The lamina adventitia is the major site of immune cell accumulation in standard chow-fed apolipoprotein E-deficient mice.
Cells of adaptive immunity have been implicated in atherogenesis. Though substantial information is available on immune cells in atherosclerotic lesions of the lamina intima, cells in the lamina adventitia have received less attention. The composition of immune cells in the innominate artery and abdominal aorta was examined in young, adult, and old apolipoprotein (apo) E(-/-) and wild-type mice on standard mouse chow. In the innominate artery of apoE(-/-) mice, adventitial T cells increased at 32, 52, and 78 weeks exceeding those of the intima by 6-, 24-, and 85-fold. Single T cells dominated in young mice, later T/B cell clusters emerged, and lymphoid-like structures reminiscent of inflammatory follicles formed preferentially in the abdominal aorta of old mice. Follicles contained organized sets of immune response-regulating cells: Interdigitating dendritic cells, T cell effectors, proliferating B cells, and plasma cells. Adventitial T cell inflammation was associated with a marked increase in transcripts of the chemokine MIP-1alpha in the aorta but not in spleen or liver. Adventitial lymphocyte infiltration and formation of inflammatory follicle-like structures in the abdominal aorta of old apoE(-/-) mice point to the adventitia as a site of local adaptive immune reactions during atherogenesis in hyperlipidemic mice.


Finding the gaps: an assessment of infection control surveillance needs in British Columbia acute care facilities.
This paper reports on an infection prevention and control surveillance survey of acute care facilities (ACFs) performed by the Provincial Infection Control Network of British Columbia. A surveillance questionnaire was sent to all health care facilities that had access to an infection control professional. The questionnaire incorporated questions on organism-specific, disease-specific, and general surveillance activities. Questionnaires were returned from 47 of 51 (92%) of the ACFs surveyed. Participation in surveillance of methicillin-resistant Staphylococcus aureus-, vancomycin-resistant Enterococci-, and Clostridium difficile-associated disease ranged from 97% to 100%, but surveillance methodologies were inconsistent. Surgical-site infection surveillance did not correlate with the most commonly performed operations or with those procedures associated with higher morbidity and mortality from a postoperative infection. Considerable variation in data collection methods and case definitions was also identified. Surveillance for urinary tract infections, bloodstream infections, and ventilator-associated pneumonia was present in 28%, 51%, and 23% of responding ACFs, respectively. The current lack of a standardized surveillance system in British Columbia limits the ability of facilities to set appropriate benchmarks to assist in prioritizing and applying infection control interventions. The survey, however, has assisted in prioritizing implementation of surveillance activities and identifying the resources that would be required.


Evaluation of (177)Lu-CHX-A''-DTPA-Bevacizumab as a radioimmunotherapy agent targeting VEGF expressing cancers.
This study aimed at the preparation and evaluation of (177)Lu-CHX-A''-DTPA-Bevacizumab for targeting VEGF over-expressing cancers. Bevacizumab conjugated to p-NCS-Bn-CHX-A''-DTPA was radiolabeled with (177)Lu. The radioimmunoconjugate characterized by SE-HPLC exhibited radiochemical purity of 98.0±0.6%. In vitro stability was retained upto 4 days at 37°C. In vitro cell binding studies showed good uptake by VEGF expressing U937 tumor cells. Biodistribution studies in melanoma model showed significant uptake and retention of (177)Lu-CHX-A''-DTPA-Bevacizumab in tumor with reduction in uptake in presence of cold Bevacizumab confirming its specificity to VEGF.


Rapid blister formation in human skin with ammonium hydroxide.
The topical application to human skin of a 1:1 aqueous solution of ammonium hydroxide in a well drilled into a plastic block will provoke an intra-epidermal blister in an average time of about 13 min. The blister roof can be used for physico-chemical analyses of the horny layer while the base is suitable for studies of wound healing, bacterial infections, etc. The minimal blistering time (MBT) increases directly as the number of cell layers of the stratum corneum and ranges from 3 to 57 min in different regions and persons. The intensity of the dermatitis provoked by a 24 h exposure to sodium lauryl sulphate is strongly correlated with the MBT. The latter is therefore a reliable measure of cutaneous irritability. The blisters are virtually painless. The inflammatory reaction clinically and histologically is slight. Healing is rapid without scarring.


High-density linkage map construction and mapping of seed trait QTLs in chickpea (Cicer arietinum L.) using Genotyping-by-Sequencing (GBS).
This study reports the use of Genotyping-by-Sequencing (GBS) for large-scale SNP discovery and simultaneous genotyping of recombinant inbred lines (RILs) of an intra-specific mapping population of chickpea contrasting for seed traits. A total of 119,672 raw SNPs were discovered, which after stringent filtering revealed 3,977 high quality SNPs of which 39.5% were present in genic regions. Comparative analysis using physically mapped marker loci revealed a higher degree of synteny with Medicago in comparison to soybean. The SNP genotyping data was utilized to construct one of the most saturated intra-specific genetic linkage maps of chickpea having 3,363 mapped positions including 3,228 SNPs on 8 linkage groups spanning 1006.98 cM at an average inter marker distance of 0.33 cM. The map was utilized to identify 20 quantitative trait loci (QTLs) associated with seed traits accounting for phenotypic variations ranging from 9.97% to 29.71%. Analysis of the genomic sequence corresponding to five robust QTLs led to the identification of 684 putative candidate genes whose expression profiling revealed that 101 genes exhibited seed specific expression. The integrated approach utilizing the identified QTLs along with the available genome and transcriptome could serve as a platform for candidate gene identification for molecular breeding of chickpea.


Measurements of relative distribution constants of vaporized hydrocarbons between air and polydimethylsiloxane via capillary columns for the calculation of headspace hydrocarbon compositions.
This study focused on the measurements and validity of relative distribution constants of vaporized hydrocarbons between air and polydimethylsiloxane (PDMS) using commercially available capillary columns. Capillary column gas chromatography (CCGC) measurements, using two columns containing a PDMS stationary phase with different film thicknesses, were conducted to determine the relative distribution constants of n-heptane, toluene, n-octane, p-xylene, n-nonane, and 1,2,4-trimethylbenzene between air and PDMS at 90 and 120 °C. To validate the accuracy of the relative distribution constants via CCGC, the compositions of three headspace samples containing different amounts of hydrocarbons were calculated using the relative distribution constants via CCGC and extracted amounts via PDMS solid phase microextraction (SPME) at 90 and 120 °C. It was found that calculated hydrocarbon compositions of headspace samples were comparable to true headspace hydrocarbon compositions via direct vapor analysis, with an average absolute relative error of 3.2%. Our results indicate that CCGC is an alternative method that can provide a reliable and convenient method to determine the relative distribution constants of various hydrocarbons between air and PDMS for quantitative chemical analysis of headspace.


Mark and recapture of adult Ixodes pacificus (Acari: Ixodidae) to determine the effect of repeated removal sampling on tick abundance.
The effect of biweekly flagging on adult Ixodes pacificus Cooley & Kohls abundance was determined by using mark-recapture techniques. Ticks were recaptured up to three times during the 12-wk study, and increasingly higher proportions of marked ticks were recaptured as the study progressed. By week 6 of the study, 46% of the collected ticks had been marked, and on the final sampling date, all ticks had been captured previously. Removal sampling would have substantially reduced estimates of the abundance of the questing I. pacificus adult population. For ecological studies that require the repeated sampling of a given habitat, the most representative data are obtained by returning flagged ticks to their collection site.


One-stage debridement and plastic repair of compound comminuted depressed skull fractures with methyl methacrylate.
A one-stage technique is described for repair and debridement of compound, comminuted depressed skull fractures using methyl methacrylate, which appears to be simple, effective, and safe, provided that the paranasal sinuses are not involved. If so, a two-stage debridement and repair are recommended. In the series reported, of 25 patients, only one developed infection, which was successfully treated with further operative repair and antibiotics.


Influence of doping on semiconductor nanocrystals mediated charge transfer and photocatalytic organic reaction.
Doped and undoped ZnS semiconductor nanocrystals having different recombination pathways are explored to study the charge transfer reaction between the nanocrystals and the 4-nitrophenol/sodium borohydride redox couple.


Survey research: a primer for hand surgery.
Survey research is an important and commonly used research tool. The findings of survey research help set national practice guidelines and guide health care policy decision making. The process of survey design and administration is rigorous, complex, and involved. The Journal of Hand Surgery contains on average 3 articles involving surveys per issue. This report serves as a reference for readers of the many survey articles published in this journal. It also provides a guide for hand surgeons or others interested in how to conduct survey research.


Unique patterns of medial meniscus extrusion during walking and its association with limb kinematics in patients with knee osteoarthritis.
Medial meniscus extrusion (MME) is exacerbated by repeated mechanical stress. Various factors would affect MME; however, there is limited information about the behaviour of the medial meniscus during walking in patients with knee osteoarthritis (KOA). This study aimed to investigate the pattern of MME during walking and its association with limb biomechanics in patients with KOA. Fifty-five patients with KOA and ten older adult volunteers as a control group were involved in this study. The MME and limb biomechanics during walking were evaluated simultaneously by ultrasound and a motion analysis system, respectively. The waveform was constructed from the values of MME, and the point showing the highest value of MME was identified during the gait cycle. According to the peak timing of MME in the waveform, the pattern of the waveform was evaluated and compared to the control group. Lateral thrust, knee adduction moment (KAM), and flexion moment were obtained from motion analysis, and their association with the MME was evaluated. The patients with KOA demonstrated unique peak timing during walking. Compared to the control group, there were three groups of MME waveforms, early (< 59%), normal (60-83%), and late (> 84%) from the peak timing in the gait cycle. The pattern of MME waveform in early, normal, and late groups was correlated with the first KAM and lateral thrust, second KAM, and knee flexion moment, respectively. A unique MME pattern during walking was demonstrated, and these patterns were associated with limb biomechanics in patients with KOA.


Time-dependent amplification of helical bias in self-assembled dye nanorods directed by the sergeants-and-soldiers principle.
A pronounced sergeants-and-soldiers directed chiral amplification is observed for the self-assembly of merocyanine dye nanorods and the amplification process is shown to become slower for decreasing fraction of sergeant molecules.


