Comparison of test results from two separate video head impulse test systems in a cohort of patients diagnosed with a unilateral vestibular schwannoma.
Video head impulse testing (vHIT) is a relatively new technology enabling evaluation of vestibular function. The aim of this study was to compare the test results from two separate vHIT systems in a group of patients diagnosed with a unilateral vestibular schwannoma (VS) with regards to sensitivity, specificity and inter-examiner differences. Forty-two patients were examined with two separate vHIT systems: EyeSeeCam® (system A) and ICS Impulse® (system B), by one of two examiners. All six semicircular canals (SCCs) were tested under standardized conditions, and strict criteria were set up for post-test interpretation. With the majority of test parameters, the two test systems were in agreement. Vestibular deficits were found in 40.5% (system A) to 45% (system B) of patients with a VS on the tested side; corresponding to a positive predictive value (PPV) of 86.4% (system B) to 94.4% (system A). The specificity was 97.6% for system A and 92.9% for system B. An overall agreement between the two vHIT systems measured as kappa was computed to be 0.61. There were no significant inter-examiner differences. When testing the vertical SCCs, a tendency of too high mean gain values was seen with system A but not with system B. In patients with unilateral VS, vHIT is a test with moderate sensitivity and high specificity in regard to identification of a vestibular deficit. There were no significant differences in test results between the two vHIT systems.


Polymeric nanoparticles for siRNA delivery and gene silencing.
Gene silencing using small interfering RNA (siRNA) has several potential therapeutic applications. In the present study, we investigated nanoparticles formulated using the biodegradable polymer, poly(d,l-lactide-co-glycolide) (PLGA) for siRNA delivery. A cationic polymer, polyethylenimine (PEI), was incorporated in the PLGA matrix to improve siRNA encapsulation in PLGA nanoparticles. PLGA-PEI nanoparticles were formulated using double emulsion-solvent evaporation technique and characterized for siRNA encapsulation and in vitro release. The effectiveness of siRNA-loaded PLGA-PEI nanoparticles in silencing a model gene, fire-fly luciferase, was investigated in cell culture. Presence of PEI in PLGA nanoparticle matrix increased siRNA encapsulation by about 2-fold and also improved the siRNA release profile. PLGA-PEI nanoparticles carrying luciferase-targeted siRNA enabled effective silencing of the gene in cells stably expressing luciferase as well as in cells that could be induced to overexpress the gene. Quantitative studies indicated that presence of PEI in PLGA nanoparticles resulted in 2-fold higher cellular uptake of nanoparticles while fluorescence microscopy studies showed that PLGA-PEI nanoparticles delivered the encapsulated siRNA in the cellular cytoplasm; both higher uptake and greater cytosolic delivery could have contributed to the gene silencing effectiveness of PLGA-PEI nanoparticles. Serum stability and lack of cytotoxicity further add to the potential of PLGA-PEI nanoparticles in gene silencing-based therapeutic applications.


Stocking-only versus additional eccentric compression after below-the-knee truncal vein sclerotherapy: A SOVAECS prospective randomized within-person trial.
After foam sclerotherapy in the truncal saphenous vein, the clinical effects of additional eccentric compression has not yet been explored. Between April 2020 and February 2021, we enrolled 42 patients (84 limbs) who underwent bilateral endovenous combined therapy for great saphenous vein (GSV) reflux. Each patient received the same type of endovenous ablation in both above-the-knee GSVs (laser, radiofrequency, cyanoacrylate glue), and combined foam sclerotherapy was performed on both below-the-knee GSVs. Subsequently, we conducted a prospective randomized, single-blind, within-person study in which each patient's bilateral truncal saphenous vein of the calves underwent two different compression therapies: wearing of a regular class II compression stocking on one side (RC group) and additional eccentric compression on the other side (AC group). The primary end point was the occlusion range (score, 0-10) of the below-the-knee truncal GSV after foam sclerotherapy. The secondary outcomes were the pain score (visual analog scale score range, 0-10) of the paired limb, the required number of additional foam sclerotherapy sessions, compliance with compression therapy, and procedure-related complications. For the above-the-knee GSV, endovenous laser treatment (n = 44), endovenous radiofrequency ablation (n = 14), and endovenous cyanoacrylate glue ablation (n = 26) were performed. The mean subcompression pressure of the medial calf in the supine and standing positions were 16.7 ± 2.34 mm Hg and 24.5 ± 6.6 mm Hg in the RC group and 38.5 ± 5.5 mm Hg and 45.3 ± 8.2 mm Hg in the AC group, respectively (P = .000). The secondary outcomes of pain score, number of additional foam sclerotherapy sessions, and pigmentation were not significantly different statistically between the two groups. The patient-reported satisfaction scores (range, 0-10) on compression at 24 hours postoperatively were 8.03 ± 1.9 for the AC group and 7.98 ± 1.9 for the RC group (P = .317; Wilcoxon signed ranks test). In both groups, the closure rate of the above-the-knee GSV at 1 month postoperatively was 100%. No procedure-related complications were identified within 1 month postoperatively, including no deep vein thrombosis, numbness, or skin necrosis requiring additional medical attention. The 24 hours of additional eccentric compression on the truncal GSV compared with the use of a conventional knee-level stocking only did not yield any clinical advantages in terms of the occlusion range, postoperative pain, need for additional sclerotherapy, or skin pigmentation after foam sclerotherapy. The decision on which type of compression therapy to perform after foam sclerotherapy in the truncal vein should be comprehensively determined.


Systematic comparison of beta spectra calculations using improved analytical screening correction with experimental shape factors.
From a review of the available literature, a database of experimental shape factors from measured beta spectra was created in previous work. Classical assumptions applied in beta spectra calculations which avoid the determination of the electron and nuclear wave functions were tested by comparison with each measured spectrum present in the database. From this systematic comparison, it was demonstrated that the typical assumption λk=1 is inappropriate for all forbidden unique transitions. Moreover, the equally common ξ-approximation was also proved to be incorrect for about half of the listed first forbidden non-unique transitions and for all second non-unique ones. In present work, this study has been performed once again using an improved analytical screening correction. General results from previous study still remain the same. Except for allowed transitions, the mean energies in current nuclear databases are expected to be erroneous. Some selected beta spectra are also given to illustrate these results.


Subunit composition specific to axonally transported tubulin.
One week after injection of L-[35S]methionine into the dorsal motor nuclei of the guinea-pig, labelled tubulin carried down the vagal nerve by the slow phase of axonal transport was analysed by one- and two-dimensional gel electrophoresis. Transported tubulin showed a much stronger labelling of the beta-subunit. Isoelectric focussing revealed that both alpha- and beta-subunits were composed of several components. Labelled tubulin was isolated from the brain by cycles of polymerisation and depolymerisation after injection of L-[35S]methionine into the lateral ventricle, for comparison with transported tubulin from the vagal nerve. In addition to the two alpha-components and three beta-components detected in both preparations, axonally transported tubulin contained an extra component (TAX) with a molecular weight corresponding to that of beta-tubulin and with the same isoelectric point as alpha-tubulin. The axon-specific component TAX co-polymerised with tubulin isolated from the brain. Upon peptide mapping by limited proteolysis, the peptide pattern generated from TAX was similar to that of the alpha-tubulin. It is concluded that the axonally transported tubulin contains a modified alpha-subunit which is not found in the bulk of brain tubulin.


Patterns of axis II comorbidity in early-onset versus late-onset panic disorder in Japan.
Early onset of psychiatric disorders has been reported to be associated with increased familial risk or more severe clinical symptoms. In this study, we specifically examine the association between clinical severity and early versus late onset in panic disorder. We hypothesize the existence of differences in rates of axis II disorders in these two groups that will relate to clinical severity. Subjects were a consecutive clinical case series of 105 panic disorder patients (age, 18.3 to 70.9 years). Thirty-one panic disorder patients were classified as early onset (age of onset < or = 25 years) and 74 as late onset (age of onset >25). We compared symptomatology and rates of comorbid axis II disorders (diagnosed by structured clinical interview) between the early- and the late-onset groups. We found a statistically significant increase in the number of suicide attempts and likelihood of comorbid axis II disorders in the early-onset group compared to the late-onset group. In logistic regression analyses, cluster B personality disorders (PDs), especially borderline and histrionic, were statistically significantly associated with the presence of suicide attempts. The following limitations are present: first, we have not taken into consideration comorbidity of other axis I disorders, especially major depression. Second, there is imprecision associated with efforts to date the onset of panic disorder retrospectively. We conclude that comorbid axis II disorders are more likely to occur in early-onset panic disorder patients. Cluster B PDs, especially borderline or histrionic, may be associated with a high frequency of suicide attempts in this group. In clinical practice, efforts to aggressively detect and treat axis II disorders in early-onset panic disorder patients are warranted.


