P wave dispersion predicts recurrence of paroxysmal atrial fibrillation in patients with atrioventricular nodal reentrant tachycardia treated with radiofrequency catheter ablation.
Paroxysmal atrial fibrillation (AF) recurs in up to one-third of patients with atrioventricular nodal reentrant tachycardia (AVNRT) treated with slow pathway ablation. Therefore, identification of patients at risk for recurrence of AF after slow pathway ablation is important because of the necessity for additional therapies. The purpose of this study was to determine whether successful slow pathway ablation influences P wave parameters and whether these parameters predict the recurrence of paroxysmal AF in patients with both AVNRT and paroxysmal AF after ablation. Thirty-six patients with AVNRT and documented paroxysmal AF (Group 1) were compared to 36 age-matched controls with AVNRT only (Group 2). P wave durations and P dispersion were measured before and after ablation. No significant differences were observed between P wave parameters observed before and after ablation. Maximum P wave durations (Pmax) and P dispersion (Pdisp) were significantly higher in Group 1 than in Group 2 (P < 0.001 for both) whereas minimum P wave durations did not differ between groups, both before and after ablation. Ten patients (28%) in Group-1 had recurrence of AF during a mean follow-up of 34 +/- 11 months. Univariate predictors of AF recurrence were Pdisp > or =35.5 ms (P < 0.010), left atrial diameter >40 mm (P < 0.010), mitral or aortic calcification (P < 0.010), Pmax > or =112 ms (P < 0.050), valvular heart disease (P < 0.050), and atrial vulnerability (induction of AF lasting >30 second) after ablation (P < 0.050). However, only Pdisp > or =35.5 ms (P < 0.050) and left atrial diameter >40 mm (P < 0.010) were independent predictors of AF recurrences. This study suggests that P wave dispersion could identify patients with AVNRT susceptible to recurrence of AF after slow pathway ablation.


Urinary bladder hemangioma -a rare urinary bladder tumor in a child.
Urinary bladder hemangiomas are rare, accounting for 0.6% of the urinary bladder tumors. Hemangioma is considered arising from embryonic stem cells of an angioblastic lineage. A 3-year old boy presented with hematuria. He had past operative history of excision of extensive lymphatic malformation involving retroperitoneum, pelvis and upper thigh. Computed tomography scan of abdomen and pelvis with contrast revealed a large soft tissue mass arising from the dome of the bladder. Partial cystectomy was done. Histopathology confirmed the mass as cavernous hemangioma of urinary bladder.


Dependence of gastro-intestinal tumors on gastro-intestinal hormones: pentagastrin stimulates growth of transplanted colon adenocarcinoma in mice.
Gastrin was administered several times to mice with transplantable hepatoma, sarcomas, colon adenocarcinoma and adenocarcinoma of small intestine. Injections of gastrin stimulated the growth of colon adenocarcinoma in mice but not of the other tumors tested. Dependence upon gastro-intestinal hormones of "spontaneous" carcinogenesis in gastro-intestinal tract and the growth of many gastro-intestinal pancreatic and liver tumors is suggested. This hormone dependence could be used for the treatment and prophylaxis of some tumors of the gastro-intestinal tract.


Transcriptional modulation of SLC26A3 (DRA) by sphingosine-1-phosphate.
SLC26A3 or Downregulated in adenoma (DRA) is the major Cl(-)/HCO3 (-) exchanger involved in electroneutral NaCl absorption in the mammalian intestine. Alterations in DRA function and expression have been implicated in diarrheal diseases associated with inflammation or infection. Therefore, agents that upregulate DRA activity may serve as potential antidiarrheals. In this regard, sphingosine-1-phosphate (S1P), a member of the bioactive sphingolipid family, has been shown to modulate various cellular processes including improvement of intestinal barrier function. However, the role of S1P in modulating intestinal chloride absorption by regulating DRA is not known. Therefore, the present studies were designed to examine the direct effects of S1P on apical Cl(-)/HCO3 (-) exchange activity and DRA expression. S1P significantly increased Cl(-)/HCO3 (-) exchange activity and also significantly increased DRA mRNA and protein expression. Increased DRA mRNA by S1P was accompanied by enhanced DRA promoter activity, indicating involvement of transcriptional mechanisms. The specific S1P receptor subtype-2 (S1PR2) antagonist JTE-013 blocked the stimulatory effects of S1P on DRA promoter activity, indicating the involvement of S1PR2 S1P-mediated increase in DRA promoter activity involved PI3K/Akt pathway. Progressive deletions of the DRA promoter indicated that the putative S1P-responsive elements are present in the -790/-398 region of the DRA promoter. Furthermore, results obtained from electrophoretic mobility shift assay showed that S1P stimulated DRA promoter activity via increased binding of Ying-Yang1 (YY1) in the S1P-responsive region. In conclusion, transcriptional modulation of DRA expression and function in response to S1P through a PI3/Akt pathway represents a novel role of S1P as a potential proabsorptive agent.


Liver X receptor and retinoic X receptor agonists modulate the expression of genes involved in lipid metabolism in human endothelial cells.
The cooperation of liver X receptors (LXRs) alpha and beta, and retinoic X receptor (RXR) modulate the expression of several genes involved in lipid metabolism in hepatocyte and macrophages. Using cDNA microarray technology, we have shown previously that several of these genes are also expressed in endothelial cells. In the present study, we investigated whether the activation of LXR and RXR affects the expression of genes involved in lipid metabolism in human endothelial cells. Relative expression of ABCA-1, CETP, SR-B1, EL, LPL, PLTP, ApoE and LDLR was investigated in HUVECs, human fibroblasts (hFB) and HepG2 cells by quantitative real-time PCR. For CETP and EL mRNA expression, the results were HUVECs > hFB > HEPG2; for PLTP, LDLR and LPL: hFB > HUVECs > HEPG2; for SR-B1 and ApoE: HEPG2 > HUVECs > hFB; and for ABCA-1 HEPG2: > hFB > HUVECs. Incubation of HUVECs with LXR agonists as 22-(R)-hydroxycholesterol (22-(R)-HC) or T0901317-induced ABCA1 (20.1- and 17.8-fold), LPL (3.46- and 7.03-fold) and CETP (6.34- and 3.98-fold) expression; EL, LDLR and SR-B1 expression was induced only upon incubation with T0901317 (2.40-, 2.83- and 2.19-fold, respectively) while 22-(R)-HC had no effect on EL and SR-B1 expression (0.8- and 0.9-fold) and decreased LDLR expression (0.4-fold). No effect of either 22-(R)-HC or T0901317 on PLTP and ApoE expression was observed. The RXR agonist, 9-cis retinoic acid (9CRA) alone induced the expression of CETP, LPL and SR-B1 (2.8-, 8.2- and 2.4-fold). No effect of 9CRA on ABCA-1, EL, PLTP, ApoE, and LDLR expression was observed. Association of 9CRA with 22-(R)-HC or T0901317 increased the expression of CETP and LPL while no effect on ABCA-1 or LDLR was observed. Activation of LXRs and RXRs in endothelial cells represents a new target of LXR and RXR agonist in the arterial wall. Modulation of gene expression in the endothelium should be taken into account when studying the effects of LXR and RXR agonists on lipid metabolism in the arterial wall.


Effect of Flagellin Pre-Exposure on the Inflammatory and Antifungal Response of Bronchial Epithelial Cells to Fungal Pathogens.
Bronchial epithelial cells (BEC) play a crucial role in innate immunity against inhaled fungi. Indeed, in response to microorganisms, BEC synthesize proinflammatory cytokines involved in the recruitment of neutrophils. We have recently shown that BEC exert antifungal activity against Aspergillus fumigatus by inhibiting filament growth. In the present study, we first analyzed the inflammatory and antifungal responses of BEC infected by several fungal species such as Aspergillus spp., Scedosporium apiospermum and Candida albicans, which are frequently isolated from the sputum of people with chronic pulmonary diseases. The airways of these patients, such as people with cystic fibrosis (pwCF), are mainly colonized by P. aeruginosa and secondary by fungal pathogens. We have previously demonstrated that BEC are capable of innate immune memory, allowing them to increase their inflammatory response against A. fumigatus following a previous contact with Pseudomonas aeruginosa flagellin. To identify the impact of bacteria exposure on BEC responses to other fungal infections, we extended the analysis of BEC innate immune memory to Aspergillus spp., Scedosporium apiospermum and Candida albicans infection. Our results show that BEC are able to recognize and respond to Aspergillus spp., S. apiospermum and C. albicans infection and that the modulation of BEC responses by pre-exposure to flagellin varies according to the fungal species encountered. Deepening our knowledge of the innate immune memory of BEC should open new therapeutic avenues to modulate the inflammatory response against polymicrobial infections observed in chronic pulmonary diseases such as CF.


Identification of surgical forceps using YOLACT++ in different lighted environments.
Forceps tracking in laparoscopic surgery contributes to improved surgical outcomes. We identified forceps using YOLACT++ for fast and accurate segmentation. Differences in the illumination of the environment can affect the image recognition accuracy in deep learning. Therefore, we examined the speed and accuracy of YOLACT++ forceps identification in different illuminated environments. We expected that this experiment would help us understand the optimal lighted environments for YOLACT++ and to further improve the performance of the forceps identification model. The greatest accuracy was obtained under a light-shielded environment with light shining only on the suture area. Although a laparotomy with a clear view of the surgical site is easier for the physician to operate in, we concluded that the forceps identification model of YOLACT++ can be used more effectively in the laparoscopic surgical environment.Clinical Relevance- This study contributes to analyzing the cause of surgical errors in laparoscopic surgery.


Potential of prevention strategies for the modifiable risk factor type 2 diabetes with relation to the future number of dementia patients in Germany- a multi-state projection through 2040.
We assess the impact of prevention strategies regarding type 2 diabetes as a modifiable risk factor for dementia and its consequences for the future number of dementia patients in Germany. We used a random sample of health claims data (N = 250,000) of insured persons aged 50+ drawn in 2014, and data on population size and death rates in 2015 from the Human Mortality Database. Using exponential hazard models, we calculated age- and sex-specific transition probabilities and death rates between the states (no diabetes/no dementia, diabetes/no dementia, no diabetes/dementia, diabetes/dementia). In multi-state projections, we estimated the future number of dementia cases aged 75+ through 2040 depending on the development of the incidence of diabetes among persons without diabetes and without dementia, and the dementia incidence among persons with and without diabetes. In 2015 there were 1.53 million people with dementia aged 75+ in Germany. A relative annual reduction in death rates of 2.5% and in dementia incidence in persons without diabetes of 1% will increase this number to 3.38 million by 2040. A relative reduction of diabetes incidence by 1% annually would decrease dementia cases by around 30,000, while a reduction of dementia incidence among people with diabetes by 1% would result in 220,000 fewer dementia cases. Both prevention strategies combined would prevent 240,000 dementia cases in 2040. The increase in life expectancy is decisive for the future number of people with dementia. Strategies of better diabetes treatment have the potential to lower the increase in the number of dementia patients in the coming decades.