Activation of persulfate by LaFe1-xCoxO3 perovskite catalysts for the degradation of phenolics: Effect of synthetic method and metal substitution.
The presence of resistant organic pollutants in environmental substrates requires the development and finding of novel decontamination methods. Advanced oxidation processes are among the most effective methods used for degradation of these pollutants through their oxidation and degradation into non-toxic and harmless, for the environment, final products. Ιn this research, a series of perovskites of ABO3-type, with La and Fe and/or Co in A and B positions respectively, LaFe1-xCoxO3 (x = 0, 0.25, 0.5, 0.75, 1), were synthesized with two different methods, a soft template method using anionic surfactant and by glycine combustion method and studied for their catalytic activity towards the degradation of phenolic compounds, a major class of environmental pollutants, through persulfate activation. The catalytic activity depended both by the B metal ion of perovskites and their ratio as well as by the synthesis method. LaCoO3 prepared with the anionic surfactant method, showed the highest catalytic activity with a rate constant of 0.024 min-1. Furthermore, the synthesis method also influenced the stability of perovskites as metal leaching studies showed that perovskites synthesized with the anionic surfactant showed greater stability. Quenching experiments were also used in order to shed light on the catalytic activation mechanism of persulfate for the degradation of phenolics. Overall, the results showed that the synthesis method can significantly affect the catalytic activity of the materials and their stability since the same materials synthesized with different methods show significantly different catalytic properties.


Periprosthetic joint infection diagnosis: a complete understanding of white blood cell count and differential.
Recent research has raised doubts regarding the utility of serum white blood cell count (WBC) for diagnosis of periprosthetic joint infection (PJI). As synovial WBC and neutrophil (PMN) percentage have been adopted as accurate markers of PJI, this study investigated the correlation of WBC in serum versus joint fluid and diagnostic value of all WBC levels for failed arthroplasty patients. 153 patients (73 PJI) undergoing revision knee arthroplasty were identified. Weak correlations between joint fluid and serum for WBC (R = 0.19), PMN count (R = 0.31), and lymphocyte count (R = -0.22) were observed. Diagnostic accuracy of PMN (93%) and WBC (93%) synovial count relative to serum was similar to synovial WBC (93%) and PMN% (95%) alone. Serum WBC analysis does little to improve the accurate diagnosis of PJI.


The poxviral scrapin MV-LAP requires a myxoma viral infection context to efficiently downregulate MHC-I molecules.
Downregulation of MHC class I molecules is a strategy developed by some viruses to escape cellular immune responses. Myxoma virus (MV), a poxvirus causing rabbit myxomatosis, encodes MV-LAP that is known to increase MHC-I endocytosis and degradation through a C(4)HC(3) motif critical for an E3 ubiquitin ligase activity. Here, we performed a functional mapping of MV-LAP and showed that not only the C(4)HC(3) motif is necessary for a marked downregulation of MHC-I but also a conserved region in the C-terminal part of the protein. We also showed that the putative transmembrane domains are responsible for a specific subcellular localization of the protein: they retain MV-LAP in the ER in transfected cells and in the endolysosomal compartments in infected cells. We observed that a specific MV infection context is necessary for a fully efficient downregulation of MHC-I. Our data suggest that the functionality of viral LAP factors, inherited by herpes- and poxviruses from mammalian cells, is more complex than anticipated.


Limited ability of three commonly used thermoplasticized gutta-percha techniques in filling oval-shaped canals.
The present study was designed to compare the percentage of gutta-percha-filled area (PGFA) achieved in oval-shaped canals after filling by 3 thermoplasticized techniques. Eighty-seven oval-shaped root canals were prepared and root-filled as follows: lateral condensation (n = 20), thermomechanical compaction (n = 20), wave of condensation (n = 20), and Thermafil system (n = 20). A cross section of each tooth was made 5 mm from the apex, and the samples were prepared for microscopic analysis. Digital image measurements of the cross-sectioned area of the canal and the gutta-percha were performed, and the PGFA was calculated. Nonparametric statistical analysis was performed with the Kruskal-Wallis H test and post hoc Dunn test. Overall, PGFAs were variable among the experimental groups, ranging from 37.1%-98.5%, and the pooled data from all techniques had a general mean of 69.6% +/- 18%. Thermafil system, wave of condensation, and thermomechanical compaction produced significantly higher PGFAs than lateral condensation (P < .05); however, no significant differences among these techniques were detected (P > .05). Therefore, a limited ability to fill oval-shaped canals was achieved in the 3 thermoplasticized techniques tested.


Crosstalk of Brucella abortus nucleomodulin BspG and host DNA replication process/mitochondrial respiratory pathway promote anti-apoptosis and infection.
The secretory proteins of Brucella mediate the expression of the bacterium in the host, thereby facilitating intracellular parasitism. With the exception of the recently reported BspJ, the Brucella nucleomodulin has not yet been characterized. We defined the Brucella nucleomodulin BspG and verified six proteins (PCBP1, KMT5C, NDUFS6, PCNA, CIAO2B, and SDHB) that interacted with BspG using a yeast two-hybrid assay and co-immunoprecipitation (CO-IP) screening. The deletion of BspG decreased the intracellular proliferation of B. abortus in both in vivo and in vitro experiments. The analysis found that these interacting proteins were related to energy generation, gene expression, and apoptosis of host cells. The crosstalk between B. abortus nucleomodulin BspG and host DNA replication/mitochondrial respiratory pathways promotes anti-apoptosis and infection, but the mechanism needs additional study.


Drk-mediated signaling to Rho kinase is required for anesthesia-resistant memory in Drosophila.
Anesthesia-resistant memory (ARM) was described decades ago, but the mechanisms that underlie this protein synthesis-independent form of consolidated memory in Drosophila remain poorly understood. Whether the several signaling molecules, receptors, and synaptic proteins currently implicated in ARM operate in one or more pathways and how they function in the process remain unclear. We present evidence that Drk, the Drosophila ortholog of the adaptor protein Grb2, is essential for ARM within adult mushroom body neurons. Significantly, Drk signals engage the Rho kinase Drok, implicating dynamic cytoskeletal changes in ARM, and this is supported by reduced F-actin in the mutants and after pharmacological inhibition of Drok. Interestingly, Drk-Drok signaling appears independent of the function of Radish (Rsh), a protein long implicated in ARM, suggesting that the process involves at least two distinct molecular pathways. Based on these results, we propose that signaling pathways involved in structural plasticity likely underlie this form of translation-independent memory.


Recent immunohistochemical markers in the differential diagnosis of primary and metastatic carcinomas of the liver.
Differential diagnosis of primary and metastatic carcinomas of the liver can be problematic and may require immunohistochemical work-up. Recently, new immunohistochemical markers have been introduced with promising results in this area. We studied three of these markers, human hepatocyte antibody (HepPar-1), human epithelial-related antigen (MOC-31), and thyroid transcription factor-1 (TTF-1), in cell-block sections of fine-needle aspirations from 30 hepatocellular carcinomas and 27 metastatic carcinomas from various sites. Of 27 metastatic carcinomas, all but one were positive for MOC-31 and, all but one were negative for HepPar-1. TTF-1 was positive only in the nuclei of metastatic poorly differentiated neuroendocrine carcinoma from the lung. Of 30 hepatocellular carcinomas, 26 were positive for HepPar-1 and all were negative for MOC-31, while TTF-1 showed cytoplasmic staining in 23 cases. HepPar-1, MOC-31, and TTF-1 are complementary markers in the differential diagnosis of primary and metastatic carcinomas of the liver, with high sensitivity and specificity.


Transcriptional enhancer factor (TEF)-1 and its cell-specific co-activator activate human papillomavirus-16 E6 and E7 oncogene transcription in keratinocytes and cervical carcinoma cells.
The human papillomavirus (HPV)-16 oncogenes, E6 and E7, are transcribed preferentially in keratinocytes and cervical carcinoma cells due to a 5' enhancer. An abundant peptide binding to a 37 nt enhancer element was purified from human keratinocytes by sequence-specific DNA chromatography. This protein was identified as transcriptional enhancer factor (TEF)-1 by complex mobility, binding to wild-type and mutant SV40 and HPV-16 enhansons and antigenic reactivity with two anti-TEF-1 antibodies. TEF-1 is cell-specific, but its transactivation also depends on a limiting, cell-specific TEF-1 'co-activator'. We show that both TEF-1 and the TEF-1 co-activator are active in human keratinocytes and essential for HPV-16 transcription. TEF-1 binding in vivo was necessary for HPV-16 P97 promoter activity. Excess TEF-1 and chimeric GAL4-TEF-1 specifically inhibited the P97 promoter by 'squelching', indicating that HPV-16 transcription also requires a limiting TEF-1 co-activator. TEF-1 and the TEF-1 co-activator functions mirrored HPV-16 transcription by their presence in keratinocytes and cervical carcinoma cells and their absence from lymphoid B-cells, but also functioned in liver cells where the HPV-16 promoter is inactive. TEF-1 and its associated co-activator are thus part of a complex mechanism which determines the restricted cell range of the HPV-16 E6 and E7 oncogene promoter.


Oncologic Emergencies in the Chest, Abdomen, and Pelvis.
Oncology patients can present with acute, life-threatening conditions that may arise either due to underlying malignancy or secondary to cancer therapy. Select oncologic emergencies show characteristic imaging findings on radiographs, ultrasound, computed tomography, and MRI that helps in timely diagnosis. Radiologists need to be aware of typical imaging findings in such patients in an emergency setting and should be able to guide the clinicians for proper patient management. Appropriate knowledge of the treatment and its timing is pivotal in diagnosing treatment-related complications.


Ultrasound-guided intratumoral indigo carmine injection for intraoperative, surgeon-performed tumor localization.
The purpose of this study was to evaluate the feasibility of ultrasound-guided intratumoral indigo carmine injections for intraoperative localization of small head and neck tumors and to introduce our surgeon-performed technique. In total, 23 patients who had tumors ≤1.5 cm that were not palpable by 2 head and neck surgeons were enrolled in this prospective study. Ultrasound-guided intratumoral indigo carmine injections successfully targeted tumors in 22 patients (95.7%). The mean preinjection target tumor size was 0.8 cm. After an average injection of 0.7 mL indigo carmine, the mean target tumor size increased to 1.0 cm, which enhanced visual demarcation because of the increased tumor size. In these patients, we successfully and uneventfully resected the target tumors with ultrasound-guided intratumoral indigo carmine injection assistance. Ultrasound-guided intratumoral indigo carmine injections were technically feasible as an intraoperative procedure and were performed safely by a head and neck surgeon to facilitate localization of small head and neck tumors, even in revision cases.


