Coronary stent durability and fracture: an independent bench comparison of six contemporary designs using a repetitive bend test.
Stent fracture is important because it may cause adverse events. The interventional cardiologist needs independent data to aid stent selection. Stent designers need data to improve stent design. We used a repetitive bend test to compare durability and fracture for different stent designs. Tested were 15 examples of six designs (BioMatrix Flex, Vision, MULTI-LINK 8, Element, Promus PREMIER and Integrity). One end of a nominally deployed stent was mounted on a fixed mandrel. The other end was translated a distance of ±3.5 mm at a rate of 6 Hz until fracture or 10 million cycles completed. The numbers of cycles to fracture for the Vision design (288,411±193,391) and the MULTI-LINK 8 (314,475±239,869) were significantly greater than for the BioMatrix Flex design (38,904±13,160), p<0.001. The difference between Vision and MULTI-LINK 8 was not significant (p=0.79). The Element, PREMIER, and Integrity designs did not fracture. Most fractures were in the curved portions of connectors between hoops. The stent design which fractured most readily was the BioMatrix Flex. The most flexible designs did not fracture and, in general, stents with three connectors were more likely to fracture than those with two connectors between loops.


Tritiated digoxin: studies in renal disease in human subjects.
Digoxin is excreted primarily in the urine as the unchanged glycoside: 60-80% can be recovered from the urine in 7 days after a single intravenous dose in the human subject. Definition of the role of the kidney in digoxin excretion, turnover and metabolism was studied in 57 patients with renal disease, transplant candidates and/or donors and recipients of renal transplants. A single dose of 3H digoxin was given to the subjects, frequent serum samples were obtained and all urine and stools were saved for 7 days. All specimens were extracted with chloroform and digoxin, and its metabolites were separated by column chromatography. Results reveal that the serum T1/2 and the dominant T1/2 of digoxin are prolonged in renal disease in direct proportion to the reduction in creatinine clearance (r = 0.833). The blood urea nitrogen (BUN) is also related to digoxin clearance (r = 0.742). The higher the BUN, the less digoxin excreted in the urine. Anephric patients excrete more digoxin in stool, but this does not compensate for the lack of renal excretion. Transplanted kidneys excrete digoxin in proportion to renal functional capacity, as do patients who have experienced unilateral nephrectomy. Peritoneal or hemodialysis is not effective in removing digoxin from the human subject and may lead to digitalis intoxication if K+ is allowed to fall to critical levels. Digoxin excretion is not volume related, as patients with nephritogenic diabetes insipidus excrete the drug normally with urine volumes of 12 liters a day. Digoxin doses in renal insufficiency should be dictated by knowledge of renal functional ability of the kidneys and after "normal" loading doses, and maintenance doses should be 1/4 to 1/2 those usually administered.


Mga is essential for the survival of pluripotent cells during peri-implantation development.
The maintenance and control of pluripotency is of great interest in stem cell biology. The dual specificity T-box/basic-helix-loop-helix-zipper transcription factor Mga is expressed in the pluripotent cells of the inner cell mass (ICM) and epiblast of the peri-implantation mouse embryo, but its function has not been investigated previously. Here, we use a loss-of-function allele and RNA knockdown to demonstrate that Mga depletion leads to the death of proliferating pluripotent ICM cells in vivo and in vitro, and the death of embryonic stem cells (ESCs) in vitro. Additionally, quiescent pluripotent cells lacking Mga are lost during embryonic diapause. Expression of Odc1, the rate-limiting enzyme in the conversion of ornithine into putrescine in the synthesis of polyamines, is reduced in Mga mutant cells, and the survival of mutant ICM cells as well as ESCs is rescued in culture by the addition of exogenous putrescine. These results suggest a mechanism whereby Mga influences pluripotent cell survival through regulation of the polyamine pool in pluripotent cells of the embryo, whether they are in a proliferative or quiescent state.


Medulloblastoma and retinoblastoma: oncology recapitulates ontogeny.
One major factor hindering progress of pediatric cancers of the nervous system has been the lack of satisfactory model systems for testing novel therapies. A mouse strain, mutant for the Rb1 gene was generated 12 years ago in the hope of producing a model in which to study retinoblastoma. Surprisingly, the Rb(+/-) mice never developed retinoblastoma. Now, Zhang, Schweers and Dyer produce triply deficient Rb, p107 and p53 mutant retinal progenitor cells. All such mice develop intraocular retinoblastoma with invasion of the tumor into the anterior chamber of the eye. This dramatic finding represents the first description of a heritable mouse model of retinoblastoma, which has eluded investigators for the last 12 years. Such models provide an unprecedented opportunity to advance knowledge of tumorigenesis and to develop non-toxic intervention strategies which eradicate disease.


Radiation from the uranium collimators of the Varian 4-MeV accelerator.
The uranium collimator of the Varian 4-MeV accelerator produces a dose rate of 100 mR/h near the collimator opening. It can be decreased to 4% by a 6-mm Lucite shield at the level of the collimator opening. A better solution is a lead glass-mylar (EM) shield which decreases the uranium radiation to less than 3% and also provides better skin sparing during treatment than the open collimator.


Patient with systemic emboli in the setting of Klebsiella oxytoca tricuspid valve endocarditis and patent foramen ovale treated with NobleStitch and AngioVac.
A 34-year-old man with a medical history of injection drug use presented with 2 weeks of weakness, nausea, vomiting and septic shock secondary to infective endocarditis of a native tricuspid valve. On admission, CT chest demonstrated multiple cavitary lesions as well as numerous small infarcts seen on MRI brain concerning for systemic septic emboli. Subsequent transthoracic echo with bubble study revealed a large patent foramen ovale (PFO). The patient later received surgical debulking of his tricuspid valve vegetation with AngioVac. Subsequently, PFO closure was performed with a NobleStitch device. The case presented here demonstrates the importance of having a high index of suspicion with right-sided endocarditis and the development of other systemic signs and symptoms. It also underscores the necessity of a multidisciplinary team of cardiologists, surgeons, infectious disease specialists and intensivists in the treatment of these complicated patients.


Intraclonal diversity in the VH genes expressed by CD5- chronic lymphocytic leukemia-producing pathologic IgM rheumatoid factor.
The leukemic cells from 95% of patients with B cell chronic lymphocytic leukemia (CLL) coexpress B cell differentiation antigens and the pan-T lymphocyte surface antigen CD5 (Leu 1). As such, CLL generally may be considered a malignancy of the CD5 B cell, a minor B cell subpopulation implicated in the production of autoantibodies. Recent data indicate that CD5+ leukemic cells may express autoantibody-associated V region genes with little or no somatic mutation. We examined the Heavy chain V genes expressed by an unusual CLL that secretes rheumatoid factor (RF) autoantibodies but does not express the CD5 surface Ag. Nucleic acid sequence analyses of the rearranged VH genes of three independent rDNA clones demonstrated intraclonal diversity not apparent in previously studied cases of CD5+ CLL. Comparison of the rearranged VH genes reveals that they belong to the VH4 gene subgroup and share highest homology with a rearranged VH gene (Ab44) that encodes a polyreactive autoantibody. That these productively rearranged VH genes encode the RF generated by this unusual CLL population is demonstrated by immunoblotting of the RF paraprotein using primary sequence dependent antipeptide antisera. These results indicate that CD5- CLL, like their CD5+ counterparts, may produce RF. However, unlike CD5+ CLL examined to date, CD5- CLL may have intraclonal diversity in their expressed Ig genes.


[Improvement of the function of islet beta and alpha cells by intervention against glucotoxicity: experiment with rats].
To investigate the effects of intervention against glucotoxicity on improvement of the function and pathological changes of islet beta and alpha cells. Thirty-six male Sprague Dawley rats were randomly divided into four equal groups: normal control (NC) group, fed with standard chow, high-fat (HF) group, fed with extra high-fat chow; diabetes mellitus (DM) control group, fed with high-fat chow for 8 weeks followed by 30 mg/kg streptozotocin injection to establish DM models; and insulin (INS) group, treated with subcutaneous injection of long-acting insulin (glargine, 0.5 U x kg(-1) x d(-1)) for 4 weeks after the establishment of DM models. 48 h, 2 weeks, and 4 weeks after the STZ injection to the 2 DM groups oral glucose tolerance test (OGTT) was performed to all rats. Peripheral blood samples were collected from the caudal vein. Serum insulin level was assayed by radioimmunoassay. Total serum cholesterol (TC) and triglyceride (TG) were measured by enzyme-colorimetric method. By the end of experiment the rats were killed with their pancreases taken out. Immunohistochemistry was used to observe the morphological changes of the islet beta and alpha cells. Beta cell and alpha cell masses were calculated by the proportions of positive area in the islet. Proinsulin mRNA level was detected by RT-PCR. Insulin protein content in islets was detected by Western blotting. Four weeks after the insulin intervention against glucotoxicity, the fasting blood glucose and blood glucose 2 h after sugar-taking of the INS group were both significantly lower than those of the DM group (both P < 0.01). The relative beta cell mass of the INS group was 0.38 +/- 0.08, significantly bigger, 2.45 times, that of the DM group (0.11 +/- 0.05, P < 0.01). The relative alpha cells mass in islets of the INS group was 0.16 +/- 0.04, significantly lower, by 43%, than that of the DM group (0.28 +/- 0.15, P < 0.01). The insulin contents in beta cells of the INS group was 0.58 +/- 0.03, significantly higher, by 70.6%, than that of the DM group (0.34 +/- 0.14, P < 0.01). The proinsulin mRNA level of the INS group was 1.52 +/- 0.14, significantly higher, by 20.6%, than that of the DM group. The morphology of islet beta, alpha cells in diabetic rats was improved by four weeks of Intervention against glucotoxicity improves the pathology of islet beta and alpha cells in diabetic and insulin synthesis.


[An update on DNA sequencing].
The planned acquisition of Pacific Biosciences by Illumina could signal a big change in the DNA sequencing landscape, and provides the incentive for an update on a field that still has a number of players and could be disrupted by innovative technologies.


The HIV transmission gradient: relationship patterns of protection.
We describe a gradient of potential HIV transmission from HIV-infected persons to their partners and thence to uninfected populations. The effect of this newly discovered transmission gradient is to limit the spread of HIV. We roughly estimate a 2% long-term transmission probability for sex and 14% for drug injection for two-step transmission. Then we test theories to account for this pattern on a network sample of 267 inner city drug users and nonusers. Although HIV positive persons engaged in a high level of risk with one another, they engaged in less risk with HIV negative partners, and these partners engaged in even lower levels of risk with other HIV negative persons. Analyses suggest that the primary motivation for sexual risk reduction is partner protection, while emotional closeness is the major barrier. Hypotheses accounting for risk in terms of self protection, social norms, gender power, and drug use were weakly supported or unsupported.


