Auditory research involving antioxidants.
The role of antioxidants in the management of hearing loss has generated considerable interest over the past several years. Research efforts in this field have yielded many new insights into the molecular and cellular nature of several types of hearing impairment, including age-related, noise-induced, and drug-induced hearing loss. The objective of this paper is to highlight some of the important studies published over the past several years that have further contributed to our understanding of the mechanism of antioxidants in attenuating hearing loss. There is compelling evidence to suggest that antioxidant therapy is beneficial in attenuating, improving, or reversing the effects of several types of acquired hearing loss. Cellular and subcellular changes resulting from these types of hearing impairment are remarkably similar and seem to have a common putative mechanism of oxidative stress and damage. Recent studies have lent further credibility to the notion that antioxidant therapy can be of considerable benefit in the treatment of hearing loss. The increasing body of literature pertaining to human studies will shed further light into this fascinating area of research. This review elucidates the role of antioxidants in hearing loss and illustrates the continued evolution of research efforts in this field.


Automated testing of the controlled resistance exercise device (C-red) for spaceflight.
Resistance exercise is an effective countermeasure to the muscle and bone atrophy associated with the unloading experienced during spaceflight. Accordingly, the Controlled Resistance Exercise Device (C-RED) developed for NASA uses an electric motor for resistance and capitalizes upon a two-to-one mechanical advantage by loading only one side of the barbell. While this allows for a reduction in the required motor size and weight, the ground reaction force from previous human subject studies has shown higher loads on the motor side, which could be accentuated by the person's unilateral strength bias or lifting technique. Therefore, an automated testing system was developed to test the bilateral symmetry of only the device without human bias. In addition, the effect of the winching material (cord or strap) on the bilateral symmetry of loading was explored. Findings show that cord leads to a more symmetric loading but is prone to fraying and subsequent breaking below the specified strength. Straps have higher strength and wear resistance properties but lead to slightly less symmetric loading outcomes. In general, the C-RED retains some asymmetric loading regardless of winching material; however the marginally higher bilateral asymmetry of the strap is offset by the gains in strength and wear resistance.


Differential effects of HSV-1 and HCMV infection on adhesion molecule expression on human corneal keratocytes.
Previous studies have shown that keratoplasty buttons obtained at surgery from patients with herpes simplex virus-1 (HSV-1) keratitis have elevated localized expression of the adhesion molecule ICAM-1, which plays a critical role in the initiation and amplification of an immune response. We performed studies to determine whether changes in expression of ICAM-1 and HLA class I are direct effects of productive infection of human corneal fibroblasts with HSV-1. Immunocytologic and flow cytometric analyses were performed to analyze the ability of HSV-1 to induce ICAM-1 and HLA class I expression in a primary cornea-derived keratocyte cell line, E-2. Positive controls for these experiments were E-2 cells infected with human cytomegalovirus (HCMV), which has been shown to increase ICAM-1 expression in selected cells, and E-2 cells treated with IFN-gamma, which upregulates both ICAM-1 and HLA class I expression in most cell types. Kinetic cytometric analysis indicated decreased ICAM-1 expression 3 hours following HSV-1 infection of E-2 cells. In contrast, HCMV led to detectable increases in ICAM-1 expression starting 6 hours after infection. Infections with either HSV-1 or HCMV resulted in reduced HLA class I expression on E-2 and SF cells. These studies suggest that increased ICAM-1 expression seen on corneal stromal cells during clinical HSV-1 infection is not a direct result of productive viral infection, but of other mechanisms such as cytokine release by infiltrating mononuclear cells.


[Vessels of the cerebral cortex and cerebellum of the human brain].
This study is divided in two parts: a. the cerebral cortical vessels: pial arteries and veins at the gyrus surface are described as well as their anastomoses. Intracortical arteries and veins are divided into 5 groups according to their degree of cortical penetration. A correlation between cytoarchitecture and angioarchitecture is established. b. The cerebellar cortical vessels: they are compared to the cerebral vessels. The vascularization of Purkinje cells is especially described: the Purkinje cells are in close contact with an arterial network which is situated parallel to the cortical surface; it is probable that the nutrition of the Purkinje cells is obtained through the wall of this parallel arterial network.


[Clinical analysis of renal cell carcinoma: report of 271 cases].
To study the diagnosis and treatment of renal cell carcinoma. From January 1993 to December 2000 the data of 271 cases of renal cell carcinoma were reviewed. Ultrasonography and CT scanning were still the main diagnostic methods. Surgical operation was performed on 234 patients. Radical nephrectomy was performed on 197 patients (72.6%); Nephron sparing surgery was performed on 19 patients; Metastatic tumor resection was performed on 6 patients and other procedures for 12. The pathological results showed that 137 cases (61.4%) were clear cell carcinoma, 18 cases (8. 1%) of granular cell carcinoma, 32 cases (14. 3%) being combination of the above two varieties, 23 cases (10.3%) of renal papillary adenocarcinoma, 13 cases being renal cell of other types. And 210 cases (77.5%) had been successfully followed up. The 1, 3, 5 and 10 year survival rates were 95.3% (182/191), 88.7% (107/122), 74.7% (56/75) and 32.1% (10/31) respectively. Ultrasonography is the first select examination method of detecting of renal cell carcinoma, and CT scanning is the most valuable diagnostic mean. Early diagnosis and prompt radical nephrectomy or nephron sparing nephrectomy are the critical points for achieving long-term survivals of patients with renal cell carcinoma.


Antibacterial activity of sucralfate versus aluminum chloride in simulated gastric fluid.
Studies have previously demonstrated that sucralfate possesses intrinsic antibacterial activity. This study was designed to indirectly assess whether aluminum is the active antibacterial component of sucralfate and to further evaluate factors that may influence this agent's antibacterial activity. Utilizing an in vitro model, the antibacterial activity of sucralfate, an equivalent quantity of aluminum in the form of aluminum chloride, and a control were compared. In addition, the influences of bacterial species (Enterobacter cloacae and Pseudomonas aeruginosa), time (0-24 h) and environmental pH (3,5,7) on the agents' antibacterial activities were evaluated. Equivalent quantities of aluminum, as either sucralfate or aluminum chloride, were added to two of three flasks containing approximately 10(5) cfu/ml of bacteria in pH-adjusted simulated gastric fluid. The third flask served as a control. Samples were obtained over 24 h, diluted and subcultured onto agar plates. The experiments demonstrated that bacterial growth was influenced by pH, time and treatment (aluminum chloride or sucralfate). Regardless of pH or bacterial species, bacterial death occurred within 20 min following the addition of aluminum chloride. In contrast, bacterial death following the addition of sucralfate was more variable and appeared to be pH dependent. In conclusion, sucralfate and aluminum chloride both possess antibacterial activity, even at pH values that normally support bacterial growth in gastric fluid. Although differences in the antibacterial activity of the two agents may in part be related to drug-induced changes in pH, these differences also support data suggesting that aluminum release from sucralfate is incomplete and is dependent on pH.


Minimally Invasive Surgery for Congenital Abdominal Cystic Lesions in Newborns and Infants.
In the variety of congenital abdominal cystic lesions (CACL) of different origin, ovarian cyst is the most common intra-abdominal pathology in female neonates. The prognosis and timing of treatment varies depending on the nature of CACL. This study aimed to assess the results of diagnostics and treatment of CACL. A retrospective analysis was performed of 39 cases of CACL, with the spectrum including ovarian, enteric, mesenteric and pancreatic origin. Outcome of minimally invasive surgery, open surgery or conservative approach was analyzed. Twenty-eight neonates underwent surgery, while 11 were treated conservatively. Twenty patients were treated with a laparoscopic technique and eight with laparotomy combined with laparoscopy. Final diagnosis included: Fifteen cases of ovarian pathology (ovarian torsion in 11 cases), 12 treated laparoscopically and three with laparotomy, six enteric duplications (four laparoscopic and two laparotomic), three mesenteric cysts (one laparoscopic and two laparotomic), two pancreatic cysts (both laparoscopic only), two duodenal stenoses, including duodenal septum (both laparotomies with Heineke-Mikulicz plasty). No blood transfusion apart from two cases requiring re-laparotomy and no early complications were observed in any case; no death occurred. With the strategy of management based on ultrasound and laboratory data, a laparoscopically assisted minimal access approach resulted in minimal risk of complications and complete recovery in all patients, leading to exclusion of oncological risk.


Cross-ethnic symptom differences in schizophrenia: the influence of culture and minority status.
The two objectives of this tri-ethnic study were (1) to test competing hypotheses from the minority status and ethnic culture perspectives in examining cross-ethnic symptom differences in schizophrenia and (2) to test cultural mediators of the symptom differences. Analyses were done on samples of minority (African-American and Latino) and nonminority (white) groups. Hypothesized cross-ethnic symptom differences were tested, and indicators of sociocentricity were examined as cultural mediators of symptom differences. The sample consisted of 184 individuals (51.6% white, 32.6% African-American, 15.8% Latino, 75% male) diagnosed with schizophrenia in an outpatient, urban setting. Symptom variables were obtained from the Brief Psychiatric Rating Scale and the Quality of Life Scale. Two sociocentric indicators (empathy and social competence) were used to differentiate minority from nonminority groups. Multiple regression was used to test the mediational influence of the sociocentric indicators on the symptom differences. After controlling for social class, significant differences were found in eight symptom variables. These showed the nonminority group to be consistently more symptomatic than the ethnic minority groups, findings which supported the ethnic culture hypothesis. Sociocentric indicators were found to be significant mediators of the cross-ethnic symptom differences. This study supported the ethnic culture hypothesis, which predicted lower symptoms for the ethnic minority groups, and showed that sociocentric variables strongly mediated the more benign symptom profile for the ethnic minority groups. The study indicates that culture should be more fully integrated into current biopsychosocial models of schizophrenia.


