Reverse transcription-polymerase chain reaction analysis of genes involved in gonadal differentiation in pigs.
In mammals, testis development is initiated in the embryo as a response to the expression of the sex-determining gene, SRY. The time course of SRY expression during gonadal differentiation in the male has been described in detail only in mice and sheep. In this study, we used reverse transcription-polymerase chain reaction analysis to define the SRY transcription profile in pig genital ridges. SRY transcripts were first detectable from 23 days postcoitum (dpc), then declined sharply after 35 dpc. None were detected at 60 dpc. In addition, we analyzed temporal expression of other genes known to be involved in mammalian sex determination: WT-1, SF-1, SOX9, and AMH. A key stage seems to be 28 dpc, in which SOX9 expression switches between the male and female, and AMH expression begins to attest to Sertoli cell differentiation and to correspond to seminiferous cord formation in the male. Expression of gonadotropin receptors and aromatase was also investigated in porcine gonads, and we showed that their transcripts were detected very early on, especially in the male: 25 dpc for the LH receptor (rLH) and aromatase, and 28 dpc for the FSH receptor (rFSH). In the female, aromatase transcripts were not detected until 70 dpc, and rFSH expression occurred later: at 45 dpc at the onset of meiosis. Moreover, no difference was observed between the sexes for the onset of rLH transcription at 25 dpc. Such a thorough study has never been performed on pigs; developmental analysis will be useful for investigating sex-reversed gonads and determining ontogeny in intersexuality, a common pathology in pigs.


Superior results with continuous passive motion compared to active motion after periosteal transplantation. A retrospective study of human patella cartilage defect treatment.
Fifty-seven consecutive patients (33 men and 24 women), with a mean age of 32 years (range 16-53 years), who suffered from an isolated full-thickness cartilage defect of the patella and disabling knee pain of long duration, were treated by autologous periosteal transplantation to the cartilage defect. The first 38 consecutive patients (group A) were postoperatively treated with continuous passive motion (CPM), and the next 19 consecutive patients (group B) were treated with active motion for the first 5 days postoperatively. In both groups, the initial regimens were followed by active motion, slowly progressive strength training, and slowly progressive weight bearing. In group A, after a mean follow-up of 51 months (range 33-92 months), 29 patients (76%) were graded as excellent or good, 7 patients (19%) were graded as fair, and 2 patients (5%) were graded as poor. In group B, after a mean follow-up of 21 months (range 14-28 months), 10 patients (53%) were graded as excellent or good, 6 patients (32%) were graded as fair, and 3 patients (15%) were graded as poor. Altogether, nine of the fair or poor cases (50%) were diagnosed with chondromalacia of the patella. Our results, after performing autologous periosteal transplantation in patients with full-thickness cartilage defects of the patella and disabling knee pain, are good if CPM is used postoperatively. The clinical results using active motion postoperatively are not acceptable, especially not in patients with chondromalacia of the patella.


The effect of emulsifying salts on the turbidity of a diluted milk system with varying pH and protein concentration.
Solutions of 10 commonly used emulsifying salts (ES) listed in the Code of Federal Regulations (21CFR133.179) for pasteurized process cheese were tested for their effect on the turbidity of a diluted milk system at different pH and protein concentrations to characterize the conditions that affect micellar structure. Emulsifying salt solutions were made by mixing the ES in a 1-in-20 dilution of water in skim milk ultrafiltrate (3 kDa molecular weight cut-off) to obtain ES concentrations from 0 to 248 mM. Skim milk was added to solutions containing nanopure water, skim milk ultrafiltrate, and a specific ES ranging in concentration from 0 to 248 mM and pH 5, 5.8, 6.8, 7.8, and 8.8. The turbidity of the samples was measured as the optical density at 400 nm immediately after mixing (time, t = 0), after 30 s (t = 30s), and after 30 min (t = 30min). Emulsifying salts were found to cause a decrease in the turbidity of the system, which was modeled using an exponential decay model, where C* represents a threshold salt concentration at which rapid dissociation occurs. At pH values 5.8 and 6.8, the ES caused the greatest decrease in turbidity of the diluted milk system. At pH 5, the ES had the least effect on the turbidity of the system. Sodium hexametaphosphate was found to have the strongest dissociative effect, with a C* value of 0.33 mM for t = 0 at pH 6.8. In contrast, the largest C* value calculated at pH 6.8 was monosodium phosphate at 278.22 mM. Increased time resulted in lower C* values. The model established for this study can be used to predict the dissociation of casein micelles in the presence of various types of ES.


Surface receptors for serum albumin in group C and G streptococci show three different types of albumin specificity.
A total of 100 bacterial strains were tested for binding uptake of radiolabeled albumin preparations from 15 mammalian species. Three types of surface structures with specific binding sites for albumin were defined. A previously described receptor for albumin was separated into type a in Streptococcus equisimilis strains and in human group G streptococcal strains and type b in bovine group C streptococci. A new type of albumin receptor, type c, was found in Streptococcus dysgalactiae strains, the only receptor type so far with high affinity for bovine serum albumin. Type of albumin receptor correlated with bacterial species. The three receptor types showed high binding capacities; 2 X 10(8) bacterial organisms bound from 5 to 16 micrograms of albumin. All types of albumin receptors were stable to heat treatment at 80 degrees C for 5 min, but susceptible to both pepsin and trypsin treatment. Bacteria-bound albumin preparations were eluted at various concentrations of KSCN, reflecting differences in affinity. Up to 500 micrograms of human fibrinogen or polyclonal human immunoglobulin G had no inhibitory effect on the uptake of albumin, indicating a separate molecular localization of receptors for these proteins.


Correlation of daptomycin bactericidal activity and membrane depolarization in Staphylococcus aureus.
The objective of this study was to further elucidate the role of membrane potential in the mechanism of action of daptomycin, a novel lipopeptide antibiotic. Membrane depolarization was measured by both fluorimetric and flow cytometric assays. Adding daptomycin (5 micro g/ml) to Staphylococcus aureus gradually dissipated membrane potential. In both assays, cell viability was reduced by >99% and membrane potential was reduced by >90% within 30 min of adding daptomycin. Cell viability decreased in parallel with changes in membrane potential, demonstrating a temporal correlation between bactericidal activity and membrane depolarization. Decreases in viability and potential also showed a dose-dependent correlation. Depolarization is indicative of ion movement across the cytoplasmic membrane. Fluorescent probes were used to demonstrate Ca(2+)-dependent, daptomycin-triggered potassium release from S. aureus. Potassium release was also correlated with bactericidal activity. This study demonstrates a clear correlation between dissipation of membrane potential and the bactericidal activity of daptomycin. A multistep model for daptomycin's mechanism of action is proposed.


Determination of vascular endothelial growth factor (VEGF) overexpression in soft tissue sarcomas and the role of overexpression in leiomyosarcoma.
To evaluate the prevalence and role of vascular endothelial growth factor (VEGF) overexpression in soft tissue sarcoma (STS). VEGF expression was detected by the avidin-biotin-complex method using Santa Cruz biotechnology (SC 7629). The expression of VEGF was assessed according to the percentage of immunoreactive cells: more than 10% of the cells staining were graded as positive. No detectable staining or <10% (of cells) staining was graded as negative. Two hundred and seventy-three patients (164 females and 109 males) with a mean age of 56 years (range: 1-93 years) were included in the study. Sixty-eight of the 273 (24.91%) patients diagnosed with STS between 1986 and 2001 revealed VEGF overexpression. VEGF overexpression was predominantly seen in 30% (15/50) of patients with malignant fibrous histiocytoma (MFH), 20.45% (9/44) of dermatofibrosarcomas (DFS), 25% (9/36) of leiomyosarcomas (LMS), and 30% (6/20) of patients with carcinosarcomas (CS). Despite overexpression being seen in about a quarter of patients with STS, VEGF overexpression was of prognostic value in only those patients with the LMS histologic type, as VEGF overexpression was associated with a shorter survival in this subgroup( P=0.01, by log-rank sum test). Twenty-four point nine percent of STS overexpress VEGF and interestingly there is diversity seen in VEGF expression amongst the various histologic subtypes of STS. LMS, CS, and MFH are more likely to reveal overexpression of VEGF than the other histologic subtypes. There was no relationship between survival and VEGF status in any subtype of STS, except LMS. There is an urgent need for larger studies to validate our findings. In addition, randomized clinical trials evaluating the efficacy of angiogenesis inhibitors in soft tissue sarcomas, especially LMS, are warranted.


Corneal lymphangiogenesis facilitates ocular surface inflammation and cell trafficking in dry eye disease.
While the normal cornea has limited innervation by the lymphatic system, chronic immune-inflammatory disorders such as dry eye (DE) can induce lymphangiogenesis in the ocular surface. Using a conditional knock-down murine model, Lyve-1Cre;VEGFR2flox mice, this study investigated the role of lymphangiogenesis in the pathophysiology of DE. DE was induced in both wild type (WT) B6 and Lyve-1Cre;VEGFR2flox mice. Tissue immunostaining and volumetric gross measurements were used to assess changes in the ocular surface, skin, and lymph nodes (LNs). The expression of lymphangiogenic factors (TNF-α, IL-6/-8/-12/-17, VEGF-C/-D, IFN-γ, VEGFR-2/-3, Lyve-1, and podoplanin) and the frequency of immune cells (CD4, CD11b, and CD207) on the ocular surface and lacrimal glands were quantified by real-time polymerase chain reaction and flow cytometry. Compared to WT mice, there were fewer lymphatic vessels and a reduction in lymphangiogenic markers in the ocular surface and skin of Lyve-1Cre;VEGFR2flox mice. After DE induction, mRNA levels of TNF-α, IL-8, and IFN-γ were significantly reduced in Lyve-1Cre;VEGFR2flox mice compared to WT mice (p < .01). Surprisingly, the LNs from Lyve-1Cre;VEGFR2flox mice with DE were significantly smaller and populated by fewer dendritic cells and effector T cells than those from WT mice (p < .001). Furthermore, immunostaining showed corneal nerves in the DE-induced Lyve-1Cre;VEGFR2flox mice were notably intact like in the naïve condition. Inhibition of lymphangiogenesis in the cornea effectively attenuates not only the inflammatory response including trafficking of immune cells but also preserves corneal nerves under desiccating stress. Corneal lymphangiogenesis might be a contributing factor in deterioration on the ocular surface homeostasis.


