bluuebunny/crossref_metadata_2025 huggingface dataset:
Circulating T helper 9 cells and increased serum interleukin‐9 levels in patients with knee osteoarthritis
Authors: Qi Changlin , Shan Yuxing , Wang Jing , Ding Fupeng , Zhao Ding , Yang Teng , Jiang Yanfang
Published: March 2016

The purpose of this study was to examine the roles of T helper 9 (Th9) cells and the serum interleukin (IL)‐9 level in the pathogenesis of osteoarthritis (OA). The numbers of IL‐9+ CD4+ CD8− T cells, interferon (IFN)‐γ+ CD4+ CD8− T cells, IL‐4+ CD4+ CD8− T cells, and IL‐17A+ CD4+ CD8− T cells in 25 OA patients and 13 healthy controls (HC) were examined by flow cytometry. The serum concentrations of IL‐9, IL‐4, IL‐17A, and IFN‐γ were also determined. The numbers of CD4+CD45RO+ T cells, Th9 cells, Th1 cells, and Th17 cells in OA patients were significantly higher than those in HCs. Furthermore, serum IL‐9, IL‐17A, and IFN‐γ levels in OA patients were higher than those in HCs. The number of Th9 cells was positively correlated with the number of Th17 cells in OA patients. Furthermore, greater numbers of Th9 cells were positively associated with elevated C‐reactive protein, and both Th9 cells and IL‐9 levels were positively correlated with the Western Ontario and McMaster Universities Osteoarthritis index in OA patients. Th9 cell numbers and IL‐9 levels are correlated with OA patient symptoms and joint functionality and may be a marker of disease activity.
‘All About That Bass’? Is non‐ideal‐weight discrimination unlawful in the UK?
Authors: Hervey Tamara , Rostant Philip
Published: March 2016

People of non‐ideal‐weight (overweight or severely underweight) are subjected to discrimination, in the workplace and elsewhere, based on attitudinal assumptions and negative inferences from their membership of a group, such as that they are insufficiently self‐motivated to make good employees. But is that discrimination unlawful in the UK? The Equality Act 2010 offers only a very tenuous route for protection, because the Act is based largely on a ‘medical model’ of disability. EU law, which embraces a ‘social model’ of disability, drawing from the UN Convention on the Rights of Persons with Disabilities, offers more, at least in theory. But the mechanisms for enforcing individual EU law rights mean that entitlements in EU law are likely to be enforceable in practice only against state employers. This situation leaves a gap in the law which is remediable only by legislative reform.
Fraud by Abuse of Position and Unlicensed Gangmasters
Authors: Collins Jennifer
Published: March 2016

This article analyses the Court of Appeal's interpretation of the fraud by abuse of position offence in R v Valujevs. Two issues are explored: first, the Court's welcome clarification of the meaning of a relevant ‘expectation’; second, the inadequacy of the Court's reasoning in deciding that an unlicensed gangmaster ‘is expected to safeguard, or not to act against, the financial interests’ of his workers.
Predictors of Gaps in Patient Safety and Quality in U.S. Hospitals
Authors: Unruh Lynn , Hofler Richard
Published: March 2016

Objective

To explore predictors of gaps between observed and best possible Hospital Compare scores in U.S. hospitals.

Data Sources

American Hospital Association Annual Survey; Area Resource Files; Centers for Medicare and Medicaid Services Medicare Provider and Analysis Review; and Hospital Compare data.

Study Design

Using Stochastic Frontier Analysis and secondary cross‐sectional data, gaps between the best possible and actual scores of Hospital Compare quality measures were estimated. Poisson regressions were used to ascertain financial, organizational, and market predictors of those gaps.

Data Extraction

Data were cleaned and matched based on hospital Medicare IDs. All U.S. hospitals that matched on analysis variables in 2007 were in the study (1,823–2,747, depending upon gap variable).

Principal Findings

Most hospitals have a greater than 10 percent gap in quality indicators. Payer mix, registered nurse staffing, size, case mix index, accreditation, being a teaching hospital, market competition, urban location, and region were strong predictors of gaps, although the direction of the association with gaps was not uniform across outcomes.

Conclusions

A significant percentage of hospitals have gaps between their best possible and observed quality scores. It may be better to use gap scores than observed scores in payments systems. More SFA research is needed to know how to lower gaps through changes in hospital and market characteristics.
Use of serum lactate levels to predict survival for patients with out‐of‐hospital cardiac arrest: A cohort study
Authors: Williams Teresa A , Martin Ry , Celenza Antonio , Bremner Alexandra , Fatovich Daniel , Krause Joel , Arena Steven , Finn Judith
Published: March 2016

Objectives

We examined the association of serum lactate levels and early lactate clearance with survival to hospital discharge for patients suffering an out‐of‐hospital cardiac arrest (OHCA).

Methods

A retrospective cohort analysis was performed of patients with OHCA transported by ambulance to two adult tertiary hospitals in Perth, Western Australia. Exclusion criteria were traumatic cardiac arrest, return of spontaneous circulation prior to the arrival of the ambulance, age less than 18 years and no serum lactate levels recorded. Serum lactate levels recorded for up to 48 h post‐arrest were obtained from the hospital clinical information system, and lactate clearance over 48 h was calculated. Descriptive and logistic regression analyses were conducted.

Results

There were 518 patients with lactate values, of whom 126 (24.3%) survived to hospital discharge. Survivors and non‐survivors had different mean initial lactate levels (mean ± SD 6.9 ± 4.7 and 12.2 ± 5.5 mmol/L, respectively; P < 0.001). Lactate clearance was higher in survivors. Lactate levels for non‐survivors did not decrease below 2 mmol/L until at least 30 h after the ambulance call.