A Mineralocorticoid Receptor Deficiency in Myeloid Cells Reduces Liver Steatosis by Impairing Activation of CD8+ T Cells in a Nonalcoholic Steatohepatitis Mouse Model.
The mineralocorticoid receptor (MR) and renin-angiotensin-aldosterone system (RAAS) are implicated in non-alcoholic liver fatty disease (NALFD). However, inflammatory mechanisms linking MR and RAAS with disease pathology remain unclear. Here we aimed to evaluate the contribution of myeloid MR to the inflammatory response in an animal model of non-alcoholic steatohepatitis (NASH), induced with a methionine-choline deficient diet (MCD). Mice with a conditional deficiency of MR in myeloid cells (MyMRKO) and their counterpart floxed control mice (FC) were fed for 18 days with MCD or chow diet, respectively. Serum levels of aminotransferases and aldosterone levels were measured and hepatic steatosis, inflammation and fibrosis scored histologically. Hepatic triglyceride content (HTC) and hepatic mRNA levels of pro-inflammatory pro-fibrotic-associated genes were also assessed. Deep flow cytometric analysis was used to dissect the immune response during NASH development. MyMRKO mice fed with an MCD diet exhibited reduced hepatic inflammation and lower HTC than controls. Absolute number and percentage of liver inflammatory infiltrate cells (except for CD8+ T lymphocytes) were similar in both MyMRKO and control mice fed with an MCD diet but expression of the costimulatory molecule CD86 by dendritic cells and the CD25 activation marker in CD8+ T cells were significantly reduced in MyMRKO. Proinflammatory cells are functionally suppressed in the absence of MR. We hypothesized that loss of MR in myeloid cells reduces lipid accumulation in the liver, in part through modulating the adaptive immune response, which is pivotal for the development of steatosis.


Renal artery stenosis with erythrocytosis after renal transplantation.
We present here results of studies on four patients (three men, one woman) who had had cadaver renal transplants and in whom renal artery stenosis and hypertension developed. Erythropoietin-dependent erythrocytosis developed in association with these changes in the three men. All patients had stable renal function and the hypertension was well controlled. Absolute erythrocytosis thought to be secondary to local renal hypoxia due to decreased renal blood flow developed in two of the men. Erythrocytosis developed in the other man but his RBC mass was at the upper limit of normal. In these patients, we suspect that the erythropoietin-dependent erythrocytosis is secondary to intrarenal hypoxia due to renal artery stenosis. Erythrocytosis or elevated erythropoietin levels failed to develop in the woman despite severe renal artery stenosis. Possible reasons for this discrepancy are discussed.


Protease-activated receptor dependent and independent signaling by kallikreins 1 and 6 in CNS neuron and astroglial cell lines.
While protease-activated receptors (PARs) are known to mediate signaling events in CNS, contributing both to normal function and pathogenesis, the endogenous activators of CNS PARs are poorly characterized. In this study, we test the hypothesis that kallikreins (KLKs) represent an important pool of endogenous activators of CNS PARs. Specifically, KLK1 and KLK6 were examined for their ability to evoke intracellular Ca(2+) flux in a PAR-dependent fashion in NSC34 neurons and Neu7 astrocytes. Both KLKs were also examined for their ability to activate mitogen-activated protein kinases (extracellular signal-regulated kinases, C-Jun N-terminal kinases, and p38) and protein kinase B (AKT) intracellular signaling cascades. Cumulatively, these studies show that KLK6, but not KLK1, signals through PARs. KLK6 evoked intracellular Ca(2+) flux was mediated by PAR1 in neurons and both PAR1 and PAR2 in astrocytes. Importantly, both KLK1 and KLK6 altered the activation state of mitogen-activated protein kinases and AKT, suggestive of important roles for each in CNS neuron and glial differentiation, and survival. The cellular specificity of CNS-KLK activity was underscored by observations that both proteases promoted AKT activation in astrocytes, but inhibited such signaling in neurons. PAR1 and bradykinin receptor inhibitors were used to demonstrate that KLK1-mediated activation of extracellular signal-regulated kinases in neurons occurred in a non-PAR, bradykinin 2 (B2) receptor-dependent fashion, while similar signaling by KLK6 was mediated by the combined activation of PAR1 and B2. Cumulatively results indicate KLK6, but not KLK1 is an activator of CNS PARs, and that both KLKs are poised to signal in a B2 receptor-dependent fashion to regulate multiple signal transduction pathways relevant to CNS physiologic function and dysfunction.


Vasopressin deficiency and pressor hypersensitivity in hemodynamically unstable organ donors.
Solid organ donors often develop hypotension due to vasodilation, and recently we observed that a variety of vasodilatory states are characterized by vasopressin deficiency and hypersensitivity. Thus, we investigated the prevalence of vasopressin deficiency in hypotensive solid organ donors without clinical evidence of diabetes insipidus; we also investigated the vasopressor effect of vasopressin replacement in hypotensive donors. Fifty organ donors were evaluated for hemodynamic instability, (mean arterial pressure [MAP]</= 70 mm Hg despite the use of catecholamine vasopressors), and in those unstable donors who were not already receiving exogenous vasopressin, low-dose vasopressin was administered as a continuous infusion (0. 04 to 0.1 U/min). MAP, catecholamine requirements, serum vasopressin, and serum osmolality were obtained before and after vasopressin administration. Ten patients meeting the enrollment criteria received vasopressin and MAP increased from 72.2+/-3.5 to 89.8+/-4.2 mm Hg, (P<0.05), allowing for complete discontinuation of catecholamine pressors in 4 (40%) patients and a decrement in pressor dose in 4 (40%). Plasma vasopressin levels (2.9+/-0.8 pg/mL) were low for the degree of hypotension. Hemodynamically unstable organ donors without clinically apparent diabetes insipidus display a defect in the baroreflex-mediated secretion of vasopressin. In these patients, low-dose vasopressin significantly increases blood pressure with a pressor response sufficient to reduce catecholamine administration.


New Drugs from Marine Organisms in Alzheimer's Disease.
Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder. Current approved drugs may only ameliorate symptoms in a restricted number of patients and for a restricted period of time. Currently, there is a translational research challenge into identifying the new effective drugs and their respective new therapeutic targets in AD and other neurodegenerative disorders. In this review, selected examples of marine-derived compounds in neurodegeneration, specifically in AD field are reported. The emphasis has been done on compounds and their possible relevant biological activities. The proposed drug development paradigm and current hypotheses should be accurately investigated in the future of AD therapy directions although taking into account successful examples of such approach represented by Cytarabine, Trabectedin, Eribulin and Ziconotide. We review a complexity of the translational research for such a development of new therapies for AD. Bryostatin is a prominent candidate for the therapy of AD and other types of dementia in humans.


Technical note: Computing options for genetic evaluation with a large number of genetic markers.
Two simulated data sets and one commercial data set were used to evaluate computing options for models in which the effects attributable to QTL were fit as covariables. The simulated data sets included records on 24,000 animals for 10 traits. Data sets 1 and 2 were simulated with low and high correlations among traits, respectively. The model included an overall mean, 160 covariables as effects attributable to QTL, the random animal genetic effect, and the random residual effect. A commercial data set included records on approximately 110,000 animals for 11 growth, reproduction, and other traits. The model included the effects usually fitted for these traits as well as 116 covariables as effects attributable to QTL; models including the number of covariables varied by trait. Initial computing was by the BLUP90IOD program, which applies iterations on data by using a preconditioned conjugate gradient algorithm with a diagonal preconditioner. Modifications included adding block preconditioners for effects attributable to QTL (BQ) and for traits (BT). With the simulated data sets and the original program, one-trait analyses without the covariables took 7 s, whereas the 10-trait analyses with the covariables took 15 min for a data set with low correlations and 1 h 40 m for a data set with high correlations. The BQ improved the convergence rate but increased the computing time. The BT decreased the computing time from 1.5 times (low correlations) to 7 times (high correlation) at a cost of greater memory requirements. For the commercial data and the complete model, computing took 10.3 h with the unmodified program and was reduced to 6 h with BT. Relative changes in computing time and convergence rate with the commercial data set were close to those of the simulated data set, with low correlations among the traits. The BQ decreased the number of rounds by less than expected. Genetic evaluation with a large number of effects attributable to QTL fit as covariables is feasible.


A comparison of simultaneously collected arterial, mixed venous, jugular venous and cephalic venous blood samples in the assessment of blood-gas and acid-base status in the dog.
Blood samples were collected simultaneously from the pulmonary artery, jugular vein, cephalic vein, and carotid artery in awake dogs. Blood-gas and acid-base values were measured from these blood samples in normal dogs and in dogs after production of metabolic acidosis and metabolic alkalosis. The values obtained from each of the venous sites were compared with those obtained from arterial blood to determine if venous blood from various sites accurately reflected acid-base balance and could therefore be used in the clinical patient. The results of this study demonstrated significant differences between the blood from various venous sites and the arterial site for PCO2 and pH in all acid-base states. Significant differences for standard bicarbonate (SHCO3) were found only when jugular and cephalic venous blood were compared with arterial blood in dogs with a metabolic acidosis. No significant differences were found for BE when blood from the venous sites was compared with arterial blood. The values for pH, HCO3, TCO2, BE, and SHCO3 measured on blood collected at the various venous sites were found to correlate well with those obtained from arterial blood, with a correlation coefficient of 0.99 for HCO3, TCO2, BE, and SHCO3. These correlation coefficients, together with similar values in BE at all collection sites, indicate that, in the dog with normal circulatory status, blood from any venous site will accurately reflect the acid-base status of the patient.


