Use of Vasopressor Increases the Risk of Mortality in Traumatic Hemorrhagic Shock: A Nationwide Cohort Study in Japan.
To evaluate the possible association of vasopressor use with mortality in traumatic hemorrhagic shock patients. Retrospective cohort study. Traumatic hemorrhagic shock patients at 260 emergency hospitals in Japan between 2004 and 2015. Three-thousand five-hundred fifty-one traumatic hemorrhagic shock patients who had systolic hypotension (< 90 mm Hg) on arrival at the emergency department and a blood transfusion received within the first 24 hours. The use of vasopressor for traumatic hemorrhagic shock within the first 24 hours. Among 236,698 trauma patients, 3,551 were included in the study. Overall, 198 of 459 patients (43%) in the vasopressor+ group expired compared with 481 of 3,092 patients (16%) in the vasopressor- group. Use of vasopressor had an odds ratio of 2.172 (95% CI, 1.666-2.833) for in-hospital mortality adjusted for age, gender, year of onset, cause of injury, mechanism of injury, vital signs at the emergency department, Injury Severity Score, use of prehospital IV fluid, and volume of blood transfusion within the first 24 hours. In the propensity score-matched cohort and two subgroup analyses (massive transfusion and survivable injury models), use of vasopressor was associated with higher mortality (odds ratio, 2.168; 95% C, 1.442-3.320), (odds ratio, 2.029; 95% CI, 1.414-2.911; massive transfusion model), and (odds ratio, 1.959; 95% CI, 1.364-2.814; survivable injury model). Use of vasopressor for traumatic hemorrhagic shock was associated with mortality after controlling for biases (trauma severity; volume of fluid resuscitation).


Angiographic characteristics of the infarct-related coronary artery in patients with angina pectoris after myocardial infarction.
To elucidate the pathophysiology of angina pectoris after myocardial infarction, we analyzed the coronary stenoses in 45 subjects (28 men, 17 women, aged 33 to 67 years) with recent (less than or equal to 60 days) infarction, significant narrowing of only the infarct-related artery, and residual anterograde flow in this artery. Postinfarction angina was absent in 19 (group I) and present in 26 (group II). The groups were similar in age, left ventricular function, incidence with which each coronary artery was involved, as well as stenosis diameter (1.0 +/- 0.3 vs 0.9 +/- 0.4 mm [mean +/- standard deviation], respectively, difference not significant), stenosis area (0.9 +/- 0.4 vs 0.8 +/- 0.8 mm2, respectively, difference not significant), percent diameter narrowing (65 +/- 5 vs 66 +/- 9, respectively, difference not significant), and stenosis eccentricity. However, those with postinfarction angina had longer stenoses (group I, 4.3 +/- 1.4 mm; group II, 10.3 +/- 4.0 mm; p less than 0.001). Thus, patients with postinfarction angina and residual anterograde flow in the infarct artery may have angina due to a marked reduction in anterograde flow, caused by a long stenosis. There is no apparent relation between stenosis eccentricity and postinfarction angina.


Effects of early spatial training on water maze performance: a longitudinal study in mice.
The aim of the present study is to establish whether in mice the effects of an early experience in the Morris water maze are maintained after a long period. A longitudinal study was performed in which mice of two different strains (NMRI and C57) received spatial training at 2 months of age and their performance was re-evaluated 8 and 16 months later. In both strains, results showed a beneficial effect of prior experience on this spatial memory task even 8 months after the initial training. At 18 months of age, performance of C57 mice that were trained at 2 months of age for the first time was similar to those who received their first training at 10 months of age. These findings suggest that the beneficial effect of previous training could be limited by time. In addition, water maze performance of 18 month-old C57 mice did not differ from their earlier performance when they were 10 months of age, which would indicate that experience in this task could prevent some of the age-related spatial learning deficits observed in mice.


The effects of enzymes on the blood factors associated with the FV system of bovine erythrocytes.
Treatment of cattle red cells (CRC) with proteases and neuraminidase revealed at least one trypsin- or pronase-sensitive type and a protease-resistant type of sialoglycoprotein. The antigen F itself and the antigen IM in the F/F and F/V type of CRC were associated with the protease-resistant glycoprotein. Moreover, they were demonstrable in the agglutination test, but only after treatment with proteases. The antigen V, allelic to F, was, however, associated with a pronase-sensitive protein and the antigen IM in the V/V type of CRC with a trypsin- or pronase-sensitive glycoprotein. The antigen N' was inactivated by chymotrypsin or pronase, irrespective of whether it was transmitted with the F or with the V. While the antigens IM, N' and the antigen reacting with rabbit serum, in addition to the antigen F in the F/F type of CRC, showed no or only very weak (titre 1:2) reactions, these same antigens, in addition to the antigen V in the V/V type of CRC, all showed high titres (1:32 to 1:128) in the anti-globulin test.


