Purification and Characterization of β-Glucosidase from Agaricus bisporus (White Button Mushroom).
β-Glucosidase (β-D-glucoside glucohydrolase, EC 126.96.36.199) is a catalytic enzyme present in both prokaryotes and eukaryotes that selectively catalyzes either the linkage between two glycone residues or between glycone and aryl or alkyl aglycone residue. Growing edible mushrooms in the soil with increased cellulose content can lead to the production of glucose, which is a process dependent on β-glucosidase. In this study, β-glucosidase was isolated from Agaricus bisporus (white button mushroom) using ammonium sulfate precipitation and hydrophobic interaction chromatography, giving 10.12-fold purification. Biochemical properties of the enzyme were investigated and complete characterization was performed. The enzyme is a dimer with two subunits of approximately 46 and 62 kDa. Optimum pH for the enzyme is 4.0, while the optimum temperature is 55 °C. The enzyme was found to be exceptionally thermostable. The most suitable commercial substrate for this enzyme is p-NPGlu with Km and Vmax values of 1.751 mM and 833 U/mg, respectively. Enzyme was inhibited in a competitive manner by both glucose and δ-gluconolactone with IC50 values of 19.185 and 0.39 mM, respectively and Ki values of 9.402 mM and 7.2 µM, respectively. Heavy metal ions that were found to inhibit β-glucosidase activity are I(-), Zn(2+), Fe(3+), Ag(+), and Cu(2+). This is the first study giving complete biochemical characterization of A. bisporus β-glucosidase.


Barrett's esophagus and adenocarcinoma.
Sixty-two cases of Barrett's esophagus were observed among 707 patients with hiatal hernia (8.7%). The symptomatology of this condition is described. An additional 10 adenocarcinomas were associated with a Barrett's esophagus--a carcinoma prevalence of 13.8%. Differences in pathology and clinical manifestations of nonmalignant and malignant cases were determined. Fifty-one patients with nonmalignant Barrett's esophagus were operated upon conservatively, while 11 underwent resection. Our results favor conservative surgery via an abdominal approach. The patients with adenocarcinomas underwent esophageal resection with six apparent cures from 6 months to 5 years. Histological study showed specialized epithelium in 8 of 10 cases and severe dysplasia in 5. Our clinical study of Barrett's esophagus shows an incidence of malignancy equal to 1 new case per 274 patient-years (1.72%). It is still not firmly established whether correction of reflux will influence the level of columnar epithelium in the esophagus, esophageal dysplasia, and the risk of malignancy.


The virtual histology intravascular ultrasound appearance of newly placed drug-eluting stents.
Intravascular ultrasound (IVUS) is used before and after intervention and at follow-up to assess the quality of the acute result as well as the long-term effects of stent implantation. Virtual histology (VH) IVUS classifies tissue into fibrous and fibrofatty plaque, dense calcium, and necrotic core. Although most interventional procedures include stent implantation, VH IVUS classification of stent metal has not been validated. In this study, the VH IVUS appearance of acutely implanted stents was assessed in 27 patients (30 lesions). Most stent struts (80%) appeared white (misclassified as "calcium") surrounded by red (misclassified as "necrotic core"); 2% appeared just white, and 17% were not detectable (compared with grayscale IVUS because of the software-imposed gray medial stripe). The rate of "white surrounded by red" was similar over the lengths of the stents; however, undetectable struts were mostly at the distal edges (31%). Quantitatively, including the struts within the regions of interest increased the amount of "calcium" from 0.23 +/- 0.35 to 1.07 +/- 0.66 mm(2) (p <0.0001) and the amount of "necrotic core" from 0.59 +/- 0.65 to 1.31 +/- 0.87 mm(2) (p <0.0001). Most important, because this appearance occurs acutely, it is an artifact, and the red appearance should not be interpreted as peristrut inflammation or necrotic core when it is seen at follow-up. In conclusion, acutely implanted stents have an appearance that can be misclassified by VH IVUS as "calcium with or without necrotic core." It is important not to overinterpret VH IVUS studies of chronically implanted stents when this appearance is observed at follow-up. A separate classification for stent struts is necessary to avoid these misconceptions and misclassifications.


Cervical cancer: a preventable problem.
Incidence of cervical cancer appears to be increasing among younger women. With effective screening, treatment and health education, it is almost entirely preventable.


No effect of perianal application of topical anaesthetic on patient comfort during nonsedated flexible sigmoidoscopy: a randomized, placebo-controlled clinical trial.
A literature review revealed no data on the effects of topical anaesthetic on patient comfort during flexible sigmoidoscopy. We therefore aimed to evaluate this in a randomized manner. One hundred and forty-six patients who underwent flexible sigmoidoscopy were randomly allocated to one of three groups. Vaseline (n = 49), 2% lidocaine gel (n = 51) or a cream of 2.5% lidocaine plus 2.5% prilocaine (n = 46) were applied to the patients 30 min before the procedure. Demographic data and haemodynamic monitoring during procedures were recorded. Pain was assessed by visual analogue scale (VAS) and anxiety levels by the State-Trait Anxiety Inventory (STAI-I and STA-II). Median pre-procedural STAI-I scores were 45, 46 and 40.5 and median post-procedural STAI-I scores were 35, 34 and 33.5 for the vaseline, lidocaine, and lidocaine/prilocaine treatments, respectively. There was no statistical difference among the groups in terms of STAI-I and II scores. However, post-procedural STAI-I scores were significantly lower than pre-procedural values in each group (P < 0.001). There was no significant difference in VAS scores among the groups. In all groups there were statistically higher VAS scores during the procedure compared with the pre- and post-procedural scores (P < 0.001). Perianal application of topical anaesthetic does not influence patient comfort during sigmoidoscopy.


Effective size of populations under partial inbreeding and selection on a set of linked additive genes.
The prediction theory of effective population size (Ne) is extended to cover selection on a set of linked additive genes and partial inbreeding (partial selfing or partial full-sib mating). Ne under selection is generally expressed as a function of the cumulative change in frequency of a neutral gene due to the random association between the neutral and selected genes generated by finite sampling. In this study, the association under partial selfing was classified into two types, the association between the neutral and selected genes on the same gamete, and the association between the neutral and selected genes each on the different gametes in the same parent. For partial full-sib mating, an additional association, i.e., the association between the neutral and selected genes each in the different parents in the same family, was included in the model. According to this classification of the association, the coefficient accounting for the cumulative change in frequency of the neutral gene was partitioned into two or three components. A method for computing the partitioned coefficients was obtained from the transition matrix approach, in which the joint effect of linkage, selection and partial inbreeding was taken into account. To assess the joint effects of linkage, selection and partial inbreeding on Ne, numerical computations with the obtained expressions were carried out. The effect of linkage on Ne was generally small, except for an extremely small genome size, while the partial inbreeding resulted in a drastic reduction in Ne. For a given genome size, Ne was essentially independent of the length and number of chromosomes. Some of these results were verified by stochastic simulations.


Application of continuous passive motion in patients with distal radius fractures: A randomized clinical trial.
The aim of this study was to know if applying continuous passive motion (CPM) in addition to routine exercises is more effective than routine exercises alone in pain reduction, range of motion (ROM) and function improvement after distal radius fractures (DRFs). In this randomized controlled trial, 21 patients with non-stabilized DRF after pin removal were randomly assigned to experimental and control groups. The experimental group received stretching exercises with CPM machine for 2×15min per session. Both groups received routine exercises for 1h, three times a week for 4 weeks. The primary outcome measure was pain evaluated on a visual analog scale (VAS), and the secondary outcome measures were disability evaluated by the patient-rated wrist/hand evaluation and ROM (goniometry) at 4, 6, and 12 weeks. Univariate analysis of covariance (ANCOVA) and a one-way repeated measure mixed model analysis of variance (ANOVA) were used for data analysis. Twenty-one participants completed the 12-week follow-up. Pain relief, ROM and functional improvement revealed that the treatment was successful in both groups. We detected no significant differences (p>0.05) between the two groups at the end of the follow-up period regarding pain, ROM, and function. Using a CPM machine had no additional effect on pain reduction, ROM and function improvement compared with routine exercises in patients with DRF.


Cognitive performance and electroencephalographic variations in air traffic controllers under various mental workload and time of day.
The aim of this study was to investigate the effects of mental workload (MWL) and time of day on cognitive performance and electroencephalographic (EEG) parameters of air traffic controllers. EEG signals recorded while 20 professional air traffic controllers performed cognitive tasks [A-X Continuous Performance Test (AX-CPT) and 3-back working memory task] after they were exposed to two levels of task difficulty (high and low MWL) in the morning and afternoon. Significant decreases in cognitive performance were found when the levels of task difficulty increased in both tasks. The results confirmed the sensitivity of the theta and beta activities to levels of task difficulty in the 3-back task, while they were not affected in the AX-CPT. Theta and beta activities were influenced by time of day in the AX-CPT. The findings provide guidance for application of changes in EEG parameters when MWL level is manipulated during the day that could be implemented in future for the development of real-time monitoring systems to improve aviation safety.


[Static stress of tibiofibular syndesmosis].
The tension-patterns of the tibiofibular syndesmosis during stance and push-off phases of gait are still unknown. Therefore a strain-gauge study was done, using an anatomically prepared human leg with the syndesmosis removed and the gauges fixed on the bone, avoiding bending influences. Syndesmotic tension forces measured under sequential axial loading up to 500 N in neutral ankle position were 6.5 N for anterior and 10 N for posterior ligaments under maximum load. With 10 degrees ankle dorsiflexion and no load applied about 5 N of tension were measured in each of the anterior and posterior ligaments. Application of axial load under same conditions resulted in a decrease to negligible tension in the anterior ligament and an increase of tension in the posterior ligament. In evaluating the load tests, which were done in 10 degrees dorsiflexion and the so-called neutral-zero-position of the ankle, we found that our data correlated well with the elasticity and tearing resistance, measured by Sauer. According to the pathomechanics of trauma exact measurements of these forces in the weightbearing ankle are of interest for postoperative treatment of ankle fractures.


