bluuebunny/crossref_metadata_2025 huggingface dataset:
SPAK Sensitive Regulation of the Epithelial Na+ Channel ENaC
Authors: Ahmed Musaab , Salker Madhuri S. , Elvira Bernat , Umbach Anja T. , Fakhri Hajar , Saeed Amal M. , Shumilina Ekaterina , Hosseinzadeh Zohreh , Lang Florian
Published: April 2017

Background/Aims: The WNK-dependent STE20/SPS1-related proline/alanine-rich kinase SPAK participates in the regulation of NaCl and Na+,K+,2Cl- cotransport and thus renal salt excretion. The present study explored whether SPAK has similarly the potential to regulate the epithelial Na+ channel (ENaC). Methods: ENaC was expressed in Xenopus oocytes with or without additional expression of wild type SPAK, constitutively active T233ESPAK, WNK insensitive T233ASPAK or catalytically inactive D212ASPAK, and ENaC activity estimated from amiloride (50 µM) sensitive current (Iamil) in dual electrode voltage clamp experiments. Moreover, Ussing chamber was employed to determine Iamil in colonic tissue from wild type mice (spakwt/wt) and from gene targeted mice carrying WNK insensitive SPAK (spaktg/tg). Results: Iamil was observed in ENaC-expressing oocytes, but not in water-injected oocytes. In ENaC expressing oocytes Iamil was significantly increased following coexpression of wild-type SPAK and T233ESPAK, but not following coexpression of T233ASPAK or D212ASPAK. Colonic Iamil was significantly higher in spakwt/wt than in spaktg/tg mice. Conclusion: SPAK has the potential to up-regulate ENaC.
The Expression and Significance of NLRP3 Inflammasome in Patients with Primary Glomerular Diseases
Authors: Xiong Jing , Wang Yang , Shao Ning , Gao Pao , Tang Hui , Su Hua , Zhang Chun , Meng Xian-Fang
Published: April 2017

Background/Aims: Primary glomerulonephritis (PGN) is the most common reason inducing end stage renal disease in China, however, its pathogenesis remains unclear. The present study was designed to test the hypothesis that the formation and activation of NLRP3 (Nod-like receptor family pyrin domain containing 3) inflammasomes is an important initiating mechanism resulting in PGN. Methods: Serum samples and frozen sections were collected from 38 cases with PGN, and renal tissues were obtained from 22 of them. NLRP3 inflammasomes were detected by RT-PCR and immunofluoresence methods. The relationship between NLRP3 and clinical/pathologic indexes was analyzed. Results: RT-PCR analyses demonstrated that the mRNA levels of NLRP3 and caspase-1 genes were elevated significantly in renal tissues of PGN patients compared to those from normal pericarcinoma tissues. Moreover, the increased level of NLRP3 mRNA was correlative with a decrease in nephrin mRNA level and an increase in desmin mRNA level, which indicates that NLRP3 participates in podocyte injury in PGN patients. Immunofluorescence analysis also showed the protein expressions of NLRP3 and caspase-1 were increased in the glomeruli of PGN patients. Neverthless, there was no obvious regularity was presented in further subgroup analysis according to pathological types. In addition, increased NLRP3 was associated with the deterioration of renal function and glomerulosclerosis. IL-1β, a product of NLRP3 inflammasome activation, had a significant correlation with proteinuria. Conclusions: The formation and activation of NLRP3 inflammasomes in podocytes has been importantly implicated in the development of PGN-associated glomerular injury.
Long-term Outcomes of Parathyroidectomy in Kidney Transplant Recipients with Persistent Hyperparathyroidism
Authors: Tseng Po-Yu , Yang Wu-Chang , Yang Chih-Yu , Tarng Der-Cherng
Published: April 2017

Background/Aims: Hyperparathyroidism (HPT) is a common complication of chronic kidney disease and contributes to hypertension and cardiovascular risks. Successful kidney transplantation corrects abnormal mineral metabolism, but persistent HPT is still observed in up to 25% of patients one year after transplantation despite renal function improvement. The purpose of this study was to examine the long-term effects of parathyroidectomy (PTX) on blood pressure (BP) and graft function in patients with persistent post-transplant HPT. Methods: This is a retrospective study of renal allograft recipients at a single institute. Records from all the patients who received kidney transplantation at the Taipei Veterans General Hospital between 2004 and 2012 were reviewed and enrolled 19 patients who underwent PTX for persistent post-transplant HPT. Preoperative and postoperative clinical and biochemical data were compared. Matched controls (n = 19) in the corresponding time span were enrolled for graft function comparisons. Results: The mean systolic BP (127.7 ± 14.3 to 119.5 ± 12.7 mmHg, p = 0.028, 1 year after PTX; 127.7 ± 14.3 to 117 ± 12.4 mmHg, p = 0.007, 2 years after PTX) and pulse pressure (PP) (51.3 ± 10.7 to 44.3 ± 11.6, p = 0.019 1 year after PTX; 51.3 ± 10.7 to 44.9 ± 12.5 mmHg, p = 0.028, 2 years after PTX) reduced significantly at 1 year and 2 years of follow-up. However, no significant change of diastolic BP was observed. The improvement of SBP, DBP and PP was not correlated with the reduction of serum calcium level 1 year after PTX. The estimated glomerular filtration rate decreased significantly from 74.0 ± 20.5 mL/min/1.73m2 preoperatively to 68.2 ± 24.8 mL/min/1.73 m2 12 months after PTX but recovered at 15 months and lasted to 2 years after PTX. The all-cause hospitalization rate 1 year after PTX tended to be higher than that 1 year before PTX (105.3 versus 47.4 per 100 patient-years; RR, 2.22; 95 % CI: 0.97-5.54), but there was no significant difference between them. Conclusions: Our study demonstrated systolic BP and PP reduced 2 years after PTX and there was no significant difference between the peri-operative all-cause hospitalization rates. In addition, kidney allograft function impaired temporarily 12 months after PTX, but recovered 15 months after PTX.
Vitamin D-Rich Diet in Mice Modulates Erythrocyte Survival
Authors: Lang Elisabeth , Jilani Kashif , Bissinger Rosi , Rexhepaj Rexhep , Zelenak Christine , Lupescu Adrian , Lang Florian , Qadri Syed M.
Published: April 2017