The stem cell factor SALL4 is an essential transcriptional regulator in mixed lineage leukemia-rearranged leukemogenesis.
The stem cell factor spalt-like transcription factor 4 (SALL4) plays important roles in normal hematopoiesis and also in leukemogenesis. We previously reported that SALL4 exerts its effect by recruiting important epigenetic factors such as DNA methyltransferases DNMT1 and lysine-specific demethylase 1 (LSD1/KDM1A). Both of these proteins are critically involved in mixed lineage leukemia (MLL)-rearranged (MLL-r) leukemia, which has a very poor clinical prognosis. Recently, SALL4 has been further linked to the functions of MLL and its target gene homeobox A9 (HOXA9). However, it remains unclear whether SALL4 is indeed a key player in MLL-r leukemia pathogenesis. Using a mouse bone marrow retroviral transduction/ transplantation approach combined with tamoxifen-inducible, CreERT2-mediated Sall4 gene deletion, we studied SALL4 functions in leukemic transformation that was induced by MLL-AF9-one of the most common MLL-r oncoproteins found in patients. In addition, the underlying transcriptional and epigenetic mechanisms were explored using chromatin immunoprecipitation (ChIP) sequencing (ChIP-Seq), mRNA microarray, qRT-PCR, histone modification, co-immunoprecipitation (co-IP), cell cycle, and apoptosis assays. The effects of SALL4 loss on normal hematopoiesis in mice were also investigated. In vitro and in vivo studies revealed that SALL4 expression is critically required for MLL-AF9-induced leukemic transformation and disease progression in mice. Loss of SALL4 in MLL-AF9-transformed cells induced apoptosis and cell cycle arrest at G1. ChIP-Seq assay identified that Sall4 binds to key MLL-AF9 target genes and important MLL-r or non-MLL-r leukemia-related genes. ChIP-PCR assays indicated that SALL4 affects the levels of the histone modification markers H3K79me2/3 and H3K4me3 at MLL-AF9 target gene promoters by physically interacting with DOT1-like histone H3K79 methyltransferase (DOT1l) and LSD1/KDM1A, and thereby regulates transcript expression. Surprisingly, normal Sall4 f/f /CreERT2 mice treated with tamoxifen or vav-Cre-mediated (hematopoietic-specific) Sall4 -/- mice were healthy and displayed no significant hematopoietic defects. Our findings indicate that SALL4 critically contributes to MLL-AF9-induced leukemia, unraveling the underlying transcriptional and epigenetic mechanisms in this disease and suggesting that selectively targeting the SALL4 pathway may be a promising approach for managing human MLL-r leukemia.


A protein-protein interaction underlies the molecular basis for substrate recognition by an adenosine-to-inosine RNA-editing enzyme.
Adenosine deaminases that act on RNA (ADARs) convert adenosine to inosine within double-stranded regions of RNA, resulting in increased transcriptomic diversity, as well as protection of cellular double-stranded RNA (dsRNA) from silencing and improper immune activation. The presence of dsRNA-binding domains (dsRBDs) in all ADARs suggests these domains are important for substrate recognition; however, the role of dsRBDs in vivo remains largely unknown. Herein, our studies indicate the Caenorhabditis elegans ADAR enzyme, ADR-2, has low affinity for dsRNA, but interacts with ADR-1, an editing-deficient member of the ADAR family, which has a 100-fold higher affinity for dsRNA. ADR-1 uses one dsRBD to physically interact with ADR-2 and a second dsRBD to bind to dsRNAs, thereby tethering ADR-2 to substrates. ADR-2 interacts with >1200 transcripts in vivo, and ADR-1 is required for 80% of these interactions. Our results identify a novel mode of substrate recognition for ADAR enzymes and indicate that protein-protein interactions can guide substrate recognition for RNA editors.


Prospective Study of Radial Artery Occlusion Following Transradial Arterial Access during IR Procedures.
To prospectively determine the rate of radial artery occlusion (RAO) in patients undergoing transradial access for intra-arterial interventions. Seventy-seven patients undergoing transradial access from August 2019 to March 2021 for 120 intra-arterial procedures (yttrium-90 mapping [n = 39] and radioembolization [n = 38], uterine artery embolization [n = 19], transarterial chemoembolization [n = 10], active bleed embolization [n = 8], angiomyolipoma embolization [n = 4], and other [n = 2]) were enrolled. The average patient age was 59 years ± 13.1 (range, 30-90 years), and 43 (55.8%) of the 77 patients were men. The patients underwent radial artery (RA) palpation, ultrasound evaluation, the Barbeau test, and the reverse Barbeau test prior to and following the intervention. Verapamil, nitroglycerin, and heparin were administered in a total of 114 (95%) of the 120 procedures prior to starting the procedure. The incidence of RAO and radial artery spasm (RAS) was calculated, and univariate logistic regression was performed to analyze the predictors of RAS. The preprocedural RA diameter (3.0 mm ± 0.67) was not significantly different from the postprocedural RA diameter (3.0 mm ± 0.65, P = .904). The RAO rate was determined to be 0.8% (1/120), and this artery recanalized within 1 week. Due to the small number of occlusions, statistical analysis of predictors of RAO was not performed. The rate of RAS was 22.7% (27/119). None of the variables tested-including age, sex, RA diameter, initial versus repeat access, operator experience, and artery puncture technique-showed significant prediction for RAS. Patients were seen for follow-up after 111 (92.5%) of the 120 procedures. Transradial access resulted in a <1% rate of RAO.


Dietary patterns of 6-24-month-old children are associated with nutrient content and quality of the diet.
We determined the associations of dietary patterns with energy/nutrient intakes and diet quality. Previously collected single 24-hr dietary recalls for children aged 6-11 months (n = 1,585), 12-17 months (n = 1,131), and 18-24 months (n = 620) from four independent studies in low socio-economic populations in South Africa were pooled. A maximum-likelihood factor model, with the principal-factor method, was used to derive dietary (food) patterns. Associations between dietary pattern scores and nutrient intakes were determined using Kendall's Rank Correlations, with Bonferroni-adjusted significance levels. For both 6-11 months and 12-17 months, the formula milk/reverse breast milk pattern was positively associated with energy and protein intake and mean adequacy ratio (MAR). The family foods pattern (6-11 months) and rice and legume pattern (12-17 months) were positively associated with plant protein, fibre, and PU fat; both for total intake and nutrient density of the complementary diet. These two patterns were also associated with the dietary diversity score (DDS; r = 0.2636 and r = 0.2024, respectively). The rice pattern (18-24 months) showed inverse associations for nutrient intakes and nutrient densities, probably because of its inverse association with fortified maize meal. The more westernized pattern (18-24 months) was positively associated with unfavourable nutrients, for example, saturated fat and cholesterol. These results highlight that underlying dietary patterns varied in terms of energy/nutrient composition, nutrient adequacy, nutrient densities of the complementary diet, and dietary diversity.


simpiTB - a pipeline designed to extract meaningful information from whole genome sequencing data of Mycobacterium tuberculosis complex, allows to combine genomic, phylogenetic and clustering analyses in existing SITVIT databases.
Data obtained from new sequencing technologies are evolving rapidly, leading to the development of specific bioinformatic tools, pipelines and softwares. Several algorithms and tools are today available allowing a better identification and description of Mycobacterium tuberculosis complex (MTBC) isolates worldwide. Our approach consists in applying existing methods to analyze DNA sequencing data (from FASTA or FASTQ files), and tentatively extract meaningful information that would facilitate identification as well as a better understanding and management of MTBC isolates (taking into account whole genome sequencing and classical genotyping data). The aim of this study is to propose a pipeline analysis allowing to potentially simplify MTBC data analysis by providing different ways to interpret genomic or genotyping information based on existing tools. Furthermore, we propose a "reconciledTB" list making a link with results directly obtained from whole genome sequencing (WGS) data and results obtained from classical genotyping analysis (data inferred from SpoTyping and MIRUReader). Data visualization graphics and trees generated provide additional elements to better understand and confer associations among information overlap analyses. Additionally, comparison between data entered in an international genotyping database (SITVITEXTEND) and ensuing data obtained from the pipeline not only provide meaningful information, but further suggest that simpiTB could also be suitable for new data integration in specific TB genotyping databases.


An evaluation of pain and postoperative nausea and vomiting following the introduction of guidelines for tonsillectomy.
Tonsillectomy and adenotonsillectomy have a high incidence of postoperative pain, and postoperative nausea and vomiting (PONV). Pain is traditionally controlled with morphine but this increases the risk of PONV and may cause respiratory depression. Antiemetics reduce PONV but their routine use has been questioned on safety grounds. After determining the current anesthetic management of elective tonsillectomy and adenotonsillectomy patients in our hospital, guidelines were developed to avoid the routine use of morphine and antiemetics. The effect on pain and PONV was then evaluated over a 3 month period. Postoperative pain was scored using the Oucher visual analog scale and nausea scored using a five point scale. We analysed 34 cases to determine our current practice and 37 cases to evaluate the effect of introducing guidelines. Postguidelines, the median Oucher pain score at 4 h was 10, and at 8, 12, 16 h was zero. Despite receiving no antiemetics, only two children vomited (5%) after introduction of guidelines. Guidelines which use a combination of paracetamol, nonsteroidal anti-inflammatory drugs and fentanyl, provide excellent analgesia with minimal PONV after elective tonsillectomy and adenotonsillectomy. As a result the routine use of morphine and antiemetics can be avoided.


Perfume dermatitis.
The most common reaction to fragrance materials seen by practicing dermatologists is allergic contact dermatitis. Photodermatitis is occasionally seen, as is contact urticaria, irritation, and depigmentation. Fragrances are the leading cause of allergic contact dermatitis due to cosmetics. The fragrance mixture can cause false-positive reactions; therefore, it is more desirable to test with a separate series of fragrance materials.


Early derailment of firing properties in CA1 pyramidal cells of the ventral hippocampus in an Alzheimer's disease mouse model.
Gradual decline in cognitive and non-cognitive functions are considered clinical hallmarks of Alzheimer's Disease (AD). Post-mortem autoptic analysis shows the presence of amyloid β deposits, neuroinflammation and severe brain atrophy. However, brain circuit alterations and cellular derailments, assessed in very early stages of AD, still remain elusive. The understanding of these early alterations is crucial to tackle defective mechanisms. In a previous study we proved that the Tg2576 mouse model of AD displays functional deficits in the dorsal hippocampus and relevant behavioural AD-related alterations. We had shown that these deficits in Tg2576 mice correlate with the precocious degeneration of dopamine (DA) neurons in the Ventral Tegmental Area (VTA) and can be restored by L-DOPA treatment. Due to the distinct functionality and connectivity of dorsal versus ventral hippocampus, here we investigated neuronal excitability and synaptic functionality in the ventral CA1 hippocampal sub-region of Tg2576 mice. We found an age-dependent alteration of cell excitability and firing in pyramidal neurons starting at 3 months of age, that correlates with reduced levels in the ventral CA1 of tyrosine hydroxylase - the rate-limiting enzyme of DA synthesis. Additionally, at odds with the dorsal hippocampus, we found no alterations in basal glutamatergic transmission and long-term plasticity of ventral neurons in 8-month old Tg2576 mice compared to age-matched controls. Last, we used computational analysis to model the early derailments of firing properties observed and hypothesize that the neuronal alterations found could depend on dysfunctional sodium and potassium conductances, leading to anticipated depolarization-block of action potential firing. The present study depicts that impairment of cell excitability and homeostatic control of firing in ventral CA1 pyramidal neurons is a prodromal feature in Tg2576 AD mice.