The Prospective Influence of Perceived Social Norms on Bystander Actions Against Sexual Violence and Relationship Abuse: A Multiple Mediation Model.
The present study assessed support for an innovative model of the direct and indirect paths through which perceived peer norms regarding the prevalence and acceptability of sexual violence (SV) and relationship abuse (RA) may influence the decisional process leading to bystander intervention. Analyses included baseline and 6-month follow-up data collected from a large sample of high school students (N = 2,303) across 27 schools in the Northeastern United States. Path analyses were conducted to test a multiple mediation model of the direct and indirect associations among the sequential predictors of perceived descriptive and injunctive norms, personal attitudes, abuse perceptions, risk recognition, and dependent measures of bystander behaviors at baseline and 6-month follow-up. Higher perceptions of the prevalence (descriptive norms) and acceptability (injunctive norms) of SV and RA among peers were associated with more accepting personal attitudes toward SV and RA, which were associated with lower abuse perceptions and risk recognition. Furthermore, lower abuse perceptions and risk recognition were associated with decreases in bystander behaviors at both time points. Mediational analyses revealed several significant indirect paths through which higher perceptions of descriptive and injunctive norms contributed to decreases in bystander behavior. Findings provide novel evidence of the prospective influence of perceived norms on bystander intervention behavior in situations of SV and RA.


Inferring foliar water uptake using stable isotopes of water.
A growing number of studies have described the direct absorption of water into leaves, a phenomenon known as foliar water uptake. The resultant increase in the amount of water in the leaf can be important for plant function. Exposing leaves to isotopically enriched or depleted water sources has become a common method for establishing whether or not a plant is capable of carrying out foliar water uptake. However, a careful inspection of our understanding of the fluxes of water isotopes between leaves and the atmosphere under high humidity conditions shows that there can clearly be isotopic exchange between the two pools even in the absence of a change in the mass of water in the leaf. We provide experimental evidence that while leaf water isotope ratios may change following exposure to a fog event using water with a depleted oxygen isotope ratio, leaf mass only changes when leaves are experiencing a water deficit that creates a driving gradient for the uptake of water by the leaf. Studies that rely on stable isotopes of water as a means of studying plant water use, particularly with respect to foliar water uptake, must consider the effects of these isotopic exchange processes.


Receptor recognition by the peroxisomal AAA complex depends on the presence of the ubiquitin moiety and is mediated by Pex1p.
The receptor cycle of type I peroxisomal matrix protein import is completed by ubiquitination of the membrane-bound peroxisome biogenesis factor 5 (Pex5p) and its subsequent export back to the cytosol. The receptor export is the only ATP-dependent step of the whole process and is facilitated by two members of the AAA family of proteins (ATPases associated with various cellular activities), namely Pex1p and Pex6p. To gain further insight into substrate recognition by the AAA complex, we generated an N-terminally linked ubiquitin-Pex5p fusion protein. This fusion protein displayed biological activity because it is able to functionally complement a PEX5-deletion in Saccharomyces cerevisiae. In vitro assays revealed its interaction at WT level with the native cargo protein Pcs60p and Pex14p, a constituent of the receptor docking complex. We also demonstrate in vitro deubiquitination by the deubiquitinating enzyme Ubp15p. In vitro pulldown assays and cross-linking studies demonstrate that Pex5p recognition by the AAA complex depends on the presence of the ubiquitin moiety and is mediated by Pex1p.


[Surgery of post-resectional syndrome of alimentary dystrophy].
In clinic there were treated 554 patients for postresectional syndrome of alimentary dystrophy (SAD), including functional one--230 (41.5%), organic--228 (41.1%), combined--96 (17.4%). In 91% of patients prominent disorders of digestion up to severe alimentary dystrophy were noted. Three patients died because of cachexia during preoperative preparation, 1--on the first day after it. Reduodenization operation is the surgical treatment method of choice for the treatment of functional and combined postresectional SAD. Excellent result was noted in 30%, good--in 47%, the digestion processes improvement was noted in 87% of observations.


Generation and activity of equine osteoclasts in vitro: effects of the bisphosphonate pamidronate (APD).
Equine osteoclast-like cells (OCLs) were generated from the bone marrow (BM) of two ponies and one horse in the presence of RANKL, the receptor activator of NF kappa B ligand and macrophage colony-stimulating factor (M-CSF). The phenotype of these cells was confirmed by demonstration of characteristics typical of osteoclasts (OCs) including: the expression of tartrate-resistant acid phosphatase (TRAP), the vitronectin receptor (VNR) and the calcitonin receptor (CTR), the demonstration of responsiveness to calcitonin (CT) and the ability to form resorption lacunae on ivory slices and calcium phosphate films. The bisphosphonate pamidronate (APD) dose-dependently inhibited resorption of calcium phosphate films by equine OCLs with an IC(50) of 5.8 x 10(-7) M in one horse. APD also dose-dependently inhibited the number of OCLs present in BM cultures after 7 days. However, this effect is most likely attributable to increased OCL death rather than decreased OCL formation. Paradoxically, ADP appeared to cause an early, transient, increase in OCL formation in BM cultures, however, this effect was reversed after 7 days. These preliminary in vitro data support the potential use of APD in clinical conditions characterised by increased bone turnover such as osteomyelitis, osteitis, septic osteoarthritis, navicular disease, cystic bone lesions and immobilisation-induced osteoporosis and provide useful information for future pharmacokinetic studies and clinical trials in vivo.


Dietary intake of 9-10-year-old and 11-12-year-old children in Liverpool.
To describe the eating habits of children in Liverpool and compare two age groups that bridge the transition from primary to secondary school. Two cross-sectional studies carried out one year apart using a food intake questionnaire that records whether or not each child claims to have eaten specific marker foods on the previous day. Primary and secondary schools in Liverpool. Six hundred and forty-nine children aged 11 or 12 years and 3556 children aged 9 or 10 years. Fewer older children ate breakfast (68-82%), especially the girls, and not eating breakfast was associated with eating on the way to school in the younger children. More of the older girls ate nothing at breakfast or on the way to school. Overall, the less desirable foods were reported to have been eaten by more children, of both ages, than the more desirable foods. Fruit, however, was mentioned by most children (69-77%) but the next 10 foods mentioned by most children were all less desirable ones. Only 31% of primary and 21% of secondary children ate both fruit and vegetables but 23% of primary and 26% of secondary children ate neither fruit nor vegetables. Overall, more of the girls of both age groups claimed to have eaten foods that would normally be encouraged. Food choice changes appreciably between primary and secondary school and, in some key respects, for the worse. In particular, far more children of both age groups need to be eating fruit and vegetables every day.


The effect of Persian shallot (Allium hirtifolium Boiss.) extract on blood sugar and serum levels of some hormones in diabetic rats.
Diabetes mellitus (DM) is caused by hyperglycemia, resulting from defective insulin secretion or function. It is widely believed that the antioxidant micronutrients obtained from plants afford significant protection against diseases like diabetes mellitus. Present study was aimed to examine the effects of Persian shallot (Allium hirtifolium Boiss) on FBS, HbA1c, insulin, triiodothyronine (T3) and thyroxine (T4) levels in type 1 diabetic rats. Thirty two male Wistar rats were divided into 4 groups of 8. The diabetic groups received 100 and 200 mg/kg Persian shallot extract, diabetic control and normal control received %0.9 saline for 30 days. At the end of treatments, fasting blood specimens were collected. The levels of FBS, HbA1c, insulin, T3 and T4 were measured. Our findings indicated that hydroalcoholic extract of Persian shallot significantly decreased serum levels of FBS and HbA1c in treated groups (in a dose dependent manner) (p<0.05). The serum levels of insulin and T3 slightly increased by Persian shallot but the T4 serum level was declined. These beneficial effects of Persian shallot extracts in diabetic rats could probably be due to the antioxidant capacity of its phenolic and diallyl disulfide content.


COMPONENTS OF PHENOTYPIC SELECTION: POLLEN EXPORT AND FLOWER COROLLA WIDTH IN IPOMOPSIS AGGREGATA.
In the hummingbird-pollinated herb Ipomopsis aggregata, selection through male function during pollination favors wide corolla tubes. We explored the mechanisms behind this selection, using phenotypic selection analysis to compare effects of corolla width on two components of male pollination success, pollinator visit rate and pollen exported per visit. During single visits by captive hummingbirds, flowers with wider corollas exported more pollen, and more dye used as a pollen analogue, to stigmas of recipient flowers. Corolla width was less strongly related to visit rate in the field, and had no direct effect on visit rate after nectar production and corolla length were controlled for. Moreover, the phenotypic selection differential was 80% higher for the effect on pollen exported per visit, suggesting that this is the more important mechanism of selection.


Relationships among and variation within rare breeds of swine.
Extinction of rare breeds of livestock threatens to reduce the total genetic variation available for selection in the face of the changing environment and new diseases. Swine breeds facing extinction typically share characteristics such as small size, slow growth rate, and high fat percentage, which limit them from contributing to commercial production. Compounding the risk of loss of variation is the lack of pedigree information for many rare breeds due to inadequate herd books, which increases the chance that producers are breeding closely related individuals. By making genetic data available, producers can make more educated breeding decisions to preserve genetic diversity in future generations, and conservation organizations can prioritize investments in breed preservation. The objective of this study was to characterize genetic variation within and among breeds of swine and prioritize heritage breeds for preservation. Genotypes from the Illumina PorcineSNP60 BeadChip (GeneSeek, Lincoln, NE) were obtained for Guinea, Ossabaw Island, Red Wattle, American Saddleback, Mulefoot, British Saddleback, Duroc, Landrace, Large White, Pietrain, and Tamworth pigs. A whole-genome analysis toolset was used to construct a genomic relationship matrix and to calculate inbreeding coefficients for the animals within each breed. Relatedness and average inbreeding coefficient differed among breeds, and pigs from rare breeds were generally more closely related and more inbred ( < 0.05). A multidimensional scaling diagram was constructed based on the SNP genotypes. Animals within breeds clustered tightly together except for 2 Guinea pigs. Tamworth, Duroc, and Mulefoot tended to not cluster with the other 7 breeds.