Background/Aims: Epidemiological evidence suggests that vitamin D deficiency is associated with anemia. The potent metabolite 1,25(OH)2 vitamin D3 [1,25(OH)2D3] activates various signaling cascades regulating a myriad of cellular functions including suicidal cell death or apoptosis. Suicidal death of erythrocytes or eryptosis is characterized by cell shrinkage and cell membrane scrambling leading to phosphatidylserine (PS) externalization. Stimulation of eryptosis may limit lifespan of circulating erythrocytes and thus cause anemia. In the present study, we explored the effect of a high vitamin D diet (10,000 I.U. vitamin D for 14 days) in mice on eryptosis. Methods: Plasma concentrations of erythropoietin were estimated using an immunoassay kit, blood count using an electronic hematology particle counter, relative reticulocyte numbers using Retic-COUNT® reagent, PS exposure at the cell surface from annexin V binding, cell volume from forward scatter, and cytosolic Ca2+ ([Ca2+]i) from Fluo3-fluorescence in FACS analysis. Results: Vitamin D treatment decreased mean corpuscular volume, reticulocyte count, and plasma erythropoietin levels. Vitamin D treatment slightly but significantly decreased forward scatter but did not significantly modify spontaneous PS exposure and [Ca2+]i of freshly drawn erythrocytes. Vitamin D treatment augmented the stimulation of PS exposure and cell shrinkage following exposure to hyperosmotic shock (addition of 550 mM sucrose) or energy depletion (glucose removal) without significantly modifying [Ca2+]i. Conclusions: The present observations point to a subtle effect of exogenous vitamin D supplementation on erythrocyte survival.
De novo Evolution of a Small Choroidal Melanoma
Authors: Aleksidze Nino , Medina Carlos A. , Singh Arun D.
Published: April 2017

Aim: To report the evolution of a de novo choroidal melanoma. Method: This is a case report of a 22-year-old white male patient who has been undergoing periodic examination for a choroidal ‘freckle' since 10 years of age. Results: In 2007, a fundus photograph of the left eye showed a nondescript area of choroidal hyperpigmentation temporal to the fovea. Progressive growth was observed and, by 2012, the lesion had become well circumscribed and raised. One year later, a 4.5 × 4.5 × 1.5 mm, dome-shaped, pigmented, choroidal mass with subretinal fluid and orange pigmentation was evident. The lesion was classified as a small choroidal melanoma. Six months after plaque radiotherapy, tumor regression with total resolution of the subretinal fluid was documented. Conclusion: The distinction between small choroidal melanoma and choroidal nevus is not absolute; therefore, some choroidal melanomas may initially be mislabeled as choroidal nevi because of their small size until continued growth identifies them to be small choroidal melanomas. In our case, the documented growth of the choroidal lesion on each consecutive visit and its high-risk features strongly suggest that it had been a melanoma from the beginning. To our knowledge, this is only the second documented case of a de novo evolution of a small choroidal melanoma. © 2014 S. Karger AG, Basel
Ezetimibe-Mediated Protection of Vascular Smooth Muscle Cells from Cholesterol Accumulation through the Regulation of Lipid Metabolism-Related Gene Expression
Authors: Gong Yong-Zhen , Sun Shao-Wei , Yuan Hao-Yu , Xie Xue-Jiao , Tuo Qin-Hui , Yang Xue-Feng , Tan Xi , Zheng Xi-Long , Xiong Yan , Liao Duan-Fang
Published: April 2017

Background: Ezetimibe is a potent inhibitor of Niemann-Pick type C1-Like 1 and has been approved for the treatment of hypercholesterolemia. Our preliminary study showed that ezetimibe promotes cholesterol efflux from vascular smooth muscle cells (VSMCs). Our aim was to investigate the cellular mechanisms underlying the ezetimibe actions. Methods and Results: Rat VSMCs were converted to foam cells by incubation with cholesterol:methyl-F-cyclodextrin. The intracellular free cholesterol, total cholesterol, and the ratio of cholesteryl ester to total cholesterol were decreased after the incubation of VSMCs with different concentrations of ezetimibe (3, 10, 30, and 30 Vmol/l) or treated with 30 Vmol/l of ezetimibe for different time periods (6, 12, 24, and 48 h). Our results also showed that the expression of caveolin-1, liver X receptor E, and ATP-binding cassette transporter ABCA1 was enhanced, but the expression of nSREBP-1c was decreased in a concentration- and time-dependent manner. RNA interference was used to determine the roles of caveolin-1 and SREBP-1 in the lipid-lowering effect of ezetimibe. The results showed that caveolin-1 was involved in the regulation of intracellular cholesterol content, and the expression of caveolin-1 was repressed by SREBP-1. Conclusion: The present study indicates that ezetimibe protects VSMCs from cholesterol accumulation by regulating the expression of lipid metabolism-related genes. i 2014 S. Karger AG, Basel
A Mouse Splice-Site Mutant and Individuals with Atypical Chromosome 22q11.2 Deletions Demonstrate the Crucial Role for Crkl in Craniofacial and Pharyngeal Development
Authors: Miller Kerry A. , Tan Tiong Y. , Welfare Megan F. , White Susan M. , Stark Zornitza , Savarirayan Ravi , Burgess Trent , Heggie Andrew A. , Caruana Georgina , Bertram John F. , Bateman John F. , Farlie Peter G.
Published: April 2017