Thread-embedding acupuncture may improve symptom resolution in patients with gastroesophageal reflux disease: A randomized controlled trial.
Various traditional medicine treatments have been investigated to treat GERD. Among those, thread-embedding acupuncture (TEA) has the advantage that patients need to undergo the procedure infrequently; however, its efficacy is unclear. This study evaluated the efficacy of TEA in treating GERD. A randomized controlled trial was conducted with 66 participants with GERD: 33 received two sessions of TEA + standard therapy (proton-pump inhibitor [PPI]) (TEA+PPI group) and 33 received PPI alone (PPI group). Primary outcomes included GerdQ score and heartburn and regurgitation resolution. Secondary outcomes were antacids requirement, the Frequency Scale for Symptoms of GERD (FSSG) score, and Gastroesophageal Reflux Disease-Health Related Quality of Life (GERD-HRQL) score. The safety outcome was adverse events (AEs). After four weeks of treatment, the TEA+PPI group significantly reduced the GerdQ score (mean difference [MD] and 95% confidence interval [CI]: -1.8 [-2.4, -1.1]) and increased the rate of heartburn and regurgitation resolution compared to PPI (54.5% versus 9.1%, respectively) compared to PPI. The TEA+PPI group also significantly reduced the number of antacid packs used (MD [95%-CI]: -9.4 [-12.1, -6.7]), FSSG score (MD [95%-CI]: -9.4 [-11.0, -7.8]), and GERD-HRQL score (MD [95%-CI]: -5.6 [-7.7, -3.5]) compared to PPI. Five patients experienced AEs, which were mild local complications at the acupoints. TEA combined with PPI is more effective than PPI alone in treating GERD. Further studies with longer follow-ups are required to confirm these findings. ClinicalTrials.gov, NCT05353933.


The Morphology of Coronary Artery Disease in South Asians vs White Caucasians and Its Implications.
South Asians (SAs) experience a higher prevalence and earlier onset of coronary artery disease and have worse outcomes compared with White Caucasians (WCs) following invasive revascularisation procedures, a mainstay of coronary artery disease (CAD) management. We sought to review the differences in the CAD pattern and risk factors between SA and WC patients and to discuss their potential impact on the development of coronary disease, acute coronary syndrome, and revascularisation outcomes. SAs have a more diffuse pattern with multivessel involvement compared with WCs. However, less is known about other morphologic characteristics, such as calcification of atherosclerotic plaque and coronary diameter in SA populations. Despite a similar coronary calcification burden, higher noncalcified plaque composition, elevated thrombosis, and inflammatory markers likely contribute to the disease pattern. Although the current evidence on the role of coronary vessel size remains inconsistent, smaller diameters in SAs could play a potential role in the higher disease prevalence. This is especially important given the impact of coronary artery diameter on revascularisation outcomes. In conclusion, SAs have a unique CAD risk profile composed of traditional and novel risk factors. Our findings highlight the need for additional awareness of health professionals of this specific risk profile and potential therapeutic targets, as well as the need for further research in this vulnerable population.


Genome-wide dissection of changes in maize root system architecture during modern breeding.
Appropriate root system architecture (RSA) can improve maize yields in densely planted fields, but little is known about its genetic basis in maize. Here we performed root phenotyping of 14,301 field-grown plants from an association mapping panel to study the genetic architecture of maize RSA. A genome-wide association study identified 81 high-confidence RSA-associated candidate genes and revealed that 28 (24.3%) of known root-related genes were selected during maize domestication and improvement. We found that modern maize breeding has selected for a steeply angled root system. Favourable alleles related to steep root system angle have continuously accumulated over the course of modern breeding, and our data pinpoint the root-related genes that have been selected in different breeding eras. We confirm that two auxin-related genes, ZmRSA3.1 and ZmRSA3.2, contribute to the regulation of root angle and depth in maize. Our genome-wide identification of RSA-associated genes provides new strategies and genetic resources for breeding maize suitable for high-density planting.


Outcome for stage II and III rectal and colon cancer equally good after treatment improvement over three decades.
This study aimed to investigate the outcome for stage II and III rectal cancer patients compared to stage II and III colonic cancer patients with regard to 5-year cause-specific survival (CSS), overall survival, and local and combined recurrence rates over time. This prospective cohort study identified 3,355 consecutive patients with adenocarcinoma of the colon or rectum and treated in our colorectal unit between 1981 and 2011, for investigation. The study was restricted to International Union Against Cancer (UICC) stages II and III. Postoperative mortality and histological incomplete resection were excluded, which left 995 patients with colonic cancer and 726 patients with rectal cancer for further analysis. Five-year CSS rates improved for colonic cancer from 65.0% for patients treated between 1981 and 1986 to 88.1% for patients treated between 2007 and 2011. For rectal cancer patients, the respective 5-year CSS rates improved from 53.4% in the first observation period to 89.8% in the second one. The local recurrence rate for rectal cancer dropped from 34.2% in the years 1981-1986 to 2.1% in the years 2007-2011. In the last decade of observation, prognosis for rectal cancer was equal to that for colon cancer (CSS 88.6 vs. 86.7%, p = 0.409). Survival of patients with colon and rectal cancer has continued to improve over the last three decades. After major changes in treatment strategy including introduction of total mesorectal excision and neoadjuvant (radio)chemotherapy, prognosis for stage II and III rectal cancer is at least as good as for stage II and III colonic cancer.


Transdifferentiation of vocal-fold stellate cells and all-trans retinol-induced deactivation.
The maculae flavae of the human vocal folds include dense extracellular matrices and compacted cells with a stellate morphology. These vocal-fold stellate cells are thought to participate in the metabolism of extracellular matrices essential in maintaining vocal-fold viscoelasticity required for phonation. We have isolated and cultured these new cells and have tested the hypothesis that they maintain a distinct cellular and biochemical phenotype. We have compared proliferation rates, changes on immunophenotype, and intracellular lipid and vitamin A storage. Vocal-fold stellate cells undergo culture-induced transdifferentiation to a myofibroblast-like phenotype with an altered phenotype resembling, but not identical to, activated hepatic and pancreatic stellate cells. Our results reveal that these cells are capable of responding to exogenous all-trans retinol in culture. Exposure to this synthetic co-factor causes deactivation characterized by decreased proliferation, loss of the activated stellate cell marker, alpha-smooth muscle actin, and restoration of intracellular lipid and vitamin A metabolite storage. These data establish a new and distinct cellular target for future investigations of the viscoelastic properties of the vocal-fold mucosa during normal phonation, aging, vocal-fold scarring, laryngeal fibrosis, and myofibroblastoma.


Cardiovascular Disease Risk Associated With Familial Hypercholesterolemia: A Systematic Review of the Literature.
The goal of this study was to determine cardiovascular disease (CVD) risk associated with familial hypercholesterolemia (FH). A systematic review of the published literature was conducted. All publications describing FH risk from PubMed ("cardiovascular disease risk + familial hypercholesterolaemia," 2004-2015), Internet and Medline search of FH registries, and associated references were screened for FH-related CVD risk in titles, abstracts, and study methods. CVD risk expressed as rates, odds, or ratios of mortality and morbidity were extracted. Each article was reviewed for bias by 2 reviewers within 17 items in 7 categories; a modified Newcastle-Ottawa assessment scale was used for nonrandomized studies. The complete literature search identified 712 potential publications: 549 from PubMed (Medline), 150 from registries, and 13 from references. Fourteen articles met the inclusion criteria: 8 from registries in the United Kingdom, the Netherlands, Norway, and Spain; 5 from single hospitals or families in Japan, Denmark, the Netherlands, and the United Kingdom; and a population survey in Denmark. Across studies, attrition bias was low in 22 (80%) of 28 items. Risk of selection bias was high in 35 (63%) of 56 items. Selection bias risk was due to low representativeness and lack of a non-FH comparator group within the same study; detection bias risk was due to variable definitions of CVD outcomes/measurement; and performance bias risk was due to long-term, intensive treatment, the most common limitations for registries. Studies from single hospitals and families lacked generalizability. In contrast, the Danish study revealed a low bias in each of the 4 selection bias criteria and 2 attrition risk criteria. Fatal and nonfatal CVD events were collected in the study. Comparing patients with FH versus non-FH patients, the odds ratios for coronary artery disease were 10.3 (95% CI, 7.8-13.8) and 13.2 (95% CI, 10.0-17.4) in subjects treated and not treated with lipid-lowering therapy, respectively. These ratios fall within the ranges of ratios reported in other studies but are generally higher than the ratios from registries and clinics, in which intensive specialized management is available. There is a lack of available data describing CVD risk in patients with FH, and many of the existing studies have biases in their design that could affect their risk estimates. A Danish study had the highest quality based on a predefined quality check list, providing the most credible estimates of the increase in CVD risk in patients with FH. The CVD risk due to FH is high and represents unmet medical need for patients with FH. Further research is warranted to validate the magnitude of risk.


Glucuronidation of [6]-shogaol, [8]-shogaol and [10]-shogaol by human tissues and expressed UGT enzymes: identification of UGT2B7 as the major contributor.
Shogaols, mainly [6]-shogaol (6S), [8]-shogaol (8S) and [10]-shogaol (10S), the predominant and characteristic pungent phytochemicals in ginger, are responsible for most of its beneficial effects. However, poor oral bioavailability owing to extensive glucuronidation limits their application. The present study aimed to characterize the glucuronidation pathways of 6S, 8S and 10S by using pooled human liver microsomes (HLM), human intestine microsomes (HIM) and recombinant human UDP-glucosyltransferases (UGTs). The rates of glucuronidation were determined by incubating shogaols with uridine diphosphate glucuronic acid-supplemented microsomes. Kinetic parameters were derived by appropriate model fitting. Reaction phenotyping assays, activity correlation analyses and relative activity factors were performed to identify the main UGT isoforms. As a result, one mono-4'-O-glucuronide was detected after incubating each shogaol with HLM and HIM. Enzymes kinetic analysis demonstrated that glucuronidation of shogaols consistently displayed the substrate inhibition profile, and the liver showed higher metabolic activity for shogaols (CLint = 1.37-2.87 mL min-1 mg-1) than the intestine (CLint = 0.67-0.85 mL min-1 mg-1). Besides, reaction phenotyping assays revealed that UGT2B7 displayed the highest catalytic ability (CLint = 0.47-1.17 mL min-1 mg-1) among all tested UGTs. In addition, glucuronidation of shogaols was strongly correlated with AZT glucuronidation (r = 0.886, 0.803 and 0.871 for glucuronidation of 6S, 8S and 10S, respectively; p < 0.01) in a bank of individual HLMs (n = 9). Furthermore, UGT2B7 contributed to 40.8%, 34.2% and 36.0% for the glucuronidation of 6S, 8S and 10S in HLM, respectively. Taken altogether, shogaols were efficiently metabolized through the glucuronidation pathway, and UGT2B7 was the main contributor to their glucuronidation.