Kidney stones: natural remedies and lifestyle modifications to alleviate their burden.
Kidney stones (KSs), in fact, have been considered one of the most ancient and prevalent medical conditions that impact a significant number of human beings all around the world. Such stones can range greatly in size and can be detected in any part of the urinary system, including the kidneys, ureters, or bladder itself. The development of stones is caused by the mineral's crystallization, which then interacts with each other and adheres together. Kidney stone formation can represent a prime medical condition for which there are numerous therapies available, among them natural ones. Recurrence of stones after curing is very common, and strategies available to prevent their reoccurrence or even their development for the first time are numerous, with enhanced fluid consumption or avoiding dehydration being the most important one. The current review article aims to draw attention to the potential of natural remedies besides lifestyle modification in the management and prevention of KSs. This is not arbitrary but based on real, documented scientific evidence. The natural remedies mentioned in the context of this manuscript were chosen for their availability in almost all nations, or perhaps even in every home. The findings of the present article are very promising and exhibit the potential benefit of natural remedies in addition to shifting to a healthy lifestyle in both the treatment and prevention of KSs.


[In vitro sensitivity to 5-fluorocytosine and amphotericin B of yeasts of the Candida genus isolated in Barcelona].
In 200 strains of Candida sp, 38.5% were found to have intermediate sensitivity or to be resistant to amphotericin B and/or 5-fluorocytosine by the agar diffusion method. When the minimal inhibitory concentrations of these strains were measured, only 7.8% were resistant to amphotericin B and 2.8% to 5-fluorocytosine. The species with the highest levels of resistance were C. parapsilosis, C. tropicalis and Torulopsis glabrata. Candida albicans did not show resistance to 5-fluorocytosine.


Correction to: Impact of migraine on workplace productivity and monetary loss: a study of employees in banking sector in Malaysia.
An amendment to this paper has been published and can be accessed via the original article.


Environmentally safe production of 7-aminodeacetoxycephalosporanic acid (7-ADCA) using recombinant strains of Acremonium chrysogenum.
Medically useful semisynthetic cephalosporins are made from 7-aminodeacetoxycephalosporanic acid (7-ADCA) or 7-aminocephalosporanic acid (7-ACA). Here we describe a new industrially amenable bioprocess for the production of the important intermediate 7-ADCA that can replace the expensive and environmentally unfriendly chemical method classically used. The method is based on the disruption and one-step replacement of the cefEF gene, encoding the bifunctional expandase/hydroxylase activity, of an actual industrial cephalosporin C production strain of Acremonium chrysogenum. Subsequent cloning and expression of the cefE gene from Streptomyces clavuligerus in A. chrysogenum yield recombinant strains producing high titers of deacetoxycephalosporin C (DAOC). Production level of DAOC is nearly equivalent (75-80%) to the total beta-lactams biosynthesized by the parental overproducing strain. DAOC deacylation is carried out by two final enzymatic bioconversions catalyzed by D-amino acid oxidase (DAO) and glutaryl acylase (GLA) yielding 7-ADCA. In contrast to the data reported for recombinant strains of Penicillium chrysogenum expressing ring expansion activity, no detectable contamination with other cephalosporin intermediates occurred.


Misconceptions and Facts About Beta-Blockers.
Beta-blockers are commonly used medications, and they have been traditionally considered "cardioprotective." Their clinical use appears to be more widespread than the available evidence base supporting their role in cardioprotection. Beta-blockers counteract neurohumoral activation in heart failure with reduced ejection fraction and offer both symptomatic improvement and reduction in adverse events. On the other hand, the use of beta-blockers in uncomplicated hypertension results in suboptimal outcomes compared to the established first-line antihypertensive agents. Providers at all levels should be familiar with common misconceptions regarding beta-blocker use in routine clinical practice.


Nonsurgical Management of Lymph Node Basins in Melanoma.
In this article we provide a critical review of the evidence available for surgical management of the nodal basin in melanoma, with an aim to ensure an understanding of risks and benefits for all lymph node surgery offered to patients, and alternatives to surgical management where appropriate.


Astrocytes and synaptosomes transport and metabolize lactate and acetate differently.
Astrocytes transport the monocarboxylate acetate, but synaptosomes do not. The reason for this is unknown, because both preparations express monocarboxylate transporters (MCT). The transport and metabolism of lactate, another monocarboxylate, was examined in these two preparations, and the results were compared to those for acetate. Lactate transport is more rapid in astrocytes than in synaptosomes, but of lower affinity (Kms of 17 and 4 mM, respectively). Lactate (0.2 mM) is metabolized to CO2 more rapidly in synaptosomes than in astrocytes (rates of 0.37 and 0.07 nmol x mg protein(-1) x min(-1), respectively). The reason for this is unclear, but cellular differences in lactate dehydrogenase isotype expression may be involved. Acetate is metabolized to CO2 more rapidly in astrocytes than in synaptosomes (rates of 0.43 and 0.02 nmol x mg protein(-1) x min(-1), respectively). This is likely due to cellular differences in the expression of monocarboxylate transporter subtypes.


Normative values of the Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) in an Arab population: Corrected for age, sex and education.
Background Cognitive impairment is common in multiple sclerosis (MS) patients with 43-70% of patients being affected. The international cognitive assessment for MS BICAMS is a new battery for cognitive assessment in MS patients. It was suggested in 2012 that international validation efforts be undertaken. Objective To utilize regression to provide normative values for the BICAMS while correcting for age, gender and education, as well as assess test-retest reliability, in an Arab population. Methods Healthy subjects were recruited from different areas in Dubai. Corrections for demographics were calculated using multiple linear regression. Test-retest reliability was assessed using the Pearson correlation coefficient. Results Two hundred eighty-one healthy subjects were enrolled (174 women, mean age 30±10.3 years, mean education 17.8±3.7 years). Test re-test results showed significant correlation between baseline and retest scores. Regression-based equations were derived for the BICAMS. Conclusion This large-scale validation study provides evidence to support the facilitation of international implementation of the BICAMS assessment by focusing on the Arab population. Next steps include validation efforts in an Arab MS patient population to further support the use of the BICAMS in day to day practice and for longitudinal patient assessment.


Atopic dermatitis: the role of recombinant interferon-gamma therapy.
Atopic dermatitis is a common, chronic, relapsing cutaneous disease with typical cellular and humoral immunologic abnormalities that can result in significant physical and psychological morbidity to the patient. Atopic dermatitis typically begins in childhood and can often persist through adolescence into adulthood. Although there are a variety of treatments for atopic dermatitis, many patients' symptoms do not improve or they have adverse reactions to medications, requiring the search for other, effective therapeutic agents. A number of inflammatory and immunological abnormalities have long been noted in patients with atopic dermatitis. Although great strides have been made in understanding the causes, the complex pathophysiology of atopic dermatitis is still not completely understood. Most notably, patients with atopic dermatitis often have an elevation of serum immunoglobulin (Ig) E levels, depressed cellular immunity, elevated blood eosinophilia, and increased interleukin (IL)-4 production. In addition, peripheral blood mononuclear cells of patients with atopic dermatitis produce reduced levels of interferon-gamma spontaneously and in response to stimuli. Due to this constellation of features, atopic dermatitis was initially viewed as a prototypical type 2 helper T lymphocyte (T(h2)) disease. These immunological findings led to a number of clinical trials with recombinant interferon-gamma in patients who had severe, unremitting atopic dermatitis. Treatment with recombinant interferon-gamma was postulated to be able to correct the immunological imbalances in patients with atopic dermatitis by decreasing serum IgE levels, IL-4 levels, restoring immune balance, and thereby leading to clinical improvement. Initial open-label studies, a double-blind placebo trial, and long-term open-label studies have demonstrated the clinical efficacy and tolerability of recombinant interferon-gamma in a subset of patients with severe, unremitting atopic dermatitis. Patients receiving treatment often had marked decreases in severity of clinical parameters: erythema, edema/indurations, pruritus, excoriations, dryness, lichenification and associated reduction in total body surface area involvement. Surprisingly, treatment with recombinant interferon-gamma did not lower serum IgE levels refuting the hypothesized mechanism by which interferon-gamma would bring about clinical improvement in patients with atopic dermatitis. Instead, decreases were noted in absolute white blood cell and eosinophil counts that tended to correlate with clinical improvement. Although the exact mechanism by which recombinant interferon-gamma brings about clinical changes in patients with atopic dermatitis is unknown, recombinant interferon-gamma should be considered a possible therapy for patients with atopic dermatitis.


The molecular genetics of lung morphogenesis and injury repair.
Lung development, as well as epithelial injury repair, is tightly coordinated by a fine balance between stimulatory versus inhibitory genes that appear to co-regulate the function of stem/progenitor cells in the lung. Recently, it has been noted that many of the same genes direct development of the respiratory organs (tracheae) in the fruit fly Drosophila as in mice and men. For example, FGF receptor tyrosine kinase signaling is essential for respiratory organogenesis in both fly and mouse and is negatively regulated by the sprouty genes, a family of inducible FGF pathway inhibitors. Additionally, FGF signaling is required for formation of new alveoli, protection of alveolar epithelial cells from injury, as well as migration and proliferation of putative alveolar stem/progenitor cells during lung repair. Conversely, TGFbeta receptor serine-threonine kinase signaling via Smads 2, 3 and 4 inhibits lung morphogenesis and can inhibit postnatal alveolar development, while excessive TGFbeta signaling via Smad3 causes interstitial fibrosis. On the other hand, BMP4 stimulates morphogenesis of intact embryonic lung, while inhibiting proliferation of isolated epithelium. We speculate that evolutionary-developmental, functional conservation of the FGF- FGFR-SPROUTY stimulatory pathway as well as of the TGFbeta/BMP-SMAD modulatory pathways identifies them as potential therapeutic targets for rational therapy. Novel therapy to activate lung stem/progenitor cells, ameliorate lung injury, augment lung repair and/or induce lung regeneration could be highly beneficial in both children and adults with intractable pulmonary insufficiency.