Pilot study of a novel transmembranous electromyography device for assessment of oral cavity and oropharyngeal muscles.
Electromyography (EMG) can provide valuable insights into the pathophysiology of oropharyngeal muscles in various disease states, but the invasive nature of the conventional needle EMG (nEMG) has its limitations in this setting. We aimed to examine the inter-rater reliability (IRR) of a novel transmembranous EMG (tmEMG) sensor as a non-invasive technique for assessment of oral cavity and oropharyngeal muscles for neuromuscular pathology. The study was a prospective, cohort, pilot study with blinded data analysis in healthy participants (n = 6), patients with moderate to severe obstructive sleep apnea (OSA) (n = 5) and bulbar amyotrophic lateral sclerosis (ALS) (n = 5). Each patient underwent sampling from bilateral palatoglossus (PG) and genioglossus (GG), using both tmEMG and nEMG. IRR was expressed as percentage agreement and prevalence-adjusted bias-adjusted kappa coefficient (PABAK). Substantial IRR was found for participants with ALS (81.6%, PABAK 0.63) and OSA (78.8%, PABAK 0.61), and in healthy participants (87.1%, PABAK 0.74). A better IRR was seen with tmEMG (95.7%, PABAK 0.92) than with nEMG (73.9%, PABAK 0.48) for healthy participants and also for those with OSA. Studies from GG had higher IRR than PG. Only one participant had a minor adverse event (sore throat). The current study shows that analysis of PG and GG in both healthy and disease states using tmEMG has high IRR compared with nEMG analysis. Further validation studies can be undertaken to test its utility in analysis of oral cavity and oropharyngeal muscles.


Partial trisomy 20q due to paternal t(8;20) translocation. Case report and review of the literature.
In this report we present a malformed female newborn with partial trisomy 20q who was the unbalanced product of a paternal 8p/20q translocation (46,XY,t(8;20) (p23.1;q11].


Compliance in the community with consultants' recommendations for developmentally handicapped children.
A cross-sectional analytical survey was carried out to determine the extent and associations of compliance with consultants' recommendations for developmentally handicapped children to parents and front-line community professionals. Non-compliance was found to be a substantial problem. Several significant associations were found between clients' attitudes and beliefs about the recommendations and their compliance with them. These findings may prove useful in identifying clients at risk for non-compliance, and in developing strategies to enhance compliance among clients of developmental disability consultation services.


Knockdown of HURP inhibits the proliferation of hepacellular carcinoma cells via downregulation of gankyrin and accumulation of p53.
We determined earlier that the hepatoma upregulated protein (HURP) is overexpressed in hepatocellular carcinoma (HCC), but the role of this protein during cancer development and progression remains unknown. Here, we observed that the overexpression of HURP in HEK293 cells promoted the ubiquitination of p53 and its degradation by the proteasome. In contrast, HURP knockdown using short-hairpin RNA reversed these effects. Knockdown of HURP promoted the accumulation of p53 in SK-Hep-1 cells (p53+/-), and these cells showed reduced proliferation, while the p53-mutant Mahlavu cells were not affected. HURP knockdown did not affect the proliferation of H1299 lung carcinoma cells and Hep3B HCC cells which lack p53. Knockdown of HURP also sensitized SK-Hep-1 cells to cisplatin. On the other hand, the expression of exogenous p53 in H1299 and Hep3B cells was decreased following overexpression of HURP, and these cells showed decreased sensitivity to cisplatin-induced apoptosis. Importantly, overexpression of HURP promoted the proliferation of HEK293 cells in an anchorage-independent manner, and inoculation of SK-Hep-1 cancer cells that expressed short-hairpin RNA to knockdown HURP resulted in smaller tumors in nude mice. Gankyrin, a positive regulator of the E3 ubiquitin ligase MDM2, was found to be upregulated following HURP expression, and gankyrin knockdown decreased the HURP-mediated downregulation of p53. Notably, we detected a positive correlation between elevated HURP and gankyrin protein levels in HCC patients (r(2) = 0.778; N = 9). Taken together, these results indicate that HURP represents an oncogene that may play a role in HCC progression and chemoresistance.


Does pelvic floor muscle training augment the effect of surgery in women with pelvic organ prolapse? A systematic review of randomized controlled trials.
Pelvic floor muscle training (PFMT) is often used as a treatment for pelvic organ prolapse (POP) and can improve function. However, the effectiveness of this modality as an adjunct to prolapse surgery for women with POP is unknown. To evaluate whether the use of pelvic floor muscle training as an adjunct to prolapse surgery is superior to surgery alone for women with pelvic organ prolapse. We searched PubMed, Embase, the Cochrane Library, and the Web of Science from their inception dates to June 30, 2014 for data describing randomized controlled trials (RCTs) that compare the efficacy of PFMT with or without lifestyle modification plus surgery versus surgery alone for women with POP. Additional relevant studies were identified by searching the references of retrieved articles and using Google Scholar. Two investigators independently reviewed and selected relevant studies that met the pre-specified inclusion criteria, extracted the data, and assessed the risk of bias in the included studies according to the Cochrane Handbook, version 5.1.0. Due to great heterogeneity in the choice and reporting of outcome measures and the different durations of follow-up among the studies, this analysis is confined to a qualitative systematic review. Five RCTs involving 591 women were reviewed (treatment group [TG], 292 cases; control group [CG], 299 cases). Generally, the five RCTs exhibited low risk of bias. This study indicated no significant improvement in prolapse symptoms, in quality of life, or in the degree of prolapse for women with POP in the TG compared to those in the CG. Insufficient evidence was found to support adding perioperative PFMT to surgery over the use of surgery alone in women undergoing surgery for POP. Adequately, powered RCTs with longer follow-up periods are required to evaluate the long-term effect of perioperative PFMT. Neurourol. Urodynam. 35:666-674, 2016. © 2015 Wiley Periodicals, Inc.


The structural basis of receptor-binding by Escherichia coli associated with diarrhea and septicemia.
GafD in Escherichia coli G (F17) fimbriae is associated with diarrheal disease, and the structure of the ligand-binding domain, GafD1-178, has been determined at 1.7A resolution in the presence of the receptor sugar N-acetyl-D-glucosamine. The overall fold is a beta-barrel jelly-roll fold. The ligand-binding site was identified and localized to the side of the molecule. Receptor binding is mediated by side-chain as well main-chain interactions. Ala43-Asn44, Ser116-Thr117 form the sugar acetamide specificity pocket, while Asp88 confers tight binding and Trp109 appears to position the ligand. There is a disulfide bond that rigidifies the acetamide specificity pocket. The three fimbrial lectins, GafD, FimH and PapG share similar beta-barrel folds but display different ligand-binding regions and disulfide-bond patterns. We suggest an evolutionary path for the evolution of the very diverse fimbrial lectins from a common ancestral fold.


Kin recognition by tadpoles and froglets of the wood frog Rana sylvatica.
We investigated kin recognition by the wood frog Rana sylvatica in blind laboratory experiments using spatial proximity as a recognition assay. Tadpoles were tested for the ability to discriminate between: 1) familiar full-sibs and unfamiliar non-kin, 2) unfamiliar paternal half-sibs and unfamiliar non-kin, and 3) familiar and unfamiliar full-sibs. Tadpoles discriminated full- and paternal half-sibs from unrelated conspecifics, but did not discriminate between familiar and unfamiliar full-sibs. Froglets from the same laboratory population were tested for the ability to discriminate between 1) familiar full-sibs and unfamiliar non-kin, and 2) unfamiliar paternal half-sibs and unfamiliar non-kin. Froglets preferentially associated with full- and half-sibs over unrelated conspecifics. Our results show that familiarity, i.e., prior association, is not necessary for kin recognition in tadpoles and froglets. The ability of tadpoles and froglets to recognize unfamiliar paternal half-sibs demonstrates that a common maternal factor is not necessary for kin recognition, and indicates that the recognition cue has a genetic component. Our results add to the increasing evidence that a variety of vertebrate and invertebrate animals have the ability to recognize unfamiliar kin by using genetically specified recognition cues.


Normal tissue tolerance to intraoperative radiotherapy.
Much experimental evidence has been accumulated assessing the tolerance of various tissues to IORT, and much of the tolerance data have resulted from the use of canine models. Guidelines of IORT tissue tolerance established in experimental models have been used in the clinical application of IORT at numerous institutions. Although the radiotolerance of differing tissues can vary among species, sufficient clinical experience has accumulated to validate the canine tissue tolerance model as representative of human tissue responses to IORT. Cellular effects from radiation principally stem from direct damage to DNA, and thus proliferating tissues are among the most radiosensitive, with arrested or abnormal cell division. These tissues can manifest striking early toxicity, reflecting the rate of cell division that is affected by the radiation. Irradiation of nonproliferating or slowly proliferating tissues may show little or no early toxicity, but late effects can be manifested to considerable and varying degrees. In much of this late toxicity, pathologic changes develop from progressive ischemia, brought about by the gradual obliteration of small blood vessels. Irradiated endothelium often becomes replaced by a thickened fibrous layer, which, in small vessels, leads to occlusion and ischemic necrotic changes in the supplied tissue. In larger vessels, fibrosis can lead to wall weakening and aneurysmal dilatation, rupture, or thrombosis. The common denominator, then, of radiation damage to many tissues is related to vascular effects. Although the tolerance to IORT-induced toxicity can vary considerably among tissues, doses ranging to 25 Gy can generally be tolerated without significant toxicity. Vital areas where IORT dose must be carefully monitored include critical vasculature, gastrointestinal viscera, ureter, significant motor or sensory nerve trunks, and central nervous system structures. Higher doses can generally be delivered safely to anatomic areas at risk for tumor that are at a distance from sensitive organs or tissues. The general principle providing the rationale of IORT should always be practiced: maximize the radiation dose to the tumor and tumor-harboring tissues while minimizing dose exposure to surrounding normal tissues.


Low clinical ischemic threshold for cerebral blood flow in severe acute brain trauma. Case report.
A case of severe acute brain trauma is presented in which the patient made a satisfactory recovery after suffering a marked reduction in cerebral blood flow, to a level previously reported in association with impending brain death (10 ml/100 gm/min). This is believed to be the first report of a patient with severe acute brain injury in whom serial clinical and physiological assessments allowed documentation of the reversibility of such a critical level of cerebral hypoperfusion.


Effect of tingenone, a quinonoid triterpene, on growth and macromolecule biosynthesis in Trypanosoma cruzi.
Tingenone and horminone, two natural quinonoid substances, inhibited the in vitro growth of Trypanosoma cruzi, 30 microM drug concentration producing total inhibition of growth. Tingenone inhibited total uptake and incorporation of [3H]thymidine, [3H]uridine, L-[3H]leucine into parasite macromolecules. Other quinonoids assayed were either less effective (abruquinone A) or even quite inactive (visminone B and ferruginin B). Investigation of several mechanisms for the cytotoxic action of tingenone pointed to the interaction with DNA as the most likely factor involved. Tingenone also inhibited the growth of Crithidia fasciculata, but the drug was significantly less active on this organism than on T. cruzi.