Crystal structure of the monocupin ring-cleaving dioxygenase 5-nitrosalicylate 1,2-dioxygenase from Bradyrhizobium sp.
5-Nitrosalicylate 1,2-dioxygenase (5NSDO) is an iron(II)-dependent dioxygenase involved in the aerobic degradation of 5-nitroanthranilic acid by the bacterium Bradyrhizobium sp. It catalyzes the opening of the 5-nitrosalicylate aromatic ring, a key step in the degradation pathway. Besides 5-nitrosalicylate, the enzyme is also active towards 5-chlorosalicylate. The X-ray crystallographic structure of the enzyme was solved at 2.1 Å resolution by molecular replacement using a model from the AI program AlphaFold. The enzyme crystallized in the monoclinic space group P21, with unit-cell parameters a = 50.42, b = 143.17, c = 60.07 Å, β = 107.3°. 5NSDO belongs to the third class of ring-cleaving dioxygenases. Members of this family convert para-diols or hydroxylated aromatic carboxylic acids and belong to the cupin superfamily, which is one of the most functionally diverse protein classes and is named on the basis of a conserved β-barrel fold. 5NSDO is a tetramer composed of four identical subunits, each folded as a monocupin domain. The iron(II) ion in the enzyme active site is coordinated by His96, His98 and His136 and three water molecules with a distorted octahedral geometry. The residues in the active site are poorly conserved compared with other dioxygenases of the third class, such as gentisate 1,2-dioxygenase and salicylate 1,2-dioxygenase. Comparison with these other representatives of the same class and docking of the substrate into the active site of 5NSDO allowed the identification of residues which are crucial for the catalytic mechanism and enzyme selectivity.


The aryl hydrocarbon receptor as a model PAS sensor.
Proteins containing PER-ARNT-SIM (PAS) domains are commonly associated with environmental adaptation in a variety of organisms. The PAS domain is found in proteins throughout Archaea, Bacteria, and Eukarya and often binds small-molecules, supports protein-protein interactions, and transduces input signals to mediate an adaptive physiological response. Signaling events mediated by PAS sensors can occur through induced phosphorelays or genomic events that are often dependent upon PAS domain interactions. In this perspective, we briefly discuss the diversity of PAS domain containing proteins, with particular emphasis on the prototype member, the aryl hydrocarbon receptor (AHR). This ligand-activated transcription factor acts as a sensor of the chemical environment in humans and many chordates. We conclude with the idea that since mammalian PAS proteins often act through PAS-PAS dimers, undocumented interactions of this type may link biological processes that we currently think of as independent. To support this idea, we present a framework to guide future experiments aimed at fully elucidating the spectrum of PAS-PAS interactions with an eye towards understanding how they might influence environmental sensing in human and wildlife populations.


Evaluation of sutureless anastomosis after ileostomy takedown using the self-forming magnet anastomosis system in a porcine model.
Current standard of care for creation of small bowel anastomoses after a loop ileostomy reversal includes the use of stapler devices and sutures. Compression anastomosis devices have been used for decades, aimed toward improved outcomes with a "staple free" & "suture free" anastomosis. The self-forming magnet (SFM) device is a type of compression anastomosis device used to safely and effectively create an end-to-end small bowel anastomosis without the localized inflammatory response seen with sutures or staples, as no foreign bodies are left behind. A Good Laboratory Practice preclinical study using a porcine model to evaluate creating an in vivo anastomosis via magnetic compression between two segments of small bowel (jejunum or ileum) was performed. Magnetic anastomoses were compared to stapled and handsewn anastomoses. Six animals were used for the magnetic anastomosis and eight for the two control groups for a total of 14 subjects. Mean creation times were 17.1 min (SD 6.06) for the SFM group, 10.3 min (SD 6.55, CI 95%) for the stapled anastomosis group, and 28.3 min (SD 2.63, CI 95%) for the suture anastomosis group, with a statistically significant difference among groups (p < 0.0021). All evaluated SFM anastomosis, stapled anastomosis, and handsewn anastomosis underwent a burst test with a pressure of 1.3 PSI. All six magnets used for anastomoses were naturally expelled. The range of days to expel magnets was 10-17 days. Intestinal anastomoses using magnets had considerably less residual scarring and intestinal distortion than anastomoses done with either suture or staples. This preclinical study documents the safety and efficacy of creating end-to-end small bowel anastomoses after ileostomy takedown using a magnetic compression device. The result is an anastomosis free of foreign objects with less inflammation, scarring, distortion, and mural thickening than seen in sutured or stapled anastomoses.


Why nursing students need an allocation to operating theatres.
Student placements in operating theatres are being discontinued in some hospitals. Here, the author explores the reasons for this and highlights what nursing students can achieve during a placement in theatre.


Long-term outcome of macular shift after retinal detachment repair.
This study aimed to evaluate the long-term change of postoperative retinal shift after pars plana vitrectomy for macular off retinal detachment. In this retrospective study, patients with retinal shift after pars plana vitrectomy for macula-off rhegmatogenous retinal detachment (RRD) were examined at 3 weeks and 12 months postoperatively. Fundus autofluorescence images were obtained to visualize retinal rotation. Best-corrected visual acuity was measured and metamorphopsia assessed using the Amsler grid. Nine patients with postoperative retinal shift were included in the study. Retinal shift decreased significantly in these patients, on average by 1.07° (range 0.52-1.62, p = 0.002) after 12 months. However, more patients complained of distorted vision after 12 months (odds ratio for change = 3.0, 95% CI: 0.24 to 157.49). The main reason was the new formation of an epiretinal membrane (odds ratio for change = infinity, 95% CI: 0.41 to infinity). There was no change in visual acuity observed (p = 0.16). Postoperative retinal shift after RRD repair decreases over a 1-year span. While retinal shift is the main cause for metamorphopsia in the early postoperative period, formation of an ERM is the main reason for distorted vision long term.


Human IgE mRNA expression by peripheral blood lymphocytes stimulated with interleukin 4 and pokeweed mitogen.
Expression of human IgE mRNA by peripheral blood lymphocytes (PBL) and an IgE-producing myeloma cell line, U-266, was examined by Northern blot hybridization and compared with IgE levels in culture supernatants. A 2.35-kb IgE mRNA was detected in unstimulated atopic PBL and U-266 cells but not in normal PBL, and its levels correlated with IgE protein levels in the supernatant. Upon stimulation with interleukin 4, a new 1.75-kb transcript was revealed in both atopic and normal PBL but not in U-266 cells. Its expression did not correlate with IgE levels in the supernatant. Pokeweed mitogen also induced the expression of the 1.75-kb transcript without concomitant induction of IgE synthesis by normal PBL and even suppressed the spontaneous expression of the 2.35-kb transcript and IgE protein synthesis by atopic PBL. Interferon-gamma, which suppressed both the 2.35-kb transcript and IgE protein production, had no inhibitory effect on the 1.75-kb transcript. Expression of the 1.75-kb transcript was already high after 2 days of stimulation and peaked around day 4. The length of the transcript is smaller than that of mRNA coding for secreted human IgG and IgA and contains all four C epsilon exon sequences, suggesting it might be a truncated transcript without v region and might be a human counterpart of the murine germ-line C epsilon transcript.


Purification and complete primary structure of the first PLA2 from Lachesis stenophrys (the Central American Bushmaster) snake venom.
The first PLA(2) (LsPA-1) from L. stenophrys snake venom was purified to homogeneity using three chromatographic steps and had its complete primary structure determined. An average molecular mass of 13,870.3 kDa was determined by mass spectrometry and a 3.3-fold increase in the PLA(2) activity was observed for LsPA-1 as compared to the whole venom. Multiple alignment of PLA(2) from Lachesis spp. snakes suggested the existence of two geographical clades for this genus in the New World, which is in accordance with morphological, behavioral and mtDNA data obtained by others. Phospholipases A(2) from Crotalus spp. snake venoms were similarly distributed into two groups. Intergroup analysis indicated that most amino acid substitutions were observed in the amino- and carboxy-terminal regions of the molecules in each clade. Both regions have been suggested to play important roles in determining the biological properties of PLA(2) from snake venoms. The dendogram derived for PLA(2) from Lachesis and Crotalus snakes highlighted the phylogenetic relationships between these two genera in the New World.


Carotid artery erosion in a 4-year child.
The carotid erosion occurs most commonly in patients receiving radiotherapy for head and neck cancer and is associated with high mortality. We report a case of carotid blow out in a 4-year-old child who presented with massive parapharyngeal space abscess. The common carotid artery (CCA) was ligated and child recovered without any neurological sequel.


Necrolytic migratory erythema, first symptom of a malignant glucagonoma: treatment by long-acting somatostatin and surgical resection. Report of three cases.
We report three cases of malignant glucagonoma with necrolytic migratory erythema as the first clinical symptom. Long-acting somatostatin analogue was the first step of a multimodal therapeutic strategy which included surgical resection of the primary tumour in every case. Liver metastases which were present in two patients were treated by hepatic arterial chemoembolization and systemic chemotherapy in one case and by liver resection for cytoreduction and hepatic arterial chemoembolization in another case. Skin lesions resolved in all three patients.


Intra-carotid arterial administration of autologous peripheral blood-derived endothelial progenitor cells improves acute ischemic stroke neurological outcomes in rats.
We tested the hypothesis that transfusion of autologous peripheral blood-derived endothelial progenitor cells (PBDEPC) via the internal carotid artery could reduce brain-infarct zone (BIZ) and neurological deficit in rats following acute ischemic stroke (IS) induced by 50-min left middle cerebral artery occlusion. Adult male Sprague-Dawley rats (n=60) were equally divided into group 1 [sham control (SC)], group 2 [SC-PBDEPC (5.7 × 10(6)/kg)], group 3 (IS), group 4 [IS-low-dose PBDEPC (1.7 × 10(6)/kg)], group 5 [IS-high-dose PBDEPC (5.7×10(6)/kg)]. Groups 2 to 5 received G-CSF (35 μg/kg subcutaneously) for 4 days before drawing blood for PBDEPC culture. By day 90, BIZ determined by histopathology (area) and brain MRI (volume) were highest in group 3, lowest in groups 1 and 2, higher in group 4 than in group 5 (all p<0.0001), and not significantly different between groups 1 and 2. Sensorimotor functional results exhibited an opposite pattern of BIZ among groups 3 to 5 (p<0.005). Angiogenesis biomarkers (SDF-1α, CXCR4, VEGF, angiopoietin-1) significantly increased progressively from groups 1 and 2 to group 5 (all p<0.0001). Oxidative-stress (NOX-1, NOX-2, oxidized protein), apoptotic (cleaved caspase 3 and PARP, mitochondrial Bax), inflammatory (MMP-9, TNF-α, AQP-4, GFAP, iNOS), and brain-damaged (cytosolic cytochrome-C) biomarkers showed an identical pattern, whereas anti-inflammatory (Bcl-2), mitochondrial preservation (mitochondrial cytochrome-C, PGC-1α), and endothelial function (CD31+, vWF+, eNOS) biomarkers, and vessel density showed an opposite pattern of BIZ among these five groups (all p<0.001). Higher-dose was superior to lower-dose EPC treatment for reducing BIZ and improving neurological functional outcome.