Toll like receptor7 polymorphisms in relation to disease susceptibility and progression in Chinese patients with chronic HBV infection.
Toll-like receptors (TLRs) play a key role in innate and adaptive immunity, protecting the host from viral pathogens. We studied the effect of TLR7 polymorphisms on disease susceptibility and progression of chronic hepatitis B (CHB) infection in Chinese adults. Blood samples were taken from 612 patients with confirmed CHB, hepatitis B virus (HBV)-related liver cirrhosis (LC) or hepatocellular carcinoma (HCC) and 293 controls. TLR7 polymorphisms (rs179010-C > T, rs2074109-T > C, and rs179009-A > G) were analyzed by PCR-based sequencing. A significantly higher frequency of TLR7 rs179010 C allele was found in male CHB patients than in controls (74.8% vs 59.5%, P = 0.002). The frequency of rs179009 G allele was markedly increased with disease progression when male patients with CHB, LC and HCC were compared (P = 0.012). The haplotype CTA was significantly associated with an increased susceptibility to CHB among male patients (P = 0.000). Frequency of the haplotype CTG was higher in male patients with HCC than CHB (P = 0.005). No such differences in these allele frequencies were found between female patients and controls. Our results indicated that TLR7 polymorphisms play an important role in disease susceptibility and the progression of CHB infections in Chinese adults, and may partly explain the high incidence of HBV related diseases in Chinese men.


Cloning and sequence analysis of a rat liver cDNA encoding acyl-peptide hydrolase.
Acyl-peptide hydrolase catalyzes the removal of an N alpha-acetylated amino acid residue from an N alpha-acetylated peptide. Two overlapping degenerate oligonucleotide probes based on the sequence of a CNBr tryptic peptide, derived from purified rat acyl-peptide hydrolase, were synthesized and used to screen a rat liver lambda gt11 cDNA library. A 2.5-kilobase cDNA was cloned and sequenced. This clone contained 2364 base pairs of rat acyl-peptide hydrolase sequence but lacked a translational initiation codon. Using a 220-base pair probe derived from near the 5'-end of this almost full-length cDNA to rescreen the library, full-length clones were isolated, which contained an in-frame ATG codon at nucleotides 6-8 and encoded the NH2-terminal sequence, Met-Glu-Arg-Gln.... The DNA sequence encoded a protein of 732 amino acid residues, 40% of which were confirmed by protein sequence data from 19 CNBr or CNBr tryptic peptides. The isolated enzyme is NH2-terminally blocked (Kobayashi, K., and Smith, J. A. (1987) J. Biol. Chem. 262, 11435-11445), and based on the NH2-terminal protein sequence deduced from the DNA sequence and the sequence of the most NH2-terminal CNBr peptide, it is likely that the NH2-terminal residue is an acetylated methionine residue, since such residues are frequently juxtaposed to glutamyl residues (Persson, B., Flinta, C., von Heijne, G., and Jornvall, H. (1985) Eur. J. Biochem. 152, 523-527). The RNA blot analysis revealed a single message of 2.7 kilobases in various rat tissues examined. Although this enzyme is known to be inhibited by diisopropyl fluorophosphate and acetylalanine chloromethyl ketone (Kobayashi, K., and Smith, J. A. (1987) J. Biol. Chem. 262, 11435-11445), no strong similarity in protein sequence has been found with other serine proteases. This result suggests that acyl-peptide hydrolase may be a unique serine protease.


Efficacy of combined metronidazole and triple tetracycline therapy in the treatment of non-gonococcal urethritis.
In a double-blind placebo-controlled trial using triple tetracycline (Deteclo, Lederle) 300 mg twice daily for two weeks in conjunction with metronidazole (Flagyl, May & Baker) 400 mg or matching placebo twice daily for seven days, it was shown that the addition of anti-anaerobic therapy did not significantly affect the number of cases of persistent urethritis or the relapse of patients with non-gonococcal urethritis (NGU).


Rupture of the stomach: a rare complication of resuscitation. Case report.
Rupture of the stomach following resuscitation is a rare event and only five such cases have been published before. A case is presented and the pathological anatomy, clinical picture and treatment discussed.


Genetics of neural crest and neurocutaneous syndromes.
Neural crest progenitor cells are identified at the lateral margins of the neural placode at the time of gastrulation. With folding of the placode, these precursors are brought to the dorsal midline of the neural tube at the site of closure, become committed to neural crest lineage and almost immediately migrate peripherally to various predetermined sites in the body and then differentiate as a variety of cellular types in all three of the traditional "germ layers." All of these processes of migration and differentiation of neural crest are precisely genetically programed, temporally and spatially, by a variety of genes. Primary neurocutaneous syndromes are all very different diseases with different genetic mutations, but the unifying factor amongst them is that all are neurocristopathies and can be explained as such, including the tumor-suppressor function of several of these genes, especially those of neurofibromatosis 1 and 2 and tuberous sclerosis. This chapter reviews the principal genes that program neural crest development and also are documented, implicated, or suspected in the pathogenesis of neurocutaneous syndromes. Recent genetic discoveries are noted in epidermal nevus syndrome, including Proteus syndrome and their association with hemimegalencephaly and congenital infiltrating lipomatosis of the face.


Embryologic considerations of diphallus and associated anomalies.
Two patients, 1 adult and 1 infant, with complete duplication of the penis are described. The adult had a single bladder, a bifid scrotum, a low abdominal wall hernia, separation of the symphysis pubis, bilateral inguinal hernias, rectal prolapse, bilateral vesicoureteral reflux and bilateral staghorn calculi. The infant had duplication of the bladder, hypoplasia of the left kidney, lumbosacral anomalies, a hypoplastic left lower extremity, an imperforate anus, a infraumbilical wall hernia and separation of the symphysis pubis. A survey of the anomalies accompanying the 2 main types of diphallus (shaft and glans, and glans alone)showed that there was a preponderance of anomalies of posterior structures such as colon, bladder and spine in the shaft and glans diphallus, and a higher incidence of isolated exstrophy of the bladder in diphallus of the glans alone. The embryogenic implications of these findings are discussed.


Unintended Perioperative Hypothermia and Surgical Site Infection in Children.
Unintended perioperative hypothermia is associated with surgical site infection (SSI) in adults, prompting exhaustive efforts to maintain perioperative normothermia. Although these efforts are also made for pediatric patients, the association between hypothermia and SSI has not been demonstrated in children. We sought to determine whether perioperative hypothermia and other risk factors and clinical outcomes are associated with SSI in the pediatric population. This case-control study took place from January 2014 through December 2016 and included patients at a National Surgical Quality Improvement Program-participant academic children's hospital. All surgical patients were included in this retrospective analysis. SSI rates were determined. A univariate analysis was performed to determine clinical factors associated with SSI. A multivariate regression analysis was then performed to determine the predictive effect of minimum perioperative temperature for SSI. This study included 3541 patients, of which 92 (2.6%) developed SSI. A univariate analysis showed associations among SSI and higher perioperative temperatures, surgical specialty of otolaryngology and general surgery, and wound classification (American Society of Anesthesiologists [ASA] classification III and IV). A multivariate analysis determined the odds of SSI increased by a factor of 1.6 for every 1°C increase in minimum perioperative temperature. Unintended perioperative hypothermia in our pediatric patients was inversely associated with SSI. This finding suggests that pediatric SSI prevention may not require the efforts made for adult patients to maintain normothermia.


Topographical distribution of acetylcholinesterase and butyrylcholinesterase in the diencephalon and mesencephalon of the garden lizard (Calotes versicolor).
The present report incorporates the histochemical mapping of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) among the various nuclei and fiber tracts of the diencephalon and mesencephalon of Calotes veriscolor. The various nuclei, for both enzymes, present varying degrees of staining, ranging from negative nuclei, on the one hand, to mild and intense staining on the other hand. Almost all of the fiber tracts reveal intense activity in BChE preparations, while they demonstrate mild and moderate activities for AChE. The nature of the various nuclei in relation to enzymatic patterns is discussed.


Ventilator-assisted youth: appraisal and nursing care.
An interdisciplinary review of 16 ventilator-assisted, cervical-cord injured youth, aged 3-19 years, was completed to explore long-term outcomes and develop recommendations for care. Ten youths were younger than 12 years; 6 were adolescents. The mean initial hospital length of stay was 192 days. Discharged youths were followed for 1-73 months after hospitalization. Nursing implications were developed using a systems approach with North American Nursing Diagnosis Association (NANDA) approved diagnoses. Nursing case management was used to coordinate discharge planning and continuity of care. At the time of data collection 13 youths had been successfully reintegrated to home, school and community, the least restrictive environments for all.