Saccharomyces cerevisiae MSA1 mRNA has a sequence for localization at the bud tip.
MSA1 mRNA encodes Msa1p, a protein associated with the SCB-binding factor (SBF) and MCB-binding factor (MBF) complex. Msa1p promotes the transcription of G1 phase-specific genes, and is subjected to cell cycle-dependent regulation for its abundance and subcellular localization. MSA1 mRNA and Msa1p levels oscillate in the cell cycle with peaks at the late M/early G1 phase and early G1 phase, respectively. Phosphorylation by CDK1 negatively regulates the nuclear localization of Msa1p. In the present study, we identified MSA1 mRNA as a bud tip-localized mRNA in screening using a Tag-GFP system. A fragmentation analysis revealed a sequence of ~145 bases for the bud tip localization. Endogenous MSA1 mRNA localized at the bud tip in a manner that depended on SHE2. Msa1p levels were also affected by SHE2 in cells constitutively expressing MSA1 mRNA. These results suggest the existence of a regulatory mechanism for Msa1p through the localized control of MSA1 mRNA.


Screening families with young children for child maltreatment potential.
The incidence of child maltreatment in the United States is increasing. According to the third National Incidence Study of Child Abuse and Neglect (NIS-3), the number of abused and neglected children doubled between the years 1986 and 1993 to 2.8 million (Sedlak & Broadhurst, 1996). This same study found that the number of children who were seriously injured quadrupled during this period of time to nearly 570,000. Conservative estimates suggest that 10% to 20% of children under 12 years of age experience physical or sexual abuse or neglect. In over 80% of these circumstances, the perpetrator is a family member. Risk indicators have been identified that significantly increase the likelihood of abuse or neglect of children. Interventions that reduce these risk factors have been found to be associated with a decreased incidence of abuse and neglect (Andrews, 1994; Barber-Madden, Cohn, & Scholesser, 1988; Garbarino, 1986; Helfer, 1987). However, existing risk assessment or intervention guides for use with families of children under the age of 3 years are not concise enough for use in a busy primary care setting. For this reason, the Parenting Maltreatment Risk and Intervention Protocol was designed to aid in the identification of families with children under the age of 3 who are at risk for child abuse and neglect and to guide initial intervention, referral, and follow-up care.


Socially learned preferences for differentially rewarded tokens in the brown capuchin monkey (Cebus apella).
Social learning is assumed to underlie traditions, yet evidence indicating social learning in capuchin monkeys (Cebus apella), which exhibit traditions, is sparse. The authors tested capuchins for their ability to learn the value of novel tokens using a previously familiar token-exchange economy. Capuchins change their preferences in favor of a token worth a high-value food reward after watching a conspecific model exchange 2 differentially rewarded tokens, yet they fail to develop a similar preference after watching tokens paired with foods in the absence of a conspecific model. They also fail to learn that the value of familiar tokens has changed. Information about token value is available in all situations, but capuchins seem to pay more attention in a social situation involving novel tokens.


Diagnosing barriers to safety and efficiency in robotic surgery.
Recent studies exploring the effects of surgical robots on teamwork are revealing challenges not reflected in clinical studies. This study is a sub analysis of observational data collected from 89 procedures utilising the da Vinci systems. Previous analyses had demonstrated interactions between flow disruptions and contextual factors. This study sought a more granular analysis to provide better insight for improvement. Raters sub-classified disruptions, based upon the original notes, grouped according to four operative phases (pre-robot; docking; surgeon on console; undocking; and finish). The need for repeated utterances; additional supplies retrieval; fogging or matter on the endoscope and procedure-specific training were particularly disruptive. Variations across phases reflect differing demands across the operative course. Combined qualitative and quantitative observational methodologies can identify otherwise undocumented sources of process variation and potential failure. Future observational frameworks should attempt to merge human reliability analysis, a priori modelling, and post hoc analyses of observational data. Practioner Summary: Robotic surgery introduces new challenges into the operating room. Direct observation was used to classify and identify flow disruptions in order to diagnose problems in need of improvement. This technique complements other error prediction and system diagnostic methods which may not account for the complexity and transparency of health care.


Pyridinium cationic lipids in gene delivery: a structure-activity correlation study.
Three series of pyridinium cationic lipids useful as nonviral gene delivery agents were prepared by reaction of pyrylium salts with aminodiols, followed by acylation with fatty acyl chlorides. On the basis of this set of compounds, we undertook a comprehensive structure-activity relationship study at the level of the linker, hydrophobic anchor, and counterion in order to identify the structural elements that generate the highest transfection efficiency for this new type of cationic lipid. The results revealed that when formulated with cholesterol at a 1:1 molar ratio, the 1-(1,3-dimyristoyloxyprop-2-yl)-2,4,6-trimethylpyridinium, under the form of hexafluorophosphate (5AMyr) or chloride (5DMyr), was able to transfect NCI-H23 lung carcinoma with efficiencies surpassing classic DOTAP-based formulations and with lower cytotoxicity. Subsequent tests on other malignancies yielded similarly promising results.


Skin damage from acetylcysteine leak during percutaneous abscess drainage.
A patient experienced severe cutaneous pain and excoriation during acetylcysteine infusion at percutaneous abscess drainage. The mucolytic agent leaked back along the catheter track, causing the local reaction. Cessation of the acetylcysteine treatment, and catheter exchange resulted in improvement within a few days.


Parallel β-Sheet Structure of Alanine Tetrapeptide in the Solid State As Studied by Solid-State NMR Spectroscopy.
The structural analysis of alanine oligopeptides is important for understanding the crystalline region in silks from spiders and wild silkworms and also the mechanism of cellular toxicity of human diseases arising from expansion in polyalanine sequences. The atomic-level structures of alanine tripeptide and tetrapeptide with antiparallel β-sheet structures (AP-Ala3 and AP-Ala4, respectively) together with alanine tripeptide with parallel β-sheet structures (P-Ala3) have been determined, but alanine tetrapeptide with a parallel β-sheet structure (P-Ala4) has not been reported yet. In this article, first, we established the preparation protocol of P-Ala4 from more stable AP-Ala4. Second, complete assignments of the (13)C, (15)N, and (1)H solid-state NMR spectra were performed with (13)C- and (15)N-labeled Ala4 samples using several solid-state NMR techniques. Then, the structural constraints were obtained, for example, the amide proton peaks of P-Ala4 in the (1)H double-quantum magic-angle spinning NMR spectrum were heavily overlapped and observed at about 7.4 ppm, which was a much higher field than that of 8.7-9.1 ppm observed for AP-Ala4, indicating that the intermolecular hydrogen-bond lengths across strands (N-H···O═C) were considerably longer for P-Ala4, that is, 2.21-2.34 Å, than those reported for AP-Ala4, that is, 1.8-1.9 Å. The structural model was proposed for P-Ala4 by NMR results and MD calculations.


Delta(9)-THC administered into the medial prefrontal cortex disrupts the spatial working memory.
Delta(9)-Tetrahydrocannabinol (Delta(9)-THC) disrupts working memory. The prefrontal cortex (PFC) is involved in the processing of working memory, and its medial portion (mPFC) is part of a brain reward circuit as constituted by the mesocorticolimbic dopaminergic system. This study examined the involvement of the mPFC in the effects of Delta(9)-THC on spatial working memory. Ten male Wistar rats well-trained in a radial arm maze and with bilateral cannula implanted in the mPFC received Delta(9)-THC intra-cortically (Delta(9)-THC IC) at doses of 0 (VEH), 32, 100 or 180 microg, 5 min before a 5-s or a 1-h delayed task in order to measure a short- or long-term spatial working memory, respectively. By contrast, 11 other animals received Delta(9)-THC intraperitoneally (Delta(9)-THC IP) at doses of 0 (VEH), 0.32, 1 or 1.8 mg/kg, 30 min before a 5-s or a 1-h delayed task. Additionally, after a 15-day washout, the effect of an IP or IC pre-exposure of Delta(9)-THC was examined by repeating both dose-effect curves in a crossover order for the routes of administration. Delta(9)-THC IP produced significantly larger number of errors at doses of 0.32 or 1 mg/kg as compared to VEH in the 1-h post-delay performance. Delta(9)-THC 100 microg IC also produced significantly larger number of errors as compared to VEH and also to the other doses (32 or 180 microg) IC in the 1-h post-delay performance. Previous exposure to Delta(9)-THC IP or IC did not significantly affect the disruptive effect of this cannabinoid. Delta(9)-THC administered directly in the mPFC impaired 1-h delayed task in the radial arm maze in a manner similar to that observed for its systemic administration, suggesting that the mPFC is involved in the disruptive effects of Delta(9)-THC on spatial working memory.


Effects of short- and long-term administration of phenobarbital on endogenous ACTH concentration and results of ACTH stimulation tests in dogs.
The effects of short-term phenobarbital administration were evaluated in 6 adult mixed-breed dogs that received phenobarbital (5 mg/kg of body weight, PO, q 12 h) for 8 consecutive weeks. Six additional dogs served as untreated controls. At 2-week intervals, endogenous adrenocorticotropic hormone (ACTH) concentration and cortisol concentration before and 2 hours after administration of porcine aqueous ACTH (2.2 IU/kg, IM) were measured. By means of one-way ANOVA, we were not able to detect a significant (P > or = 0.05) difference in endogenous ACTH concentration and cortisol concentration before and after exogenous ACTH administration within groups over time or between groups at any time. To evaluate effects of long-term phenobarbital administration, sera and plasma were collected from 5 epileptic dogs that had received phenobarbital for > 2 years and had serum phenobarbital concentrations > 20 micrograms/dl. Endogenous ACTH concentration and cortisol concentration, before and after administration of ACTH, were within established reference ranges for all 5 dogs. Together, these results suggest that phenobarbital administration alone does not affect endogenous ACTH concentration or response to exogenous ACTH administration in dogs, and that these may be valid screening tests for hyperadrenocorticism in most dogs receiving phenobarbital.