Linkage group alignment of sorghum RFLP maps using a RIL mapping population.
Several molecular maps have been constructed in sorghum (Sorghum bicolor L. Moench) using a variety of probes from different grass species such as sorghum, maize, sugarcane, rice, oat, and barley. In order to enhance the utility of the existing mapping information by the sorghum research community, alignment and integration of all major molecular maps is necessary. To achieve this objective, a genetic map of 214 loci with a total map distance of 1200 cM was constructed using 98 F7 sorghum recombinant inbred lines (RILs) from a cross between two inbred lines, B35 and Tx7000. Few cDNA clones of sorghum and maize related to photosynthesis and drought stress were mapped on this map for the first time. Five major restriction fragment length polymorphism (RFLP) maps independently developed in this species were used for alignment purpose. The distributions of previously mapped markers were compared with their respective sorghum maps to align each of the linkage groups. In general, consistent linear order among markers was maintained in all the linkage maps. The successful alignment of these RFLP maps will now allow selection of a large number of markers for any region of the sorghum genome with many potential applications ranging from fine mapping and marker-assisted selection to map-based cloning for the improvement of sorghum and related species.


Novel findings in patients with primary hyperoxaluria type III and implications for advanced molecular testing strategies.
Identification of mutations in the HOGA1 gene as the cause of autosomal recessive primary hyperoxaluria (PH) type III has revitalized research in the field of PH and related stone disease. In contrast to the well-characterized entities of PH type I and type II, the pathophysiology and prevalence of type III is largely unknown. In this study, we analyzed a large cohort of subjects previously tested negative for type I/II by complete HOGA1 sequencing. Seven distinct mutations, among them four novel, were found in 15 patients. In patients of non-consanguineous European descent the previously reported c.700+5G>T splice-site mutation was predominant and represents a potential founder mutation, while in consanguineous families private homozygous mutations were identified throughout the gene. Furthermore, we identified a family where a homozygous mutation in HOGA1 (p.P190L) segregated in two siblings with an additional AGXT mutation (p.D201E). The two girls exhibiting triallelic inheritance presented a more severe phenotype than their only mildly affected p.P190L homozygous father. In silico analysis of five mutations reveals that HOGA1 deficiency is causing type III, yet reduced HOGA1 expression or aberrant subcellular protein targeting is unlikely to be the responsible pathomechanism. Our results strongly suggest HOGA1 as a major cause of PH, indicate a greater genetic heterogeneity of hyperoxaluria, and point to a favorable outcome of type III in the context of PH despite incomplete or absent biochemical remission. Multiallelic inheritance could have implications for genetic testing strategies and might represent an unrecognized mechanism for phenotype variability in PH.


Induced hypersensitivity to barbital in the female rat.
Female rats, treated with two daily anesthetic doses of barbital, exhibit 1 month later a significant increase in sleeping time over that of control animals. Hypersensitive animals, as compared to controls, show no alteration in liver weight (as percentage of body weight), but they manifest a significant shortening of time for induction of anesthesia. Induced hypersensitivity to barbiturates is apparently not the result of alterations in the metabolism of these agents, but it may be related to enhanced susceptibility of the central nervous system to these drugs.


Diode laser assisted excision of a gingival pyogenic granuloma: A case report.
Pyogenic granuloma is a non-neoplastic, exuberant, reactive lesion seen in response to local irritation or trauma caused by dental calculus, bacterial plaque, caries and restorations, with a strong predilection for the gingiva. It is among the frequently encountered oral lesions, occurring at a challenging oral site, the gingiva. Herein, we report a 71-year-old medically compromised Caucasian female who presented with a relatively large lobulated pyogenic granuloma on the buccal gingiva of the maxillary molar-premolar region. Total surgical excision was performed with an 840nm diode laser followed by the placement of hyaluronate gel and relevant periodontal dressing. Two weeks after surgical excision, complete healing was observed, but patient denied replacement of dental restoration. After 4 months of follow-up, an overall reduction of associated teeth mobility was also observed, with a minor recurrence in gingival inflammation. The objective of this report is to briefly review clinical, radiographic and histological findings of pyogenic granuloma along with a detailed discussion on its management through a diode laser.


Predicting local cell deformations in engineered tissue constructs: a multilevel finite element approach.
A multilevel finite element approach is applied to predict local cell deformations in engineered tissue constructs. Cell deformations are predicted from detailed nonlinear FE analysis of the microstructure, consisting of an arrangement of cells embedded in matrix material. Effective macroscopic tissue behavior is derived by a computational homogenization procedure. To illustrate this approach, we simulated the compression of a skeletal muscle tissue construct and studied the influence of microstructural heterogeneity on local cell deformations. Results show that heterogeneity has a profound impact on local cell deformations, which highly exceed macroscopic deformations. Moreover, microstructural heterogeneity and the presence of neighboring cells leads to complex cell shapes and causes non-uniform deformations within a cell.


Association between swallowing disorder and prevertebral hyperintensity on magnetic resonance imaging in patients after cervical cord injury without major fracture.
This study aimed to clarify the association between swallowing disorder and prevertebral hyperintensity on magnetic resonance imaging (MRI) in patients with cervical spinal cord injury (CSCI) without a major fracture. This retrospective observational study included 30 patients who were diagnosed with acute CSCI without a major fracture (mean age: 69.3 years, 27 men). Swallowing disorder was defined as tube-dependent nutrition because of obvious aspiration 28 days after injury. The high-intensity area (HIA) and anteroposterior width (HIW) of the prevertebral space at C1-7 levels were measured using MRI short-TI inversion recovery midsagittal images. Receiver operating characteristic curve analysis was used to determine the optimal cutoff values of the HIA for predicting swallowing disorder. The incidence of swallowing disorder after CSCI was 16.7%. The HIA was significantly higher in the swallowing disorder group (median, 409.0 mm2) than in the non- swallowing disorder group (median, 159.1 mm2) (P = .04). There was no significant difference in HIW between the two groups. The optimal cutoff point of the HIA was measured at 203.2 mm2 with 80.0% and 20.0% sensitivity and specificity, respectively, with an area under the curve of 0.848 (95% confidence interval, 0.657-1.000, P = .01). The prevertebral hyperintensity area on MRI for swallowing disorder in patients after cervical cord injury without skeletal injury is associated with swallowing disorder. The optimal cutoff point of the area was determined to be 203.2 mm2.


Serum triglyceride levels in newborns and mothers at parturition.
From August 1980 to March 1981, paired cord venous blood and maternal antecubital venous blood were measured for triglyceride concentrations with the enzymatic method of triglyceride G-3-PDH UV end point assay, using the Hitachi Model 716 autoanalyser. The mean value of cord serum triglyceride concentrations in the cohort of 100 normal newborns was 28 ng/100 ml and the cut-off point of P95 was 48 mg/100 ml. In normotriglyceridemic newborns and hypertriglyceridemic newborns the mean values were 29 mg/100 ml and 66 mg/100 ml, respectively. However, the mean values of the corresponding triglyceride concentrations of maternal blood were not remarkably different among these 3 groups; they ranged from 190 to 193 mg/100 ml. The cord blood triglyceride level was much lower than that of maternal blood levels, with a ratio of 15% in the cohort of normal population of newborns and mothers. These findings showed that the cord serum triglyceride level was independent of the maternal serum triglyceride concentration and was of fetal origin. The relative impermeability of the placenta to this serum constituent and the lack of utilization of fat as a major source of energy in the period of normal intrauterine fetal life may, in part, account for the low serum triglyceride level in cord blood.


Understanding students' perceptions of a high school course designed to enhance school connectedness.
This study was a part of an evaluation of a 4-year high school course to enhance students' school connectedness from freshman to senior year with primarily an Asian and Pacific Islander student body in Hawai'i. The purpose of this study was to understand how the course may impact students' sense of school connectedness and identify factors important in course effectiveness. Focus group guides were developed in collaboration with course instructors. Approximately 70 students from each grade level were randomly selected to participate in focus groups. All focus groups occurred during the 30-minute lunch period and lunch was provided. Focus groups conducted with 67 students revealed that students perceive teachers to play an essential role in the effectiveness of the course. Students also viewed the small class size and staying in the same class for all 4 years as important components in supporting the relationship-building aspect of the course, which enhances students' level of academic motivation and school involvement. Suggestions for ways that teachers can help build students' sense of school connectedness through the course included integrating their personal experiences into the lessons and facilitating more interactive discussions and team-building activities. Our findings suggest that students recognize the course as a valuable opportunity to build personal relationships that are essential to their sense of school connectedness. Schools should make more effort at incorporating strategies that build students' sense of school connectedness by providing relationship-building opportunities.


Effect of pulpal pressure on the microtensile bond strength of luting resin cements to human dentin.
The objectives of this study were to examine the effect of pulpal pressure on the microtensile bond strength (mTBS) of luting resin cements to human dentin and the permeability of dentin surfaces pre-treated with an adhesive and a self-etching primer. Cylindrical composite blocks were luted with resin cements (RelyX ARC, 3M ESPE: ARC; Panavia F, Kuraray Medical Inc.: PF; RelyX Unicem, 3M ESPE: UN) in the absence or presence of simulated pulpal pressure. The application of Adper Single Bond 2 (3M ESPE) and ED primer 2.0 (Kuraray) was performed under 0 cm H(2)O. After each resin cement was applied, the pulpal pressure group was subjected to 20 cm H(2)O of hydrostatic pressure for 10 min during the initial setting period. Testing for mTBS was performed on 0.9 mm x 0.9 mm sectioned beams after 24h water-storage. Scanning electron microscopy was performed to investigate the fractured surfaces after mTBS testing and additional dentin surfaces that were treated by an etchant, ED primer 2.0 and UN. Fluid permeability was measured on dentin surfaces that were applied with Adper Single Bond 2 and ED primer 2.0. Application of pulpal pressure reduced mTBS significantly in groups ARC and PF. Porous bonding interfaces due to water permeability through the cured adhesive were observed on fractured surfaces. Dentin surfaces that were applied with the adhesive and the primer were more permeable than smear layer-covered dentin. The mTBS of UN was significantly lower than ARC and PF regardless of the absence/presence of pulpal pressure. Fluid permeation during the initial setting period deteriorated the bonding quality of resin cements.


[Functional hearing loss in children].
The cases of children diagnosed with pseudohypacusis in the Department of Pediatric Otolaryngology were presented. Probable mechanism of its pathogenesis was described. The main stress was put on its correct diagnosis particularly in children with co-existing organic changes. Diagnosis of pseudohypacusis in children is not problematic provided that the occurence of this disease is taken into consideration during diagnostic procedures.