The impact of associated diabetic retinopathy on stroke and severe bleeding risk in diabetic patients with atrial fibrillation: the loire valley atrial fibrillation project.
Diabetes mellitus is recognized as a stroke risk factor in atrial fibrillation (AF). Patients with diabetes with retinopathy have an increased risk for systemic cardiovascular complications, and severe diabetic retinopathy predisposes to ocular bleeding. We hypothesized that patients with diabetes, retinopathy, and AF have increased stroke/thromboembolism (TE) and severe bleeding risks when compared with patients with diabetes and AF who do not have retinopathy or to patients with AF and without diabetes. We tested our hypothesis in a large "real-world" cohort of individuals with AF from the Loire Valley Atrial Fibrillation project. Of 8,962 patients with AF in our dataset, 1,409 (16%) had documented diabetes mellitus. Of these, 163 (1.8% of the whole cohort) were patients with diabetic retinopathy. After a follow-up of 31 ± 36 months, when compared with patients without diabetes, the risk of stroke/TE in patients with diabetes with no retinopathy increased 1.3-fold (relative risk [RR], 1.30; 95% CI, 1.07-1.59; P = .01); in patients with diabetes with retinopathy, the risk of stroke/TE was increased 1.58-fold (RR, 1.58; 95% CI, 1.07-2.32; P = .02). There was no significant difference when patients with diabetes with no retinopathy were compared with patients with diabetes with retinopathy (RR, 1.21; 95% CI, 0.80-1.84; P = .37). A similar pattern was seen for mortality and severe bleeding. On multivariate analysis, the presence of diabetic retinopathy did not emerge as an independent predictor for stroke/TE or severe bleeding. Crude rates of stroke/TE increased in a stepwise fashion when patients without diabetes and with AF were compared with patients with diabetes with no retinopathy and patients with diabetes with retinopathy. However, we have shown for the first time, to our knowledge, that the presence of diabetic retinopathy did not emerge as an independent predictor for stroke/TE or severe bleeding on multivariate analysis.


Deciphering the Proteome Dynamics during Development of Neurons Derived from Induced Pluripotent Stem Cells.
Neuronal development is a complex multistep process that shapes neurons by progressing though several typical stages, including axon outgrowth, dendrite formation, and synaptogenesis. Knowledge of the mechanisms of neuronal development is mostly derived from the study of animal models. Advances in stem cell technology now enable us to generate neurons from human induced pluripotent stem cells (iPSCs). Here we provide a mass spectrometry-based quantitative proteomic signature of human iPSC-derived neurons, i.e., iPSC-derived induced glutamatergic neurons and iPSC-derived motor neurons, throughout neuronal differentiation. Tandem mass tag 10-plex labeling was carried out to perform proteomic profiling of cells at different time points. Our analysis reveals significant expression changes (FDR < 0.001) of several key proteins during the differentiation process, e.g., proteins involved in the Wnt and Notch signaling pathways. Overall, our data provide a rich resource of information on protein expression during human iPSC neuron differentiation.


Persistent left superior vena cava: clinical implications for central venous cannulation.
In general, persistence of the left superior vena cava (LSVC), the most common anomaly of the venous circulation, is asymptomatic. Diagnosis of a catheter in a persistent LSVC is not straight forward, and a LSVC can create difficulties during central venous and pulmonary artery catheterization. We discuss the differential diagnosis of left-sided central venous catheters (CVC). Finally a directive is given to prevent dilator-induced vessel injuries. We report the cannulation of an unsuspected persistent LSVC in two patients. A dilator-induced vessel injury contributed significantly to the fatal outcome in the first case. On a plain chest X-ray, a catheter in a LSVC will run down the left mediastinal border and can be confused with other intravascular malpositions and extravascular malpositions. Contrast-enhanced lateral chest radiograph is an inexpensive and readily available method that can be used to determine exact position.


Calcium Channel Blocker Overdose Treated with Calcium Resulting in Pancreatitis: A Case Report.
Calcium channel blockers (CCBs) are a mainstay for the treatment of hypertension. Here we report a case of a male who after intentionally ingesting amlodipine presented with overdose symptomology. His QTc (corrected QT) was 525 ms (millisecond) on admission, he was treated with calcium intravenous infusion and subsequently his QTc narrowed to 393 ms, but he also developed iatrogenic pancreatitis. His serum calcium levels were not checked during the infusion. He was treated with supportive care, which led to the normalization of serum calcium levels and a favorable outcome. Further studies are required regarding how frequently calcium levels should be checked during infusions.


Interaction of gallium nitrate with fludarabine and iron chelators: effects on the proliferation of human leukemic HL60 cells.
Earlier studies have shown that transferrin-gallium inhibits cellular iron incorporation and blocks DNA synthesis by decreasing the activity of the iron-dependent M2 subunit of ribonucleotide reductase. We examined the growth-inhibitory effects of gallium nitrate in combination with clinically relevant inhibitors of ribonucleotide reductase fludarabine (an M1 subunit inhibitor), and iron chelators (M2 subunit inhibitors). Fludarabine and gallium nitrate in combination produced a significant increase in cell growth inhibition when compared with either agent alone; however, this effect was partially reversible up to 24 h and was best seen with continuous exposure of cells to both drugs. Incubation of cells with desferrioxamine and gallium nitrate resulted in reversal of gallium-induced growth inhibition. Incubation of cells with N,N'-bis(o-hydroxybenzyl)ethylenediamine-N,N'-diacetic acid and gallium nitrate resulted in a slight increase in gallium-induced growth inhibition, with partial restoration of cell growth occurring only at a single high concentration of N,N'-bis(o-hydroxybenzyl)ethylenediamine-N,N'-diacetic acid. Both chelators inhibited 67Ga uptake by cells and increased cell surface transferrin receptors. In contrast to the coincubation studies, sequential exposure of cells to desferrioxamine or N,N'-bis(o-hydroxybenzyl)ethylenediamine-N,N'-diacetic acid and gallium nitrate resulted in a significant potentiation of the growth-inhibitory effects of gallium nitrate. Our studies show that cellular iron deprivation results in enhanced sensitivity of cells to gallium. Furthermore, the combined effects of fludarabine and gallium on cell growth may be of clinical relevance, since both agents are active against lymphoid cancers.


From co-expression to co-regulation: how many microarray experiments do we need?
Cluster analysis is often used to infer regulatory modules or biological function by associating unknown genes with other genes that have similar expression patterns and known regulatory elements or functions. However, clustering results may not have any biological relevance. We applied various clustering algorithms to microarray datasets with different sizes, and we evaluated the clustering results by determining the fraction of gene pairs from the same clusters that share at least one known common transcription factor. We used both yeast transcription factor databases (SCPD, YPD) and chromatin immunoprecipitation (ChIP) data to evaluate our clustering results. We showed that the ability to identify co-regulated genes from clustering results is strongly dependent on the number of microarray experiments used in cluster analysis and the accuracy of these associations plateaus at between 50 and 100 experiments on yeast data. Moreover, the model-based clustering algorithm MCLUST consistently outperforms more traditional methods in accurately assigning co-regulated genes to the same clusters on standardized data. Our results are consistent with respect to independent evaluation criteria that strengthen our confidence in our results. However, when one compares ChIP data to YPD, the false-negative rate is approximately 80% using the recommended p-value of 0.001. In addition, we showed that even with large numbers of experiments, the false-positive rate may exceed the true-positive rate. In particular, even when all experiments are included, the best results produce clusters with only a 28% true-positive rate using known gene transcription factor interactions.


Medical students' involvement in patient care.
In a recent issue of The Journal of Clinical Ethics, Peter A. Ubel and Ari Silver-Isenstadt reported on patients' willingness to participate in medical education. Their findings and other data they refer to suggest that patients are generally willing to interact with medical students, but that this willingness may vary depending upon the clinical setting. The authors concluded that patients hold a right to information regarding students' participation in their care and that openness in this regard is valuable. The Council on Ethical and Judicial Affairs (CEJA) of the American Medical Association (AMA) recently developed a policy that addresses the issues that were investigated by Ubel and Silver-Isenstadt.


The promoter of the mouse tissue transglutaminase gene directs tissue-specific, retinoid-regulated and apoptosis-linked expression.
Tissue transglutaminase is a multifunctional enzyme that accumulates to high levels in cells undergoing apoptosis. Retinoids act as an acute and direct regulator of tissue transglutaminase gene transcription. The studies reported here were carried out to elucidate the molecular mechanisms involved in the regulation of tissue transglutaminase expression. We have isolated and characterized the mouse tissue transglutaminase gene promoter and 3.8 kb of 5'-flanking DNA. A large fragment of the promoter that includes both the core promoter and 3.8 kb of 5'-flanking DNA shows retinoid-dependent transcriptional activity when stably transfected into HeLa cells. In these stably transfected HeLa cells both the endogenous tissue transglutaminase gene and transfected mouse tissue transglutaminase promoter are activated by all-trans retinoic acid and by retinoic acid receptor (RAR)-specific and retinoid X receptor (RXR)-specific retinoids. In embryos made transgenic with a transglutaminase promoter-beta-galactosidase reporter gene, the transgene shows specific patterns of expression during limb development. The transglutaminase transgene is expressed in cartilage, the cells of the apical ectodermal ridge, and in regions of apoptotic cell death of the interdigital mesenchyme. It appears that cis-acting elements responsible for the complex retinoid regulation, tissue- and apoptosis-specific expression are embedded within the proximal 3.8 kb of DNA flanking the 5'-end of the mouse tissue transglutaminase gene.


Differences in the distribution of triggers among resting state networks in patients with juvenile myoclonic epilepsy explained by network analysis.
Juvenile myoclonus epilepsy (JME) is an idiopathic generalized epilepsy syndrome. Functional connectivity studies based on graph theory have demonstrated changes in functional connectivity among different brain regions in patients with JME and healthy controls. However, previous studies have not been able to clarify why visual stimulation or increased cognitive load induces epilepsy symptoms in only some patients with JME. This study constructed a small-world network for the visualization of functional connectivity of brain regions in patients with JME, based on system mapping. We used the node reduction method repeatedly to identify the core nodes of the resting brain network of patients with JME. Thereafter, a functional connectivity network of the core brain regions in patients with JME was established, and it was analyzed manually with white matter tracks restriction to explain the differences in symptom distribution in patients with JME. Patients with JME had 21 different functional connections in their resting state, and no significant differences in their distribution were noted. The thalamus, cerebellum, basal ganglia, supplementary motor area, visual cortex, and prefrontal lobe were the core brain regions that comprised the functional connectivity network in patients with JME during their resting state. The betweenness centrality of the prefrontal lobe and the visual cortex in the core functional connectivity network of patients with JME was lower than that of the other brain regions. The functional connectivity and node importance of brain regions of patients with JME changed dynamically in the resting state. Abnormal discharges originating from the thalamus, cerebellum, basal ganglia, supplementary motor area, visual cortex, and prefrontal cortex are most likely to lead to seizures in patients with JME. Further, the low average value of betweenness centrality of the prefrontal and visual cortices explains why visual stimulation or increased cognitive load can induce epileptic symptoms in only some patients with JME.