Do the younger siblings of learning-disabled children see them as similar or different?
Pre-school siblings' comments about, and behaviour towards, their older, learning-disabled brothers and sisters are reported. Initially, some of the very young siblings want to be similar, and attempt to imitate their brothers and sisters, particularly if he or she is also physically disabled; this may be because of the immediate visibility of physical disability, which makes it appear interesting and important to the younger child. Before they are 2 years old, children are able to recognize that their older brothers and sisters are different, and often imitate the parents' behaviour towards the older child.


Cell dispensing in low-volume range with the immediate drop-on-demand technology (I-DOT).
Handling and dosing of cells comprise the most critical step in the microfabrication of cell-based assay systems for screening and toxicity testing. Therefore, the immediate drop-on-demand technology (I-DOT) was developed to provide a flexible noncontact liquid handling system enabling dispensing of cells and liquid without the risk of cross-contamination down to a precise volume in the nanoliter range. Liquid is dispensed from a source plate within nozzles at the bottom by a short compressed air pulse that is given through a quick release valve into the well, thus exceeding the capillary pressure in the nozzle. Droplets of a defined volume can be spotted directly onto microplates or other cell culture devices. We present a study on the performance and biological impact of this technology by applying the cell line MCF-7, human fibroblasts, and human mesenchymal stem cells (hMSCs). For all cell types tested, viability after dispensing is comparable to the control and exhibits similar proliferation rates in the absence of apoptotic cells, and the differentiation potential of hMSCs is not impaired. The immediate drop-on-demand technology enables accurate cell dosage and offers promising potential for single-cell applications.


Temporary postoperative visual loss associated with intracerebral hemorrhage after laparoscopic appendectomy: a case report.
Postoperative visual loss (POVL) after non-ophthalmic surgery is rare, with a reported incidence ranging from 0.013 to 0.2%. Most perioperative visual loss is associated with spine operations and cardiac bypass procedures. The most common cause of POVL is ischemic optic neuropathy. However, there are no previous reports of postoperative visual loss after laparoscopic appendectomy. A 43-year-old female with no underlying disease underwent laparoscopic appendectomy; the operation was completed in one hour and her blood pressure was stable during the perioperative period. In the post-anesthetic care unit, the patient complained of nausea and headache, but she did not complain of any unusual visual symptoms. Approximately one hour after arriving at the ward, the patient complained of visual disturbance. Neurologic examination revealed left homonymous hemianopsia, and subarachnoid hemorrhage and intracerebral hemorrhage were found in the occipital area on brain MRI.


Sildenafil improves heart rate variability in dogs with asymptomatic myxomatous mitral valve degeneration.
Myxomatous mitral valve degeneration (MMVD) causes an imbalance of sympathovagal activity resulted in poor cardiac outcomes. Phosphodiesterase-5 inhibitors have been revealed cardioprotective effect in patients with heart diseases. This study aimed to 1) compare the heart rate variability (HRV) between asymptomatic MMVD and healthy dogs and 2) assess long-term effects of sildenafil and enalapril on time- and frequency-domains analyzes. Thirty-four dogs with MMVD stage B1 or B2 and thirteen healthy dogs were recruited into the study. MMVD dogs were divided into 3 subgroups: control (n=13), sildenafil (n=12) and enalapril (n=9). HRV was analyzed from 1-hr Holter recording at baseline (D0) in all dogs and at 30, 90 and 180 days after treatment. The results showed that MMVD dogs had significant higher heart rate (HR), systemic blood pressures, the ratio of low to high frequency (LF/HF) and had significant decreased standard deviation of all normal to normal RR intervals (SDNN) and the percentage of the number of normal-to-normal sinus RR intervals with differences >50 msec computed over the entire recording (pNN50) when compared with healthy dogs (P<0.05). Neither time nor frequency domain parameters were different among subgroups of MMVD dogs at D0. After treatment with sildenafil for 90 days, both time- and frequency-domain parameters were significantly increased when compared with control and enalapril groups. This study demonstrated that sildenafil improves HRV in asymptomatic MMVD dogs suggesting that sildenafil should be used in the MMVD dogs to restore the sympathovagal balance.


Nutritional therapy in Crohn's disease.
The value of nutritional support in the prevention and treatment of malnutrition in Crohn's disease is undisputed but its role in primary therapy continues to be debated. Controlled trials have demonstrated that enteral nutrition induces remission rates comparable to that of corticosteroid therapy in Crohn's disease and remains the treatment of choice for specific subgroups such as children with signs of growth impairment and patients with intolerable steroid-induced side effects. The mechanism by which an enteral diet induces remission in Crohn's disease is unclear. Bowel rest, reduced antigenic load, nutritional effects, the provision of trophic amino acids, modification of gut flora, intestinal permeability, or fecal pH have been proposed. Equally, the fat profile of the feed may reduce pro-inflammatory ecosanoid synthesis and thus modify disease activity. Maintaining long-term remission remains a challenge in the management of this disease. Cyclic administration of enteral diets, maintenance drug therapy, fat manipulated formulas, or fish oil therapy may be strategies to prolong diet-induced remission. In the future, nutrient derivatives that play a role in the protective processes of the intestinal mucosa may have application in nutritional therapy in Crohn's disease.


Evolution of techniques of stapedectomy from the total stapedectomy to the small fenestra stapedectomy.
No consensus exists among surgeons about how much of the footplate to remove in stapes surgery. By comparing ideal cases with identical surgical techniques, it may be possible to select an optimal amount of the stapes footplate to remove. This article details the evolution of techniques of stapedectomy from the total stapedectomy to the small fenestra stapedectomy.


Endoluminal cryotherapy to prevent recanalization after endovascular occlusion with platinum coils.
Endovascular embolization with platinum coils is sometimes followed by recanalization. The present study was undertaken to assess whether cryoablation of the endothelial lining could prevent recanalization after coil occlusion. Recanalization rates of canine maxillary and vertebral arteries (n = 20) occluded with platinum coils with or without previous cryoablation (with temperatures of -40 degrees C to -45 degrees C for 90 seconds) were analyzed by angiography immediately and at 1 and 3 months in five animals. Pathologic recanalization and fibrosis was assessed at 3 months with use of a qualitative scoring system. Findings were compared with Mann-Whitney tests. Recanalization after coil occlusion occurred in 50% and 60% of cases with cryoablation at 1 and 3 months, respectively, compared with 100% without ablation (P = .012 and P= .029). There was no significant difference in pathologic scores (P = .348). The brachial plexus in the vicinity of vertebral arteries was injured by cryotherapy in three animals in which an ipsilateral neurologic deficit developed. Cryotherapy was moderately effective in the prevention of recanalization after coil occlusion. Deep nerve injury was excessive with the protocol used in the present study.


[Not Available].
An important scientific problem is discussed--the formation of human ideas about health as a national property. Based on positions of class differentiation and party, the authors attempt to elucidate the meaning and essence of this basic notion, equally from the standpoint of medicine and history, and from the standpoint of science in general. Man's health is not merely personal, individual or familial concern. It is conditioned, first and foremost, on a social ground. In this case, the social-economical conditions play a decisive role. The health of people is socially substantiated--attainable by all. On its part, it exerts effect upon the social conditions and society. In socialism and communism only are really human conditions created for the proper development of mankind, not merely in moral and cultural respect, but also in terms of improving vital functions and health state.


Estimation of reliability of predictions and model applicability domain evaluation in the analysis of acute toxicity (LD50).
This study presents a new type of acute toxicity (LD(50)) prediction that enables automated assessment of the reliability of predictions (which is synonymous with the assessment of the Model Applicability Domain as defined by the Organization for Economic Cooperation and Development). Analysis involved nearly 75,000 compounds from six animal systems (acute rat toxicity after oral and intraperitoneal administration; acute mouse toxicity after oral, intraperitoneal, intravenous, and subcutaneous administration). Fragmental Partial Least Squares (PLS) with 100 bootstraps yielded baseline predictions that were automatically corrected for non-linear effects in local chemical spaces--a combination called Global, Adjusted Locally According to Similarity (GALAS) modelling methodology. Each prediction obtained in this manner is provided with a reliability index value that depends on both compound's similarity to the training set (that accounts for similar trends in LD(50) variations within multiple bootstraps) and consistency of experimental results with regard to the baseline model in the local chemical environment. The actual performance of the Reliability Index (RI) was proven by its good (and uniform) correlations with Root Mean Square Error (RMSE) in all validation sets, thus providing quantitative assessment of the Model Applicability Domain. The obtained models can be used for compound screening in the early stages of drug development and prioritization for experimental in vitro testing or later in vivo animal acute toxicity studies.


Autotransplatation of immature third molars as substitutes for congenitally missing second premolars: an alternative solution in a young patient with oligodontia.
Auto transplantation of immature donor teeth can be a strategic therapeutic solution in young patients. It is preferable to choose this approach instead of prosthetic restorations because it offers a unique and definitive solution. Orthodontic space closure is not always deemed desirable, especially in non-extraction cases (53,54). Successful auto transplantations allow alveolar growth through eruption of donor teeth together with the adjacent dentition when skeletal and dental development is not yet completed. Auto transplantation of third molars is less well-recognised and less documented. The available literature shows promising success rates. Immature donor teeth are reportedly associated with better outcomes than mature donor teeth. Aim of this case report was to analyse the short-term outcomes of auto transplantation of immature maxillary third molars to replace the missing mandibular second premolars in a 17-year-old healthy female with oligodontia. The surgical procedure was performed as a single step. Left and right lower second deciduous molars (7.5-8.5), close to exfoliation, were extracted. Donor upper third molars with developing root were extracted as a traumatically as possible and immediately placed into the surgically modified recipient sites. They were stabilized by a sectional wire. One year after surgery, the survival of both transplanted teeth was achieved. They showed periodontal health, normal mobility and continuation of root development during the follow-up period. The upper left third molar responded to all success criteria, no signs of ankylosis, root resorption (infection or inflammatory), and pulp necrosis. The upper right third molar had long-standing evidence of not progressive cervical external inflammatory root resorption without any clinical signs. Further research is needed to determine their long-term survival and success rates.