Three new BLM gene mutations associated with Bloom syndrome.
Bloom's syndrome (BS) is a rare autosomal recessive disease predisposing patients to all types of cancers affecting the general population. BS cells display a high level of genetic instability, including a 10-fold increase in the rate of sister chromatid exchanges, currently the only objective criterion for BS diagnosis. We have developed a method for screening the BLM gene for mutations based on direct genomic DNA sequencing. A questionnaire based on clinical information, cytogenetic features, and family history was addressed to physicians prescribing BS genetic screening, with the aim of confirming or guiding diagnosis. We report here four BLM gene mutations, three of which have not been described before. Three of the mutations are frameshift mutations, and the fourth is a nonsense mutation. All these mutations introduce a stop codon, and may therefore be considered to have deleterious biological effect. This approach should make it possible to identify new mutations and to correlate them with clinical information.


Baseline MELD-XI score and outcome from veno-arterial extracorporeal membrane oxygenation support for acute decompensated heart failure.
Acute decompensated heart failure is the most common acute heart failure phenotype. Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) can provide bridging support for patients with acute decompensated heart failure to transplantation. We studied the association between baseline (<6 months), pre-ECMO (<24 h) parameters and outcome of VA-ECMO support in patients with severe acute decompensated heart failure. We included 26 consecutive patients with acute decompensated heart failure (acute myocarditis, myocardial infarction or post-cardiotomy shock were excluded) who were bridged with peripheral VA-ECMO to transplantation. Data within six months (baseline) and immediately pre-ECMO were collected. Model for end-stage liver disease (MELD) with sodium (MELD-Na) and without international normalized ratio (MELD-XI) scores were calculated. Outcome was defined as death at 30 days following VA-ECMO support. Thirteen of the 26 patients died within 30 days of VA-ECMO support. Univariate associations with 30-day mortality were baseline MELD-XI, baseline sodium, creatinine, bilirubin, pre-ECMO alanine aminotransferase and lactate. However, only baseline MELD-XI score (hazard ratio 2.678 (95% CI 1.085-6.607), p=0.033) was associated 30-day survival on logistic regression analysis. Survivors demonstrated greater reduction in inotropic and vasoactive drug support and improvement in alanine aminotransferase and lactate levels. Using a threshold based on the median MELD-XI of 14.1, 30-day survival in patients with a baseline MELD-XI ⩽ 14.1 was 69% compared with 31% in patients with baseline MELD-XI > 14.1 ( p=0.046). Baseline MELD-XI score, but not pre-ECMO parameters, is independently associated with outcomes from VA-ECMO support in patients with acute decompensated heart failure.


Reversible regulation of thrombin adsorption and desorption based on photoresponsive-aptamer modified gold nanoparticles.
In the protein separation, adsorption and desorption of target protein have been using different buffer condition. Different buffer will change the structure and activity of target protein in some cases. This work describes the use of different wavelength light for remote regulation of adsorption and desorption of target protein in the same buffer solutions. A dynamic system that captured and released protein in response to light is reported. Matrix gold nanoparticles and light-responsive affinity ligand comprising thrombin aptamer (APT15), polyethylene glycol linker, and azobenzene-modified complementary sequence were used. UV light induced a trans-cis isomerization of the azobenzene that destabilized the duplex of aptamer and azobenzene-modified complementary sequence, resulting in thrombin binding to aptamer sequence. Visible light irradiation resulted in DNA duplex rehybridization and thrombin released. Our work demonstrates that different light wavelengths effectively regulated the adsorption and desorption of thrombin in the same buffer, and this system also can capture and release prothrombin from plasma with different wavelength light. Furthermore, this method can be widely applied to a variety of different protein separation process.


Effect of oral antiseptic agents on phospholipase and proteinase enzymes of Candida albicans.
Candida-associated denture stomatitis is the most prevalent form of oral candida infections among the denture wearers. Generally, antiseptic oral rinses used in the treatment of these infections are considered as an adjunct or alternative antifungal treatment. Studies have suggested that the intraoral concentrations of antiseptics decrease substantially to the sub-therapeutic levels on account of the dynamics of the oral cavity. This condition yields the question about the minimum antiseptic concentration that effect the character or pathogenesis of Candida during treatment. The extracellular phospholipase and proteinase enzymes of Candida albicans are regarded to have a crucial role in the pathogenesis of human fungal infections. Therefore, the aim of this study was to investigate the effect of different sub-therapeutic concentrations of chlorhexidine gluconate, hexetidine and triclosan on the production of these enzymes by C. albicans strains isolated from 20 patients with denture stomatitis. Phospholipase test was done by using Sabouraud dextrose agar with egg yolk, proteinase test was done by using bovine serum albumin agar. Phospholipase test was done by using Sabouraud dextrose agar with egg yolk, proteinase test was done by using bovine serum albumin agar. Exoenzyme production of 20 strains which were brief exposured to sub-therapeutic concentrations of three antiseptic agents decreased significantly compared with the strains that were not exposured with antiseptic values (p<0.05). There was significant difference between the sub-therapeutic concentrations of each of three antiseptics (p<0.05). When the same concentrations of each antiseptic was compared, there were no significant differences between enzymatic activities (p>0.05). The results of this study show that sub-therapeutic levels of each antiseptic may modulate candidal exoenzyme production, consequently suppressing pathogenicity of C. albicans.