Origin, proliferation, and fate of cerebrospinal fluid cells. A review on cerebrospinal fluid cell kinetics.
Four aspects of cytokinetic investigations of cerebrospinal fluid cells were reviewed: the origin of these cells, their ability to divide, their fate, and the alterations occurring under pathologic conditions. Animal experiments and in vitro reactions of human cerebrospinal fluid cells indicated that, under normal and pathologic conditions, blood lymphocytes and blood monocytes are capable of leaving the vascular system inside the subarachnoid space. When these cells are located extravascularily, they seldom divide in the subarachnoid space under normal conditions. Migration via lymphatic pathways is possible, at lest under pathologic conditions. Cell turnover, as a whole, is extremely low under normal conditions. It is markedly altered by meningeal inflammation and meningeal tumor cell dissemination. Diagnostic significance other than morphology cannot yet result from cytokinetic investigations of cerebrospinal fluid cytology; prognostic significance may be possible.


Healing of colon anastomoses covered with fibrin glue after immediate postoperative intraperitoneal administration of 5-fluorouracil.
The aim of this experimental study was to investigate whether covering the colonic anastomoses with fibrin glue can protect the colonic healing from the adverse effects of 5-fluorouracil (5-FU), when it is injected intraperitoneally immediately after colon resection. Sixty-four rats were randomized to one of four groups. After resection of a 1-cm segment of the transverse colon, an end-to-end sutured anastomosis was performed. Rats of the control group and the fibrin glue group were injected with 6 ml of solution 0.9 percent NaCl intraperitoneally. Rats in the 5-FU and the 5-FU + fibrin glue groups received 5-FU intraperitoneally. The colonic anastomoses of the rats in the fibrin glue group and in the 5-FU + fibrin glue group were covered with fibrin glue. All rats were killed on the 8th postoperative day and the anastomoses were examined macroscopically. The bursting pressure measurements were recorded and the anastomoses were graded histologically. The leakage rate of the anastomoses was significantly higher in the rats of the 5-FU group than in those of the fibrin glue group and those of the 5-FU + fibrin glue group (37.5 percent vs. 0 percent, P = 0.020). The adhesion formation score was significantly higher in rats of the 5-FU group than in the other groups. Bursting pressures were also significantly lower in the 5-FUgroup than in the other groups ( P < 0.001). Rats in the 5-FU + fibrin glue group developed significantly more marked neoagiogenesis than rats in the other groups. Rats in the 5-FU + fibrin glue group also presented significantly more fibroblast activity than those in the 5-FU group. ( P = 0.004) The immediate postoperative, intraperitoneal administration of 5-FU inhibited wound healing. However, when the colonic anastomoses were covered with fibrin glue, the injection of 5-FU had no adverse effects on the healing of the anastomoses.


[Construction of FANCA mutant protein from Fanconi anemia patient and analysis of its function].
To study FANCA protein expression in Fanconi anemia patient's (FA) cells and explore its function. FANCA protein expression was analyzed in 3 lymphoblast cell lines derived from 3 cases of type A FA (FA-A) patients using Western blot. Nucleus and cytoplasm localization of FANCA protein was analyzed in one case of FA-A which contained a truncated FANCA (exon 5 deletion). The FANCA mutant was constructed from the same patient and its interaction with FANCG was evaluated by mammalian two-hybrid (M2H) assay. FANCA protein was not detected in the 3 FA-A patients by rabbit anti-human MoAb, but a truncated FANCA protein was detected in 1 of them by mouse anti-human MoAb. The truncated FANCA could not transport from cytoplasm into nucleus. The disease-associated FANCA mutant was defective in binding to FANCG in M2H system. FANCA proteins are defective in the 3 FA-A patients. Disfunction of disease-associated FANCA mutant proved to be the pathogenic mutations in FANCA gene. Exon 5 of FANCA gene was involved in the interaction between FANCA and FANCG.


Spatial cover and carbon fluxes of urbanized Sonoran Desert biological soil crusts.
Biological soil crusts (BSC) are important contributors to nutrient cycling in arid environments such as the Sonoran Desert. BSC at an urban (University Indian Ruins) and at a non-urban site (Santa Rita Experimental Range) were compared to determine if their structure or function was influenced by proximity to an urban environment. The Step Point method was used in the field to determine ground cover; which was found to be similar between sites. However, the spatial distribution of the BSCs was significantly different, such that more BSCs were found under plants at the non-urban site (P < 0.05). Relative gross photosynthesis was measured in the lab by addition of a watering event. Gross photosynthesis was found to be higher in the non-urban BSCs (P < 0.001), indicating lowered productivity in urban BSCs due to effects caused by proximity to urban environments. This study provides evidence that BSCs at urbanized sites are affected functionally, and therefore may be contributing differently to carbon and nitrogen cycling in these ecosystems.


Caffeine's effect on intermittent sprint cycling performance with different rest intervals.
The purpose of this study was to investigate the effects of caffeine ingestion on the performance of an intermittent sprint cycling test (ISCT) with different rest intervals. Fourteen males with team sport experience consumed 6 mg kg(-1) of caffeine or a placebo 60 min prior to completing two sets of an ISCT with 4-min rest intervals. Each set consisted of 12 × 4-s sprints with 20- or 90-s active recovery intervals at 60-70 rpm. Blood lactate was collected at baseline and immediately following the completion of six sprints in each set. At 20-s recovery intervals, peak power and total work were not significantly different between conditions during the ISCT (P > 0.05); but caffeine reduced 6.31% effort for mean power in Sprint 10 of the later stage, as well as an increased fatigue index and elevated blood lactate levels during the ISCT (P < 0.05). At 90-s recovery intervals, peak power, mean power, and total work under caffeine conditions were significantly higher than under placebo conditions during the ISCT (P < 0.05), but no differences were apparent in fatigue index and blood lactate levels (P > 0.05). In conclusion, caffeine ingestion may be ergolytic, affecting performance and fatigue development in the later stage during a prolonged and intermittent sprint test with a short recovery interval. However, caffeine produces an ergogenic effect in the initial stage of an intermittent sprint performance with a longer recovery interval.


CXCL1 activates TRPV1 via Gi/o protein and actin filaments.
CXCL1 is a chemokine with pleiotropic effects, including pain and itch. Itch, an unpleasant sensation that elicits the desire or reflex to scratch, it is evoked mainly from the skin and implicates activation of a specific subset of IB4+, C-type primary afferents. In previous studies we showed that acute application of CXCL1 induced a Ca2+ influx of low amplitude and slow kinetics in a subpopulation of transient receptor potential vanilloid type 1 (TRPV1)+/isolectin B4 (IB4)+dorsal root ganglia neurons which also responded to other itch-inducing agents. In this study we explored the mechanism behind the Ca2+ influx to better understand how CXCL1 acts on primary sensitive neurons to induce itch. Intracellular Ca2+ imaging and patch-clamp recordings on dorsal root ganglia neurons primary cultures and HEK293T cell transiently transfected with TRPV1 and CXCR2 plasmids were used to investigate the acute effect (12min application) of 4nM CXCL1. In primary cultures, the focus was on TRPV1+/IB4+ cells to which the itch-sensitive neurons belong. The results showed that the Ca2+ influx induced by the acute application of CXCL1 is mediated mainly by TRPV1 receptors and depends on extracellular Ca2+ not on intracellular stores. TRPV1 was activated, not sensitized by CXCL1, in a CXCR2 receptors- and actin filaments-dependent manner, since specific blockers and actin depolymerizing agents disrupted the CXCL1 effect. This study brings additional data about the itch inducing mechanism of CXCL1 chemokine and about a new mechanism of TRPV1 activation via actin filaments.


Multisession Gamma Knife Radiosurgery for Orbital Apex Tumors.
This study was performed to analyze the outcome of multisession gamma knife radiosurgery (GKS) in benign tumors located at the orbital apex. Medical records of 23 patients who underwent multisession GKS for benign orbital apex tumors were reviewed retrospectively. Three patients were diagnosed by histology, and the other 20 patients were given the diagnoses on the basis of clinical and radiological findings. Diagnoses included cavernous hemangioma (8 cases), meningioma (8 cases), and schwannoma (7 cases). All patients were treated with 4 sessions of GKS with 12 hours of interval. Median marginal dose in each session was 5 Gy (range, 4.5-5.5 Gy) at the 50% isodose line (range, 50%-55%). Mean clinical and imaging follow-up duration after treatment were 52.1 and 34.2 months, respectively. Tumor control was achieved in 22 patients (95.7%). Significant tumor shrinkage was observed in 17 patients (73.9%), and mean tumor volume reduction rate was 53.9%. Visual function was improved in 16 patients (69.6%) and stable in 4 patients (17.4%). Deterioration of visual acuity was reported by 3 patients (13.0%). Clinical and radiological response to multisession GKS was most excellent in cavernous hemangiomas with tumor control in all patients, and the mean tumor volume reduction rate was 68.3%. Multisession GKS proved to be an effective and safe management strategy for benign orbital apex tumors. Response to treatment was different according to the pathology, and multisession GKS may be considered as the initial treatment of choice for specific pathology such as cavernous hemangioma.


Effect of pH on hexavalent and total chromium removal from aqueous solutions by avocado shell using batch and continuous systems.
Solution pH appears to be the most important regulator of the biosorptive removal of chromium ions from aqueous solutions. This work presents a kinetic study of the effects of solution pH on Cr(VI) and total chromium removal from aqueous solution by Hass avocado shell (HAS) in batch and continuous packed bed column systems. Different Cr(VI) and total chromium removal performances of HAS were obtained in pH-shift batch, pH-controlled batch, and continuous systems. These results emphasize the great importance of determining the most appropriate pH for Cr(VI) and total chromium removal, considering the operational mode of the proposed large-scale treatment system. Total chromium biosorption batch kinetics was well described by the Elovich model, whereas in the continuous system, the fitness of the kinetic models to the experimental data was pH dependent. X-ray photoelectron spectroscopy and kinetic studies clearly indicated that the reaction mechanism of Cr(VI) with HAS was the reductive biotransformation of Cr(VI) to Cr(III), which was partially released to the aqueous solution and partially biosorbed onto HAS.