The 22q11.2 deletion syndrome (22q11DS) is thought to be a contiguous gene syndrome caused by haploinsufficiency for a variable number of genes with overlapping function during the development of the craniofacial, pharyngeal and cardiac structures. The complexity of genetic and developmental anomalies resulting in 22q11DS has made attributing causation to specific genes difficult. The CRKL gene resides within the common 3-Mb region, most frequently affected in 22q11DS, and has been shown to play an essential role in the development of tissues affected in 22q11DS. Here, we report the characterisation of a mouse strain we named ‘snoopy', harbouring a novel Crkl splice-site mutation that results in a loss of Crkl expression. The snoopy strain exhibits a variable phenotype that includes micrognathia, pharyngeal occlusion, aglossia and holoprosencephaly, and altered retinoic acid and endothelin signalling. Together, these features are reminiscent of malformations occurring in auriculocondylar syndrome and agnathia-otocephaly complex, 2 conditions not previously associated with the CRKL function. Comparison of the features of a cohort of patients harbouring small 22q11.2 deletions centred over the CRKL gene, but sparing TBX1, highlights the role of CRKL in contributing to the craniofacial features of 22q11DS. These analyses demonstrate the central role of Crkl in regulating signalling events in the developing oropharyngeal complex and its potential to contribute to dysmorphology.
Survey of Clinical Practice for Irritable Bowel Syndrome in East Asian Countries
Authors: Fukudo Shin , Hahm Ki-Baik , Zhu Qi , Sollano Jose D. , Rani Abdul A. , Syam Ari F. , Kachintorn Udom , Suzuki Hidekazu , Kamiya Takeshi , Joh Takashi , Uchiyama Kazuhiko , Naito Yuji , Takahashi Shin'ichi , Kinoshita Yoshikazu , Ueno Fumiaki , Yamagami Hirokazu , Chan Francis K.L. , Fock Kwong M. , Arakawa Tetsuo ,   The International Gastrointestinal Consensus Symposium Study Group
Published: April 2017

Aim: Sociocultural factors are important because their different effects on the features of irritable bowel syndrome (IBS) between countries will provide clues towards solving this problem. The aims of this study were to depict the clinical realities of IBS in East Asian countries and test the hypothesis that the diagnosis and treatment of IBS differ between countries. Subjects and Methods: Study participants were 251 physicians involved in the clinical practice of IBS at major institutions in Japan, South Korea, China, the Philippines, Indonesia and Singapore. The questionnaire contained 45 questions focused on the clinical practice of IBS. Results: Subjects in Japan, South Korea, China, Indonesia, the Philippines and Singapore accounted for 55.4, 17.9, 8.8, 8.0, 6.4 and 3.6% of the study cohort, respectively. Amongst East Asian physicians, the most important symptom was considered to be abdominal pain by 33.4%, whilst 24.3% regarded alternating diarrhea and constipation to be the most important symptoms. Total colonoscopy and histopathology use showed no difference among countries. Prescriptions given for mild (p < 0.0001), moderate (p < 0.0001), severe (p < 0.0001), intractable (p = 0.002), diarrheal (p < 0.0001) and constipating (p < 0.0001) patients with IBS significantly differed between the countries. Except for several minor points, IBS specialists showed no significant difference in their diagnosis and treatment of IBS when compared to nonspecialists. Conclusion: This survey provided data on the clinical treatment of IBS among East Asian countries. The results supported the hypothesis that the diagnosis and treatment of IBS differs between countries.
Bilateral Cervical Fistulas from Heterotopic Salivary Gland Tissues
Authors: Ogawa Kei , Kondoh Kenji , Kanaya Kaori , Ochi Atsushi , Sakamoto Takashi , Yamasoba Tatsuya
Published: April 2017

A 24-year-old male was referred to our department with intermittent clear drainage in both sides of the middle neck that did not increase while eating. On physical examination, there were fistulas in both sides of the neck, anterior to the sternocleidomastoid muscles. Fistulography revealed a 9-mm-long sinus from the left fistula, extending in the medial-caudal direction. On the right side, cannulation was not possible. Surgical excision of the lesion was performed on both sides, and the pathological examination revealed heterotopic salivary gland tissue (HSGT). From a literature review of reports of bilateral neck HSGT, we found that it is often associated with a family history of HSGT and other congenital anomalies. However, our case was different from the previously reported cases in that, although it was a bilateral case, it lacked any family history of HSGT or other congenital anomalies. Clinicians should include HSGT in the differential diagnosis of neck sinuses.
Urine Output Assessment as a Clinical Quality Measure
Authors: Macedo Etienne
Published: April 2017

Urine output (UO) is a relevant marker of kidney function and an independent marker of serum creatinine. Although oliguria can be the result of transitory changes in volume status or due to external influences, such as drug administration, UO is currently included as a criterion to diagnose and stage acute kidney injury (AKI). In clinical practice, the potential of earlier alert of kidney injury with frequent assessment of UO can help patient screening and risk assessment. In this review, we will discuss recent studies applying UO for AKI diagnosis and prognostication and propose methods to assess UO and improve quality of care.
Copy Number Analysis of the DLX4 and ERBB2 Genes in South African Breast Cancer Patients
Authors: Langa Bridget C. , Oliveira Márcia M.C. , Pereira Silma R.F. , Lupicki Kamil , Marian Catalin , Govender Dhirendra , Panieri Eugenio , Hiss Donavon , J. Cavalli Iglenir , Abdul-Rasool Sahar , Cavalli Luciane R.
Published: April 2017