Native Void Space for Maximum Volumetric Capacity in Silicon-Based Anodes.
Volumetric energy density is considered a primary factor in developing high-energy batteries. Despite its significance, less efforts have been devoted to its improvement. Silicon-based materials have emerged as next-generation anodes for lithium-ion batteries due to their high specific capacity. However, their volumetric capacities are limited by the volume expansion rate of silicon, which restricts mass loading in the electrodes. To address this challenge, we introduce porous silicon templated from earth-abundant minerals with native internal voids, capable of alleviating volumetric expansion during repeated cycles. In situ transmission electron microscopy analysis allows the precise determination of the expansion rate of silicon, thus presenting an analytical model for finding the optimal content in silicon/graphite composites. The inner pores in silicon reduce problems associated with its expansion and allow higher silicon loading of 42% beyond the conventional limitations of 13-14%. Consequently, the anode designed in this work can deliver a volumetric capacity of 978 mAh cc-1. Thus, suppressing volume expansion with natural abundant template-assisted materials opens new avenues for cost-effective fabrication of high volumetric capacity batteries.


[Percutaneous mandibular nerve block using neuro-stimulation guiding through the sigmoid indentation in facial surgery].
Mandibular nerve block is a simple and effective but rarely used technique. It decreases peri-operative pain in mandibular osteotomy. It improves surgical field visibility by decreasing bleeding. Mandibular nerve block allows cutaneous surgery without general anesthesia and is one of the alternative treatments for chronic facial pain. The mandibular nerve is located using a needle connected to a neurostimulator. After local disinfection, a neurostimulation needle is inserted below the zygomatic arch, between the coronoid apophysis in front, and the condyle process in back, with a 45 to 60° angle. The needle is pushed to a 40 mm depth. Masticator muscle contraction confirms mandibular nerve stimulation. After a careful negative aspiration, 5 mL of ropivacaine 0.5% are injected slowly, and in increments. The complications with this technique, such as failure or arterial puncture, are rare and limited if a nerve stimulator is used. Patient's comfort is improved by intravenous remifentanil sedation in target control infusion mode, associated to prior use of prilocaine and lidocaine cutaneous cream.


Late temporal lobe necrosis after conventional radiotherapy for carcinoma of maxillary sinus.
Cerebral radiation necrosis is a serious late complication after conventional radiotherapy that can present with focal neurologic deficits or with more generalized signs and symptoms of increased intracranial pressure, depending on the location. The incidence and severity of radionecrosis are dose-volume dependent. We report a case of cerebral radiation necrosis 5 years after radiotherapy for a maxillary sinus carcinoma.


Laparoscopic ventriculoperitoneal shunts: benefits to resident training and patient safety.
Symptomatic hydrocephalus is a surprisingly common clinical condition. Neurosurgeons are expert at ventriculostomy, but minimally invasive peritoneal access is outside the realm of their current training. We have adopted a multidisciplinary approach, with general surgeons positioning the distal shunt. Our objective was to review this recent experience. All distal shunts were placed by a single surgeon with resident assistance. After ventriculostomy, the shunt tubing was tunneled onto the anterior abdominal wall. A Veress needle was placed through the tunnel incision and the abdomen insufflated. A 5-mm optical access trocar and camera were introduced via a separate stab incision. The shunt tubing was then directed into the abdominal cavity using a Hickman introducer kit, with flow confirmed visually. Study patients who had between 0 and 10 previous abdominal operations received 111 consecutive shunts. There was one intraoperative complication, a colon injury during trocar placement. In this case, the colotomy was repaired and the shunt placed in the pleural space. There were no conversions to the open abdominal approach. Postoperatively, there were no wound infections, no cases of shunt malpositioning, and there were no deaths. Laparoscopic placement of ventriculoperitoneal shunts is feasible, safe, and carries a low rate of complications. The value to resident education in the practice of this procedure has not been previously emphasized. In the era of increased awareness of patient safety, laparoscopic VP shunting serves as a model for accomplishing both goals of improved outcomes and quality surgical education.


Murine cytomegalovirus and fertility: potential sexual transmission and the effect of this virus on fertilization in vitro.
Male mice were inoculated with murine cytomegalovirus (MCMV) to produce an acute generalized infection. Infections virus was recovered from both epididymal sperm and seminal vesicles as well as from uterine sperm collected from mated females, suggesting that MCMV might be transmitted sexually. Because the presence of virus in the ejaculate might affect the fertilization process, the effect of MCMV on the fertilization of mouse gametes and on subsequent embryonic development was studied in vitro. Although the fertilization rate was reduced when sperm were preincubated with infectious virus, this was also the case when heat-inactivated virus was used, leading to the conclusion that this effect was not due to a direct infectious interaction between virus and gametes. Subsequent embryonic development was normal, and there was no evidence of productive infection of the preimplantation embryo.