Optimizing the MAC Protocol in Localization Systems Based on IEEE 802.15.4 Networks.
Radio frequency signals are commonly used in the development of indoor localization systems. The infrastructure of these systems includes some beacons placed at known positions that exchange radio packets with users to be located. When the system is implemented using wireless sensor networks, the wireless transceivers integrated in the network motes are usually based on the IEEE 802.15.4 standard. But, the CSMA-CA, which is the basis for the medium access protocols in this category of communication systems, is not suitable when several users want to exchange bursts of radio packets with the same beacon to acquire the radio signal strength indicator (RSSI) values needed in the location process. Therefore, new protocols are necessary to avoid the packet collisions that appear when multiple users try to communicate with the same beacons. On the other hand, the RSSI sampling process should be carried out very quickly because some systems cannot tolerate a large delay in the location process. This is even more important when the RSSI sampling process includes measures with different signal power levels or frequency channels. The principal objective of this work is to speed up the RSSI sampling process in indoor localization systems. To achieve this objective, the main contribution is the proposal of a new MAC protocol that eliminates the medium access contention periods and decreases the number of packet collisions to accelerate the RSSI collection process. Moreover, the protocol increases the overall network throughput taking advantage of the frequency channel diversity. The presented results show the suitability of this protocol for reducing the RSSI gathering delay and increasing the network throughput in simulated and real environments.


Induction of plant virus defense response by brassinosteroids and brassinosteroid signaling in Arabidopsis thaliana.
Our study demonstrated that CMV resistance was upregulated by brassinosteroids (BRs) treatment, and BR signaling was needed for this BRs-induced CMV tolerance. Plant steroid hormones, brassinosteroids (BRs), play essential roles in variety of plant developmental processes and adaptation to various biotic and abiotic stresses. BR signal through plasma membrane-localized receptor and other components to modulate several transcription factors that modulate thousands of target genes including certain stress-responsive genes. To study the effects of BRs on plant virus defense and how BRs induce plant virus stress tolerance, we manipulated the BRs levels in Arabidopsis thaliana and found that BRs levels were positively correlated with the tolerance to Cucumber mosaic virus (CMV). We also showed that BRs treatment alleviated photosystem damage, enhanced antioxidant enzymes activity and induced defense-associated genes expression under CMV stress in Arabidopsis. To see whether BR signaling is essential for the plant virus defense response, we made use of BR signaling mutants (a weak allele of the BRs receptor mutant bri1-5 and constitutive BRs response mutant bes1-D). Compared with wild-type Arabidopsis plants, bri1-5 displayed reversed tolerance to CMV, but the resistance was enhanced in bes1-D. Together our results suggest that BRs can induce plant virus defense response through BR signaling.


Experimental assessment of new stent technologies: validation of a comparative paired rabbit iliac artery study model.
Preventing coronary in-stent restenosis is a major challenge for physicians and industry. To assess new stent technologies, a comparative paired iliac artery model in rabbits is proposed. One tubular stent was implanted in each external iliac artery in 12 rabbits (i.e., 24 stents). An artery overdilatation level of 20% was strictly observed. Restenosis was examined at 30 days by angiography, intravascular ultrasound (IVUS) examination, and histomorphometry. On quantitative angiography, the mean loss of angiographic diameter was 9.8 +/- 4.4% in the right as compared to 9.3 +/- 55% in the left artery (p = 0.75). On IVUS, the volume of intrastent neointimal proliferation was 26.6 +/- 4.9 mm(3) in the right and 25.8 +/- 3.5 mm(3) in the left artery (p = 0.58). In histomorphometry, the neointimal proliferation area was 0.78 +/- 17 mm(2) in the right and 0.76 +/- 0.17 mm(2) in the left artery (p = 0.87). Intrastent neointimal proliferation was comparable between the left and right arteries of all rabbits. The model has three main advantages: (1) arterial dilatation and thus arterial wall aggression are controlled, (2) pairing makes each animal its own control subject, and (3) the statistical power for comparative testing is maximized. The model enables the effect of a new drug-delivery device to be assessed.


Safety of quadrivalent human papillomavirus vaccine (Gardasil) in pregnancy: adverse events among non-manufacturer reports in the Vaccine Adverse Event Reporting System, 2006-2013.
In 2006, quadrivalent human papillomavirus (HPV4; Gardasil, Merck & Co., Inc.) vaccine was licensed in the US for use in females aged 9-26 years. HPV4 is not recommended during pregnancy; however, inadvertent administration during pregnancy may occur. To evaluate and summarize reports to the Vaccine Adverse Event Reporting System (VAERS) in pregnant women who received HPV4 vaccine and assess for potentially concerning adverse events among non-manufacturer reports. We searched the VAERS database for non-manufacturer reports of adverse events (AEs) in pregnant women who received HPV4 vaccine from 6/1/2006 to 12/31/2013. We conducted clinical review of reports and available medical records. We found 147 reports after HPV4 vaccine administered to pregnant women. The most frequent pregnancy-specific AE was spontaneous abortion in 15 (10.2%) reports, followed by elective terminations in 6 (4.1%). Maternal fever was the most frequent non-pregnancy-specific AE in 3 reports. Two reports of major birth defects were received. No maternal deaths were noted. One hundred-three (70.1%) reports did not describe an AE. This review of VAERS non-manufacturer reports following vaccination with HPV4 in pregnancy did not find any unexpected patterns in maternal or fetal outcomes.


Reconstruction of partial hypopharyngeal defects following total laryngectomy: Pectoralis major myofascial versus myocutaneous flaps.
To date, few comparative studies exist for partial hypopharyngeal defect reconstruction following total laryngectomy. In the absence of objective evidence from comparative studies, the ideal flap choice remains controversial, leading to heterogeneity in institutional treatment protocols. Comparative studies between different reconstructive techniques are required. Therefore, this study compared postoperative outcomes of pectoralis major myocutaneous (PMMC) and myofascial (PMMF) flaps. A single-center retrospective cohort study was performed between 2000 and 2022, which included all consecutive patients who underwent a PMMC or PMMF flap reconstruction following total laryngectomy and partial hypopharyngectomy. Primary outcomes were suture line leakages (conservative management), fistulas (surgical management), and strictures. Secondary outcomes included flap failure, donor-site morbidity, and the start of oral intake. In total, 122 patients were included (109 PMMC and 13 PMMF flap reconstructions). The incidence of suture line leakage was significantly higher (p = 0.007) after PMMC flaps (57%) compared with PMMF flaps (15%). Between PMMC and PMMF flaps, fistula (19% vs. 0%) and stricture rates (22% vs. 15%) did not differ significantly. No differences in flap failure, donor-site morbidity, or start of oral intake were observed. PMMF flaps have inherent advantages (e.g., reduced bulk, increased pliability) over conventional PMMC flaps and have non-inferior results compared to the latter in terms of postoperative complications. Although the final choice for reconstruction should be patient-tailored, a PMMF flap can be considered a reliable primary choice that is feasible in most patients.


[Thrombosis of a cardiopulmonary bypass circuit despite recommended hypocoagulation with danaparoid during the acute phase of type II heparin-induced thrombocytopenia].
A 36-year-old patient was admitted to our hospital with ischaemic stroke. The initial assessment allowed the diagnosis of an antiphospholipid syndrome (APS) and an intracardiac mass suggestive of a heart tumour. The patient was treated with unfractionated heparin. Type II heparin-induced thrombopenia (HIT) was diagnosed on the 18th day of therapy. Given the risk of stroke recurrence it was decided to remove the cardiac tumour surgically. Cardiopulmonary bypass (CPB) was performed using danaparoid in a state of deep hypothermia, in accordance with the well-established protocol in use in our department. As the CPB and surgical procedure came to an end a massive thrombus began forming in the circuit, requiring immediate displacement of the CPB cannulae. The anti-Xa activity level obtained had been considered effective at an estimated 1.20 IU/ml, although, the level recommended by Magnani is between 1.50 and 2.0 IU/ml. There was no clinical consequence and postoperative recovery was uneventful. The discrepancy between the satisfactory level of anti-Xa activity and the thrombus formation in the CPB circuit raises the issue of the diversity of published anticoagulation protocols, the difficulty to extrapolate within a surgical team, the need for intensive laboratory monitoring within a narrow therapeutic range, as well as the patient profiles variability with concurrent disorders complicating their clinical management.


The attitude of physicians towards education and rehabilitation of patients on chronic dialysis: a questionnaire survey.
In this study, we aimed to evaluate the attitude of physicians in the Kingdom of Saudi Arabia (KSA) towards the education and rehabilitation of chronic dialysis patients Questionnaires were sent to 155 physicians working in 148 dialysis centers. They included 109 centers (73.6 %) in the Ministry of Health (MOH), 18 (12.2%) in governmental non-MOH sector and 21 centers (14.2 %) in private hospitals that together care for a population of more than 7,900 chronic dialysis patients. The study was performed between January and March 2006. Responses were received from 141 physicians (90.9%) from 140 (94.5%) dialysis centers. There were 134 (97.1%) respondents who believed that the ideal ratio of patients per dialysis nurse should be < or = 3, 132 (97.1%) believed that the ideal ratio of patients per physician should be < or = 25, 120 (88.9%) believed that the ideal ratio of patients per dietitian should be < or = 50, and 102 respondents (81.0%) believed that the ideal ratio of patients per social worker should be < or =50. There were 46 respondents (32.6%) who always and 53 (37.6%) who mostly found time to educate the patients about the various options available for renal failure treatment. Educational tools, such as reading materials and audiovisuals, were only available to 56 respondents (42.7%). There were 88 (63.3%) respondents who always discussed results of laboratory tests in detail with their dialysis patients, while 48 (34.5%) informed patients when any abnormality was discovered. There were 130 respondents (94.9%) who believed that their patients were satisfied with services of the physicians, 53 (39.0%) with the dietitian's, 57 (42.5%) with the social worker's, and 131 (94.9%) with the nurses' services. Our survey suggests that that the current practices concerning education and rehabilitation of patients in the dialysis centers in the KSA may not be satisfactory. More studies are needed to explore these issues.