Conclusion

In OHCA patients who had serum lactate levels measured, both lower initial serum lactate and early lactate clearance in the first 48 h following OHCA were associated with increased likelihood of survival. However, the use of lactate in isolation as a predictor of survival or neurological outcome is not recommended. Prospective studies that minimise selection bias are required to determine the clinical utility of serum lactate levels in OHCA patients.
Liver Support With Albumin Dialysis Reduces Hepatitis C Virus Viremia and Facilitates Antiviral Treatment of Severe Hepatitis C Virus Recurrence After Liver Transplantation
Authors: Ibáñez‐Samaniego Luis , Catalina María‐Vega , Rincón Diego , Lo Iacono Oreste , Fernández Ainhoa , Clemente Gerardo , Bañares Rafael , Vaquero Javier , Salcedo Magdalena
Published: March 2016

Patients with severe hepatitis C virus (HCV) recurrence after liver transplantation (LT) present an ominous prognosis, rarely achieving sustained virological response (SVR). Dialysis procedures may transiently decrease the HCV viral load, but the effect of albumin dialysis is currently unknown. Here, we evaluated the impact of albumin dialysis using the Molecular Adsorbent Recirculating System (MARS) used as a co‐adjuvant antiviral treatment for severe HCV recurrence after LT. Thirteen patients (11 males, median age 48 years) with fibrosing cholestatic hepatitis or METAVIR fibrosis score ≥ F3 with severe portal hypertension underwent three consecutive MARS sessions. Antiviral therapy was initiated in 11 patients within 24 h after the MARS sessions. A contemporary cohort of seven patients who did not follow the MARS protocol is shown for comparison. MARS treatment resulted in consistent decreases of viral load from 7.59 log10 IU/mL [6.15–8.90] to 6.79 log10 IU/mL [5.18–7.84] (P = 0.003) as well as in decreases of serum bilirubin, gamma‐glutamyl transpeptidase, alanine aminotransferase and aspartate aminotransferase (all P < 0.05). The overall rate of SVR was 0% in the Control group and 54.6% in patients initiating antiviral therapy within 24 h after MARS. Survival at 1 and 3 years was, respectively, 93% and 70% in patients undergoing MARS, compared with 29% and 14% in the Control group (P = 0.001). No major adverse events related to MARS treatment were observed. In conclusion, the use of MARS may facilitate the achievement of SVR and improve the prognosis of patients with severe HCV‐recurrence after LT by reducing viral load and improving liver function prior to antiviral therapy.
Quantitative Analysis of Bioactive Compounds from Aromatic Plants by Means of Dynamic Headspace Extraction and Multiple Headspace Extraction‐Gas Chromatography‐Mass Spectrometry
Authors: Omar Jone , Olivares Maitane , Alonso Ibone , Vallejo Asier , Aizpurua‐Olaizola Oier , Etxebarria Nestor
Published: March 2016

Seven monoterpenes in 4 aromatic plants (sage, cardamom, lavender, and rosemary) were quantified in liquid extracts and directly in solid samples by means of dynamic headspace‐gas chromatography‐mass spectrometry (DHS‐GC‐MS) and multiple headspace extraction‐gas chromatography‐mass spectrometry (MHSE), respectively. The monoterpenes were 1st extracted by means of supercritical fluid extraction (SFE) and analyzed by an optimized DHS‐GC‐MS. The optimization of the dynamic extraction step and the desorption/cryo‐focusing step were tackled independently by experimental design assays. The best working conditions were set at 30 °C for the incubation temperature, 5 min of incubation time, and 40 mL of purge volume for the dynamic extraction step of these bioactive molecules. The conditions of the desorption/cryo‐trapping step from the Tenax TA trap were set at follows: the temperature was increased from 30 to 300 °C at 150 °C/min, although the cryo‐trapping was maintained at −70 °C. In order to estimate the efficiency of the SFE process, the analysis of monoterpenes in the 4 aromatic plants was directly carried out by means of MHSE because it did not require any sample preparation. Good linearity (r2 > 0.99) and reproducibility (relative standard deviation % <12) was obtained for solid and liquid quantification approaches, in the ranges of 0.5 to 200 ng and 10 to 500 ng/mL, respectively. The developed methods were applied to analyze the concentration of 7 monoterpenes in aromatic plants obtaining concentrations in the range of 2 to 6000 ng/g and 0.25 to 110 μg/mg, respectively.
Integrated analysis of different microarray studies to identify candidate genes in type 1 diabetes
Authors: Jia Xiaowei , Yu Haotian , Zhang Hui , Si Yanfang , Tian Dengmei , Zhao Xin , Luan Jin , Jia Hetang
Published: March 2016

Background

Type 1 diabetes (T1D), an autoimmune disease, occurs most commonly in children. Identifying altered gene expression in peripheral blood mononuclear cells (PBMCs) of T1D may lead to new strategies for preserving or improving β‐ell function in patients with T1D.

Methods

The Gene Expression Omnibus database was searched for microarray studies in PBMCs of T1D. Subsequently, gene expression datasets from multiple microarray studies were integrated to obtain differentially expressed genes (DEGs) between T1D and normal controls (NC). Gene function analysis was performed to determine the functions of the DEGs identified.