Phylogenetic and DNA-DNA hybridization analyses of Bradyrhizobium species.
The 16S rDNA sequence of Bradyrhizobium liaoningense was determined and analysed together with sequences of other Bradyrhizobium species and related taxa. In addition, DNA-DNA hybridizations were performed between representative strains of the three Bradyrhizobium species. Bradyrhizobium liaoningense is genotypically highly related to Bradyrhizobium japonicum, whereas Bradyrhizobium elkanii is more distantly related to these two species. The fact that Afipia, Agromonas, Blastobacter, Nitrobacter and Rhodopseudomonas are phylogenetically more closely related to Bradyrhizobium japonicum than to Bradyrhizobium elkanii is discussed.


A non-canonical promoter element drives spurious transcription of horizontally acquired bacterial genes.
RNA polymerases initiate transcription at DNA sequences called promoters. In bacteria, the best conserved promoter feature is the AT-rich -10 element; a sequence essential for DNA unwinding. Further elements, and gene regulatory proteins, are needed to recruit RNA polymerase to the -10 sequence. Hence, -10 elements cannot function in isolation. Many horizontally acquired genes also have a high AT-content. Consequently, sequences that resemble the -10 element occur frequently. As a result, foreign genes are predisposed to spurious transcription. However, it is not clear how RNA polymerase initially recognizes such sequences. Here, we identify a non-canonical promoter element that plays a key role. The sequence, itself a short AT-tract, resides 5 base pairs upstream of otherwise cryptic -10 elements. The AT-tract alters DNA conformation and enhances contacts between the DNA backbone and RNA polymerase.


Lateral external fixation--a new surgical technique for displaced unreducible supracondylar humeral fractures in children.
Percutaneous Kirschner wire fixation represents the classic treatment for displaced supracondylar humeral fractures in childhood. This type of treatment first requires satisfactory reduction of the fracture. Failure to achieve a satisfactory reduction or inadequate stabilization can result in instability of the fracture fragments, which can result in either an unsatisfactory cosmetic or functional outcome. In our experience, these problems can be overcome with the use of a small lateral external fixator. Between 1999 and 2005, thirty-one of 170 Gartland type-III supracondylar humeral fractures were treated with a lateral external fixator. The outcome of treatment was analyzed with regard to limb alignment, elbow movement, cosmetic appearance, and patient satisfaction. In twenty-eight of the thirty-one patients, a satisfactory reduction was achieved with closed methods. All children except one had a normal or good range of movement. The cosmetic result was excellent in all cases. All of the children and their parents stated that they would choose this treatment again. The use of a small lateral external fixator seems to be a safe alternative for the treatment of displaced supracondylar fractures of the humerus when a closed reduction appears to be unattainable by means of manipulation alone or when sufficient stability is not achieved with standard methods of Kirschner wire fixation.


Population structure and molecular genetic characterization of 5-flucytosine-susceptible and -resistant clinical Candida dubliniensis isolates from Kuwait.
Candida dubliniensis and Candida albicans are two closely related species. Although C. dubliniensis is less pathogenic, it has a higher propensity to develop resistance to fluconazole and some strains exhibit intrinsic resistance to 5-flucytosine (5-FC). All 5-FC-resistant isolates from Kuwait were previously shown to belong to one of seven internal transcribed spacer (ITS) region of rDNA-based haplotypes. This study performed fingerprinting of C. dubliniensis isolates by multilocus sequence typing (MLST) to determine population structure of 5-FC-resistant and -susceptible strains and compared the results with data from a global collection of isolates. Fifty-two C. dubliniensis isolates previously analyzed and 58 additional isolates mostly collected during 2010-2013 and characterized by phenotypic and molecular methods were used. ITS-based haplotypes were identified by haplotype-specific PCR and/or by PCR-DNA sequencing of rDNA. Population structure was determined by 8-loci-based MLST. E-test was used to determine susceptibility to 5-FC, fluconazole, voriconazole and amphotericin B. Five ITS haplotypes (ITSH) were detected among 110 C. dubliniensis isolates. The ITSH1 was most common (n = 80 isolates) followed by ITSH4 (n = 25 isolates). Two isolates each belonged to ITSH5 and ITSH8 while one isolate belonged to ITSH7. MLST identified 16 diploid sequence types (DSTs) including six new DSTs. DST11 (n = 52) and DST14 (n = 25) were dominant genotypes and were confined (together with DST21) to Middle-Eastern countries. Other DSTs (excluding some new DSTs) had a wider global distribution as they were identified from various other countries. Only ITSH4 isolates (n = 25) belonged to DST14, were resistant to 5-FC and contained S29L mutation in CdFCA1. ITSH5, ITSH7 and ITSH8 isolates belonged to different DSTs. Thus, clinical C. dubliniensis isolates in Kuwait exhibited limited genotypic heterogeneity and most isolates belonged to region-specific DSTs. All 5-FC-resistant C. dubliniensis isolates belonged to ITSH4 and MLST-based DST14 genotype. Placement of some isolates into additional ITS haplotypes is also supported by MLST data.


In silico prediction of chemical aquatic toxicity for marine crustaceans via machine learning.
Aquatic toxicity is a crucial endpoint for evaluating chemically adverse effects on ecosystems. Therefore, we developed in silico methods for the prediction of chemical aquatic toxicity in marine environment. At first, a diverse data set including different crustacean species was constructed. We then built local binary models using Mysidae data and global binary models using Mysidae, Palaemonidae, and Penaeidae data. Molecular fingerprints and descriptors were employed to represent chemical structures separately. All the models were built by six machine learning methods. The AUC (area under the receiver operating characteristic curve) values of the better local and global models were around 0.8 and 0.9 for the test sets, respectively. We also identified several chemicals with selective toxicity on different species. The analysis of selective toxicity would promote to design greener chemicals in a specific environment. Finally, to understand and interpret the models, we explored the relationships between chemical aquatic toxicity and the molecular descriptors. Our study would be helpful in gaining further insights into marine organisms, prediction of chemical aquatic toxicity and prioritization of environmental hazard assessment.


IMMUNOLOGY: Enhanced: Thymic Regulation-Hidden in Plain Sight.
The thymus is the nursery where T cell precursors mature into T cells of the and lineages. In a Perspective, Rothenberg discusses intriguing findings that reveal a new level of regulation in the thymus (Silva-Santos et al.). Apparently, double-positive T cells that are destined to mature into T cells directly regulate the development of the T-cell lineage through the production of lymphotoxin and the action of a transcription factor called RORt.


mrpA, a gene with roles in resistance to Na+ and adaptation to alkaline pH in the cyanobacterium Anabaena sp. PCC7120.
Transposon mutagenesis of Anabaena sp. PCC7120 led to the isolation of a mutant strain, PHB11, which grew poorly at pH values above 10. The mutant strain exhibited pronounced Na+ sensitivity; this sensitivity was higher under basic conditions. Mutant PHB11 also showed an inhibition of photosynthesis that was much more pronounced at alkaline pH. Reconstruction of the transposon mutation of PHB11 in the wild-type strain reproduced the phenotype of the original mutant. The wild-type version of the mutated gene was cloned and the mutation complemented. In mutant strain PHB11, the transposon had inserted within an ORF that is part of a seven-ORF operon with significant sequence similarity to a family of bacterial operons that are believed to code for a novel multiprotein cation/proton antiporter primarily involved in resistance to salt stress and adaptation to alkaline pH. The Anabaena operon was denoted mrp (multiple resistance and pH adaptation) following the nomenclature of the Bacillus subtilis operon; the ORF mutated in PHB11 corresponded to mrpA. Computer analysis suggested that all seven predicted Anabaena Mrp proteins were highly hydrophobic with several transmembrane domains; in fact, the predicted protein sequences encoded by mrpA, mrpB and mrpC showed significant similarity to hydrophobic subunits of the proton pumping NADH : ubiquinone oxidoreductase. In vivo expression studies indicated that mrpA is induced with increasing external Na+ concentrations and alkaline pH; mrpA is also upregulated under inorganic carbon (Ci) limitation. The biological significance of a putative cyanobacterial Mrp complex is discussed.


Is magnetic resonance imaging reliable in predicting clinical outcome after articular cartilage repair of the knee? A systematic review and meta-analysis.
While MRI can provide a detailed morphological evaluation after articular cartilage repair, its additional value in determining clinical outcome has yet to be determined. To evaluate the correlation between MRI and clinical outcome after cartilage repair and to identify parameters that are most important in determining clinical outcome. Systematic review and meta-analysis. A systematic search was performed in Embase, MEDLINE, and the Cochrane Collaboration. Articles were screened for relevance and appraised for quality. Guidelines in the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) Statement were used. Chi-square tests were performed to find variables that could determine correlation between clinical and radiological parameters. A total of 32 articles (total number of patients, 1019) were included. A majority (81%) were case series or cohort studies that used similar standardized MRI techniques. The mean Coleman score was 63 (range, 42-96). For the majority of MRI parameters, limited or no correlation was found. Nine studies (28%) found a correlation between clinical outcome and the composite magnetic resonance observation of cartilage repair tissue (MOCART) or Henderson score and 7 (22%) with defect fill. In 5 studies, a weak to moderate correlation was found between clinical outcome and the T2 index (mean Pearson coefficient r = .53). Strong evidence to determine whether morphological MRI is reliable in predicting clinical outcome after cartilage repair is lacking. Future research aiming specifically at clinical sensitivity of advanced morphological and biochemical MRI techniques after articular cartilage repair could be of great importance to the field.


Dysphagia: its nature, assessment and management.
Dysphagia impacts on the health and quality of life of individuals and contributes to the cost of health care. This paper summarises current literature regarding the nature, assessment and management of acquired oro-pharyngeal dysphagia in older adults. It examines the aetiology, prevalence and consequences of dysphagia, as well as issues regarding medication administration. Assessment of dysphagia is explored in terms of multidisciplinary screening, speech and language therapist clinical swallowing evaluation and instrumental assessment.


Combining Structured and Unstructured Data for Predicting Risk of Readmission for Heart Failure Patients.
Researchers have studied many models for predicting the risk of readmission for heart failure over the last decade. Most models have used a parametric statistical approach while a few have ventured into using machine learning methods such as statistical natural language processing. We created three predictive models by combining these two techniques for the cohort of 1,629 patients from six hosptials using structured data along with their 136,963 clinical notes till their index admission, stored in the EMR system over five years. The AUCs for structured and combined models were very close (0.6494 and 0.6447) and that for the unstructured model was 0.5219. The clinical impact of the models using decision curve analysis showed that, at a threshold predicted probability of 0.20, the combined model offered 15%, 30%, and 70% net benefit over its individual counterparts, treat-all, and treat-none strategy respectively.