Adjunctive use of celecoxib with anti-tuberculosis drugs: evaluation in a whole-blood bactericidal activity model.
COX-2 inhibition may be of benefit in the treatment of tuberculosis (TB) through a number of pathways including efflux pump inhibition (increasing intracellular TB drug levels) and diverse effects on inflammation and the immune response. We investigated celecoxib (a COX-2 inhibitor) alone and with standard anti-tuberculosis drugs in the whole-blood bactericidal activity (WBA) model. Healthy volunteers took a single dose of celecoxib (400 mg), followed (after 1 week) by a single dose of either rifampicin (10 mg/kg) or pyrazinamide (25 mg/kg), followed (after 2 or 7 days respectively) by the same anti-tuberculosis drug with celecoxib. WBA was measured at intervals until 8 hours post-dose (by inoculating blood samples with Mycobacterium tuberculosis and estimating the change in bacterial colony forming units after 72 hours incubation). Celecoxib had no activity alone in the WBA assay (cumulative WBA over 8 hours post-dose: 0.03 ± 0.01ΔlogCFU, p = 1.00 versus zero). Celecoxib did not increase cumulative WBA of standard TB drugs (mean cumulative WBA -0.10 ± 0.13ΔlogCFU versus -0.10 ± 0.12ΔlogCFU for TB drugs alone versus TB drugs and celecoxib; mean difference -0.01, 95% CI -0.02 to 0.00; p = 0.16). The lack of benefit of celecoxib suggests that efflux pump inhibition or eicosanoid pathway-related responses are of limited importance in mycobacterial killing in the WBA assay.


Electrophoretic isolation and partial characterization of a major secretory glycoprotein from the submandibular glands of the mouse.
After either cholinergic or adrenergic stimulation of the submandibular glands of the mouse, a major protein of the incubation medium could be isolated by electrophoresis, designated the AM2 protein. About 5 per cent of the secreted proteins and 2.4 per cent of the secreted protein-bound sialic acid was recovered as the purified AM2 protein. The AM2 protein appeared to be electrophoretically pure in 7.5% polyacrylamide gel both at pH 8.9 and at pH 4.3. In sodium dodecyl sulfate-electrophoresis the molecular weight was estimated to be about 80 000 for the major component and about 40 000 for the minor component. By isoelectric focusing the isoelectric point has been determined to be 4.7. The amino acid analysis indicated Glx, Asx, Leu and Ala as the major amino acids, comprising 15.0, 10.6, 9.2 and 9.1 per cent of the amino acid residues, respectively. The ratio of the acidic amino acids and their amides (Glx plus Asx) to the basic amino acids (Lys plus Arg) was 2.2. The sugar analysis showed that the AM2 glycoprotein consists of 17.3 per cent of carbohydrate, with as major carbohydrate component glucosamine. The molar ratio of the sugars was Man : Gal : Glc : GlcNH2 : sialic acid = 2.3 : 1.0 : 4.7 : 9.8 : 2.9. Galactosamine could be detected as a trace component and fucose was not detectable.


Single-shot optical neural network.
Analog optical and electronic hardware has emerged as a promising alternative to digital electronics to improve the efficiency of deep neural networks (DNNs). However, previous work has been limited in scalability (input vector length K ≈ 100 elements) or has required nonstandard DNN models and retraining, hindering widespread adoption. Here, we present an analog, CMOS-compatible DNN processor that uses free-space optics to reconfigurably distribute an input vector and optoelectronics for static, updatable weighting and the nonlinearity-with K ≈ 1000 and beyond. We demonstrate single-shot-per-layer classification of the MNIST, Fashion-MNIST, and QuickDraw datasets with standard fully connected DNNs, achieving respective accuracies of 95.6, 83.3, and 79.0% without preprocessing or retraining. We also experimentally determine the fundamental upper bound on throughput (∼0.9 exaMAC/s), set by the maximum optical bandwidth before substantial increase in error. Our combination of wide spectral and spatial bandwidths enables highly efficient computing for next-generation DNNs.