Results

Four microarray studies were available for analysis, including 199 T1D samples and 74 NC samples. Analysis revealed 695 genes that were significantly differentially expressed in PBMCs from T1D compared with NC samples, with 450 upregulated and 245 downregulated. Signal transduction (gene ontology [GO]: 0007165; false discovery rate [FDR] = 1.54 × 10–7) and protein binding (GO: 0005515; FDR = 2.93 × 10–24) were significantly enriched for the GO categories of biological processes and molecular functions, respectively. The most significant pathway in the Kyoto Encyclopedia of Genes and Genomes analysis was arachidonic acid metabolism (FDR = 1.44 × 10–3). Protein–protein interaction network analysis showed that the significant hub proteins contained immature colon carcinoma transcript 1 (ICT1; degree = 214; clustering coefficient [C] = 4.39 × 10–5), zinc finger and BTB domain containing 16 (ZBTB16; degree = 112; C = 8.04 × 10–4), and SERTA domain containing 1 (SERTAD1; degree = 38; C = 0.0014).

Conclusions

This integrated analysis will help develop improved therapies and interventions for T1D by identifying novel drug targets.
New resources for genetic studies in Populus nigra: genome‐wide SNP discovery and development of a 12k Infinium array
Authors: Faivre‐Rampant P. , Zaina G. , Jorge V. , Giacomello S. , Segura V. , Scalabrin S. , Guérin V. , De Paoli E. , Aluome C. , Viger M. , Cattonaro F. , Payne A. , PaulStephenRaj P. , Le Paslier M. C. , Berard A. , Allwright M. R. , Villar M. , Taylor G. , Bastien C. , Morgante M.
Published: March 2016

Whole genome resequencing of 51 Populus nigra (L.) individuals from across Western Europe was performed using Illumina platforms. A total number of 1 878 727 SNPs distributed along the P. nigra reference sequence were identified. The SNP calling accuracy was validated with Sanger sequencing. SNPs were selected within 14 previously identified QTL regions, 2916 expressional candidate genes related to rust resistance, wood properties, water‐use efficiency and bud phenology and 1732 genes randomly spread across the genome. Over 10 000 SNPs were selected for the construction of a 12k Infinium Bead‐Chip array dedicated to association mapping. The SNP genotyping assay was performed with 888 P. nigra individuals. The genotyping success rate was 91%. Our high success rate was due to the discovery panel design and the stringent parameters applied for SNP calling and selection. In the same set of P. nigra genotypes, linkage disequilibrium throughout the genome decayed on average within 5–7 kb to half of its maximum value. As an application test, ADMIXTURE analysis was performed with a selection of 600 SNPs spread throughout the genome and 706 individuals collected along 12 river basins. The admixture pattern was consistent with genetic diversity revealed by neutral markers and the geographical distribution of the populations. These newly developed SNP resources and genotyping array provide a valuable tool for population genetic studies and identification of QTLs through natural‐population based genetic association studies in P. nigra.
Hybridization relics complicate barcode‐based identification of species in earthworms
Authors: Dupont L. , Porco D. , Symondson W. O. C. , Roy V.
Published: March 2016

Introgressive hybridization results in mito‐nuclear discordance which could obscure the delimitation of closely related taxa. Although such events are increasingly reported, they have been poorly studied in earthworms. Here, we propose a method for investigating the degree of introgressive hybridization between three taxa of the Allolobophora chlorotica aggregate within two field populations (N = 67 and N = 105) using a reference data set including published DNA barcoding and microsatellite data of all known A. chlorotica lineages (N = 85). For this, we used both molecular phylogenetic and population genetic approaches. The test of correspondence between mitochondrial cytochrome c oxidase I (COI) lineages and clusters of nuclear microsatellite genotypes allowed individuals to be sorted in three categories (matching, admixed and nonmatching) and additional markers (mitochondrial NADH dehydrogenase subunit 1, nuclear Histone 3 and Internal transcribed Spacer Region 2) were used for phylogenetic reconstructions in order to check assignments. Although 15 admixed individuals were observed, no early‐generation hybrids were detected within the two populations. Interestingly, 14 nonmatching individuals (i.e. with a mtDNA haplotype that did not correspond to their nuclear cluster) were detected, a pattern that would result after multiple generations of unidirectional hybridization of female from one taxon to male of the other taxon. Because earthworms are simultaneous hermaphrodites, these events of unidirectional hybridization suggest sterility of the male function in several crosses and highlight that some individuals can be misidentified if reliance is placed on COI barcodes alone. These findings could improve the use of these barcodes in earthworms for species delineation.
Gastroscopic removal of a giant fibrovascular polyp from the esophagus
Authors: Li Jie , Yu Hua , Pu Renfu , Lu Zhongsheng
Published: March 2016

Giant polyps in the esophagus are rarely occurring benign tumors and may contain lipomas, fibrovascular polyps, fibrolipomas or neurofibromas polyps. Clinical symptoms include dysphagia, vomiting, retrosternal pain, shortness of breath, and asthma. In some cases, the polyps are regurgitated into the oral cavity and represent a spectacular manifestation. The reported case in this study was of a 50‐year‐old man who complained of emesia for half a year and dysphagia for one month before being hospitalized. Occasionally, a fleshly mass reached into his mouth. The results of endoscopic ultrasonography, barium swallow in the upper digestive tract, and a computed tomography scan demonstrated a giant polyp in the esophagus, which was subsequently removed by gastroscopy. Pathological examination determined a fibrovascular polyp.
Alpha‐Tocopherol Counteracts the Effect of Ethanol on Cortical Spreading Depression in Rats of Various Ages, With and Without Ethanol Abstinence
Authors: Abadie‐Guedes Ricardo , Bezerra Ranilson de Souza , Guedes Rubem Carlos Araújo
Published: March 2016

Background

We previously demonstrated that acute and chronic treatment with ethanol (EtOH), respectively, decelerated and accelerated the propagation of cortical spreading depression (CSD) in rats and that the antioxidant carotenoid astaxanthin counteracted these effects. Here, we investigated whether noncarotenoid antioxidants exert the same action by testing α‐tocopherol in rats of various ages, with and without 5 to 10 days of EtOH abstinence.