Subtle cavus foot: diagnosis and management.
The subtle cavovarus foot (SCF) is a mild malalignment caused by either primary hindfoot varus or a plantarflexed first ray, resulting in a typical constellation of symptoms because of altered foot mechanics. Key clinical signs are a peek-a-boo heel and a positive Coleman block test. The cavovarus position places lateral ankle soft-tissue structures, such as the anterior talofibular ligament and the peroneal tendons, on stretch during normal gait. This can lead to common conditions such as lateral ankle instability, peroneal tendon tears, and stress fractures of the lateral metatarsals and cuboid. The gait cycle is altered because a greater proportion of time is spent with the transverse tarsal joints locked due to the overall varus foot position. In contradistinction to physiologic valgus at heel strike, which maintains the transverse tarsal joints unlocked and affords approximately 50% force dissipation, the increased rigidity of the foot causes a maldistribution of forces that leads to accelerated wear of the midfoot joints and increased stresses along the plantar fascia and the Achilles tendon insertion. Successful nonsurgical management requires correction of the biomechanical anomaly; surgical management of a subtle cavovarus foot typically is part of a comprehensive plan for correcting the symptoms and the malalignment.


Water, sanitation and hygiene survey - Use of hydrogen sulfide strip at field level as a point-of-care test: A pilot study.
Safe drinking water is a basic element of primary health care. The government of India in its Indian Public Health Standards recommends the hydrogen sulfide (H2S) strip test as a desirable component at primary health centers for screening water for fecal coliforms. The objective of the present study was to conduct a water, sanitation and hygiene (WASH) survey followed by a H2S strip test of drinking water in a village with ninety households. The test was positive in 88% at the source and the point of consumption, with 100% concordance between both the points of test. A subsample of water samples was subjected to testing in microbiology laboratory, and fecal contamination was confirmed in all of them. To conclude, H2S strip test can be conveniently used at field level, and its ease of use and visual nature of results make it a useful point-of-care test of environmental and public health.


Reduced striatal dopamine D2/3 receptor availability in Body Dysmorphic Disorder.
Though the dopaminergic system is implicated in Obsessive Compulsive and Related Disorders (OCRD), the dopaminergic system has never been investigated in-vivo in Body Dysmorphic Disorder (BDD). In line with consistent findings of reduced striatal dopamine D2/3 receptor availability in Obsessive Compulsive Disorder (OCD), we hypothesized that the dopamine D2/3 receptor availability in the striatum will be lower in patients with BDD in comparison to healthy subjects. Striatal dopamine D2/3 receptor Binding Potential (BPND) was examined in 12 drug-free BDD patients and 12 control subjects pairwise matched by age, sex, and handedness using [(123)I]iodobenzamide Single Photon Emission Computed Tomography (SPECT; bolus/constant infusion technique). Regions of interest were the caudate nucleus and the putamen. BPND was calculated as the ratio of specific striatal to binding in the occipital cortex (representing nonspecific binding). Compared to controls, dopamine D2/3 receptor BPND was significantly lower in BDD, both in the putamen (p=0.017) and caudate nucleus (p=0.022). This study provides the first evidence of a disturbed dopaminergic system in BDD patients. Although previously BDD was classified as a separate disorder (somatoform disorder), our findings give pathophysiological support for the recent reclassification of BDD to the OCRD in DSM-5.


Usefulness of allogeneic hematopoietic stem cell transplantation in first complete remission for pediatric blastic plasmacytoid dendritic cell neoplasm with skin involvement: a case report and review of literature.
No standard treatment has been established in childhood blastic plasmacytoid dendritic cell neoplasma (BPDCN) because of its rarity. We treated with acute lymphoblastic leukemia-type regimen for a child with BPDCN with skin and leukemic involvement. She has been disease-free for 4 years after allogeneic bone marrow transplantation in first complete remission. In 33 cases of pediatric BPDCN, the over survival was significantly lower in the patients with skin manifestation than those without cutaneous involvement. Accordingly, it is important to determine whether allogeneic hematopoietic stem cell transplantation should be applied to first complete remission in the patients with poor prognosis.


Phytate-phosphorus and phytase on performance, bone characteristics, tissue and serum mineral concentration on broilers.
Male broiler chickens (384), Cobb 500, were housed in metabolic cages to assess the efficacy of phytase in diets with low and high phytate-phosphorus on the performance, bone physical characteristics, tissue and serum mineral deposits. Birds were distributed in four treatments with a 2 x 2 factorial arrangement in a completely randomized block design. Experimental diets based on maize-soybean meal were T1 - diet low phytate-phosphorus; T2 - diet low phytate-phosphorus and phytase (500 FTU/kg); T3 - diet high phytate-phosphorus; T4 - diet high phytate-phosphorus and phytase (500 FTU/kg). Feed intake, body weight, weight gain and feed conversion ratio were assessed. Two left tibias per experimental unit were analyzed for physical characteristics and mineral concentration; a section of skinless breast muscle and blood were collected to measure the concentration of calcium, phosphorus and sodium. Results showed interaction between bone stiffness and serum calcium. The inclusion of phytase in diets with low and high phytate-phosphorus did not alter performance, bone resistance and flexibility, mineral deposits in the tibia and breast muscle, but increased bone stiffness after 22 days of age. It also provided a higher serum calcium rate in broilers fed diets with low phytate-phosphorus up to 32 days of age.


Muscle atrophy in chronic obstructive pulmonary disease: molecular basis and potential therapeutic targets.
Patients with chronic obstructive pulmonary disease (COPD) experience several systemic manifestations such skeletal muscle dysfunction with and without muscle mass loss. Moreover, frequent comorbidities such as nutritional abnormalities, heart failure, and pulmonary hypertension, which are frequently associated with COPD may further contribute to skeletal muscle mass loss and dysfunction. Muscle dysfunction impairs the patients' exercise capacity and quality of life as daily life activities may be hampered by this problem. Importantly, impaired muscle function and mass loss have been shown to impact negatively on the patients' prognosis and survival in several studies. Thus, this is a major clinical problem that deserves special attention in clinical settings. During the course of exacerbations muscle mass loss takes place, hence aggravating muscle status and performance even after hospital discharge, especially in the frequently exacerbator patients. Several factors and biological mechanisms are involved in the etiology of COPD muscle dysfunction. The biological mechanisms identified so far offer a niche for therapeutic interventions in the patients. In the current review, a general overview of the most relevant etiologic factors and their target biological mechanisms through which muscle mass loss and dysfunction take place in both the respiratory and lower limb muscles in COPD patients is provided. We conclude that more clinical research is still needed targeted to test several therapeutic interventions. Given its prognostic value, the assessment of skeletal muscle dysfunction should be included in the routine evaluation of patients with chronic respiratory disorders and in critical care settings.


Pediatric islet autotransplantation: indication, technique, and outcome.
Chronic pancreatitis is a rare disease in childhood. However, when severe, a total pancreatectomy may be the only option to relieve pain and restore quality of life. An islet autotransplant performed at the time of pancreatectomy can prevent or minimize the postsurgical diabetes that would otherwise result from pancreatectomy alone. In this procedure, the resected pancreas is mechanically disrupted and enzymatically digested to separate the islets from the surrounding exocrine tissue, and the isolated islets are infused into the portal vein and engraft in the liver. Because patients are receiving their own tissue, no immunosuppression is required. Islet autotransplant is successful in two thirds of children-these patients are insulin independent or require little insulin to maintain euglycemia. Factors associated with a more successful outcome include a younger age at transplant (<13 years), more islets transplanted, and lack of prior surgical procedures on the pancreas (partial pancreatectomy or surgical drainage procedures).


The cost of asthma: can it be reduced?
Asthma is a major public health problem in developed countries, where it consumes a large and increasing share of scarce health resources. Ideally, medical management should be both optimal in terms of improving the patient's quality of life, and cost-effective for society. At present, there is very little information relating to costs and economic efficiency of current asthma management. Although the true total cost of asthma is unknown, current estimates suggest it is high. The main value of recent total cost estimates is that they identify the most expensive areas of asthma costs, and ideally, formal cost-effectiveness analyses should be concentrated on these areas. Asthma is still under- or inappropriately diagnosed, and undertreated. Several national and international consensus plans for the optimal management of asthma in children and adults have been published. If these inadequacies in asthma management were corrected, using current treatment recommendations, the overall cost of asthma from both the community and patient perspective should fall. The situation requires increased use of preventative medications {sodium cromoglycate (cromolyn sodium) or inhaled corticosteroids}, more widespread use of written crisis plans, more proactive medical consultations (rather than reactive or urgent consultations), further expansion of asthma education programmes, and further education of medical practitioners about the optimum management of both long term asthma and the acute exacerbation of asthma in the patient's home, the doctor's office, the hospital emergency room and the hospital inpatient setting. The increased costs associated with these measures would be more than offset by reduced expenditure on bronchodilator drugs, less widespread use of nebulisers at home and in hospitals, reduced antibiotic usage, reduced need for expensive emergency medical care and particularly reduced utilisation of hospital resources. To ensure that resources are being directed into the most cost-effective areas of asthma care, clinical trials of asthma should include utilisation of healthcare resources as an outcome measure, and estimates of the costs of the treatment under study. In addition, since the intangible cost (quality of life) is one of the most important effects of treatment from the patient's perspective, this should be more widely used as an outcome measure in clinical trials. Ultimately, prevention of asthma is the long term goal. If the hypothesis that sensitisation to house dust mite in early infancy is a major contributor to the subsequent development of asthma, then prevention may require drastic and expensive changes to current housing.