Breast cancer is one of the main causes of cancer death among South African women. Although several risk factors can be attributed to the observed high mortality rate, the biology of the tumors is not extensively investigated. Copy number gain of the DLX4 homeobox gene has been observed in breast cancer in association with poor prognosis and specific racial groups. Therefore, we aimed to assess the copy number and prognostic role of DLX4 in breast cancer from South African patients. Due to the co-location of ERBB2 and DLX4 in the 17q21 region, its copy number was also evaluated. Our results in the analysis of 66 cases demonstrated copy number gains of DLX4 and ERBB2 in 24.1 and 29.7% of the cases, respectively. Linear regression analysis showed no dependency between the copy number alterations in these genes. Although not significant, patients with DLX4 and ERBB2 gains presented a higher frequency of advanced-grade tumors. In addition, copy number alterations of these genes were not significantly differently observed in the 3 main racial groups of the Western Cape population: Colored, White, and Black. These findings indicate that gains of DLX4 and ERBB2 occur in South African breast cancer patients irrespectively of their race and factors known to influence prognosis.
Safety and Outcome of Pharmacy-Led Vancomycin Dosing and Monitoring
Authors: Momattin Hisham , Zogheib Mohammed , Homoud Ali , Al-Tawfiq Jaffar A.
Published: April 2017

Background: Therapeutic vancomycin trough levels correlate with therapeutic success and the development of renal failure. In this study, we aimed to describe the safety and outcome of pharmacy-led vancomycin dosing and monitoring. Methods: We included adults requiring vancomycin for >48 h and who had a vancomycin trough level drawn near steady state. The primary outcome of the comparison was the achievement of therapeutic trough levels, defined as 10-20 µg/ml. Secondary outcome included acute renal failure. We compared these outcomes before and after the implementation of pharmacy-led vancomycin dosing and monitoring. Result: During the study period, a total of 278 patients were in the preimplementation phase and 286 were in the postintervention phase. There was a clear increase in the percentage of patients achieving the therapeutic range (50.5 vs. 79.7%, p = 0.0001) and an increase in the percentage of levels within the therapeutic range (31.6 vs. 59.1%; p = 0.0001). The number of cases receiving vancomycin increased by 5% and the duration of therapy decreased by 19.5%. More patients attained a therapeutic range of 10-20 µg/ml (i.e. the level was 31.6% in the preintervention and 59.1% in the postintervention phase). Conclusions: A higher percentage of patients achieved a therapeutic range and less nephrotoxicity when using a pharmacy-led protocol for vancomycin dosing.
Leucocyte Telomere Length and Risk of Cardiovascular Disease in a Cohort of 1,397 Danish Men and Women
Authors: Ellehoj Hanne , Bendix Laila , Osler Merete
Published: April 2017

Objectives: Short leucocyte telomere length (LTL) might be a risk factor for cardiovascular diseases (CVD). The present study examines the relation between LTL and incident fatal or non-fatal CVD, ischaemic heart disease (IHD) and stroke in a Danish cohort followed for 29 years. Methods: In total, 1,397 men and women who participated in health examinations with blood sampling in 1981-1984 were followed for CVD outcomes until the end of 2012 by linkage to national registers. Cox proportional hazard regression models were used to analyse the relation between LTL and CVD adjusting for potential confounding CVD risk factors. Results: During the follow-up, 603 participants experienced an incident fatal or non-fatal CVD. The survival analysis showed that baseline LTL was not associated with CVD outcomes. In the subanalysis with IHD as outcome, those with middle and short LTL had an increased hazard rate ratio of 1.97 (95% CI 1.31-2.93) and 1.55 (95% CI 1.02-2.35), respectively, which was attenuated when confounding factors were adjusted for. For stroke, the pattern of associations was similar but less precisely estimated. Conclusions: In this study short, LTL was not associated with an increased risk of CVD, but modestly associated with an increased risk of IHD.
Paleopathology of Spleens in South American Mummies
Authors: O''Neill Kelsey D. , Banning James Scott , Chow Woon N. , Gerszten Enrique
Published: April 2017

This study analyzed 19 naturally mummified pre-Columbian individuals excavated from desert regions of southern Peru and northern Chile. In the majority of autopsies of mummies, the spleen cannot be identified due to rapid autolysis and decomposition; therefore, our aim was to identify, in the cases in which the spleen was found, any normal and abnormal structures from mummified spleen tissues. The research consisted of gross and microscopic examinations of the spleen. Pathological features were identified, but no evidence of specific diseases was determined.
Associations between STAT Gene Polymorphisms and Psoriasis in Northeastern China
Authors: Zhou Jing , Li Yuzhen , Sun Donglin
Published: April 2017

Background: Psoriasis is an autoimmune disease with genetic and environmental factors. Based on the roles of STATs (signaling transducers and activators of transcription) in autoimmune diseases, it is assumed STAT gene polymorphisms are associated with psoriasis. Objectives: To study the association between STAT gene polymorphisms and psoriasis in the northeastern Chinese population. Methods: Eight single-nucleotide polymorphisms were genotyped: rs2293152, rs3816769, rs4796793, and rs744166 in STAT3, rs7574865 and rs3024866 in STAT4, and rs324011 and rs3024974 in STAT6, using SNaPshot methods. The genotype, allele, and haplotype frequencies were compared between 400 psoriasis patients and 398 healthy individuals in northeastern China. Results: rs744166GG in STAT3 and rs7574865TT in STAT4 had higher frequencies in the case than the control group, suggesting these 2 genotypes increase the susceptibility to psoriasis (p < 0.05). Three haplotypes (H3, H6, and H7) were found to be associated with psoriasis in the study (p < 0.05). Conclusions: These results indicate a role of STAT genes in the pathogenesis of psoriasis.
Das geriatrische Assessment ist wichtig für die Vorhersagbarkeit von postoperativen Komplikationen
Authors: Kolb Gerald
Published: April 2017