Methods

Male Wistar young adult (60 to 80 days old) and mature adult (150 to 180 days old) rats received per gavage acute (1 day) or chronic (21 days) treatment with 3 g/kg/d EtOH combined with acute (300 mg/kg) or chronic (85 mg/kg/d) treatment with α‐tocopherol or vehicle‐only treatment (olive oil and water for α‐tocopherol and EtOH, respectively). CSD was recorded over 4 hours and the velocity of CSD propagation was calculated. On both ages, animals under chronic EtOH treatment were subjected to CSD recording immediately after EtOH treatment or after a 5‐ to 10‐day period of EtOH abstinence.

Results

In both age groups, acute and chronic EtOH exposure decelerated and accelerated CSD, respectively, versus the corresponding control groups. Addition of α‐tocopherol counteracted the effects of EtOH on CSD, returning CSD velocities to levels in control groups (p < 0.05). Chronic α‐tocopherol (85 mg/kg/d) did not alter CSD.

Conclusions

Our data reinforce the counteracting role of antioxidants on brain processes involved in the action of EtOH on CSD and suggest that this role is not a particular property of carotenoids; furthermore, this general feature of antioxidants is not substantially influenced by age or by 5 to 10 days of EtOH abstinence.
Testing the Relations Among Family Disorganization, Delay Discounting, and Adolescent Alcohol Use: A Genetically Informed Study
Authors: Wang Frances L. , Pandika Danielle , Chassin Laurie , Lee Matthew , King Kevin
Published: March 2016

Background

Delay discounting is a potential etiological factor in adolescents' alcohol use, making it important to understand its antecedents. Family disorganization might contribute to delay discounting, but few studies have tested this relation. Moreover, because delay discounting is heritable, the effects of family disorganization on delay discounting might be moderated by adolescents' genetic risk for delay discounting. Thus, the current study examined the role of family disorganization, in interaction with genetic risk, in predicting adolescents' delay discounting and subsequent alcohol use.

Methods

Adolescents participated in 4 waves of data collection. Adolescents self‐reported their family disorganization at T1, completed a delay discounting questionnaire at T3, and self‐reported their alcohol use both at T2 (covariate) and T4 (outcome). Using results from an independent sample, we created a polygenic risk score consisting of dopaminergic genes to index genetic risk for delay discounting.

Results

Greater family disorganization predicted adolescents' greater delay discounting, but only for adolescents with low levels of genetic risk for delay discounting. Adolescents with high and mean levels of genetic risk for delay discounting showed elevated delay discounting regardless of their family's disorganization. Greater delay discounting prospectively predicted adolescents' greater alcohol use. Finally, the effects of family disorganization on adolescents' alcohol use were mediated through delay discounting, but only for adolescents with low levels of genetic risk.

Conclusions

Results suggest multiple pathways to delay discounting. Although there are genetically influenced pathways to delay discounting, family disorganization might represent an environmental pathway to delay discounting (and subsequent alcohol use) for a subset of adolescents at low genetic risk. These findings reinforce the utility of family interventions for reducing adolescents' delay discounting and alcohol use, at least for a subgroup of adolescents. Because higher family organization did not buffer against delay discounting among adolescents with high genetic risk, future research should explore other early environmental influences that could protect these high‐risk adolescents from developing these risky behaviors.
Blood Alcohol Concentrations in Suicide and Motor Vehicle Crash Decedents Ages 18 to 54
Authors: Conner Kenneth R. , Lathrop Sarah , Caetano Raul , Silenzio Vincent , Nolte Kurt B.
Published: March 2016

Background

Using postmortem data, we examined the hypotheses that high (and very high) blood alcohol concentrations (BACs) are more common among motor vehicle crash decedents (MVCs) than among suicide decedents, whereas low alcohol levels are more common among suicides.

Methods

We examined BAC in 224 suicide decedents and 166 MVCs ages 18 to 54 in the state of New Mexico in 2012. Comparisons between the groups were made based on differing BAC levels using 0.080 g/dl categories including low (0.001 to 0.079 g/dl), high (0.080 to 0.159 g/dl), and very high BAC (≥0.160 g/dl), and based on 0.100 g/dl categories including low (0.001 to 0.099 g/dl), high (0.100 to 0.199 g/dl), and very high BAC (≥0.200 g/dl), with these groups compared with a no‐alcohol reference (0.000 g/dl) in separate analyses. Multivariate logistic regressions compared suicides with MVCs that adjusted for age, sex, and race/ethnicity.

Results

Support for the hypothesis that suicides are more likely to have a low BAC level was supported in the analysis using the 0.100 g/dl categorizations. Neither analysis supported the hypothesis that MVCs are more likely to have high (or very high) BACs compared with suicides. Among both injury groups with positive BACs, low BACs were least common.