Would a Large tPA Trial for Those 4.5 to 6.0 Hours from Stroke Onset Be Good Value for Information?
To quantify the potential value of new research in patients treated with thrombolytic treatment (tissue-type plasminogen activator [tPA]) in the 4.5- to 6.0-hour time window after stroke onset and to determine the optimal size of a future trial using value of information analysis. Expected value of partial perfect and sample information (EVPPI and EVSI) analyses were conducted using a probabilistic Markov model. Data for modified Rankin Scale (mRS) distributions in patients 4.5 to 6.0 hours since stroke onset for tPA (n = 576) and placebo (n = 543) were obtained from pooled randomized controlled trials. EVSI was quantified with net monetary benefit (assuming willingness to pay for health as $100,000/QALY). We calculated discounted population-level EVSI by multiplying per-person EVSI by the annual number of eligible patients with stroke in the United States and assuming a 10-year time frame of treatment use. Study costs were based on administrative costs and the costs of tPA. The base-case lifetime cost-effectiveness analysis showed that tPA was dominated by placebo in this patient group. EVPPI for mRS distributions was $1003 per person. On the basis of EVSI, the optimal sample size of a new trial collecting data on tPA efficacy in these patients would be 5600 across study arms with expected population-level societal returns (EVSI minus study costs) of $68.7 million. Expanding research attention to the 4.5- to 6.0-hour time window for tPA treatment of patients with acute ischemic stroke is justified because the expected returns are substantial. Even a relatively large trial in which more information on treatment efficacy on the basis of mRS scores is collected would represent good value for information.


miR-375 negatively regulates the synthesis and secretion of catecholamines by targeting Sp1 in rat adrenal medulla.
The adrenal gland is an important endocrine gland in balancing homeostasis and the response to stress by synthesizing and secreting catecholamines (CATs), and it has been confirmed that microRNA-375 (miR-375) is highly expressed in adrenal medulla. However, up to now there are few reports about the functions and related mechanisms in adrenal medulla. The present study was thus designed to study the roles and related mechanisms in rat adrenal medulla. Our results showed that miR-375 was specifically expressed in rat adrenal medulla chromaffin cells, and its expression was downregulated when rats were exposed to stress. The further functional studies demonstrated that the inhibition of endogenous miR-375 induced the secretion of CATs in primary rat medulla chromaffin cells and PC12 cells, whereas miR-375 overexpression resulted in a decline of CAT secretion. In addition, our results showed that miR-375 negatively regulated tyrosine hydroxylase (TH) and dopamine-β-hydroxylase (DBH) and mediated adrenomedullary CAT biosynthesis. These functions of miR-375 were accomplished by its binding to the 3'-untranslated region of Sp1, which was involved in the regulation of TH and DBH expressions. These novel findings suggest that miR-375 acts as a potent negative mediator in regulating the synthesis and secretion of CATs in the adrenal medulla during the maintenance of homeostasis under stress.


Paradoxical preexcitation during cryoablation of a concealed parahisian accessory pathway.
A 16-year-old male presented with an orthodromic atrioventricular reentrant tachycardia over a concealed parahisian accessory pathway (AP). Cryoablation of the AP resulted in transient manifestation of a fully preexcited sinus rhythm of parahisian AP morphology. Potential causes for the paradoxical preexcitation include inadvertent atrioventricular nodal block, sourse-sink mismatch, as well as the activation of a dormant AP capable of anterograde conduction.


Extraction, assay, and analysis of antimicrobials from plants with activity against dental pathogens (Streptococcus sp.)
Many dental and periodontal diseases are largely a question of bacterial etiology. Dental caries develop due to an increase of strongly acidogenic and aciduric gram-positive bacteria while common forms of periodontal disease are linked to anaerobic gram-negative bacteria in subgingival plaque. Many plants and plant-derived antimicrobial components are used in folklore therapeutics for the treatment of periodontal disorders and for the purposes of oral hygiene. Some have been evaluated for possible use in modern medicine, while thousands of other potentially useful/plants have not been tested. In this study, we evaluated the feasibility of screening for antibacterials isolated from plants with activity against three representatives of oral streptococci. We developed and tested the following methodologies: (1) Extraction of antibacterial components from plants; (2) Assays for antibacterial activity; (3) Chromatographic methods for initial analysis of compounds of interest. The screening process for plant antimicrobials consisted of extraction of plant material and assay of antibacterial activity using a spotting test with the selected oral streptococci as indicator strains. In addition, we developed chromatographic procedures that allow characterization and optimization of initial isolation steps. Depending on the indicator microorganisms used, the screening assay can target additional pathogens including other streptococci (group A and B, and pneumococci) and periodontal pathogens such as Porphyromonas. Also, we noted that the activity of some extracts varied against different oral bacteria. Our conclusion, supported by extensive data, was that the screening for antimicrobials from plants is a feasible approach to the identification of natural compounds with antimicrobial properties against dental pathogens.


The association between bullying victimization in childhood and fibromyalgia. Data from the nationwide Finnish health and social support (HeSSup) study based on a sample of 64,797 individuals.
Fibromyalgia is a functional pain syndrome presenting with various psychological symptoms. Several studies have shown that adverse life events are associated with fibromyalgia. The aim of the current study is to explore the association between self-reported bullying victimization in childhood and self-reported fibromyalgia in adulthood. The basic study setting is cross-sectional - with focused use of retrospective data - derived from a large on-going postal follow up survey (sample N = 64,797) initiated in Finland in 1998. Only respondents having answered the questions on fibromyalgia in both follow ups in 2003 and 2012 were included (N = 11,924). Severity of bullying was divided into three groups starting from no bullying followed by minor and severe bullying. Covariates having shown statistically significant associations with fibromyalgia in cross tabulation using Pearson's chi-squared test were included in the final multiple logistic regression analyses. In our study, 50.6% of the respondents reported victimization of minor and 19.6% of severe bullying in childhood. Participants reporting fibromyalgia in adulthood reported more bullying, and in females alone this association was statistically significant (p = .027). In multiple logistic regression analysis statistically significant associations between bullying victimization in childhood (reference: no bullying) and fibromyalgia were found: adjusted odds ratio (OR) for minor bullying was 1.35 (95% CI 1.09-1.67) and for severe bullying 1.58 (95% CI 1.21-2.06). However, in log-linear and logistic regression interaction models the association between bullying and fibromyalgia was not statistically significant when depression was included in the models. Our results suggest that peer bullying victimization might be associated with fibromyalgia. However, in logistic log linear and logistic interaction models there was no statistically significant association when depression was included. As a result, there is need for further, preferably prospective cohort studies. The findings also emphasize the importance of actions to prevent childhood bullying.


Evaluation of the wound healing activity of methanol extract of Pedilanthus tithymaloides (L.) Poit leaf and its isolated active constituents in topical formulation.
Pedilanthus tithymaloides leaves are widely used in Indian medicine to heal wounds, burn, mouth ulcers. However, systematic evaluation of these activities is lacking. Thus, the present study aimed to assesses the wound healing activity of Pedilanthus leaves and its isolated constituents in topical ointment formulation. Bioassay-guided chromatographic fractionation of the methanol extract of leaves resulted in the isolation of 2-(3,4-dihydroxy-phenyl)-5,7-dihydroxy-chromen-4-one and 1, 2-tetradecanediol, 1-(hydrogen sulfate), sodium salt. The ointment formulation of methanol extract (2.5%, 5% w/w) and isolated compounds (0.25% w/w) was prepared and evaluated on excision, incision and dead space wound models in rats. The effects of formulations on wound healing were assessed by the rate of wound closure, period of epithelialization, tensile strength, granulation tissue weight, hydroxyproline content and histopathology. Significant wound healing activity was observed with methanol extract and isolated constituents. Topical application of isolated compound ointments caused faster epithelialization, significant wound contraction (95.41%), and better tensile strength (565.33 g) on 16 post-wounding day, while 5% extract showed wound epithelialization with 95.55% contraction on 18th post-wounding day, better than the control group (76.39% on 22 day). The tensile strength of incision wound was significantly increased in extract and compound treated animals. Moreover, in dead space model the extract significantly increased granuloma tissue weight, tensile strength and hydroxyproline content. The tissue histology of ointment treated groups showed complete epithelialization with increased collagenation, compared to the povidone-iodine group. The results validated the traditional use of Pedilanthus tithymaloides for cutaneous wound management.


Phospholipase C-delta gene of the spontaneously hypertensive rat harbors point mutations causing amino acid substitutions in a catalytic domain.
This study was undertaken in order to investigate the newly discovered spontaneously hypertensive rat (SHR)-specific restriction fragment length polymorphism (RFLP) at the genomic locus of (poly)phosphoinositide-specific phospholipase C (PLC)-delta at a DNA sequence level. Our aim was to clone the PLC-delta complimentary DNA (cDNA) from SHR and analyse the genomic DNA obtained from two hypertensive rat strains such as SHR and its stroke-prone substrain (SHR-SP) and three normotensive rat strains such as Sprague-Dawley, Donryu and Wistar-Kyoto (WKY) by preparing an aortic cDNA library of SHR, hybridization cloning of PLC-delta cDNA and an analysis of the genomic DNA by polymerase chain reaction. By digesting with restriction enzyme XhoI, we discovered an RFLP band displaying only in SHR and SHR-SP, not in Sprague-Dawley, Donryu and WKY rats. DNA sequencing of PLC-delta cDNA cloned from an aortic cDNA library of SHR revealed a total of three SHR-specific point mutations, two of which resulted in amino acid substitutions. The first point mutation (A to T) was detected at the XhoI site, changing a threonine(ACG) to a serine(TCG), and the second point mutation (A to G) was discovered in the vicinity of the first one, changing an isoleucine(ATA) to a methionine(ATG). This is the first demonstration of the mutations in the SHR genome changing amino acid sequences. These amino acid substitutions, situated in the putative catalytic X domain of PLC-delta, may be the major cause of the augmented PLC activity observed in the SHR, possibly leading to hypertension-related phenonemoma such as abnormal calcium homeostasis and increased intracellular calcium ion concentrations.


DNA repair capacity, DNA-strand break repair gene polymorphisms, and the incidence of hepatocellular carcinoma in southwestern Guangxi of China.
The associations between DNA repair capacity (DRC), DNA repair gene polymorphisms, and the incidence of hepatocellular carcinoma (HCC) have not been determined in high-risk areas. The aims of this study were to investigate whether DRC is related to the incidence of HCC and to determine whether polymorphisms in the DNA repair genes that regulate DRC are associated with the risk of HCC. First, a small case-control study was conducted to examine the association between DRC and the incidence of HCC and the environmental and genetic factors regulating DRC. Then, a large case-control study was conducted to determine whether those DNA repair gene polymorphisms shown to regulate DRC were related to the risk of HCC. The median DRC was significantly lower among the cases (0.80) than the controls (0.93). A multivariate linear regression analysis showed that the HBsAg status (p<0.01), ethnicity (p=0.01), and polymorphisms in the XRCC3-241 (p=0.01) and APE1-148 (p=0.03) gene loci may be impact factors for DRC. In the large case-control study, a stratified analysis showed that individuals with the APE1-148-combined genotype GT+TT likely had a significantly higher HCC risk compared with those with only the GG genotype (crude odds ratio=1.93, 95% confidence interval=1.17-3.17) among the Zhuang ethnicity. However, nonsignificant differences were observed between XRCC3-241 polymorphisms and the HCC risk. DRC may be related to the incidence of HCC as determined by environmental and genetic factors found in southwestern part of the Guangxi Province. Gene-environment interactions play an important role in the incidence and progression of HCC.