Ziele: Ziel der Studie war es herauszufinden, ob das «Comprehensive Geriatric Assessment» (CGA) geeignet ist, Komplikationen nach der Operation eines kolorektalen Karzinoms (CRC) vorherzusagen und die Probleme zu identifizieren. Wir verglichen hierzu den prognostischen Wert des CGA mit Patientencharakteristika und bestimmten prädiktiven Scores. Methoden: Insgesamt 156 Patienten im Alter ab 75 Jahren, die sich an der Universitätsklinik von Osaka in Japan einer CRC-Operation unterzogen, wurden in die Studie eingeschlossen. Jeder Patient wurde prospektiv nach CGA untersucht; alle postoperativen Komplikationen wurden den Krankenakten entnommen. Das CGA umfasste den Barthel-Index (BI), den Vitalitätsindex, die «Instrumental Activities Of Daily Living» (iADL)-Skala, die «Mini-Mental State Examination» (MMSE) und den «Geriatric Depression Score» (GDS). Alle Elemente wurden bei Patienten mit und ohne postoperative Komplikationen wie z.B. Delir, postoperative Wundinfektion und Ileus retrospektiv verglichen. Ergebnisse: Insgesamt traten bei 76 Patienten (48,7%) postoperative Komplikationen auf. BI und MMSE waren mit der Komplikationsinzidenz assoziiert und BI, iADL, MMSE sowie GDS waren signifikant mit dem Auftreten von Delirium assoziiert. Multivariate logistische Analysen identifizierten den MMSE als signifikante Determinante postoperativer Komplikationen nach Bereinigung um andere ermittelte prognostische Scores, darunter «Prognostic Nutritional Index» und «Performance Status». Schlussfolgerung: Die Anwendung der CGA vor einer CRC-Operation erwies sich als sinnvoller Prädiktor für postoperative Komplikationen bei älteren Patienten.
Metastatic Melanoma: Treatment and Survival in the US after the Introduction of Ipilimumab and Vemurafenib
Authors: Enewold Lindsey , Sharon Elad , Harlan Linda C.
Published: April 2017

Introduction: The 5-year survival of metastatic melanoma is < 18%. Historically, treatment options were limited. In 2011, 2 new agents were approved. Methods: We re-abstracted the medical records of a random sample (n = 520) of metastatic melanoma patients who had been diagnosed in 2011 and reported to population-based registries in the U.S. We also queried their treating physicians. Factors associated with treatment and survival were assessed using logistic and Cox proportional hazards regressions, respectively. Results: 21.4% of patients received no treatment, 20.8% received ipilimumab and 57.5% of patients with BRAF-positive tumors received vemurafenib/dabrafenib. Receipt of ipilimumab was less likely among patients of 75 years or older (vs. < 55 years: odds ratio (OR) 0.32; 95% confidence interval (CI) 0.15-0.66) and patients without private/military insurance. 46.8% of patients received BRAF testing. Receipt of BRAF testing was less likely among patients of 65 years or more and uninsured patients (OR 0.22; 95% CI 0.07-0.65). Receipt of ipilimumab was associated with better survival during the first 18 months after diagnosis (hazard ratio (HR) 0.66; 95% CI 0.51-0.84) and vemurafenib/dabrafenib with better survival during the first 10 months after diagnosis (HR 0.51; 95% CI 0.36-0.73). Conclusion: The initial dissemination of ipilimumab and vemurafenib/dabrafenib was limited. Additional research is needed to investigate the apparent lack of long-term survival benefit from these agents.
Pneumothorax during Pazopanib Treatment in Patients with Soft-Tissue Sarcoma: Two Case Reports and a Review of the Literature
Authors: Nakahara Yoshiro , Fukui Tomoya , Katono Ken , Nishizawa Yuuki , Okuma Yusuke , Ikegami Masachika , Sasaki Jiichiro , Masuda Noriyuki
Published: April 2017

Pazopanib, a multitargeting tyrosine kinase inhibitor, has single-agent activity in patients with advanced soft-tissue sarcoma. Herein, we describe 2 cases of pneumothorax that occurred during pazopanib treatment in patients with soft-tissue sarcoma. These 2 patients had multiple lung metastases. According to previous reports and our past experience, the risk of pneumothorax may be higher in patients with multiple lung metastases. Although a causal relationship is uncertain, the risk of pneumothorax when prescribing pazopanib for these patients should be considered.
Extracellular Matrix Mediates BMP-2 in a Model of Temporomandibular Joint Osteoarthritis
Authors: Shirakura Maya , Kram Vardit , Robinson Jennifer , Sikka Sheena , Kilts Tina M. , Wadhwa Sunil , Young Marian F.
Published: April 2017