Conclusions

Low BAC levels may be more likely to be observed among suicides compared with MVCs, a possible reflection of the more varied role that alcohol plays in suicide compared with MVC. Nonetheless, high (and very high) BAC is the predominant scenario in both suicides and MVCs with positive BAC.
The restoration of traumatized teeth
Authors: Liddelow G , Carmichael G
Published: March 2016

The restoration of a traumatized tooth may require minimally invasive or more extensive treatment options. The majority of injuries occur in the younger population, so management should consider the long‐term outcome, failure and future treatment needs over the course of, often, many decades. The aim should be to provide a tooth‐restoration complex that closely mimics the functional and aesthetic qualities of an intact tooth for as long as possible. This narrative review will assess the relevant literature pertinent to restoration of traumatized teeth in order to provide guidance for the practising clinician.
Life cycles of traumatized teeth: long‐term observations from a cohort of dental trauma victims
Authors: Heithersay GS
Published: March 2016

Life cycles of dental trauma victims can provide important clinical information, especially when viewed over many years. In this first series of life cycles, the pulp and periodontal responses to traumatic injuries of four patients are documented over periods varying from 26 to 51 years. The dynamics of pulp survival following an intrusive luxation and two avulsions are followed, with particular reference to pulp canal calcification to which a new term, root canal stenosis, has been proposed. The life cycles include the successful management of inflammatory root resorption in a replanted tooth with an open apex contrasting with the early prophylactic endodontic treatment of two replanted teeth in a patient with mature apices. The long‐term development of invasive cervical resorption in one of the patient's life cycle highlights the importance of ongoing follow‐up examinations for dental trauma victims.
Neto2 Influences on Kainate Receptor Pharmacology and Function
Authors: Han Liwei , Howe James R. , Pickering Darryl S.
Published: March 2016

Neuropilin tolloid‐like protein 2 (Neto2) is an auxiliary subunit of kainate receptors (KARs). It specifically regulates KARs, for example slows desensitization and deactivation, increases the rate of recovery from desensitization, promotes modal gating and increases agonist sensitivity. Although the mechanism of Neto2 modulation is still unclear, gain‐of‐function results from the characterization of GluK1–GluA2 chimeras indicate that the GluK1 sequences included in these chimeras (part or all of the TMD and part of the linkers between the TMDs and LBD) play a key role in Neto2 modulation of KAR. In addition, GluK2 M3–S2 linkers and the D1–D1 dimer interface were also recently identified to be important for Neto2 modulation, and some studies suggested that Neto2's N‐terminal regions, LDLa domain and the C‐terminal regions are important for its modulation of KARs. Although more studies are needed to confirm the roles of these domains and to identify all the domains and residues essential for KAR modulation, these results facilitate our understanding of Neto2 modulation at the structural level, which could potentially aid the development of novel therapies for the treatment of diseases that are associated with KARs, for example epilepsies, non‐syndromic autosomal recessive mental retardation, schizophrenia and bipolar disorder.
How Are Motor Skills Linked to Children's School Performance and Academic Achievement?
Authors: Cameron Claire E. , Cottone Elizabeth A. , Murrah William M. , Grissmer David W.
Published: March 2016

Children need a range of skills to transition successfully to formal schooling. In early childhood classrooms, children must master their fine and gross motor skills. In this article, we review the evidence that links motor skills to diverse school outcomes, then describe three sets of cognitive processes—motor coordination, executive function, and visuospatial skills—that are tapped by motor assessments. We then use these processes to explain how motor skills are implicated in children's self‐regulation and their emergent literacy and numeracy. We conclude by encouraging theoretical and methodological approaches to clarify the mechanisms that implicate motor skills in school performance and achievement.
Expanding the phenotype of CRB2 mutations – A new ciliopathy syndrome?
Authors: Jaron R. , Rosenfeld N. , Zahdeh F. , Carmi S. , Beni‐Adani L. , Doviner V. , Picard E. , Segel R. , Zeligson S. , Carmel L. , Renbaum P. , Levy‐Lahad E.
Published: March 2016

Recessive CRB2 mutations were recently reported to cause both steroid resistant nephrotic syndrome and prenatal onset ventriculomegaly with kidney disease. We report two Ashkenazi Jewish siblings clinically diagnosed with ciliopathy. Both presented with severe congenital hydrocephalus and mild urinary tract anomalies. One affected sibling also has lung hypoplasia and heart defects. Exome sequencing and further CRB2 analysis revealed that both siblings are compound heterozygotes for CRB2 mutations p.N800K and p.Gly1036Alafs*43, and heterozygous for a deleterious splice variant in the ciliopathy gene TTCB21. CRB2 is a polarity protein which plays a role in ciliogenesis and ciliary function. Biallelic CRB2 mutations in animal models result in phenotypes consistent with ciliopathy. This report expands the phenotype of CRB2 mutations to include lung hypoplasia and uretero‐pelvic renal anomalies, and confirms cardiac malformation as a feature. We suggest that CRB2‐associated disease is a new ciliopathy syndrome with possible digenic/triallelic inheritance, as observed in other ciliopathies. Clinically, CRB2 should be assessed when ciliopathy is suspected, especially in Ashkenazi Jews, where we found that p.N800K carrier frequency is 1 of 64. Patients harboring CRB2 mutations should be tested for the complete range of ciliopathy manifestations.
Titanium implants coated with UV‐irradiated vitamin D precursor and vitamin E: in vivo performance and coating stability
Authors: Satué María , Monjo Marta , Ronold Hans Jacob , Lyngstadaas Staale Petter , Ramis Joana M.
Published: March 2016

Objectives

This study aimed at evaluating the biological response of titanium implants coated with UV‐irradiated 7‐dehydrocholesterol (7‐DHC) and vitamin E (VitE) in vivo and analyzing the effects of aging on their stability and bioactivity in vitro.

Material and methods

Titanium surfaces were coated with 7‐DHC and VitE, UV‐irradiated and incubated for 48 h at 23°C to allow cholecalciferol synthesis. The in vivo biological response was tested using a rabbit tibia model after 8 weeks of healing by analyzing the wound fluid and the mRNA levels of several markers at the bone–implant interface (N = 8). The stability of the coating after storage up to 12 weeks was determined using HPLC analysis, and the bioactivity of the stored modified implants was studied by an in vitro study with MC3T3‐E1 cells (N = 6).