Timing recalibration in childhood Tourette syndrome associated with persistent pimozide treatment.
In this study, we have tested the effects of the dopamine D2 receptor blocker pimozide on timing performance in patients with Tourette syndrome (TS). Nine children with TS were tested off-medication and following 3 months of daily treatment with pimozide. Subjects completed a time reproduction and a time production task using supra-second temporal intervals. We show that pimozide improves motor timing performance by reducing the patients' variability in reproducing the duration of visual stimuli. On the other hand, this medication has no effect on the reproduction accuracy and on both variability and accuracy of the performance on the time production task. Our results suggest that pimozide might have improved motor timing variability as a result of its beneficial side effect on endogenous dopamine levels (i.e., normalization).


Cigarette smoking as a confounder of the relationship between relative weight and long-term mortality. The Framingham Heart Study.
Cigarette smoking is a potential confounder of the relationship between obesity and mortality, and statistical control for this factor requires careful consideration. Framingham Heart Study subjects were weighed, their stature measured, and cigarette smoking histories obtained at the first biennial examination starting in 1949. Of men under desirable weight (Metropolitan relative weight [MRW], less than 100%), more than 80% were smokers, while only about 55% of the extremely overweight men were cigarette smokers. When age-, smoking-, and MRW-specific mortalities for 26 years of follow-up were calculated in these men, it was found that smokers had higher mortality than nonsmokers but that in the smokers and nonsmokers, minimum mortalities occurred for subjects who were initially in the "desirable weight" group (MRW, 100% to 109%). Among cigarette smokers, lean men (MRW, less than 100%) experienced considerably elevated mortality, often higher than that in all but the most overweight cigarette smokers. These findings suggest that elevated mortality in low-weight American men results from the mortality risks associated with cigarette smoking and demonstrates the need for controlling for cigarette smoking when considering the relationship between relative weight and mortality. Furthermore, the concept of "desirable weight" developed by the Metropolitan Life Insurance Co in 1959 and subsequently distributed in tabular form is validated by this long-term study. Thus, even those men who were near the average weight (about 20% above "desirable weight") showed appreciably elevated mortality. This finding is contrary to the widely held view that moderate overweight carries no increased risk.


The isometric horizontal push test correlates with jumping and sprinting performance among athletes and recreationally active controls.
The aim of this study was two-fold: (i) to examine the relationships between force outputs measured in the isometric horizontal push test (IHPT) and athletic performances; (ii) to compare IHPT outputs between football players and recreationally active controls. Thirty-two male subjects (football players, n = 16; university students, n = 16) completed the IHPT, countermovement jump (CMJ), standing long jump (SLJ), 5 m, 10 m and 20 m sprint tests, randomly across two testing sessions. Multivariate linear regression analysis was used to examine the relationships between IHPT outputs and athletic performances by accounting for the subjects' athletic background. An independent sample t-test was used to compare the IHPT outputs between groups. Moderate to very strong linear relationships (r2 range: 0.16-0.56) were found between the IHPT and all athletic performances (all p < .026). Percent variance explained by the IHPT outputs after accounting for groups difference was 16%, 56%, 54%, 48% and 40% for CMJ height, SLJ distance, 5 m, 10 m and 20 m sprint performances, respectively. Compared to controls (6.18 ± 0.89 N/kg), football players (10.09 ± 1.57 N/kg) achieved greater IHPT force outputs (p < .001, Hedges' g = 3.2, large ES). The IHPT is clearly correlated to horizontal and vertical athletic performances and can adequately distinguish between athletes and recreationally active controls based on their IHPT results. Future studies should examine the usefulness of the IHPT as a testing tool informing training prescription and performance monitoring practices.


Molecular rotors as intracellular probes of red blood cell stiffness.
The deformability of red blood cells is an essential parameter that controls the rheology of blood as well as its circulation in the body. Characterizing the rigidity of the cells and their heterogeneity in a blood sample is thus a key point in the understanding of occlusive phenomena, particularly in the case of erythrocytic diseases in which healthy cells coexist with pathological cells. However, measuring intracellular rheology in small biological compartments requires the development of specific techniques. We propose a technique based on molecular rotors - viscosity-sensitive fluorescent probes - to evaluate the above key point. DASPI molecular rotor has been identified with spectral fluorescence properties decoupled from those of hemoglobin, the main component of the cytosol. After validation of the rotor as a viscosity probe in model fluids, we showed by confocal microscopy that, in addition to binding to the membrane, the rotor penetrates spontaneously and uniformly into red blood cells. Experiments on red blood cells whose rigidity is varied with temperature, show that molecular rotors can detect variations in their overall rigidity. A simple model allowed us to separate the contribution of the cytosol from that of the membrane, allowing a qualitative determination of the variation of cytosol viscosity with temperature, consistent with independent measurements of the viscosity of hemoglobin solutions. Our experiments show that the rotor can be used to study the intracellular rheology of red blood cells at the cellular level, as well as the heterogeneity of this stiffness in a blood sample. This opens up new possibilities for biomedical applications, diagnosis and disease monitoring.


Cotton HILIC SPE microtips for microscale purification and enrichment of glycans and glycopeptides.
Solid-phase extraction microtips are important devices in modern bioanalytics, as they allow miniaturized sample preparation for mass spectrometric analysis. Here we introduce the use of cotton wool for the preparation of filter-free HILIC SPE microtips. To this end, pieces of cotton wool pads (approximately 500 μg) were packed into 10 μL pipet tips. The performance of the tips was evaluated for microscale purification of tryptic IgG Fc N-glycopeptides. Cotton wool HILIC SPE microtips allowed the removal of salts, most nonglycosylated peptides, and detergents such as SDS from glycoconjugate samples. MALDI-TOF-MS glycopeptide profiles were very repeatable with different tips as well as reused tips, and very similar profiles were obtained with different brands of cotton wool pads. In addition, we used cotton HILIC microtips to purify N-glycans after N-glycosidase F treatment of IgG and transferrin followed by MALDI-TOF-MS detection. In conclusion, we establish cotton wool microtips for glycan and glycopeptide purification with subsequent mass spectrometric detection.


[Role of connections in the formation of protein structures, containing 4-helical segments].
The packing of alpha-helices in protein molecules and domains consisting of four consecutive alpha-helices in primary structures in analyzed. Such 4-alpha-helical complexes can have two "mirror-symmetrical" structures. Analysis is hydrophobic interactions, hydrogen and salt bonds is insufficient for an unambiguous choice of one of the two structures. It is shown in the present paper that severe sterical restrictions are superimposed on the packing of alpha-helices by interhelical regions, or simply connections. Thus, if two alpha-helices are joined by a short connection from two peptide units, this unambiguously sets the packing of these helices within the 4 alpha-helical complex. An unambiguous packing of the entire complex is achieved if the short connection joins the second and third alpha-helices or there are two short connections between the first and second and also the third and fourth alpha-helices. If the short connection joins only the first and second helices, then the length of the connection between the second and third helices should not exceed three peptide units for an unambiguous packing of the 4 alpha-helical complex.


[A case of giant gastric GIST with multiple hepatic metastases with long-term survival after multimodal therapy].
A male patient in his 40s presented with abdominal pain and mass palpitation. He was diagnosed with a submucosal gastric tumor and referred to our clinic. Computed topography (CT) scan revealed a large gastric tumor and multiple hepatic metastases. He was diagnosed with unresectable gastrointestinal stromal tumor (GIST) and began imatinib treatment. However, 2 weeks later, the patient developed a high fever and abdominal pain. Tumor necrosis and abscess formation was observed on the CT scan. We performed emergency surgery, which comprised partial gastrectomy, distal pancreatectomy, and splenectomy, combined with radiofrequency ablation (RFA) for the hepatic metastases. Subsequently, he continued imatinib therapy. However, a new lesion developed in the liver and was diagnosed as imatinib-resistant disease. The new lesion was treated with RFA. Eight years after the treatment, a new lesion occurred in the liver, which was difficult to excise owing to the location. Accordingly, a right-hepatic lobectomy was performed. Currently, he is alive and continues on imatinib therapy.


A randomised, active- and placebo-controlled, three-period crossover trial to investigate short-term effects of the dipeptidyl peptidase-4 inhibitor linagliptin on macro- and microvascular endothelial function in type 2 diabetes.
Studies of dipeptidyl peptidase (DPP)-4 inhibitors report heterogeneous effects on endothelial function in patients with type 2 diabetes (T2D). This study assessed the effects of the DPP-4 inhibitor linagliptin versus the sulphonylurea glimepiride and placebo on measures of macro- and microvascular endothelial function in patients with T2D who represented a primary cardiovascular disease prevention population. This crossover study randomised T2D patients (n = 42) with glycated haemoglobin (HbA1c) ≤7.5%, no diagnosed macro- or microvascular disease and on stable metformin background to linagliptin 5 mg qd, glimepiride 1-4 mg qd or placebo for 28 days. Fasting and postprandial macrovascular endothelial function, measured using brachial flow-mediated vasodilation, and microvascular function, measured using laser-Doppler on the dorsal thenar site of the right hand, were analysed after 28 days. Baseline mean (standard deviation) age, body mass index and HbA1c were 60.3 (6.0) years, 30.3 (3.0) kg/m2 and 7.41 (0.61)%, respectively. After 28 days, changes in fasting flow-mediated vasodilation were similar between the three study arms (treatment ratio, gMean [90% confidence interval]: linagliptin vs glimepiride, 0.884 [0.633-1.235]; linagliptin vs placebo, 0.884 [0.632-1.235]; glimepiride vs placebo, 1.000 [0.715-1.397]; P = not significant for all comparisons). Similarly, no differences were seen in postprandial flow-mediated vasodilation. However, under fasting conditions, linagliptin significantly improved microvascular function as shown by a 34% increase in hyperaemia area (P = 0.045 vs glimepiride), a 34% increase in resting blow flow (P = 0.011 vs glimepiride, P = 0.003 vs placebo), and a 25% increase in peak blood flow (P = 0.009 vs glimepiride, P = 0.003 vs placebo). There were no significant differences between treatments in postprandial changes. Linagliptin had no effect on heart rate or blood pressure. Rates of overall adverse events with linagliptin, glimepiride and placebo were 27.5, 61.0 and 35.0%, respectively. Fewer hypoglycaemic events were seen with linagliptin (5.0%) and placebo (2.5%) than with glimepiride (39.0%). Linagliptin had no effect on macrovascular function in T2D, but significantly improved microvascular function in the fasting state. Trial registration ClinicalTrials.gov identifier-NCT01703286; registered October 1, 2012.