Temporomandibular joint (TMJ) osteoarthritis (OA) is a complex disease that affects both cartilage and subchondral bone. It is accompanied by loss of extracellular matrix (ECM) and may be controlled by bone morphogenetic protein-2 (BMP-2). We analyzed the effect of BMP-2 in both cartilage and subchondral bone in a TMJ-OA animal model that is deficient in biglycan (Bgn) and fibromodulin (Fmod) (Bgn-/-Fmod-/-). Whole mandibles were dissected from 3-week-old wild-type (WT) and Bgn-/-Fmod-/- mice and incubated with and without 250 µg/mL BMP-2 for 2 days using an explant culture system. Condyle growth was measured by microCT and the expression levels of cartilage and bone-related genes were analyzed using RT-PCR or by immunohistochemistry from condyles that contained an intact cartilage/subchondral bone interface. Osteoclast activity was estimated by tartrate-resistant acid phosphatase (TRAP) staining and by TRAP, Rankl, and Adamts4 mRNA expression levels. Our results showed that most parameters examined were slightly up-regulated in WT samples treated with BMP-2, and this up-regulation was significantly enhanced in the Bgn-/-Fmod-/- mice. The up-regulation of both catabolic and anabolic agents did not appear to positively affect the overall growth of Bgn-/-Fmod-/- condyles compared to WT controls. In summary, the up-regulation of both anabolic and catabolic genes in the WT and Bgn-/-Fmod-/- TMJs treated with BMP-2 suggests that BMP increases matrix turnover in the condyle, and, further, that Bgn and Fmod could have protective roles in regulating this process.
Dynamics of L-Carnitine in Plasma and Urine in Patients Undergoing Cisplatin Chemotherapy
Authors: Gomi Daisuke , Tanaka Aika , Fukushima Toshirou , Kobayashi Takashi , Matsushita Hirohide , Sekiguchi Nodoka , Sakamoto Akiyuki , Sasaki Shigeru , Mamiya Keiko , Koizumi Tomonobu
Published: April 2017

Background and Aims: Several studies have indicated that cisplatin (cis-diamminedichloroplatinum II; CDDP) causes urinary excretion of L-carnitine (LC). However, the underlying cofactors affecting the increased urinary excretion remain unclear. The present study was performed to evaluate the dynamics of LC in plasma and urine after CDDP chemotherapy and to examine the relations with clinical parameters, such as gender, body mass index (BMI), and renal function. Methods: Twenty-two patients treated with CDDP therapy were selected. Blood and urine samples were taken from patients before starting CDDP treatment (day 0), on the next day (day 1), and on the seventh day (day 7). We measured plasma and urine concentrations of total, free, and acyl-LC, and examined the relationships with gender, age, treatment cycle, skeletal muscle mass, BMI, glomerular filtration rate, and change in creatinine concentration after CDDP administration. Results: Both urinary and plasma concentrations of 3 types of LC increased markedly on day 1 and subsequently reverted to the pre-CDDP level on day 7. There was a positive correlation between the % changes in plasma and urine LC (correlation coefficient 0.59, p = 0.003) on day 1, but no significant relations were seen in other clinical parameters. Conclusions: CDDP transiently increased plasma LC levels. The mechanism seemed to involve recruitment for marked urinary loss of LC. However, these changes in plasma and urinary LC levels were not related to clinical factors, suggesting that the dynamics of LC were independent of preexisting physical parameters.
Hemolytic Uremic Syndrome and Kidney Transplantation: A Case Series and Review of the Literature
Authors: Milan Manani Sabrina , Virzì Grazia Maria , Giuliani Anna , Clementi Anna , Brocca Alessandra , Dissegna Daniela , Martino Francesca , d''Amore Emanuele Stefano Giovanni , Ronco Claudio
Published: April 2017

Background: Hemolytic uremic syndrome (HUS) can be triggered by Shiga toxin producing Escherichia coli (STEC) infection or it can be defined as atypical HUS (aHUS) if it is related to uncontrolled complement activation. aHUS is characterized by a high incidence of recurrence after kidney transplantation, and it can also occur de novo in transplant recipients. Eculizumab is used both to prevent and to treat aHUS following kidney transplantation. In this paper, we report our centre experience and we present 4 cases of HUS in patients who underwent kidney transplantation. Methods: This is a single-center experience about HUS development in transplanted patients. Results: Patient 1 with end-stage renal disease (ESRD) due to STEC-HUS undergoing kidney transplantation without prophylactic therapy with eculizumab. Patient 2 with HUS secondary to an episode of diarrhea at 8 years old. After a slow progression to ESRD, she underwent kidney transplantation and she received prophylactic therapy with eculizumab due to the presence of anti-complement factor H antibodies. Patient 3 underwent pre-emptive living donor ABO-incompatible kidney transplantation and developed HUS secondary to antibody-mediated rejection. Patient 4 developed de novo HUS 16 years after kidney transplantation without a known cause. Conclusion: The correct diagnosis of HUS and the identification of the complement component alterations in case of aHUS are important parameters required to predict the risk of post-transplant recurrence of the disease. In the cases we reported, eculizumab has been found to be effective both to prevent and to treat aHUS following kidney transplantation.
Fuchs Syndrome: Medical Treatment of 1 Case and Literature Review
Authors: Gossart Rémy , Malthiery Eve , Aguilar Fanny , Torres Jacques-Henri , Fauroux Marie-Alix
Published: April 2017

Fuchs syndrome is a particular type of erythema multiforme major; the lesions are only found on the mucosae and specifically affect oral, ocular, and genital mucosae. The cause is not always immediately apparent, which is why this pathology requires a rigorous, detailed clinical examination to eliminate a differential diagnosis. The severity of the symptoms, particularly of oral and ocular symptoms, requires immediate treatment. The treatment of this pathology requires a multiple-drug regime. Through a clinical case study, the objective of this work is to help guide practitioners when diagnosing and treating this pathology as no current consensus exists on these 2 subjects. The authors present the case of a 29-year-old patient who was suffering from a recurring outbreak of Fuchs syndrome, suspected of having been triggered by Mycoplasma pneumoniae. After completing the treatment program based on colchicine and prednisolone, the patient was relieved from pain and has not suffered from any further periodic eruptions of erythema multiforme.
Alain Badiou, the Maoist Investigation, and the Party-Form
Authors: Hoffman Marcelo
Published: April 2017