Career burnout among pediatric oncologists.
Burnout is a work-related syndrome consisting of emotional exhaustion, depersonalization, and diminished feelings of personal accomplishment. Physicians who care for patients with life-threatening illnesses are at high risk for developing burnout. This survey evaluates the prevalence of burnout among pediatric oncologists, and assesses risk factors associated with the development of burnout. A questionnaire was sent via email to 1,047 practicing pediatric oncologists. The survey included the 22 question Maslach Burnout Inventory (MBI), as well as questions regarding work-related and lifestyle-related factors associated with developing burnout. Four hundred ten pediatric oncologists (40%) responded to the survey. Thirty-eight percent of pediatric oncologists had high levels of burnout on the MBI, while 72% had at least moderate levels of burnout. Women (47% vs. 32%, P < 0.004) and physicians practicing for <10 years (50% vs. 33%, P < 0.004) had significantly higher rates of burnout. Physicians who reported satisfaction with their lives outside of work were less likely to have burnout (odds ratio 0.238, 0.143-0.396, P < 0.001). The availability of a forum for debriefing, and services for physicians affected by burnout were both associated with lower rates of burnout (24% vs. 46%, P < 0.001 and 23% vs. 46%, P < 0.001). Thirty-six percent of respondents reported their institution has a forum for debriefing and 40% of respondents reported their institution has services available for physicians experiencing symptoms of burnout. Approximately three quarters of pediatric oncologists experience burnout. Further research is needed on the effectiveness of interventions aimed at preventing and treating work-related burnout.


Do Genetic Markers of Inflammation Modify the Relationship between Periodontitis and Nonalcoholic Fatty Liver Disease? Findings from the SHIP Study.
An association between periodontitis and nonalcoholic fatty liver disease (NAFLD) has been reported by experimental animal and epidemiologic studies. This study investigated whether circulating levels of serum C-reactive protein (CRP) and a weighted genetic CRP score representing markers of inflammatory burden modify the association between periodontitis and NAFLD. Data came from 2,481 participants of the Study of Health in Pomerania who attended baseline examination that occurred between 1997 and 2001. Periodontitis was defined as the percentage of sites (0%, <30%, ≥30%) with probing pocket depth (PD) ≥4 mm, and NAFLD status was determined using liver ultrasound assessment. Serum CRP levels were assayed at a central laboratory, and single-nucleotide polymorphisms previously identified through genome-wide association studies as robustly associated with serum CRP were combined into a weighted genetic CRP score (wGSCRP). Logistic regression models estimated the association between periodontitis and NAFLD within strata of serum CRP and separately within strata of the wGSCRP. The prevalence of NAFLD was 26.4% (95% confidence interval [CI], 24.6, 28.1) while 17.8% (95% CI, 16.0-19.6) had ≥30% of sites with PD ≥4 mm. Whereas the wGSCRP was not a modifier ( Pinteraction = 0.8) on the multiplicative scale, serum CRP modified the relationship between periodontitis and NAFLD ( Pinteraction = 0.01). The covariate-adjusted prevalence odds ratio of NAFLD comparing participants with ≥30% of sites with PD ≥4 mm to those with no site affected was 2.39 (95% CI, 1.32-4.31) among participants with serum CRP <1 mg/L. The corresponding estimate was 0.97 (95% CI, 0.57-1.66) for participants with serum CRP levels of 1 to 3 mg/L and 1.12 (95% CI, 0.65-1.93) for participants with serum CRP >3 mg/L. Periodontitis was positively associated with higher prevalence odds of NAFLD, and this relationship was modified by serum CRP levels.


Obinutuzumab plus chlorambucil in patients with CLL and coexisting conditions.
The monoclonal anti-CD20 antibody rituximab, combined with chemotherapeutic agents, has been shown to prolong overall survival in physically fit patients with previously untreated chronic lymphocytic leukemia (CLL) but not in those with coexisting conditions. We investigated the benefit of the type 2, glycoengineered antibody obinutuzumab (also known as GA101) as compared with that of rituximab, each combined with chlorambucil, in patients with previously untreated CLL and coexisting conditions. We randomly assigned 781 patients with previously untreated CLL and a score higher than 6 on the Cumulative Illness Rating Scale (CIRS) (range, 0 to 56, with higher scores indicating worse health status) or an estimated creatinine clearance of 30 to 69 ml per minute to receive chlorambucil, obinutuzumab plus chlorambucil, or rituximab plus chlorambucil. The primary end point was investigator-assessed progression-free survival. The patients had a median age of 73 years, creatinine clearance of 62 ml per minute, and CIRS score of 8 at baseline. Treatment with obinutuzumab-chlorambucil or rituximab-chlorambucil, as compared with chlorambucil monotherapy, increased response rates and prolonged progression-free survival (median progression-free survival, 26.7 months with obinutuzumab-chlorambucil vs. 11.1 months with chlorambucil alone; hazard ratio for progression or death, 0.18; 95% confidence interval [CI], 0.13 to 0.24; P<0.001; and 16.3 months with rituximab-chlorambucil vs. 11.1 months with chlorambucil alone; hazard ratio, 0.44; 95% CI, 0.34 to 0.57; P<0.001). Treatment with obinutuzumab-chlorambucil, as compared with chlorambucil alone, prolonged overall survival (hazard ratio for death, 0.41; 95% CI, 0.23 to 0.74; P=0.002). Treatment with obinutuzumab-chlorambucil, as compared with rituximab-chlorambucil, resulted in prolongation of progression-free survival (hazard ratio, 0.39; 95% CI, 0.31 to 0.49; P<0.001) and higher rates of complete response (20.7% vs. 7.0%) and molecular response. Infusion-related reactions and neutropenia were more common with obinutuzumab-chlorambucil than with rituximab-chlorambucil, but the risk of infection was not increased. Combining an anti-CD20 antibody with chemotherapy improved outcomes in patients with CLL and coexisting conditions. In this patient population, obinutuzumab was superior to rituximab when each was combined with chlorambucil. (Funded by F. Hoffmann-La Roche; ClinicalTrials.gov number, NCT01010061.).


Inhibition of phosphatidylcholine synthesis in mammary tissue by 2-chloroethyltrimethylammonium chloride.
The incorporation of choline into phosphatidylcholine in mammary tissue from lactating cows is impeded by 2-chloroethyltrimethylammonium chloride at concentrations ranging from 0.3 to 9mm. This compound is a non-competitive inhibitor of choline kinase (K(m) 0.25mm), having K(i) 17mm. It is suggested that 2-chloroethyltrimethylammonium chloride may inhibit choline entry into the tissue.


Eating patterns of Turkish adolescents: a cross-sectional survey.
Adolescence is a crucial period for development of dietary behaviors that continue into adulthood and influence the risk of chronic diseases later in life. The aim of this study was to determine the eating patterns of adolescents' and their compliance with the Food Guide Pyramid. 625 students, aged between 11-15 years, from an elementary school in Istanbul, Turkey were enrolled in this cross-sectional survey. A questionnaire of eating patterns (QEP) was administered to all participants. QEP is consisted of questions assessing the knowledge and behaviors on healthy eating, factors affecting food choice, physical activity status and demographical variables. Height and weight of all participants were measured. Physical activity status was determined by questioning about participation in regular sport activities, how much time spent watching TV, playing computer games or doing homework. The mean age of the participants was 12.15 ± 1.15 and 50.5% were female. According to body mass index (BMI) percentiles, 8.3% (52) were obese and 10.2% were overweight. 51% had breakfast every day and only 1.9% met all the recommendations of the Food Guide Pyramid. Among the participants, 31% have fast food at least once every day and 60.8% skip meals. When participants were asked to rate the factors effecting their food choice according to a 10 point Likert scale, the highest mean scores (high impact on food choice) were for the factors; family, health, body perception, teachers and friends; 7.5 ± 3.1, 7.4 ± 3.1, 6.1 ± 3.2, 4.8 ± 3.3 and 4.2 ± 3.0 respectively. Total mean time spent on all passive activities (TV, computer, reading homework etc) per day was 9.8 ± 4.7 hours. In this study we have demonstrated that, adolescents do not have healthy eating patterns. Educational interventions should be planned to decrease the health risks attributable to their eating behaviors.


Similarities and differences in the nutritional composition of nuts and seeds in Serbia.
Nuts and seeds are an indispensable part of the plant-based diet, which is becoming increasingly popular due to the evidence of their health benefits and contribution to sustainability and planetary health. Since the health effects of consuming nuts and seeds directly depend on their nutritional composition and consumed amount, it is essential to know the exact chemical composition of each nut and seed so that appropriate dietary interventions can be adequately planned. The present study aimed to examine the chemical composition of nuts and seeds obtained from the Serbian market and to highlight the similarities and differences in their nutritional composition. In twenty-four samples of nuts and seeds, the content of total lipids, including fatty acid profile, total proteins, including amino acid profile, total carbohydrates (sugars and fibers), phytosterols, and minerals were determined. Content of selected nutrients in grams (g) or milligrams (mg) of nuts and seeds was expressed in one portion (28 g) and as a percentage of contribution of Reference Intakes (% RI) and Dietary Reference Value (% DRV) for macronutrients and minerals, respectively. Some of the seed representatives appeared to be rich sources of essential omega-3 fatty acid, α-linolenic acid (ALA) (flax seed vs. walnut, 6.50 vs. 0.56 g per portion, respectively), dietary fibers (chia seed vs. raw almond, 10.6 vs. 3.4 g per portion, respectively), calcium (black sesame seed vs. almond roasted, 32.4% NRV vs. 8.1% NRV per portion, respectively), magnesium (hemp seed vs. Brazil nut, 38.3% NRV vs. 27.8% NRV per portion, respectively), and zinc (hemp seed vs. pine nut, 21.4% NRV vs. 17.6% NRV per portion, respectively). Our results highlighted the crucial role of seeds in the diet, especially as a better source of nutrients compared to nuts. Furthermore, it was seen that nuts and seeds are different and complementary in their composition. Thus, in order to meet the needs for certain nutrients for which nuts and seeds are used as dietary sources (essential fatty acids, minerals, dietary fibers), it would be beneficial to combine both nuts and seeds as a part of a healthy dietary pattern.


Grapevine Red Blotch-Associated Virus, an Emerging Threat to the Grapevine Industry.
Grapevine red blotch-associated virus (GRBaV) is a newly identified virus of grapevines and a putative member of a new genus within the family Geminiviridae. This virus is associated with red blotch disease that was first reported in California in 2008. It affects the profitability of vineyards by substantially reducing fruit quality and ripening. In red-berried grapevine cultivars, foliar disease symptoms consist of red blotches early in the season that can expand and coalesce across most of the leaf blade later in the season. In white-berried grapevine cultivars, foliar disease symptoms are less conspicuous and generally involve irregular chlorotic areas that may become necrotic late in the season. Determining the GRBaV genome sequence yielded critical information for the design of primers for polymerase chain reaction-based diagnostics. To date, GRBaV has been reported in the major grape-growing areas in North America and two distinct phylogenetic clades have been described. Spread of GRBaV is suspected in certain vineyards but a vector of epidemiological significance has yet to be identified. Future research will need to focus on virus spread, the production of clean planting stocks, and the development of management options that are effective, economical, and environmentally friendly.


