Negative Symptoms in Patients With Alzheimer's Disease.
This study applies the concept of "negative symptoms," previously used in schizophrenia, to dementia of the Alzheimer type (DAT) and examines the relationship of negative symptoms to cognitive deficits and depression. The negative symptom subscale of the Positive and Negative Symptom Scale (PANSS-N), the Hamilton Depression Scale (Ham-D), and the Mini-Mental State Examination (MMSE) were administered to 26 patients with DAT and to 13 normal control subjects. The mean PANSS-N score in DAT patients was significantly higher than in control subjects. DAT patients demonstrated significant correlation between negative symptoms and cognitive deficits. Ham-D scores did not significantly correlate with MMSE or PANSS-N scores. These results indicate that negative symptoms are prevalent in DAT and do not result from depression.


A Novel Intraoperative Posture-Adjustment Apparatus for Correction of Cervical Lordosis in Anterior Cervical Surgery.
Cervical alignment is a crucial factor related to the success of anterior cervical surgical procedures. In patients with severe spinal cord compression, a traditional neck pillow (TNP) may not adequately correct cervical position during surgery. Therefore, the aim of this study was to introduce this innovative intraoperative posture-adjustment apparatus (IPAA), and explored its clinical and radiological results in cervical angle correction against TNP in patients who had undergone anterior cervical surgery. The clinical and radiological data of 86 patients who underwent anterior cervical surgery with a minimum follow-up period of 1 year were retrospectively reviewed. Of these, 58 patients underwent IPAA, whereas 28 underwent TNP. Radiological parameters such as the degree of C2-C7 lordosis (CL), functional spinal unit angle (FSUA), C7 slope (C7S), fusion rate, and adjacent segment disease (ASD) were recorded and compared between the groups. Clinical outcomes including the Japanese Orthopaedic Association (JOA), neck disability index (NDI), visual analogue scale (VAS) for neck and arm were recorded. Complications such as kyphosis, dysphagia, Braden Scale score, revision surgery, hematoma, cerebrospinal fluid leakage, wound infection, and deep venous thrombosis were also recorded. The independent t-test or Mann-Whitney U test was used to compare continuous data, and categorical variables were assessed using the Pearson's chi-square test or Fisher's exact test. Compared with the pre-operative data, the post-operative CL, FSUA, and C7S were significantly increased in both groups. CL, FSUA, and C7S in the IPAA group (14.44 ± 4.94°, 7.36 ± 2.91°, 16.54 ± 4.63°) were significantly higher than those in the TNP group (7.17 ± 8.19°, 4.99 ± 5.36°, 14.19 ± 4.48°; P < 0.05). Although there were no significant differences between the groups in terms of VAS arm and JOA scores, the post-operative and final follow-up NDI and VAS neck scores in the IPAA group were significantly lower than those in the TNP group (p < 0.05). At the last follow-up, the TNP group had significantly more kyphotic patients than the IPAA group (2 vs. 0, p = 0,041). There was no significant difference between the groups in terms of fusion rate, ASD, or complications such as dysphagia, Braden's Scale score, revision surgery, hematoma, cerebrospinal fluid leakage, wound infection, or deep venous thrombosis. IPAA was shown to be more effective than TNP in adjusting cervical alignment (CL, FSUA, and C7S). These findings suggest that IPAA could be used as an alternative way to TNP in neck setting and cervical alignment adjustment and IPAA could potentially improve clinical outcomes after anterior cervical surgery.


Pattern of alcohol administration and physical dependence.
The purpose of this work was to study the influence of the pattern of alcohol administration on the intensity of withdrawal syndrome. Some rats were intoxicated by inhalation of ethanol vapor. The ethanol concentration in atmosphere was increased throughout the whole experiment in such a manner that the blood alcohol concentration (BAC) during the experiment increased as a linear function of time. When the area under BAC curve was varied by changing the duration of alcohol administration and keeping constant the slope of BAC increase, the intensity of withdrawal syndrome increased with the duration of alcohol intoxication. When the duration of alcohol administration and the slopes of the BAC curves were varied in such a manner that the area under the BAC curves was kept constant, the severity of the withdrawal syndrome increased with the slope of the BAC curves.


Adoptively transferred experimental allergic encephalomyelitis in chimeric rats: identification of transferred cells in the lesions of the central nervous system.
Experimental allergic encephalomyelitis (EAE) was induced by adoptive transfer of myelin basic protein (MBP)-activated LEW spleen cells into (LEW x PVG/c) F1----LEW chimeras. By double-immunofluorescent staining using OX27, which is specific for RT1c, and monoclonal antibodies (mAb) against various T-cell antigens (TAg), inflammatory cells in the lesions of the central nervous system (CNS) were categorized into MBP-activated and transferred LEW T cells (TAg+ OX27-), accompanying T cells (TAg+ OX27+) of chimera origin and non-T cells (TAg- OX27+). Examination of the lesions at various stages of EAE revealed that transferred OX19 (CD5)+ T cells accounted for 46% of the total number of inflammatory cells at the preclinical stage, became reduced to 23% at the clinical stage and recovered to a level between those of the preclinical and clinical stages at the recovery stage. In parenchymal infiltrates, 93% of the total T cells were transferred cells at the preclinical stage, whereas 66% were present in perivascular aggregates. At the clinical stage, the proportion of transferred T cells in the parenchyma was not different from that in the perivascular cuffs. At the recovery stage, the proportion of transferred T cells in the parenchyma was increased. Collectively, MBP-activated and transferred T cells first appeared in the CNS parenchyma followed by infiltration of T and non-T cells of recipient (chimera) origin. All these inflammatory cells formed the lesions of full-blown EAE. At the recovery stage, inflammatory cells decreased in number in all the compartments of the CNS. Transferred T cells formed the major proportion of parenchymal infiltrates at this stage. These findings strongly suggest that transferred T cells remain in the CNS parenchyma longer than cells of chimera origin and that antigen-activated T cells have well-expressed CNS-homing activity.


Multiple test procedures of disease prevalence based on stratified partially validated series in the presence of a gold standard.
This paper discusses the problem of disease prevalence in clinical studies, focusing on multiple comparisons based on stratified partially validated series in the presence of a gold standard. Five test statistics, including two Wald-type test statistics, the inverse hyperbolic tangent transformation test statistic, likelihood ratio test statistic, and score test statistic, are proposed to conduct multiple comparisons. To control the overall type I error rate, several adjustment procedures are developed, namely the Bonferroni, Single-step adjusted MaxT, Single-step adjusted MinP, Holm's Step-down, and Hochberg's step-up procedures, based on these test statistics. The performance of the proposed methods is evaluated through simulation studies in terms of the empirical type I error rate and empirical power. Simulation results show that the Single-step adjusted MaxT procedure and Single-step adjusted MinP procedure generally outperform the other three procedures, and these two test procedures based on all test statistics have satisfactory performance. Notably, the Single-step adjusted MinP procedure tends to exhibit higher empirical power than the Single-step adjusted MaxT procedure. Furthermore, the Step-down and Step-up procedures show greater power compared to the Bonferroni method. The study also observes that as the validated ratio increases, the empirical type I errors of all test procedures approach the nominal level while maintaining higher power. Two real examples are presented to illustrate the proposed methods.


The effect of liver transplantation in a 13-year-old boy with erythropoietic protoporphyria.
A 13-year-old boy who had had recurrent photosensitive skin reactions due to erythropoietic protoporphyria from 18 months of age, suddenly developed rapidly progressive hepatic failure with increasing cholestatic jaundice and variceal bleeding. Liver biopsy confirmed extensive protoporphyrin deposition with cirrhosis, and so orthotopic liver transplantation was performed. Postoperatively his skin rash settled within 72 hr, and in spite of subsequent exposure to the sun he has had no further skin reaction or blistering, although he does still have some itching. He made a good recovery and was able to return to school within six months of operation. Prior to liver transplantation, the hepatic ferrochelatase activity was reduced to only 0.81 nmol zinc-protoporphyrin formed/mg protein/hr (controls 3.30 +/- 1.00 nmol zinc-protoporphyrin formed/mg protein/hr, while the red cell protoporphyrin level was markedly elevated at 188 mumol/L red cells (normal less than 1.6 mumol/L red cells). The free plasma porphyrin level of 0.95 mumol/L (normal less than 0.02 mumol/L), and the urinary and fecal porphyrin levels were also raised. Following liver grafting these elevated porphyrin levels fell rapidly, with the red cell protoporphyrin level dropping to 10% of its preoperative value, and the rest returning to virtually normal within three months of operation.


A Review Study about the Effect of Chitosan Nanocarrier on Improving the Efficacy of Amphotericin B in the Treatment of Leishmania from 2010 to 2020.
In the present review study, the published articles from 2010-2020 that evaluated the effect of chitosan nanocarrier on the efficacy of amphotericin B (AmB) in the treatment of leishmaniasis, have been considered. Leishmania is a parasitic tropical disease in the world and is treated with AmB as one of the main therapeutic agents. However, the clinical application of AmB is limited due to its toxicity and insolubility issues. Using nanoparticles and, in particular, chitosan, nanocarrier seems a promising approach to overcome these problems. Therefore, various doses of AmB have been loaded in chitosan nanoparticles in different studies and the results of these studies demonstrated that by increasing the drug loading efficiency and decreasing the toxicity, the potency of the nanoformulation to inhibit and to kill the parasite is increased. In this regard, the results of a study performed in 2018, demonstrated that chitosan nanoparticles with the higher dose of drug loading were the most effective formulation to inhibit and kill the parasite. Thus, chitosan nanocarrier can consider as an appropriate candidate in the future to inhibit and kill the Leishmania parasite without causing side effects.


A perfect stimuli-responsive magnetic nanocomposite for intracellular delivery of doxorubicin.
Iron oxide nanoparticles (IONs) have been extensively applied in cancer therapy and theranostics due to their admissible magnetic properties, excellent chemical stability and biocompatibility. Herein, a novel stimuli-responsive magnetic nanocomposite was synthesized for cancer therapy; thereby, the triblock copolymer of poly[(2-succinyloxyethylmethacrylate)-b-(N-isopropylacrylamide)-b-dimethylaminoethylmethacrylate) [poly(SEMA-b-NIPAM-b-DMAEMA)] was prepared by reversible addition of fragmentation chain transfer (RAFT) polymerization. This triblock copolymer with carboxylic groups of succinyloxyethylmethacrylate was adsorbed onto the surface of Fe3O4 nanoparticles. The morphology, nanocomposite properties and stimuli-responsive behaviours were investigated by field emission scanning electron microscopy, X-ray diffraction, dynamic light scattering, vibrating sample magnetometer (VSM) and thermogravimetric analysis. Doxorubicin (DOX) encapsulation efficacy was 94.3%. Release behaviours of DOX from the magnetic nanocomposite exhibited that the rate of DOX release could be efficiently controlled through temperature and pH. The cytotoxicity of the drug was investigated in vitro against breast cancer cell line (MCF7) using (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) (MTT) assays, 4',6-diamidino-2-phenylindole (DAPI) staining and cellular uptake. In conclusion, the synthesized DOX@nanocomposite can be applied in theranostic applications and anticancer drug delivery owing to admissible properties.