Gray-scale ultrasonography of the thyroid.
Gray-scale ultrasonography of the thyroid was performed in 33 patients, utilizing a commercially available scanning unit and an aqueous gel coupling medium. Solid and cystic lesions could readily be differentiated, but it was impossible to tell benign lesions from malignant tumors. The ultrasound appearance of thyroid cysts, adenoma, goiter, and carcinoma is illustrated.


Lymphoid cells of the liver.
Lymphoid cells resident in the liver possess a considerable importance for maintaining the homeostasis in this organ, under conditions for both normal development and response to certain pathological stimuli. This review analyze various fundamental aspects of their physiology, discussing: the types of lymphocytes (granular and agranular) found in the liver and their distribution patterns in the tissue, under both normal and pathological circumstances; the functional characteristics of these cells in vitro; and the factors that control the dynamics of their location in the liver in vivo.


Assignment of bovine synteny groups U27 and U8 to R-banded chromosome 12 and 27, respectively.
Two microsatellite-containing cosmids, clOBT361 and clOBT355 were localized to bovine R-banded chromosome 12 and 27, respectively, by fluorescence in situ hybridization. The two microsatellites were subcloned from the cosmids and named INRA209 and INRA206, respectively. Primers were designed from the sequence information and used for PCR amplification with a panel of 36 previously characterized hamster/bovine somatic cell hybrids. This allowed the assignment of the two microsatellites to bovine synteny groups U27 and U8, respectively. The result permits the conclusion that bovine synteny U27 corresponds to BTA12 and that bovine synteny group U8 corresponds to BTA27, reducing to five the number of unassigned bovine synteny groups. Furthermore, as a high level of polymorphism was revealed by the two microsatellites, they have all the required characteristics for good genetic map markers.


Mitotic spindle damage induced by 3,4-dichloroaniline in V79 Chinese hamster cells examined by differential staining of the spindle apparatus and chromosomes.
3,4-Dichloroaniline (3,4-DCA), an intermediate in various chemical syntheses, has been detected as an environmental contaminant in surface waters and in the effluents from dye manufacturing plants. Previously we showed that the compound caused mitotic spindle damage. In the present study a preparation and staining technique has been used that allows a direct examination of the spindle apparatus and chromosome behaviour of 3,4-DCA-exposed V79 Chinese hamster cells. After a 3 h exposure the compound caused monopolar mitoses and metaphase arrest in a dose-dependent manner, most probably by interfering with centriole separation. At a concentration of 1 mM, increased levels of aneuploid cells could be observed in cells exposed for two cell division cycles.


Severe obstructive sleep apnea after cerivastatin therapy: a case report.
All available 3-hydroxy-3-methyglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins) have been implicated in causing rhabdomyolysis either as monotherapy or in combination with other myotoxic drugs such as cyclosporine, colchicine and fibrates. Cerivastatin (Baycol) is a third generation statin, which has been implicated in cases of fatal rhabdomyolysis. It was voluntary withdrawn from the U.S. market by Bayer after reports of fatal rhabdomyolysis appeared in the literature. We present here a case of an 85-year-old woman who developed rhabdomyolysis and severe obstructive sleep apnea (OSA) symptoms after having been started on cerivastatin therapy for hypercholesteremia.


Visualization of epidermal and dermal alteration in papulonodular mucinosis by multiphoton microscopy.
Papulonodular mucinosis (PM) is a cutaneous clue to the presence and activity of silent lupus erythematosus (LE), but the exact pathogenesis is still under secret. Moreover, the currently available treatments for PM are not satisfactory. To demonstrate the possibility of multiphoton microscopy (MPM) to trace the pathological state of PM and evaluate the treatment efficacy, epidermal and dermal alteration in skin lesion with PM before and after treatment was examined using MPM. Microstructure of epidermis as well as content and distribution of collagen and elastin in dermis were quantified to characterize the pathological states of PM. The results showed significant morphological difference between skin lesion before and after treatment, indicating the possibility of MPM to assess the therapeutic efficacy. With the advancement on MPM miniaturization and enhancement of contrast and depth of imaging, the MPM technique can be applied in in vivo tracking PM formation and progression, and leading the better understanding the PM pathogenesis and mechanism of response to any treatment, helping to establish novel effective therapies for PM.


Safety of a quadrivalent meningococcal serogroups A, C, W and Y conjugate vaccine (MenACWY-CRM) administered with routine infant vaccinations: results of an open-label, randomized, phase 3b controlled study in healthy infants.
The highest risk for invasive meningococcal disease (IMD) is in infants aged <1 year. Quadrivalent meningococcal conjugate vaccination has the potential to prevent IMD caused by serogroups A, C, W and Y. This phase 3b, multinational, open-label, randomized, parallel-group, multicenter study evaluated the safety of a 4-dose series of MenACWY-CRM, a quadrivalent meningococcal conjugate vaccine, concomitantly administered with routine vaccinations to healthy infants. Two-month-old infants were randomized 3:1 to receive MenACWY-CRM with routine vaccines or routine vaccines alone at ages 2, 4, 6 and 12 months. Adverse events (AEs) that were medically attended and serious adverse events (SAEs) were collected from all subjects from enrollment through 18 months of age. In a subset, detailed safety data (local and systemic solicited reactions and all AEs) were collected for 7 days post vaccination. The primary objective was a non-inferiority comparison of the percentages of subjects with ≥1 severe systemic reaction during Days 1-7 after any vaccination of MenACWY-CRM plus routine vaccinations versus routine vaccinations alone (criterion: upper limit of 95% confidence interval [CI] of group difference <6%). A total of 7744 subjects were randomized with 1898 in the detailed safety arm. The percentage of subjects with severe systemic reactions was 16% after MenACWY-CRM plus routine vaccines and 13% after routine vaccines alone (group difference 3.0% (95% CI -0.8, 6.4%). Although the non-inferiority criterion was not met, post hoc analysis controlling for significant center and group-by-center differences revealed that MenACWY-CRM plus routine vaccinations was non-inferior to routine vaccinations alone (group difference -0.1% [95% CI -4.9%, 4.7%]). Rates of solicited AEs, medically attended AEs, and SAEs were similar across groups. In a large multinational safety study, a 4-dose series of MenACWY-CRM concomitantly administered with routine vaccines was clinically acceptable with a similar safety profile to routine vaccines given alone.


Bivariate random effects meta-analysis of ROC curves.
Meta-analysis of receiver operating characteristic (ROC)-curve data is often done with fixed-effects models, which suffer many shortcomings. Some random-effects models have been proposed to execute a meta-analysis of ROC-curve data, but these models are not often used in practice. Straightforward modeling techniques for multivariate random-effects meta-analysis of ROC-curve data are needed. The 1st aim of this article is to present a practical method that addresses the drawbacks of the fixed-effects summary ROC (SROC) method of Littenberg and Moses. Sensitivities and specificities are analyzed simultaneously using a bivariate random-effects model. The 2nd aim is to show that other SROC curves can also be derived from the bivariate model through different characterizations of the estimated bivariate normal distribution. Thereby the authors show that the bivariate random-effects approach not only extends the SROC approach but also provides a unifying framework for other approaches. The authors bring the statistical meta-analysis of ROC-curve data back into a framework of relatively standard multivariate meta-analysis with random effects. The analyses were carried out using the software package SAS (Proc NLMIXED).


Fever of unknown origin in childhood: difficulties in diagnosis.
We have described a child with systemic onset juvenile chronic arthritis who presented initially with fever of unknown origin. Treatment of a presumed infection led to a severe allergic response with Stevens-Johnson syndrome, renal failure and DIC. This reaction obscured the features of the underlying disease and delayed the diagnosis.


Carriage of multiple subtypes of methicillin-resistant Staphylococcus aureus by intensive care unit patients.
To determine how consistently patients are colonized with methicillin-resistant Staphylococcus aureus (MRSA) at various sites and how many subtypes can be carried simultaneously by a single patient. A 28-bed Intensive care unit in a tertiary-care referral hospital. A total of 1,181 patients were screened by culture of swab specimens obtained from the nose, throat, groin, and axilla on admission to the intensive care unit (ICU), twice weekly during their ICU stay, and at discharge. MRSA was isolated at least once from 224 patients. Of these isolates, 359 were selected from 32 patients to be subtyped using pulsed-field gel electrophoresis. The rate of compliance with collection of swab specimens was 79.9%. The combination of sites colonized varied frequently over time for many patients. Of patients who had swab specimens obtained twice in 1 day, 8.7% had discordant results from the 2 swab sets. No patient had a clinical isolate that was not of an identical subtype to an isolate from an anatomical site that was sampled for screening. Half the patients carried multiple subtypes during their stay, with up to 4 subtypes per patient. The findings of this study may indicate that these patients have been colonized with MRSA on more than one occasion, possibly because of multiple breaches in infection control procedure. In MRSA-colonized patients, anatomical sites were intermittently colonized and carriage of multiple subtypes was common. These findings indicate that MRSA carriage is not a fixed state but may vary over time.


Quantitative analysis of molecular surfaces: areas, volumes, electrostatic potentials and average local ionization energies.
We describe a procedure for performing quantitative analyses of fields f(r) on molecular surfaces, including statistical quantities and locating and evaluating their local extrema. Our approach avoids the need for explicit mathematical representation of the surface and can be implemented easily in existing graphical software, as it is based on the very popular representation of a surface as collection of polygons. We discuss applications involving the volumes, surface areas and molecular surface electrostatic potentials, and local ionization energies of a group of 11 molecules.


Characteristics of Inpatient Falls not Reported in an Incident Reporting System.
An incident reporting system is the most commonly used method to identify patient safety incidents in a hospital. However, non-reporting of incidents for various reasons is a serious problem. We studied the rate of inpatient falls that were not reported in an incident reporting system but were recorded in medical charts and we evaluated characteristics of those falls by comparing with the falls reported in incident reports in a Japanese acute care hospital setting. Falls recorded in medical charts were detected by using a text mining method followed by a manual chart review. About 25% of the recorded falls were not reported in incident reports. Male patients, first fall, long lag time until recording, no witness at the time of the fall and physician profession were shown to be significant factors associated with non-reporting. Our results show that the rate of non-reporting of inpatient falls in a Japanese acute care hospital is compable to that shown in previous studies in other conutries and that the same barriers to incident reporting as those found in previous studies exist in the medical staff.