Inhibition of AT1 receptor internalization by concanavalin A blocks angiotensin II-induced ERK activation in vascular smooth muscle cells. Involvement of epidermal growth factor receptor proteolysis but not AT1 receptor internalization.
Recent studies of beta(2)-adrenergic receptor suggest that agonist-promoted receptor internalization may play an important role in extracellular signal-regulated kinase (ERK) activation by G protein-coupled receptors. In the present study, we explored the effects of angiotensin II (Ang II) type-1 receptor (AT(1)) internalization on Ang II-induced activation of ERK using the receptor internalization blocker concanavalin A (ConA) and the carboxyl terminus-truncated receptor mutants with impaired internalization. ConA inhibited AT(1) receptor internalization without affecting ligand binding to the receptor, Ang II-induced generation of second messengers, and activation of tyrosine kinases Src and Pyk2 in vascular smooth muscle cells (VSMC). ConA blocked ERK activation evoked by Ang II and the calcium ionophore A23187. Impairment of AT(1) receptor internalization by truncating the receptor carboxyl terminus did not affect Ang II-induced ERK activation. ConA induced proteolytic cleavage of the epidermal growth factor (EGF) receptor at carboxyl terminus and abolished Ang II-induced transactivation of the EGF receptor, which is critical for ERK activation by Ang II in VSMC. ConA also induced proteolysis of erbB-2 but not platelet-derived growth factor receptor. Thus, ConA blocks Ang II-induced ERK activation in VSMC through a distinct mechanism, the ConA-mediated proteolysis of the EGF receptor.


The effects of artificial lung inflation on pulmonary blood flow and heart rate in the turtle Trachemys scripta.
As for most ectothermic vertebrates, the breathing pattern of turtles is episodic, and pulmonary blood flow (Qpul) and heart rate (fH) normally increase several-fold during spontaneous ventilation. While some previous studies suggest that these cardiovascular changes are caused by stimulation of pulmonary stretch receptors (PSRs) during ventilation, it has been noted in other studies that blood flows often change prior to the initiation of breathing. Given the uncertainty regarding the role of PSRs in the regulation of central vascular blood flows, we examined the effect of manipulating lung volume (and therefore PSR stimulation) on blood flows and heart rate in the freshwater turtle Trachemys scripta. Turtles were instrumented with blood flow probes on the left aortic arch and the left pulmonary artery for measurements of blood flow, and catheters were inserted into both lungs for manipulation of lung volume. In both anaesthetized and fully recovered animals, reductions or increases in lung volume by withdrawal of lung gas or injection of air, N2, O2 or 10% CO2 (in room air) had no effect on blood flows. Furthermore, simulations of normal breathing bouts by withdrawal and injection of lung gas did not alter Qpul or fH. We conclude that stimulation of PSRs is not sufficient to elicit cardiovascular changes and that the large increase in Qpul and fH normally observed during spontaneous ventilation are probably caused by a simultaneous feedforward control of central origin.


A survey for prevalence of coronary artery disease and its risk factors in an urban population in Andhra Pradesh.
The present cross-sectional community-based study was conducted to assess the prevalence and risk factors for coronary artery disease (CAD) in an urban community in Tenali, Andhra Pradesh. A survey was carried out in two localities of Tenali town, Andhra Pradesh (A.P) namely Gandhinagar and Nazarpet between July 2009 and October 2009. A total of 534 people aged 20 years and above in randomly selected houses in each street of the 2 localities were examined. All of them underwent oral glucose tolerance test and lipid profile estimation and a 12-lead electrocardiogram. CAD was diagnosed based on previous medical history and documented myocardial infarction and/or coronary intervention procedures or Minnesota coding of ECGs. The overall prevalence rate of CAD was 5.4% (age standardized prevalence rate = 5.1%). The prevalence rate of CAD were 3.0%, 23.5% and 11.3% in persons with normal glucose tolerance impaired glucose tolerance and diabetes mellitus respectively. Prevalence of CAD increased with an increase in total cholesterol (P < 0.01), serum triglycerides (P < 0.01) low density lipoprotein (LDL) cholesterol (P < 0.01) and total cholesterol/high density lipoprotein cholesterol ratio (P < 0.01). Multiple logistic regression analysis identified age (odds ratio O.R.1.068, P = 0.0001), LDL Cholesterol (O.R. 0.98, P = 0.03), total cholesterol (O.R.1.107, P = 0.059) had a significant association with CAD. Observations from our community based study indicate that prevalence of CAD in urban Andhra Pradesh is alarmingly high as observed in other parts of India and urgent steps are to be taken to adopt life style changes and to control risk factors.


Quantitative study of plasticity in the auditory nuclei of chick under conditions of prenatal sound attenuation and overstimulation with species specific and music sound stimuli.
Morphological effects of prenatal sound attenuation and sound overstimulation by species specific and music sounds on the brainstem auditory nuclei of chick have been evaluated quantitatively. Changes in length, volume, neuron number, size of neuronal nuclei and glial numbers of second and third order auditory nuclei, n. magnocellularis (NM) and n. laminaris (NL), were determined from thionine-stained serial sections of control and experimental groups on posthatch day 1 using stereological methods. Significant increase in volume of both auditory nuclei attributable to increase in length of nucleus, number and size of neurons, number of glia as well as neuropil was observed in response to both species specific and music overstimulation given during the critical period of development. The enhanced development of auditory nuclei in response to enriched environment prenatally indicates a positive effect of activity on neurons which may have clinical implications in addition to providing explanation for preference to auditory cues in the postnatal life. Reduction in neuron number with a small increase in proportion of cell nuclei of large size as well as an increase in glial numbers was seen in both NM and NL of the prenatally sound attenuated chicks. The increase in size of some neuronal nuclei may probably be evidence of enhanced synthesis of proteins involved in cell death or an attempt at recovery. The dissociated response of neurons and glia under sound attenuated and auditory stimulated conditions suggests that they are independently regulated by activity-dependent signals with glia also being under influence of other signals for a role in removal of dead cell debris.


Effects of relaxation associated with brief restricted environmental stimulation therapy (REST) on plasma cortisol, ACTH, and LH.
Restricted Environmental Stimulation Therapy (REST), which involves placing an individual into an environment of severely reduced stimulation for brief periods, has been subjectively reported to produce deep relaxation. The present study determines the effects of REST-assisted relaxation on plasma cortisol, ACTH, and luteinizing hormone (LH). These parameters were also measured in a group exposed to a similar relaxation paradigm, but without REST (non-REST). Each subject experienced two baseline sessions (1 and 2), four REST (or non-REST) relaxation sessions (3, 4, 5, 6), and two follow-up sessions (7 and 8). Pre- and postsession plasma hormone levels were measured in sessions 1, 2, 5, and 8. Both REST and non-REST subjects reported that the experience was relaxing. During the treatment period (session 5) pre- to postsession changes in cortisol and ACTH, but not in LH, were significantly greater for the REST group than for the non-REST group. Plasma cortisol level also decreased across sessions in the REST group, with levels in sessions 5 and 8 significantly lower than the baseline (sessions 1 and 2). Non-Rest subjects showed no change in plasma cortisol across sessions. No significant change in plasma ACTH or LH occurred across sessions in the REST or non-REST groups, although ACTH showed a decreasing trend. These data demonstrate that repeated brief REST-assisted relaxation produces a relaxation state associated with specific decreases in pituitary-adrenal axis activity.


Predictors of prehospital delay in patients with acute myocardial infarction in kashan city.
The prehospital delay might result in death in patients with acute myocardial infarction (AMI). This study aimed to investigate the prehospital delay and its related factors in patients with AMI admitted to Kashan's Shahid Beheshti Hospital. This cross-sectional study was conducted on 117 patients with AMI in the second half of 2013. The interval between the onset of symptoms and arrival at the hospital was noted and in cases of delay, the factors leading to the delay were investigated using a questionnaire. The content validity of the questionnaire was confirmed through content validity method and its internal consistency was confirmed using Cronbach's alpha coefficient. Chi-square test, odds ratio, and logistic regression analysis were used in data analysis. The median delay was 129 minutes (mean ± SD, 240.44 ± 295.30). Overall, 32.5% of patients were admitted within 90 minutes of symptom onset. The long distance between living locations to the hospital was the most common cause of delay to hospital admission (31.7%). Significant associations were observed between the delay time and location of residency (P = 0.00) and type of transportation vehicle (P = 0.003). Multivariate logistic regression analysis showed that the location of residency and type of transportation vehicle could significantly predict the delay time in patients with AMI (P = 0.039 and 0.036, respectively). The delay time from symptom onset to hospital admission was high in patients with AMI. It is necessary to create emergency medical system (EMS) stations in suburbs and train the public on the importance of quick contact with the EMS when the symptoms of an AMI are observed.


Jacalin: a new laboratory tool in immunochemistry and cellular immunology.
In recent years, a new lectin--jacalin--has raised the interest of immunologists because of its original properties with respect to human immunoglobulins and lymphocytes. Its structure and carbohydrate binding specificity are now well documented, and it can be purified easily from jackfruit seeds by ion exchange or affinity chromatography. The binding and precipitating specificities of jacalin with heavy chains of human immunoglobulins allow its use as a diagnostic (IgA subclass typing) and preparative tool (purification of IgA and IgD, removal of IgA from biologic samples and preparations). Other possible applications of jacalin's binding properties also can be envisaged. In addition, the lectin displays a mitogenic activity specific for human CD4 T-lymphocytes; consequently, the proliferative response induced by jacalin appears to represent a new and interesting assay for a functional study of CD4 cells, with obvious applications in primary and acquired, especially AIDS, immune deficiency states.


The response of Kodak EDR2 film in high-energy electron beams.
Kodak XV2 film has been a key dosimeter in radiation therapy for many years. The advantages of the recently introduced Kodak EDR2 film for photon beam dosimetry have been the focus of several IMRT verification dosimetry publications. However, no description of this film's response to electron beams exists in the literature. We initiated a study to characterize the response and utility of this film for electron beam dosimetry. We exposed a series of EDR2 films to 6, 9, 12, 16, and 20 MeV electrons in addition to 6 and 18 MV x rays to develop standard characteristic curves. The linac was first calibrated to ensure that the delivered dose was known accurately. All irradiations were done at dmax in polystyrene for both photons and electrons, all films were from the same batch, and were developed at the same time. We also exposed the EDR2 films in a solid water phantom to produce central axis depth dose curves. These data were compared against percent depth dose curves measured in a water phantom using an IC-10 ion chamber, Kodak XV2 film, and a PTW electron diode. The response of this film was the same for both 6 and 18 MV x rays, but showed an apparent energy-dependent enhancement for electron beams. The response of the film also increased with increasing electron energy. This caused the percent depth dose curves using film to be shifted toward the surface compared to the ion chamber data.