[The interferon status in helminthiases. 1. Human unilocular hydatid disease].
In 51 patients with Echinococcus granulosus infection, blood IF alpha and IF gamma levels were measured using vesicular stomatitis virus culture. In patients with progressing disease, the IF alpha and IF gamma levels were significantly lower than in the benign form of the disease--144 +/- 28.8 and 51.6 +/- 10.1 U/ml, respectively (in healthy controls the levels were 1024 +/- 28.8 and 187.7 +/- 16.9 U/ml). The lowest levels of IF alpha and IF gamma were found in patients with primary localization of cysts in the lungs and multiorgan damages affecting the lungs--160 +/- 38.5 and 44.4 +/- 13.5 U/ml; 146.7 +/- 80.1 and 89.5 +/- 19.2 U/ml, respectively. After 5-6 thirty-day courses of mebendazole therapy (50 mg/kg body weight) at 30-day intervals, the average levels of IF alpha and IF gamma were 4 and 5 times higher. Measurement of IF levels in echinococcosis may be of prognostic value for the estimation of the efficacy of surgical and/or specific treatment.


Mutations within the pathogenic region of herpes simplex virus 1 gK signal sequences alter cell surface expression and neurovirulence.
To investigate the role of the signal sequences of herpes simplex virus 1 (HSV-1) gK on virus replication and viral pathogenesis, we constructed recombinant viruses with or without mutations within the signal sequences of gK. These recombinant viruses expressed two additional copies of the mutated (MgK) or native (NgK) form of the gK gene in place of the latency-associated transcript with a myc epitope tag to facilitate detection at their 3' ends. The replication of MgK virus was similar to that of NgK both in vitro and in vivo, as well as in the trigeminal ganglia (TG) of latently infected mice. The levels of gB and gK transcripts in the corneas, TG, and brains of infected mice on days 3 and 5 postinfection were markedly virus and time dependent, as well as tissue specific. Mutation in the signal sequence of gK in MgK virus blocked cell surface expression of gK-myc in rabbit skin cells, increased 50% lethal dose, and decreased corneal scarring in ocularly infected mice compared to the NgK or revertant (RgK) virus. MgK and NgK viruses, and not the RgK virus, showed a reduced extent of explant reactivation at the lower dose of ocular infection but not at the higher dose. However, the time of reactivation was not affected by overexpression of the different forms of gK. Taken together, these results strongly suggest that the 8mer peptide (ITAYGLVL) within the signal sequence of gK promotes cell surface expression of gK in infected cells and ocular pathogenesis in infected mice. In this study, we show for the first time that mutations within the signal sequence of gK blocked cell surface expression of inserted recombinant gK in vitro. Furthermore, this blockage in cell surface expression was correlated with higher 50% lethal dose and less corneal scarring in vivo. Thus, these studies point to a key role for the 8mer within the signal sequence of gK in HSV-1-induced pathogenicity.


Orientation of functional and nonfunctional PTS permease signal sequences in lipid bilayers. A polarized attenuated total reflection infrared study.
Synthetic peptides corresponding to the N-terminal 23 and 22 residues, respectively, of two integral plasma membrane proteins of Escherichia coli, namely the mannitol- and glucitol-specific permeases of the bacterial sugar phosphotransferase system, were incorporated into single planar phospholipid bilayers supported on germanium plates. Polarized attenuated total reflection infrared spectra were recorded, and order parameters were derived from the measured dichroic ratios. The order parameters of the two wild-type peptides which form amphiphilic alpha-helices in membranes were -0.4 to -0.5, indicating a preferential alignment of the alpha-helix long axis parallel to the membrane surface. Nonfunctional mutant peptides of the mannitol permease sequence in which serine-3 or aspartate-4 were substituted with prolines (S3P and D4P) or lysine (D4K), but which were still largely alpha-helical, exhibited peptide order parameters close to zero, indicating a high degree of disorder of these peptides in the lipid bilayers. The lipid was well ordered at low concentrations of peptides in the membranes but became disordered at high peptide concentrations. This effect of lipid disordering was more pronounced for the D4K mutant than for the wild-type mannitol peptide.


The empowerment of patients with chronic urinary tract infection.
Living with a chronic illness affects every aspect of a person's life, including his or her sense of self, family relationships and work. It may be particularly hard to cope with an illness that is invisible, such as chronic urinary tract infection. Nurses can work with patients to help them feel empowered to take control of their condition.


Exercise physiology: health indicators and cardiovascular risk factors during childhood and adolescence.
Low risk strategies use favourable levels of different behavioural and physiological parameters, which may be accepted as health indicators. High risk strategies are oriented to protect people from the potential risk levels of the same behavioural and physiological parameters. Both strategies are first applied to adults; but the established levels of risk in adults cannot be explained only by their living conditions, these factors must have some genetic and educational roots in childhood and adolescence. Based on several cross-sectional and longitudinal studies of 1652 subjects it was shown that trained and untrained adolescents did not differ in family history of CHD but clearly had different behavioural risk factors. The early identification of children and adolescents with a high risk of developing CHD should be intensified using integrated risk indicators. Thus collaboration between exercise physiology and preventive cardiology should be centered more on studies of children and adolescents.


Evaluating the bone tissue regeneration capability of the Chinese herbal decoction Danggui Buxue Tang from a molecular biology perspective.
Large bone defects are a considerable challenge to reconstructive surgeons. Numerous traditional Chinese herbal medicines have been used to repair and regenerate bone tissue. This study investigated the bone regeneration potential of Danggui Buxue Tang (DBT), a Chinese herbal decoction prepared from Radix Astragali (RA) and Radix Angelicae Sinensis (RAS), from a molecular biology perspective. The optimal ratio of RA and RAS used in DBT for osteoblast culture was obtained by colorimetric and alkaline phosphatase (ALP) activity assays. Moreover, the optimal concentration of DBT for bone cell culture was also determined by colorimetric, ALP activity, nodule formation, Western blotting, wound-healing, and tartrate-resistant acid phosphatase activity assays. Consequently, the most appropriate weight ratio of RA to RAS for the proliferation and differentiation of osteoblasts was 5:1. Moreover, the most effective concentration of DBT was 1,000 μg/mL, which significantly increased the number of osteoblasts, intracellular ALP levels, and nodule numbers, while inhibiting osteoclast activity. Additionally, 1,000 μg/mL of DBT was able to stimulate p-ERK and p-JNK signal pathway. Therefore, DBT is highly promising for use in accelerating fracture healing in the middle or late healing periods.


Multibody scattering, correlation, molecular conduction, and the 0.7 anomaly.
We describe a new grid-based (or localized orbital-based) method for treating the effects of exchange and correlation on electronic transmission through a molecular target where there are initially other bound electrons. Our algorithm combines the approaches of (i) solid-state grid-based algorithms using self-energies and (ii) the complex Kohn method from electron-molecule scattering. For the general problem of a molecular target with n-electrons, our algorithm should ideally solve for electronic transmission with a computational cost scaling as n(2), although the present implementation is limited to one-dimensional problems. In this paper, we implement our algorithm to solve three one-dimensional model problems involving two electrons: (i) Single-channel resonant transmission through a double-barrier well (DBW), where the target already contains one bound-state electron [Rejec et al., Phys. Rev. B 67, 075311 (2003)]; (ii) multichannel resonant transmission through a DBW, where the incoming electron can exchange energy with the bound electron; (iii) transmission through a triple-barrier well (TBW), where the incoming electron can knock forward the bound electron, yielding a physical model of electron-assisted electron transfer. This article offers some insight about the role and size of exchange and correlation effects in molecular conduction, where few such rigorous calculations have yet been made. Such multibody effects have already been experimentally identified in mesoscopic electron transport, giving rise to the "0.7 anomaly," whereby electrons traveling through a narrow channel pair up as singlets and triplets. We expect the effect of electronic correlation to be even more visible for conduction through molecules, where electrons should partially localize into bonding and antibonding orbitals.


Ultrahigh-resolution OCT imaging of the human cornea.
We present imaging of corneal pathologies using optical coherence tomography (OCT) with high resolution. To this end, an ultrahigh-resolution spectral domain OCT (UHR-OCT) system based on a broad bandwidth Ti:sapphire laser is employed. With a central wavelength of 800 nm, the imaging device allows to acquire OCT data at the central, paracentral and peripheral cornea as well as the limbal region with 1.2 µm x 20 µm (axial x lateral) resolution at a rate of 140 000 A-scans/s. Structures of the anterior segment of the eye, not accessible with commercial OCT systems, are visualized. These include corneal nerves, limbal palisades of Vogt as well as several corneal pathologies. Cases such as keratoconus and Fuchs's endothelial dystrophy as well as infectious changes caused by diseases like Acanthamoeba keratitis and scarring after herpetic keratitis are presented. We also demonstrate the applicability of our system to visualize epithelial erosion and intracorneal foreign body after corneal trauma as well as chemical burns. Finally, results after Descemet's membrane endothelial keratoplasty (DMEK) are imaged. These clinical cases show the potential of UHR-OCT to help in clinical decision-making and follow-up. Our results and experience indicate that UHR-OCT of the cornea is a promising technique for the use in clinical practice, but can also help to gain novel insight in the physiology and pathophysiology of the human cornea.