Nature and strength of interlayer binding in graphite.
We compute the interlayer bonding properties of graphite using an ab initio many-body theory. We carry out variational and diffusion quantum Monte Carlo calculations and find an equilibrium interlayer binding energy in good agreement with most recent experiments. We also analyze the behavior of the total energy as a function of interlayer separation at large distances comparing the results with the predictions of the random phase approximation.


Effects of surface charge and palladium on hepatic and kidney injury induced by polystyrene nanoparticles co-administered to mice with paraquat and cisplatin.
Recently, with the advancement of nanotechnology, various nanoparticles have been developed and used in fields such as electronics, cosmetics, and foods. However, the toxicity of nanoparticles has yet to be fully investigated. In particular, the interactions between nanoparticles and therapeutic drugs require further study. We previously reported that unmodified polystyrene nanoparticles with a particle size of 50 nm (NPP50) co-administered with paraquat (PQ) or cisplatin (CDDP) induce hepatic and kidney injury. Here, we determined if NPP50 modified with the amino group (NPP50-NH2), carboxyl group (NPP50-COOH), or palladium (Pd-NPP50) caused liver or kidney injury when co-administered with PQ or CDDP. The results showed that when NPP50-NH2, NPP50-COOH, or Pd-NPP50 was administered alone via the mouse tail vein, serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and blood urea nitrogen (BUN) did not increase or cause injury. When NPP50, NPP50-NH2, NPP50-COOH, or Pd-NPP50 was co-administered with PQ, serum levels of ALT and AST increased in the NPP50 group but did not increase in the NPP50-NH2, NPP50-COOH, or Pd-NPP50 groups. When NPP50-NH2, NPP50-COOH, or Pd-NPP50 was co-administered with CDDP, ALT, AST, and BUN values did not increase. These data suggest that injury due to the interaction of polystyrene nanoparticles with CDDP or PQ can be suppressed by changes in the surface charge of nanoparticles or by Pd modification.


Vulnerable windows define susceptibility to alternans and spatial discordance.
Electrophysiological alternans is a beat-to-beat alternation of the action potential duration and/or Ca(2+) transient amplitude and is linked to ventricular arrhythmias. We investigated the significance of various rate parameters under different experimental conditions with respect to alternans incidence and the propensity for spiral wave formation. Voltage and Ca(2+) were optically mapped in monolayers of neonatal rat ventricular myocytes. Alternans did not occur at physiological temperature, but its incidence increased significantly at lowered temperatures. Pacing cycle length for spatially concordant alternans onset (PCL(C)), PCL for spatially discordant alternans onset (PCL(D)), and minimum cycle length for loss of 1:1 or 2:2 capture (MCL) also significantly increased with lower temperature but in a way such that the differences between PCL(C) and MCL and between PCL(D) and MCL widened. These results provided the rationale to identify the former difference as the alternans vulnerable window (AVW; in ms) and the latter difference as the discordant alternans vulnerable window (AVW(D); in ms). Computational simulations showed that interventions that widen AVW, including altered Ca(2+) cycling and enhanced K(+) currents, also promote alternans, regardless of whether PCL(C) or MCL increased or decreased. The simulation results were confirmed experimentally by addition of the ATP-sensitive K(+) channel agonist pinacidil. Mathematical analysis provided a theoretical basis linking the size of AVW to the incidence of alternans. Finally, experiments showed that the size of AVW(D) is related to the incidence of spatially discordant alternans and, additionally, to the incidence of spiral wave formation. In conclusion, vulnerable windows can be defined that are strongly correlated with alternans incidence, spatial discordance, and spiral wave formation.


Crystal structure of type 1 ribonuclease H from hyperthermophilic archaeon Sulfolobus tokodaii: role of arginine 118 and C-terminal anchoring.
The crystal structure of ribonuclease HI from the hyperthermophilic archaeon Sulfolobus tokodaii (Sto-RNase HI) was determined at 1.6 A resolution. Sto-RNase HI exhibits not only RNase H activity but also double-stranded RNA-dependent ribonuclease (dsRNase) activity. The main-chain fold and steric configurations of the four acidic active-site residues of Sto-RNase HI are very similar to those of other type 1 RNases H. However, Arg118 of Sto-RNase HI is located at the position in which His124 of E. coli RNase HI, His539 of HIV-1 RNase H, and Glu188 of Bacillus halodurans RNase H are located. The mutation of this residue to Ala considerably reduced both the RNase H and dsRNase activities without seriously affecting substrate binding, suggesting that Arg118 is involved in catalytic function. This residue may promote product release by perturbing the coordination of the metal ion A as proposed for Glu188 of B. halodurans RNase H. In addition, the extreme C-terminal region of Sto-RNase HI is anchored to its core region by one disulfide bond and several hydrogen bonds. Differential scanning calorimetry measurements indicated that Sto-RNase HI is a hyperstable protein with a melting temperature of 102 degrees C. The mutations of the cysteine residues forming disulfide bond or elimination of the extreme C-terminal region greatly destabilized the protein, indicating that anchoring of the C-terminal tail is responsible for hyperstabilization of Sto-RNase HI.


Optimization of vascular-targeting drugs in a computational model of tumor growth.
A biophysical tool is introduced that seeks to provide a theoretical basis for helping drug design teams assess the most promising drug targets and design optimal treatment strategies. The tool is grounded in a previously validated computational model of the feedback that occurs between a growing tumor and the evolving vasculature. In this paper, the model is particularly used to explore the therapeutic effectiveness of two drugs that target the tumor vasculature: angiogenesis inhibitors (AIs) and vascular disrupting agents (VDAs). Using sensitivity analyses, the impact of VDA dosing parameters is explored, as is the effects of administering a VDA with an AI. Further, a stochastic optimization scheme is utilized to identify an optimal dosing schedule for treatment with an AI and a chemotherapeutic. The treatment regimen identified can successfully halt simulated tumor growth, even after the cessation of therapy.


Inertial Separation of Particles Assisted by Symmetrical Sheath Flows in a Straight Microchannel.
Over the past two decades, inertial microfluidics, which works at an intermediate range of Reynolds number (∼1 < Re < ∼100), has been widely used for particle separation due to its high-throughput and label-free features. This work proposes a novel method for continuous separation of particles by size using inertial microfluidics, with the assistance of symmetrical sheath flows in a straight microchannel. Here, larger particles (>3 μm) are arranged close to the channel sidewalls, while smaller particles (<2 μm) remain flowing along the channel centerline. This conclusion is supported by experimental data with particles of different sizes ranging from 0.79 to 10.5 μm. Symmetrical Newtonian sheath flows are injected on both sides of particle mixtures into a straight rectangular microchannel with an aspect ratio (AR = height/width) of 2.5. Results show that the separation performance of the developed microfluidic device is affected by three main factors: channel length, total flow rate, and flow rate ratio of sheath to sample. Besides, separation of platelets from whole blood is demonstrated. The developed microfluidic platform owns the advantages of low fabrication cost, simple experiment setup, versatile selections of particle candidates, and stable operations. This systematic study provides a new perspective for particle separation, which is expected to find applications across various fields spanning physics, biology, biomedicine, and industry.


Effect of High-Volume Injection, Platelet-Rich Plasma, and Sham Treatment in Chronic Midportion Achilles Tendinopathy: A Randomized Double-Blinded Prospective Study.
Injection therapies are often considered alongside exercise for chronic midportion Achilles tendinopathy (AT), although evidence of their efficacy is sparse. To determine whether eccentric training in combination with high-volume injection (HVI) or platelet-rich plasma (PRP) injections improves outcomes in AT. Randomized controlled trial; Level of evidence, 1. A total of 60 men (age, 18-59 years) with chronic (>3 months) AT were included and followed for 6 months (n = 57). All participants performed eccentric training combined with either (1) one HVI (steroid, saline, and local anesthetic), (2) four PRP injections each 14 days apart, or (3) placebo (a few drops of saline under the skin). Randomization was stratified for age, function, and symptom severity (Victorian Institute of Sports Assessment-Achilles [VISA-A]). Outcomes included function and symptoms (VISA-A), self-reported tendon pain during activity (visual analog pain scale [VAS]), tendon thickness and intratendinous vascularity (ultrasonographic imaging and Doppler signal), and muscle function (heel-rise test). Outcomes were assessed at baseline and at 6, 12, and 24 weeks of follow-up. VISA-A scores improved in all groups at all time points ( P < .05), with greater improvement in the HVI group (mean ± SEM, 6 weeks = 27 ± 3 points; 12 weeks = 29 ± 4 points) versus PRP (6 weeks = 14 ± 4; 12 weeks = 15 ± 3) and placebo (6 weeks = 10 ± 3; 12 weeks = 11 ± 3) at 6 and 12 weeks ( P < .01) and in the HVI (22 ± 5) and PRP (20 ± 5) groups versus placebo (9 ± 3) at 24 weeks ( P < .01). VAS scores improved in all groups at all time points ( P < .05), with greater decrease in HVI (6 weeks = 49 ± 4 mm; 12 weeks = 45 ± 6 mm; 24 weeks = 34 ± 6 mm) and PRP (6 weeks = 37 ± 7 mm; 12 weeks = 41 ± 7 mm; 24 weeks = 37 ± 6 mm) versus placebo (6 weeks = 23 ± 6 mm; 12 weeks = 30 ± 5 mm; 24 weeks = 18 ± 6 mm) at all time points ( P < .05) and in HVI versus PRP at 6 weeks ( P < .05). Tendon thickness showed a significant decrease only in HVI and PRP groups during the intervention, and this was greater in the HVI versus PRP and placebo groups at 6 and 12 weeks ( P < .05) and in the HVI and PRP groups versus the placebo group at 24 weeks ( P < .05). Muscle function improved in the entire cohort with no difference between the groups. Treatment with HVI or PRP in combination with eccentric training in chronic AT seems more effective in reducing pain, improving activity level, and reducing tendon thickness and intratendinous vascularity than eccentric training alone. HVI may be more effective in improving outcomes of chronic AT than PRP in the short term. Registration: NCT02417987 ( ClinicalTrials.gov identifier).