Assessment of somatic embryogenesis potency in Indian soybean [Glycine max (L.) Merr.] cultivars.
Majority of the Indian soybean cultivars are recalcitrant to tissue culture regeneration. The present communication reports the development of somatic embryogenesis in a liquid culture medium from immature cotyledons of G. max. Following induction with 2,4-dichlorophenoxyacetic acid (2,4-D) or naphthalene acetic acid (NAA), the number of somatic embryos and percentage of explants that responded were higher with 45.24 microM 2,4-D. The proliferation of somatic embryos for three successive cycles was achieved in 22.62 microM 2,4-D. Histodifferentiation of somatic embryos under NAA (10.74 microM) indicated that better embryo development and maturation was achieved without any growth regulator. The amino acids such as L-glutamine favoured the somatic embryo induction and histodifferentiation at 20 and 30 mM respectively, where as L-asparagine at 10 mM concentration enhanced the somatic embryo proliferation. In addition, somatic embryos that were desiccated (air-drying method) for 5 days showed better germination (40.88%). The Indian soybean cultivars also showed strict genotypic influence and cv. Pusa 16 was emerged as a best responding cultivar for somatic embryo induction with 74.42% of response.


Peripheral Innate Immune Activation Correlates With Disease Severity in GRN Haploinsufficiency.
Objective: To investigate associations between peripheral innate immune activation and frontotemporal lobar degeneration (FTLD) in progranulin gene (GRN) haploinsufficiency. Methods: In this cross-sectional study, ELISA was used to measure six markers of innate immunity (sCD163, CCL18, LBP, sCD14, IL-18, and CRP) in plasma from 30 GRN mutation carriers (17 asymptomatic, 13 symptomatic) and 29 controls. Voxel based morphometry was used to model associations between marker levels and brain atrophy in mutation carriers relative to controls. Linear regression was used to model relationships between plasma marker levels with mean frontal white matter integrity [fractional anisotropy (FA)] and the FTLD modified Clinical Dementia Rating Scale sum of boxes score (FTLD-CDR SB). Results: Plasma sCD163 was higher in symptomatic GRN carriers [mean 321 ng/ml (SD 125)] compared to controls [mean 248 ng/ml (SD 58); p < 0.05]. Plasma CCL18 was higher in symptomatic GRN carriers [mean 56.9 pg/ml (SD 19)] compared to controls [mean 40.5 pg/ml (SD 14); p < 0.05]. Elevation of plasma LBP was associated with white matter atrophy in the right frontal pole and left inferior frontal gyrus (p FWE corrected <0.05) in all mutation carriers relative to controls. Plasma LBP levels inversely correlated with bilateral frontal white matter FA (R2 = 0.59, p = 0.009) in mutation carriers. Elevation in plasma was positively correlated with CDR-FTLD SB (b = 2.27 CDR units/μg LBP/ml plasma, R2 = 0.76, p = 0.003) in symptomatic carriers. Conclusion: FTLD-GRN is associated with elevations in peripheral biomarkers of macrophage-mediated innate immunity, including sCD163 and CCL18. Clinical disease severity and white matter integrity are correlated with blood LBP, suggesting a role for peripheral immune activation in FTLD-GRN.


Homologue of macrophage-activating lipoprotein in Mycoplasma gallisepticum is not essential for growth and pathogenicity in tracheal organ cultures.
While the genomes of a number of Mycoplasma species have been fully determined, there has been limited characterization of which genes are essential. The surface protein (p47) identified by monoclonal antibody B3 is the basis for an enzyme-linked immunosorbent assay for serological detection of Mycoplasma gallisepticum infection and appears to be constitutively expressed. Its gene was cloned, and the DNA sequence was determined. Subsequent analysis of the p47 amino acid sequence and searches of DNA databases found homologous gene sequences in the genomes of M. pneumoniae and M. genitalium and identity with a gene family in Ureaplasma urealyticum and genes in M. agalactiae and M. fermentans. The proteins encoded by these genes were found to belong to a family of basic membrane proteins (BMP) that are found in a wide range of bacteria, including a number of pathogens. Several of the BMP family members, including p47, contain selective lipoprotein-associated motifs that are found in macrophage-activating lipoprotein 404 of M. fermentans and lipoprotein P48 of M. agalactiae. The p47 gene was predicted to encode a 59-kDa peptide, but affinity-purified p47 had a molecular mass of approximately 47 kDa, as determined by polyacrylamide gel analysis. Analysis of native and recombinant p47 by mass peptide fingerprinting revealed the absence of the carboxyl end of the protein encoded by the p47 gene in native p47, which would account for the difference seen in the predicted and measured molecular weights and indicated posttranslational cleavage of the lipoprotein at its carboxyl end. A DNA construct containing the p47 gene interrupted by the gene encoding tetracycline resistance was used to transform M. gallisepticum cells. A tetracycline-resistant mycoplasma clone, P2, contained the construct inserted within the genomic p47 gene, with crossovers occurring between 73 bp upstream and 304 bp downstream of the inserted tetracycline resistance gene. The absence of p47 protein in clone P2 was determined by the lack of reactivity with rabbit anti-p47 sera or monoclonal antibody B3 in Western blots of whole-cell proteins. There was no difference between the p47(-) mutant and wild-type M. gallisepticum in pathogenicity in chicken tracheal organ cultures. Thus, p47, although homologous to genes that occur in many prokaryotes, is not essential for growth in vitro or for attachment and the initial stages of pathogenesis in chickens.


Surgery versus prolonged conservative treatment for sciatica: 5-year results of a randomised controlled trial.
This study describes the 5 years' results of the Sciatica trial focused on pain, disability, (un)satisfactory recovery and predictors for unsatisfactory recovery. A randomised controlled trial. Nine Dutch hospitals. Five years' follow-up data from 231 of 283 patients (82%) were collected. Early surgery or an intended 6 months of conservative treatment. Scores from Roland disability questionnaire, visual analogue scale (VAS) for leg and back pain and a Likert self-rating scale of global perceived recovery were analysed. There were no significant differences between groups on the 5 years' primary outcome scores. Despite at least 6 months of conservative treatment 46% of the conservatively allocated patients were treated surgically because of severe leg pain and disability. Forty-nine (21%) patients had an unsatisfactory recovery at 5 years and the recovery pattern showed that there was a variable group of 66 patients (31%) with at least one unsatisfactory outcome at 1, 2 or 5 years of follow-up. Multivariate logistic regression showed that age (>40; OR 2.42 (95% CI 1.16 to 5.02)), severity of leg pain (VAS >70; OR 3.32 (95% CI 1.69 to 6.54)) and the Mc Gill affective score (score >3; OR 6.23 (95% CI 2.23 to 17.38)) were the only significant predictors for an unsatisfactory outcome at 5 years. In the long term, 8% of the patients with sciatica never showed any recovery and in at least 23%, sciatica appears to result in ongoing complaints, which fluctuate over time, irrespective of treatment. Prolonged conservative care might give patients a fair chance for pain and disability to resolve without surgery, but with the risk to receive delayed surgery after prolonged suffering of sciatica. Age above 40 years, severe leg pain at baseline and a higher affective Mc Gill pain score were predictors for unsatisfactory recovery. Trial Registry ISRCT No 26872154.


Quality evaluation of fish and other seafood by traditional and nondestructive instrumental methods: Advantages and limitations.
Although being one of the most vulnerable and perishable products, fish and other seafoods provide a wide range of health-promoting compounds. Recently, the growing interest of consumers in food quality and safety issues has contributed to the increasing demand for sensitive and rapid analytical technologies. Several traditional physicochemical, textural, sensory, and electrical methods have been used to evaluate freshness and authentication of fish and other seafood products. Despite the importance of these standard methods, they are expensive and time-consuming, and often susceptible to large sources of variation. Recently, spectroscopic methods and other emerging techniques have shown great potential due to speed of analysis, minimal sample preparation, high repeatability, low cost, and, most of all, the fact that these techniques are noninvasive and nondestructive and, therefore, could be applied to any online monitoring system. This review describes firstly and briefly the basic principles of multivariate data analysis, followed by the most commonly traditional methods used for the determination of the freshness and authenticity of fish and other seafood products. A special focus is put on the use of rapid and nondestructive techniques (spectroscopic techniques and instrumental sensors) to address several issues related to the quality of these products. Moreover, the advantages and limitations of each technique are reviewed and some perspectives are also given.


Factors associated with decision to hospitalize emergency department patients with skin and soft tissue infection.
Emergency department (ED) hospitalizations for skin and soft tissue infection (SSTI) have increased, while concern for costs has grown and outpatient parenteral antibiotic options have expanded. To identify opportunities to reduce admissions, we explored factors that influence the decision to hospitalize an ED patient with a SSTI. We conducted a prospective study of adults presenting to 12 U.S. EDs with a SSTI in which physicians were surveyed as to reason(s) for admission, and clinical characteristics were correlated with disposition. We employed chi-square binary recursive partitioning to assess independent predictors of admission. Serious adverse events were recorded. Among 619 patients, median age was 38.7 years. The median duration of symptoms was 4.0 days, 96 (15.5%) had a history of fever, and 46 (7.5%) had failed treatment. Median maximal length of erythema was 4.0cm (IQR, 2.0-7.0). Upon presentation, 39 (6.3%) had temperature >38°C, 81 (13.1%) tachycardia, 35 (5.7%), tachypnea, and 5 (0.8%) hypotension; at the time of the ED disposition decision, these findings were present in 9 (1.5%), 11 (1.8%), 7 (1.1%), and 3 (0.5%) patients, respectively. Ninety-four patients (15.2%) were admitted, 3 (0.5%) to the intensive care unit (ICU). Common reasons for admission were need for intravenous antibiotics in 80 (85.1%; the only reason in 41.5%), surgery in 23 (24.5%), and underlying disease in 11 (11.7%). Hospitalization was significantly associated with the following factors in decreasing order of importance: history of fever (present in 43.6% of those admitted, and 10.5% discharged; maximal length of erythema >10cm (43.6%, 11.3%); history of failed treatment (16.1%, 6.0%); any co-morbidity (61.7%, 27.2%); and age >65 years (5.4%, 1.3%). Two patients required amputation and none had ICU transfer or died. ED SSTI patients with fever, larger lesions, and co-morbidities tend to be hospitalized, almost all to non-critical areas and rarely do they suffer serious complications. The most common reason for admission is administration of intravenous antibiotics, which is frequently the only reason for hospitalization. With the increasing outpatient intravenous antibiotic therapy options, these results suggest that many hospitalized patients with SSTI could be managed safely and effectively as outpatients.