Assessing the standard of care for child and adolescent attention-deficit hyperactivity disorder in Elgin County, Ontario: a pilot study.
To examine the current practice of rural family physicians in managing children with attention-deficit hyperactivity disorder (ADHD). Chart review of children and adolescents with a recorded diagnosis of ADHD. The data collected include the patient's age at diagnosis, the diagnosing physician, the number and type of presenting symptoms, whether the Diagnostic Statistical Manual, 4th ed (DSM-IV) criteria were met, pertinent treatment regimens, family history and comorbid conditions. Participating physicians were asked to complete a questionnaire. Elgin County, Ontario. Thirty-six family physicians were contacted and 11 agreed to participate. Thirty-nine charts were reviewed. The average number of presenting symptoms was 2.9 for ADHD-inattentive subtype and 2.1 for ADHD-hyperactivity subtype. A diagnostic protocol was included in 20.5% of the charts. Of the 39 charts reviewed, 25.6% had sufficient information for the patients to meet the ADHD criteria. Family physicians diagnosed 5.1% of the cases, and the duration of time between referral to specialist and appointment was 47.2 weeks. Together the lack of symptom recording, the long duration between referrals, and the low percentage of family physicians diagnosing ADHD all suggest the need for developing diagnostic protocols for family physicians and increasing their knowledge of diagnosing and managing ADHD.


Bacterial enrichment in the surface microlayer of an Anopheles quadrimaculatus (diptera: culicidae) larval habitat.
Sampling of the surface microlayer of water in a marsh habitat of Anopheles quadrimaculatus Say in Michigan revealed it to be enriched with bacteria compared with subsurface water samples. Concentrations of total numbers of bacteria ranged from 18.8 x 10(6)/ml to 65.4 x 10(6)/ml (mean, 35.9 x 10(6)/ml; n = 13) in surface microlayer samples, and from 3.8 x 10(6)/ml to 14.3 x 10(6)/ml, (mean, 7.8 x 10(6)/ml; n = 13) in subsurface samples. Specifically, the surface microlayer had higher concentrations of three morphotypes of bacteria (cocci, rods, and rods attached to detritus particles). Given that bacteria are an important food of mosquito larvae, we suggest that the interfacial feeding behavior of An. quadrimaculatus larvae allows them to exploit the surface microlayer, a food-rich zone.


Alteration in cell division, morphology and motility induced by the toxic principle of lupinosis.
A number of experiments are described in which the effect of the toxins causing lupinosis on cell morphology and motility is examined. The toxins arrested cells in metaphase leading to abnormal profiles, and inhibited leucocyte migration. Similar results were obtained with colchicine on cell division and, from the evidence obtained, it is suggested that the mechanism of action of the two agents is similar and that the same binding sites are probably involved.


Influence of surgeons' experience on postoperative sepsis.
A prospective study was performed on 635 patients with appendicitis operated on by 7 trainees and 119 patients operated on by 6 senior surgeons with more than 8 years of surgical experience. In patients with normal appendices, postoperative sepsis was extremely low. For early and late appendicitis, the infection rates of the trainees decreased as experiences accumulated, but they were still higher than that of the senior surgeons. The difference in infection rates in acute appendicitis did not reach statistical significance between any of the training stages and between the various stages and the rate of the senior surgeons. The differences in infection rates in late appendicitis between stage 1 and stage 3 was significant, as was the difference in infection rates between stage 1 and the infection rate of the senior surgeons. Therefore, we have concluded that overall, the limited experience of trainees is related to the rate of postoperative sepsis in late appendicitis, although the infection rates of individual trainees vary a lot.


Trophic position, altitudinal distribution, and water dependence as determining factors for mercury concentrations in tropical montane anurans.
Mercury (Hg) is a widespread and toxic contaminant with potential for long-range atmospheric transport. Previous work has shown that temperate and subtropical montane ecosystems have great potential for deposition of this element. However, little information exists regarding Hg dynamics in tropical mountains. In present study, we evaluated the influence of altitudinal distribution, size, trophic position, and degree of water dependence on Hg concentration in amphibians. For this purpose, we determined the mercury concentration in topsoil and amphibian samples collected at 32 points distributed between 327 and 2181 m above sea level in Serra dos Órgãos, a mountainous complex located in southeastern Brazil. We analyzed the concentration of mercury in whole body samples of 200 individuals of 30 amphibian species. Trophic position of the specimens was estimated by nitrogen stable isotope (δ15N) composition in muscle tissues. We observed a positive relationship between elevation and Hg concentration in topsoil samples from rainforest sites. However, in samples from nebular forest and campos de altitude (highland grasslands) sites, the concentration of Hg was considered lower than expected by the trend in rainforest points, indicating that the vegetation structure plays an important role in the deposition of atmospheric mercury. Mercury concentration in amphibians varies according to the functional characteristics of the species and the environment in which the individual is inserted. Elevation, trophic level and water dependence explained at least some degree of variation in Hg concentration in amphibian tissues. Thus, this community-level analysis suggests that mountainous areas in the tropical region, as recorded for temperate and subtropical mountains, act as regional convergence and deposition sites for atmospheric mercury.


A self-powered photoanode-supported photoelectrochemical immunosensor for CYFRA 21-1 detection based on In2O3/In2S3/CdIn2S4 heterojunction.
A self-powered photoanode-supported photoelectrochemical (PEC) immunosensor was designed based on In2O3/In2S3/CdIn2S4 as photoanode and PDA@CNTs as biocathode for the detection of CYFRA 21-1. In this proposal, In2O3/In2S3/CdIn2S4 heterojunction modified indium-tin oxide (ITO) electrode was served as a substitute for platinum (Pt) counter electrode to provide an evident and stable photocurrent signal. The matched band structure of In2O3, In2S3 and CdIn2S4 as well as the unique hollow porous structure of In2O3/In2S3/CdIn2S4 played a pivotal role in accelerating the separation and transfer of photocarrier. Meanwhile, PDA@CNTs with excellent conductivity further enhanced the photocurrent which was provided by photoanode In2O3/In2S3/CdIn2S4 heterojunction. Besides, PDA could effectively capture the antibody (Ab) through Michael addition. Separating photoanode from the sensing biocathode was conducive to improve the anti-interference capability of PEC sensor because the reductive species in biologic media will change PEC properties of the photoanode interface. Under optimal conditions, the PEC immunosensor have realized the detection of CYFRA 21-1 (0.5 pg/mL - 50 ng/mL) and the detection limitation with 0.16 pg/mL. In addition, the proposed self-powered PEC sensor with acceptable selectivity, reproducibility, and stability provide a new horizon for designing PEC immunosensing platform in bioassays.


Sb(III) resistance mechanism and oxidation characteristics of Klebsiella aerogenes X.
Resistant bacteria are potential natural materials for the bioremediation of soil metalloid pollution. A strain isolated from farmland soil chronically exposed to Sb was identified as K. aerogenes X with high antimonite [Sb(III)] tolerance and oxidation ability. The resistance mechanism of K. aerogenes X and its extracellular polymeric substances (EPS), antioxidant enzymes, and oxidation characteristics in Sb(III) stress were investigated in this study by stress incubation experiments and FTIR. The biotoxicity of Sb was limited by the binding of the organic compounds in EPS, and the anionic functional groups (e.g., amino, carboxyl and hydroxyl groups, etc.) present in the cell envelope were the components primarily responsible for the metalloid-binding capability of K. aerogenes X. The K. aerogenes X can oxidize Sb(III), and its metabolites induce changes in reactive oxygen species (ROS), catalase (CAT), total superoxide dismutase (SOD) and glutathione s-transferase (GSH-S) activity, indicating that the resistance mechanisms of K. aerogenes X are mediated by oxidative stress, EPS restriction and cell damage. Oxidation of Sb(III) is driven by interactions in intracellular oxidation, cell electron transport, extracellular metabolism including proteins and low molecular weight components (LMWs). LMWs (molecular weight <3 kDa) are the main driving factor of Sb(III) oxidation. In addition, Sb resistance genes arsA, arsB, arsC, arsD and acr3 and potential oxidation gene arsH were identified in K. aerogenes X. Owing to its natural origin, high tolerance and oxidation ability, K. aerogenes X could serve as a potential bioremediation material for the mitigation of Sb(III) in contaminated areas.


Proinflammatory cytokine expression in cyclooxygenase-2-deficient primary osteoblasts.
Many of the proinflammatory effects of interleukin (IL)-1beta and tumor necrosis factor-alpha (TNF-alpha) are mediated through cyclooxygenase-2 (COX-2)-dependent prostaglandin E2 (PGE2). The purpose of this study was to examine the expression of IL-1beta and TNF-alpha in COX-2-deficient osteoblasts during inflammation. Primary osteoblasts prepared from wild-type (WT) and COX-2 knockout (K/O) mice were exposed to lipopolysaccharide (LPS) and endodontic obturation materials. An enzyme-linked immunosorbent assay was used to measure cytokine levels. LPS treatment led to a significant upregulation in IL-1beta and TNF-alpha levels in both WT and K/O cells. TNF-alpha upregulation in response to LPS was much more pronounced in K/O cells compared with WT cells (p < 0.05). All materials tested except for gutta percha caused an increase in IL-1beta expression. In conclusion, there appears to be a positive feedback regulation between TNF-alpha and COX-2-dependent PGE2 during LPS-induced inflammatory reactions.