Preliminary biological evaluation of ¹²⁵I-labeled anti-carbonic anhydrase IX monoclonal antibody in the mice bearing HT-29 tumors.
To evaluate ¹²⁵I-labeled anti-carbonic anhydrase IX monoclonal antibody (¹²⁵I-MAb) as a novel single-photon emission computed tomography tracer for imaging carbonic anhydrase IX in the mice bearing HT-29 tumors. Anti-carbonic anhydrase IX monoclonal antibody was labeled with iodine-125 by the iodogen method. The radiochemical purity of ¹²⁵I-MAb was measured by radio-thin-layer chromatography. The in-vitro stability of ¹²⁵I-MAb was determined in PBS (0.05 mol/l, pH 7.4) or new-born calf serum at 37°C, and analyzed by radio-thin-layer chromatography. A biodistribution study and planar imaging were carried out in the mice bearing HT-29 tumors. The expression of CA IX in HT-29 tumors was analyzed by immunohistochemistry. ¹²⁵I-MAb was obtained with a radiolabeling efficiency of 98%, and showed high stability in PBS and new-born calf serum. Furthermore, the biodistribution study showed specific tumor uptake in the mice bearing HT-29 tumors, and planar imaging with ¹²⁵I-MAb 48 h post injection showed a high concentration of radioactivity in tumors and a much decreased concentration in tumors in the blocking group. An immunohistochemical analysis showed the expression of CA IX in HT-29 tumors. The preliminary biodistribution study and results from planar imaging showed the potential of ¹²⁵I-MAb as an agent for tumor diagnosis and encouraged further investigation.


Does strong hypertrophic condition induce fast mitochondrial DNA mutation of rabbit heart?
Homo- and heteroplasmic mitochondrial DNA (mtDNA) mutations were observed and identified in an isoproterenol-induced rabbit model of cardiac hypertrophy. Genes encoding proteins essential for catalyzing mitochondrial electron transfer and for generating the proton motive force, such as NADH dehydrogenases (ND2, ND3, ND4, and ND6), cytochrome b, and ATPase 8, showed increased susceptibility for mutation. Specifically, five mutations caused amino acid changes and were located in Complex I and Complex V gene clusters. To our knowledge, this is the first demonstration of a relationship between cardiac hypertrophy induced by a strong sympathetic load and rapid mtDNA mutations.


Rare manifestation of the thrombotic microangiopathy in a patient with sarcoidosis, common variable immunodeficiency and large B-cell non-hodgkin lymphoma: case report.
58-year old Caucasian woman was diagnosed with sarcoidosis. Low immunoglobulin levels were found and common variable immunodeficiency (CVID) was diagnosed 1year later. Laboratory tests and clinical course at this time revealed thrombotic microangiopathy (TMA). Therapeutic plasma exchange was started and her clinical status and laboratory parameters improved. According to CVID she received human immunoglobulin intravenously. Four months later we noticed swelling of the parotid glands and generalized lymphadenopathy. Histology of cervical lymph node confirmed large B-cell non-Hodgkin lymphoma (B-cell NHL). To the best of our knowledge, TMA complicating the course of sarcoidosis, CVID and B-cell NHL has never been reported.


Sense of life worth living (ikigai) and incident functional disability in elderly Japanese: The Tsurugaya Project.
To test the hypothesis that elderly persons who feel ikigai (a sense of life worth living) have a lower risk of incident functional disability than those who do not. Recent studies have suggested that ikigai impacts on mortality. However, its impact upon disability is unknown. The aim of the present study was to investigate the association between ikigai and incident functional disability among elderly persons. We conducted a prospective cohort study of 830 Japanese elderly persons aged ≥70 years as a comprehensive geriatric assessment in 2003. Information on ikigai was collected by self-reported questionnaire. Data on functional disability were retrieved from the public Long-term Care Insurance database in which participants were followed up for 11 years. Hazard ratios (HRs) and 95% confidence intervals (CIs) for incidence of functional disability were calculated for three groups delineated according to the presence of ikigai ("no", "uncertain" or "yes") using the Cox proportional hazards regression model. The 11-year incidence of functional disability was 53.3% (442 cases). As compared with the "no" group, the multiple-adjusted HR (95% CI) of incident functional disability was 0.61 (0.36–1.02) for the "uncertain" group and 0.50 (0.30–0.84) for the "yes" group. A stronger degree of ikigai is significantly associated with a lower risk of incident functional disability.


Morphology of the suburethral pubocervical fascia in women with stress urinary incontinence: a comparison of histologic and MRI findings.
To correlate MRI with histologic findings of the suburethral pubocervical fascia in women with urodynamic stress incontinence. Thirty-one women with urodynamically proven stress urinary incontinence without relevant prolapse underwent preoperative MRI. Tissue specimens obtained from the pubocervical fascia were examined immunohistochemically (types I and III collagen, smooth muscle actin) and the results compared with the MRI findings. MRI demonstrated an intact pubocervical fascia in 61.3% of the cases and a fascial defect in 38.7%. A fascial defect demonstrated by MRI was associated with a decrease in actin (P<0.09) and an increase in collagen III (P<0.01) compared to an intact fascia. In women with stress urinary incontinence, smooth muscle actin in the pubocervical fascia is decreased, changed in structure, and replaced by type III collagen. MRI allows evaluation of the pubocervical fascia and its morphologic changes.


Electro-thermal therapy: Microsecond duration pulsed electric field tissue ablation with dynamic temperature control algorithms.
Electro-thermal therapy (ETT) is a new cancer treatment modality which combines the use of high voltage pulsed electric fields, dynamic energy delivery rates, and closed loop thermal control algorithms to rapidly and reproducibly create focal ablations. This study examines the ablative potential and profile of pulsed electric field treatments delivered in conjunction with precise temperature control algorithms. An ex vivo perfused liver model was utilized to demonstrate the capability of 5000 V 2 μs duration bipolar electrical pulses and dynamic temperature control algorithms to produce ablations. Using a three applicator array, 4 cm ablation zones were created in under 27 min. In this configuration, the algorithms were able to rapidly achieve and maintain temperatures of 80 °C at the tissue-electrode interface. A simplified single applicator and grounding pad approach was used to correlate the measured ablation zones to electric field isocontours in order to determine lethal electric field thresholds of 708 V/cm and 867 V/cm for 45 °C and 60 °C treatments, respectively. These results establish ETT as a viable method for hepatic tumor treatment with ablation profiles equivalent to other energy based techniques. The single applicator and multi-applicator approaches demonstrated may enable the treatment of complex tumor geometries. The flexibility of ETT temperature control yields a malleable intervention which gives clinicians robust control over the ablation modality, treatment time, and safety profile.


Recent Advances in Understanding of Alzheimer's Disease Progression through Mass Spectrometry-Based Metabolomics.
Alzheimer's disease (AD) is the leading cause of dementia in the aging population, but despite extensive research, there is no consensus on the biological cause of AD. While AD research is dominated by protein/peptide-centric research based on the amyloid hypothesis, a theory that designates dysfunction in beta-amyloid production, accumulation, or disposal as the primary cause of AD, many studies focus on metabolomics as a means of understanding the biological processes behind AD progression. In this review, we discuss mass spectrometry (MS)-based AD metabolomics studies, including sample type and preparation, mass spectrometry specifications, and data analysis, as well as biological insights gleaned from these studies, with the hope of informing future AD metabolomic studies.


Use of the Western blot technique to identify the immunogenic proteins of Borrelia burgdorferi for developing a Lyme disease vaccine.
Lyme disease is a serious infectious disease having a restricted worldwide distribution for which there is no vaccine available for human use. This study was designed to determine common reactive antigens involved in Borrelia burgdorferi (Bb) infection that are recognized in mammalian sera that may be useful for vaccine development. Blood samples were collected from patients with documented Lyme disease, and from rabbits and mice experimentally infected with either tick-transmitted or culture-grown Borrelia burgdorferi. All samples were then processed for sera. For performing the Western blots, sonicated Bb organisms (whole cell lysates) and protein ladders were separated by protein gel electrophoresis. Immune reactivities of the electrophoresed proteins with the serum samples were then probed with anti-HRP IgG reagent. Rabbit, mouse and human sera consistently reacted with the 41 kDa band of Bb which corresponded to the flagellin protein - the major protein component of this organism's periplasmic flagella, also known as axial filaments or fibrils. Various other Bb antigens of wide molecular weight ranges were also recognized by rabbit and human sera, and less frequently with mouse sera. The strong immune response to the 41 kDa flagellin protein by the different mammalian species suggests the utility of a possible vaccine targeting this protein, although other proteins may also be appropriate, for preventing Lyme disease following a bite from an infected tick.


Preparation of CNC-dispersed Fe3O4 nanoparticles and their application in conductive paper.
Well-dispersed Fe3O4 nanoparticles (NPs) were synthesized by a co-precipitation method in the presence of cellulose nano-crystals (CNC) as the template. The thus prepared Fe3O4 NPs were then used as a coating agent for the preparation of conductive paper. Fourier transform infrared spectroscopy (FTIR) results revealed that the Fe3O4 NPs were immobilized on the CNC through interactions between the hydroxyl groups of CNC and Fe3O4. Scanning transmission electron microscopy (STEM) images showed that the Fe3O4 NPs prepared in the presence of CNC can be dispersed in the CNC network, while the Fe3O4 NPs prepared in the absence of CNC tended to aggregate in aqueous solutions. The conductivity of the Fe3O4 NPs coated paper can reach to 0.0269 S/m at the coating amount of 14.75 g/m(2) Fe3O4/CNC nanocomposites. Therefore, the thus obtained coated paper can be potentially used as anti-static packaging material in the packaging field.