Divergent DNA methylation contributes to duplicated gene evolution and chilling response in tea plants.
The tea plant (Camellia sinensis) is a thermophilic cash crop and contains a highly duplicated and repeat-rich genome. It is still unclear how DNA methylation regulates the evolution of duplicated genes and chilling stress in tea plants. We therefore generated a single-base-resolution DNA methylation map of tea plants under chilling stress. We found that, compared with other plants, the tea plant genome is highly methylated in all three sequence contexts, including CG, CHG and CHH (where H = A, T, or C), which is further proven to be correlated with its repeat content and genome size. We show that DNA methylation in the gene body negatively regulates the gene expression of tea plants, whereas non-CG methylation in the flanking region enables a positive regulation of gene expression. We demonstrate that transposable element-mediated methylation dynamics significantly drives the expression divergence of duplicated genes in tea plants. The DNA methylation and expression divergence of duplicated genes in the tea plant increases with evolutionary age and selective pressure. Moreover, we detect thousands of differentially methylated genes, some of which are functionally associated with chilling stress. We also experimentally reveal that DNA methyltransferase genes of tea plants are significantly downregulated, whereas demethylase genes are upregulated at the initial stage of chilling stress, which is in line with the significant loss of DNA methylation of three well-known cold-responsive genes at their promoter and gene body regions. Overall, our findings underscore the importance of DNA methylation regulation and offer new insights into duplicated gene evolution and chilling tolerance in tea plants.


Endoscopy-guided ablation of pancreatic lesions: Technical possibilities and clinical outlook.
Endoscopic ultrasound (EUS) and endoscopic retrograde cholangiopancreatography (ERCP)-guided ablation procedures are emerging as a minimally invasive therapeutic alternative to radiological and surgical treatments for locally advanced pancreatic cancer (LAPC), pancreatic neuroendocrine tumours (PNETs), and pancreatic cystic lesions (PCLs). The advantages of treatment under endoscopic control are the real-time imaging guidance and the possibility to reach a deep target like the pancreas. Currently, radiofrequency probes specifically designed for ERCP or EUS ablation are available as well as hybrid cryotherm probe combining radiofrequency with cryotechnology. To date, many reports and case series have confirmed the safety and feasibility of that kind of ablation technique in the pancreatic setting. Moreover, EUS-guided fine-needle injection is emerging as a method to deliver ablative and anti-tumoral agents inside the tumuor. Ethanol injection has been proposed mostly for the treatment of PCLs and for symptomatic functioning PNETs, and the use of gemcitabine and paclitaxel is also interesting in this setting. EUS-guided injection of chemical or biological agents including mixed lymphocyte culture, oncolytic viruses, and immature dendritic cells has been investigated for the treatment of LAPC. Data on the long-term efficacy of these approaches, and large prospective randomized studies are needed to confirm the real clinical benefits of these techniques for the management of pancreatic lesions.


Induction of leukocyte infiltration at metastatic site mediates the protective effect of NGcGM3-based vaccine.
While the NGcGM3/VSSP vaccine, a preparation consisting in very small sized proteoliposomes (VSSP) obtained by the incorporation of the NGcGM3 ganglioside into the outer membrane protein (OMP) complex of Neisseria meningitides, is currently studied in late stage clinical trials in breast cancer and melanoma patients, mechanisms involved in the vaccine's antitumor effect are insufficiently understood. Here we have addressed the role of adaptive and innate immune cells in mediating the protective effect of the vaccine. To this aim we selected the 3LL-D122 Lewis lung spontaneous metastasis model. Unexpectedly, inoculation of the vaccine in tumor bearing C57BL/6 mice, either by subcutaneous (sc) or intraperitoneal (ip) routes, induced similar anti-metastatic effect. Regardless the T-independent nature of NGcGM3 ganglioside as antigen, the antimetastatic effect of NGcGM3/VSSP is dependent on CD4(+) T cells. In a further step we found that the vaccine was able to promote the increase, maturation, and cytokine secretion of conventional DCs and the maturation of Bone Marrow-derived plasmacytoid DCs. In line with this result the in vivo IFNα serum level in ip vaccinated mice increased as soon as 2h after treatment. On the other hand the infiltration of NK1.1(+)CD3(-) and NK1.1(+)CD3(+) cells in lungs of vaccinated mice was significantly increased, compared with the presence of these cells in control animal lungs. In the same way NGcGM3/VSSP mobilized acquired immunity effector cells into the lungs of vaccinated tumor bearing mice. Finally and not less noteworthy, leukocyte infiltration in lungs of tumor bearing mice correlates with vaccine induced inhibition of lung metastization.


Risk Factor Assessment and the Incidence of Neonatal Hypoglycemia in the Postnatal Period.
The aim of this study was to evaluate risk factors used for the assessment of neonatal hypoglycemia and to examine the follow-up outcomes observed in the first 48 hours of postnatal life. The records of infants born between 2015 and 2017 (3 years) at Şişli Hamidiye Etfal Training and Research Hospital who had a blood glucose level test performed within the first 24 hours after birth and who had follow-up results for 48 hours were included in the study. Data of gestational age; birth weight; gender; antenatal, natal and postnatal characteristics; blood glucose measurement method and time during the first 48 hours postpartum; glucose values and follow-up; nutritional status; and the need for hospitalization due to a low blood glucose value were recorded. Groups were created based on data of a diabetic mother, small for gestational age (SGA), large for gestational age (LGA), late preterm birth (34-36+6/7 gestational weeks), fetal distress, and feeding intolerance. Blood glucose measurement values and reasons for hypoglycemia and assessment were compared in subgroups. The data of 9480 infants were reviewed and included in the study. It was determined that blood levels were checked in 28.7% (n=2720). The mean birth weight and gestational age of the infants was 3143±804 g and 37.7±2.5 weeks, respectively. In the study group, 54.7% were male, and 57.5% were delivered via cesarean section. The most frequent factors prompting blood glucose measurement were LGA status (25.9%), prematurity (18%), transient tachypnea (17.3%), and SGA status (11.6%). Results revealed that the blood glucose values of 2009 (73.9%) infants were within normal limits, and there was no further monitoring of blood glucose level during the first 48 hours. In 711 (26.1%), a low blood glucose level finding led to follow-up assessment. The incidence of hospitalization with a preliminary diagnosis of hypoglycemia was 2.5% (n=67). Subgroup analysis indicated that at the first hour, the mean blood glucose value of the patients with multiple factors that were risks for hypoglycemia suggesting further evaluation was lower than those with transient tachypnea and fetal distress (p<0.001), and the mean blood glucose value of premature and LGA neonates were significantly lower than the infants of diabetic mothers at the sixth hour (p<0.001). In the postnatal period, the rate of monitoring blood glucose levels in newborn babies was found to be 28.7% and the most commonly predicted risk factor was LGA babies. The frequency of postpartum hospitalization due to hypoglycemia was found to be 2.5%, and blood sugar levels were lower in the first hour in groups with multiple causes.


Treatment of Radial Nonunion with Corticocancellous Bone Graft and Fascia of Anterolateral Thigh Free Flap: The Wrap Technique.
The management of nonunion of the forearm bones is a challenging task. Multiple factors have been associated with the establishment of forearm nonunion, such as the fracture position and complexity, general condition of the patient, and the previously utilized surgical technique. The optimal surgical treatment of a bone gap remains a subject of discussion. Autogenous corticocancellous bone grafts and vascularized bone flaps have been used with differing results. The authors describe a technique for the treatment of posttraumatic nonunion of the radius with a 5-cm bone gap using the free anterolateral thigh fascial flap wrapped around a tricortical iliac bone graft. The fracture healed after 5 weeks. The use of a vascularized tissue wrapped around the bone graft resulted in a well-healed bone and no signs of resorption after 2 years of follow-up. A bone graft wrapped by a fascial flap could magnify the restorative effect on the bone defect because of its dual role of constructing vascularization and inducing tissue regeneration.


CACNA1B mutation is linked to unique myoclonus-dystonia syndrome.
Using exome sequencing and linkage analysis in a three-generation family with a unique dominant myoclonus-dystonia-like syndrome with cardiac arrhythmias, we identified a mutation in the CACNA1B gene, coding for neuronal voltage-gated calcium channels CaV2.2. This mutation (c.4166G>A;p.Arg1389His) is a disruptive missense mutation in the outer region of the ion pore. The functional consequences of the identified mutation were studied using whole-cell and single-channel patch recordings. High-resolution analyses at the single-channel level showed that, when open, R1389H CaV2.2 channels carried less current compared with WT channels. Other biophysical channel properties were unaltered in R1389H channels including ion selectivity, voltage-dependent activation or voltage-dependent inactivation. CaV2.2 channels regulate transmitter release at inhibitory and excitatory synapses. Functional changes could be consistent with a gain-of-function causing the observed hyperexcitability characteristic of this unique myoclonus-dystonia-like syndrome associated with cardiac arrhythmias.


Morphological and secretory characterization of extrafloral nectaries in plants of coastal Veracruz, Mexico.
Morphological descriptions of the extrafloral nectaries (EFNs) of certain plant species are common in the literature, but they rarely relate morphology with histology, gland distribution and secretory attributes. In this study a morphological/secretory characterization of EFNs occurring on several plant species in a tropical coastal community is made and the implications of gland attributes discussed from a functional perspective. The morphology and nectar secretion of the EFNs of 20 plant species are characterized through scanning electron microscopy, histochemical detection of reducing sugars (Fehling's reagent) and nectar volume/concentration estimates. Sixty-five per cent of plant species in coastal communities had EFNs on vegetative structures and 35 % of species had glands on reproductive and vegetative organs. The Fabaceae is the plant family with the most species with EFNs and most diversity of gland morphologies. Four types of vascularized nectaries and four of glandular trichomes are described; sugar-secreting trichomes are characterized using Fehling's technique, and the first descriptions of unicellular and peltate trichomes functioning as EFNs are provided. Glands of ten plant species and six genera are described for the first time. Four plant species possess more than one morphological type of EFN. Eleven species have EFNs in more than one location or organ. More complex glands secrete more nectar, but are functionally homologous to the aggregations of numerous secretory trichomes on specific and valuable plant organs. Important diversity of EFN morphology was foundin the coastal plant community studied. Both vascularized and non-vascularized EFNs are observed in plants and, for the latter, previously non-existent morpho-secretory characterizations are provided with a methodological approach to study them. It is recommended that studies relating EFN attributes (i.e. morphology, distribution) with their differential visitation by insects (i.e. ants) and the cost of maintenance to the plants are carried out to understand the evolution of these glands.