Comparison of economic and clinical outcomes between patients undergoing laparoscopic bariatric surgery with powered versus manual endoscopic surgical staplers.
To compare economic and clinical outcomes between patients undergoing laparoscopic Roux-en-Y gastric bypass (LRY) or laparoscopic sleeve gastrectomy (LSG) with use of powered vs manual endoscopic surgical staplers. Patients (aged ≥21 years) who underwent LRY or LSG during a hospital admission (January 1, 2012-September 30, 2015) were identified from the Premier Perspective Hospital Database. Use of powered vs manual staplers was identified from hospital administrative billing records. Multivariable analyses were used to compare the following outcomes between the powered and manual stapler groups, adjusting for patient and hospital characteristics and hospital-level clustering: hospital length of stay (LOS), total hospital costs, medical/surgical supply costs, room and board costs, operating room costs, operating room time, discharge status, bleeding/transfusion during the hospital admission, and 30, 60, and 90-day all-cause readmissions. The powered and manual stapler groups comprised 9,851 patients (mean age = 44.6 years; 79.3% female) and 21,558 patients (mean age = 45.0 years; 78.0% female), respectively. In the multivariable analyses, adjusted mean hospital LOS was 2.1 days for both the powered and manual stapler groups (p = .981). Adjusted mean total hospital costs ($12,415 vs $13,547, p = .003), adjusted mean supply costs ($4,629 vs $5,217, p = .011), and adjusted mean operating room costs ($4,126 vs $4,413, p = .009) were significantly lower in the powered vs manual stapler group. The adjusted rate of bleeding and/or transfusion during the hospital admission (2.46% vs 3.22%, p = .025) was significantly lower in the powered vs manual stapler group. The adjusted rates of 30, 60, and 90-day all-cause readmissions were similar between the groups (all p > .05). Sub-analysis by manufacturer showed similar results. This observational study cannot establish causal linkages. In this analysis of patients who underwent LRY or LSG, the use of powered staplers was associated with better economic outcomes, and a lower rate of bleeding/transfusion vs manual staplers in the real-world setting.


Partially sequestered fourth ventricle: CT and MR diagnosis of an unusual entity.
Encystment of the fourth ventricle, due to occlusion of the aqueduct as well as the foramina of Magendie and Luschka has been described previously. Partial sequestration such as that encountered in two cases described is a less common entity. In these two cases, the aqueduct of Sylvius was occluded, but the basal foramina (Magendie and Luschka) were patent. We discuss this partial sequestration or communicating hydrocephalus of the fourth ventricle on the basis of MR and CT scan findings. Although computed tomography following water soluble cisternography did diagnose the entity indirectly MRI proved to be a superior tool. It permitted direct visualization of the basal foramina noninvasively.


Spatial intensity distribution model of fluorescence emission considering the spatial attenuation effect of excitation light.
The fluorescence quantitative analysis method of a solution is widely applied in chemical analysis, clinical medicine testing, environmental monitoring, food safety detection, and so on. It is based on the linear relationship between the intensity of fluorescence emission and the concentration of the substance in solution. Without consideration of the spatial attenuation effect of excitation light, it is applied only to a dilute solution. In this research, a fluorescence emission model is established based on the interaction and propagation law between the excitation light and the fluorescent substances. The spatial attenuation effect of excitation light is analyzed by an element analysis method, and the spatial intensity distribution of fluorescence is revealed. Further, a high accuracy model between the received fluorescence intensity and concentration is obtained. Applications of this model and further design will allow for high throughput fluorescence analysis and the analysis of fluorescent substances with ultra-wide range concentration, such as on-line testing fluorescent dyes in the textile industry, monitoring protein plasma in biomedical field, and high-throughput DNA fluorescence analysis etc. As an example, based on this model, an ultra-wide concentration range (0.02 - 250 mg/L) detection of tryptophan with high accuracy (R2 = 0.9994, RRMSE = 0.0356) is realized.


A new visual analogue scale for assessment of dyspnoea in congestive heart failure.
A new (quality of life) visual analogue scale of dyspnoea has been designed to evaluate the severity of dyspnoea in patients with congestive heart failure (CHF). The index has 10 numerical values, rated on a scale from 0-10, each value corresponding to an intensity of breathlessness. Since dyspnoea is a primary symptom that restricts the quality of life in patients with congestive heart failure, the new scale provided a simple, easily comprehensible and inexpensive instrument to assess the severity of breathlessness. We also report the sensitivity of the visual scale of dyspnoea before and after the administration of intravenous injection of a diuretic (frusemide) in CHF patients.


Short Exposure to Ethanol Diminishes Caspase-1 and ASC Activation in Human HepG2 Cells In Vitro.
This paper discusses how the assembly of pro-caspase-1 and apoptosis-associated speck-like protein containing a caspase-recruitment domain (ASC) in macromolecular protein complexes, inflammasomes, activates caspase-1. The present study investigates the molecular mechanisms of inflammasome activation in HepG2 cells and examines how short exposures to ethanol (EtOH) affect inflammasome activation. HepG2 cells were treated with lipopolysaccharide (LPS), ATP or nigericin (NIG) in a two-step model. After LPS priming, ATP or NIG were added. As inhibitors, sodium orthovanadate (general inhibitor of tyrosine phosphatases), AC-YVAD-CMK (caspase-1 inhibitor) or AZ10606120 (purinergic receptor P2X7R inhibitor) were applied after LPS priming. To monitor the inflammasome activation, the caspase-1 activity, ASC speck formation, reactive oxygen species (ROS) production and cell death were analyzed. To elucidate the mechanistical approach of EtOH to the inflammasome assembly, the cells were treated with EtOH either under simultaneous LPS administration or concurrently with ATP or NIG application. The co-stimulation with LPS and ATP induced a significant ASC speck formation, caspase-1 activation, cell death and ROS generation. The inhibition of the ATP-dependent purinoreceptor P2X7 decreased the caspase-1 activation, whereas sodium orthovanadate significantly induced caspase-1. Additional treatment with EtOH reversed the LPS and ATP-induced caspase-1 activation, ASC speck formation and ROS production. The ASC speck formation and caspase-1 induction require a two-step signaling with LPS and ATP in HepG2 cells. Inflammasome activation may depend on P2X7. The molecular pathway of an acute effect of EtOH on inflammasomes may involve a reduction in ROS generation, which in turn may increase the activity of tyrosine phosphatases.


Sustained conservation of CD4+ T cells in multiprotein triple modality-immunized rhesus macaques after intrarectal challenge with simian immunodeficiency virus.
As part of a European multicenter study designed to determine the optimal combination and order of a mixed-modality vaccine against acquired immunodeficiency syndrome, rhesus monkeys received a combination of three different vectors, all expressing the same Simian Immunodeficiency Virus (SIV) genes followed by mucosal challenge with highly pathogenic SIV. In the study reported here, animals were primed with DNA followed by one booster immunization with Semliki Forest Virus (SFV) and two immunizations with modified Vaccinia Ankara (MVA). To address the relevance of mucosal immunization, we compared systemic versus a combination of systemic and mucosal antigen application. Although all vaccinees became infected after intrarectal challenge with SIV, most (six of eight) were protected from profound loss of CD4+ cells. In addition, vaccinees showed lower viral loads than did controls (p < 0.05). Overall, these protective effects were more pronounced in those animals whose schedule included immunization via the mucosa. In summary, the vaccine regimen used here achieved one important criterion of efficacy: the suppression of disease development as indicated by conservation of CD4+ cells.


Three-dimensional cellular focusing utilizing a combination of insulator-based and metallic dielectrophoresis.
Particle focusing in microfluidic devices is a necessary step in medical applications, such as detection, sorting, counting, and flow cytometry. This study proposes a microdevice that combines insulator-based and metal-electrode dielectrophoresis for the three-dimensional focusing of biological cells. Four insulating structures, which form an X pattern, are employed to confine the electric field in a conducting solution, thereby creating localized field minima in the microchannel. These electrodes, 56-μm-wide at the top and bottom surfaces, are connected to one electric pole of the power source. The electrodes connected to the opposite pole, which are at the sides of the microchannel, have one of three patterns: planar, dual-planar, or three-dimensional. Therefore, low-electric-field regions at the center of the microchannel are generated to restrain the viable HeLa cells with negative dielectrophoretic response. The array of insulating structures aforementioned is used to enhance the performance of confinement. According to numerical simulations, three-dimensional electrodes exhibit the best focusing performance, followed by dual-planar and planar electrodes. Experimental results reveal that increasing the strength of the applied electric field or decreasing the inlet flow rate significantly enhances focusing performance. The smallest width of focusing is 17 μm for an applied voltage and an inlet flow rate of 35 V and 0.5 μl/min, respectively. The effect of the inlet flow rate on focusing is insignificant for an applied voltage of 35 V. The proposed design retains the advantages of insulator-based dielectrophoresis with a relatively low required voltage. Additionally, complicated flow controls are unnecessary for the three-dimensional focusing of cells.


Clinical and translational science sustainability: overcoming integration issues between electronic health records (EHR) and clinical research data management systems "separate but equal".
The use of health information technology (HIT) is growing rapidly for patient care systems required to test, diagnose and treat patients, and to bill for these services. Today's Electronic Health Record (EHR) systems are a response to this pressure, enabling feature rich computer-assisted decisions and communication. And even though EHR benefits dramatically outweigh the costs, required investments are nonetheless significant. Continuing to invest in HIT at a revolutionary rate is unsustainable given institutional financial constraints and continuing reimbursement cuts. Future improvements must come from new treatments, test methods, drugs and devices - from research. But data management information systems for clinical research receive less funding than patient care systems, and in less coherent ways. It is easy to imagine using the high cost, patient-based EHRs for clinical research data management, and thus accelerate the speed of translating new medical discoveries into standard practice. But taking this step requires thoughtful planning to overcome significant technology, legal/regulatory, policy, process, and administrative issues.


Gel-aided sample preparation (GASP)--a simplified method for gel-assisted proteomic sample generation from protein extracts and intact cells.
We describe a "gel-assisted" proteomic sample preparation method for MS analysis. Solubilized protein extracts or intact cells are copolymerized with acrylamide, facilitating denaturation, reduction, quantitative cysteine alkylation, and matrix formation. Gel-aided sample preparation has been optimized to be highly flexible, scalable, and to allow reproducible sample generation from 50 cells to milligrams of protein extracts. This methodology is fast, sensitive, easy-to-use on a wide range of sample types, and accessible to nonspecialists.


Staphylococcus aureus lipoproteins in infectious diseases.
Infections with the Gram-positive bacterial pathogen Staphylococcus aureus remain a major challenge for the healthcare system and demand new treatment options. The increasing antibiotic resistance of S. aureus poses additional challenges, consequently inflicting a huge strain in the society due to enormous healthcare costs. S. aureus expresses multiple molecules, including bacterial lipoproteins (Lpps), which play a role not only in immune response but also in disease pathogenesis. S. aureus Lpps, the predominant ligands of TLR2, are important for bacterial survival as they maintain the metabolic activity of the bacteria. Moreover, Lpps possess many diverse properties that are of vital importance for the bacteria. They also contribute to host cell invasion but so far their role in different staphylococcal infections has not been fully defined. In this review, we summarize the current knowledge about S. aureus Lpps and their distinct roles in various infectious disease animal models, such as septic arthritis, sepsis, and skin and soft tissue infections. The molecular and cellular response of the host to S. aureus Lpp exposure is also a primary focus.