Cytotoxicity and cellular uptake of tri-block copolymer nanoparticles with different size and surface characteristics.
Polymer nanoparticles (PNP) are becoming increasingly important in nanomedicine and food-based applications. Size and surface characteristics are often considered to be important factors in the cellular interactions of these PNP, although systematic investigations on the role of surface properties on cellular interactions and toxicity of PNP are scarce. Fluorescent, monodisperse tri-block copolymer nanoparticles with different sizes (45 and 90 nm) and surface charges (positive and negative) were synthesized, characterized and studied for uptake and cytotoxicity in NR8383 and Caco-2 cells. All types of PNP were taken up by the cells. The positive smaller PNP45 (45 nm) showed a higher cytotoxicity compared to the positive bigger PNP(90) (90 nm) particles including reduction in mitochondrial membrane potential (ΔΨ(m)), induction of reactive oxygen species (ROS) production, ATP depletion and TNF-α release. The negative PNP did not show any cytotoxic effect. Reduction in mitochondrial membrane potential (ΔΨ(m)), uncoupling of the electron transfer chain in mitochondria and the resulting ATP depletion, induction of ROS and oxidative stress may all play a role in the possible mode of action for the cytotoxicity of these PNP. The role of receptor-mediated endocytosis in the intracellular uptake of different PNP was studied by confocal laser scanning microscopy (CLSM). Involvement of size and charge in the cellular uptake of PNP by clathrin (for positive PNP), caveolin (for negative PNP) and mannose receptors (for hydroxylated PNP) were found with smaller PNP45 showing stronger interactions with the receptors than bigger PNP(90). The size and surface characteristics of polymer nanoparticles (PNP; 45 and 90 nm with different surface charges) play a crucial role in cellular uptake. Specific interactions with cell membrane-bound receptors (clathrin, caveolin and mannose) leading to cellular internalization were observed to depend on size and surface properties of the different PNP. These properties of the nanoparticles also dominate their cytotoxicity, which was analyzed for many factors. The effective reduction in the mitochondrial membrane potential (ΔΨ(m)), uncoupling of the electron transfer chain in mitochondria and resulting ATP depletion, induction of ROS and oxidative stress likely all play a role in the mechanisms behind the cytotoxicity of these PNP.


Simple and complex carotid paragangliomas. Three decades of experience and literature review.
Carotid paragangliomas are rare tumors. They are usually unique, non-secreting, resectable, and benign. However, additional rare cases of complex tumors (bilateral, secretory, nonresectable, or malignant) complicate the management and final outcomes. Records of paragangliomas from our hospital are reviewed. Criteria defining complex paragangliomas have been previously defined. These are compared with those of the simple group. Fifty patients, two groups: simple (n = 39) and complex (n = 11). The patients in the complex group were significantly younger (47.7 vs 63.8 years). Postoperative nerve complications (45.4% vs 6.3%) and mortality during follow-up (27.3% vs 0%) were significantly more common in the complex group. Vascular complications (0% vs 3.1%) and early mortality (0%) were similarly in both groups. Patients with complex carotid paragangliomas are heterogeneous. The former are younger, exhibit a high degree of diagnostic and therapeutic complexity, and have poorer morbidity and mortality. Surgical experience and interdisciplinary collaboration are essential.


Can ocean warming alter sub-lethal effects of antiepileptic and antihistaminic pharmaceuticals in marine bivalves?
The negative effects induced in marine organisms by Climate Change related abiotic factors consequences, namely ocean warming, are well-known. However, few works studied the combined impacts of ocean warming and contaminants, as pharmaceutical drugs. Carbamazepine (CBZ) and cetirizine (CTZ) occur in the marine environment, showing negative effects in marine organisms. This study aimed to evaluate the impacts of ocean warming on the effects of CBZ and CTZ, when acting individually and combined (drug vs drug), in the edible clam Ruditapes philippinarum. For that, drugs concentration, bioconcentration factors and biochemical parameters, related with clam's metabolic capacity and oxidative stress, were evaluated after 28 days exposure to environmentally relevant scenarios of these stressors. The results showed limited impacts of the drugs (single and combined) at control and warming condition. Indeed, it appeared that warming improved the oxidative status of contaminated clams (higher reduced to oxidized glutathione ratio, lower lipid peroxidation and protein carbonylation levels), especially when both drugs were combined. This may result from clam's defence mechanisms activation and reduced metabolic capacity that, respectively, increased elimination and limited production of reactive oxygen species. At low stress levels, defence mechanisms were not activated which resulted into oxidative stress. The present findings highlighted that under higher stress levels clams may be able to activate defence strategies that were sufficient to avoid cellular damages and loss of redox homeostasis. Nevertheless, low concentrations were tested in the present study and the observed responses may greatly change under increased pollution levels or temperatures. Further research on this topic is needed since marine heat waves are increasing in frequency and intensity and pollution levels of some pharmaceuticals are also increasing in coastal systems.


Repeated lumbar sympathetic blockade for complex regional pain syndromes type I--a case report.
The causal mechanisms of reflex sympathetic dystrophy are not limited purely to sympathetic hyperactivity, but sympathetic blockade and physical therapy are still the mainstays of current treatment modalities. We reported a case of reflex sympathetic dystrophy over the left lower leg, who was successfully treated with repeated lumbar sympathetic blocks and physical therapy.


Assignment of the human coproporphyrinogen oxidase to chromosome 9.
By using somatic cell hybrids between human fibroblasts and hamster or mouse cells, we have assigned the gene for human coproporphyrinogen oxidase to chromosome 9.


Limitations of the standard linear solid model of intervertebral discs subject to prolonged loading and low-frequency vibration in axial compression.
The purpose of this study was to answer the following questions: (1) Can the standard linear solid model for viscoelastic material simulate the influence of disc level and degeneration on the ability of a disc to withstand prolonged loading and low-frequency vibration? (2) How well does the SLS model explain the relationship between the ability of a disc to resist prolonged loading and its ability to resist dynamic loads and dissipate energy when subjected to low-frequency vibration? Responses of human thoracic and lumbar discs were measured in axial compression under a constant load, and for cyclic deformations at three frequencies. Parameters of the SLS model for each disc were determined by a least-squares fit to the experimental creep response. The model was subsequently used to predict the disc's response to cyclic deformations. The SLS model was able to qualitatively simulate the effects of disc level and degeneration on the ability of an intervertebral disc to resist both prolonged loading and low-frequency vibration. However, the model underestimated the stress relaxation, dynamic modulus and hysteresis of thoracic and lumbar discs subjected to low-frequency vibration. The SLS model was unable to explain the relationship between the ability of a disc to resist prolonged loading and its ability to resist dynamic loads and dissipate energy when subjected to low-frequency vibration. Although in the lumbar discs the steady-state predictions of the SLS model were significantly correlated to the experimental response, the strength of model predictions decreased with increasing frequency, particularly for hysteresis.


Bronchogenic carcinoma, leukemoid reaction, marantic endocarditis, and consumptive thrombocytopathy.
This paper details the simultaneous occurrence of a severe leukemoid reaction, non-bacterial thrombotic endocarditis (NBTE) (marantic endocarditis), and a consumptive thrombocytopathy without signs of micro-angiopathic hemolysis on peripheral blood smear in a patient with terminal metastatic, undifferentiated, large cell bronchogenic carcinoma. The case is presented and the condition is discussed in detail.


Relationship Between Bariatric Surgery and Bone Mineral Density: a Meta-analysis.
A meta-analysis regarding bone loss after bariatric surgery, designed to compare surgical and nonsurgical groups, has not yet been performed. Therefore, we performed a meta-analysis to compare the differences between bariatric surgical groups and nonoperated controls with regard to bone mineral density. In March 2015, we performed a review of the literature using PubMed, EMBASE, and the Cochrane Library. The search focused on retrospective and prospective studies, including but not limited to randomized studies published in English. Among 1299 studies that were initially screened, ten met the selection criteria. For all types of bariatric surgery, bone density at the femoral neck was lower in the surgical group than in the nonsurgical control group (mean difference [MD] -0.05 g/cm(2); 95 % confidence interval [CI], -0.07 to -0.02; p = 0.001); no difference in bone density was found between the two groups at the lumbar spine (MD -0.01 g/cm(2); 95 % CI -0.07 to 0.05; p = 0.661). The analysis of Roux-en-Y gastric bypass showed similar results. Bone density at the femoral neck decreased after bariatric surgery, compared to that in nonsurgical controls, whereas bone density at the lumbar spine did not show a difference between groups. Further larger scale studies with comparative nonsurgical controls are warranted to overcome the heterogeneity among studies in this analysis and to add evidence of possible bone loss subsequent to bariatric surgical procedures.