As scholarly interest in the experience of French Maoism has been undergoing something of a renaissance, it is unsurprising that the Maoist practice of investigations has elicited varying degrees of attention in recent years. But this attention has tended to be subsumed within, if not overshadowed by, much broader historical and exegetical undertakings. This paper seeks to redress this limitation in the literature by focusing on the lengthiest and most detailed summary of Maoist investigations among peasants in the French countryside,The Book of Poor Peasants, published by Alain Badiou’s Group for the Foundation of the Union of Communists of France Marxist-Leninist (ucfml) in 1976. This book vividly demonstrates the difficulties and limitations associated with the practice of investigations. It thus affords a more critical appreciation of this practice. The book also casts Badiou’s shift toward a ‘politics without party’ in a new light.
Gramsci’s Spatial Dialectics
Authors: Ledwith Sean
Published: April 2017

This review-essay contends that Gramsci: Space, Nature, Politics is essential reading for an appreciation of the relevance of the eponymous thinker to a number of seminal theoretical debates and to a wider strategic discussion on the trajectory of the left in the twenty-first century. The book provides a vigorous vindication of Gramsci’s utilisation of concepts such as passive revolution, dialectical nature and a relational view of the mind. There are incisive discussions of ecology and intersectionality through a Gramscian lens. The collection also includes outstanding analyses of class struggles in a number of developing capitalist states, including Brazil and South Africa. The review argues that a distillation of the ideas contained in the work would be an asset to Marxists engaged in theoretical and practical activity.
Diversity, distribution and preliminary conservation status of the flora of Burkina Faso
Authors: SCHMIDT MARCO , ZIZKA ALEXANDER , TRAORÉ SALIFOU , ATAHOLO MANDINGO , CHATELAIN CYRILLE , DAGET PHILIPPE , DRESSLER STEFAN , HAHN KAREN , KIRCHMAIR IVANA , KROHMER JULIA , MBAYNGONE ELISÉE , MÜLLER JONAS V. , NACOULMA BLANDINE , OUÉDRAOGO AMADÉ , OUÉDRAOGO OUMAROU , SAMBARÉ OUMAROU , SCHUMANN KATHARINA , WIERINGA JAN J. , ZIZKA GEORG , THIOMBIANO ADJIMA
Published: April 2017

West Africa is a floristically understudied region that is facing severe environmental changes in the 21st century. Basic distribution data and information on the conservation status for most plant species of the region are scarce, and good information only exists for small areas of interest or for key species. This lack of knowledge seriously hampers urgently needed regional conservation efforts. Here we present comprehensive distribution information and preliminary, automated species conservation assessments for the flora of Burkina Faso, a country in tropical West Africa with a flora and vegetation typical for the savanna belt of the region. We documented and analysed the distribution of 1,568 species or 80% of the flora of Burkina Faso based on an expert curated dataset comprising ca. 150,000 occurrence records from herbarium specimens and vegetation surveys. We used this dataset and environmental niche models to calculate three indicator variables for a preliminary, automated conservation assessment. We classified 350 species (18% of the flora, excluding introduced species) as potentially "Critically Endangered", "Endangered", "Vulnerable" or "Near-Threatened" on the national level. The analyses confirmed species-rich areas in the south-west and south-east of the country, and showed a particular concentration of potentially Endangered species in the south. Furthermore, the proportion of potentially Endangered species differed between plant families, growth forms and habitats. Our results set the base for further plant geographical and ecological studies and are a data-driven baseline for further conservation assessments and large scale conservation strategies of the West African flora.
Hersilia aadi Pravalikha, Srinivasulu & Srinivasulu, 2014 a junior synonym of Hersilia savignyi Lucas, 1836 (Araneae: Hersiliidae)
Authors: CALEB JOHN T.D. , PRAVALIKHA G.B. , JOHNSON BENAIAH EBENEZER , MANYU MITEMLU , MUNGKUNG SOREIPHY , MATHAI MANU THOMAS
Published: April 2017

The genus Hersilia was established by Audouin in 1826 with H. caudata Audouin, 1826 as the type species. It is the most speciose hersiliid genus presently comprising 79 described species worldwide (World Spider Catalog 2017, version 18). There are seven species known from India: H. aadi Pravalikha, Srinivasulu & Srinivasulu, 2014, H. longivulva Sen et al., 2010, H. orvakalensis Javed et al., 2010, H. savignyi Lucas, 1836, H. striata Wang & Yin, 1985, H. sumatrana (Thorell, 1890), H. tibialis Baehr & Baehr, 1993. This paper is based on fresh material collected from the patches of scrub jungle enclosed within the Madras Christian College campus, Chennai, Tamil Nadu, India. Both sexes of H. savignyi are illustrated. H. aadi Pravalikha, Srinivasulu & Srinivasulu, 2014 is synonymized with H. savignyi Lucas, 1836.
Macrocyrtus imomzodai Barševskis, 2016, a new synonym of Metapocyrtus (Orthocyrtus) orbiferoides Schultze, 1918 (Coleoptera: Curculionidae: Entiminae)
Authors: YOSHITAKE HIRAKU
Published: April 2017

Metapocyrtus (Orthocyrtus) orbiferoides Schultze, 1918 was described based on the female holotype collected from Ilocos Norte, North Luzon, Philippines. Since that time, it has been left unstudied for almost a century until I examined the holotype of M. (O.) orbiferoides in 2010 at Senckenberg Naturhistorische Sammlungen, Museum für Tierkunde, Dresden (SMTD). Recently, Barševskis (2016) described Macrocyrtus imomzodai based on two female specimens from Ilocos Norte, Luzon. Judging from the original description and dorsal and lateral habitus images, it is quite apparent that M. imomzodai is conspecific with M. (O.) orbiferoides. Here I propose a new synonymy based on these examinations. I thank Klaus-Dieter Klass, Olaf Jäger, Christian Schmidt, and Matthias Nuss (SMTD) for their support during my stay in Dresden. My thanks are also due to Steve R. Davis (American Natural History Museum, New York) and Naoko Nakahara (Tsukuba) for their help for preparing the manuscript.
Validation of the replacement name Eusceliotes Stebbing, 1888 for the pelagic hyperiidean amphipod genus Euscelus Claus, 1879 (Crustacea: Amphipoda: Hyperiidea: Parascelidae), preoccupied by Euscelus Schoenherr, 1833 (Insecta: Coleoptera: Attelabidae)
Authors: ZEIDLER WOLFGANG
Published: April 2017