Realtime recognition of complex human daily activities using human motion and location data.
Daily activity recognition is very useful in robot-assisted living systems. In this paper, we proposed a method to recognize complex human daily activities which consist of simultaneous body activities and hand gestures in an indoor environment. A wireless power-aware motion sensor node is developed which consists of a commercial orientation sensor, a wireless communication module, and a power management unit. To recognize complex daily activities, three motion sensor nodes are attached to the right thigh, the waist, and the right hand of a human subject, while an optical motion capture system is used to obtain his/her location information. A three-level dynamic Bayesian network (DBN) is implemented to model the intratemporal and intertemporal constraints among the location, body activity, and hand gesture. The body activity and hand gesture are estimated using a Bayesian filter and a short-time Viterbi algorithm, which reduces the computational complexity and memory usage. We conducted experiments in a mock apartment environment and the obtained results showed the effectiveness and accuracy of our method.


Intravenous Carbamazepine for Adults With Seizures.
To review the pharmacology, pharmacokinetics, efficacy, safety, dosage and administration, potential drug-drug interactions, and place in therapy of the intravenous (IV) formulation of carbamazepine (Carnexiv) for the treatment of seizures in adult patients. A comprehensive PubMed and EBSCOhost search (1945 to August 2017) was performed utilizing the keywords carbamazepine, Carnexiv, carbamazepine intravenous, IV carbamazepine, seizures, epilepsy, and seizure disorder. Additional data were obtained from literature review citations, manufacturer's product labeling, and Lundbeck website as well as Clinicaltrials.gov and governmental sources. All English-language trials evaluating IV carbamazepine were analyzed for this review. IV carbamazepine is FDA approved as temporary replacement therapy for treatment of adult seizures. Based on a phase I trial and pooled data from 2 open-label bioavailability studies comparing oral with IV dosing, there was no noted indication of loss of seizure control in patients switched to short-term replacement antiepileptic drug therapy with IV carbamazepine. The recommended dose of IV carbamazepine is 70% of the patient's oral dose, given every 6 hours via 30-minute infusions. The adverse effect profile of IV carbamazepine is similar to that of the oral formulation, with the exception of added infusion-site reactions. IV carbamazepine is a reasonable option for adults with generalized tonic-clonic or focal seizures, previously stabilized on oral carbamazepine, who are unable to tolerate oral medications for up to 7 days. Unknown acquisition cost and lack of availability in the United States limit its use currently.


Technical-methodological report: a nomogram for peak leg power output in the vertical jump.
Leg power is an important component in assessing both performance-related and health-related fitness. The Lewis equation and nomogram have been used for years to estimate leg power. A recent evaluation of the Lewis equation and further research led to the development of the Sayers equation. This equation provides an estimate of peak leg power, which has greater relevance than average power. Our purpose was to provide a simple and effective nomogram for calculating peak leg power output. The Sayers equation was transformed to an alignment nomogram and evaluated for facility of use and accuracy. The resultant alignment nomogram is easy to use and generates values for peak leg power in the vertical jump, which are well within the precision of the regression equation (r > 0.9999, CV < 0.2%). Interobserver error was less than 0.3% with a correlation of 0.9999. The Keir nomogram provides a simple and effective representation of the Sayers equation for use in both performance-related and health-related fitness assessments.


Speaking a common language: the international consensus on bicuspid aortic valve nomenclature and classification.
The congenital bicuspid aortic valve (BAV) condition is a valvulo-aortopathy with heterogeneous phenotypic expressions and clinical outcomes. A multitude of pre-existing classification systems, some extensive and some succinct, utilize combinations of numbers and/or letters to describe the condition. These diverse nomenclature systems are used according to the random preference of clinicians and researchers, generating confusion in clinical practice and research alike, effectively creating a barrier of communication at multiple levels. Based on imaging, pathology, surgery and clinical history evidence-based principles, and in utilizing the English language, the international nomenclature and classification consensus on the congenital BAV and its aortopathy offers a simple nosologic and phenotypic format that covers all possible phenotypes and clinical presentations of the bicuspid valvulo-aortopathy. From the nosology perspective, the valvulo-aortopathy has three major clinical presentations: (I) typical valvulo-aortopathy; (II) complex valvulo-aortopathy; and (III) undiagnosed or uncomplicated valvulo-aortopathy. From the valvular perspective, the congenital BAV has three major phenotypic expressions: (I) the fused BAV; (II) the 2-sinus BAV; and (III) the partial fusion (forme fruste) BAV. From the aortopathy perspective, the condition has three major phenotypic expressions: (I) ascending phenotype; (II) root phenotype; and (III) extended phenotypes. The international consensus is intended for universal use by Clinicians (pediatric and adult), echocardiography sonographers and physicians, cardiovascular advanced-imaging specialists, interventional cardiologists, cardiovascular surgeons, pathologists, geneticists and researchers encompassing clinical and basic research areas. When new landmark research is available, this international consensus may be subject to change in accordance with evidence-based data.


Application of physiologically based absorption modeling to formulation development of a low solubility, low permeability weak base: mechanistic investigation of food effect.
Physiologically based pharmacokinetic (PBPK) modeling has been broadly used to facilitate drug development, hereby we developed a PBPK model to systematically investigate the underlying mechanisms of the observed positive food effect of compound X (cpd X) and to strategically explore the feasible approaches to mitigate the food effect. Cpd X is a weak base with pH-dependent solubility; the compound displays significant and dose-dependent food effect in humans, leading to a nonadherence of drug administration. A GastroPlus Opt logD Model was selected for pharmacokinetic simulation under both fasted and fed conditions, where the biopharmaceutic parameters (e.g., solubility and permeability) for cpd X were determined in vitro, and human pharmacokinetic disposition properties were predicted from preclinical data and then optimized with clinical pharmacokinetic data. A parameter sensitivity analysis was performed to evaluate the effect of particle size on the cpd X absorption. A PBPK model was successfully developed for cpd X; its pharmacokinetic parameters (e.g., C max, AUCinf, and t max) predicted at different oral doses were within ±25% of the observed mean values. The in vivo solubility (in duodenum) and mean precipitation time under fed conditions were estimated to be 7.4- and 3.4-fold higher than those under fasted conditions, respectively. The PBPK modeling analysis provided a reasonable explanation for the underlying mechanism for the observed positive food effect of the cpd X in humans. Oral absorption of the cpd X can be increased by reducing the particle size (<100 nm) of an active pharmaceutical ingredient under fasted conditions and therefore, reduce the cpd X food effect correspondingly.


Non-targeted and targeted protein movement through plasmodesmata in leaves in different developmental and physiological states.
Plant cells rely on plasmodesmata for intercellular transport of small signaling molecules as well as larger informational macromolecules such as proteins. A green fluorescent protein (GFP) reporter and low-pressure microprojectile bombardment were used to quantify the degree of symplastic continuity between cells of the leaf at different developmental stages and under different growth conditions. Plasmodesmata were observed to be closed to the transport of GFP or dilated to allow the traffic of GFP. In sink leaves, between 34% and 67% of the cells transport GFP (27 kD), and between 30% and 46% of the cells transport double GFP (54 kD). In leaves in transition transport was reduced; between 21% and 46% and between 2% and 9% of cells transport single and double GFP, respectively. Thus, leaf age dramatically affects the ability of cells to exchange proteins nonselectively. Further, the number of cells allowing GFP or double GFP movement was sensitive to growth conditions because greenhouse-grown plants exhibited higher diffusion rates than culture-grown plants. These studies reveal that leaf cell plasmodesmata are dynamic and do not have a set size exclusion limit. We also examined targeted movement of the movement protein of tobacco mosaic virus fused to GFP, P30::GFP. This 58-kD fusion protein localizes to plasmodesmata, consistently transits from up to 78% of transfected cells, and was not sensitive to developmental age or growth conditions. The relative number of cells containing dilated plasmodesmata varies between different species of tobacco, with Nicotiana clevelandii exhibiting greater diffusion of proteins than Nicotiana tabacum.


Development of a DNA-launched replicon as a vaccine for porcine reproductive and respiratory syndrome virus.
Though a modified live attenuated vaccine (MLV) is available against porcine reproductive and respiratory syndrome virus (PRRSV), its limitations in protective efficacy, safety and few others warrant the development of newer vaccines. In this study, we have constructed a propagation-defective DNA-launched PRRSV replicon as a vaccine candidate and evaluated its immunogenicity and protective efficacy in a group of pigs along with MLV vaccinated group. Our data showed that prior to the intranasal challenge with a homologous strain of PRRSV, only MLV vaccinated pigs developed antibody response measured by ELISA and none of the pigs in any group developed PRRSV neutralizing antibodies in serum. The MLV vaccinated group also showed high PRRSV-specific INF-γ response, whereas the replicon-vaccinated pigs showed low but detectable INF-γ response. After 14 days post challenge, all groups showed similar PRRSV-specific serum neutralizing titers and were positive for PRRSV-specific ELISA antibody. In addition, the replicon-vaccinated group showed a significant reduction in viremia in comparison to the control group. In conclusion, vaccination with the PRRSV DNA-launched replicon decreased the viremia and viral load in bronchoalveolar lavage fluids of the PRRSV-challenged pigs and increased numbers of IFN-γ producing cells. Thus, the vaccine is partially protective and is a potential vaccine candidate for future with further improvement. The possible means of improvement is the expression of immunostimulatory genes by the replicon. We demonstrated the feasibility of this approach by expression of a foreign gene encoding firefly luciferase after transfection of cultured cells with the replicon plasmid DNA.