Indicators of Self-Determination in Therapeutic Songwriting Lyrics Created by Adults with High LDL Cholesterol.
Individuals with low-density lipoprotein cholesterol ≥190 mg/dL are at high risk for atherosclerotic cardiovascular disease events. Our goal was to determine if adults with this condition would express important psychological, health, and motivation themes when generating lyrics during music therapy. Thirty-one participants each created their own original song with the help of a music therapist. The lyrics were analyzed using a deductive approach guided by Self-Determination Theory (specifically the satisfaction or frustration of basic psychological needs): (1) for each entire song (macro-analysis) and (2) line-by-line (micro-analysis). Song lyrics generated during music therapy sessions by patients with a low-density lipoprotein cholesterol ≥190 mg/dL revealed the presence of the three basic needs (autonomy, competence, and relatedness) of Self-Determination Theory. The most prevalent theme identified in the macro-analysis of songs was autonomy satisfaction, coded in 25 songs (27.17% of all macro codes), and followed by competence satisfaction in 17 songs (18.48%) and relatedness satisfaction in 15 songs (16.3%). Line-by-line micro-analysis of lyrics revealed that at least one basic need of Self-Determination Theory was present in 277 of the unique lyric lines (50%); 107 (19%) for relatedness, 101 (18%) for autonomy, and 69 (13%) for competence. Need satisfaction occurred more frequently than need frustration in both analyses. However, depending on the level of analysis (macro or micro), results differed as to which themes were most prevalent. These results indicate that therapeutic songwriting may be a unique way to identify the basic psychological needs that, when satisfied, indicate self-determination.


Itching for change: Embracing modern flea and tick product development.
The development and regulatory approval of ectoparasiticides, including flea and tick control products, involves decades-old methods and the use of large numbers of animals to evaluate toxicity and efficacy. Animals also are used to rear (breed and feed) fleas and ticks for later use in testing. Non-animal methods for regulatory-required testing and rearing currently exist and, with further development, others could soon become available. Here we provide an overview of the state-of-the-science of non-animal methods for rearing and regulatory-required efficacy testing of flea and tick control products. Several remaining challenges as well as recommendations on the steps needed to replace animals in the evaluation of these products are discussed.


Rapid Investigation of Functional Roles of Genes in Regulation of Leaf Senescence Using Arabidopsis Protoplasts.
Leaf senescence is the final stage of leaf development preceding death, which involves a significant cellular metabolic transition from anabolism to catabolism. Several processes during leaf senescence require coordinated regulation by senescence regulatory genes. In this study, we developed a rapid and systematic cellular approach to dissect the functional roles of genes in senescence regulation through their transient expression in Arabidopsis protoplasts. We established and validated this system by monitoring the differential expression of a luciferase-based reporter that was driven by promoters of SEN4 and SAG12, early and late senescence-responsive genes, depending on effectors of known positive and negative senescence regulators. Overexpression of positive senescence regulators, including ORE1, RPK1, and RAV1, increased the expression of both SEN4- and SAG12-LUC while ORE7, a negative senescence regulator decreased their expression. Consistently with overexpression, knockdown of target genes using amiRNAs resulted in opposite SAG12-LUC expression patterns. The timing and patterns of reporter responses induced by senescence regulators provided molecular evidence for their distinct kinetic involvement in leaf senescence regulation. Remarkably, ORE1 and RPK1 are involved in cell death responses, with more prominent and earlier involvement of ORE1 than RPK1. Consistent with the results in protoplasts, further time series of reactive oxygen species (ROS) and cell death assays using different tobacco transient systems reveal that ORE1 causes acute cell death and RPK1 mediates superoxide-dependent intermediate cell death signaling during leaf senescence. Overall, our results indicated that the luciferase-based reporter system in protoplasts is a reliable experimental system that can be effectively used to examine the regulatory roles of Arabidopsis senescence-associated genes.


Exploring the role of cyclosporine in reducing homograft degeneration post-Ross.
The Ross procedure is safe and effective for children with aortic valve disease. Pulmonary homograft degeneration, proposed to be immune-mediated, is a major cause of reoperation. Cyclosporine increased homograft valve survival in animals, but has not been studied in humans. To investigate the efficacy of low-dose cyclosporine in preventing homograft degeneration and complications, a retrospective historical-controlled study was performed on data of all children who underwent Ross procedure and received cyclosporine. The primary endpoint was homograft function at the last follow-up; secondary endpoints were readmission, reoperation, death, and safety. Seventeen patients were matched with 16 controls. At the end of the follow-up period (cyclosporine, 6.7 years; controls, 8 years), homograft stenosis and/or regurgitation were present in half of all patients. Three (18%) patients in the cyclosporine group and 5 (29%) in the control group were readmitted. Surgical intervention due to homograft failure was needed in 1 (6%) cyclosporine patient and 3 (19%) of the controls. Although cyclosporine failed to show a significant difference in signs of homograft degeneration, it might decrease the need for reoperation following the Ross procedure. Larger prospective well-designed studies are required to confirm these findings.


Rats learn to eat more to avoid hunger.
Several recent experiments have provided evidence that the ingestion of a distinctive food by rats can be a learnt instrumental act as well as an associatively conditioned reaction. In the previous work, maintenance food was withheld for shorter and longer durations on different days following access to the training food. Extra eating before the longer fast was interpreted as avoidance of hunger. This interpretation was based on the evidence showing that extra eating as a result of classical conditioning comes from pairing food stimuli with the presence of little or no hunger because of repletion with energy nutrients. The theory that the extra eating arose from a response-depletion contingency was tested in the present experiment by training rats on only a long fast or only a short fast. Greater increase in intake was seen before the longer fast. The results also replicated previously seen cycles of increase, decrease, and renewed increase in putative deficit-avoidant eating over about three trials, indicating that the extra eating reduces the response-reinforcing hunger and that the consequent part-extinction restores reinforcement. The shape of the learning curve was consistent with these cycles occurring from the start of training, further supporting the view that the increase in food intake before a long delay in refeeding is hunger-reinforced instrumental behaviour.


Expression and characterization of Aspergillus thermostable phytases in Pichia pastoris.
Two thermostable phytases were identified from Thai isolates of Aspergillus japonicus BCC18313 (TR86) and Aspergillus niger BCC18081 (TR170). Both genes of 1404 bp length, coding for putative phytases of 468 amino acid residues, were cloned and transferred into Pichia pastoris. The recombinant phytases, r-PhyA86 and r-PhyA170, were expressed as active extracellular, glycosylated proteins with activities of 140 and 100 U mL(-1), respectively. Both recombinant phytases exhibited high affinity for phytate but not for p-nitrophenyl phosphate. Optimal phytase activity was observed at 50 degrees C and pH 5.5. High thermostability, which is partly dependent on glycosylation, was demonstrated for both enzymes, as >50% activity was retained after heating at 100 degrees C for 10 min. The recombinant phytases also exhibited broad pH stability from 2.0 to 8.0 and are resistant to pepsin. In vitro digestibility tests suggested that r-PhyA86 and r-PhyA170 are at least as efficient as commercial phytase for hydrolyzing phytate in corn-based animal feed and are therefore suitable sources of phytase supplement.


Effect of the duration of labor on postpartum postvoid residual bladder volume.
In order to investigate the possibility of protracted labor as a risk factor for postpartum urinary retention and to study the relation between duration of labor and postpartum day 1 postvoid residual bladder volume, the postpartum postvoid residual bladder volume (PVRBV) of a group of patients was studied using ultrasonography. Out of 707 patients investigated during a 2-month study period, a homogeneous group of 164 patients, with possible risk factors for postpartum urinary retention being controlled, was studied. The homogeneous group's postpartum day 1 postvoid residual bladder volumes were assessed by ultrasonography and analyzed with respect to the duration of labor. The incidence of postpartum urinary retention ( > or = 150 ml) was 11% in this homogeneous group. Labor duration longer than or equal to 800 min was associated with a higher incidence of postpartum urinary retention (chi2 test; p < 0.05). Moreover, there is a direct relationship between the duration of labor and PVRBV which is described by a quadratic regression curve. Protracted labor longer than or equal to 800 min is a risk factor for postpartum urinary retention. The PVRBV is directly related to the duration of labor.


Motor Compensation Strategies for Reduced Upper Limb Function Among Individuals With Duchenne Muscular Dystrophy.
The purpose of this longitudinal study was to identify and verify the compensatory motor strategies for upper limb functioning of individuals with Duchenne Muscular Dystrophy (DMD). We evaluated 32 patients diagnosed with DMD (aged 6-19 years) for cognitive and motor functioning using the Mini Mental State Examination (MMSE), Vignos Scale Jebsen Taylor Test (JTT) and Functional Skill Scale (FSS) at baseline testing and over retest intervals of six and 12 months. We used the MMSE to screen participants for capacity to engage in the research, and we analyzed absolute and percentile changes in the frequency distribution of motor strategies participants used on each JTT subtest. We also used analysis of variance with repeated measures and Bonferroni post-hoc testing of multiple comparisons to identify disease progression through FSS scores. We observed an increased frequency of compensatory motor strategies over six months. We recommend the associated use of the JTT and FSS to assess patients with DMD, since we observed worsened movement quality over a time interval of six months even while essential motor competence was maintained.


Retroelement dynamics and a novel type of chordate retrovirus-like element in the miniature genome of the tunicate Oikopleura dioica.
Retrotransposable elements have played an important role in shaping eukaryotic DNA, and their activity and turnover rate directly influence the size of genomes. With approximately 15,000 genes within 65-75 megabases, the marine tunicate Oikopleura dioica, a nonvertebrate chordate, has the smallest and most compact genome ever found in animals. Consistent with a massive elimination of retroelements, only one apparently novel clade of non-long terminal repeat (non-LTR) retrotransposons was detected within 41 megabases of nonredundant genomic sequences. In contrast, at least six clades of non-LTR elements were identified in the less compact genome of the tunicate Ciona intestinalis. Unexpectedly, Ty3/gypsy-related Tor LTR retrotransposons presented an astonishing level of diversity in O. dioica. They were generally poorly or apparently not corrupted, indicating recent activity. Both Tor3 and Tor4b families bore an envelope-like open reading frame, suggesting possible horizontal acquisition through infection. The Tor4b envelope-like gene might have been obtained from a paramyxovirus (RNA virus). Tor3 and Tor4b are phylogenetically clearly distinct from vertebrate retroviruses (Retroviridae) and are more reminiscent of certain insect and plant sequences. Tor elements potentially represent a so far unknown, ancient type of infectious retroelement in chordates. Their distribution and transmission dynamics in tunicates and other chordates deserve further study.