Vaccine-induced protection against hepatitis B in pediatric solid organ transplant patients.
Vaccination against hepatitis B virus (HBV) has led to a worldwide reduction in disease burden and mortality. Vaccine immunogenicity data in transplanted children are limited, and vaccine-induced protection may be reduced. We evaluated HBV vaccination coverage, seroprotection rates, and factors influencing vaccine immunity among pediatric solid organ transplant (SOT) patients. We retrospectively identified patients ≤21 years of age evaluated for SOT and/or transplanted at our center between January 1, 2015, and December 31, 2018. A detailed chart review was conducted using a standard questionnaire to gather information on demographic, clinical, and laboratory features of patients' HBV vaccination, and hepatitis B surface antibody (HBsAb) titers. A total of 381 patients undergoing evaluation and/or transplantation were included: 139 (36.5%) liver, 138 (36.2%) kidney, and 104 (27.3%) heart. Overall, HBsAb at evaluation was reactive in 216 (56.7%), indeterminate in 17 (4.5%), non-reactive in 138 (36.2%), and not available in 10 (2.6%). Of those that completed a primary HBV vaccine series (n = 304), HBsAb was reactive in 164 (53.9%), indeterminate in 13 (4.3%), non-reactive in 119 (39.1%), and not available in 8 (2.6%). For those up to date for age on HBV vaccinations with non-reactive/indeterminate titers at evaluation, revaccination and a follow-up HBsAb were available in 45 patients of which 33 (73.3%) seroconverted to a reactive HBsAb titer. Vaccine-induced protection against HBV infection among high-risk pediatric SOT recipients can be improved by serology-based intervention. Though the absence of HBsAb does not always indicate loss of protection, boosting or completing primary series is recommended.


SUMOylation of the cardiac sodium channel NaV1.5 modifies inward current and cardiac excitability.
Decreased peak sodium current (INa) and increased late sodium current (INa,L), through the cardiac sodium channel NaV1.5 encoded by SCN5A, cause arrhythmias. Many NaV1.5 posttranslational modifications have been reported. A recent report concluded that acute hypoxia increases INa,L by increasing a small ubiquitin-like modifier (SUMOylation) at K442-NaV1.5. The purpose of this study was to determine whether and by what mechanisms SUMOylation alters INa, INa,L, and cardiac electrophysiology. SUMOylation of NaV1.5 was detected by immunoprecipitation and immunoblotting. INa was measured by patch clamp with/without SUMO1 overexpression in HEK293 cells expressing wild-type (WT) or K442R-NaV1.5 and in neonatal rat cardiac myocytes (NRCMs). SUMOylation effects were studied in vivo by electrocardiograms and ambulatory telemetry using Scn5a heterozygous knockout (SCN5A+/-) mice and the de-SUMOylating protein SENP2 (AAV9-SENP2), AAV9-SUMO1, or the SUMOylation inhibitor anacardic acid. NaV1.5 trafficking was detected by immunofluorescence. NaV1.5 was SUMOylated in HEK293 cells, NRCMs, and human heart tissue. HyperSUMOylation at NaV1.5-K442 increased INa in NRCMs and in HEK cells overexpressing WT but not K442R-Nav1.5. SUMOylation did not alter other channel properties including INa,L. AAV9-SENP2 or anacardic acid decreased INa, prolonged QRS duration, and produced heart block and arrhythmias in SCN5A+/- mice, whereas AAV9-SUMO1 increased INa and shortened QRS duration. SUMO1 overexpression enhanced membrane localization of NaV1.5. SUMOylation of K442-Nav1.5 increases peak INa without changing INa,L, at least in part by altering membrane abundance. Our findings do not support SUMOylation as a mechanism for changes in INa,L. Nav1.5 SUMOylation may modify arrhythmic risk in disease states and represents a potential target for pharmacologic manipulation.


Self-Rehabilitation Guided by a Mobile Application After Anterior Cruciate Ligament Reconstruction Leads to Improved Early Motion and Less Pain.
To evaluate the adherence rate and the contribution of self-rehabilitation (SR) guided by a mobile application after anterior cruciate ligament reconstruction (ACLR) in combination with physical therapy sessions on early knee function. This study was a retrospective analysis of prospectively collected data from a single health care facility. All patients who underwent ACLR by a single surgeon from December 2019 to September 2020 were included. Two groups were formed and compared based on use of the mobile app: users (>10 days of use) and nonusers (≤10 days of use). Outcomes included physical examination at 3 and 6 weeks postoperatively. A total of 65 patients were analyzed: 19 in the nonuser group and 46 in the user group. Adherence rate was 91% at 10 days, 71% at 15 days, 62% at 21 days, and 44% at 45 days. At 3 weeks, the user group was 3.86 times [range 1.12 to 13.3] as likely to lock the quadriceps during gait with crutches and was 4.2 times [range 1.2 to 14.3] as likely to be pain free. There was a tendency to have less flexion contracture in the user group (17% versus 32%, P = .32). At 6 weeks, the differences leveled out, but the user group still had slightly better quadriceps locking during gait without crutches (87% versus 79%, P = .46). SR guided by a mobile app combined with a standard rehabilitation protocol is correlated with better knee function at initial follow-up. IV, therapeutic case series.


Silk fibroin double-layer microneedles for the encapsulation and controlled release of triptorelin.
A double-layer silk fibroin microneedles (SF-MNs) was proposed for the transdermal delivery of triptorelin. Two-step pouring and centrifugation were employed to prepare SF-MNs. Triptorelin was wrapped in MNs in the form of microcrystals with a size of ∼1 μm. β-sheet nanocrystals (the secondary structure of silk fibroin) were adjusted in content by methanol-vapor treatment to manipulate the characteristics of SF-MNs prepared with two concentrations of silk fibroin. The mechanical strength of MNs was measured and analyzed in proportion to the β-sheet content. The triptorelin in MNs could be released sustainedly in phosphate-buffered saline for 168 h, and the release amount decreased with increasing β-sheet content. The Ritger-Peppas equation was employed to fit the release data. A linear decreasing relationship was observed between the diffusion coefficient and increased β-sheet content. After administration to rats, SF-MNs exhibited long-term testosterone inhibition and maintained castration levels for ≥7 d. Manipulable mechanical properties and release behavior combined with biocompatibility and biodegradability render SF-MNs as viable long-term transdermal delivery devices for triptorelin.


Hemostatic net in rhytidoplasty: an efficient and safe method for preventing hematoma in 405 consecutive patients.
Hematoma is the most common postoperative complication of rhytidoplasty, resulting in higher morbidity and longer recovery. Quilting suture for closure of the undermined area in abdominoplasty avoids the occurrence of seroma. Based on this principle and with the objective of reducing the number of patients with hematomas in rhytidoplasty, a similar surgical tactic was developed in which a hemostatic net is created with a running transfixing suture of 5-0 nylon encompassing the skin and the superficial musculoaponeurotic system-platysma. The study enrolled 525 consecutive patients who underwent rhytidoplasty between July 2009 and February 2013. The first 120 patients (group A) were evaluated retrospectively and considered control subjects. The remaining 405 patients (group B) had application of the described tactic, with data collected prospectively. The occurrence of hematoma, ischemia, and necrosis was observed during the first 72 h after surgery. Control group A included 17 patients with hematoma (14.2 %) during the first 72 h, whereas no patient in group B experienced such a complication (p < 0.001). The surgical tactic did not significantly increase the occurrence of ischemia. This complication was experienced by 11 patients in group A (9.2 %) and 26 patients in group B (6.4 %) (p = 0.408). The tactic also did not change the incidence of necrosis, which was present in three group A patients (2.5 %) and six group B patients (1.5 %) (p = 0.723). The hemostatic net is an efficient and safe method for preventing early hematomas in rhytidoplasties. LEVEL OF EVIDENCE III This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .


Flash evoked potentials in the ectostriatum of the zebra finch: a current source-density analysis.
Recent research has demonstrated that ipsilaterally visually evoked potentials (VEPs) can be measured within the ectostriatum, the telencephalic target area of the tectofugal visual pathway in birds. In this paper we systematically measured contra- and ipsilateral VEPs within the ectostriatal complex to obtain more detailed information on the processing of contra- and ipsilateral stimuli. The similarity of neighbouring VEPs at equal depth and a comparison of a one dimensional and a three dimensional analysis of current source-densities (CSDs) for identical coordinates suggested that a one dimensional current source-density analysis might be applicable. The one dimensional current source-density analysis demonstrated largely corresponding patterns in the sink-source sequences of the current source-density depth profiles for the contra- and ipsilateral stimulus responses. The occurrence of a large sink in the centre of the ectostriatal core, together with the results of multiunit recordings, shows that the ectostriatal core is the location of the generators for both the contra- and the ipsilaterally evoked responses. The occurrence of macroscopic sinks and sources and the fact that VEPs can be recorded from the ectostriatum shows that there is a higher degree of order in the ectostriatum than has been previously demonstrated by anatomical methods. The time coincidence between the maximum spike rate of multiunit responses, the negative peak of the evoked potential, and the large central sink demonstrates that the influence of ipsi- as well as of contralateral stimuli is predominantly excitatory.


Differential diagnosis between uterine carcinosarcoma versus carcinoma with sarcomatous metaplasia: an immunohistochemical and ultrastructural case study.
Uterine carcinosarcomas are biphasic neoplasms with carcinomatous and sarcomatous elements. However, several elements suggest that carcinosarcomas may be more closely related to carcinoma of the endometrium and that they arise from an unique stem cell. Recently, the authors observed an uterine tumor that at histologic examination showed an apparently double population of cells: malignant epithelial element admixed with mesenchymal spindle-shaped cells. The immunohistochemical stainings instead showed cytokeratin positivity and negativity for stromal markers. Electron microscopy showed the neoplastic tissue to be made of a single population of poorly differentiated epithelial cells, thus confirming the immunohistochemical findings and leading to the diagnosis of uterine metaplastic carcinoma.


Voltammetric investigation of diethylstilbestrol.
In this work electrooxidation of diethylstilbestrol (DES) was investigated by cyclic voltammetry (CV) and differential pulse voltammetry (DPV) using a glassy carbon (GC) electrode. It was statistically shown that both methods could be used for the determination of DES in the concentration range of 2 x 10(-5)-6 x 10(-4) M by CV and 1 x 10(-5)-1 x 10(-3) M in methanol (MeOH) and 4 x 10(-5)-6 x 10(-4) M in acetonitrile (ACN) by DPV and both of the methods could be applied to human serum. A mechanism was proposed about the electrooxidation of this substance.


Inhibin B is the major form of inhibin secreted from testes in male Japanese macaques ( Macaca fuscata).
In order to clarify the cellular source and forms of bioactive inhibin in male Japanese macaques ( Macaca fuscata), circulating concentrations of inhibin A and B, and immunohistochemical localization of inhibin subunits in testis were studied. Plasma concentrations of testosterone were also measured. The present study showed that inhibin B was clearly detected in the plasma of male Japanese macaques. Moreover, concentrations of both inhibin B and testosterone during the breeding (mating) season were significantly higher than those of the non-breeding season. On the other hand, plasma inhibin A was detected neither during the breeding seasons nor during the non-breeding seasons. Positive stainings with alpha and betaB subunit antibodies were observed in the Sertoli cells, however staining with betaA subunit antibody was not observed in the testicular samples. These results indicate that inhibin B is the major circulating inhibin and probably secreting from Sertoli cells in male Japanese macaques.