Is urea pulsing in toadfish related to environmental O2 or CO2 levels?
The neurochemical, serotonin (5-hydroxytryptamine; 5-HT) is involved in the regulation of toadfish pulsatile urea excretion as well as the teleost hypoxia response. Thus, the goal of this study was to determine whether environmental conditions that activate branchial chemoreceptors also trigger pulsatile urea excretion in toadfish, since environmental dissolved oxygen levels in a typical toadfish habitat show significant diel fluctuations, often reaching hypoxic conditions at dawn. Toadfish were fitted with arterial, venous and/or buccal catheters and were exposed to various environmental conditions, and/or injected with the O(2) chemoreceptor agonist NaCN or the 5-HT(2) receptor agonist alpha-methyl-5HT. Arterial PO(2), as well as ammonia and urea excretion were monitored. Natural fluctuations in arterial PO(2) levels in toadfish did not correlate with the occurrence of a urea pulse. Chronic exposure (24 h) of toadfish to hyperoxia was without effect on nitrogen excretion, however, exposure to hypoxia caused a significant reduction in the frequency of urea pulses, and exposure to hypercapnia resulted in a reduction in the percentage of nitrogen waste excreted as urea. Of toadfish exposed acutely to hypoxia, 20% pulsed within 1 h, whereas none pulsed after normoxic or hypercapnic treatments. Furthermore, 20% of fish injected intravenously with NaCN pulsed within 1 h of injection, but no fish pulsed after injection of NaCN into the buccal cavity. To test whether environmental conditions affected 5-HT(2) receptors, toadfish were injected with alpha-methyl-5HT, which elicits urea pulses in toadfish. No significant differences in pulse size occurred among the various environmental treatments. Our findings suggest that neither the environmental conditions of hypoxia, hyperoxia or hypercapnia, nor direct branchial chemoreceptor activation by NaCN play a major role in the regulation of pulsatile urea excretion in toadfish.


Human skeletal muscle lactate dehydrogenase activity in the presence of some alcohol dehydrogenase inhibitors.
Methanol, ethylene glycol and other alcohol intoxications are complicated by severe acidosis which could be caused by formation of metabolic acids and additionally lactic acid production. An increasing nicotinamide adenine dinucleotide reduced/nicotinamide adenine dinucleotide oxidized (NADH/NAD) ratio during alcohol biotransformation is responsible for the induction of lactic acidosis. The main purpose of the present paper was to evaluate the effect of 4-methylpyrazole, cimetidine, ethylenediaminetetraacetic acid disodium salt, ethanol and methanol on lactate dehydrogenase (E.C. 188.8.131.52) activity and to discuss this issue. The activity of the enzyme was determined spectrophotometrically, in vitro using human enzyme skeletal muscle homogenates. 4-Methylpyrazole, cimetidine and ethylenediaminetetraacetic acid disodium salt at concentrations 0.01, 0.1, 1.0 mM and 12.5, 25.0, 50.0 mM of ethanol and methanol were studied. Our results showed that cimetidine increased lactate dehydrogenase activity as compared to the control at all tested concentrations. Such activity was noted for 4-methylpyrazole at 0.1 mM and higher concentration. By contrast, no significant effect on lactate dehydrogenase activity in the presence of ethylenediaminetetraacetic acid disodium salt, methanol and ethanol was observed.


Maskless laser direct patterning of PEDOT/PSS layer for soluble process organic thin film transistor.
In this work, we have fabricated TIPS-pentacene TFTs with conductive polymer (3,4-ethylenedioxythiophene):poly(4-stylenesulfonate) (PEDOT:PSS) source/drain electrodes which is patterned by maskless laser direct patterning (LDP). The 5-microm resolution of source and drain patterns with PEDOT:PSS were clearly defined. Furthermore, the OTFTs with 10-microm channel length were successfully achieved by exposing the focused Neodymium:Yttrium Aluminum Garnet (Nd:YAG) laser beam onto the spin-coated PEDOT:PSS films and developing with deionized water. The electrical performance of the TIPS-pentacene TFTs with PEDOT:PSS source/drain electrodes were improved with decrease of the sheet resistance of PEDOT:PSS films when the PEDOT:PSS films were annealed at the temperature above 200 degrees C.


Didelphys Uterus: A Case Report and Review of the Literature.
Background. Mullerian duct anomalies (MDAs) are congenital defects of the female genital system that arise from abnormal embryological development of the Mullerian ducts. A didelphys uterus, also known as a "double uterus," is one of the least common amongst MDAs. This report discusses a case of didelphys uterus that successfully conceived, carried her pregnancy to term, and delivered vaginally without any significant complications. Case. Patient is a 29-year-old G2P0010 from Bangladesh, initially came a year prior in her first pregnancy, with spontaneous abortion (SAB). Pelvic Sonogram at that time showed a diagnosis of bicornuate versus didelphys uterus. There were no renal anomalies on subsequent abdominal CT scan. Patient presented with the second pregnancy and had uncomplicated prenatal care and did not have signs of preterm labor; fetus showed appropriate growth and the pregnancy was carried in the left uterus. Patient presented at 38 4/7 wks with Premature Rupture of Membrane and underwent induction of labor with Cytotec. Antibiotics were started for chorioamnionitis. Patient had a vaginal delivery with left mediolateral episiotomy and complete tear of vaginal septum. Third stage of labor was complicated with retained placenta, which was removed manually in the operating room with total EBL of 600 cc.


Effect of interfacial adhesion on the ultrasonic interaction with adhesive joints: A theoretical study using spring-type interfaces.
The effect of interfacial properties on the reflection and transmission characteristics of ultrasonic waves at adhesively bonded joints is theoretically investigated. An adhesive joint is modeled as a double-interface model, namely, a homogeneous layer coupled to adherends by two spring-type interfaces with different interfacial stiffnesses. For the normal incidence of a one-dimensional longitudinal wave, theoretical results are obtained and validated by finite element simulation. When the thickness of the adhesive layer is sufficiently small compared to the wavelength, the amplitude reflection and transmission coefficients show monotonic dependence on frequency, which can be explained by the theoretical relation of the double-interface model to a single spring-type interface model. The reflection and transmission behavior is invariant if the values of the two interfacial stiffnesses are interchanged. For a relatively thick adhesive layer, on the other hand, the reflection coefficient shows local minima at multiple frequencies. As one interfacial stiffness decreases, the local minimum frequencies decrease and the local minima increase. If the values of the two interfacial stiffnesses are interchanged, the reflection coefficient remains invariant but the reflection waveform shows different features. The obtained reflection and transmission characteristics are discussed in light of the characterization of the interfacial adhesion.


Pathological Features in 100 Deceased Patients With COVID-19 in Correlation With Clinical and Laboratory Data.
Background: Autopsies on COVID-19 deceased patients have many limitations due to necessary epidemiologic and preventative measures. The ongoing pandemic has caused a significant strain on healthcare systems and is being extensively studied around the world. Clinical data does not always corelate with post-mortem findings. The goal of our study was to find pathognomonic factors associated with COVID-19 mortality in 100 post-mortem full body autopsies. Materials and Methods: Following necessary safety protocol, we performed 100 autopsies on patients who were diagnosed with COVID-19 related death. The macroscopic and microscopic pathologies were evaluated along with clinical and laboratory findings. Results: Extensive coagulopathic changes are seen throughout the bodies of diseased patients. Diffuse alveolar damage is pathognomonic of COVID-19 viral pneumonia, and is the leading cause of lethal outcome in younger patients. Extrapulmonary pathology is predominantly seen in the liver and spleen. Intravascular thrombosis is often widespread and signs of septic shock are often present. Conclusion: The described pathological manifestations of COVID-19 in deceased patients are an insight into the main mechanisms of SARS-CoV-2 associated lethal outcome. The disease bears no obvious bias in severity, but seems to be more severe in some patients, hinting at genetic or epigenetic factors at play.


Some current issues for health visiting.
Michael Traynor argues that recent legislation with its emphasis not only on targeted, measurable and effective service but also on the importance of health promotion offers exciting opportunities for health visiting. But to take advantage of these, health visitors will need to become familiar with the growing body of research into the evaluation of health visitors' preventive, supportive and health promotion roles.


An outbreak of Pantoea spp. in a neonatal intensive care unit secondary to contaminated parenteral nutrition.
Contaminated parenteral nutrition (PN) is an important source of infection in neonates. Many organisms have been reported to cause contamination that results in outbreaks in intensive care units. The objective of this study was to investigate an outbreak caused by Pantoea spp., which contaminates PN, in a neonatal intensive care unit (NICU). This was a descriptive study of an outbreak of sepsis in an NICU of a tertiary teaching hospital in Malaysia. Pantoea spp. infection was detected in eight patients over a three-day period from 24 to 27 January 2004 following the administration of PN. Seven of the eight patients died due to the infection. Extensive environmental samplings for culture were performed. PN solution from the NICU and the pharmacy were also cultured during the outbreak period. Pantoea spp. was isolated from blood cultures of all infected patients, and the unused PN from the pharmacy and the NICU. All the strains of Pantoea spp. had a similar antibiotic susceptibility pattern and biochemical reaction. From the results, we concluded that PN was the source of the outbreak and the contamination may have occurred during its preparation in the pharmacy. A thorough investigation has been carried out and, where possible, corrective measures have been taken to avoid similar outbreaks in the future.


Traversing a wormhole to combat Parkinson's disease.
Human movement disorders represent a significant and unresolved societal burden. Among these, the most prevalent is Parkinson's disease (PD), a disorder afflicting millions worldwide. Despite major advances, stemming primarily from human genetics, there remains a significant gap in our understanding of what factors underlie disease susceptibility, onset, and progression. Innovative strategies to discern specific intracellular targets for subsequent drug development are needed to more rapidly translate basic findings to the clinic. Here we briefly review the recent contributions of research using the nematode roundworm Caenorhabditis elegans as a model system for identifying and characterizing gene products associated with PD. As a microscopic but multicellular and genetically tractable animal with a well-defined nervous system and an experimentally tenable lifespan, C. elegans affords significant advantages to researchers attempting to determine causative and therapeutic factors that influence neuronal dysfunction and age-associated neurodegeneration. The rapidity with which traditional genetic, large-scale genomic, and pharmacological screening can be applied to C. elegans epitomizes the utility of this animal for disease research. Moreover, with mature bioinformatic and functional genomic data readily available, the nematode is well positioned to play an increasingly important role in PD-associated discoveries.