Is Mitochondrial Oxidative Stress the Key Contributor to Diaphragm Atrophy and Dysfunction in Critically Ill Patients?
Diaphragm dysfunction is prevalent in the progress of respiratory dysfunction in various critical illnesses. Respiratory muscle weakness may result in insufficient ventilation, coughing reflection suppression, pulmonary infection, and difficulty in weaning off respirators. All of these further induce respiratory dysfunction and even threaten the patients' survival. The potential mechanisms of diaphragm atrophy and dysfunction include impairment of myofiber protein anabolism, enhancement of myofiber protein degradation, release of inflammatory mediators, imbalance of metabolic hormones, myonuclear apoptosis, autophagy, and oxidative stress. Among these contributors, mitochondrial oxidative stress is strongly implicated to play a key role in the process as it modulates diaphragm protein synthesis and degradation, induces protein oxidation and functional alteration, enhances apoptosis and autophagy, reduces mitochondrial energy supply, and is regulated by inflammatory cytokines via related signaling molecules. This review aims to provide a concise overview of pathological mechanisms of diaphragmatic dysfunction in critically ill patients, with special emphasis on the role and modulating mechanisms of mitochondrial oxidative stress.


Competing fragmentation processes of β-substituted propanoate ions upon collision-induced dissociation.
When subjected to collisional activation, gas-phase carboxylate ions typically undergo decarboxylation. However, alternative fragmentation processes dominate when the carboxylate group is located within certain structural motifs. In this work, the fragmentation processes of β-substituted carboxylate ions are characterized to improve correlations between reactivity and structure. Mass spectra were collected using both ion trap and triple quadrupole mass spectrometers operating in the negative ion mode; collision-induced dissociation (CID) of ions was used to study the relationship between product ions and the structures of their precursor ions. Quantum mechanical computations were performed on a full range of reaction geometries at the MP2/6-311++G(2d,p)//B3LYP/6-31++G(2d,p) level of theory. For a series of β-substituted carboxylate ions, a product ion corresponding to the anion of the β-substituent was obtained upon CID. Detailed computations indicated that decarboxylative elimination and at least one other fragmentation mechanism had feasible energetics for the formation of substituent anions differing in their gas-phase basicities. Predicted energetics for anti- and synperiplanar alignments in the transition structures for decarboxylative elimination correlated with the positions of crossover points in breakdown curves acquired for conformationally constrained ions. The feasibility of more than one mechanism was established for the fragmentation of β-substituted propanoates. The contribution of each mechanistic pathway to the formation of the substituent anion was influenced by structural variations and conformational constraints, but mostly depended on the nature of the substituent. Copyright © 2016 John Wiley & Sons, Ltd.


Possible links between sickle cell crisis and pentavalent antimony.
For over 60 years, pentavalent antimony (Sb(v)) has been the first-line treatment of leishmaniasis. Sickle cell anemia is a disease caused by a defect in red blood cells, which among other things can cause vasooclusive crisis. We report the case of a 6-year-old child with leishmaniasis who during treatment with meglumine antimoniate developed a sickle cell crisis (SCC). No previous reports describing the relationship between antimonial drugs and sickle cell disease were found. Reviews of both the pathophysiology of SCC and the mechanism of action of Sb(v) revealed that a common pathway (glutathione) may have resulted in the SCC. ChemoText, a novel database created to predict chemical-protein-disease interactions, was used to perform a more expansive and systematic review that was able to support the association between glutathione, Sb(v), and SCC. Although suggestive evidence to support the hypothesis, additional research at the bench would be needed to prove Sb(v) caused the SCC.


Enhanced production of interleukin-6 in mice with type II collagen-induced arthritis.
We established an interleukin-6 (IL-6)-dependent cell line from murine plasmacytoma MOPC-104E cells. This cell line (designated PIL-6) was found to respond to murine and to human IL-6, but not to any other cytokines. We used this cell line to investigate the involvement of IL-6 production in type II collagen-induced arthritis in DBA/1 mice. Only marginal IL-6 activity was detected in sera from DBA/1 mice inoculated with Freund's complete adjuvant (FCA) alone, with an unrelated protein (bovine serum albumin) plus FCA, or with type II collagen plus Freund's incomplete adjuvant. However, enhanced IL-6 activity was observed in DBA/1 mice that had been injected with type II collagen plus FCA to induce arthritis. The elevated level of serum IL-6 activity was associated with high levels of IL-6 produced when lymph node cells from arthritic mice were stimulated in vitro with type II collagen. We also found that the L3T4+ T cell subset is responsible for the enhanced production of IL-6 in arthritic mice. The results are discussed in the context of potential roles of IL-6 in the induction and/or expression of chronic, progressive arthritis.


[Fracture of the glenoid fossa without mandibular condylar dislocation or fracture: two case reports].
The mandibular condyle region which protects the middle cranial fossa from facial and jaw traumas has an excellent osteomuscular structure. Condylar structures reduce or limit the force of trauma. Most importantly, the condylar neck is the weakest part of the mandible and is easily fractured without dislocation. Generally, this mechanism prevents condylar penetration into the middle cranial fossa; however, there are condylar penetration into the middle cranial fossa can be rarely. Glenoid fossa fractures without mandibular condylar fracture and dislocation can be made. In this article, we present two cases to assess the isolated glenoid fossa fractures of the temporal bone.


Podocyte-specific overexpression of GLUT1 surprisingly reduces mesangial matrix expansion in diabetic nephropathy in mice.
Increased expression of the facilitative glucose transporter, GLUT1, leads to glomerulopathy that resembles diabetic nephropathy, whereas prevention of enhanced GLUT1 expression retards nephropathy. While many of the GLUT1-mediated effects are likely due to mesangial cell effects, we hypothesized that increased GLUT1 expression in podocytes also contributes to the progression of diabetic nephropathy. Therefore, we generated two podocyte-specific GLUT1 transgenic mouse lines (driven by a podocin promoter) on a db/m C57BLKS background. Progeny of the two founders were used to generate diabetic db/db and control db/m littermate mice. Immunoblots of glomerular lysates showed that transgenic mice had a 3.5-fold (line 1) and 2.1-fold (line 2) increase in GLUT1 content compared with wild-type mice. Both lines showed similar increases in fasting blood glucose and body weights at 24 wk of age compared with wild-type mice. Mesangial index (percent PAS-positive material in the mesangial tuft) increased 88% (line 1) and 75% (line 2) in the wild-type diabetic mice but only 48% (line 1) and 39% (line 2) in the diabetic transgenic mice (P < 0.05, transgenic vs. wild-type mice). This reduction in mesangial expansion was accompanied by a reduction in fibronectin accumulation, and vascular endothelial growth factor (VEGF) levels increased only half as much in the transgenic diabetic mice as in wild-type diabetic mice. Levels of nephrin, neph1, CD2AP, podocin, and GLUT4 were not significantly different in transgenic compared with wild-type mice. Taken together, increased podocyte GLUT1 expression in diabetic mice does not contribute to early diabetic nephropathy; surprisingly, it protects against mesangial expansion and fibronectin accumulation possibly by blunting podocyte VEGF increases.


[The functioning of emergency medical care in the Russian Federation: analysis of report documentation keeping].
The development of functioning of emergency medical care is one of directions of national health care development. The article presents analysis of indices of functioning of emergency medical care in the Russian Federation: number of stations (departments), medical personnel supply, rate of completed visits of emergency teams, number ofpersons cared during visits, number of hospitalized patients transported by emergency teams (shifts), number of cars of emergency medical care, number of road accidents visited by emergency teams, number of victims of road accidents, immediacy offunctioning. The history ofmaintenance of report documentation of emergency medical care is presented and its complicity of its filling-in is marked.


A new automated interpretation system for the 16PF.
A new computerized interpretation system for the 16PF is described. This system is based on the novel concept of attempting to simulate directly the diagnostic report-writing capabilities of a single clinician. Certain considerations regarding the problem of validity in respect to this area are brought up, and the general operation of the system is outlined.


Protein profile of cotyledon, tegument, and embryonic axis of mature acorns from a non-orthodox plant species: Quercus ilex.
Contrary to the orthodox seeds, recalcitrant Holm oak seeds possess the enzymatic machinery to start germination during the maturation phase. The protein profile of the different parts, mature seeds, of the Holm oak, a non-orthodox plant species, has been characterized using one- and two-dimensional gel electrophoresis coupled to matrix-assisted laser desorption ionization-time of flight mass spectrometry. Protein content and profiles of the three seed tissues (cotyledon, embryonic axis and tegument) were quite different. The embryonic axis showed 4-fold and 20-fold higher protein content than the cotyledon and the tegument, respectively. Two hundred and twenty-six variable proteins among the three seed parts were identified, being classified according to their function into eight main groups. The cotyledon presented the highest number of metabolic and storage proteins (89% of them are legumin) compared to the embryonic axis and tegument. The embryonic axis had the highest number of the species within the protein fate group. The tegument presented the largest number of the defense-/stress-related and cytoskeleton proteins. This distribution is in good agreement with the biological role of the tissues. The study of the seed tissue proteome demonstrated a compartmentalization of pathways and a division of metabolic tasks between embryonic axis, cotyledon and tegument. This compartmentalization uncovered in our study should provide a starting point for understanding, at the molecular level, the particularities of the recalcitrant seeds.


Effect of a brief video intervention on incident infection among patients attending sexually transmitted disease clinics.
Sexually transmitted disease (STD) prevention remains a public health priority. Simple, practical interventions to reduce STD incidence that can be easily and inexpensively administered in high-volume clinical settings are needed. We evaluated whether a brief video, which contained STD prevention messages targeted to all patients in the waiting room, reduced acquisition of new infections after that clinic visit. In a controlled trial among patients attending three publicly funded STD clinics (one in each of three US cities) from December 2003 to August 2005, all patients (n = 38,635) were systematically assigned to either a theory-based 23-min video depicting couples overcoming barriers to safer sexual behaviors, or the standard waiting room environment. Condition assignment alternated every 4 wk and was determined by which condition (intervention or control) was in place in the clinic waiting room during the patient's first visit within the study period. An intent-to-treat analysis was used to compare STD incidence between intervention and control patients. The primary endpoint was time to diagnosis of incident laboratory-confirmed infections (gonorrhea, chlamydia, trichomoniasis, syphilis, and HIV), as identified through review of medical records and county STD surveillance registries. During 14.8 mo (average) of follow-up, 2,042 patients (5.3%) were diagnosed with incident STD (4.9%, intervention condition; 5.7%, control condition). In survival analysis, patients assigned to the intervention condition had significantly fewer STDs compared with the control condition (hazard ratio [HR], 0.91; 95% confidence interval [CI], 0.84 to 0.99). Showing a brief video in STD clinic waiting rooms reduced new infections nearly 10% overall in three clinics. This simple, low-intensity intervention may be appropriate for adoption by clinics that serve similar patient populations. http://www.ClinicalTrials.gov (#NCT00137670).