Reliability of 3D Lower Extremity Movement Analysis by Means of Inertial Sensor Technology during Transitional Tasks.
This study assesses the reliability and agreement of trunk and lower limb joints' 3D kinematics, measured by inertial measurement units, during walking and more demanding movement tasks. For data analysis, tasks were divided in open and closed chain phases. Twenty healthy participants were included. On day one, measurements were conducted by "Operator 1" and "Operator 2" to determine between-operator reliability/agreement. On day two, the measurements were conducted by Operator 1, in order to determine within-session reliability/agreement. Furthermore, between-session reliability/agreement was assessed based on data from Operator 1, captured on day one and two. Within-session reliability/agreement was high, and better than between-session and between-operator results for all tasks. The results for walking were generally better than for other movement tasks, for all joint kinematics, and for both open and closed chain phases. Only for the ab/adduction and flexion/extension angles during forward and sideward lunge, reliability and agreement results were comparable to walking, for both the open and closed chain phases. The fact that lunges show similar reliability results than walking for open and closed chain phases, but require more motor control to perform, indicates that the performance of lunges might be interesting to use in further research aiming to identify kinematic differences between populations.


Promising bioprocesses for the efficient removal of antibiotics and antibiotic-resistance genes from urban and hospital wastewaters: Potentialities of aerobic granular systems.
The use, overuse, and improper use of antibiotics have resulted in higher levels of antibiotic-resistant bacteria (ARB) and antibiotic-resistance genes (ARGs), which have profoundly disturbed the equilibrium of the environment. Furthermore, once antibiotic agents are excreted in urine and feces, these substances often can reach wastewater treatment plants (WWTPs), in which improper treatments have been highlighted as the main reason for stronger dissemination of antibiotics, ARB, and ARGs to the receiving bodies. Hence, achieving better antibiotic removal capacities in WWTPs is proposed as an adequate approach to limit the spread of antibiotics, ARB, and ARGs into the environment. In this review, we highlight hospital wastewater (WW) as a critical hotspot for the dissemination of antibiotic resistance due to its high level of antibiotics and pathogens. Hence, monitoring the composition and structure of the bacterial communities related to hospital WW is a key factor in controlling the spread of ARGs. In addition, we discuss the advantages and drawbacks of the current biological WW treatments regarding the antibiotic-resistance phenomenon. Widely used conventional activated sludge technology has proved to be ineffective in mitigating the dissemination of ARB and ARGs to the environment. However, aerobic granular sludge (AGS) technology is a promising technology-with broad adaptability and excellent performance-that could successfully reduce antibiotics, ARB, and ARGs in the generated effluents. We also outline the main operational parameters involved in mitigating antibiotics, ARB, and ARGs in WWTPs. In this regard, WW operation under long hydraulic and solid retention times allows better removal of antibiotics, ARB, and ARGs independently of the WW technology employed. Finally, we address the current knowledge of the adsorption and degradation of antibiotics and their importance in removing ARB and ARGs. Notably, AGS can enhance the removal of antibiotics, ARB, and ARGs due to the complex microbial metabolism within the granular biomass.


Re-evaluation of the retention time prediction "polarity" model in the context of the development of a stationary phase variable.
The Abraham-Carr retention time prediction model was reviewed and developed in the context of the introduction of a new stationary phase variable. The new variable consists of a binary mixture dielectric constant and a stationary phase descriptor that was derived from the Snyder-Dolan column descriptors theory. In this work, data reported by Torres-Lapasio were investigated (in-silico) in the context of the linearity behavior of the Abraham-Carr theorem logk = f(PNm). This proposed model has been replaced by several experiments that have shown that the stationary phase constant PNS, which is represented by a variable, does not require laboratory experiments. The new model, which contains stationary and mobile phase variables, shows an improved correlation for the majority of the Torres-Lapasio compounds between Iogk and DeltaPN (mobile and stationary phase variables expression). The discussion regarding the model's behavior in the presence of secondary interactions led to research using a polar column and "bulky" compounds as reported by Szymański. Newly developed tacrine 4-fluorobenzoic acid derivatives, potential drugs in Alzheimer's disease treatment, are homologs and were found problematic to separate using regular C18 sorbent. The obtained results show that in the range of 30-70% acetonitrile, a single retention model using Agilent Zorbax SB-cyano sorbent is present, which is confirmed by two investigated models (R2 > 0.95).


The role of blood osmolality and volume in regulating vasopressin secretion in the rat.
A sensitive and specific radioimmunoassay for plasma arginine vasopressin (AVP) has been used to study the effects of blood osmolality and volume in regulating AVP secretion in unanesthetized rats. Under basal conditions, plasma AVP and osmolality were relatively constant, averaging 2.3+/-0.9 (SD) pg/ml and 294+/-1.4 mosmol/kg, respectively. Fluid restriction, which increased osmolality and decreased volume, resulted in a progressive rise in plasma AVP to about 10 times basal levels after 96 h. A 2-3-fold increase in plasma AVP occurred as early as 12 h, when osmolality and volume had each changed by less than 2%. Intraperitoneal injections of hypertonic saline, which had no effect on blood volume, also produced a rise in plasma AVP that was linearly correlated with the rise in osmolality (r > 0.9) and quantitatively similar to that found during fluid restriction (plasma AVP increased 2-4-fold with each 1% increase in osmolality). Intraperitoneal injection of polyethylene glycol, which decreased blood volume without altering osmolality, also increased plasma AVP but this response followed an exponential pattern and did not become significant until volume had decreased by 8% or more. At these levels of hypovolemia, the osmoregulatory system continued to function but showed a lower threshold and increase sensitivity to osmotic stimulation. We conclude that AVP secretion is regulated principally by blood osmolality but that the responsiveness of this mechanism may be significantly altered by modest changes in blood volume.


Validity of the Functional Loewenstein Occupational Therapy Cognitive Assessment (FLOTCA).
The Functional Loewenstein Occupational Therapy Cognitive Assessment (FLOTCA) was developed to assess integrative higher cognitive abilities in people with traumatic brain injury (TBI). The FLOTCA measures performance on three tasks: navigating on a map, organizing a toolbox, and planning a daily schedule. This study assessed the psychometric properties of the FLOTCA with a sample of 25 participants with TBI ages 18-49 and 25 matched healthy participants. The FLOTCA showed high interrater reliability (intraclass correlation = .996) and internal consistency reliability for the total score (α = .82). Construct validity was supported for the total score, t (48) = -5.48, d = 1.52, and the separate tasks. Moderate ecological validity was obtained with the combined FIM™ and Functional Assessment Measure, r (19) = .44, p < .05. The results indicate that the FLOTCA can be used to assess higher cognitive abilities in functioning and can serve as the basis for intervention planning.


Caenorhabditis elegans as a Model for Microbiome Research.
The nematode Caenorhabditis elegans is used as a central model system across biological disciplines. Surprisingly, almost all research with this worm is performed in the absence of its native microbiome, possibly affecting generality of the obtained results. In fact, the C. elegans microbiome had been unknown until recently. This review brings together results from the first three studies on C. elegans microbiomes, all published in 2016. Meta-analysis of the data demonstrates a considerable conservation in the composition of the microbial communities, despite the distinct geographical sample origins, study approaches, labs involved and perturbations during worm processing. The C. elegans microbiome is enriched and in some cases selective for distinct phylotypes compared to corresponding substrate samples (e.g., rotting fruits, decomposing plant matter, and compost soil). The dominant bacterial groups include several Gammaproteobacteria (Enterobacteriaceae, Pseudomonaceae, and Xanthomonodaceae) and Bacteroidetes (Sphingobacteriaceae, Weeksellaceae, Flavobacteriaceae). They are consistently joined by several rare putative keystone taxa like Acetobacteriaceae. The bacteria are able to enhance growth of nematode populations, as well as resistance to biotic and abiotic stressors, including high/low temperatures, osmotic stress, and pathogenic bacteria and fungi. The associated microbes thus appear to display a variety of effects beneficial for the worm. The characteristics of these effects, their relevance for C. elegans fitness, the presence of specific co-adaptations between microbiome members and the worm, and the molecular underpinnings of microbiome-host interactions represent promising areas of future research, for which the advantages of C. elegans as an experimental system should prove of particular value.


Effect of improvement in left ventricular ejection fraction on long-term survival in revascularized patients with ischaemic left ventricular systolic dysfunction.
The importance of improvement in the ejection fraction to the prognosis of revascularized patients with ischaemic left ventricular (LV) dysfunction is uncertain. Eighty-seven patients with ischaemic LV dysfunction (mean ejection fraction 29 ± 8% by biplane Simpson's) had dobutamine echocardiography before revascularization (coronary bypass graft surgery-81, percutaneous intervention-6). Follow-up echocardiograms were performed a mean of 4.8 ± 6.2 months after revascularization. An 8% increase in the ejection fraction was considered significant (two times the inter-observer difference of 3.7%). Patients were followed for cardiac death. During a mean follow-up of 5.2 ± 3.9 years, there were 20 (23%) cardiac deaths. Class 3/4 heart failure, increasing low-dose wall motion score, increasing % non-viable myocardium, and digoxin use in follow-up were univariate predictors of death. Beta-blocker use, ejection fraction improvement, angina, aspirin use, and increasing fractional shortening were univariate predictors of survival. Ejection fraction improvement [P= 0.02, hazard ratio (HR) = 0.26], digoxin use in follow-up (P= 0.006, HR = 5.85), and low-dose wall motion score (P= 0.017, HR = 4.78) were independent predictors of outcome. In step-wise analysis, low-dose wall motion score added incremental prognostic value to ejection fraction improvement (P= 0.003), and digoxin use in follow-up (P= 0.003) added incremental value to a low-dose score and ejection fraction improvement. Ejection fraction improvement is an independent predictor of long-term outcome in revascularized patients but viability (low-dose wall motion score) and digoxin use in follow-up are also independent predictors and add incremental prognostic value to ejection fraction improvement.