Results

A significant increase in gene expression levels of osteocalcin was found in the bone tissue attached to implants coated with the low dose of 7‐DHC and VitE, together with a higher ALP activity in the wound fluid. Implants treated with the high dose of 7‐DHC and VitE showed increased tissue necrosis and inflammation. Regarding the aging effects, coated implants were stable and bioactive up to 12 weeks when stored at 4°C and avoiding oxygen, light and moisture.

Conclusion

This study demonstrates that Ti implants coated with UV‐irradiated 7‐DHC and VitE promote in vivo gene expression of bone formation markers and ALP activity, while they keep their osteopromotive potential in vitro and composition when stored up to 12 weeks at 4°C.
Level of use and safety of botanical products for itching vulvar dermatoses. Are patch tests useful?
Authors: Corazza Monica , Virgili Annarosa , Toni Giulia , Minghetti Sara , Tiengo Silvia , Borghi Alessandro
Published: March 2016

Background

Topical remedies based on botanical ingredients are popular.

Objectives

To assess: (i) the usage of botanical substances in subjects affected with itching and chronic vulvar complaints; (ii) the incidence of side‐effects associated with their use and the frequency of contact allergy; (iii) the diagnostic usefulness of patch testing.

Methods

Sixty‐six patients were provided with a questionnaire to assess the prevalence and type of topical botanical preparations used and the occurrence of adverse reactions. Patients were patch tested with (i) the Italian baseline series, (ii) a topical medicament series, and (iii) a botanical series.

Results

Forty‐two patients (63.6%) reported the use of natural topical products on the vulva. Seven (16.7%) noted adverse reactions; 27 showed positive reactions with the baseline series; 14 (21.2%) had at least one relevant reaction, mainly to allergens in topical products and cosmetics; and 2 (3%) showed positive reactions to the botanical series. Of the 7 patients complaining of adverse effects of botanical products, 3 (42.8%) showed relevant sensitization.

Conclusions

The use of natural topical products is widespread among women affected with itching vulvar diseases. Contact dermatitis is a possible adverse effect. Botanical series are of questionable usefulness, owing to the wide variety of botanical ingredients.
Antibody responses to influenza vaccine in pre‐ and post‐lung transplant patients
Authors: Miller Ryan M. , Rohde Kalynn A. , Tingle Michael T.A. , Moran John J.M. , Hayney Mary S.
Published: March 2016

Background

Although pre‐transplant immunization is routinely recommended, this recommendation is based on little data. The primary objective of this study was to compare antibody responses in lung transplant patients who received influenza vaccine before the transplant, within the first six months of transplant, between 13 and 60 months post‐transplant, and 110 months or beyond transplant.

Methods

This prospective cohort study included 357 total immunization events performed over five yr to measure H1N1, H3N2, and B antibody responses to the influenza vaccine in pre‐ and post‐lung transplant patients. Geometric mean titers, seroprotection (antibody titer at least 1:40), seroconversion (fourfold increase between pre and post), and mean fold increases were compared.

Results

The geometric mean titer distributions were different for H3N2 and B (ANOVA; p = 0.002 for both). Pre‐transplant antibody concentrations were higher compared to the 13‐ to 60‐month group for H3N2 (corrected p = 0.002) and the healthy group for B (corrected p = 0.001). The ≥110‐month group had higher seroconversion rates compared to the 13‐ to 60‐month group for H3N2 and B viruses.

Conclusion

Lung pre‐transplant patients and the long‐term survivors have higher responses to the influenza vaccine than early post‐transplant and the transplant control groups.
Comparison of live donor pre‐transplant and recipient post‐transplant renal volumes
Authors: Yanishi Masaaki , Kinoshita Hidefumi , Yoshida Takashi , Takayasu Kenta , Yoshida Kenji , Mishima Takao , Sugi Motohiko , Tsukaguchi Hiroyasu , Kawa Gen , Matsuda Tadashi
Published: March 2016

Background

Live donor pre‐transplant and recipient post‐transplant kidney volumes based on three‐dimensional computed tomography (3DCT) have been related to post‐transplant renal function. We examined this association and the effect of sex/size differences between donor and recipient on kidney growth rate.

Methods

We retrospectively reviewed 30 live donors who underwent pre‐transplant and post‐transplant 3DCT. We determined donor (Dvol) and recipient renal volumes (Rvol) based on 3DCT and calculated changes in graft volume after transplantation (Vol‐ratio). We also divided Dvol by recipient body weight (Dvol/RWgt) and compared the correlations between Vol‐ratio and Dvol/RWgt and post‐transplant renal function after one yr. We determined the rates of change in kidney volume and renal function according to the sexes of the donor and recipient.

Results

The mean Dvol and Rvol were 141.7 and 178.4 mL, respectively. The mean Vol‐ratio was 127.3%. Dvol/RWgt showed a significant linear correlation with remaining renal function after one yr (r = 0.6745, p < 0.0001). The combination of female donor and male recipient resulted in the fastest increase in kidney volume (p < 0.001) and highest level of proteinuria (p < 0.001).

Conclusions

Pre‐transplant and post‐transplant kidney volumes are correlated with post‐transplant graft function, and graft growth is affected by the relative sexes of the recipient and donor.
Impact of pre‐operative statin use on risk of mortality and early atrial fibrillation after heart transplantation
Authors: Krishnan Balaji , Vakil Kairav P. , Sankar Ashwini , Duprez Daniel , Benditt David G.
Published: March 2016

Background

Pre‐operative statin use has shown to reduce the incidence of post‐operative atrial fibrillation (AF), but not mortality in patients undergoing cardiac surgery. This association, however, has not been examined in a heart transplant (HT) cohort.