DNA content in non-Hodgkin's lymphoma. Comparison between flow cytometry and cytogenetics in fresh and paraffin-embedded tissue.
DNA content of 36-non-Hodgkin's lymphomas was analyzed by flow cytometry (FCM) and cytogenetics (CG), 21 in fresh and 15 in paraffin-embedded tissue. The results of both techniques were coincident in 60% of the fresh tissue samples and in 45% of the paraffin-embedded ones, the reason for this difference could be the poor resolution of DNA histograms from paraffin-embedded tissue. All samples judged as aneuploid by FCM were aneuploid also by CG. Some samples with a hyperdiploid population by CG gave a diploid population by FCM with a 'false' high DNA-synthesis (S) fraction. From a technical point of view, CG and FCM have to be performed on the same fresh tissue.


Analysis of dose, dose-rate and treatment time in the production of injuries by radium treatment for cancer of the uterine cervix.
A retrospective study has been made of 15 patients who had developed severe complications to the bladder, rectum and ureters after radiation therapy for carcinoma of the cervix. Comprehensive dose distribution in the pelvis were calculated with computer assistance to visualize how the normal organs had been irradiated. The risk of normal tissue injury was analysed graphically with respect to the maximum radium dose, dose-rate and irradiation time. The two groups of data representing the injured and non-injured organs separate much better in a dose-rate versus dose plot than in a conventional Strandqvist type dose-time plot. This implies that in radium therapy, the dose-rate rather than the treatment time, is the important parameter in modifying the risk of normal tissue injury. Our results show a good separation of injured from non-injured cases only when the maximum values of dose and dose-rate were used. This suggests that clinically significant injury may develop from relatively small regions of high dose and dose-rate. Since the dose-rate varies from point to point in the pelvis (unlike treatment time), comprehensive determinations of dose-rate distributions are required in order to locate the sites of potential injuries.


[Cryptococcoma and amphotericin B. Therapy of cryptococcosis - animal experiments. 2nd Communication: Patho-histological results (author's transl)].
Since cryptococcosis is characterized by cryptococcoma formation, the antimycotic effect of amphothericin B was examined in view of such pathological-anatomical conditions. In white mice (NMRI), cryptococcoma formation was induced by intramuscular injection of Cryptococcus neoformans strain W71 into the hind leg (STAIB, 1962), using a suspension (0.2 ml) containing approximately 2.8 times 10-7 cells/ml. The mice were treated daily with 1 mg amphotericin B in 5% dimethyl sulfoxide by gastric intubation. Course of infection and effectivity of therapy were assessed by microbiological and patho-histological examination of the organs. In the present paper (2nd Communication) comparative patho-histological results in mice, treated with amphotericin B either immediately or from the 16th day p.i. or not at all, are reported. In the non-treated animals the course of infection we controlled by sacrificing 2 animals per day from the 2nd to the 25th day. Cryptococcoma found in the muscle, fat, and connective tissue in the hind leg of these animals were characterized by the two different patho-histological alterations: a) Masses of encapsulated cryptococci side by side were filling a paucireactive or non-reactive reticular structure with blood capillaries. b) Non-specific granulomatous tissue. The fungi were less abundantly found as non-encapsulated cells. On the 5th day after infection the first alterations due to dissemination were found in the lungs, then in other parenchymatous organs. Under immediate amphotericin B-therapy, no cryptococcoma was found at the place of infection; after a therapy of 30 days duration, C. neoformans could be detected in small conglomerates of non-encapsulated cells in muscle, fat and connective tissue. Histologically, a septic dissemination of the agent could not be found in this group. After a therapy of 25 days duration a shrinking of cryptococcoma was observed in animals treated from the 15th day after infection. Presumably this was caused by a loss of capsule and formation of non-specific granulomatous tissue. In the surroundings of blood vessels non-encapsulated cells were detectable. After therapy with amphotericin B, single cryptococci e.g. such disseminated into the lungs were increasingly showing morphological alterations which might be explained as forms of degeneration. The animal experiment in connection with microbiological and patho-histological follow-up studies is discussed with a view to the therapy of cryptococcosis in man. Because of the variable virulence of C. neoformans it has to be mentioned that this experiment was carried out with a strain of C. neoformans characterized by its capability to form cryptococcoma in mice.


A novel aminosaccharide compound blocks immune responses by Toll-like receptors and nucleotide-binding domain, leucine-rich repeat proteins.
Toll-like receptors (TLRs) and nucleotide-binding domain, leucine-rich repeat (NLR) proteins are two major forms of innate immune receptors that trigger inflammatory responses by various biological mechanisms such as cytokine production, recruitment of inflammatory cells, or activation of adaptive immunity. Although the innate immune system is designed to fight against infectious pathogens, excessive activation of TLR or NLR signaling pathways may lead to unwarranted inflammation with hazardous outcomes, including septic shock or inflammatory diseases. As part of the search for effective therapeutics to regulate these responses, here we show that a novel aminosaccharide compound, named DFK1012, inhibits immune responses caused by TLR and NLR activation. Treatment with DFK1012, but not its derivatives DFK845 or DFK846, strongly inhibited pro-inflammatory cytokine production upon stimulation via either TLR or NLR proteins in macrophages. Importantly, we have not observed cytotoxicity in any range of its working concentration. Treatment with DFK1012 did not interfere with TLR- or NLR-induced activation of p38 and JNK, phosphorylation/degradation of IκB, and subsequent nuclear translocation of NF-κB subunit p65, suggesting that the inhibitory activity of DFK1012 is not due to the suppression of downstream signaling. Indeed, DFK1012 did not impair transcription of pro-inflammatory cytokine genes but rather promoted post-translational degradation of pro-inflammatory cytokines. Therefore, DFK1012 is a novel anti-inflammatory compound that drives proteolysis of proinflammatory cytokines induced by TLR and NLR stimulation. DFK1012 may represent a novel class of potential therapeutic agents aimed at the treatment of inflammatory disorders.


Reversal of chronic molecular and cellular abnormalities due to heart failure by passive mechanical ventricular containment.
Passive mechanical containment of failing left ventricle (LV) with the Acorn Cardiac Support Device (CSD) was shown to prevent progressive LV dilation in dogs with heart failure (HF) and increase ejection fraction. To examine possible mechanisms for improved LV function with the CSD, we examined the effect of CSD therapy on the expression of cardiac stretch response proteins, myocyte hypertrophy, sarcoplasmic reticulum Ca2+-ATPase activity and uptake, and mRNA gene expression for myosin heavy chain (MHC) isoforms. HF was produced in 12 dogs by intracoronary microembolization. Six dogs were implanted with the CSD and 6 served as concurrent controls. LV tissue from 6 normal dogs was used for comparison. Compared with normal dogs, untreated HF dogs showed reduced cardiomyocyte contraction and relaxation, upregulation of stretch response proteins (p21ras, c-fos, and p38 alpha/beta mitogen-activated protein kinase), increased myocyte hypertrophy, reduced SERCA2a activity with unchanged affinity for calcium, reduced proportion of mRNA gene expression for alpha-MHC, and increased proportion of beta-MHC. Therapy with the CSD was associated with improved cardiomyocyte contraction and relaxation, downregulation of stretch response proteins, attenuation of cardiomyocyte hypertrophy, increased affinity of the pump for calcium, and restoration of alpha- and beta-MHC isoforms ratio. The results suggest that preventing LV dilation and stretch with the CSD promotes downregulation of stretch response proteins, attenuates myocyte hypertrophy and improves SR calcium cycling. These data offer possible mechanisms for improvement of LV function after CSD therapy.


Hepatitis B-related events in autologous hematopoietic stem cell transplantation recipients.
To investigate the frequency of occult hepatitis B, the clinical course of hepatitis B virus (HBV) reactivation and reverse seroconversion and associated risk factors in autologous hematopoietic stem cell transplantation (HSCT) recipients. This study was conducted in 90 patients undergoing autologous HSCT. Occult HBV infection was investigated by HBV-DNA analysis prior to transplantation, while HBV serology and liver function tests were screened prior to and serially after transplantation. HBV-related events including reverse seroconversion and reactivation were recorded in all patients. None of the patients had occult HBV prior to transplantation. Six (6.7%) patients were positive for HBV surface antigen (HBsAg) prior to transplantation and received lamivudine prophylaxis; they did not develop HBV reactivation after transplantation. Clinical HBV infection emerged in three patients after transplantation who had negative HBV-DNA prior to HSCT. Two of these three patients had HBV reactivation while one patient developed acute hepatitis B. Three patients had anti-HBc as the sole hepatitis B-related antibody prior to transplantation, two of whom developed hepatitis B reactivation while none of the patients with antibody to HBV surface antigen (anti-HBs) did so. The 14 anti-HBs- and/or anti-HBc-positive patients among the 90 HSCT recipients experienced either persistent (8 patients) or transient (6 patients) disappearance of anti-HBs and/or anti-HBc. HBsAg seroconversion and clinical hepatitis did not develop in these patients. Female gender and multiple myeloma emerged as risk factors for loss of antibody in regression analysis (P < 0.05). Anti-HBc as the sole HBV marker seems to be a risk factor for reactivation after autologous HSCT. Lamivudine prophylaxis in HbsAg-positive patients continues to be effective.


Skin Barrier Damage due to Prolonged Mask Use among Healthcare Workers and the General Population during the COVID-19 Pandemic: A Prospective Cross-Sectional Survey in China.
Coronavirus disease 2019 (COVID-19) has resurged in localized areas in China. Individuals wear masks to prevent the spread of droplets. However, skin barrier damage occurs because of the prolonged use of masks. To investigate the prevalence and associated risk factors of skin injuries among healthcare workers (HCWs) and the general population during the COVID-19 outbreak. A multicenter cross-sectional study of skin barrier damage caused by wearing masks was conducted using an online questionnaire between December 10 and December 31, 2020. Data regarding demographics, characteristics of facial skin damage, and information on masks were registered. Multivariate logistic regression was used to analyze factors associated with skin barrier damage, and odds ratios (OR) with 95% confidence intervals (CI) were used to establish correlation strength. A total of 1,538 responses were retrieved from 1,700 questionnaires (response rate, 90.47%), and 1,409 questionnaires were valid (effective response rate, 91.61%). The respondents comprised 567 HCWs (40.24%) and 842 individuals from the general population (59.76%). The prevalence of skin injuries was 46.03% among HCWs and 46.20% among the general population. History of chronic skin disease (OR, 6.01; 95% CI, 4.75-7.75), type of mask used (OR, 2.77; 95% CI, 1.95-3.93), daily wearing time (OR, 1.57; 95% CI, 1.36-1.82), and mask replacement cycle (OR, 0.76; 95% CI, 0.68-0.86) were associated with skin barrier damage. There was a high incidence of skin barrier damage due to prolonged mask use among HCWs and the general population, and treatment and prevention were inadequate. Attention needs to be given to strengthening comprehensive health education and popularization of science.