Seven days of hot water heat acclimation does not modulate the change in heart rate variability during passive heat exposure.
We examined if the change in heart rate variability during passive heat exposure is modified by hot water heat acclimation (HA). Sixteen healthy adults (28 ± 5 years, 5 females/11 males) underwent heat exposure in a water-perfused suit, before and after 7 days of HA (60 min at rectal temperature ≥38.6 °C). During passive heat exposure, heart rate, the standard deviation of NN intervals (SDNN), the square root of the mean squared differences of successive NN intervals (RMSSD), and the power in the high-frequency range (HF) were measured. No difference in heart rate (P = 0.22), SDNN (P = 0.87), RMSSD (P = 0.79), and HF (P = 0.23) was observed at baseline. The increase in HR (pre-HA, 43 ± 10; post-HA, 42 ± 9 bpm; P = 0.57) and the decrease of SDNN (pre-HA, -54.1 ± 41.0; post-HA, -52.2 ± 36.8 ms; P = 0.85), RMSSD (pre-HA, -70.8 ± 49.5; post-HA, -72.7 ± 50.4 ms; P = 0.91) and HF (pre-HA, -28.0% ± 14.5; post-HA, -23.2% ± 17.1%; P = 0.27) were not different between experimental visits at fixed increases in esophageal temperature. These results suggest that 7 consecutive days of hot water HA does not modify the change in heart rate variability indices during passive heat exposure. Novelty: It remains unclear if HA alters the change in heart rate variability that occurs during passive heat exposure. At matched levels of thermal strain, 7 consecutive days of hot water immersion did not modulate the change in indices of heart rate variability during passive heat exposure.


The sensing of respiratory gases in fish: Mechanisms and signalling pathways.
Chemoreception in fish is critical for sensing changes in the chemical composition of the external and internal environments and is often the first step in a cascade of events leading to cardiorespiratory and metabolic adjustments. Of paramount importance is the ability to sense changes in the levels of the three respiratory gases, oxygen (O2), carbon dioxide (CO2) and ammonia (NH3). In this review, we discuss the role of piscine neuroepithelial cells (NEC), putative peripheral chemoreceptors, as tri-modal sensors of O2, CO2 and NH3. Where possible, we elaborate on the signalling pathways linking NEC stimulation to afferent responses, the potential role of neurotransmitters in activating downstream neuronal pathways and the impact of altered levels of the respiratory gases on NEC structure and function. Although serotonin, the major neurotransmitter contained within NECs, is presumed to be the principal agent eliciting the reflex responses to altered levels of the respiratory gases, there is accumulating evidence for the involvement of "gasomitters", a class of gaseous neurotransmitters which includes nitric oxide (NO), carbon monoxide (CO) and hydrogen sulphide (H2S). Recent data suggest that CO inhibits and H2S stimulates NEC activity whereas NO can either be inhibitory or stimulatory depending on developmental age.


The BDA Dental Academic Staff Group Student Elective Workshop.
In the current climate in dental education, many schools are re-evaluating the role of the student elective in the curriculum, with two schools no longer running elective programmes. In order to discuss the future of student electives in the dental curriculum, the Dental Academic Staff Group (DASG) of the British Dental Association organised a Student Elective Workshop, which attracted 42 delegates including nine student representatives. The following article is an account of the Workshop and its conclusions.


Interactions of macromolecules with salt ions: an electrostatic theory for the Hofmeister effect.
Salting-out of proteins was discovered in the nineteenth century and is widely used for protein separation and crystallization. It is generally believed that salting-out occurs because at high concentrations salts and the protein compete for solvation water. Debye and Kirkwood suggested ideas for explaining salting-out (Debeye and MacAulay, Physik Z; 1925;131:22-29; Kirkwood, In: Proteins, amino acids and peptides as ions and dipolar ions. New York: Reinhold; 1943. p 586-622). However, a quantitative theory has not been developed, and such a theory is presented here. It is built on Kirkwood's idea that a salt ion has a repulsive interaction with an image charge inside a low dielectric cavity. Explicit treatment is given for the effect of other salt ions on the interaction between a salt ion and its image charge. When combined with the Debye-Hückel effect of salts on the solvation energy of protein charges (i.e., salting-in), the characteristic curve of protein solubility versus salt concentration is obtained. The theory yields a direct link between the salting-out effect and surface tension and is able to provide rationalizations for the effects of salt on the folding stability of several proteins.


Hypothermia for the treatment of postsurgical greatly accelerated junctional ectopic tachycardia.
Three infants developed greatly accelerated junctional ectopic tachycardia with a heart rate greater than 200 beats/min after open heart surgery. When the heart rate exceeded 200 beats/min for 5 hours, all the infants had congestive heart failure and clinical signs of low cardiac output. Conventional therapy (cardioversion, lidocaine, verapamil, digoxin and ice to face) has been shown in the past to be unsuccessful in controlling the heart rate. Because hypothermia is known to decrease automaticity of the heart, these patients were treated with induced hypothermia. The goal was to arbitrarily decrease the junctional ectopic rate to less than 180 beats/min to increase cardiac filling time. The duration of the junctional ectopic tachycardia greater than 180 beats/min ranged from 0.5 to 17 hours after cooling began. The duration of the hypothermia ranged from 4 to 24 hours. Spontaneous reversion to sinus rhythm occurred either during the hypothermia or shortly thereafter in all three patients. The blood pressure and urinary output remained stable during hypothermia. Hypothermia is an effective means of controlling the rate of greatly accelerated junctional ectopic tachycardia after open heart surgery in infants. Although hypothermia does not convert junctional ectopic tachycardia to sinus rhythm, it slows the rate to a more acceptable level, allowing the infants' survival and eventual recovery of sinus rhythm.


Patterns of stress responses shift during seasonal life-history transitions: An analysis comparing baseline, maximal and integrated corticosterone in female red-sided garter snakes (Thamnophis sirtalis parietalis).
Glucocorticoids often rise and fall with a variety of external and internal cues and frequently vary among life-history stages. This suggests that changing glucocorticoids may coordinate life-history transitions. To explore this hypothesis, we asked if the time-course of stress-induced glucocorticoid levels differ between two life-history transitions (i.e., spring and fall migration) in female red-sided garter snakes (Thamnophis sirtalis parietalis). We collected non-migratory females from a communal den and migratory females from a road along the migration route and treated them with 4h of capture stress; plasma corticosterone was measured before, during and after capture stress. During the spring, den-collected females exhibited a stress-induced peak in corticosterone at an earlier sampling time than migrating, road-collected females. Because the pattern of corticosterone responses varied with migratory state, negative feedback on and/or sensitivity of the hypothalamus-pituitaryadrenal (HPA) axis may be linked to spring migration. During the fall, capture stress elicited an increase in corticosterone in den-collected females but not in migrating, road-collected females. Baseline corticosterone was higher and both maximal and integrated corticosterone responses were lower during the fall compared to spring, indicating that stress responses are smaller when baseline corticosterone is elevated, perhaps due to a "ceiling effect". These data suggest that HPA axis regulation changes during seasonal migration, possibly via altering negative feedback, HPA axis sensitivity, or some other mechanism. This study supports the hypothesis that glucocorticoids coordinate life-history events and suggests that examining a suite of stress response characteristics is most informative for understanding the function of HPA modulation.


Transcriptional activity of human brain estrogen receptor-α splice variants: evidence for cell type-specific regulation.
Estrogen receptor α (ERα) isoforms with complex types of alternative splicing are naturally present in the human brain and may affect canonical receptor signaling. In the present study we investigated transcriptional activity of common ERα splice variants from this group with different molecular defects: MB1 (intron retention), TADDI (small deletion between exons 3 and 4 with an insert), the Δ (deletion) 3(⁎)-7(*)/819 (complete skipping of exons 4, 5 and 6 and partial deletion of exons 3 and 7) and the Δ3-6 (lacking exons 3, 4, 5 and 6) in HeLa and M17 cells upon stimulation with (17β)estradiol or insulin-like growth factor 1 (IGF-1). In HeLa cells, all these splice variants showed the dominant negative function that was more pronounced for the TADDI. In M17 cells the dominant negative variants appeared to be the MB1 and the Δ3-6, whereas TADDI turned out to be a clearly dominant positive variant. In M17 cells mRNA levels of Δ3-6 and Δ3(*)-7(*)/819 variants increased following (17β)estradiol administration. In Hela cells (17β)estradiol up-regulated the IGF-1 receptor mRNA levels in cultures transfected with MB1, TADDI and Δ3(*)-7(*)/819. Our data demonstrate that ERα splice variants show differential levels of the transcriptional activity in a cell type-specific way and that IGF-1 signaling pathways are differentially employed in a cell-type specific manner depending on the level of the discrete ERα splice variants expressed. Functional properties of various ERα splice variants and their cell type-specificity should, thus, be considered as potential confounders of estrogen therapy effects on the brain.


Protein synthesis and axonal transport in goldfish retinal ganglion cells during regeneration accelerated by a conditioning lesion.
Axonal outgrowth in goldfish retinal ganglion cells following a testing lesion of the optic axons is accelerated by a prior conditioning lesion. Changes in protein synthesis and axonal transport were examined during the accelerated regeneration. The conditioning lesion was an optic tract cut made 2 weeks prior to the testing lesion, which consisted of a tract cut at the chiasma, so that nerves subjected to either a conditioning lesion ('conditioned nerves') or a sham operation ('sham-conditioned nerves') could be examined in the same animal. In the retinal ganglion cells of conditioned nerves, the incorporation of [3H]proline into protein began to increase between 1 and 8 days after the testing lesion. The amount of fast-transported labeled protein was elevated to about 8 X normal by 1 day after the testing lesion but had decreased to about 3-5X normal at 8 and 22 days. The 8 and 22 day values were not significantly different from those in sham-conditioned nerves or nerves that had received a testing lesion alone. For slow protein transport, the instantaneous amount transported was 15-16 X normal in the conditioned nerves at 1 and 8 days after the testing lesion, and the velocity of slow transport, which was already elevated above normal by 1 day after the testing lesion, was elevated still further by 8 days--to a value in excess of 1.5 mm/day (compared to 0.2-0.4 mm/day in normal animals). We believe that the enhanced outgrowth resulting from the conditioning lesion is due to a transient increase in the amount of fast transport (possibly responsible for a decreased delay in the initiation of sprouting), and a sustained increase in the amount and velocity of slow transport (which may account for an increased rate of elongation).