Facile Fabrication of Biomimetic Chitosan Membrane with Honeycomb-Like Structure for Enrichment of Glycosylated Peptides.
In the study of glycoproteomics with mass spectrometry, certain pretreatments of samples are required for eliminating the interference of nonglycopeptides and improving the efficiency of glycopeptides detection. Although hydrophilic interaction chromatography (HILIC) has been developed for enrichment of glycosylated peptides, a plethora of hydrophilic materials always suffered from large steric hindrance, great cost, and difficulty with modifications of high-density hydrophilic groups. In this work, a 1 mm thick biomimetic honeycomb chitosan membrane (BHCM) with honeycomb-like accessible macropores was directly prepared by the freeze-casting method as an adsorbent for HILIC. The N-glycopeptides from trypsin digests of immunoglobulin G (IgG), mixture of IgG and bovine serum albumin (BSA), and serum proteins were enriched using this material and compared with a commercial material ZIC-HILIC. The biomimetic membrane could identify as many as 32 N-glycopeptides from the IgG digest, exhibiting high sensitivity (about 50 fmol) and a wide scope for glycopeptide enrichment. A molar ratio of IgG trypsin digest to bovine serum albumin trypsin digest as low as 1/500 verified the outstanding specificity and efficiency for glycopeptide enrichment. In addition, 270 unique N-glycosylation sites of 400 unique glycopeptides from 146 glycosylated proteins were identified from the triplicate analysis of 2 μL human serum. Furthermore, 48 unique O-glycosylation sites of 278 unique O-glycopeptides were identified from the triplicate analysis of 30 μg deglycosylated fetuin digest. These results indicated that the chitosan-based membrane prepared in this work had great potential for pretreatment of samples in glycoproteomics.


A resilience concept based on system functioning: A dynamical systems perspective.
We introduce a new framework for resilience, which is traditionally understood as the ability of a system to absorb disturbances and maintain its state, by proposing a shift from a state-based to a system functioning-based approach to resilience, which takes into account that several different coexisting stable states could fulfill the same functioning. As a consequence, not every regime shift, i.e., transition from one stable state to another, is associated with a lack or loss of resilience. We emphasize the importance of flexibility-the ability of a system to shift between different stable states while still maintaining system functioning. Furthermore, we provide a classification of system responses based on the phenomenological properties of possible disturbances, including the role of their timescales. Therefore, we discern fluctuations, shocks, press disturbances, and trends as possible disturbances. We distinguish between two types of mechanisms of resilience: (i) tolerance and flexibility, which are properties of the system, and (ii) adaptation and transformation, which are processes that alter the system's tolerance and flexibility. Furthermore, we discuss quantitative methods to investigate resilience in model systems based on approaches developed in dynamical systems theory.


Synaesthesia.
Synaesthesia is the intriguing, involuntary experience of feeling one sensation in response to a different sensory stimulus. Recognised since described in 1890 by John Locke and clarified by Galton in the 1880s, it has been analysed in the last 50 years. Grapheme-colour synaesthesia is the commonest form, but many other sensory linkages are reported. Experiments show that it is a genuine immediate perception, not merely a memory or learned association. Many of the mechanisms posited are based on indirect methods, and we know little of the neurophysiological mechanisms.


[Surgical approach to recurrent papillary thyroid carcinoma involving the larynx: a case report].
A 54-year-old male patient presented with a complaint of a mass in the anterior aspect of the neck of three-month duration. He had a history of total and near-total thyroidectomy in the right and left lobes, respectively, and right modified radical neck dissection at another center 12 months before. Physical examination showed a laryngeal mass, 4 x 5 cm in size, in the midline of the neck, and bilateral and multiple lymphadenopathies. Fiberoptic laryngoscopy showed a lobular contour mass filling the laryngeal lumen and involving the anterior commissure and a fixed right vocal cord. Biopsy result of the lesion was consistent with papillary carcinoma of the thyroid. The patient underwent total laryngectomy and bilateral neck dissection followed by reconstruction with the pectoralis major myocutaneous flap. Histopathologic examination showed laryngeal infiltration of the recurrent papillary thyroid carcinoma. Postoperative radioiodine (I-131) therapy was administered. No recurrences or distant metastasis were detected within a follow-up period of 10 months.


Comparison of the organic matrix found in intestinal CaCO3 precipitates produced by several marine teleost species.
Marine bony fish poses the unique ability to hydrate from imbibed seawater. They accomplish this, in part, by the precipitation of inorganic carbonate mineral in their intestine, which lowers luminal osmotic pressure and allows for water uptake. It has recently been described that in the Gulf toadfish (Opsanus beta) this Ca(Mg)CO3 precipitation occurs under the regulation of an organic matrix. To date no investigations have aimed to determine if this phenomenon applies more generally to marine fish. Here, intestinally derived precipitates were collected from gray snapper (Lutjanus griseus), white grunt (Haemulon plumieri), European flounder (Platichthys flesus), as well as Gulf toadfish, and their matrices were extracted. The ability of these matrices to regulate CaCO3 production was determined using an in vitro calcification assay, which revealed that the matrix derived from each of the tested species increased precipitation at low concentrations, while inhibiting it at higher concentrations in full agreement with the earlier studies on toadfish. Matrix extracted from European flounder precipitates was then analyzed by mass spectrometry, leading to the identification of over 50 unique proteins. When the identities of these proteins were compared to previous investigation of toadfish precipitate matrix, nearly 35% were found to overlap between the flounder and toadfish analyses, suggesting conserved mechanisms of precipitation control. The effects of using different sodium hypochlorite (NaOCl) solutions during precipitate purification on the resulting organic matrix are also discussed.


[Pregnancies following kidney transplantation--clinical problems and genetic studies].
Successful transplantations of the kidney by means of the medical rehabilitation also improve the reproductive rehabilitation of the young patients with distinct wish for children. In these cases the increased infectious, genetic, rejection and tumour risks as well as a limited transplant survival time require particular consideration. On 15 pregnancies among 151 patients in the Regional Dispensary for Patients who underwent kidney transplantations in Halle the clinical and genetic problems are discussed. A patient with preexisting risk factors under interdisciplinary intensive care bore a healthy child who is now 10 years old. The mother is still alive 12 years after the transplantation. Studies on 6 pregnancies in 3 patients who underwent a transplantation revealed 1 normal delivery and 5 interruptions for somatic and genetic indications. 2 female patients are alive 5 and 12 years after transplantation, 1 female patient again undergoes dialysis. From 9 pregnancies by 8 fathers who underwent transplantation 8 children were born (4-10 years) and 1 interruption had to be made. 4 patients live in the 8th to 11th year with the first transplant and 1 patient lives with the second transplant for 8 years. 4 patients again underwent dialysis, one patient died. Human-genetic problems are existing in the autosomal-recessively hereditary Alport-syndrome by the daughter as gene-carrier. 15 analyses of chromosomes on 396 investigated mitoses resulted in chromosomal break rates of 2, 4.7 and 5% in three children at the end of the second year of age, in the mother of 7% in the 4th year and in 2 fathers of 4 and 22% in the 4th and 5th year after transplantation.(ABSTRACT TRUNCATED AT 250 WORDS)


Development of a 32P-postlabeling method for the detection of 1, N2-propanodeoxyguanosine adducts of 2-hexenal in vivo.
2-Hexenal is an alpha,beta-unsaturated carbonyl compound which forms cyclic 1,N2-propano adducts in vitro. The adduct formation in vivo was not reported by others to date. Because this type of adduct is considered promutagenic (2-hexenal is actually mutagenic and genotoxic) and humans are permanently exposed to this compound via vegetarian food, 2-hexenal may play a role in carcinogenicity. To improve the cancer risk assessment, we developed a new 32P-postlabeling technique for this compound and optimized the different steps of the postlabeling procedure. The results of the postlabeling methods are shown. A labeling efficiency of 35%, a recovery of 10% for the synthesized standards, and a detection limit of three 2-hexenal adducts per 10(8) nucleotides was achieved. After gavage of 500 mg/kg of body weight to male Fischer 344 rats, the respective DNA adducts were detected in rat liver DNA. With this study, we demonstrate in vivo adduct formation of 2-hexenal for the first time. Highest adduct levels were found 2 days after gavage, and after 4 days, the level was even higher than after 1 day. No adducts were detected 8 h after gavage. The respective adducts could not be found as a background in tissues of untreated rats or in calf thymus DNA at the limit of detection.


Endovascular Treatments for Ruptured Intracranial Vertebral Artery Dissecting Aneurysms: Experience in 16 Patients.
Intracranial vertebral artery dissecting aneurysms are rare lesions that are considered an important cause of spontaneous subarachnoid hemorrhage. We report our decade-long experience in treating ruptured intracranial vertebral artery dissecting aneurysms. This retrospective single-center study included 21 consecutive patients between February 2005 and March 2015. Their clinical features included radiologic finding at the initial examination, treatment modality, functional outcome at the last follow-up, mortality, and radiologic outcome at more than 6 months after the initial treatment. All 16 aneurysms were treated endovascularly; aneurysm trapping was performed in 9 patients and vascular reconstruction was performed in 7 patients. For 6 aneurysms involving the posterior inferior cerebellar artery (PICA), the modalities of treatment were aneurysm trapping in 3 patients and vascular reconstruction in 3 patients. The mean duration of follow-up was 29 months (range, 6-70 months). Five patients expired, indicating a mortality rate of 31%. In surviving patients, the unfavorable outcome rate (modified Rankin Scale [mRS] > 2) was 36%. The overall mean mRS for survivors was 1.8. Angiographic follow-up in 11 survivors at 13 months, (range, 6-46 months) revealed recanalization of the aneurysm in one patient. Ruptured intracranial vertebral artery dissecting aneurysm is associated with poor functional outcome and high mortality. More immediate treatments are needed due to the high rebleeding rate in this disease condition. Endovascular treatment may be a useful option for ruptured intracranial vertebral artery dissecting aneurysms.


Study of the infradiaphragmatic total anomalous pulmonary venous connection with cross-sectional and pulsed Doppler echocardiography.
We studied neonates with the infradiaphragmatic form of total anomalous pulmonary venous drainage by a combination of cross-sectional echocardiography and pulsed Doppler ultrasound. The diagnosis by ultrasound was made prospectively in all six patients. Three large vascular channels could be observed passing through the diaphragm from the subcostal parasagittal plane. The vessels were identified as the descending aorta (to the left), the inferior vena cava (to the right), and the anomalous pulmonary venous channel (in the center). The vessels were insonated in turn, with pulsed Doppler ultrasound, and the characteristic normal flow signals in the aorta and inferior vena cava were obtained. The signal from the anomalous pulmonary vein was a continuous venous signal, the direction of flow being away from the heart. Pulsed Doppler ultrasound allows accurate recognition of the anomalous pulmonary venous channel without the use of contrast echocardiography.