Precise measurements of the absolute γ-ray emission probabilities of (223)Ra and decay progeny in equilibrium.
Precise measurements of the absolute γ-ray emission probabilities have been made of radiochemically pure solutions of (223)Ra in equilibrium with its decay progeny, which had been previously standardised by 4π(liquid scintillation)-γ digital coincidence counting techniques. Two high-purity germanium γ-ray spectrometers were used which had been accurately calibrated using a suite of primary and secondary radioactive standards. Comparison of the activity concentration determined by the primary technique against γ-ray spectrometry measurements using the nuclear data evaluations of the Decay Data Evaluation Project exhibited a range of ~18% in the most intense γ-ray emissions (>1% probability) of the (223)Ra decay series. Absolute γ-ray emission probabilities and standard uncertainties have been determined for the decay of (223)Ra, (219)Rn, (215)Po, (211)Pb, (211)Bi and (207)Tl in equilibrium. The standard uncertainties of the measured γ-ray emission probabilities quoted in this work show a significant improvement over previously reported γ-ray emission probabilities. Correlation coefficients for pairs of the measured γ-ray emission probabilities from the decays of the radionuclides (223)Ra, (219)Rn and (211)Pb have been determined and are presented. The α-transition probabilities of the (223)Ra have been deduced from P(γ+ce) balance using the γ-ray emission probabilities determined in this work with some agreement observed with the published experimental values of the α-emission probabilities.


Stapled peptides for intracellular drug targets.
Proteins that engage in intracellular interactions with other proteins are widely considered among the most biologically appealing yet chemically intractable targets for drug discovery. The critical interaction surfaces of these proteins typically lack the deep hydrophobic involutions that enable potent, selective targeting by small organic molecules, and their localization within the cell puts them beyond the reach of protein therapeutics. Considerable interest has therefore arisen in next-generation targeting molecules that combine the broad target recognition capabilities of protein therapeutics with the robust cell-penetrating ability of small molecules. One type that has shown promise in early-stage studies is hydrocarbon-stapled α-helical peptides, a novel class of synthetic miniproteins locked into their bioactive α-helical fold through the site-specific introduction of a chemical brace, an all-hydrocarbon staple. Stapling can greatly improve the pharmacologic performance of peptides, increasing their target affinity, proteolytic resistance, and serum half-life while conferring on them high levels of cell penetration through endocytic vesicle trafficking. Here, we discuss considerations crucial to the successful design and evaluation of potent stapled peptide interactions, our intention being to facilitate the broad application of this technology to intractable targets of both basic biologic interest and potential therapeutic value.


Expression and regulation of Cyr61 in human breast cancer cell lines.
We have shown that Cyr61, an angiogenic regulator, is overexpressed in invasive and metastatic human breast cancer cells and tumor biopsies. We have further demonstrated that Cyr61 promotes acquisition of estrogen-independence and anti-estrogen resistance in vivo in breast cancer cells. Moreover, we have demonstrated that Cyr61 induces tumor formation and tumor vascularization in vivo, events mediated through the activation of the MAPK and the Akt signaling pathways. Here we investigate how Cyr61 expression is regulated in both estrogen receptor (ER)-positive and ER-negative breast cancer cells. We demonstrate that Cyr61 mRNA and protein expression is inducible by estrogen and anti-estrogens in ER-positive breast cancer cells. We show that a labile protein as well as a negative regulator might be involved in Cyr61 expression in estrogen-dependent breast cancer cells. Other important regulators of Cyr61 expression in breast cancer cells that we found are the phorbol ester TPA, vitamin D, and retinoic acid. TPA causes positive regulation of Cyr61 expression in ER-positive MCF-7 cells. Vitamin D induces a transient stimulatory effect on Cyr61 gene expression. Lastly, retinoic acid has a negative effect on Cyr61 expression and downregulates its expression in MCF-7 cells. Interestingly, most of these effects are not seen in aggressive breast cancer cells that do not express ER and express high levels of Cyr61, such as the MDA-MB-231 cells. Our results are in agreement with our knowledge that Cyr61 promotes tumor growth, and that tumor-promoting agents have a positive impact on cells that express low levels of Cyr61, such as the ER-positive breast cancer cells; however, these agents have no significant effect on cells that express high levels of Cyr61. Our findings suggest an association between increased Cyr61 expression and an aggressive phenotype of breast cancer cells.


Water quality pollution assessment and source apportionment of lake wetlands: A case study of Xianghai Lake in the Northeast China Plain.
Surface water pollution has always posed a serious challenge to water quality management. Improving water quality management requires figuring out how to comprehend water quality conditions scientifically and effectively as well as quantitatively identify regional pollution sources. In this study, Xianghai Lake, a typical lake-type wetland on the Northeast China Plain, was taken as the research area. Based on a geographic information system (GIS) method and 11 water quality parameters, the single-factor evaluation and comprehensive water quality index (WQI) methods were used to comprehensively evaluate the water quality of the lake-type wetland in the level period. Four key water quality parameters were determined by the principal component analysis (PCA) method, and more convenient comprehensive water quality evaluation models, the minimum WQI considering weights (WQImin-w) and the minimum WQI without considering weights (WQImin-nw) were established. The multiple statistical method and the absolute principal component score-multiple liner regression (APCS-MLR) model were combined to analyse the lake pollution sources based on the spatial changes in pollutants. The findings demonstrated that the WQImin-nw model's water quality evaluation outcome was more accurate when weights were not taken into account. The WQImin-nw model can be used as a simple and convenient way to comprehend the variations in water quality in wetlands of lakes and reservoirs. It was concluded that the comprehensive water quality in the study area was at a "medium" level, and CODMn was the main limiting factor. Nonpoint source pollution (such as agricultural planting and livestock breeding) was the most important factor affecting the water quality of Xianghai Lake (with a comprehensive contribution rate of 31.65%). The comprehensive contribution rates of sediment endogenous and geological sources, phytoplankton and other plants, and water diversion and other hydrodynamic impacts accounted for 25.12%, 19.65%, and 23.58% of the total impact, respectively. This study can provide a scientific method for water quality assessment and management of lake wetlands, and an effective support for migration of migratory birds, habitat protection and grain production security.


Valproic acid enhances pamidronate-sensitized cytotoxicity of Vδ2+ T cells against EBV-related lymphoproliferative cells.
Therapeutic options for Epstein-Barr virus (EBV)-associated post-transplantation lymphoproliferative diseases (PTLD) are currently limited, accompanying with some off-target toxicities. We previously demonstrated that early recovery of Vδ2+ T cells inversely correlated to EBV reactivation after allogeneic hematopoietic cell transplantation. Studies in vitro and in the mouse models showed the cytotoxic activity of Vδ2+ T cells on EBV-transformed lymphoproliferative cells, but the efficacy was moderate. Bisphosphonate, such as pamidronate (PAM), have been reported as a sensitizer to trigger tumor cells for Vδ2+ T cells recognition. Valproic acid (VPA) has attracted attentions due to its adjuvant anti-tumor effect with chemotherapy or immunotherapy. Whether PAM and VPA facilitate the immunogenicity of EBV-infected cells towards Vδ2+ T cells cytotoxicity remains unknown. Herein, we demonstrated that lower dosage of VPA and/or PAM did not induce apoptosis of EBV-transformed B lymphoblastoid cell lines (EBV-LCLs) or Vδ2+ T cells. Notably, pre-treatment with PAM significantly increased the cell death of EBV-LCLs after co-culture with Vδ2+ T cells at different ratios. Combining treatment with VPA reinforced the sensitizing effect of PAM. This efficacy was through inducing the accumulation of mevalonate pathway intermediates and dependent on the γδ T cell receptor of Vδ2+ T cells. Similar sensitizing effects of PAM and PAM plus VPA were also demonstrated on the primary PTLD cells. These results highlight the roles of PAM and VPA in the enhancement of immune surveillance and expand the fields of these two drugs in the treatment of different types of malignancies.


[Detection of multiresistance Aeromonas with TEM type resistant genes in patients with cirrhosis].
To study the status of beta-lactamase produced by multiresistant Aeromonas selected from cirrhosis patients to provide reference for treatment and reduce resistance and control spreading. Four multiresistant Aeromonas strains isolated from serious liver cirrhosis patients from the No. 302 hospital. The TEM resistant genes were detected by PCR and agarose gel electrophoresis. Three TEM-1 positive strains were detected from four multiresistant Aeromonas isolates consisting of one Aeromonas sobria and three Aeromonas hydrophila isolated from blood and ascites. This was further confirmed by gene sequencing. The multiresistance to antibiotics was higher in four Aeromonas isolates. All strains tested were resistant to ampicillin, cefazolin and cefmetazole.The cirrhosis patients who suffered from Aeromonas infection had poor prognosis and had mortality rate of 3/4. The beta-lactamase TEM-1 resistant genes was detected in clinical multiresistant Aeromonas strain isolated from serious cirrhosis patients.The results suggested that TEM-1 was the main resistance mechanism of Aeromonas strain and was reduced by adding enzyme inhibitor.


Correction: Linking cognitive flexibility to entrepreneurial alertness and entrepreneurial intention among medical students with the moderating role of entrepreneurial self-efficacy: A second-order moderated mediation model.
[This corrects the article DOI: 10.1371/journal.pone.0256420.].


Ethical issues, dilemmas and controversies in 'cosmetic' or aesthetic dentistry. A personal opinion.
Stephen Hancocks' elegant editorial of 11 December 2011 raises interesting questions which deserve discussion. Most experienced dentists would agree that the less that is done to teeth for cosmetic reasons, the lesser are the risks of disappointment, failure of expectation, or threat of litigation. Yet there is an increasing number of cases where aesthetics are the primary concern for dentists and patients alike and some patients are consenting to treatment without being properly informed of the destructive nature of the procedures to their sound tooth tissue and structures to achieve the desired 'cosmetic' outcome. This raises ethical issues, as much of this overtreatment is unnecessarily destructive and goes against the healing and caring principles of the dental profession.


Predicting Patient No-show Behavior: a Study in a Bariatric Clinic.
No-shows of patients to their scheduled appointments have a significant impact on healthcare systems, including lower clinical efficiency and higher costs. The purpose of this study was to investigate the factors associated with patient no-shows in a bariatric surgery clinic. We performed a retrospective study of 13,230 records for 2660 patients in a clinic located in Rio de Janeiro, Brazil, over a 17-month period (January 2015-May 2016). Logistic regression analyses were conducted to explore and model the influence of certain variables on no-show rates. This work also developed a predictive model stratified for each medical specialty. The overall proportion of no-shows was 21.9%. According to multiple logistic regression, there is a significant association between the patient no-shows and eight variables examined. This association revealed a pattern in the increase of patient no-shows: appointment in the later hours of the day, appointments not in the summer months, post-surgery appointment, high lead time, higher no-show history, fewer numbers of previous appointments, home address 20 to 50 km away from the clinic, or scheduled for another specialty other than a bariatric surgeon. Age group, forms of payment, gender, and weekday were not significant predictors. Predictive models were developed with an accuracy of 71%. Understanding the characteristics of patient no-shows allows making improvements in management practice, and the predictive models can be incorporated into the clinic dynamic scheduling system, allowing the use of a new appointment policy that takes into account each patient's no-show probability.