Spinnability of Starch Pastes.
We have developed apparatus to assess spinnability that uses an impedance to prevent of electrolysis. The spinning distance and the stress confirmed by measurement of dial gauge. A total of 10 starch pastes was prepared from corn, sago, katakuri, sweet potato, kuzu, edible canna, cassava, Indian lotus root, bracken, and potato, at 2% and 4% concentrations. The spinning distance of each starch paste showed a dependence on the concentration and the tensile velocity. The strain at the point of maximum stress increased in all samples with increases in the tensile velocity. The spinning energy increased with increase in the tensile velocity, with a particularly large dependence on the tensile velocity of potato. Cluster analysis was done using the spinning property values of 4% starch pastes as the parameters, which showed a division at a distance of 20, yielding four clusters, with each cluster showing a distinctive spinning pattern.


Tyrphostin AG490 agent modestly but significantly prevents onset of type 1 in NOD mouse; implication of immunologic and metabolic effects of a Jak-Stat pathway inhibitor.
Previously, we have reported that the Jak-Stat signaling pathway is defective in NOD mice. In this study, prediabetic female NOD mice (4 weeks) were treated by intraperitoneal injection either with AG490 or DMSO three times per week for 4 consecutive weeks, followed by once a week for an additional 6 weeks. The onset of diabetes was attenuated in NOD mice treated with AG490 relative to DMSO treated control mice (p < 0.02). From an immunological standpoint, AG490 induced the expression of Foxp3 in CD4(+)CD25(-) T-cells and down-regulated expression of co-stimulatory molecules in dendritic cells (DC) both in vitro and in vivo. AG490 treated CD4+CD25- T-cells and DC in vitro, acquired regulatory functions; namely, the ability to suppress proliferation of a responding cell population in vitro. AG490 treatment resulted in significant reduction of blood glucose values and increased expression of PPARγ in splenocytes and markedly increased expression PPARγ2 but not PPARγ1 in adipocyte in vitro. Presence of multiple Stat5 DNA binding consensus sequences within the promoter region of the PPARγ gene in human and in mouse suggests that PPARγ is downstream to the Jak-Stat signaling pathway. This study highlights a critical role of the Jak-Stat signaling pathway in the pathogenesis of T1D and suggests that blocking the Jak-Stat signaling pathway by AG490 as a tyrosine kinase inhibitor may provide an effective means for preventing autoimmune T1D via both immunological and metabolic effects.


Attachment of Actinobacillus suis H91-0380 and Its Isogenic Adhesin Mutants to Extracellular Matrix Components of the Tonsils of the Soft Palate of Swine.
Tonsils conduct immune surveillance of antigens entering the upper respiratory tract. Despite their immunological function, they are also sites of persistence and invasion of bacterial pathogens. Actinobacillus suis is a common resident of the tonsils of the soft palate in pigs, but under certain circumstances it can invade, causing septicemia and related sequelae. Twenty-four putative adhesins are predicted in the A. suis genome, but to date, little is known about how they might participate in colonization or invasion. To better understand these processes, swine tonsil lysates were characterized by mass spectrometry. Fifty-nine extracellular matrix (ECM) proteins were identified, including small leucine-rich proteoglycans, integrins, and other cell surface receptors. Additionally, attachment of the wild type and 3 adhesin mutants to 5 ECM components was evaluated. Exponential cultures of wild-type A. suis adhered significantly more than stationary cultures to all ECM components studied except collagen I. During exponential growth, the A. suis Δflp1 mutant attached less to collagen IV while the ΔompA mutant attached less to all ECMs. The ΔcomE1 strain attached less to collagen IV, fibronectin, and vitronectin during exponential growth and exhibited differential attachment to collagen I over short adherence time points. These results suggest that Flp1, OmpA, and ComE1 are important during early stages of attachment to ECM components found in tonsils, which supports the notion that other adhesins have compensatory effects during later stages of attachment.


Is Surgical or Catheter-based Interventions an Option After an Unsuccessful Mitral Clip?
The objective of this study was to assess the results of catheter-based and surgical reinterventions in primary mitral regurgitation after failed MitraClip therapy. We report on 21 consecutive symptomatic patients with primary mitral regurgitation (median age 78 years) who underwent either repeat MitraClip therapy (n = 7) or mitral valve surgery (n = 14) after failure of the index procedure with 1-2 MitraClip implantations. At the time of reinterventions, 193 (interquartile range [IQR]: 32-622) days after the index procedure, patients had recurrent or persistent grade 3 mitral regurgitation. Early mortality at 30 days was 4.8%. Cardiac-related survival at 2 years was 85.4% (4 cardiac and 4 noncardiac deaths). Three of 7 patients with percutaneous reintervention were converted to surgery at 34, 52, and 56 days because repeat MitraClip therapy was ineffective because of pre-existing clip detachment or leaflet tear. Final therapy was biological mitral valve replacement in 14 of 21 patients (66.7%); 4 were treated with percutaneous repeat MitraClip repair (19%), and in 3 patients, surgical repairs were performed (14.3%). At follow-up with a median of 708 days, New York Heart Association class had improved significantly to class 2 (IQR: 1.0-2.5) (P = 0.0004), and the left ventricular end-diastolic diameter had decreased from 56 (IQR: 52-59) mm to 51 (48-58) mm (P = 0.0378), respectively. Recurrence of significant mitral regurgitation was absent in all but 1 patient with unsuccessful repeat MitraClip therapy who was deemed inoperable. Our data show that both repeat MitraClip and also mitral valve surgery are feasible and safe alternatives in patients without an excessively increased perioperative risk. We conclude that whenever leaflet insertion is not compromised, repeat catheter-based repair is a reasonable redo concept; in the remaining cases, surgery should be offered to the patient.


Reproductive and Obstetric Factors Are Key Predictors of Maternal Anemia during Pregnancy in Ethiopia: Evidence from Demographic and Health Survey (2011).
Anemia is a major public health problem worldwide. In Ethiopia, a nationally representative and consistent evidence is lacking on the prevalence and determinants during pregnancy. We conducted an in-depth analysis of demographic and health survey for the year 2011 which is a representative data collected from all regions in Ethiopia. Considering maternal anemia as an outcome variable, predicting variables from sociodemographic, household, and reproductive/obstetric characteristics were identified for analyses. Logistic regression model was applied to identify predictors at P < 0.05. The prevalence of anemia among pregnant women was 23%. Maternal age, region, pregnancy trimester, number of under five children, previous history of abortion (termination of pregnancy), breastfeeding practices, and number of antenatal care visits were key independent predictors of anemia during pregnancy. In conclusion, the level of anemia during pregnancy is a moderate public health problem in Ethiopia. Yet, special preventive measures should be undertaken for pregnant women who are older in age and having too many under five children and previous history of abortion. Further evidence is expected to be generated concerning why pregnant mothers from the eastern part of the country and those with better access to radio disproportionately develop anemia more than their counterparts.


Molecular biology of the human pyruvate dehydrogenase complex: structural aspects of the E2 and E3 components.
The availability of the primary amino acid sequences of the E2 of PDC, alpha-KGDC and BCKADC from several prokaryotic and eukaryotic species has allowed us to compare the structural aspects of human PDC-E2 with those of the E2 components from the other complexes. The PDC-E2 components from all the species examined so far contain three structurally identifiable regions: the lipoyl-bearing domain, the E3-binding site, and the catalytic domain. The primary structure of the lipoyl-bearing domain shows considerable variation in its size, ranging from one to three repeating units of approximately 110 amino acids, but essentially preserving its function in the E2 components. In contrast, the sizes of the E3-binding site and the catalytic domain of PDC-E2 from several species are essentially similar and show considerable conservation of specific amino acid residues. Obviously, additional studies are warranted to better understand the structure-function relationships of these domains and the evolutionary conservation of PDC-E2 in different species. Similarly, the availability of the primary amino acid sequences of E3 from several prokaryotes and eukaryotes has also permitted comparison of the structural domains of these proteins with that of the known structure of human GR, a flavoprotein member of the pyridine nucleotide-disulfide oxidoreductase family. Four structural domains (FAD, NAD+, central, and interface domains) have been identified in the E3 components. On the basis of the comparison of the secondary structural elements of GR and E3, the core structure of these two proteins are shown to be similar. It is hoped that further analysis of E3 using site-directed mutagenesis and determination of its crystal structure will provide better insight into its structure-function relationships.


Nonlinear localization of high energy long wave laser pulses in fully correlated 3D turbulence.
We study the interplay between three-dimensional (3D) fully correlated optical turbulence and nonlinearity in time and 3D space resolved long-wavelength infrared pulsed beam propagation. Here the average self-trapped beam waist exceeds the inner scale in contrast to near-infrared filaments, and we find that their nonlinear self-channeling remains robust even in the presence of strong turbulence. More surprisingly, our simulation results invite a conjecture that in regimes where diffraction and nonlinearity are roughly balanced, turbulence can result in a tighter localization of the nonlinear beam core.


Use of a Motorlance to Deliver Emergency Medical Services; a Prospective Cross Sectional Study.
Access time to patients with critical or emergent situations outside the hospital is a critical factor that affects both severity of injury and survival. This study aimed to compare the access time to the scene of an emergency situation between a traditional ambulance and motorlance. This prospective cross sectional study was conducted on all users of emergency call, Srinagarind Hospital, Thailand, from June to December 2018, who received a registration number from the command center. 504 emergency-service operations were examined over a six-month period, 252 (50%) of which were carried out by motorlance. The mean activation time for motorlance and ambulance were 0.57 ± 0.22 minutes and 1.11 ± 0.18 minutes, respectively (p<0.001). Mean response time for motorlance was significantly lower (5.57 ± 1.21 versus 7.29 ± 1.32 minutes; p < 0.001). The response times during 6 a.m. to 6 p.m. were 5.26 ± 1.11 minutes for motorlance and 7.15 ± 1.39 minutes for ambulance (p < 0.001). These measures for night time (6 p.m. to 6 a.m.) were 5.58 ± 1.21 minutes and 8.01 ± 1.30 minutes, respectively (p < 0.001). The mean automated external defibrillator (AED) waiting time for motorlance and ambulance were 5.26 ± 2.36 minutes and 9.24 ± 3.30 minutes, respectively (p = 0.012). The survival rate of patients after AED use in motorlance and ambulance was 80% versus 37.5%; p<0.001. Emergency service delivery by motorlance had lower mean activation time, response time, AED time, and mortality rate of cardiac arrest patients compared to ambulance. It seems that motorlance could be considered as an effective and applicable device in emergency medical service delivery, especially in crowded cities with heavy traffic.