Sequential determination of CRP, alpha 1-antitrypsin and haptoglobin in neonatal septicaemia.
In 312 preterm and term newborn infants serum concentrations of C-reactive protein (CRP), haptoglobin and alpha 1-antitrypsin were measured during several days by radial immunodiffusion. In addition white blood cell count and the ratio of band to total neutrophils (B/N-ratio) were determined. In 12 infants with proven sepsis CRP was found elevated above the upper limit of the normal range (20 mg/l). Successful therapy was followed by a decrease of CRP concentration. In infants with suspected infection high CRP values were found in most cases. In contrast, haptoglobin and alpha 1-antitrypsin concentrations differed not significantly between the group of infants without infection, with proven and with suspected infection. White blood cell count and B/N-ratio also were not appropriate for the early identification of bacterial infection in the newborn period.


Underserved farmers with disabilities: designing an AgrAbility program to address health disparities.
Awareness of health disparities is crucial for individuals with disabilities to minimize additional health-related challenges. Adding rural residence and age to disability creates a triple threat in terms of potential health disparities. Kentucky AgrAbility is developing innovative new partnerships with the goal of expanding service provision to underserved populations with disabilities in Kentucky: women, minority, and Appalachian small farmers. Kentucky AgrAbility is evolving to include a more focused approach to the needs of underresourced and underserved regions and populations of farmers in Kentucky. Through new partnerships and a commitment to addressing potential health disparities, farmers and families who can benefit from AgrAbility services will be broadly identified. It is concluded that health disparities need to be recognized and addressed in all health care service provision and education. Kentucky AgrAbility is attempting to develop and implement an innovative, multidisciplinary team of partners with a goal of providing one of a kind service and education to all Kentucky farmers with disabilities. This includes underserved farmers who are at risk of not receiving the appropriate services due to limited resources and lack of awareness.


High-frequency jet ventilation improves cardiac function after the Fontan procedure.
Pulmonary vascular resistance is an important determinant of cardiac output after the Fontan procedure and is adversely affected by elevated mean airway pressure. High-frequency jet ventilation (HFJV) is an alternate form of mechanical ventilation which supports gas exchange at lower mean airway pressure. This study was performed to determine if HFJV could lower mean airway pressure and pulmonary vascular resistance and result in an increase in cardiac output after the Fontan procedure. We prospectively evaluated 13 patients ranging in age from 0.9 to 8.5 years (mean, 3.9 years) and in weight from 6.2 to 20.1 kg (mean, 13.9 kg). Right atrial, left atrial and pulmonary artery catheters were used to measure hemodynamic parameters. Cardiac index was measured by dye dilution technique, and pulmonary vascular resistance was calculated. The patients were stabilized on mechanical ventilation to achieve a PaCO2 = 30 +/- 5 mm Hg, and baseline hemodynamic and respiratory measurements were made. HFJV was begun at settings adjusted to achieve similar gas exchange. Respiratory and hemodynamic measurements were repeated after 30-60 minutes of HFJV. Mechanical ventilation was then resumed at baseline settings, and measurements were repeated 0.5-1 hour later. There was no significant change in gas exchange. HFJV resulted in a 50% reduction in mean airway pressure (9.2 +/- 0.2 cm H2O to 4.6 +/- 0.1 cm H2O, p less than 0.001), a 59% reduction in pulmonary vascular resistance (3.82 +/- 0.36 to 1.52 +/- 0.16 Woods units, p less than 0.001), and a 25% increase in cardiac index (2.32 +/- 0.12 l/min/m2 to 2.91 +/- 0.12 l/min/m2, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)


Fed-batch culture automated by uses of continuously measured cell concentration and culture volume.
An automated control method of fed-batch culture in which the nutrient feed rate was determined from continuously measured cell concentration and culture broth volume was developed. Theoretical background was elucidated, from which it was found that the method is unique in that it controls specific substrate consumption rate of the microorganism. The method was experimentally applied to the fed-batch cultures of recombinant Escherichia coli HB101. It was observed that the specific substrate feed rate affects not only the specific growth rate but also the growth yield. If some conditions are satisfied, this type of automated fed-batch culture can be applied widely to any microbial systems and seems especially useful when the culture medium is composed of natural complex nutrient(s) because their concentrations are very difficult to detect and control.


Recombinant human parvovirus B19 vectors: erythrocyte P antigen is necessary but not sufficient for successful transduction of human hematopoietic cells.
The blood group P antigen, known to be abundantly expressed on erythroid cells, has been reported to be the cellular receptor for parvovirus B19. We have described the development of recombinant parvovirus B19 vectors with which high-efficiency, erythroid lineage-restricted transduction can be achieved (S. Ponnazhagan, K. A. Weigel, S. P. Raikwar, P. Mukherjee, M. C. Yoder, and A. Srivastava, J. Virol. 72:5224-5230, 1998). However, since a low-level transduction of nonerythroid cells could also be detected and since P antigen is expressed in nonerythroid cells, we reevaluated the role of P antigen in the viral binding and entry into cells. Cell surface expression analyses revealed that approximately 75% of primary human bone marrow mononuclear erythroid cells and approximately 31% of cells in the nonerythroid population were positive for P antigen. Two human erythroleukemia cell lines, HEL and K562, and a human promyelocytic leukemia cell line, HL-60, were also examined for P antigen expression and binding and entry of the vector. HEL and K562 cells showed intermediate levels, whereas HL-60 cells demonstrated high levels of expression of P antigen. However, the efficiency of vector binding to these cells did not correlate with P antigen expression. Moreover, despite P antigen positivity and efficient viral binding, HEL, K562, and HL-60 cells could not be transduced with the vector. Low levels of P antigen expression could also be detected in two primary cell types, human umbilical vein endothelial cells (HUVEC) and normal human lung fibroblasts (NHLF). In addition, vector binding occurred in both cell types and was inhibited by globoside, indicating the involvement of P antigen in virus binding to these cells. These primary cells could be efficiently transduced with the recombinant vector. These data suggest that (i) P antigen is expressed on a variety of cell types and is involved in binding of parvovirus B19 to human cells, (ii) the level of P antigen expression does not correlate with the efficiency of viral binding, (iii) P antigen is necessary but not sufficient for parvovirus B19 entry into cells, and (iv) parvovirus B19 vectors can be used to transduce HUVEC and NHLF. These studies further suggest the existence of a putative cellular coreceptor for efficient entry of parvovirus B19 into human cells.


Value of pre-employment radiographic assessment of the lumbar spine.
In order to test the hypothesis that pre-employment radiographic examination provides information which permits identification of individuals who are likely to develop symptoms of lumbar pain under the stress of physical labour, the study reported was undertaken. Two groups of male labourers of minimum age 35 years were matched for important variables, and differentiated by the circumstance that one group alone had the additional characteristic of a positive history of lumbar disability. Study of the radiographs of these subjects allowed tabulation of all deviations from normal, both minor and major. A computerized comparative analysis was performed on the data. It was found that there is no developmental or degenerative change or combination of such changes which has predictive value when applied to the individual. Therefore, since this examination provides no legitimate criteria for prognostication, the hypothesis as stated is invalid, and the worth of the policy of pre-employment assessment is open to serious question.


Perspective on coronary interventions & cardiac surgeries in India.
Cardiovascular disease has become the leading cause of morbidity and mortality in India during the last 3 decades. The genetic predisposition and acquisition of traditional risk factors at a rapid rate as a result of urbanization seems to be the major cause. While efforts are being made to contain this epidemic by educating public and applying preventive measures, the ever increasing burden of patients with symptomatic and life threatening manifestations of the disease is posing a major challenge. This requires a concerted effort to develop modern facilities to treat these patients. The healthcare facilities to manage these high risk patients by contemporary methods like percutaneous coronary revascularization and surgical methods have shown a very promising trend during the last decade. The facilities of modern diagnostic methods and new proven techniques to offer symptomatic relief and improve their prognosis are available in most parts of the country. The lack of social security and health insurance for the large majority of the population, however, is a serious limitation. Unregulated availability of some of the newer devices for these techniques had become a very concerning issue. However, in the last few years serious efforts have been made to streamline these procedures. Indigenous research and scientific data acquisition in relation to the modern technology for achieving coronary revascularization has also started on a promising note.


A comparison between neural-network forecasting techniques--case study: river flow forecasting.
Estimating the flows of rivers can have significant economic impact, as this can help in agricultural water management and in protection from water shortages and possible flood damage. The first goal of this paper is to apply neural networks to the problem of forecasting the flow of the River Nile in Egypt. The second goal of the paper is to utilize the time series as a benchmark to compare between several neural-network forecasting methods.We compare between four different methods to preprocess the inputs and outputs, including a novel method proposed here based on the discrete Fourier series. We also compare between three different methods for the multistep ahead forecast problem: the direct method, the recursive method, and the recursive method trained using a backpropagation through time scheme. We also include a theoretical comparison between these three methods. The final comparison is between different methods to perform longer horizon forecast, and that includes ways to partition the problem into the several subproblems of forecasting K steps ahead.


Consider muscle disease in children with elevated transaminase.
The transaminases alanine aminotransferase (ALT) and aspartate aminotransferase (AST) are markers of hepatocellular injury but are highly concentrated in muscle cells. Consequently, muscular dystrophies such as Duchenne muscular dystrophy, lead to hypertransaminasemia. Elevation in ALT and AST is most striking during the early stages of disease, before onset of or when only subtle signs of muscle disease are present. Thus, the incidental finding of elevated ALT/AST may be the presenting sign of muscle disease in many children and provides an opportunity for early diagnosis. Many physicians, however, pursue extensive workup for liver disease in children who present with the incidental finding of elevated ALT/AST. This results in delayed diagnosis and initiation of treatment and increased expense and may lead to unnecessary invasive procedures. We report 12 patients with muscle disease who presented with a variety of symptoms and were found to have an incidental finding of elevated ALT/AST. We propose a rapid screening process for evaluating children with the incidental finding of elevated ALT/AST to shorten the time to diagnosis of muscle disease.


Learning-based defect recognition for quasi-periodic HRSTEM images.
Controlling crystalline material defects is crucial, as they affect properties of the material that may be detrimental or beneficial for the final performance of a device. Defect analysis on the sub-nanometer scale is enabled by high-resolution scanning transmission electron microscopy (HRSTEM), where the identification of defects is currently carried out based on human expertise. However, the process is tedious, highly time consuming and, in some cases, yields ambiguous results. Here we propose a semi-supervised machine learning method that assists in the detection of lattice defects from atomic resolution HRSTEM images. It involves a convolutional neural network that classifies image patches as defective or non-defective, a graph-based heuristic that chooses one non-defective patch as a model, and finally an automatically generated convolutional filter bank, which highlights symmetry breaking such as stacking faults, twin defects and grain boundaries. Additionally, we suggest a variance filter to segment amorphous regions and beam defects. The algorithm is tested on III-V/Si crystalline materials and successfully evaluated against different metrics and a baseline approach, showing promising results even for extremely small training data sets and for noise compromised images. By combining the data-driven classification generality, robustness and speed of deep learning with the effectiveness of image filters in segmenting faulty symmetry arrangements, we provide a valuable open-source tool to the microscopist community that can streamline future HRSTEM analyses of crystalline materials.