Digital Training Resources in the Dutch Surgical Residency Curricula and the Perspectives of Residents: A Thematic Analysis of Resident Interviews.
Digital training resources show great promise in augmenting traditional surgical education - especially in times of social distancing and limited surgical caseload. Embedding digital resources in surgical curricula is however not current, nor common practice in Dutch hospitals. While the digital world has become part of a resident's everyday life, surprisingly little is known about surgical residents' experiences and expectations towards use of digital resources for their own surgical education. This study aims to identify digital resources currently used in Dutch surgical curricula and to describe surgical residents' perspectives towards digital education. A series of semi-structured interviews with Dutch surgical residents were conducted until data sufficiency occurred. The interviews consisted of two parts: 1) current surgical training and implemented digital resources, and 2) future surgical training and the role of digital resources therein. All interviews were digitally recorded, transcribed verbatim, and thematically analyzed. Sixteen surgical residents were interviewed - two out of each of the eight educational regions for surgery in the Netherlands. Five digital resource categories were identified and four general educational themes (requirements, advantages, disadvantages, and general education themes), overarching 13 sub-themes. In general, residents were enthusiastic with regard to using digital resources, especially when the perceived advantages supported their autonomy. Dutch surgical residents indicate that digital resources may support their educational experiences, but state that ideally they must be combined with much appreciated on-the-job training, and be offered to them tailored to their individual needs. No resources are considered to be a "magic bullet" in itself. The specific needs of residents and educators need to be addressed clearly in order to successfully adopt and implement digital resources on a larger scale.


Protein structure probed by polarization spectroscopy. I. Evidence for fibrinogen rigidity from stationary fluorescence.
Two fluorescent derivatives of human fibrinogen have been synthesized, by the covalent bonding of 1-dimethylaminoaphthalene-5-sulphonyl and methylpyrene chromophores, to investigate the internal molecular dynamics of the protein in solution. The stationary fluorescence depolarization of these derivatives under isothermal conditions is described here while in an accompanying paper (part II) a time-resolved study is reported. From the static fluorescence data it is concluded that reorientational processes in the subnanosecond and microsecond time ranges account for all the observed depolarization. The faster motion was assigned to the restricted, localized oscillations of the label while the slow motion was ascribed to the overall rotation of the protein molecule. Consequently, the protein in solution appears considerably rigid in the 10-1000 ns range, in contrast with a previous conception of a flexible fibrinogen based on non-isothermal depolarization experiments. These previous experiments are, in fact, concordant with the rigid fibrinogen proposed here if they are reinterpreted using Weber's early ideas on thermally activated depolarization (G. Weber, J. Biochem. 51 (1952) 145).


4,4'-(Ethene-1,2-diyl)dipyridinium bis(2-hy-droxy-3-meth-oxy-benzoate).
In the title double proton-transfer salt, C12H12N2 2+·2C8H7O4 -, consisting of a 1:2 ratio of 4,4'-(ethene-1,2-diyl)dipyridinium cations (trans bipyridinium ethyl-ene) to 2-hy-droxy-3-meth-oxy-benzoate anions (o-vanillate), the complete cation is generated by crystallographic inversion symmetry and it is linked to adjacent o-vanillate anions by N-H⋯O hydrogen bonds, forming trimolecular assemblies. The trimers are linked by C-H⋯O hydrogen bonds as well as aromatic π-π stacking inter-actions into a three-dimensional network. The anion features an intra-molecular O-H⋯O hydrogen bond.


Continuous glucose monitoring in adolescents with cystic fibrosis.
The presence of cystic fibrosis (CF)-related diabetes was evaluated in 19 adolescents with CF by continuous glucose monitoring system (CGMS) and oral glucose tolerance testing. CGMS confirmed diabetic glucose excursions in 7/19 subjects deemed diabetic on oral glucose tolerance testing. CGMS is a useful tool for detecting hyperglycemia in CF.


Outbreak of caterpillar dermatitis caused by airborne hairs of the mistletoe browntail moth (Euproctis edwardsi).
Caterpillars may be an under-recognised cause of skin and eye reactions. We report a four-month outbreak of recurrent papulourticarial rash among staff and visitors at a community centre. Caterpillar of the mistletoe browntail moth The cause was eventually diagnosed as airborne hairs from (Euproctis edwardsi). caterpillars of the mistletoe browntail moth (Euproctis edwardsi), which infested a eucalypt tree growing in front of the centre. To our knowledge, this is the first clear case of airborne caterpillar hairs causing dermatitis in an indoor environment.


Distribution of virulence genes in Aeromonas spp. isolated from Sardinian waters and from patients with diarrhoea.
To characterize 46 isolates of different Aeromonas spp. strains (26 Aeromonas hydrophila, 13 Aeromonas sobria and 7 Aeromonas salmonicida) isolated from coastal water and clinical sources in Sardinia, Italy. The isolates were analysed for the production of the following virulence properties: slime, haemolysin, gelatinase and protease production, and adhesion to eucaryotic epithelial cells. The presence of known virulence genes: A. hydrophila cytolytic enterotoxin gene AHCYTOEN; type IV pilus gene Tap; Bundle forming pilus genes BfpA and BfpG were investigated using polymerase chain reaction (PCR). In addition the enterobacterial repetitive intergenic consensus sequences (ERIC)-PCR fingerprinting was used to further differentiate the strains. This study confirms the presence of virulent Aeromonas strains in the Mediterranean sea. The study also found a greater prevalence of haemolysin, protease and gelatinase production, as well as a higher adhesion capacity, among strains isolated from patients with diarrhoea. This is the first time that Aeromonads have been isolated and characterized from Sardinian waters and from patients with diarrhoea in Sardinia. This study adds to our knowledge of the ecology of this micro-organism and may in the future help prevent infections both in fish and in humans.