Distribution and development of short-wavelength cones differ between Macaca monkey and human fovea.
Macaca monkey and humans have three cone types containing either long-wavelength (L), medium-wavelength (M), or short-wavelength (S)-specific opsin. The highest cone density is found in the fovea, which mediates high visual acuity. Most studies agree that the adult human fovea has a small S cone-free area, but data are conflicting concerning S-cone numbers in the adult Macaca monkey fovea, and little evidence exists for how either primate fovea develops its characteristic cone pattern. Single- and double-label in situ hybridization and immunocytochemistry have been used to determine the pattern of foveal S cones in both the fetal and adult Macaca and human. Both labels find a clear difference at all ages between monkey and human. Adult humans have a distinct but variable central zone about 100 microm wide that lacks S cones and is surrounded by a ring in which the S-cone density is 8%. This S cone-free zone is detectable at fetal week 15.5 (Fwk15.5), shortly after S opsin is expressed, and is similar to the adult by Fwk20.5. Adult monkey foveas have an overall S-cone foveal density of 10%, with several areas lacking a few S cones that are not coincident with the area of highest cone density. A surrounding zone at 200-microm eccentricity has an S-cone density averaging 25%, but, by 800 microm, this has decreased to 11%. Fetal day 77-135 monkeys all have a distribution and density of foveal S cones similar to adults, although the high-density ring is not obvious in fetal retinas. Estimates of the numbers of S cones missing in the fetal human fovea range from 234 to 328, whereas no more than 40 are missing in the fetal monkey. These results show that, in these two trichromatic primates, S-cone distribution and the developmental mechanisms determining S-cone topography are markedly different from the time that S cones are first detected.


Structural and functional studies of Peptide-carbohydrate mimicry.
Certain peptides act as molecular mimics of carbohydrates in that they are specifically recognizedby carbohydrate-binding proteins. Peptides that bind to anti-carbohydrate antibodies, carbohydrate-processingenzymes, and lectins have been identified. These peptides are potentially useful as vaccines andtherapeutics; for example, immunologically functional peptide molecular mimics (mimotopes) can strengthenor modify immune responses induced by carbohydrate antigens. However, peptides that bind specificallyto carbohydrate-binding proteins may not necessarily show the corresponding biological activity, andfurther selection based on biochemical studies is always required. The degree of structural mimicryrequired to generate the desired biological activity is therefore an interesting question. This reviewwill discuss recent structural studies of peptide-carbohydrate mimicry employing NMR spectroscopy,X-ray crystallography, and molecular modeling, as well as relevant biochemical data. These studiesprovide insights into the basis of mimicry at the molecular level. Comparisons with other carbohydrate-mimeticcompounds, namely proteins and glycopeptides, will be drawn. Finally, implications for the designof new therapeutic compounds will also be presented.


Comparison of 64-slice multidetector computed tomography with spectral analysis of intravascular ultrasound backscatter signals for characterizations of noncalcified coronary arterial plaques.
In vivo identification of plaque composition may allow the detection of vulnerable plaques before rupture. However, the clinical relevance of multidetector computed tomography (MDCT) in characterizing coronary plaques is currently a subject of debate. We compared 64-slice MDCT with virtual histology to investigate the potential role of 64-slice MDCT in the differentiation of composition of noncalcified coronary plaques. Fifty-nine consecutive patients (stable/unstable angina 34/21) were enrolled. Mean computed tomographic (CT) density (Hounsfield units) of noncalcified coronary plaques (n = 80) was compared with a relative volume of each plaque component (fibrous, fibrofatty, calcium, and necrotic core) analyzed by virtual histology. Mean heart rate during MDCT was 58 +/- 9 beats/min. There was a negative correlation between mean CT density and the necrotic core (r = -0.539, p <0.001) and a positive correlation between mean CT density and the fibrotic tissue component (r = 0.571, p <0.001). Mean CT density of the plaques with a <10% necrotic core was significantly higher than that of a >or=10% necrotic core (93.1 +/- 37.5 vs 41.3 +/- 26.4 HU, p <0.001). However, overlapping of mean CT densities between plaques with a <10% necrotic core and those with a >or=10% necrotic core was found. In conclusion, mean CT density of noncalcified coronary plaques measured by 64-slice MDCT may depend on the relative volumes of the necrotic core and fibrotic component. Sixty-four-slice MDCT may have the potential for determining composition of noncalcified coronary plaques, which needs further studies for clinical application.


Correction to: Clinical and demographic characteristics of primary progressive multiple sclerosis in Argentina: Argentinean registry cohort study (RelevarEM).
The above article was published online with incorrect figure 1.


Partial trisomy 12q associated with a familial translocation.
A case is described of a female infant, who was trisomic for the terminal bands of the long arm of chromosome 12. Congenital abnormalities were present. Cytogenetic analysis on the proband's parents revealed the father to have a rare, simple translocation involving chromosomes 12 and 18.


Economic analysis of chromosome testing in couples with recurrent miscarriage to prevent handicapped offspring.
Which strategy is least expensive to prevent the birth of a handicapped child in couples with recurrent miscarriage (RM); parental chromosome analysis followed by amniocentesis in case of carrier status of one of the parents, or amniocentesis in all ongoing pregnancies without the knowledge of parental carrier status? For virtually all couples with RM amniocentesis in all ongoing pregnancies without the knowledge of parental carrier status is less expensive in preventing the birth of a handicapped child than parental chromosome analysis followed by amniocentesis in case of carrier status of one of the parents. One of the causes of RM is a balanced chromosome abnormality in one of the partners. If one of the partners is carrier of a balanced structural chromosomal abnormality, the risk of offspring with an unbalanced structural chromosome abnormality is increased. Like all couples, couples with RM also have an age-dependent risk for fetal aneuploidy, of which trisomy 21 is most common. Model-based economic analysis to compare costs and effects of two strategies in couples with RM to prevent the birth of a handicapped child in case of ongoing pregnancy. Comparison of two strategies in women with RM: strategy (I) parental chromosome analysis followed by amniocentesis in pregnancy in case of carrier status of one of the parents and strategy (II) amniocentesis in all ongoing pregnancies without the knowledge of carrier status. No testing was the reference strategy. Data on probabilities and costs were derived from the literature. Incremental costs and effects were calculated [incremental cost-effectiveness ratio (ICER)]. Effectiveness was expressed as the number of prevented births of handicapped child equivalents compared with no testing. In these calculations, the birth of a handicapped child was valued 10 times worse than the loss of a viable pregnancy due to amniocentesis. Depending on the risk for carrier status, the ICER for Strategy I (parental chromosome analysis followed by amniocentesis in case of carrier status of one of the parents) varied between € 226,000 and € 6,556,000 per prevented handicapped child equivalent. For Strategy II (amniocentesis in all ongoing pregnancies without the knowledge of carrier status), the ICER varied between € 2000 and € 233 000 per prevented handicapped child equivalent. Strategy I was less expensive than Strategy II only for a small subgroup of couples with maternal age <23 years, three or more previous miscarriages and a family history of RM. Our analysis is not a plea for amniocentesis in all women with RM. Individual risk assessment with serum markers and nuchal translucency is probably more effective at lower cost. This analysis can be used by clinicians to explain the chances of adverse pregnancy outcome in couples with RM, as well as by policy makers in health-care economics. Future guidelines on RM might be more restrictive from the perspective of the limited health-care resources that we have available.


Self-segregation of myelin membrane lipids in model membranes.
Rapid conduction of nerve impulses requires coating of axons by myelin sheaths, which are multilamellar, lipid-rich membranes produced by oligodendrocytes in the central nervous system. To act as an insulator, myelin has to form a stable and firm membrane structure. In this study, we have analyzed the biophysical properties of myelin membranes prepared from wild-type mice and from mouse mutants that are unable to form stable myelin. Using C-Laurdan and fluorescence correlation spectroscopy, we find that lipids are tightly organized and highly ordered in myelin isolated from wild-type mice, but not from shiverer and ceramide synthase 2 null mice. Furthermore, only myelin lipids from wild-type mice laterally segregate into physically distinct lipid phases in giant unilamellar vesicles in a process that requires very long chain glycosphingolipids. Taken together, our findings suggest that oligodendrocytes exploit the potential of lipids to self-segregate to generate a highly ordered membrane for electrical insulation of axons.


Seasonality trends of scabies in a young adult population: a 20-year follow-up.
Scabies is not a notifiable disease in most countries. Therefore, its seasonality trends are usually estimated and may be inaccurate. To determine the seasonality of scabies over the long term in a large military population, including all of the Israel Defence Forces personnel. For the last two decades, the Israel Defence Forces have mandated the routine reportage of every case of scabies infestation in soldiers to the Epidemiology Department of the Army Health Branch. This database was used in the present study to analyse the incidence of scabies by season. Scabies was defined according to the report by a military physician based on the typical clinical presentation, relevant epidemiological data and, in most cases, microscopic visualization of the mite. The person-time incidence of scabies was higher in winter than summer (P < 0.001). The overall risk ratio was 1.31 (95% confidence interval 1.28-1.33). Sensitivity analysis indicated that no single year was an important source of disease heterogeneity. Scabies in a young adult population is more frequent in the cooler months of the year.