Surface modification of cellulose nanocrystals.
Chemical modification of cellulose nanocrystals is an increasingly popular topic in the literature. This review analyses the type of cellulose nanocrystal modification reactions that have been published in the literature thus far and looks at the steps that have been taken towards analysing the products of the nanocrystal modifications. The main categories of reactions carried out on cellulose nanocrystals are oxidations, esterifications, amidations, carbamations and etherifications. More recently nucleophilic substitutions have been used to introduce more complex functionality to cellulose nanocrystals. Multi-step modifications are also considered. This review emphasizes quantification of modification at the nanocrystal surface in terms of degree of substitution and the validity of conclusions drawn from different analysis techniques in this area. The mechanisms of the modification reactions are presented and considered with respect to the effect on the outcome of the reactions. While great strides have been made in the quality of analytical data published in the field of cellulose nanocrystal modification, there is still vast scope for improvement, both in data quality and the quality of analysis of data. Given the difficulty of surface analysis, cross-checking of results from different analysis techniques is fundamental for the development of reliable cellulose nanocrystal modification techniques.


[Medical electroradiology technicians: mediators in hospital care].
Beyond simply carrying out the medical imaging procedure, radiology technicians have an ambivalent position in radiology departments: working both with the patient and with the doctor, they act as a link between these two entities which rarely, if ever, meet. This socioprofessional category is a keystone to medical imaging services, yet it receives little recognition and its crucial role is often overlooked. The exact delimitation of its functions within the hospital is often misunderstood.


Supervised Gaussian process latent variable model for dimensionality reduction.
The Gaussian process latent variable model (GP-LVM) has been identified to be an effective probabilistic approach for dimensionality reduction because it can obtain a low-dimensional manifold of a data set in an unsupervised fashion. Consequently, the GP-LVM is insufficient for supervised learning tasks (e.g., classification and regression) because it ignores the class label information for dimensionality reduction. In this paper, a supervised GP-LVM is developed for supervised learning tasks, and the maximum a posteriori algorithm is introduced to estimate positions of all samples in the latent variable space. We present experimental evidences suggesting that the supervised GP-LVM is able to use the class label information effectively, and thus, it outperforms the GP-LVM and the discriminative extension of the GP-LVM consistently. The comparison with some supervised classification methods, such as Gaussian process classification and support vector machines, is also given to illustrate the advantage of the proposed method.


A Model for a Policy on HIV/AIDS and Athletics.
Human immunodeficiency virus (HIV)-infected athletes exist at the collegiate level and are engaging in competitive sports, as was revealed by a 1993 NCAA survey. Unfortunately, there is a void when the issue of policy for the HIV- positive athlete and his or her participation rights at the collegiate level is addressed. Given the controversial nature of opinion on HIV and the resultant acquired immunodeficiency syndrome (AIDS), it is recommended that a policy be in place for an HIV-infected athlete before it is needed. Ithaca College has recently developed such a policy, and it is offered here to other educational institutions as a model. It is emphasized throughout the policy that HIV-positive athletes should not be restricted from athletic participation for the reason of infection alone, that strict confidentiality guidelines should be followed, and that mandatory testing of athletes for HIV is not justified.


Mutations in ionotropic AMPA receptor 3 alter channel properties and are associated with moderate cognitive impairment in humans.
Ionotropic alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors (iGluRs) mediate the majority of excitatory synaptic transmission in the CNS and are essential for the induction and maintenance of long-term potentiation and long-term depression, two cellular models of learning and memory. We identified a genomic deletion (0.4 Mb) involving the entire GRIA3 (encoding iGluR3) by using an X-array comparative genomic hybridization (CGH) and four missense variants (G833R, M706T, R631S, and R450Q) in functional domains of iGluR3 by sequencing 400 males with X-linked mental retardation (XLMR). Three variants were found in males with moderate MR and were absent in 500 control males. Expression studies in HEK293 cells showed that G833R resulted in a 78% reduction of iGluR3 due to protein misfolding. Whole-cell recording studies of iGluR3 homomers in HEK293 cells revealed that neither iGluR3-M706T (S2 domain) nor iGluR3-R631S (near channel core) had substantial channel function, whereas R450Q (S1 domain) was associated with accelerated receptor desensitization. When forming heteromeric receptors with iGluR2 in HEK293 cells, all four iGluR3 variants had altered desensitization kinetics. Our study provides the genetic and functional evidence that mutant iGluR3 with altered kinetic properties is associated with moderate cognitive impairment in humans.


[Dopamine dysregulation syndrome in a patient with Parkinson's disease; a case report].
Both Parkinson's disease and its treatment can be associated with psychiatric symptoms. We illustrate this link by focusing on a patient suffering from Parkinson's who received not only deep brain stimulation but also excessive amounts of dopaminergic drugs, a combination that resulted in hypomania which is also known as dopamine dysregulation syndrome. We discuss the symptoms, possible aetiological pathways and the implications for clinical practice.


Clinical study on vacuum assisted closure combined with multiple flaps in the treatment of severe hand trauma.
To investigate the effect and clinical value of the application of vacuum assisted closure (VAC) combined with multiple flaps in the treatment of severe hand trauma. A total of 100 patients with severe hand trauma admitted to Harrison International Peace Hospital from September 2015 to September 2020 were selected and randomly divided into two groups according to the randomized block method: the single flap repair group and the combined repair group, with 50 patients in each group. Patients in the single flap repair group underwent flap repair according to their condition, while those in the combined repair group were treated with VAC prior to flap repair. The range of motion and hand sensation scores were compared between the two groups, and their levels of interleukin-8 (IL-8), tumor necrosis factor (TNF) and lipopolysaccharide (LPS) were tested by enzyme-linked immunosorbent assay (ELIS). Moreover, the flap survival rate and the incidence of adverse events were recorded and compared between the two groups. Compared with the single flap repair group, the combined repair group had higher range of motion and hand sensation score (p<0.05), lower levels of IL-8, TNF and LPS (p<0.05), higher flap survival rate (p<0.05), and lower incidence of adverse events (p<0.05). VAC combined with multiple flaps boasts significant trauma repair effect and preferable clinical application value in the treatment of patients with severe hand trauma, which is principally reflected in significantly improving the hand function of patients and remarkably alleviating the inflammatory response of patients.


Recent developments in the HIV neuropathies.
With the introduction of highly active antiretroviral therapy peripheral neuropathies have become the most common neurological complications in HIV infection. The frequency and spectrum of these neuropathies are changing, as the various toxic and immune factors are modified by new treatment strategies. Recent studies have provided a better understanding of the risk factors, markers and relevant pathogenic mechanisms, and a thorough review of these is critical for an improved understanding of this important and increasingly common complication. The combined use of dideoxynucleosides, in association with immune-mediated mechanisms triggered by HIV infection, are critical in the development of distal sensory polyneuropathy. Valuable markers of neuropathy such as intraepidermal nerve fiber density from skin biopsies have been validated and promise to be a valuable tool in the detection and monitoring of distal sensory polyneuropathy. Markers of virological activity have also been associated with the severity of neuropathic pain in distal sensory polyneuropathy. In some instances, the enhanced viral suppression from antiretroviral agents may actually improve or decrease the frequency of certain types of neuropathy. New evidence supports mitochondrial toxicity as a principal mechanism for dideoxynucleoside-associated sensory neuropathy, and questions arise about enhanced risk with pre-existing mitochondrial defects. Confirmed treatments are limited to the reduction of symptoms, with a need for the further investigation of corrective therapies. Increased and improved surveillance for HIV-associated neuropathy will allow earlier interventions to improve quality of life and prevent severe toxicities. A better understanding of the prevailing mechanisms will allow for more effective interventions.


Parallel emergence of negative epistasis across experimental lineages.
Epistatic interactions can greatly impact evolutionary phenomena, particularly the process of adaptation. Here, we leverage four parallel experimentally evolved lineages to study the emergence and trajectories of epistatic interactions in the social bacterium Myxococcus xanthus. A social gene (pilA) necessary for effective group swarming on soft agar had been deleted from the common ancestor of these lineages. During selection for competitiveness at the leading edge of growing colonies, two lineages evolved qualitatively novel mechanisms for greatly increased swarming on soft agar, whereas the other two lineages evolved relatively small increases in swarming. By reintroducing pilA into different genetic backgrounds along the four lineages, we tested whether parallel lineages showed similar patterns of epistasis. In particular, we tested whether a pattern of negative epistasis between accumulating mutations and pilA previously found in the fastest lineage would be found only in the two evolved lineages with the fastest and most striking swarming phenotypes, or rather was due to common epistatic structure across all lineages arising from the generic fixation of adaptive mutations. Our analysis reveals the emergence of negative epistasis across all four independent lineages. Further, we present results showing that the observed negative epistasis is not due exclusively to evolving populations approaching a maximum phenotypic value that inherently limits positive effects of pilA reintroduction, but rather involves direct antagonistic interactions between accumulating mutations and the reintroduced social gene.


Fine-needle aspiration cytodiagnosis: a simple and safe procedure for cancer of the pancreas.
One hundred fine-needle aspirations (45 percutaneous ultrasonically-guided and 55 intraoperative) were performed in 82 patients suspected of having pancreatic cancer, in order to evaluate the contribution of cytologic data to definitive diagnosis of this tumor. The overall success rate of both cytologic methods was 90.6 p. 100 in our 64 patients who were histologically proved to have pancreatic cancer. Sensitivity was 77.4 p. 100 with percutaneous and 75.5 p. 100 with intraoperative aspirations. In all 18 cases with the final diagnosis of chronic pancreatitis results of both techniques were negative. Neither relevant morbidity nor mortality were recorded in any of the 82 patients. These cytologic studies are at present reliable, rapid, highly cost-effective (especially percutaneous aspiration) and most important, safer than histologic examinations. We believe that fine-needle aspiration cytology has gained a primary role in the diagnostic process of pancreatic carcinoma. Therefore the old view of considering examination of cytologic material only as a screening procedure should be abandoned.