Further probes into quantitative aspects of competitive binding assays: allowance for effects of antigen multivalency in immunoassays.
Effects of antigen multivalency on procedures for the analysis of immunoassays are examined on the basis of a theoretical expression developed in the context of quantitative affinity chromatography [Nichol, L. W., Ward, L. D., and Winzor, D. J. (1981) Biochemistry 20, 4856-4860] but which is also pertinent to antigen-antibody interactions that may be described in terms of a single intrinsic association constant. Quantitative relationships are generated which provide the basis for more rigorous logit-log analyses of radioimmunoassays in which the antigen is multivalent, and an additional, theoretically superior, linear transform of the basic expression is developed. Simulated binding data for a tetravalent antigen system are then used to demonstrate the curvilinearity of the conventional Scatchard plot for such a system despite the homogeneity of binding sites, and the application of the various linear transforms involving logarithmic functions. Of particular interest in that regard is the observation that the traditional logit-log analyses yield linear plots with the predicted slope of unity even though antigen univalence is an implicit assumption in their application. Results obtained in a solid-phase radioimmunoassay of triiodothyronine are then presented to provide, for that system at least, experimental justification of the above-mentioned assumption that the antibody-antigen interactions may be described in terms of a single intrinsic association constant. Finally, an enzyme-linked immunoassay of ferritin is used to illustrate the possibility that a linear Scatchard plot may be obtained with a multivalent antigen under conditions where steric factors restrict participation of an antigen molecule to a single interaction with immobilized antibody.


Multiple sex chromosome drivers in a mammal with three sex chromosomes.
Eukaryotes with separate males and females display a great diversity in the way they determine sex, but it is still unclear what evolutionary forces cause transitions between sex-determining systems. Rather that the lack of hypotheses, the problem is the scarcity of adequate biological systems to test them. Here, we take advantage of the recent evolution of a feminizing X chromosome (called X∗) in the African pygmy mouse Mus minutoides to investigate one of the evolutionary forces hypothesized to cause such transitions, namely sex chromosome drive (i.e., biased transmission of sex chromosomes to the next generation). Through extensive molecular sexing of pups at weaning, we reveal the existence of a remarkable male sex chromosome drive system in this species, whereby direction and strength of drive are conditional upon the genotype of males' partners: males transmit their Y at a rate close to 80% when mating with XX or XX∗ females and only 36% when mating with X∗Y females. Using mathematical modeling, we explore the joint evolution of these unusual sex-determining and drive systems, revealing that different sequences of events could have led to the evolution of this bizarre system and that the "conditional" nature of sex chromosome drive plays a crucial role in the short- and long-term maintenance of the three sex chromosomes.


[Motor neurography: simultaneous recording using surface and needle electrodes. A comparative study of the proximal and distal latency together with the motor nerve conduction velocity].
The generally accepted interpretation that the application of surface and concentric needle electrodes for the recording of evoked muscle action potential in motor nerve neurography showed the same results has been reconsidered, especially because until now, over 20 years after the introduction of this neurophysiological method in routine clinical work, no exact statistically verified examinations have been done on this subject. Proximal and distal latency as well as motor nerve conduction velocity were determined in the following nerves in 100 subjects (71 healthy subjects and 29 patients): tibial, peroneal, ulnar, median. All neurographic parameters were obtained by means of simultaneous recording with surface and concentric needle electrodes and compared with one another. Concerning the ulnar nerve no statistically significant differences could be found. In the remaining three nerves, statistically significant differences could be detected for distal and proximal latency but not for motor nerve conduction velocity.


Activation of p47(PHOX), a cytosolic subunit of the leukocyte NADPH oxidase. Phosphorylation of ser-359 or ser-370 precedes phosphorylation at other sites and is required for activity.
The leukocyte NADPH oxidase catalyzes the reduction of oxygen to superoxide (O-2) at the expense of NADPH in phagocytes and B lymphocytes. The enzyme is dormant in resting cells but becomes active when the cells are exposed to appropriate stimuli. During oxidase activation, the highly basic cytosolic oxidase component p47(PHOX) becomes phosphorylated on several serines and migrates to the plasma membrane. We report here that p47(PHOX)-deficient B lymphoblasts expressing the p47(PHOX) S359A/S370A or p47(PHOX) S359K/S370K double mutation show dramatically reduced levels of enzyme activity and phosphorylation of p47(PHOX) as compared with the same cells expressing wild type p47(PHOX). In addition, these mutant p47(PHOX) proteins fails to translocate to the plasma membrane when the cells are stimulated. In contrast, normal phosphorylation and translocation are seen in mutants containing aspartate or glutamate at positions 359 and 370, but oxidase activity is still greatly reduced. These results imply that a negative charge at position 359 and/or 370 is sufficient to allow the phosphorylation and translocation of p47(PHOX) to take place but that features unique to a phosphorylated hydroxyamino acid are required to support O-2 production. These findings, plus those from an earlier study (Inanami, O., Johnson, J. L., McAdara, J. K., El Benna, J., Faust, L. P., Newburger, P. E., and Babior, B. M. (1998) J. Biol. Chem. 273, 9539-9543), suggest that oxidase activation requires 1) the sequential phosphorylation of at least two serines on p47(PHOX): Ser-359 or Ser-370, followed by Ser-303 or Ser-304; and 2) the translocation of p47(PHOX) to the membrane at some point after the first phosphorylation takes place.


Neuronal differentiation and synapse formation occur in space and time with fractal dimension.
The analysis of a set of experimental data obtained by an independent team of researchers confirms that neuronal differentiation or synapse formation do occur in time and space with fractal dimension. The interacting cells create first a dynamic system with its own attractor, (i.e., a fragment of time and space where the dynamic processes occur and where no further evolution of the system is possible at all owing to the action of the intrasystemic forces unless some extrasystemic forces act upon it). This attractor is then modified in the active manner by the differentiating cells until the system attains a degenerated stationary state and differentiation ends. The fractal structure of the system is also lost in the course of tumor progression. Our data indicate that the cellular system can attain the degenerated stationary state, leaving the attractor with a fractal dimension directly or undergoing diversification into many attractors and going through the areas of deterministic chaos. Since evolution of the cellular system is driven by the cooperative dynamic processes, as reflected by the changes of the mean fractal dimension between the intervals of the Gompertzian curve, it is likely that cells differentiate into neurons and create synapses with a conjugated probability and non-Gaussian distribution rather than with the classical probability and the Gaussian distribution. These findings can help to optimize features of artificial neural networks. They also define a simple in vitro biological model for biophysical and biochemical studies on natural neural networks.


Radiosynthesis and in vivo evaluation of a ¹⁸F-labelled styryl-benzoxazole derivative for β-amyloid targeting.
The formation of β-amyloid deposits is considered a histopathological feature of Alzheimer's disease (AD). In vivo molecular imaging by means of amyloid-avid radiotracers will allow for an early and conclusive diagnostic of AD. Herein, we describe the radiosynthesis of the radiofluorinated styryl benzoxazole derivative [¹⁸F]-[2-[N-methyl-N-(2'-fluoroethyl)-4'-aminostyryl]benzoxazole] ([¹⁸F]-1) and its pre-clinical evaluation, including metabolic and biodistribution studies in male Wistar rats. The in vivo biological evaluation of [¹⁸F]-1 showed that this new radiotracer has a moderate brain uptake with a slow brain washout and a poor in vivo stability.


Health-related quality of life after segmental resection of the lateral mandible: Free fibula flap versus plate reconstruction.
Segmental resection of the mandible causes functional, aesthetic and social problems affecting health-related quality of life (HRQoL). It is often assumed that reconstruction with composite free flaps guarantees better function and aesthetics than bridging the defect with reconstruction plates. Using the European Organization for Research and Treatment of Cancer questionnaires (EORTC QLQ-C30 version 3.0 and EORTC QLQ-H&N35), we compared HRQoL in patients who received free fibula flaps versus reconstruction plates after segmental resection of the lateral mandible. Thirty-seven completed questionnaires (18 fibula reconstructions and 19 patients with reconstruction plates) were available. Reconstruction with a free fibula flap did not provide clear additional benefit to bridging the defect with a reconstruction plate after segmental resection of the lateral mandible. In particular aspects known to have the most impact on HRQoL like swallowing, speech and chewing were not influenced by the type of reconstruction. Reconstruction of segmental defects of the lateral mandible with free fibula flap and reconstruction plate resulted in comparable HRQoL. If dental rehabilitation by means of dental implants is not anticipated in the fibula, then plate reconstruction with adequate soft tissue remains a suitable technique for the reconstruction of segmental defects of the lateral mandible.


Enzymatic E-colicins bind to their target receptor BtuB by presentation of a small binding epitope on a coiled-coil scaffold.
Toxins and viruses often initiate their attacks by binding to specific proteins on the surfaces of target cells. Bacterial toxins (e.g. bacteriocins) and viruses (bacteriophages) targeting Gram-negative bacteria typically bind to outer membrane proteins. Bacterial E-colicins target Escherichia coli by binding to the outer membrane cobalamin transporter BtuB. Colicins are tripartite molecules possessing receptor-binding, translocation, and toxin domains connected by long coiled-coil alpha-helices. Surprisingly, the crystal structure of colicin E3 does not possess a recognizable globular fold in its receptor-binding domain. We hypothesized that the binding epitope of enzymatic E-colicins is a short loop connecting the two alpha-helices that comprise the coiled-coil region and that this flanking coiled-coil region serves to present the loop in a binding-capable conformation. To test this hypothesis, we designed and synthesized a 34-residue peptide (E-peptide-1) corresponding to residues Ala366-Arg399 of the helix-loop-helix region of colicin E3. Cysteines placed near the ends of the peptide (I372C and A393C) enabled crosslinking for reduction of conformational entropy and formation of a peptide structure that would present the loop epitope. A fluorescent analog was also made for characterization of binding by measurement of fluorescence polarization. Our analysis shows the following. (i). E-peptide-1 is predominantly random coil in aqueous solution, but disulfide bond formation increases its alpha-helical content in both aqueous buffer and solvents that promote helix formation. (ii). Fluorescein-labeled E-peptide-1 binds to purified BtuB in a calcium-dependent manner with a Kd of 43.6 +/- 4.9 nm or 2370 +/- 670 nm in the presence or absence of calcium, respectively. (iii). In the presence of calcium, cyanocobalamin (CN-Cbl) displaces E-peptide-1 with a nanomolar inhibition constant (Ki = 78.9 +/- 5.6 nm). We conclude that the BtuB binding sites for cobalamins and enzymatic E-colicins are overlapping but inequivalent and that the distal loop and (possibly) the short alpha-helical flanking regions are sufficient for high affinity binding.