Cost-minimization analysis of degludec/liraglutide versus glargine/aspart: economic implications of the DUAL VII study outcomes.
Diabetes represents a relevant public health problem worldwide due to its increasing prevalence and socioeconomic burden. There is no doubt that tight glycemic control reduces the development of diabetic complications such as the long-term costs related to the disease. The aim of our model was to calculate total direct costs associated with the two treatments considered in DUAL VII study, and hence evaluate the potential economic benefits for the National Health System (NHS) deriving from the use of insulin degludec plus liraglutide (IDegLira) in a once-daily fixed combination. We applied the cost-minimization technique adopting the NHS point of view to the DUAL VII trial outcomes. In the model, developed in Microsoft Excel®, we calculated and compared annual costs per patient of the two therapeutic options for type 2 diabetes (T2D) patients not achieving glycemic control on basal insulin and metformin described in the trial, including costs of therapy management and side effects, both negative and positive. Annual treatment costs were calculated based on IDegLira and basal bolus end-of-trial doses resulting in a 1:2 ratio (40.4 U vs 84.1 U). Therefore, maintaining the IDegLira/basal bolus at 1:2 dose ratio, we calculated the correlation between the dose reduction and costs compared to DUAL VII doses base case scenario. Total treatment costs were obtained by adding annual cost of drug, needles, glycemic self-monitoring, hypoglycemic events, and effect on consumption of other drugs. Total annual costs of IDegLira combination resulted in €434 higher than basal bolus in DUAL VII base case (40.4 U); the two treatments reported equal costs at 34% dose reduction (26.7 U), while below this value IDegLira treatment became less expensive, with about €215 gain at 50% dose reduction (20.2 U). It is also important to notice that above the break-even point, until an IDegLira dose of 30 U, the cost difference is negligible in view of the clinical benefit provided by the fixed combination highlighted in DUAL VII trial. Adding the significant clinical findings derived from DUAL VII trial to our economic evaluation, IDegLira seems to offer an important alternative to basal-bolus therapy.


A preclinical orthotopic model for glioblastoma recapitulates key features of human tumors and demonstrates sensitivity to a combination of MEK and PI3K pathway inhibitors.
Current therapies for glioblastoma multiforme (GBM), the highest grade malignant brain tumor, are mostly ineffective, and better preclinical model systems are needed to increase the successful translation of drug discovery efforts into the clinic. Previous work describes a genetically engineered mouse (GEM) model that contains perturbations in the most frequently dysregulated networks in GBM (driven by RB, KRAS and/or PI3K signaling and PTEN) that induce development of Grade IV astrocytoma with properties of the human disease. Here, we developed and characterized an orthotopic mouse model derived from the GEM that retains the features of the GEM model in an immunocompetent background; however, this model is also tractable and efficient for preclinical evaluation of candidate therapeutic regimens. Orthotopic brain tumors are highly proliferative, invasive and vascular, and express histology markers characteristic of human GBM. Primary tumor cells were examined for sensitivity to chemotherapeutics and targeted drugs. PI3K and MAPK pathway inhibitors, when used as single agents, inhibited cell proliferation but did not result in significant apoptosis. However, in combination, these inhibitors resulted in a substantial increase in cell death. Moreover, these findings translated into the in vivo orthotopic model: PI3K or MAPK inhibitor treatment regimens resulted in incomplete pathway suppression and feedback loops, whereas dual treatment delayed tumor growth through increased apoptosis and decreased tumor cell proliferation. Analysis of downstream pathway components revealed a cooperative effect on target downregulation. These concordant results, together with the morphologic similarities to the human GBM disease characteristics of the model, validate it as a new platform for the evaluation of GBM treatment.


Microbial food safety of lettuce produced under irrigated wastewater from Onyasia River in Ghana.
Fresh produce continues to be the main source of foodborne illness outbreaks, particularly in developing countries where water stress results in the use of surface wastewater all year round for irrigation of vegetables. The objective of the current study was to evaluate the microbial quality of lettuce irrigated with wastewater from Onyasia river. Lettuce and soil were sampled from selected vegetable farms on the Eastern gate of the Ghana Atomic Energy Commission land alongside surface wastewater from the Onyasia river, which is used as the main source for irrigation. Samples were analyzed for aerobic mesophilic plate counts, total coliforms count, fecal coliforms count, Salmonella counts and intestinal parasites using standard methods. Surface wastewater was found to be contaminated with mean fecal coliform counts of log 3.50 cfu/100 mL. Enterobacter cloacae, Acinetobacter baumannii, and Klebsiella pneumonia were also isolated from the wastewater samples. No intestinal parasite egg was detected in wastewater samples. While fecal coliforms and Salmonella spp were not detected, mean aerobic mesophilic plate counts (log 4.82 cfu/g) and total coliforms count (log 3.50 cfu/g) were recorded in the lettuce samples. Enterobacter asburiae, Acinetobacter baumannii, Klebsiella variicola and Citrobacter freundii were isolated from lettuce. Infective larvae of helminths were observed on lettuce samples at a density of 36/g-648/g with a mean of 342/g. Soil samples recorded a mean aerobic mesophilic plate counts of log 6.14 cfu/g, total coliforms count of log 4.90 cfu/g while fecal coliforms and Salmonella spp were not detected (<1 cfu/g) Soil samples yielded a mean infective larval count of 1941.5 larvae/g and a Strongyle count of 12 eggs/g. Even though less than 1 cfu/g of Salmonella spp were found, the study found lettuce to be contaminated with other foodborne bacteria pathogens, opportunistic bacteria pathogens, eggs and infective larvae of intestinal parasites of health importance. As a consequence, the microbial food safety risk associated with wastewater irrigated vegetables was observed to be high with possible public health implications. It is recommended that wastewater from the Onyasia River should be treated before use for irrigation of lettuce.


Novel therapeutic strategies in the treatment of triple-negative breast cancer.
Triple-negative breast cancer (TNBC) is a heterogeneous subtype of breast cancer that is defined by negative estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) status. Treating patients with TNBC remains clinically challenging, as patients are not candidates for endocrine or HER2-directed therapy. As a result, chemotherapy with traditional agents such as anthracyclines and taxanes remains the only available option with moderate success. Recent discoveries have revealed that TNBC is a heterogeneous disease at the clinical, histological and molecular levels. The use of biomarkers to identify distinct subsets of TNBC that derive the greatest benefit from presently approved as well as novel therapeutics has become the main focus of current research. The aim of this review is to explore the clinical and biological complexity of TNBC as well as identify novel therapeutic options that target the various molecular subsets of TNBC.


Patterns of bone marrow involvement in chronic lymphocytic leukemia and small lymphocytic (well differentiated) non-Hodgkin's lymphoma. Its clinical significance in relation to their differential diagnosis and prognosis.
Forty-eight patients with chronic lymphocytic leukemia (CLL), and 12 patients with small (well differentiated) lymphocytic lymphoma (WDL) were histologically evaluated for their pattern of bone marrow (BM) involvement. Four different types of BM infiltration were recognized: nodular (N), interstitial (I), nodular and interstitial (mixed) and diffuse (D). The pattern of BM involvement was compared with the clinical, laboratory, and survival status in all patients. The extent of the disease in CLL patients, was determined by the Rai and the International Workshop on CLL Staging Systems, while in WDL patients the Ann Arbor staging system was used. In the CLL group the N pattern was found in 8%, the I in 33%, the mixed in 31%, and the D in 27% of the patients. Based on the International Workshop on CLL Staging System, the I pattern of BM involvement was more frequently found in Stage A (56%), the mixed in Stage B (68%), and the D in Stage C disease (90%). All CLL patients with D pattern required treatment from the beginning, contrary to CLL patients with the other patterns, in whom therapy was required in less than 50%. Similarly, deaths were more common in the D pattern in whom therapy pattern than in the other patterns. In the WDL patients BM involvement was found in 4 of 12, (33%) and its pattern of positivity was always nodular, although most patients (10 of 12) had advanced disease. It is concluded that the frequency of BM involvement may contribute in the differential diagnosis of WDL from CLL. In addition, the pattern of BM infiltration correlates very well with the International Staging System for CLL, and the pattern of BM positivity in CLL patients also has prognostic significance.


[Studies on the doctor-patient relationship in early Chinese missionary hospitals].
During the 19th century, missionary hospitals were set up by the missionaries in China, establishing a new doctor-patient relationship with doctors at the dominant position. In the early Chinese missionary hospitals, the doctor-patient relationship was relatively good, which could be seen from Chinese people's feelings of gratitude to the medical missionaries. The early missionary hospitals were totally controlled by the western Christians during the 1820-1860. Such good doctor-patient relationship was the results of common action of multiple factors, including Christianity, free medical charges, management idea based on humanism, the idea of the hospitals to avoid medical risks, family concept in traditional Chinese culture and so on.


Reactive oxygen species production via NADPH oxidase mediates TGF-beta-induced cytoskeletal alterations in endothelial cells.
Cytoskeletal alterations in endothelial cells have been linked to nitric oxide generation and cell-cell interactions. Transforming growth factor (TGF)-beta has been described to affect cytoskeletal rearrangement in numerous cell types; however, the underlying pathway is unclear. In the present study, we found that human umbilical vein endothelial cells (HUVEC) have marked cytoskeletal alterations with short-term TGF-beta treatment resulting in filipodia formation and F-actin assembly. The cytoskeletal alterations were blocked by the novel TGF-beta type I receptor/ALK5 kinase inhibitor (SB-505124) but not by the p38 kinase inhibitor (SB-203580). TGF-beta also induced marked stimulation of reactive oxygen species (ROS) within 5 min of TGF-beta exposure. TGF-beta stimulation of ROS was mediated by the NAPDH oxidase homolog Nox4 as DPI, an inhibitor of NADPH oxidase, and dominant-negative Nox4 adenovirus blocked ROS production. Finally, inhibition of ROS with ROS scavengers or dominant-negative Nox4 blocked the TGF-beta effect on cytoskeleton changes in endothelial cells. In conclusion, our studies show for the first time that TGF-beta-induced ROS production in human endothelial cells is via Nox4 and that TGF-beta alteration of cytoskeleton in HUVEC is mediated via a Nox4-dependent pathway.