The generic name Euscelus was originally proposed by Schoenherr (1833: 205) for a genus of Leaf Rolling weevils (Insecta: Coleoptera: Attelabidae). It is a valid name, in current use, for a relatively large genus of weevils, widespread in northern South America and central America, including the West Indies and the Caribbean (e.g. Hamilton 2007; Legalov 2007). Euscelus Claus, 1879 was established as a monotypic genus of pelagic amphipod (Crustacea: Amphipoda: Hyperiidea: Parascelidae). It is a very rare genus, still monotypic, with the only species, E. robustus Claus, 1879, having been recorded only twice in the literature prior to my review of the families and genera of the superfamily Platysceloidea (Zeidler 2016); initially by Claus (1879), from the Indian Ocean (off Zanzibar), and secondly by Spandl (1927), from the North Atlantic Ocean (off the Azores). Both authors only recorded males. While examining the collections of the Zoological Museum, University of Copenhagen (Zeidler 2016) more specimens of this rare species were located amongst the collections of the Dana expeditions of 1928–1930 (Jespersen & Tåning 1934), thus enabling a more complete description of the species including that of females. It was recently brought to my attention that, according to the data base Interim Register of Marine and Nonmarine Genera (Rees 2016), Euscelus Claus, 1879 is a junior homonym of Euscelus Schoenherr, 1833. While researching this problem I discovered that Stebbing (1888) had also become aware of this homonymy and had suggested the replacement name Eusceliotes. Unfortunately, Stebbing (1888) only refers to the name in his index (pp. 1672, 1699) and hence subsequent authors were unaware of the above homonymy and Stebbing’s replacement name, although it is listed by Neave (1939: 370). The purpose of this communication is to resolve the above homonymy by validating Stebbing’s (1888) replacement name. This action is preferred to proposing yet another new name for Euscelus Claus, 1879, in order to avoid further confusion, because Stebbing’s name, Eusceliotes, already exists in the literature (Stebbing 1888, Neave 1939).
The Influence of Atmospheric Cloud Radiative Effects on the Large-Scale Stratospheric Circulation
Authors: Li Ying , Thompson David W. J. , Huang Yi
Published: April 2017

Previous studies have explored the influence of atmospheric cloud radiative effects (ACRE) on the tropospheric circulation. Here the authors explore the influence of ACRE on the stratospheric circulation. The response of the stratospheric circulation to ACRE is assessed by comparing simulations run with and without ACRE. The stratospheric circulation response to ACRE is reproducible in a range of different GCMs and can be interpreted in the context of both a dynamically driven and a radiatively driven component.

The dynamic component is linked to ACRE-induced changes in the vertical and meridional fluxes of wave activity. The ACRE-induced changes in the vertical flux of wave activity into the stratosphere are consistent with the ACRE-induced changes in tropospheric baroclinicity and thus the amplitude of midlatitude baroclinic eddies. They account for a strengthening of the Brewer–Dobson circulation, a cooling of the tropical lower stratosphere, a weakening and warming of the polar vortex, a reduction of static stability near the tropical tropopause transition layer, and a shortening of the time scale of extratropical stratospheric variability. The ACRE-induced changes in the equatorward flux of wave activity in the low-latitude stratosphere account for a strengthening of the zonal wind in the subtropical lower to midstratosphere.

The radiative component is linked to ACRE-induced changes in the flux of longwave radiation into the lower stratosphere. The changes in radiative fluxes lead to a cooling of the extratropical lower stratosphere, changes in the static stability and cloud fraction near the extratropical tropopause, and a shortening of the time scales of extratropical stratospheric variability.

The results highlight a previously overlooked pathway through which tropospheric climate influences the stratosphere.
A Method to Extrapolate the Diffuse Upwelling Radiance Attenuation Coefficient to the Surface as Applied to the Marine Optical Buoy (MOBY)
Authors: Voss Kenneth J. , Gordon Howard R. , Flora Stephanie , Johnson B. Carol , Yarbrough Mark , Feinholz Michael , Houlihan Terrence
Published: April 2017

The upwelling radiance attenuation coefficient KLu in the upper 10 m of the water column can be significantly influenced by inelastic scattering processes and thus will vary even with homogeneous water properties. The Marine Optical Buoy (MOBY), the primary vicarious calibration site for many ocean color sensors, makes measurements of the upwelling radiance Lu at 1, 5, and 9 m, and uses these values to determine KLu and to propagate the upwelling radiance directed toward the zenith, Lu, at 1 m to and through the surface. Inelastic scattering causes the KLu derived from the measurements to be an underestimate of the true KLu from 1 m to the surface at wavelengths greater than 575 nm; thus, the derived water-leaving radiance is underestimated at wavelengths longer than 575 nm. A method to correct this KLu, based on a model of the upwelling radiance including Raman scattering and chlorophyll fluorescence, has been developed that corrects this bias. The model has been experimentally validated, and this technique can be applied to the MOBY dataset to provide new, more accurate products at these wavelengths. When applied to a 4-month MOBY deployment, the corrected water-leaving radiance Lw can increase by 5% (600 nm), 10% (650 nm), and 50% (700 nm). This method will be used to provide additional and more accurate products in the MOBY dataset.