Brain Imaging of Patients with COVID-19: Findings at an Academic Institution during the Height of the Outbreak in New York City.
A large spectrum of neurologic disease has been reported in patients with coronavirus disease 2019 (COVID-19) infection. Our aim was to investigate the yield of neuroimaging in patients with COVID-19 undergoing CT or MR imaging of the brain and to describe associated imaging findings. We performed a retrospective cohort study involving 2054 patients with laboratory-confirmed COVID-19 presenting to 2 hospitals in New York City between March 4 and May 9, 2020, of whom 278 (14%) underwent either CT or MR imaging of the brain. All images initially received a formal interpretation from a neuroradiologist within the institution and were subsequently reviewed by 2 neuroradiologists in consensus, with disputes resolved by a third neuroradiologist. The median age of these patients was 64 years (interquartile range, 50-75 years), and 43% were women. Among imaged patients, 58 (21%) demonstrated acute or subacute neuroimaging findings, the most common including cerebral infarctions (11%), parenchymal hematomas (3.6%), and posterior reversible encephalopathy syndrome (1.1%). Among the 51 patients with MR imaging examinations, 26 (51%) demonstrated acute or subacute findings; notable findings included 6 cases of cranial nerve abnormalities (including 4 patients with olfactory bulb abnormalities) and 3 patients with a microhemorrhage pattern compatible with critical illness-associated microbleeds. Our experience confirms the wide range of neurologic imaging findings in patients with COVID-19 and suggests the need for further studies to optimize management for these patients.


Heart Rate Response in Spectators of the Montreal Canadiens Hockey Team.
To our knowledge, heart rate responses have not previously been assessed in hockey fans. We quantified heart rate increases in spectators of the Montreal Canadiens, compared televised with live games, explored features associated with peak heart rates, and assessed whether increases correlate with a fan passion score. Healthy adults were enrolled, with half attending live games and half viewing televised games. All subjects completed questionnaires and had continuous Holter monitoring. Intensity of the physical stress response was defined according to previously published heart rate index thresholds as mild (< 1.33), moderate (1.33-1.83), or vigorous (> 1.83). In 20 participants, 35% women, age 46 ± 10 years, the heart rate increased by a median of 92% during the hockey game, from 60 (interquartile range, 54-65) beats per minute at rest to 114 (interquartile range, 103-129) beats per minute (P < 0.001). The heart rate increased by 110% vs 75% during live vs televised games (P < 0.001). Heart rate index (2.16 ± 0.27 vs 1.73 ± 0.15; P < 0.001) and percent maximum predicted heart rate attained (75% ± 8% vs 58% ± 7%; P < 0.001) were significantly higher during live vs televised games. Number of premature beats was nonsignificantly higher during live games (5 vs 1; P = 0.181). The fan passion score was not predictive of the heart rate response (P = 0.753). Peak heart rates most commonly occurred during overtime (40%) and scoring opportunities for (25%) and against (15%). It is exciting to watch the Montreal Canadiens! Viewing a live hockey game is associated with a heart rate response equivalent to vigorous physical stress and a televised game to moderate physical stress.


The fine structure of the parietal retinas of Anolis carolinensis and Iguana iguana.
An electron microscopic examination of the parietal retinas of Anolis carolinensis and Iguana iguana demonstrated within each retina (1) two distinct populations of neurons, (2) two populations of glia, and (3) a population of photoreceptors which could not be subdivided. A small population of very electron-dense cells, in many respects similar to photoreceptors, was also found in the iguana. Correspondingly dark processes were found in the plexiform layer of each retina. Parietal photoreceptors generally resemble cones of the lateral eye. Glial cells were sub-classified on the basis of the location of their somata and the disposition of their processes. Neurons were identified by virtue of their cytology and their reception of axosomatic ribbon synapses from unidentified plexiform layer processes. Neuronal subtypes were located on opposite sides of the plexiform layer. Neurons distal to that layer were found to project the initial segments of their processes into the plexiform layer parallel to its long axis, while neurons central to the plexiform layer projected axons centrally and dendrites radially into the plexiform layer. The existence of at least two neuronal populations and of interphotoreceptor synapses suggests that photosensory processing within the parietal retina may be more complex than previously assumed.


Changing trends of anaemia prevalence among female medical students in a metropolitan setting: Assessment through self-grading and haematological parameters.
To determine the trend of anaemia prevalence among female medical students (FMS) through self-grading along haematological parameters and its association with their nutritional indicators. This cross-sectional study was conducted at a public sector health university of Karachi among FMS from April to September 2016. After written informed consent, 216 FMS were assessed for height and weight, for nutrition habits by calculating minimum dietary diversity for women (MDD-W) and anaemia status by self-administered validated self-grading anaemia assessment questionnaire (SGAAQ). The haematological parameters were examined in venous blood sample on Sysmex (XN-3000). The data was analysed using IBM SPSS software version 24. Association between anaemia and nutritional indicators was determined by Chi-square and considered significant when p < 0.05. Anaemia prevalence was 31% with highest frequency among obese (56%) and 29% FMS achieved MDD-W. The mean SGAAQ score, Hb (g/dl), MCV (fl), MCH (pg) and Ret-He (pg) differed significantly (p = <0.001) between anaemic and non-anaemic students. The mean Hb (g/dl) level was significantly higher for FMS who scored MDD-W >5 (p= 0.04). Malnutrition and anaemia co-exist despite appropriate awareness of anaemia among FMS. It was associated with self-assessment of anaemia and BMI groups but not with dietary diversity in the present study.


Is there any association between hepatitis G virus (HGV), other hepatitis viruses (HBV, HCV) and Behçet's disease?
Infectious agents, especially viruses, have been implicated in the pathogenesis of Behçet's disease (BD). The aim of this study was to determine whether BD is associated with hepatitis viruses. In this study, the serological markers of hepatitis (HBsAg, anti-HBs, anti-HBc and anti-HCV) and viral nucleic acid (HGV-RNA) were studied in the sera of 35 patients, all of whom fulfilled the diagnostic criteria of the International Study Group for BD, and the results were compared with those of 36 healthy controls. The prevalences of HBsAg, anti-HBs, anti-HBc in BD patients were 2.9%, 45.7%, and 31.4%, respectively, which were not significantly different from those in healthy controls. None of the subjects in either group were found to be positive for anti-HCV. HGV-RNA was detected in two patients with BD and in none of the healthy controls. In conclusion, BD does not seem to be associated with hepatitis viral infections including hepatitis B, C, or G.


Baseline Plasma Tumor DNA (ctDNA) Correlates with PSA Kinetics in Metastatic Castration-Resistant Prostate Cancer (mCRPC) Treated with Abiraterone or Enzalutamide.
Background: Baseline high circulating tumor DNA (ctDNA) fraction in plasma and androgen receptor (AR) copy number (CN) gain identify mCRPC patients with worse outcomes. This study aimed to assess if ctDNA associates with PSA kinetics. Methods: In this prospective biomarker study, we evaluate ctDNA fraction and AR CN from plasma samples. We divided patients into high and low ctDNA level and in AR gain and AR normal. Results: 220 baseline samples were collected from mCRPC treated with abiraterone (n = 140) or enzalutamide (n = 80). A lower rate of PSA decline ≥ 50% was observed in patients with high ctDNA (p = 0.017) and AR gain (p = 0.0003). Combining ctDNA fraction and AR CN, we found a different median PSA progression-free survival (PFS) among four groups: (1) low ctDNA/AR normal, (2) high ctDNA/AR normal, (3) low ctDNA/AR gain, and (4) high ctDNA/AR gain (11.4 vs. 5.0 vs. 4.8 vs. 3.7 months, p < 0.0001). In a multivariable analysis, high ctDNA, AR gain, PSA DT, PSA DT velocity remained independent predictors of PSA PFS. Conclusions: Elevated ctDNA levels and AR gain are negatively and independently correlated with PSA kinetics in mCRPC men treated with abiraterone or enzalutamide.


Comparison of fasting bioavailability among 100-mg commercial, 100-mg generic, and 50-mg chewable generic sildenafil tablets in healthy male Mexican volunteers: a single-dose, 3-period, crossover study.
Sildenafil citrate (SIL) was the first oral drug registered in Mexico for the treatment of erectile dysfunction. However, succinct pharmacokinetic data are available in the Mexican population. The goals of the present work were: (1) to design a specific method to quantify SIL plasma levels by using UPLC-MS/MS; (2) to compare oral SIL bioavailability in Mexican men with pharmacokinetic data in other populations; (3) to fulfill local regulatory requests; and (4) to describe the relative tolerability of a new 50-mg chewable tablet. This was a randomized, single-dose, 3-period, 6-sequence crossover study in healthy male volunteers. In each period, subjects received single oral doses of 100 mg of sildenafil (1 commercial [reference(⁎)], 1 generic [test 1(†)], or 2 chewable generic tablets [test 2(‡)]), with a 4-day washout period between each dose. Serial blood samples were collected for up to 24 hours. SIL was measured in heparinized plasma by using a validated UPLC-MS/MS method. Pharmacokinetic parameters included C(max), T(max), AUC(0-24), and AUC(0-∞). Bioequivalence was established if 90% CIs for mean test:reference ratios of log-transformed C(max) and AUC fell within the range of 0.80 to 1.25. Tolerability was assessed on the basis of a clinical interview with the subject and monitoring of vital signs. Demographic data showed a homogeneous population. Validation of analytical method proved to be linear within the range of 1 to 1000 ng/mL, with selectivity, accuracy, and precision. 90% CIs for test 1:reference ratios were 86.52 to 113.56, 94.75 to 108.84, and 94.97 to 108.82 for the logarithm parameters C(max), AUC(0-24), and AUC(0-∞), respectively. The 90% CIs for the test 2:reference ratios were 82.14 to 107.24, 98.26 to 112.56, and 99.19 to 113.34 for C(max), AUC(0-24), and AUC(0-∞). Regarding relative tolerability, slight cephalea was the most common adverse effect. The developed analytical method was validated in compliance with local requirements and was useful for sildenafil measurement. This single-dose study under fasting conditions suggests that both test products met the Mexican regulatory criteria for assuming bioequivalence in these healthy, male Mexican volunteers. The clinical data suggest that the chewable tablets were well tolerated by volunteers.