Improved performances of catalytic G-quadruplexes (G4-DNAzymes) via the chemical modifications of the DNA backbone to provide G-quadruplexes with double 3'-external G-quartets.
Here we report on the design of a new catalytic G-quadruplex-DNA system (G4-DNAzyme) based on the modification of the DNA scaffold to provide the DNA pre-catalyst with two identical 3'-ends, known to be more catalytically proficient than the 5'-ends. To this end, we introduced a 5'-5' inversion of polarity site in the middle of the G4-forming sequences AG4A and AG6A to obtain d(3'AGG5'-5'GGA3') (or AG2-G2A) and d(3'AGGG5'-5'GGGA3') (or AG3-G3A) that fold into stable G4 whose tetramolecular nature was confirmed via nuclear magnetic resonance (NMR) and circular dichroism (CD) investigations. Both AG2-G2A and AG3-G3A display two identical external G-quartets (3'-ends) known to interact with the cofactor hemin with a high efficiency, making the resulting complex competent to perform hemoprotein-like catalysis (G4-DNAzyme). A systematic comparison of the performances of modified and unmodified G4s lends credence to the relevance of the modification exploited here (5'-5' inversion of polarity site), which represents a new chemical opportunity to improve the overall activity of catalytic G4s.


Molecular profiling and clinical implications of patients with acute myeloid leukemia and extramedullary manifestations.
Extramedullary manifestations (EM) are rare in acute myeloid leukemia (AML) and their impact on clinical outcomes is controversially discussed. We retrospectively analyzed a large multi-center cohort of 1583 newly diagnosed AML patients, of whom 225 (14.21%) had EM. AML patients with EM presented with significantly higher counts of white blood cells (p < 0.0001), peripheral blood blasts (p < 0.0001), bone marrow blasts (p = 0.019), and LDH (p < 0.0001). Regarding molecular genetics, EM AML was associated with mutations of NPM1 (OR: 1.66, p < 0.001), FLT3-ITD (OR: 1.72, p < 0.001) and PTPN11 (OR: 2.46, p < 0.001). With regard to clinical outcomes, EM AML patients were less likely to achieve complete remissions (OR: 0.62, p = 0.004), and had a higher early death rate (OR: 2.23, p = 0.003). Multivariable analysis revealed EM as an independent risk factor for reduced overall survival (hazard ratio [HR]: 1.43, p < 0.001), however, for patients who received allogeneic hematopoietic cell transplantation (HCT) survival did not differ. For patients bearing EM AML, multivariable analysis unveiled mutated TP53 and IKZF1 as independent risk factors for reduced event-free (HR: 4.45, p < 0.001, and HR: 2.05, p = 0.044, respectively) and overall survival (HR: 2.48, p = 0.026, and HR: 2.63, p = 0.008, respectively). Our analysis represents one of the largest cohorts of EM AML and establishes key molecular markers linked to EM, providing new evidence that EM is associated with adverse risk in AML and may warrant allogeneic HCT in eligible patients with EM.


Metagenomic Sequencing of Two Cultures Grown on Chemically Deconstructed Plastic Products.
We report the metagenome sequences of two microbial cultures that were grown with chemically deconstructed plastic products as their sole carbon source. These metagenomes will provide insights into the metabolic capabilities of cultures grown on deconstructed plastics and can serve as a starting point for the identification of novel plastic degradation mechanisms.


Quantum coherence on selectivity and transport of ion channels.
Recently, it has been suggested that ion channel selectivity filter may exhibit quantum coherence, which may be appropriate to explain ion selection and conduction processes. Potassium channels play a vital role in many physiological processes. One of their main physiological functions is the efficient and highly selective transfer of K+ ions through the membranes into the cells. To do this, ion channels must be highly selective, allowing only certain ions to pass through the membrane, while preventing the others. The present research is an attempt to investigate the relationship between hopping rate and maintaining coherence in ion channels. Using the Lindblad equation to describe a three-level system, the results in different quantum regimes are examined. We studied the distillable coherence and the second order coherence function of the system. The oscillation of distillable coherence from zero, after the decoherence time, and also the behavior of the coherence function clearly show the point that the system is coherent in ion channels with high throughput rates.


Two-week schedule of hypofractionated radiotherapy as a local salvage treatment for small hepatocellular carcinoma.
In cases of small hepatocellular carcinoma (HCC) where established curative treatment cannot be applied, stereotactic body radiotherapy (SBRT) has been used as a non-invasive alternative treatment modality. However, short-course SBRT may not be safe if the tumor is located around a critical normal organ. Therefore, we applied hypofractionated radiotherapy for these tumors and evaluated outcomes of this treatment. Between December 2008 and August 2011, 26 patients (28 lesions) with HCC were treated with hypofractionated radiotherapy. Inclusion criteria were HCC not suitable for surgery or other local ablative therapy, a tumor size < 6 cm, adequate hepatic function, an HCC located within 2 cm of a critical organ, and no evidence of vascular invasion. A dose of 4-5 Gy per fraction was given, with a total dose of 40-50 Gy over 2 weeks. The overall response rate was 67.9%, with seven complete responses (25.0%) and 12 partial responses (42.9%) at 3 months after radiotherapy. The overall survival rates at 1 and 2 years were 88.5% and 67.2%, respectively. The local control rate at 2 years was 87.6%. The Intrahepatic recurrence-free and distant failure-free survival rates at 2 years were 36.5% and 68.2%, respectively. Grade ≥ 3 hepatic toxicity was observed in one patient. Two-week schedule of hypofractionated radiotherapy for small HCC was feasible with good local control and safety. This fractionation schedule can be used as an alternative treatment option for HCC located close to a critical normal organ if short-course SBRT is not feasible.


Dopamine D1 receptors in human parathyroid gland: in vitro and in vivo studies.
Dopamine receptors in human parathyroid were studied in vitro using ligand binding techniques. With 3H-piflutixol as ligand, binding characteristic of the dopamine D1 receptor was observed. Administration of apomorphine, flupenthixol or metoclopramide to normal controls or acute schizophrenic patients at doses producing significant alterations in serum prolactin concentrations did not alter serum parathyroid hormone (PTH) concentrations. Whilst D1 binding sites are present in human parathyroid, the measurement of PTH after administration of dopaminergic drugs is unlikely to provide a test of D1 receptor function in man.


Protective Effect of Retrograde Reperfusion Against Hepatic Autophagy Impairment in Rat Liver Transplantation.
The retrograde reperfusion (RTR) technique was introduced in orthotopic liver transplantation (OLT) to improve initial postoperative liver function, but the related mechanisms remain unexplained. We investigated the influences of different reperfusion sequences, including initial portal reperfusion (IPR) and RTR, on hepatic ischemia/reperfusion (I/R) injury and autophagic activity in a simplified rat orthotopic liver transplantation (ROLT) model. First, we established an ROLT model of male Sprague-Dawley rats to simulate either the IPR or RTR technique. The operative times and survival rates until postoperative day (POD) 7 were recorded. Liver enzyme levels, histologic damage, and in situ apoptosis were assessed. Second, we evaluated differences in the autophagic flux of liver grafts at 1, 2, and 6 hours after reperfusion between the IPR and RTR techniques. All experimental procedures involving animals were approved by the Institutional Animal Ethics Committee of the 900th Hospital of PLA. In the first experiment, all animals survived to POD 7. In contrast to the IPR sequence, the RTR technique decreased the extent of graft I/R injury. In the second experiment, reperfusion markedly impaired the autophagic flux of ischemic liver grafts, but the RTR technique could alleviate and postpone the reduction in autophagy after I/R. A feasible modified ROLT model with the cuff method was described and could flexibly simulate 2 reperfusion techniques: IPR and RTR. The use of the RTR sequence exhibited a protective effect against I/R injury and impairment of autophagy in liver grafts.


Exploring the functional role and neural correlates of K-complexes in isolated rapid eye movement sleep behavior disorder.
Underlying neural mechanisms and cognitive implications of non-Rapid Eye Movement (NREM) sleep in isolated Rapid Eye Movement (REM) sleep behavior disorder (iRBD) are not yet fully elucidated. This study aims to evaluate brain metabolic connectivity of the anterior default mode network (ADMN) underlying a waveform that is an hallmark of NREM sleep, namely K-complex (KC) and their implication for neuropsychological functioning in iRBD patients. Combining polysomnographic and multivariate molecular imaging (FDG-PET) approaches may provide crucial insights regarding KCs role in the prodromal stages of synucleinopathies. We applied a seed-based interregional correlation analysis on FDG-PET data. iRBD patients with cognitive decline displayed a reduced KC density (KCd) in comparison to patients without cognitive impairments. KCd showed a significant positive correlation with global cognitive functioning, specifically with visuo-spatial and executive performances, two cognitive domains known to be relevant in predicting conversion into neurodegenerative disorders. Increased KCd was associated with a more preserved ADMN connectivity. Our study underlines the importance of NREM sleep in prodromal stages of synucleinopathies, and future investigations might clarify its role in iRBD.