Monitoring of fluoride concentration in ground water of Prakasham District in India: correlation with physico-chemical parameters.
Fluoride concentrations in surface and ground water samples were determined in eight villages of Prakasham district in India. Thirty-eight samples were collected and analysed for fluoride content along with pH, electrical conductivity, total dissolved solids (TDS), total hardness, total alkalinity, chlorides (C1), sulfates (SO2-) and nitrates (NO ). Fluoride concentrations in surface and ground water samples of these villages varied between 0.5 and 9.0 mg/L. Groundwater samples contained high concentrations of fluorides compared to open well and pond water samples, which could be a major source of fluoride in water since the geological formation of this area consists of fluorite and fluoropatite. From the data, it is evident that the population in the study area is severely affected by fluorosis. Dental and skeletal fluorosis and deformation of bones in children as well as adults were observed in the study area indicating the consequences of excess fluoride concentration. Fluoride concentrations showed good correlation with TDS concentrations (R2 of 0.61) compared to other physico-chemical parameters [EC (R2 - 0.36), nitrate (R - 0.24), total hardness (R - 0.12), chloride (R2 - 0.06) and sulfate (R2 - 4 x 10(-6))].


Non-invasive positive pressure ventilation for central sleep apnoea in adults.
Central sleep apnoea (CSA) is characterised by abnormal patterns of ventilation during sleep due to a dysfunctional drive to breathe. Consequently, people with CSA may present poor sleep quality, sleep fragmentation, inattention, fatigue, daytime sleepiness, and reduced quality of life. To assess the effectiveness and safety of non-invasive positive pressure ventilation (NIPV) for the treatment of adults with CSA. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, and Scopus on 6 September 2021. We applied no restrictions on language of publication. We also searched clinical trials registries for ongoing and unpublished studies, and scanned the reference lists of included studies to identify additional studies. We included randomised controlled trials (RCTs) reported in full text, those published as abstract only, and unpublished data. Two review authors independently selected studies for inclusion, extracted data, and assessed risk of bias of the included studies using the Cochrane risk of bias tool version 1.0, and the certainty of the evidence using the GRADE approach. In the case of disagreement, a third review author was consulted. We included 15 RCTs with a total of 1936 participants, ranging from 10 to 1325 participants. All studies had important methodological limitations. We assessed most studies (11 studies) as at high risk of bias for at least one domain, and all studies as at unclear risk of bias for at least two domains. The trials included participants aged > 18 years old, of which 70% to 100% were men, who were followed from one week to 60 months. The included studies assessed the effects of different modes of NIPV and CSA. Most participants had CSA associated with chronic heart failure. Because CSA encompasses a variety of causes and underlying clinical conditions, data were carefully analysed, and different conditions and populations were not pooled. The findings for the primary outcomes for the seven evaluated comparisons are presented below. Continuous positive airway pressure (CPAP) plus best supportive care versus best supportive care in CSA associated with chronic heart failure In the short term, CPAP plus best supportive care may reduce central apnoea hypopnoea index (AHI) (mean difference (MD) -14.60, 95% confidence interval (CI) -20.11 to -9.09; 1 study; 205 participants). However, CPAP plus best supportive care may result in little to no difference in cardiovascular mortality compared to best supportive care alone. The evidence for the effect of CPAP plus best supportive care on all-cause mortality is very uncertain. No adverse effects were observed with CPAP, and the results for adverse events in the best supportive care group were not reported. Adaptive servo ventilation (ASV) versus CPAP in CSA associated with chronic heart failure The evidence is very uncertain about the effect of ASV versus CPAP on quality of life evaluated in both the short and medium term. Data on adverse events were not reported, and it is not clear whether data were sought but not found. ASV versus bilevel ventilation in CSA associated with chronic heart failure In the short term, ASV may result in little to no difference in central AHI. No adverse events were detected with ASV, and the results for adverse events in the bilevel ventilation group were not reported. ASV plus best supportive care versus best supportive care in CSA associated with chronic heart failure In the medium term, ASV plus best supportive care may reduce AHI compared to best supportive care alone (MD -20.30, 95% CI -28.75 to -11.85; 1 study; 30 participants). In the long term, ASV plus best supportive care likely increases cardiovascular mortality compared to best supportive care (risk ratio (RR) 1.25, 95% CI 1.04, 1.49; 1 study; 1325 participants). The evidence suggests that ASV plus best supportive care may result in little to no difference in quality of life in the short, medium, and long term, and in all-cause mortality in the medium and long term. Data on adverse events were evaluated but not reported. ASV plus best supportive care versus best supportive care in CSA with acute heart failure with preserved ejection fraction Only adverse events were reported for this comparison, and no adverse events were recorded in either group. ASV versus CPAP maintenance in CPAP-induced CSA In the short term, ASV may slightly reduce central AHI (MD -4.10, 95% CI -6.67 to -1.53; 1 study; 60 participants), but may result in little to no difference in quality of life. Data on adverse events were not reported, and it is not clear whether data were sought but not found. ASV versus bilevel ventilation in CPAP-induced CSA In the short term, ASV may slightly reduce central AHI (MD -8.70, 95% CI -11.42 to -5.98; 1 study; 30 participants) compared to bilevel ventilation. Data on adverse events were not reported, and it is not clear whether data were sought but not found. CPAP plus best supportive care may reduce central AHI in people with CSA associated with chronic heart failure compared to best supportive care alone. Although ASV plus best supportive care may reduce AHI in people with CSA associated with chronic heart failure, it likely increases cardiovascular mortality in these individuals. In people with CPAP-induced CSA, ASV may slightly reduce central AHI compared to bilevel ventilation and to CPAP. In the absence of data showing a favourable impact on meaningful patient-centred outcomes and defining clinically important differences in outcomes in CSA patients, these findings need to be interpreted with caution. Considering the level of certainty of the available evidence and the heterogeneity of participants with CSA, we could draw no definitive conclusions, and further high-quality trials focusing on patient-centred outcomes, such as quality of life, quality of sleep, and longer-term survival, are needed to determine whether one mode of NIPV is better than another or than best supportive care for any particular CSA patient group.


Disability training for genetic counseling students: The advocates' perspective.
The genetics and disability communities have had a complicated relationship that is rooted in the history of the eugenics movement. Disability scholars claim that in order for healthcare professionals to provide optimal services to disabled patients, disability education must be implemented into healthcare training programs. No studies have explored the perspectives of disability advocates regarding the implementation and use of disability training in genetic counseling. This exploratory study recruited 13 advocates with lived experience of disability and genetic counseling exposure to participate in a semi-structured interview to share their recommendations for disability education opportunities in genetic counseling training programs and their perceived benefits of increased student exposure to disability. All advocates received genetic counseling themselves and four advocates reported working with genetic counselors in the advocacy setting. Advocates recounted their experiences working with genetic counselors, identifying qualities they deemed critical for effective counseling. All the advocates expressed interest in participating in experiential opportunities, with few concerns noted. The most frequently discussed recommendations for disability training included inviting advocates to speak in classrooms, and having students shadow disabled individuals. Advocates noted barriers to consider when implementing such educational opportunities, such as accessibility issues. Potential benefits of implementing disability education for students included providing students with a broader scope of knowledge and a deeper understanding of disability and resources available to the disability community. This novel study found that advocates are interested in participating in genetic counseling education, with recommendations on preferred experiential learning. By increasing a genetic counseling student's exposure to a disability, they may develop a comprehensive understanding of life with a disability, which may improve genetic counseling services to those with newly diagnosed disabilities.


Etiological agents of superficial mycoses in Kayseri, Turkey.
In this study, we aimed to determine the prevalence of agents that cause superficial mycoses and clinical types of superficial mycoses in terms of age and gender in our region were aimed. Five hundred samples of nails, skin and skin with hair taken from 476 children and adult patients pre-diagnosed with superficial mycoses were examined by direct microscopy and cultural methods between October 2009 and October 2010. Fungal elements were determined in 212 (42.4%) of the samples by using direct microscopy. Fungal growth was detected in 111 (22.2%) cultures of the same samples. It was found that the most common agents in superficial mycoses were Trichophyton rubrum (43.7%), Candida spp. (28%) and less often, Aspergillus spp., Malassezia spp., Saccharomyces spp., Rhodotorula spp., Trichosporon spp. and Trichophyton verrucosum. The significance of diagnosis by using direct microscopy and culturing together was again shown for the diagnosis of superficial fungal infections that follow a chronic course and affect the quality of life of patients. The most common agents in the superficial mycoses were T. rubrum. With this study, defining the aetiological agents of superficial mycoses in the Kayseri region is expected to contribute to the literature in terms of epidemiological data.


Exhaled tidal volume overestimation in mechanically ventilated patients with large cardiogenic oscillation.
In postcardiac surgery patients, we often noticed that monitored tidal volumes exceeded the ventilator settings. We investigated whether cardiogenic oscillation causes overestimation of tidal volume. Prospective, observational, clinical study. Surgical intensive care unit in a national heart institute. Eight postcardiac surgery patients (age 13-70). Patients were paralyzed and received flow-triggered volume-controlled ventilation with a tidal volume of 10 mL/kg. In random order, two types of ventilator (Bird 8400 STi and Servo-300) and two respiratory rates (5 and 10 breaths/min) were applied to each patient via a disposal ventilatory circuit and heat-and-moisture exchanger. For each ventilator, we adjusted the flow-triggering sensitivity to prevent autotriggering due to cardiogenic oscillation: 10 L/min for the Bird 8400 STi and green zone for the Servo-300. The magnitude of cardiogenic oscillation during mechanical ventilation was defined as peak expiratory flow fluctuation at end-expiration. We recorded tidal volume using the monitoring devices on the ventilators and calculated the discrepancy from the set tidal volume. Cardiogenic oscillation was significantly greater with the Bird 8400STi (4.0 +/- 1.8 L/min) than with the Servo-300 (1.7 +/- 0.8 L/min). With the Bird 8400 STi, the discrepancy between monitored tidal volume and set tidal volume ranged from 15 to 260 mL when the respiratory rate was 5 breaths/min and from -9 to 75 mL at 10 breaths/min; there was a linear correlation between the overestimation of tidal volume and the magnitude of cardiogenic oscillation. In contrast, with the Servo-300, the discrepancy was relatively small (-36 to 14 mL). In mechanically ventilated patients with large cardiogenic oscillation, exhaled tidal volume is overestimated on at least one model of ventilator.