[Complaints and health care system utilisation of ethnic German migrants from the former Soviet Union to Germany and their families].
The aim of the study is the description of subjective morbidity, health care system utilisation and complaints of ethnic German migrants from the former Soviet Union at the beginning of migration. At present no data are available concerning aspects of health behaviour among this largest immigrant population in Germany. 300 ethnic German migrants and their families (mean age 37.2 and 51% female) were interrogated shortly after migration to Germany. They answered questions about prevalence of diseases, health care system utilization, actual health status and completed the Giessen Subjective Complaints List (GSCL-24). German standards exist for all questionnaires. 237 ethnic German migrants report to have suffered from at least one disease during the course of the last year. They see the gynaecologist and dentist as often as the German population, pay fewer visits to practitioners and specialists but seek more medical advice from the medical lay system. The majority of subjects are satisfied with their health. Migrants describe their health status as lower than the German population compared to which they also report more complaints (Overall distress in GSCL-24 : 17.2 for migrants and 14.0 for Germans) and different complaints (headaches, fatigue). The different medical care system and differences in the treatment of patients could account for the less frequent use of medical services by ethnic German migrants. Actual stressors like language differences and acculturation problems are discussed as possible reasons for the increased rate of complaints among ethnic German migrants. Although they suffer from more complaints the German migrants do not seem to modify their help-seeking behaviour.


Complement and diseases: defective alternative pathway control results in kidney and eye diseases.
The complement system is a central part of innate immunity and in its normal setting aimed to recognize and eliminate microbes. For elimination toxic activation products are generated locally and are reported directly of the surface of the invading microbe. A deregulation of the alternative pathway results in defective recognition and toxic activation products can be formed on the surface of host tissues and structures. Recent studies have shown that mutated or defective regulators of the alternative pathway of complement are associated with auto immune diseases of the kidney, including the atypical form of hemolytic uremic syndrome (HUS), membranoproliferative glomerulonephritis (MPGN) and also of the eye, such as age-related macular degeneration (ARMD). Current research provides clues how mutations occurring in genes coding for single complement components or the inactivation of single regulators lead to defective alternative pathway amplification, via the convertase C3bBb. These scenarios explain how defects of a single regulator lead to local, organ specific damage.


Effectiveness of dTpa vaccination during pregnancy in preventing whooping cough in infants under 3 months of age. Bizkaia, Basque Country, Spain.
In response to an increase in the incidence of whooping cough in recent years, the Basque Country established a vaccination programme for pregnant women in the last trimester of the pregnancy seeking to protect young infants, a population that is at high risk of developing severe whooping cough. In the present study, based on the screening method, we assessed the effectiveness of this measure to prevent whooping cough in infants under 3 months of age. We found a vaccine effectiveness of 89% and 95% CI 72-96%. While the incidence of this disease remains high, we recommend continuing to vaccinate pregnant women in the last trimester of pregnancy.


Thermal hysteresis loop of the spin-state in nanoparticles of transition metal complexes: Monte Carlo simulations on an Ising-like model.
Theoretical investigation with Monte Carlo simulations predicts that thermal spin-switching hysteresis of transition-metal complexes appears even in nanoparticles, but the hysteresis width does not depend only on the interaction strength between molecules but also strongly on the shape and size of the particles.


Predictors of therapeutic effects in amitriptyline treatment--1. Plasma drug levels.
To analyze the spectrum of relationships between clinical effects of amitriptyline (At) treatment after 2 and 4 weeks (wks) and plasma levels of At, nortriptyline (Nt), At+Nt, demethylation rate of At, treatment modalities, age, and gender. Patients with major depression (ICD 10: F31-F33) and a HAMD-21 total score of 15-41 received At on a dosage schedule chosen by the doctor for at least 4 wks. Plasma drug levels were assessed at baseline and at wks 2 and 4. Of the 58 patients enrolled in the study, 47 (15males, 32 females) were eligible for statistical analysis. An early response by wk 2 (decrease in HAMD-21 score of at least 50 % from baseline) was observed in 34.0 % of patients, and after 4 wks, the response rate was 63.8 % (males 86.6 %, females 53.1 %). There was a low, negative, and significant correlation between percent reduction in HAMD and steady state At concentration only at wk 2 (n = 47 r Sp. = -0.306 p < 0.05). However, the correlation was dependent on the degree of At demethylation and treatment modalities. A ratio of Nt/At >1 was observed in 23 patients; of these, 11 (47.8 %) were non-responders by wk 4. A low rate of demethylation (Nt/At </= 1) in 24 patients was associated with a lower frequency of non-response (6/24 = 25.0 %). In the latter subgroup, the 2-wk At plasma concentration varied between 20 and 240 ng/ml, and all patients with </= 110 ng At /ml were responders by wk 4. On the other hand, in the Nt/At >1 group, the non-responders were distributed in the whole range of observed At plasma concentrations (20-150 ng/ml). Only in patients with Nt/At </= 1 and constant doses from wk 1 to wk 4 (n = 14) was a strong, linear, and negative correlation between percent reduction in HAMD and plasma At, Nt, or At+Nt concentrations found for the 2-wk data (r Sp. = -0.754, -0.716, and -0.732, respectively), but not after 4 wks. The frequently assumed dependence of clinical effects on plasma drug levels is not a simple function. There most likely exist different patterns of relationships with partially unknown backgrounds. The ratio Nt/At may become a discriminating variable in future studies on the nature of plasma level-therapeutic effect relationship in At treatment of major depression.


Improving the efficacy of peptide vaccines in cancer immunotherapy.
Peptide vaccines have shown great potential in cancer immunotherapy by targeting tumor antigens and activating the patient's immune system to mount a specific response against cancer cells. However, the efficacy of peptide vaccines in inducing a sustained immune response and achieving clinical benefit remains a major challenge. In this review, we discuss the current status of peptide vaccines in cancer immunotherapy and strategies to improve their efficacy. We summarize the recent advancements in the development of peptide vaccines in pre-clinical and clinical settings, including the use of novel adjuvants, neoantigens, nano-delivery systems, and combination therapies. We also highlight the importance of personalized cancer vaccines, which consider the unique genetic and immunological profiles of individual patients. We also discuss the strategies to enhance the immunogenicity of peptide vaccines such as multivalent peptides, conjugated peptides, fusion proteins, and self-assembled peptides. Although, peptide vaccines alone are weak immunogens, combining peptide vaccines with other immunotherapeutic approaches and developing novel approaches such as personalized vaccines can be promising methods to significantly enhance their efficacy and improve the clinical outcomes for cancer patients.


Contrasting responses in growth, photosynthesis and hydraulics of two subtropical tree species to cadmium contamination as affected by elevated CO2 and nitrogen addition.
Plant growth, photosynthesis, and hydraulics are affected by heavy metals but also by elevated atmospheric CO2 concentration (e[CO2]) and nitrogen (N) deposition. However, few studies have investigated the response of woody species to the combined effects of these three factors. We conducted an open-top chamber experiment with two common subtropical trees (Acacia auriculiformis and Syzygium hainanense) to explore the effects of cadmium (Cd)-contamination, e[CO2], and N addition on plant eco-physiological traits. We found that the growth of A. auriculiformis was insensitive to the treatments, indicating that it is a Cd-tolerant and useful afforestation species. For S. hainanense, in contrast, e[CO2] and/or N addition offset the detrimental effects of Cd addition by greatly increasing plant biomass and reducing the leaf Cd concentration. We then found that e[CO2] and/or N addition offset the detrimental Cd effects on S. hainanense biomass by increasing its photosynthetic rate, its N concentration, and the efficiency of its stem water transport network. These offsetting effects of e[CO2] and/or N addition, however, came at the expense of reduced xylem hydraulic safety resulting from wider vessels, thinner vessel walls, and therefore weaker vessel reinforcement. Our study suggests that, given future increases in global CO2 concentration and N deposition, the growth of Cd-tolerant tree species (like A. auriculiformis) will be probably stable while the growth of Cd-sensitive tree species (like S. hainanense) might be enhanced despite reduced hydraulic safety. This also suggests that both species will be useful for afforestation of Cd-contaminated soils given future global change scenarios.


Dawn of the Sino-Japan Society of Gastroenterology and Endoscopy.
The exchange of gastrointestinal endoscopy between Japan and China began in 1972. Half a century ago, Japan's endoscope technology was still developing. At the request of the Japan-China Friendship Association, I was invited to Peking Union Medical Hospital and gave a demonstration of gastrointestinal endoscopy, colonoscopy, and endoscopic retrograde cholangiopancreatography.


The antibody response to a single antigenic determinant of the tobacco mosaic virus protein: analysis using monoclonal antibodies, mutant proteins and synthetic peptides.
Three hybridomas were selected which secreted monoclonal antibodies specific to a decapeptide determinant representing residues 103-112 of the tobacco mosaic virus protein ( TMVP ). A series of proteins from several strains of TMV which differ in the amino acid sequence in this region of the protein were used as probes for specificity analysis. The fine-specificity analysis was extended by assessing the binding of the antibodies with a panel of synthetic peptide analogues of the native decapeptide with amino acid substitutions at different locations. The binding of each synthetic peptide with each of the monoclonal antibodies was determined by the ability of the radiolabeled peptide to bind with the antibody. The binding of the decapeptide with antibodies was determined by equilibrium dialysis; the relative binding affinity of each peptide of the panel was determined by the capacity of the peptide to inhibit the binding between the antibody and the radiolabeled native decapeptide. The results demonstrated that a panel of synthetic peptide analogues constitutes a powerful tool for discerning the fine specificity of antibodies directed to a given determinant of a protein antigen. The data indicated that, although all of the antibodies recognized the same nominal decapeptide determinant, their binding with the different mutant proteins or with the synthetic peptides of the panel differed greatly, indicating dramatic differences in their fine specificity. The existence of such differences should be taken into consideration when assessing residues of a protein antigen that are involved in antibody binding. The differences which were found in monoclonal antibodies produced following immunization with the whole TMVP reflect differences which occur in heterogeneous serum antibody populations and point out the complexity of antigenic recognition even of as small an epitope as a decapeptide.


Dramatic efficacy of cannabidiol on refractory chronic pain in an adolescent with sickle cell disease.
Here, we report a dramatic efficacy of cannabidiol in an adolescent with SCD suffering from chronic pain refractory to other analgesics, with complete regression of chronic pain and rapid plasma histamine level normalization after treatment.


