammatory Drug Use and Risk of Anastomotic Leakage after Anterior Resection: A Protocol-Based Study
Authors: Rutegård Martin , Westermark Sofia , Kverneng Hultberg Daniel , Haapamäki Markku , Matthiessen Peter , Rutegård Jörgen
Published: January 2016

Background: Non-steroidal anti-inflammatory drugs (NSAIDs) have been introduced as opioid-sparing analgesics in colorectal surgery. However, recent research has implicated these drugs as risk factors for anastomotic dehiscence. Methods: The Swedish Colorectal Cancer Registry was used to identify all patients operated with anterior resection for rectal cancer at centres that performed more than 25 abdominal operations per year, from 2007 to 2012, inclusive. The registry provided individual patient data on demographic variables and symptomatic anastomotic leakage. The patient exposure to NSAIDs was defined according to the protocol of the hospital at which the patient was operated. Logistic regression was employed to estimate ORs and 95% CIs, adjusting for confounders. Results: The study cohort comprised 2,605 patients operated at 21 centres. In the NSAID group, 102/1,458 (7.0%) suffered an anastomotic leak, as compared to 124/1,023 (10.8%) in the non-NSAID group. With adjustment for confounding, patients treated at NSAID hospitals had a reduced risk of developing anastomotic leakage (OR 0.68; 95% CI 0.48-0.96). Conclusions: In this retrospective protocol-based study, NSAIDs did not increase the risk of anastomotic leakage after anterior resection for rectal cancer. The postoperative use of NSAIDs may not be detrimental, but more research is warranted.
Upregulated Cellular Expression of IL-17 by CD4+ T-Cells in Osteoporotic Postmenopausal Women
Authors: Zhao Renqing , Wang Xinzheng , Feng Feifei
Published: January 2016

Aim: The study aimed to investigate cellular expression of IL-17 by CD4+ T-cells in osteoporotic postmenopausal women. Methods: We enrolled 25 postmenopausal women with osteoporosis (PostMO) and 25 postmenopausal women with normal bone mineral density measurements (PostM) to examine the production of IL-17, tumor necrosis factor a (TNFa) and receptor activator of nuclear factor γ-B ligand (RANKL) by CD4+ T-cells and IL-17, RORγt, TNFa and RANKL mRNA levels in CD4+ T-cells. Circulating concentrations of IL-17 along with IL-6, TNFa, RANKL and osteoprotegerin (OPG) were also determined. Results: Osteoporotic postmenopausal women had higher serum concentrations of IL-17 (3.7 ± 1.3 vs. 2.5 ± 1.1 ng/ml, p = 0.042), IL-6 (158 ± 56 vs. 105 ± 39 pg/ml, p = 0.044), TNFa (138 ± 41 vs. 74 ± 11 pg/ml, p < 0.001) and OPG (1.7 ± 0.4 vs. 1.3 ± 0.4 ng/ml, p = 0.039) than healthy controls. The IL-17-producing CD4+ T-cells were higher in the PostMO group than in the PostM group (7.1 ± 2.4 vs. 4.9 ± 1.4%, p = 0.0015). Additionally, osteoporotic postmenopausal women had greater mRNA levels of IL-17 (3.5 ± 2.9 vs. 1.2 ± 1.0%, p = 0.019) and RORγt (5.7 ± 2.5 vs. 2.2 ± 1.0%, p < 0.001) in CD4+ T-cells than in healthy controls. Conclusions: Our findings implied that the upregulated production of IL-17 may play an important role in regulating bone loss in osteoporotic postmenopausal women.