Human insulin and porcine insulin in the treatment of diabetic children: comparison of metabolic control and insulin antibody production.
Semisynthetic human insulin and highly purified porcine insulin were compared in a double blind crossover study in 21 diabetic children. Glycosylated haemoglobin values at the end of four month treatment periods were higher after treatment with human insulin than after treatment with porcine insulin (mean 15.7% (SD 2.3%) v 14.2% (2.3%); p less than 0.01). Higher fasting blood glucose concentrations occurred during treatment with human insulin than with porcine insulin (mean 12.0 (SD 2.1) v 11.0 (2.4) mmol/1; mean 216 (SD 38) v 198 (43) mg/100 ml; p less than 0.05), but there were no significant differences at other time points during the day. The incidence of hypoglycaemia was similar for both treatment groups. Concentrations of antibody reactive with porcine and human insulins were similar for the two treatment groups, although greater fluctuation was observed in the amount of antibody reactive with human insulin. Semisynthetic human insulin is safe and effective in diabetic children, although further work is needed to devise regimens which achieve optimal blood glucose control.


Functional genome annotation of Drosophila seminal fluid proteins using transcriptional genetic networks.
Predicting functional gene annotations remains a significant challenge, even in well-annotated genomes such as yeast and Drosophila. One promising, high-throughput method for gene annotation is to use correlated gene expression patterns to annotate target genes based on the known function of focal genes. The Drosophila melanogaster transcriptome varies genetically among wild-derived inbred lines, with strong genetic correlations among the transcripts. Here, we leveraged the genetic correlations in gene expression among known seminal fluid protein (SFP) genes and the rest of the genetically varying transcriptome to identify 176 novel candidate SFPs (cSFPs). We independently validated the correlation in gene expression between seven of the cSFPs and a known SFP gene, as well as expression in male reproductive tissues. We argue that this method can be extended to other systems for which information on genetic variation in gene expression is available.


Workforce re-entry for Japanese unemployed dental hygienists.
The aim of this study was to define the profile of unemployed dental hygienists who could be enticed to re-enter the workforce and the factors that could facilitate their re-entry into the dental field in Japan. The questionnaire was mailed with a postage-paid return envelope to a sample of 3095 licensed dental hygienists. A 50.4% response rate (S = 1477) was observed. The rate of working dental hygienists was 60.3% (n = 891), and of unemployed dental hygienists was 39.7% (n = 586). Of the latter, 31.9% (n = 187) stated intentions of returning to the workplace. The unemployed dental hygienists seeking employment were more often married and had more children, compared with working dental hygienists currently. This group also had significantly fewer total service years. Moreover, only 11.96% of them belonged to the Japan Dental Hygienists' Association, and 41.3% of those attended training workshops. According to their response, they perceived their top three major barriers to re-entry as 'lack sufficient dental hygiene skill', 'child rearing' and 'poor working atmosphere'. 'Flexibility in the work schedule' and 'location' were the most important factors for re-entry from their perspective. There were not many dental hygienists hoping to return to the dental field. The findings suggested that strategies to encourage non-practicing dental hygienists to re-entry should be emphasized in the areas of a flexible working atmosphere, easy access to information on how to return to practice and guidance on how to maintain professionalism during inactivity.


Piperine inhibits colorectal cancer migration and invasion by regulating STAT3/Snail-mediated epithelial-mesenchymal transition.
Cancer metastasis is the primary cause of death in patients diagnosed with colorectal cancer. Piperine, an active nontoxic ingredient in pepper, has potent anti-inflammatory and anti-cancer properties. However, little is known about the anti-migratory and anti-invasive effects of piperine on colorectal cancer. We demonstrated piperine inhibited the migration and invasion of colorectal cancer cells. Then, we found piperine reversed the biomarker expression of epithelial-to-mesenchymal transition (EMT), and suppressed the EMT regulator Snail. Furthermore, signal transducers and activators of transcription 3 (STAT3) was downregulated by piperine. Finally, STAT3 inhibitors were applied to observe the role of STAT3 in colorectal cancer migration, invasion and EMT. Collectively, piperine inhibits colorectal cancer migratory and invasive capacities through STAT3/Snail mediated EMT. Therefore, piperine could be applied as a possible therapeutic regimen for the prevention of colorectal cancer metastasis.


Single-cell transcriptomics reveals peripheral immune responses in non-segmental vitiligo.
Vitiligo is a common autoimmune depigmented dermatology due to destruction of melanocytes. Much evidence suggests that vitiligo is associated with systemic immune activation. Previous studies have focused on immune cell infiltration in and around lesion areas, but few studies have investigated the cell types and function of circulating immune cells in peripheral blood. Here, single cell RNA-sequencing (scRNA-seq) was used to investigate the mechanisms of peripheral immune responses in vitiligo patients. Peripheral blood was collected from five patients with progressive non-segmental vitiligo and three healthy controls. Peripheral blood mononuclear cells (PBMCs) were obtained by Ficoll-Paque density gradient centrifugation, and scRNA-seq was performed on isolated cell populations to obtain single cell transcriptomes and characterize important genes and intracellular signaling pathways. The key findings were validated with qPCR and flow cytometry assays. We identified 10 major cell types by scRNA-seq. Among these cell types, neutrophils were specifically observed in our scRNA-seq data from PBMCs. Peripheral blood effector CD8+ T cells from vitiligo patients did not show significant differences at the transcriptome level compared with healthy controls, whereas regulatory T cells showed pro-inflammatory TH1-like properties. Innate immune cells, including natural killer cells and dendritic cells, showed increased antigen processing and presentation as well as upregulated interferon responses. B cells, monocytes, and neutrophils all showed activation. B cells, especially memory B cells, had upregulated expression of genes related to humoral immunity. Monocytes showed production of proinflammatory cytokines and chemokines. Neutrophils showed strong chemokine ligand-receptor (L-R) pair (CXCR8-CXCR2) autocrine signaling pathway. This study revealed the genetic profile and signaling pathway characteristics of peripheral blood immune cells in vitiligo patients, providing new insights into its pathogenesis, which may facilitate identification of potential therapeutic targets.


[Sleep apnoea and left ventricular failure].
Nocturnal breathing disorders are rather frequently observed in patients with left ventricular failure. When an obstructive sleep apnoea is present, nCPAP therapy is the preferred treatment method; the treatment probably also positively affects the left ventricular failure itself. Central sleep apnoea and in particular, the special form Cheyne-Stokes respiration have an unfavourable prognosis with increased mortality in patients with left ventricular failure. The indication for either nCPAP therapy or adaptive servoventilation cannot yet be regarded as verified and is the subject of ongoing clinical studies.


Presence and cell growth-related variations of glycogen in human colorectal adenocarcinoma cell lines in culture.
The presence and kinetics of intracellular glycogen levels were studied, in relationship to cell growth, in asynchronous and in synchronized cultures of four human colorectal adenocarcinoma cell lines (HT-29, HRT-18, SW-480, and Caco-2). The results show that a specific pattern of glycogen accumulation occurs during the process of cell growth of the studied cell lines. The kinetics of glycogen accumulation in asynchronous cultures were similar from one cell line to another and were characterized by a low amount in the exponential phase of growth, followed by a 3- to 4-fold increase in the stationary phase. The quantities found in either phase were specific for each cell line. The maximum values found in Caco-2, HRT-18, HT-29, and SW-480 cells were, respectively, 258.5 +/- 6.9 (S.D.), 88.9 +/- 2.6, 87.5 +/- 3, and 17.5 +/- 1.8 microgram of glycogen per mg of proteins. The kinetics of glycogen accumulation during the cell cycle was also studied in synchronized cultures of HT-29 and HRT-18 cell lines. Both cell lines exhibited a common pattern of low glycogen quantities during S, G2, and M followed by an increase beginning with G1 and peaking (2.5 to 3 times the initial values) in the middle of this phase. This was followed by a symmetrical decrease in the second half of G1.


Leading in practice: a case study of how health visitors share and develop good practice.
The aim of this study was to find out more about health visitors' current situated practice in the context of national policy drivers outlining a new lead role for them in delivering co-ordinated and integrated services for children and families, tailored to local needs. The study focused on health visitors within a recently merged primary care trust and a qualitative approach was adopted with use of focus groups to generate data. The transcripts were subsequently analysed for key themes and dimensions. These related to how health visitors defined their own role and the skills with which they carried it out, the development of their expertise, role tensions and factors affecting leadership development. By drawing together the grounded experience of health visitors, policy drivers and theoretical interpretations a rich picture of existing practices was established, with recommendations made to promote distributed leadership and change.


Elimination of selected pharmaceuticals by biosolids from municipal wastewater treatment plants: importance of modest pH change and degree of mineralization.
Lab-scale batch experiments with biosolids collected from a full-scale activated sludge system (AS) and a pilot-scale membrane bioreactor (MBR) were carried out to investigate the mechanisms of elimination of 5 acidic pharmaceuticals and 2 neutral pharmaceuticals. Batch elimination experiments were conducted under the conditions of pH of 6 and 7, and a great impact of pH on elimination of pharmaceuticals was shown by the significant differences in elimination rates under different pH conditions: elimination of pharmaceuticals was enhanced under the condition of lower pH regardless of the type of biosolid. Degree of mineralization of ibuprofen was also investigated in this study by using (14)C-labeled compounds. Although ibuprofen has been considered to be a readily biodegradable pharmaceutical in previous studies, the results obtained in this study demonstrated that the degree of mineralization of ibuprofen would be limited in biological wastewater treatment including MBRs. The results obtained in this study imply that a large portion of pharmaceuticals that have been considered "biodegradable", such as ibuprofen, entering into wastewater treatment plants will eventually be discharged into natural water bodies as intermediates, although concentrations of them may look reduced on the basis of common analytical methods (i.e. GC/MS or LC/MS/MS).


Familial Linkage and Association of the NR3C1 Gene with Type 2 Diabetes and Depression Comorbidity.
Impairment in the hypothalamic-pituitary-adrenal (HPA) axis and cortisol pathway may be major contributing factors to the common pathogenesis of major depressive disorders (MDD) and type 2 diabetes (T2D). A significant player in the neuroendocrine HPA axis and cortisol response is the glucocorticoid receptor (GR), which is encoded by the nuclear receptor subfamily 3 group C member (NR3C1) gene. Variants in the NR3C1 gene have been reported in patients with MDD and obesity and found to confer reduced risk for quantitative metabolic traits and T2D in Cushing syndrome; variants have not been reported in T2D and MDD-T2D comorbid patients. We studied 212 original Italian families with a rich family history for T2D and tested 24 single nucleotide polymorphisms (SNPs) in the NR3C1 gene for linkage to and linkage disequilibrium (LD) with T2D and MDD across different inheritance models. We identified a total of 6 novel SNPs significantly linked/in LD to/with T2D (rs6196, rs10482633, rs13186836, rs13184611, rs10482681 and rs258751) and 1 SNP (rs10482668) significantly linked to/in LD with both T2D and MDD. These findings expand understanding of the role that NR3C1 variants play in modulating the risk of T2D-MDD comorbidity. Replication and functional studies are needed to confirm these findings.