Alternatives to Incomplete Colonoscopy.
A thorough and complete colonoscopy is critically important in preventing colorectal cancer. Factors associated with difficult and incomplete colonoscopy include a poor bowel preparation, severe diverticulosis, redundant colon, looping, adhesions, young and female patients, patient discomfort, and the expertise of the endoscopist. For difficult colonoscopy, focusing on bowel preparation techniques, appropriate sedation and adjunct techniques such as water immersion, abdominal pressure techniques, and patient positioning can overcome many of these challenges. Occasionally, these fail and other alternatives to incomplete colonoscopy have to be considered. If patients have low risk of polyps, then noninvasive imaging options such as computed tomography (CT) or magnetic resonance (MR) colonography can be considered. Novel applications such as Colon Capsule™ and Check-Cap are also emerging. In patients in whom a clinically significant lesion is noted on a noninvasive imaging test or if they are at a higher risk of having polyps, balloon-assisted colonoscopy can be performed with either a single- or double-balloon enteroscope or colonoscope. The application of these techniques enables complete colonoscopic examination in the vast majority of patients.


The effect of valproic acid on SCE and chromosome aberrations in epileptic children.
Sister-chromatid exchange (SCE) and chromosome aberrations have been studied in peripheral lymphocytes of 20 epileptic children treated in monotherapy with valproic acid (VPA) for 6-52 months and in 2 matched control groups. The frequencies of SCE in the VPA-treated epileptic children were significantly higher than in the 2 control groups (p less than 0.01); rates of chromosome aberrations were slightly higher but not significantly different from the 2 control groups. We also examined SCE in 10 epileptic children before and after they took sodium valproate for 6-7 months; there was a statistically significant change in SCE following VPA. 9 normal children whose lymphocytes were exposed in vitro to sodium valproate (5-20 micrograms/ml) showed a significant increase in SCE.


HA1004, an inhibitor of serine/threonine protein kinases, restores the sensitivity of thymic lymphomas to Ca2+-mediated apoptosis through a protein kinase A-independent mechanism.
Our previous reports showed that thymic lymphomas arising in TCR transgenic mice are resistant to Ca2+-mediated apoptosis. Here we show that induction of apoptosis in thymic lymphomas involves a process that is cAMP-mediated and which depends on the activation of protein kinase A (PKA) despite the lower level of PKA type I in these lymphomas compared to thymocytes. Further, we show that treatment of the lymphomas with HA1004, a serine/threonine protein kinase inhibitor, restores their susceptibility to ionomycin-induced apoptosis. Results indicate that HA1004-induced restoration of sensitivity to ionomycin proceeds through a PKA-independent mechanism. Moreover, activation of PKA instead of its inhibition induces apoptosis of lymphoma cells.


Morphology, Morphogenesis and Molecular Phylogeny of a New Soil Ciliate, Holostichides eastensis nov. spec. (Ciliophora, Hypotrichia).
A new bakuellid ciliate, Holostichides eastensis nov. spec. isolated from China, is investigated in terms of its morphology, ontogenesis, and molecular phylogenesis. It is characterized by size 150-180 µm × 45-60 µm in vivo; 27-46 macronuclear nodules; cortical granules dark brown, spherical, about 0.5 µm across, clustered in groups and then arranged longitudinally; three frontal cirri with one to four smaller cirri below the middle one, a buccal cirrus, nine to 15 frontoterminal cirri, and midventral complex composed of five to eight cirral pairs and two long midventral rows. The main events during binary fission are as follows: (1) in the proter, the undulating membrane anlage is formed from both the dedifferentiation of old undulating membranes and the basal bodies developing de novo, and the proximal part of the parental adoral zone of membranelles is renewed by a field of basal bodies that originates de novo; (2) in the opisthe, the oral primordium is formed intrakinetally; (3) besides the middle frontal cirrus and buccal cirrus, the FVT-anlagen II produces the extra one to four cirri. Phylogenetic analyses based on SSU rDNA sequence data suggest a close relationship between Holostichides eastensis nov. spec. and its congeners, indicating that the genus Holostichides is monophyletic.