[Study of biomechanical effects on the reconstruction of mandible defect with autogenous bone grafts].
The biomechanical effects of the reconstructed mandible with autogenous bone grafts were analyzed and evaluated, under simulated mechanical environment of occlusion. Based on anatomical feature of the human skeleton, muscle system and the clinical B, BS"S" and RB"S"defect patterns, the modularized model of mandible and the three finite element models of the fibula grafts and iliac crest grafts reconstruction mandible were made. The stress state calculations under bite force were also processed. The findings are as follows: Along the right connection area to left connection area (corresponding to far-end of the molar teeth alveolar ridge and the chin section respectively), the stress state on the various grafted bone all changes from compression stress to tensile stress. There is obvious change on the stress distribution between the fibula type reconstruction mandible and normal one. The stress on the grafted bone which is mainly made up of cortical bone is approximately 5 times higher than that of normal, which indicates the obvious stress shielding effect; the stress distribution of the iliac crest type reconstruction mandible is close to the normal mandible, the iliac crest used is mainly made up of cancellous. Therefore, the mechanical properties of the reconstructed mandible with iliac crest are more similar to normal mandible, which is beneficial to wound healing and further functional reconstruction.


Oral Fibroma Removal With a Er,Cr:YSSG Laser.
Fibromas often occur orally and are typically due to trauma to underlying connective tissue resulting in tissue enlargement. To prevent continuing trauma to the tissue, excision may be recommended, and biopsy is often indicated for these masses to confirm their diagnosis and to rule out a potential malignant cause. This article presents a case report in which a Er,Cr:YSSG laser was utilized for excision of an oral fibroma. This approach enabled excellent tissue response compared to the use of a scalpel or monopolar electrosurgery, with minimal patient postoperative discomfort and improved healing.


Distortion product emissions from a cochlear model with nonlinear mechanoelectrical transduction in outer hair cells.
A model of cochlear mechanics is described in which force-producing outer hair cells (OHC) are embedded in a passive cochlear partition. The OHC mechanoelectrical transduction current is nonlinearly modulated by reticular-lamina (RL) motion, and the resulting change in OHC membrane voltage produces contraction between the RL and the basilar membrane (BM). Model parameters were chosen to produce a tonotopic map typical of a human cochlea. Time-domain simulations showed compressive BM displacement responses typical of mammalian cochleae. Distortion product (DP) otoacoustic emissions at 2f(1)-f(2) are plotted as isolevel contours against primary levels (L(1),L(2)) for various primary frequencies f(1) and f(2) (f(1)<f(2)). The L(1) at which the DP reaches its maximum level increases as L(2) increases, and the slope of the "optimal" linear path decreases as f(2)/f(1) increases. When primary levels and f(2) are fixed, DP level is band passed against f(1). In the presence of a suppressor, DP level generally decreases as suppressor level increases and as suppressor frequency gets closer to f(2); however, there are exceptions. These results, being similar to data from human ears, suggest that the model could be used for testing hypotheses regarding DP generation and propagation in human cochleae.


Machine Learning of ZnO Interaction with Immunoglobulins and Blood Proteins in Medicine.
Toxoplasmosis is a zoonotic illness caused by Toxoplasma gondii. Those with a normal immune system normally recover without treatment. Immunocompromised individuals and pregnant women must be treated regularly. Toxoplasmosis is a serious illness that may reactivate in immunocompromised patients. A retrospective study using machine learning of toxoplasmosis patients at Government Fever Hospital in Gorantla, Guntur, India, included 25 women, eight of whom were pregnant. These included sex, age, symptoms and side effects, pregnancy, ophthalmic, and antitoxoplasmosis titers, and treatment regimens. Protease mobility and specific activity were increased in toxoplasmosis-infected women's sera, although not significantly (p=0.05). However, there was no discernible decline. The impacts of nanoparticle impact demonstrated a 52.24 percent drop in compound concentration in the presence of zinc nanoparticles, whereas the effect of ZnO nanoparticles was 51.37 percent. Zinc nanoparticles lowered IgA, IgG, and IgM levels in the eye.


Regulation of acetyl phosphate synthesis and degradation, and the control of flagellar expression in Escherichia coli.
We investigated the relationship between Escherichia coli flagellar expression and the regulation of acetyl phosphate synthesis and degradation. Using cells either wild type for acetyl phosphate metabolism or defective for phosphotransacetylase or acetate kinase, or both, we measured flagellar expression and the intracellular concentration of acetyl phosphate relative to growth phase and temperature. Under the conditions tested, we found that elevated levels of acetyl phosphate corresponded to inhibition of flagellar synthesis. To extend these observations, we measured the intracellular concentration of acetyl-CoA, the level of expression from the pta and ackA promoters, and the activities of phosphotransacetylase and acetate kinase derived from cell lysates. Relative to increasing culture density, acetyl-CoA levels and expression from both the pta and ackA promoters decreased. Relative to increasing temperature, expression from the ackA promoter decreased and phosphotransacetylase activity increased. In contrast, temperature had little or no effect on either acetate kinase activity or expression from the pta promoter. We propose that cells regulate intracellular acetyl phosphate concentrations relative to growth phase and temperature by modulating the availability of acetyl-CoA, the expression of ackA, and the activity of phosphotransacetylase.


Promoting influenza vaccination in older people: rationale and reality.
Influenza is a serious, preventable disease for older people. Vaccination saves lives and reduces healthcare costs. The UK should be vaccinating 85% of risk groups by 2010. The uptake of vaccination is influenced by four factors: the socioeconomic status of patients; the system of vaccination; vaccine mistrust and fear of side-effects; and health beliefs. An effective vaccination programme needs to target and be sensitive to the particular needs of older people. It should include a combination of strategies to promote vaccination (flyers, personal invitations; doctor's recommendation); acknowledgement of lay beliefs; special clinics organized around older people; and special arrangements for housebound older people and those living in care homes.


Role of SAGA in the asymmetric segregation of DNA circles during yeast ageing.
In eukaryotes, intra-chromosomal recombination generates DNA circles, but little is known about how cells react to them. In yeast, partitioning of such circles to the mother cell at mitosis ensures their loss from the population but promotes replicative ageing. Nevertheless, the mechanisms of partitioning are debated. In this study, we show that the SAGA complex mediates the interaction of non-chromosomal DNA circles with nuclear pore complexes (NPCs) and thereby promotes their confinement in the mother cell. Reciprocally, this causes retention and accumulation of NPCs, which affects the organization of ageing nuclei. Thus, SAGA prevents the spreading of DNA circles by linking them to NPCs, but unavoidably causes accumulation of circles and NPCs in the mother cell, and thereby promotes ageing. Together, our data provide a unifying model for the asymmetric segregation of DNA circles and how age affects nuclear organization.


[History and current state of the problem of negative disorders (research of nosological period)].
Pioneers of nosology in psychiatry considered mental deficit as a basic disorder obligated to all clinical forms of illness, as did E. Kraepelin in the concept of dementia praecox and E. Bleuler in the concept of schizophrenia. At the present stage of studies, this position is clearly articulated in the «deficit schizophrenia» concept of J. Klosterkotter. Negative disorders are considered in categorical approach to interpret psychopathological dimensions of schizophrenia as coordinated, strongly bound with positive syndromes (concept of «dialectical unity» of A.V. Snezhnevskiy, 1964) and classified as syndromes according to systematics of positive disorders. However, distinguished types of negative disorders are determined in terms of positive syndromes or characterological changes (asthenic, pseudopsychopathic deficit). Within a new paradigm (dimensional approach to schizophrenia), which differs from the categorical approach, negative disorders are considered as a distinct domain, primary in relation to other psychopathological phenomena of schizophrenia). A concept of primary persistent negative symptoms serves as basis of the current concept of schizophrenic deficit. Factor analysis revealed two domains of negative disorders: 1) emotional blunting: blunted affect, alogia; 2) avolition: apathy, anhedonia, asociality.


Inhibition of inflammation and fibrosis by a complement C5a receptor antagonist in DOCA-salt hypertensive rats.
The anaphylatoxin C5a generated by activation of the innate immunity complement system is a potent inflammatory peptide mediator through the G-protein-coupled receptor C5aR (CD88) present in immune-inflammatory cells, including monocytes, macrophages, neutrophils, T cells, and mast cells. Inflammatory cells infiltrate and initiate the development of fibrosis in the chronically hypertensive heart. In this study, we have investigated whether treatment with a selective C5aR antagonist prevents cardiovascular remodeling in deoxycorticosterone acetate (DOCA)-salt hypertensive rats. Control and DOCA-salt rats were treated with PMX53 (AcF-[OPdChaWR], 1 mg·kg·d oral gavage) for 32 days; structural and functional changes in cardiovascular system were determined. DOCA-salt hypertension increased leukocyte extravasation into ventricular tissue, increasing collagen deposition and ventricular stiffness; PMX53 treatment attenuated these changes, thereby improving cardiac function. Further, treatment with PMX53 suppressed an increased expression of C5aR in the left ventricle from DOCA-salt rats, consistent with the reduced infiltration of inflammatory cells. Vascular endothelial dysfunction in thoracic aortic rings was attenuated by PMX53 treatment, but systolic blood pressure was unchanged in DOCA-salt rats. In the heart, PMX53 treatment attenuated inflammatory cell infiltration, fibrosis, and ventricular stiffness, indicating that C5aR is critically involved in ventricular remodeling by regulating inflammatory responses in the hypertensive heart.


A prototypic nonprototype of a personality disorder.
The prototype model has been suggested as an alternative to the traditional categorical model of classification. A series of studies have been performed by Blashfield and his colleagues to identify cases that are prototypic of the DSM-III-R personality disorders. A case that led to diagnostic disagreement was based on the 1985 German movie Zuckerbaby ("Sugarbaby"). In earlier research, the most popular diagnosis for the case was dependent personality disorder, although schizoid, schizotypal, and borderline were almost as frequent. In the current study, the case was presented in cumulative steps to 93 randomly selected clinicians. After each step was presented, clinicians were asked to diagnose the case. With the stepwise presentation format, borderline personality disorder was the most common diagnosis. Chi-square analysis showed that, if clinicians had chosen borderline as a diagnosis by step three, they were likely to keep this decision for the rest of the case. A social-cognitive model was used to explain these results.