Methods

Adults (≥18 yr) who underwent HT between 1997 and 2007 at the University of Minnesota were retrospectively identified. Primary outcome was 30‐d mortality after HT. Secondary outcomes were 30‐d incidence of AF and time to all‐cause mortality.

Results

Data from 259 patients (mean age 52.0 ± 11.7 yr, 81% males) were analyzed. Total of 133 (51%) patients were on statin pre‐operatively at the time of HT and constituted the statin group. During a mean follow‐up of 6.7 ± 3.7 yr, 82 (32%) deaths occurred, 21 (8%) of which occurred within 30 d of HT. The incidence of 30‐d mortality was not significantly different between the statin and no‐statin groups (9% vs. 7%, p = 0.58). Further, cumulative long‐term survival after HT was not significantly different between the study groups (log‐rank p = 0.49). Pre‐transplant statin use did not impact the 30‐d incidence of post‐transplant AF (16% vs. 19%, p = 0.59).

Conclusions

Pre‐operative statin therapy does not seem to influence the risk of mortality or early post‐operative AF after HT. Future large‐scale studies are required to validate these preliminary findings.
Christianity: Maidservant to War?
Authors: Denton‐Borhaug Kelly
Published: March 2016

In this multi‐book review article, the author examines three new texts that make the case for a deeper, richer understanding of the Christian tradition of nonviolence. All three authors argue that traditions of nonviolence, and misgivings and suspicion regarding the sanctioned shedding of blood, are central to the understanding and practice of Christianity, and deserve to be taken more seriously by researchers and practitioners alike.
Sodium‐glucose co‐transporter‐2 inhibitors suppress atrial natriuretic peptide secretion in patients with newly diagnosed Type 2 diabetes
Authors: Wang Y. , Xu L. , Yuan L. , Li D. , Zhang Y. , Zheng R. , Liu C. , Feng X. , Li Q. , Li Q. , Ma J.
Published: March 2016

Aims

To observe changes in atrial natriuretic peptide levels after treatment with sodium‐glucose co‐transporter‐2 inhibitors in patients with newly diagnosed type 2 diabetes.

Methods

A total of 28 patients with newly diagnosed Type 2 diabetes and HbA1c levels of 58 –91 mmol/mol (7.5–10.5%) were randomly selected to receive sodium‐glucose co‐transporter‐2 inhibitor treatment (n = 18) or placebo (n = 10) for 24 weeks. We analysed atrial natriuretic peptide concentrations, using an enzyme‐linked immunosorbent assay. In addition, sodium and HbA1c levels were measured at baseline, 12 weeks and 24 weeks and blood lipid levels and insulin sensitivities at baseline and 24 weeks.

Results

Compared with patients treated with placebo, patients who received sodium‐glucose co‐transporter‐2 inhibitor treatment exhibited lower atrial natriuretic peptide levels (36.74 vs 56.90 pg/ml in the placebo group; P < 0.05) and higher sodium levels (144.3 vs 141.4 mmol/l in the placebo group; P < 0.01) at 24 weeks, after adjusting for baseline values. HbA1c levels were lower after sodium‐glucose co‐transporter‐2 inhibitor treatment compared with placebo (51 vs 60 mmol/mol; P < 0.01). No correlation was found between atrial natriuretic peptide and HbA1c levels. Homeostatic model assessment of β‐cell function values and lipid profiles were generally similar after 24 weeks of treatment with placebo or sodium‐glucose co‐transporter‐2 inhibitor.

Conclusions

This study shows the ability of sodium‐glucose co‐transporter‐2 inhibitors to lower atrial natriuretic peptide levels and improve glycaemic control, which may benefit the cardiovascular system.
BMP7 enhances the effect of BMSCs on extracellular matrix remodeling in a rabbit model of intervertebral disc degeneration
Authors: Xu Jun , E Xiao‐Qiang , Wang Nan‐Xiang , Wang Mo‐Nan , Xie Huan‐Xin , Cao Yan‐Hui , Sun Li‐Hua , Tian Jun , Chen Hua‐Jiang , Yan Jing‐Long
Published: March 2016

Intervertebral discs (IVDs) provide stability and flexibility to the spinal column; however, IVDs, and in particular the nucleus pulposus (NP), undergo a degenerative process characterized by changes in the disc extracellular matrix (ECM), decreased cell viability, and reduced synthesis of proteoglycan and type II collagen. Here, we investigated the efficacy and feasibility of stem cell therapy using bone marrow mesenchymal stem cells (BMSCs) over‐expressing bone morphogenetic protein 7 (BMP7) to promote ECM remodeling of degenerated IVDs. Lentivirus‐mediated BMP7 over‐expression induced differentiation of BMSCs into an NP phenotype, as indicated by expression of the NP markers collagen type II, aggrecan, SOX9 and keratins 8 and 19, increased the content of glycosaminoglycan, and up‐regulated β‐1,3‐glucuronosyl transferase 1, a regulator of chondroitin sulfate synthesis in NP cells. These effects were suppressed by Smad1 silencing, indicating that the effect of BMP7 on ECM remodeling was mediated by the Smad pathway. In vivo analysis in a rabbit model of disc degeneration showed that implantation of BMSCs over‐expressing BMP7 promoted cell differentiation and proliferation in the NP, as well as their own survival, and these effects were mediated by the Smad pathway. The results of the present study indicate the beneficial effects of BMP7 on restoring ECM homeostasis in NP cells, and suggest potential strategies for improving cell therapy for the treatment of disc diseases.
Pyrodiversity begets plant–pollinator community diversity
Authors: Ponisio Lauren C. , Wilkin Kate , M'Gonigle Leithen K. , Kulhanek Kelly , Cook Lindsay , Thorp Robbin , Griswold Terry , Kremen Claire
Published: March 2016