Varied interspecies interactions between anammox and denitrifying bacteria enhanced nitrogen removal in a single-stage simultaneous anammox and denitrification system.
The simultaneous anammox and denitrification (SAD) system has received growing interest for the enhanced nitrogen removal, while the ecological traits of microbial community including spatial distribution characteristics, assembly processes and interspecies interactions have not been fully unraveled. The present study applied metagenomics and ecological analysis methods to gain the ecological traits of microbial communities in the SAD system across different organic substrate loadings. Results showed that organic matter significantly affected the bioreactor performance, and the optimal total nitrogen removal efficiency reached 93.4 ± 0.7% under the COD concentrations of 180 ± 18.2 mg/L. Functional organisms including Candidatus Brocadia (3.9%), Denitratisoma (1.6%), Dokdonella (4.4%) and Thauera (4.6%) obviously enriched under the optimal organic loading conditions. Moreover, microbial communities were significantly governed by deterministic process under high organic concentrations, and the denitrifying organisms displayed important ecological roles in the communities. Although anammox bacteria obviously enriched at the middle of bioreactor, it possessed the highest expression activities at both bottom and middle sites. Denitrifying bacteria that enriched at the bottom sites strongly achieved nitrate reduction and provided nitrite for anammox bacteria, while these organisms trended to compete nitrite with anammox bacteria at the middle site. These findings highlight the importance of microbial ecology in the SAD systems, which may expand our understanding of the synergistic patterns between anammox and denitrifying bacteria.


Synthesis, molecular modeling and preliminary biological evaluation of a set of 3-acetyl-2,5-disubstituted-2,3-dihydro-1,3,4-oxadiazole as potential antibacterial, anti-Trypanosoma cruzi and antifungal agents.
A series of 3-acetyl-2,5-disubstituted-2,3-dihydro-1,3,4-oxadiazole derivatives was synthesized and their activity screened in vitro against Staphylococcus aureus, Trypanosoma cruzi, and Candida albicans. The bioactivity was expressed as minimum inhibitory concentration (MIC) for S. aureus strains, and as fifty-percent inhibitory concentration (IC(50)) of parasite population growth for T. cruzi. A molecular modeling approach was performed to establish qualitative relationships regarding the biological data and the compounds' physicochemical properties. The 5-(4-OC(4)H(9)Ph, 5l), and 5-(4-CO(2)CH(3)Ph, 5o) derivatives were the most active compounds for S. aureus ATCC 25923 (MIC=1.95-1.25 μg/mL) and T. cruzi (IC(50)=7.91 μM), respectively. Also, a preliminary evaluation against C. albicans involving some compounds was performed and the 5-(4-CH(3)Ph, 5e) derivative was the most active compound (MIC=3.28-2.95 μg/mL). In this preliminary study, all synthesized 3-acetyl-2,5-disubstituted-2,3-dihydro-1,3,4-oxadiazole derivatives were active against all microorganisms tested.


Antibodies and digitalis: the modern revolution in the use of an ancient drug.
Although digitalis glycosides have been widely used in clinical medicine since the classic description by William Withering in 1785, it was not until the advent of a specific immunoassay that their clinical pharmacology could be examined intensively under a wide variety of circumstances. The insights gained into the relations among dosage, plasma concentration, bioavailability, distribution, metabolism, excretion and interactions with other drugs and the manifestations of toxicity certainly have reduced the frequency of adverse reactions to this highly toxic but useful group of drugs. More recently, antibodies have also been utilized as specific antidotes for digitalis toxicity, with dramatic life-saving effect.


Laparoscopic uterine artery occlusion for symptomatic leiomyomas.
To describe a laparoscopic technique that safely occludes both uterine arteries, overcoming an altered surgical field resulting from scarring and/or uterine leiomyomatous growth. Prospective analysis (Canadian Task Force classification II-2). Nonprofit community hospital. Eight women with leiomyomas with abnormal uterine bleeding, pelvic pain or pressure, and/or anemia. Bilateral laparoscopic retroperitoneal uterine artery occlusion. Occlusion at the initial track of the uterine artery was performed by laparoscopic coated ligature in six patients. In two obese patients with deep retroperitoneal space, vascular clips were placed endoscopically using the same dissecting technique. All patients were discharged within 20 hours after the procedure. All five women with abnormal bleeding reported satisfactory decrease; none reported amenorrhea. Of eight with preoperative pain or pressure, seven reported complete disappearance and one significant relief. All three patients with anemia had normal red cell counts after 1 month. Laparoscopic uterine artery occlusion using a lateral retroperitoneal technique is safe and effective in women with pelvic scarring and altered pelvic anatomy.


Neural basis for sentence comprehension: grammatical and short-term memory components.
We monitored regional cerebral activity with BOLD fMRI while subjects were presented written sentences differing in their grammatical structure (subject-relative or object-relative center-embedded clauses) and their short-term memory demands (short or long antecedent-gap linkages). A core region of left posterior superior temporal cortex was recruited during all sentence conditions in comparison to a pseudofont baseline, suggesting that this area plays a central role in sustaining comprehension that is common to all sentences. Right posterior superior temporal cortex was recruited during sentences with long compared to short antecedent-gap linkages regardless of grammatical structure, suggesting that this brain region supports passive short-term memory during sentence comprehension. Recruitment of left inferior frontal cortex was most clearly associated with sentences that featured both an object-relative clause and a long antecedent-gap linkage, suggesting that this region supports the cognitive resources required to maintain long-distance syntactic dependencies during the comprehension of grammatically complex sentences.