ALK alterations in salivary gland carcinomas.
Salivary gland carcinomas represent a heterogeneous group of poorly characterized head and neck tumors. The purpose of this study was to evaluate ALK gene and protein aberrations in a large, well-characterized cohort of these tumors. A total of 182 salivary gland carcinomas were tested for anaplastic lymphoma kinase (ALK) positivity by immunohistochemistry (IHC) using the cut-off of 10% positive cells. ALK positive tumors were subjected to FISH analysis and followed by hybrid capture-based next generation sequencing (NGS). Of the 182 tumors, 8 were ALK positive by IHC. Further analysis using hybrid capture NGS analysis revealed a novel MYO18A (Exon1-40)-ALK (exon 20-29) gene fusion in one case of intraductal carcinoma. Additional genomic analyses resulted in the detection of inactivating mutations in BRAF and TP53, as well as amplifications of ERBB2 and ALK. ALK rearrangements are a rare entity in salivary gland carcinomas. We identified a potentially targetable novel ALK fusion in an intraductal carcinoma of minor salivary glands.


Clinical spectrum of infantile spasm at presentation.
To determine the clinical and EEG findings in children with infantile spasms at their initial presentation to the Neurophysiology Department, Children's Hospital, Lahore, Pakistan. Observational study. The Neurophysiology Department, Children's Hospital, Lahore, Pakistan, from January 2008 to December 2010. Children aged < 24 months, referred for their first EEG test was assessed for the diagnosis of infantile spasms. Clinical manifestation, EEG finding and anti-epileptic drugs being administered on presentation were analyzed by the paediatric neurologists. Among the total 2050, 410 children (20%) had infantile spasms. Mean age at presentation was 4.6 + 3.5 months. Three hundred and twenty eight presented due to infantile spasms / seizures (80%) and 82 due to psychomotor delay / regression (20%). Seventy-two percent patients presented at the age < 6 month and no patient presented after the age of 18 months. Spasm types were mixed (56%), flexors (24%), extensor (12%) and asymmetric (8%). Etiology classification was symptomatic in 58% and cryptogenic in 42%. Autonomic disturbance, impaired consciousness and abnormal eye movements were the dominant initial clinical presentations. EEG records showed hypsarrhythmic/modified hypsarrhythmic in 82% and other forms of epileptic discharges in 18%. Hormonal therapy was being administered in 12%, 40% were receiving Phenobarbitone and 34% were not being treated with any anti-epileptic agent. Patients with infantile spasms have abnormal EEG findings predominantly the hypsarrhythmic modified hypsarrhythmic discharge. To avoid improper treatment, such patients should be referred to the specialized centres.


Inhibition of hyaluronidase by dextran sulfate and its possible application in anticancer treatment.
Hyaluronidase is competitively inhibited by dextran sulfate. Hyaluronidase depolymerizes the amorphous component of the interstitial connective tissue and therefore supports tumor spread and metastasis. These processes may be reduced by dextran sulfate.


Adsorptive removal of crystal violet from wastewater using sodium alginate-gelatin-montmorillonite ternary composite microbeads.
In this study, the performance of the montmorillonite-filled sodium alginate/gelatin (SA-GEL-MMT) ternary biocomposite microbeads on the adsorptive removal of crystal violet (CV) dye was investigated. Firstly, the composites containing different weight ratios of MMT such as 10 %, 15 %, and 20 % were prepared. The composite beads were cross-linked using a calcium chloride (3%wt/v) solution. To determine the optimum sorption conditions the studies were performed at different parameters namely temperature, pH, contact time, sorbent dose, and dye concentration. From the sorption studies, the maximum capacity of the microbeads was found as 1000.0 mg/g whereas the maximum removal of the dye was 92.1 % at pH = 7 and a temperature of 25 °C. Additionally, the kinetic studies showed that the sorption of the dye followed the pseudo-second-order kinetics. Moreover, the adsorptive removal of the dye occurs spontaneously. This study suggests that the use of SA-GEL-MMT can be highly effective and reusable for the treatment of wastewater.


Measurement properties of a new wireless electrogoniometer for quantifying spasticity during the pendulum test in ARSACS patients.
Autosomal recessive spastic ataxia of Charlevoix/Saguenay (ARSACS) is a neuromuscular disorder that induces spasticity in lower limbs. The Wartenberg pendulum test is a classical method of assessing lower limb spasticity based on the dynamics of the pendular leg motion. However, in its original form, this test only provides subjective results and do not allow accurate assessment of spasticity. Thirteen ARSACS patients were assessed using a new wireless electrogoniometer to measure spasticity by quantifying oscillation amplitudes and relaxation indices during the Wartenburg pendulum test. The validity of the instrument was evaluated by comparing its measurements to a known precise goniometer whereas discriminant validity was evaluated by comparing healthy participants and ARSACS patients. Reliability was measured using intraclass correlation (ICC) between pendulum test scores obtained at different moments in time. Data from different tests show that the proposed device is accurate (standard error of measurement of 0.0005°), discriminates healthy and ARSACS patients (most variables have p=0.00) and provides repeatable results (significant ICC usually higher than 0.64 and p<0.05). The proposed tool allows the clinician to analyze pendulum oscillation amplitudes and ratios and thus, provide an index of spasticity for the patients affected by ARSACS. This is important as the original procedure is only evaluated visually and the progression cannot be detected until the condition changes drastically. Thus, the system proposed meets the requirements of being useful, precise and user-friendly in the evaluation of patients in a research as well as a clinical environment.


Qingkailing injection ameliorates cerebral ischemia-reperfusion injury and modulates the AMPK/NLRP3 Inflammasome Signalling pathway.
Cerebral ischemia is the second-leading cause of death and the main cause of permanent adult disabilities worldwide. Qingkailing (QKL) injection, a patented Chinese medicine approved by the China Food and Drug Administration, has been widely used in clinical practice to treat cerebral ischemia in China. The NOD-like receptor pyrin 3 (NLRP3) inflammasome is activated in cerebral ischemia and thus, is an effective therapeutic target. AMP-activated protein kinase (AMPK) is an important regulator inhibiting NLRP3 inflammasome activation. We investigated the potential of QKL injection to provide neuroprotection after cerebral ischemia in a rat model of middle cerebral artery occlusion (MCAO). Adult male Sprague-Dawley rats (210-230 g) were randomly divided into three groups which consist of sham, MCAO and 3 ml/kg QKL. Rats in the QKL group received intraperitoneal injections of 3 ml/kg QKL, while rats in other groups were given saline in the same volumes. After 90 min ischemia and 24 h reperfusion, neurological function, laser speckle imaging, brain infarction, brain water content and brain blood barrier permeability were examined and cell apoptosis at prefrontal cortex were evaluated 24 h after MCAO, and western blot and real-time quantitative polymerase chain reaction was also researched, respectively. Intraperitoneal administration of QKL alleviated neurological deficiencies, cerebral infarction, blood-brain barrier permeability, brain oedema and brain cell apoptosis after MCAO induction. QKL decreased pro-inflammatory cytokines, TNF-α, IL-6 and IL-1β, and increased anti-inflammatory cytokines, IL-4 and IL-10. Furthermore, QKL activated phosphorylated AMPK, decreased oxidative stress and decreased NLRP3 inflammasome activation. QKL relieved cerebral ischemia reperfusion injury and suppressed the inflammatory response by inhibiting AMPK-mediated activation of the NLRP3 inflammasome. These results suggest that QKL might have potential in treating brain inflammatory response and attenuating the cerebral ischemia-reperfusion injury.


Histocytological studies on the pituitary gland of Puntius sophorein correlation to its gonadal cycle.
Correlation between the pituitary and the gonadal cycle of Puntius sophore has been described. The cyanophils of proximal pars distalis region of pituitary undergo quantitative and qualitative changes which have been correlated to the reproductive cycle. The percentage of cyanophils remains pretty high during spawning phase, which also marks the period of their marked secretory activity.


A Cryo-pulverization Protocol for Processing Mouse Paws to Evaluate Molecular Pathways of Tissue Inflammation in a Collagen Induced Arthritis Model.
Profiling molecular changes in local tissues is crucial to understand the mechanism(s) of action of therapeutic candidates in vivo. In the field of arthritis research, many studies are focused on inflamed joints that are composed of a complex mixture of bone, cartilage, muscle, stromal cells and immune cells. Here, we established a reliable and robust mechanical method to disrupt inflamed mouse paws into homogeneous pulverized samples in a cryogenically controlled environment. Protein and RNA lysates were processed to enable proteomic and transcriptional endpoints and molecular characterization of relevant disease pathways in local tissue.


Exploring supervised neighborhood preserving embedding (SNPE) as a nonlinear feature extraction method for vibrational spectroscopic discrimination of agricultural samples according to geographical origins.
Supervised neighborhood preserving embedding (SNPE), a nonlinear dimensionality reduction method, was employed to represent near-infrared (NIR) and Raman spectral features of agricultural samples (Angelica gigas, sesame, and red pepper), and the newly constructed variables were used to discriminate their geographical origins. This study was done to evaluate the potential of SNPE for recognizing minute spectral differences between classes by preserving local relationships, in comparison with widely adopted linear feature representation methods such as principal component analysis (PCA) and partial least squares (PLS). For this purpose, diffuse reflectance NIR spectral datasets of Angelica gigas, sesame, and red pepper, and a Raman spectral dataset of the same red pepper were prepared. The spectra were represented into new variables in reduced dimensions by PCA, PLS, neighborhood preserving embedding (NPE), and SNPE, and the represented variables were used to determine the geographical origins of samples by using the k-nearest neighbor (k-NN) and support vector machine (SVM). The combination of SNPE and SVM differentiated the geographical origins with improved accuracy. Overall results demonstrate that SNPE is a valuable alternative feature representation method, especially when complex and highly overlapping vibrational spectra are used for analysis.


Conservation of HPV-16 E6/E7 ORF sequences in a cervical carcinoma.
A cervical carcinoma that contained human papillomavirus (HPV)-16 homologous DNA was analyzed. Each tumor cell genome contained a single, incomplete copy of HPV-16 DNA. The E6 and E7 open reading frames (ORFs) were completely conserved relative to other published HPV-16 sequences. Much of the non-coding region (NCR) was free of base changes, including complete conservation of several regulatory elements. Multiple mutations were identified in the remaining integrated HPV-16 DNA, which was composed of parts of the L1 and E1 ORFs. The extraordinary conservation of the E6/E7 DNA sequence, as compared with other regions of the integrated HPV-16 DNA, supports the role of E6/E7 in tumorigenesis.


Estimation of reflectance from camera responses by the regularized local linear model.
Because of the limited approximation capability of using fixed basis functions, the performance of reflectance estimation obtained by traditional linear models will not be optimal. We propose an approach based on the regularized local linear model. Our approach performs efficiently and knowledge of the spectral power distribution of the illuminant and the spectral sensitivities of the camera is not needed. Experimental results show that the proposed method performs better than some well-known methods in terms of both reflectance error and colorimetric error.