Fire has a major impact on the structure and function of many ecosystems globally. Pyrodiversity, the diversity of fires within a region (where diversity is based on fire characteristics such as extent, severity, and frequency), has been hypothesized to promote biodiversity, but changing climate and land management practices have eroded pyrodiversity. To assess whether changes in pyrodiversity will have impacts on ecological communities, we must first understand the mechanisms that might enable pyrodiversity to sustain biodiversity, and how such changes might interact with other disturbances such as drought. Focusing on plant–pollinator communities in mixed‐conifer forest with frequent fire in Yosemite National Park, California, we examine how pyrodiversity, combined with drought intensity, influences those communities. We find that pyrodiversity is positively related to the richness of the pollinators, flowering plants, and plant–pollinator interactions. On average, a 5% increase in pyrodiversity led to the gain of approximately one pollinator and one flowering plant species and nearly two interactions. We also find that a diversity of fire characteristics contributes to the spatial heterogeneity (β‐diversity) of plant and pollinator communities. Lastly, we find evidence that fire diversity buffers pollinator communities against the effects of drought‐induced floral resource scarcity. Fire diversity is thus important for the maintenance of flowering plant and pollinator diversity and predicted shifts in fire regimes to include less pyrodiversity compounded with increasing drought occurrence will negatively influence the richness of these communities in this and other forested ecosystems. In addition, lower heterogeneity of fire severity may act to reduce spatial turnover of plant–pollinator communities. The heterogeneity of community composition is a primary determinant of the total species diversity present in a landscape, and thus, lower pyrodiversity may negatively affect the richness of plant–pollinator communities across large spatial scales.
Conversion from forests to pastures in the Colombian Amazon leads to contrasting soil carbon dynamics depending on land management practices
Authors: Navarrete Diego , Sitch Stephen , Aragão Luiz E. O. C. , Pedroni Lucio
Published: March 2016

Strategies to mitigate climate change by reducing deforestation and forest degradation (e.g. REDD+) require country‐ or region‐specific information on temporal changes in forest carbon (C) pools to develop accurate emission factors. The soil C pool is one of the most important C reservoirs, but is rarely included in national forest reference emission levels due to a lack of data. Here, we present the soil organic C (SOC) dynamics along 20 years of forest‐to‐pasture conversion in two subregions with different management practices during pasture establishment in the Colombian Amazon: high‐grazing intensity (HG) and low‐grazing intensity (LG) subregions. We determined the pattern of SOC change resulting from the conversion from forest (C3 plants) to pasture (C4 plants) by analysing total SOC stocks and the natural abundance of the stable isotopes 13C along two 20‐year chronosequences identified in each subregion. We also analysed soil N stocks and the natural abundance of 15N during pasture establishment. In general, total SOC stocks at 30 cm depth in the forest were similar for both subregions, with an average of 47.1 ± 1.8 Mg C ha−1 in HG and 48.7 ± 3.1 Mg C ha−1 in LG. However, 20 years after forest‐to‐pasture conversion SOC in HG decreased by 20%, whereas in LG SOC increased by 41%. This net SOC decrease in HG was due to a larger reduction in C3‐derived input and to a comparatively smaller increase in C4‐derived C input. In LG both C3‐ and C4‐derived C input increased along the chronosequence. N stocks were generally similar in both subregions and soil N stock changes during pasture establishment were correlated with SOC changes. These results emphasize the importance of management practices involving low‐grazing intensity in cattle activities to preserve SOC stocks and to reduce C emissions after land‐cover change from forest to pasture in the Colombian Amazon.
Association Between Overall and Mentholated Cigarette Smoking With Headache in a Nationally Representative Sample
Authors: Qi Gan Wen , Estus Steve , Smith Jonathan H.
Published: March 2016

Objective

The objective of this study was to determine associations between cigarette smoking and the existence of headache in a nationally representative sample, with attention to differences in effect estimates between mentholated and non‐mentholated cigarettes smoking.

Methods

We examined cross‐sectional associations between cigarette smoking and headache in 8,399 adults who participated in the National Health and Nutrition Examination Survey (NHANES) 1999‐2004. The existence of headache was determined by an affirmative response to the question “During the past 3 months, did you have severe headaches or migraines?” Further refinement of headache diagnosis was not possible. We used logistic regression models to examine the association between cigarette smoking and headache.

Results

The current study included 8,399 participants aged 20 years and over, including 68% (n = 5491) never smokers and 32% (n = 2548) current smokers. Among the current smokers, 24% (n = 739) smoked menthol cigarettes, and 76% (n = 1719) smoked non‐menthol cigarettes. Compared with never smokers, after adjustment for potential confounding factors, current smokers were more likely to have headache (OR: 1.38; 95% CI: 1.17‐1.62; P < .001). With the increase of both the number of cigarettes smoked daily and pack‐years of smoking, the likelihood of having headache was significantly increased compared with never smokers (P for linear trend < .001). Compared with non‐mentholated smokers, mentholated smokers were not more likely to have headache (P = .302).

Conclusions

Based on a nationally representative sample, we found that cigarette smoking was associated with headache in an exposure‐response manner. Mentholated cigarette smokers were not more likely to have headache compared to non‐mentholated cigarette smokers.