Chemical composition and anti-inflammatory activity of n-butanol extract of Piper sarmentosum Roxb. In the intestinal porcine epithelial cells (IPEC-J2).
Piper sarmentosum Roxb. (PS) is a terrestrial herb primarily distributed in tropical and subtropical regions of Asia. It is widely used in folk medicine in certain countries of Southeast Asia for the treatment of fever, toothache, coughing and pleurisy, which showed the anti-inflammatory activity of PS. This study aimed to investigate the chemical constituents and the molecular mechanism and related metabolic pathway by which n-butanol extract of PS (PSE-NB) exerts its anti-inflammatory effects. Chemical constituents of PSE-NB was analyzed using ultrahigh-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) technique. Anti-inflammatory effects of PSE-NB were investigated in lipopolysaccharide (LPS)-induced IPEC-J2 cells. In total, 218 compounds, including 94 alkaloids and 26 phenolics were tentatively identified, which indicating alkaloids and phenolics were the main constituents of PSE-NB. In addition, the current cell experiment in vitro showed that PSE-NB (10-500 μg/mL) pre-treatment before LPS stimulation significantly decreased mRNA expression of IL-1β, IL-6 and TNF-α in IPEC-J2 cells compared with LPS treatment (p < 0.05). PSE-NB improved mRNA expression of tight junction proteins (ZO-1 and Occludin) and NHE3, which were reduced by LPS stimulation (p < 0.05). Moreover, PSE-NB (10 μg/mL) alleviated LPS-induced protein expression of p65 and p-p65 (p < 0.05), and reduced p65 translocation into the nucleus induced by LPS. At the same time, metabolic pathway analysis indicated that PSE-NB exerts anti-inflammatory effects mainly via augmentation of methionine metabolism in IPEC-J2 cells. Taken together, the results suggested that alkaloids and phenolics were the main constituents in PSE-NB. PSE-NB might attenuate LPS-induced inflammatory responses in IPEC-J2 cells by regulating NF-κB signaling pathway and intracellular metabolic pattern.


Endoscopic Versus Open Carpal Tunnel Surgery: Risk Factors and Rates of Revision Surgery.
The purpose of our study was to compare the 1-year revision surgery rates and outcomes of open versus endoscopic carpal tunnel release. Our hypothesis was that, compared to open release, endoscopic carpal tunnel release was an independent risk factor for revision surgery within 1-year. This was a retrospective cohort study of 4338 patients undergoing isolated endoscopic or open carpal tunnel release. Demographic data, medical comorbidities, surgical approach, need for revision surgery, hand dominance, history of prior injection, and Patient Reported Outcomes Measurement Information System upper extremity (UE), pain interference (PI) and physical function scores were analyzed. Multivariable analysis was used to identify the risk factors for revision surgery within one year of the index procedure. In total, 3280 patients (76%) underwent open and 1058 (24%) underwent endoscopic carpal tunnel release. Within one year of the index procedure, 45 patients required revision carpal tunnel release. The average time to revision was 143 days. The rate of revision carpal tunnel release in the open group was 0.71% compared to 2.08% in the endoscopic group. Multivariable analysis demonstrated that endoscopic surgery, male sex, cubital tunnel syndrome, tobacco use, and diabetes were associated independently with revision surgery. In this study, we found that endoscopic carpal tunnel release was associated independently with a 2.96 times greater likelihood of requiring revision carpal tunnel release within one year, compared to open carpal tunnel release. Male sex, concurrent cubital tunnel syndrome, tobacco use, and diabetes also were associated independently with greater risk of needing revision carpal tunnel release within one year. Prognostic II.


Patient Self-Reported Health, Clinical Quality, and Patient Satisfaction in English Primary Care: Practice-Level Longitudinal Observational Study.
To examine the association of self-reported health of patients in general practices, as measured by the EQ-5D-5L, with practice clinical quality and patient-reported satisfaction with accessibility and consultations. We used data from the General Practitioner (GP) Patient Survey to construct a practice-level EQ-5D-5L index as the health outcome. Key explanatories were patient-reported measures of satisfaction with access and consultations (also derived from the GP Patient Survey) and clinical quality measured by the achievement of clinical quality indicators reported in the Quality and Outcomes Framework. We estimated practice-level linear panel data models with random and fixed practice effects and practice and patient covariates using 2012/13 to 2016/17 data on more than 7500 English general practices. Bivariate correlations of the EQ-5D-5L index with quality measures were 0.048 for clinical quality, 0.071 for satisfaction with access, and 0.107 for satisfaction with GP consultations (all with P<.001). In both fixed effects regressions, which allow for unobserved time invariant practice characteristics, and random effects regressions which do not, the EQ-5D-5L index was positively associated with 1-year lags of patient satisfaction with access and GP consultations. Patient-reported health was positively associated with clinical quality in the fixed effects regressions. The implied effects were small in all cases. Practice-level EQ-5D-5L is positively associated with clinical quality and with 1-year lags of patient-reported satisfaction with access and GP consultations.