Strain-specific patterns of autonomic nervous system activity and heart failure susceptibility in mice.
Transgenic mice are widely used to study cardiac function, but strain-dependent differences in autonomic nervous system activity (ANSA) have not been explored. We compared 1) short-term pharmacological responses of cardiac rhythm in FVB vs. C57Black6/SV129 wild-type mice and 2) long-term physiological dynamics of cardiac rhythm and survival in tumor necrosis factor (TNF)-alpha transgenic mice with heart failure (TNF-alpha mice) on defined backgrounds. Ambulatory telemetry electrocardiographic recordings and response to saline, adrenergic, and cholinergic agents were examined in FVB and C57Black6/SV129 mice. In FVB mice, baseline heart rate (HR) was higher and did not change after injection of isoproterenol or atropine but decreased with propranolol. In C57Black6/SV129 mice, HR did not change with propranolol but increased with isoproterenol or atropine. Mean HR, but not indexes of HR variability, was an excellent predictor of response to autonomic agents. The proportion of surviving animals was higher in TNF-alpha mice on an FVB background than on a mixed FVB/C57Black6 background. The homeostatic states of ANSA are strain specific, which can explain the interstrain differences in mean HR, pharmacological responses, and survival of animals with congestive heart failure. Strain-specific differences should be considered in selecting the strains of mice used for transgenic and gene targeting experiments.


Opposite Associations Between the rs3845446 Single-Nucleotide Polymorphism of the CACNA1E Gene and Postoperative Pain-Related Phenotypes in Gastrointestinal Surgery Versus Previously Reported Orthognathic Surgery.
Cav2.3 (R-type) voltage-activated Ca(2+) channels (VACCs), encoded by the calcium channel, voltage-dependent, R-type, α1E subunit (CACNA1E) gene, are responsible for transmission of somatic inflammatory pain, and activation of antinociception elicited by visceral inflammatory pain stimuli. Carriers of the minor G allele of the rs3845446 single-nucleotide polymorphism (SNP) of the CACNA1E gene reportedly exhibit a decrease in opioid requirements to control typical somatic inflammatory pain after orthognathic surgery (ie, a painful cosmetic surgery), suggesting the downregulation of Cav2.3 VACC function that is responsible for transmission of somatic inflammatory pain in these carriers. Gastrointestinal surgery involves somatic and visceral inflammatory pain, in which visceral inflammatory pain stimuli activate Cav2.3 VACC-mediated antinociception. Unknown is whether pain-related phenotypes after gastrointestinal surgery are affected in these carriers. The present study used a correlational design to examine the effect of the rs3845446 SNP on postoperative pain-related phenotypes in 2 groups of patients who underwent gastrointestinal surgery. Carriers of the minor G allele had greater opioid requirements after laparoscopic colectomy when intravenous patient-controlled analgesia was used, and reported higher pain scores after open gastrointestinal surgery when postoperative analgesia was managed with continuous epidural analgesia and rescue analgesics. These results suggest that pain-related phenotypes after gastrointestinal surgery are enhanced in carriers of the minor G allele of the rs3845446 SNP, possibly through impairment of Cav2.3 VACC function that is responsible for the activation of visceral inflammatory pain stimulus-elicited antinociception. Carriers of the minor allele of the rs3845446 SNP of the CACNA1E gene required more opioid or reported higher pain scores after gastrointestinal surgery, and required less opioid after orthognathic surgery. The difference may result from the presence of visceral inflammatory pain stimulus that activates Cav2.3 VACCs-mediated antinociception.


Different peripheral mechanisms mediate enhanced nociception in metabolic/toxic and traumatic painful peripheral neuropathies in the rat.
Mechanisms underlying neuropathic pain states are poorly understood. We have compared mechanisms mediating enhanced nociception of four established models of neuropathic pain produced by very different types of insults to the peripheral nervous system: streptozotocin-induced hyperalgesia, a model of diabetic (metabolic) peripheral neuropathy, vincristine-induced hyperalgesia, a model of chemotherapeutic agent (toxic) peripheral neuropathy, and chronic constriction injury and partial nerve ligation, models of trauma-induced painful neuropathies. All four models resulted in prolonged mechanical hyperalgesia (>30% decrease in mechanical nociceptive threshold) and allodynia (detected by 10-209-mN-intensity von Frey hairs). In vincristine- and streptozotocin-induced hyperalgesia, the protein kinase A, protein kinase C and nitric oxide second messenger pathways in the periphery contributed to the hyperalgesia, while N-methyl-D-aspartate (NMDA) receptor-mediated events were not detected. None of these second messengers nor the NMDA receptor, which can contribute to peripheral sensitization of nociceptors, contributed to chronic constriction injury- and partial nerve ligation-induced hyperalgesia. In all four models the hyperalgesia was not antagonized by peripheral administration of a mu-opioid agonist.Our findings support the presence of a common abnormality in second messenger signaling in the periphery to the maintenance of two very different models of non-traumatic neuropathic pain, not shared by models of trauma-induced neuropathic pain.


HDTD: analyzing multi-tissue gene expression data.
By collecting multiple samples per subject, researchers can characterize intra-subject variation using physiologically relevant measurements such as gene expression profiling. This can yield important insights into fundamental biological questions ranging from cell type identity to tumour development. For each subject, the data measurements can be written as a matrix with the different subsamples (e.g. multiple tissues) indexing the columns and the genes indexing the rows. In this context, neither the genes nor the tissues are expected to be independent and straightforward application of traditional statistical methods that ignore this two-way dependence might lead to erroneous conclusions. Herein, we present a suite of tools embedded within the R/Bioconductor package HDTD for robustly estimating and performing hypothesis tests about the mean relationship and the covariance structure within the rows and columns. We illustrate the utility of HDTD by applying it to analyze data generated by the Genotype-Tissue Expression consortium. The R package HDTD is part of Bioconductor. The source code and a comprehensive user's guide are available at http://bioconductor.org/packages/release/bioc/html/HDTD.html : email@example.com Supplementary data are available at Bioinformatics online.


Immunophenotyping of angioimmunoblastic T-cell lymphomas by multiparameter flow cytometry.
Angioimmunoblastic T-cell lymphoma (AITL) is a distinct form of peripheral T-cell lymphoma (PTCL) frequently involving lymph nodes, spleen and bone marrow, and is associated with systemic symptoms. Its histologic features may be subtle at an early phase and difficult to diagnose. Despite the success of flow cytometry (FCM) in diagnosing B-cell neoplasm, FCM has not been widely accepted as a useful method for establishing the diagnosis of PTCL. Recently, the neoplastic T-cells in AITL have been shown to express CD10. We prospectively applied multiparameter FCM immunophenotyping to three cases of histologically confirmed AITL and identified a small (5-7%) population of CD4+/CD10+ T-cells in two cases. In one case, the CD4+/CD10+ population lacked surface signals of CD3 and CD7, but strongly expressed CD2, whereas CD45 expression was very weak; partial loss of surface CD3 was observed in the other. None of the lymph nodes with reactive hyperplasia, B-cell lymphomas, or Hodgkin's lymphoma studied during the same time period contained the CD4+/CD10+ population. These findings suggest that addition of CD4/CD10 and CD3/CD10 to FCM immunophenotyping panels is useful in the diagnosis of AITL. To the best of our knowledge, this is the first report to demonstrate CD10-expressing T-cells in AITL by FCM.


Range instability leads to cytonuclear discordance in a morphologically cryptic ground squirrel species complex.
The processes responsible for cytonuclear discordance frequently remain unclear. Here, we employed an exon capture data set and demographic methods to test hypotheses generated by species distribution models to examine how contrasting histories of range stability vs. fluctuation have caused cytonuclear concordance and discordance in ground squirrel lineages from the Otospermophilus beecheyi species complex. Previous studies in O. beecheyi revealed three morphologically cryptic and highly divergent mitochondrial DNA lineages (named the Northern, Central and Southern lineages based on geography) with only the Northern lineage exhibiting concordant divergence for nuclear genes. Here, we showed that these mtDNA lineages likely formed in allopatry during the Pleistocene, but responded differentially to climatic changes that occurred since the last interglacial (~120,000 years ago). We find that the Northern lineage maintained a stable range throughout this period, correlating with genetic distinctiveness among all genetic markers and low migration rates with the other lineages. In contrast, our results suggested that the Southern lineage expanded from Baja California Sur during the Late Pleistocene to overlap and potentially swamp a contracting Central lineage. High rates of intraspecific gene flow between Southern lineage individuals among expansion origin and expansion edge populations largely eroded Central ancestry from autosomal markers. However, male-biased dispersal in this system preserved signals of this past hybridization and introgression event in matrilineal-biased X-chromosome and mtDNA markers. Our results highlight the importance of range stability in maintaining the persistence of phylogeographic lineages, whereas unstable range dynamics can increase the tendency for lineages to merge upon secondary contact.


Saudi Arabian retinopathy of prematurity national telemedicine program: Achievements and challenges.
The Saudi Arabian Retinopathy of Prematurity National Telemedicine programme (SAROP) is a product of the National Committee for Retinopathy of Prematurity (ROP). The program includes ROP telescreening, diagnosis, and management of cases requiring treatment. Digital retinal images and filled ROP software requests were uploaded from 20 level-3 neonatal intensive care units (NICU) in the Kingdom of Saudi Arabia (KSA) to the King Khaled Eye Specialist Hospital server and the ROP telemedicine website. The data were accessed and reported by qualified retinal and pediatric ophthalmologists. Currently, retinal wide-angle digital cameras are available in 20 of the 31 level-3 NICUs of the Ministry of Health, Kingdom of KSA. This telemedicine approach is practical and effective in detecting and managing ROP cases. In the first 2.5 years, encouraging results were noticed with no unfavorable outcomes in the participating NICUs. Technical challenges were resolved promptly to ensure that the program ran smoothly. Therefore, this ideal state-of-the-art ROP telemedicine program could be also applied to similar and neighboring countries.