Loss of heterozygosity in endometrial carcinoma.
Inactivation of a tumor suppressor gene typically occurs in two steps, thus fulfilling Knudson hypothesis. One "hit" is frequently a point mutation or a small deletion. The other alteration is usually a large genomic loss of part of a gene, or even part of a chromosome, or the whole chromosome. However, it is not clear which of these two events occurs first. Loss of heterozygosity (LOH) analysis allows the identification of one of the 2 hits. Although microsatellite polymerase chain reaction is the technique most frequently used to assess LOH, other different approaches can also be used. The LOH can also be assessed by restriction fragment length polymorphism analysis, single strand conformation polymorphism analysis, oligonucleotide microarrays capable to simultaneously determine the genotype of thousands of single-nucleotide polymorphism (single-nucleotide polymorphism arrays), comparative genomic hybridization, multiplex amplification and probe hybridization, and multiplex ligation-dependent probe amplification. In this article, the authors review the results obtained with molecular analysis of LOH in the understanding of development and progression of endometrial carcinoma. Particular attention is given to: (1) the presence of widespread LOH in nonendometrioid carcinoma, probably reflecting the existence of chromosomal instability; and (2) specific LOH patterns associated with some clinicopathologic features.


Multiple mechanisms confer drug resistance to mitoxantrone in the human 8226 myeloma cell line.
Selection for in vitro drug resistance can result in a complex phenotype with more than one mechanism of resistance emerging concurrently or sequentially. We examined emerging mechanisms of drug resistance during selection with mitoxantrone in the human myeloma cell line 8226. A novel transport mechanism appeared early in the selection process that was associated with a 10-fold resistance to mitoxantrone in the 8226/MR4 cell line. The reduction in intracellular drug concentration was ATP-dependent and ouabain-insensitive. The 8226/MR4 cell line was 34-fold cross-resistant to the fluorescent aza-anthrapyrazole BBR 3390. The resistance to BBR 3390 coincided with a 50% reduction in intracellular drug concentration. Confocal microscopy using BBR 3390 revealed a 64% decrease in the nuclear:cytoplasmic ratio in the drug-resistant cell line. The reduction in intracellular drug concentration of both mitoxantrone and BBR 3390 was reversed by a novel chemosensitizing agent, fumitremorgin C. In contrast, fumitremorgin C had no effect on resistance to mitoxantrone or BBR 3390 in the P-glycoprotein-positive 8226/DOX6 cell line. Increasing the degree of resistance to mitoxantrone in the 8226 cell line from 10 to 37 times (8226/MR20) did not further reduce the intracellular drug concentration. However, the 8226/MR20 cell line exhibited 88 and 70% reductions in topoisomerase II beta and alpha expression, respectively, compared with the parental drug sensitive cell line. This decrease in topoisomerase expression and activity was not observed in the low-level drug-resistant, 8226/MR4 cell line. These data demonstrate that low-level mitoxantrone resistance is due to the presence of a novel, energy-dependent drug efflux pump similar to P-glycoprotein and multidrug resistance-associated protein. Reversal of resistance by blocking drug efflux with fumitremorgin C should allow for functional analysis of this novel transporter in cancer cell lines or clinical tumor samples. Increased resistance to mitoxantrone may result from reduced intracellular drug accumulation, altered nuclear/cytoplasmic drug distribution, and alterations in topoisomerase II activity.


Measurements of renal shear wave velocities in chronic kidney disease patients.
Background Chronic kidney disease (CKD) patients have advanced glomerulosclerosis and renal interstitial fibrosis. Shear wave elastography (SWE) is useful to diagnose liver fibrosis. However, there are few data available regarding evaluation of kidney function on the use of SWE. Purpose To assess the utility of SWE by evaluating the correlation between renal function and renal elasticity using SWE. Material and Methods A total of 187 participants who had available serum creatinine levels and also underwent SWE of the kidney using a transabdominal ultrasonography were recruited at Nagoya University Hospital. We measured the depth of the shear wave (SW) in the right and left kidneys and calculated the measurement success rates. The glomerular filtration rate (GFR) classification and shear wave value (SWV) were compared. Results The success rates of the right and left kidneys were 93.6% and 71.6%, respectively. Based on these results, the correlation between GFR classification and SWV were analyzed in only the right kidneys because the success rates and the number of enrolled patients were low for the left kidney. There were significant differences found between G1 and G3a, G2 and G3a, G3a and G3b, G3a and G4, and G3a and G5. SWV significantly negatively and positively correlated with the G2-G3a and G3a-G3b classifications. Conclusion There is no correlation between renal function and SW. However, we can diagnose the progression to the CKD stages G3a and G3b by observing the changes over time using the SWV.


The characteristics and comparison between young and old patients with spontaneous isolated celiac artery dissection: Analysis based on 60 reports.
Though increasing studies reported the management of spontaneous isolated celiac artery dissection (ICAD), the characteristics and etiology of ICAD in different age-stage patients have not been well-studied. Our study was designed to describe and further to compare the clinical features of spontaneous ICAD between young and old patients. We searched PubMed, Embase, and Web of Science up to March 1, 2023 for spontaneous ICAD case reports. Two reviewers screened the titles and abstracts of searched records for qualified reports according to the including and excluding criteria and extracted the data independently. Statistical analysis was performed using SPSS software (version 19.0; IBM Corp, Armonk, NY) and Stata 12.0 (Stata Corp., College Station, TX). Descriptive results were presented as the mean ± standard deviation or percent. The comparison results between young and old patients were displayed as risk ratio (RR) or standardized mean difference (SMD) with its 95% confidence intervals (CI). We totally identified 60 reports in the present analysis. The mean age of patients was 52.4 years, with the majority of patients being male (84.4%). The majority of patients were symptomatic and commonest presentation was abdominal pain (76.7%). Most patients (63.2%) had comorbidities or history and hypertension and smoking were the top 2 conditions with proportion of 63.3% and 40.5% respectively. When comparing young to old patients with ICAD, no significant difference was found in demographic and clinical features including sex, comorbidities/history, and symptoms. However, we found that young patients with ICAD experienced significantly longer dissection length (SMD 1.01, 95% CI 0.16-1.86; P = .015) and distance from ostium (SMD 0.96, 95% CI 0.07-1.85; P = .013), but no significant difference was observed in true lumen compression (SMD -0.39, 95% CI -1.22-0.44; P = .364). In addition, our results showed that ICAD in young patients extending more to distal arteries, including common hepatic artery/hepatic artery (RR 2.04, 95% CI 1.13-3.68; P = .01), splenic artery (RR 2.36, 95% CI 1.24-4.49; P = .017) and left gastric artery (RR 25.42; 95% CI 1.55-417.74; P = .04). Though spontaneous ICAD had multitudinous clinic-pathologic features, it was apt to middle-aged males and symptomatic and abdominal pain was always the commonest presentation. Hypertension and smoking were the top 2 conditions of ICAD patients. There was significant difference between young and old patients in radiographic characteristics of ICAD which may lead to different treatment and outcomes.


Adsorption of plasma proteins on to poly(ethylene oxide)/poly(propylene oxide) triblock copolymer films: a focus on fibrinogen.
Triblock copolymers of the form PEO(alpha)PPO(beta)PEO(alpha) [where PEO is poly(ethylene oxide) and PPO is poly(propylene oxide)] have many biomedical applications, many of which depend on the surface properties of the copolymers and the influence that those properties have on the adsorption of proteins. As a tool to help us better understand, predict and exploit the influence of these triblock copolymers on protein adsorption, we developed a model system in which well-defined monolayers of the copolymers are supported by solid, hydrophobic, microscopic beads. At the bead/water interface, the copolymers all form stable films in which the nominal molecular areas correspond to those of the molecules when they are packed rather tightly at the air/water interface. Beads coated with condensed films of copolymers that contain short PEO segments and elicit appreciable inflammation absorb appreciable quantities of plasma proteins, including fibrinogen, from aqueous solution. Beads coated with fibrinogen aggregate when they are stirred in the presence of thrombin, a consequence of interbead fibrin formation. Beads coated with condensed films of copolymers that contain long PEO segments and elicit little inflammation absorb little plasma protein, and they do not aggregate in the presence of thrombin. Our data and observations are consistent with the prevailing notion that the utility of triblock copolymers as agents for modifying the surface properties of blood-contacting surfaces derives from the influence of the copolymers on the adsorption of plasma proteins. In this regard, the ability of the copolymers to influence fibrinogen-mediated adhesive events may be particularly important. As to the mechanism of protein resistance, our data support the proposal that sibling PEO segments of copolymers in condensed films fold back across their parental PPO cores, limiting access of proteins to the hydrophobic cores themselves.


Adaptive Optics Microscopy with Wavefront Sensing Based on Neighbor Correlation.
Complex structures in living cells and tissues induce wavefront errors when light waves pass through them, and images observed with optical microscopes are undesirably blurred. This problem is especially serious for living plant cells because images are strikingly degraded even within a single cell. Adaptive optics (AO) is expected to be a solution to this problem by correcting such wavefront errors, thus enabling high-resolution imaging. In particular, scene-based AO involves wavefront sensing based on the image correlation between subapertures in a Shack-Hartmann wavefront sensor and thus does not require an intense point light source. However, the complex 3D structures of living cells often cause low correlation between subimages, leading to loss of accuracy in wavefront sensing. This paper proposes a novel method for scene-based sensing using only image correlations between adjacent subapertures. The method can minimize changes between subimages to be correlated and thus prevent inaccuracy in phase estimation. Using an artificial test target mimicking the optical properties of a layer of living plant cells, an imaging performance with a Strehl ratio of approximately 0.5 was confirmed. Upon observation of chloroplast autofluorescence inside living leaf cells of the moss Physcomitrium patens, recovered resolution images were successfully obtained even with complex biological structures. Under bright-field illumination, the proposed method outperformed the conventional method, demonstrating the future potential of this method for label- and damage-free AO microscopy. Several points for improvement in terms of the effect of AO correction are discussed.