A randomized, placebo- and active-controlled study of paliperidone extended-release as maintenance treatment in patients with bipolar I disorder after an acute manic or mixed episode.
Paliperidone ER monotherapy was efficacious in treating acute mania in two 3-week studies in patients with bipolar I disorder. We assessed its efficacy in a study investigating maintenance treatment of clinically stable patients with this disorder. Patients (n=766), aged 18 to 65 years inclusive, with current manic or mixed episodes were initially randomized (4:1) to flexibly-dosed paliperidone ER (3-12 mg/day) or olanzapine (5-20 mg/day; 3-week acute treatment phase); responders continued the same treatment (12-week continuation phase). Patients on paliperidone ER who achieved remission during this phase were randomized (1:1) to fixed-dose paliperidone ER (n=152) or placebo (n=148); those on olanzapine continued to receive that at fixed dose (n=83) (maintenance phase). Median time to recurrence of any mood symptoms (primary endpoint) was: 558 days (paliperidone ER), 283 days (placebo) and not observed with olanzapine (<50% of patients experienced recurrence). Time to recurrence of any mood symptoms was significantly longer with paliperidone ER than placebo (p=0.017; based on weighted Z-test at 0.0198 significance level; hazard ratio [placebo: paliperidone ER; unweighted 95% confidence interval]: 1.43 [1.03; 1.98]); the difference was significant for preventing recurrence of manic, but not depressive, symptoms. Treatment-emergent adverse events (maintenance phase) occurred more often in olanzapine group (64%) than placebo (59%) or paliperidone ER groups (55%). Responder-enriched design prevents extrapolation of data to patients not previously stabilized on paliperidone ER. Paliperidone ER significantly delayed the time to recurrence of any mood symptoms, versus placebo, in patients with bipolar I disorder. No new safety concerns emerged.


Monosomal karyotype is associated with poor outcomes in patients with Philadelphia chromosome-negative acute lymphoblastic leukemia receiving chemotherapy but not allogeneic hematopoietic stem cell transplantation.
Monosomal karyotype (MK) is associated with poor prognosis in patients with myeloid neoplasms; however, its prognostic significance in Philadelphia chromosome-negative (Ph-negative) acute lymphoblastic leukemia (ALL) remains unclear. Data of 323 patients with Ph-negative ALL treated at Peking University People's Hospital were retrospectively analyzed. MK was identified in 49 (14.8%) patients. The patients with MK had lower hemoglobin levels (P = 0.026), lower platelet count (P = 0.032), higher percentages of blasts in the peripheral blood at diagnosis (P = 0.008), and higher percentages of high-risk karyotypes (P < 0.001) compared with those without MK. The complete remission (CR) rate and the minimal residual disease negativity rate were not significantly different between patients with and without MK. In the multivariate analysis, MK was identified as an independent factor associated with higher cumulative incidence of relapse (CIR) (hazard ratio (HR), 2.07; 95% confidence interval (CI), 1.02, 4.21; P = 0.043), shorter disease-free survival (DFS) (HR, 2.80; 95% CI, 1.20, 6.54; P = 0.017) and shorter overall survival (OS) (HR, 5.75; 95% CI, 2.07, 16.03; P = 0.001) in the chemotherapy cohort; however, MK had no impact on outcomes in the allogeneic hematopoietic stem cell transplantation (allo-HSCT) cohort. Mantel-Byar analysis showed that allo-HSCT was associated with lower CIR (P < 0.001), longer DFS (P < 0.001), and longer OS (P < 0.001) in CR patients with MK. In conclusion, our study showed that MK was an independent predictor of poor outcomes in patients with Ph-negative ALL receiving chemotherapy but not allo-HSCT, and allo-HSCT could improve the outcomes of patients with MK.


Social connectedness, emotional regulation, and health behaviors as correlates of distress during lockdown for COVID-19: A diary study.
Mass lockdowns are a powerful infection-reduction strategy but are a significant stressor. This study aimed to explore whether various factors known to predict distress in normal contexts (e.g. social connectedness, emotional-regulation strategies, and health-related behaviors) are associated with daily distress under lockdown conditions. A time-based diary study evaluated how perceived social connectedness, health-promoting, and risk behaviors predicted within-person and between-person psychological distress. One hundred and nine adults completed surveys on these variables daily for 15 days while under stringent COVID-19 lockdown in Colombia. Emotional suppression and reappraisal were measured at the start of the study to explore whether they predicted distress. Distress was lower on the days that people experienced greater social connectedness (within-person analyses) but was not significantly predicted by between-participant differences in emotional regulation. Health-promoting behaviors such as exercising and meaningful activity were associated with lower distress, while watching COVID-19 news and eating high-calorie food were associated with higher distress. Looking at individual dynamics provides meaningful insights on daily behaviors associated with distress that might improve people's wellbeing during lockdown, such as social connectedness, meaningful activity, nutrition, exercise, and minimizing news exposure. Future research with alternative designs will enable causal conclusions to be drawn.


Clinical, microbiological characteristics and predictors of mortality in patients with carbapenemase-producing Enterobacterales bloodstream infections: a multicentre study.
To investigate the clinical, microbiological characteristics and outcomes of patients with bloodstream infections (BSI) due to carbapenemase-producing Enterobacterales (CPE). A multicentre retrospective observational study of patients with BSIs due to CPE admitted to six UK hospitals was conducted between 2011 and 2021. Multivariate analysis was used to identify factors predicting 30-day case fatality rate (CFR). There were 84 episodes of CPE-BSIs, 37 (44%) due to OXA-48, 35 (42%) to metallo-betalactamases (MBL) and 12 (14%) to KPC. 63% of patients were male with a median age of 64 years. Common organisms included Klebsiella spp. (61%), Escherichia coli (20%) and Enterobacter spp. (13%). Urinary devices were more often involved in OXA-48 BSIs (12/37; 32%) compared to infections caused by MBL and KPC (4/35; 11% and 1/12; 8%; P = 0.046). In contrast, central venous catheters were more frequently present in KPC-BSIs (10/12; 92%) compared with OXA-48 and MBL (11/37; 30% and 20/35; 57%; P = 0.002). Effective definitive antimicrobials were received by 72/84 (86%) patients, comprising monotherapy (32/72; 44%) or combination therapy (40/72; 56%). 30-day case fatality rate (CFR) was 38%. Sepsis or septic shock was associated with death [OR 3.81 (CI 1.19-12.14), P = 0.024]. Strategies targeting high-risk patients and adherence to infection prevention bundles for urinary devices and central venous catheters can reduce OXA-48 and KPC-BSIs. Early recognition and management of severe sepsis, prompt initiation of appropriate antimicrobial therapy and development of novel antimicrobials are crucial to mitigate the high CFR associated with CPE-BSIs.


A diagnostic challenge of Parkinson's disease: intractable hiccups.
Parkinson's disease is a common neurodegenerative disorder and the diagnosis depends mostly on clinical assessment so it is important to be aware of less common symptoms of the disease for correct diagnosis and therapy. We describe a patient with intractable hiccups as a very unusual presentation of Parkinson's disease.


[Surgery for laryngeal stenosis in infants in liable in case of failure to produce a worse condition resulting on a definitive disability (author's transl)].
The proper treatment for these stenosis is the "evolutive calibrage" which takes advantage of the normal growth of the larynx with no risk of aggravation.


Reduced temperature prevents transfer of a membrane glycoprotein to the cell surface but does not prevent terminal glycosylation.
The transport kinetics of the influenza virus hemagglutinin from its site of synthesis to the apical plasma membrane of Madin-Darby canine kidney cells, a polarized epithelial cell line, were studied by a sensitive tryptic assay. Hemagglutinin acquired terminal sugars, as judged by sensitivity to endo-beta-N-acetylglucosaminidase H, 10-15 min after synthesis, and first appeared on the apical domain 15 min later. None of the pulse-labeled hemagglutinin accumulated on the basolateral domain. At 20 degrees C, terminal glycosylation continued, but no hemagglutinin was detected on the cell surface within 2 hr. If the incubation temperature was raised from 20 degrees C to 37 degrees C, hemagglutinin was quickly externalized, demonstrating that the inhibition at low temperature was reversible.


Biologically treated industrial wastewater disinfection using the synergy of low-frequency ultrasound and H2O2/O3.
Biological wastewater treatment is mostly used in many industries to treat industrial influents. Treated water is consisting of an extremely high concentration of pathogenic microorganisms. Present work demonstrate the treatment of biologically treated sugar industry wastewater (BTSWW) using a low-frequency ultrasound (US). BTWSS consists of Enterobacter, Salmonella, and Escherichia Coli with a total coliform concentration of 2500 ± 300 CFU/mL. Experiments were performed using the individual effect of US, H2O2, and O3 and the combined effect of US with H2O2, O3, and H2O2 + O3. The complete removal of total coliform was obtained for the synergy effect of US with H2O2 and O3. The performance of the process was analyzed based on pseudo-first-order kinetic rate constant and synergy coefficient. The pseudo-first-order kinetic rate constant was 21.6 and 22.3 × 10-2 min-1 with a synergy coefficient of 2 and 1.9 for a combined effect of US with H2O2 and O3, respectively. Another advantage of the synergy of US and O3 was lower requirement of the initial dose of H2O2 (2.1 mM/L). The operational cost of the process was found to be $ 1.5 × 10-2 /MLD.


Baylisascaris procyonis larva migrans in two white-headed lemurs (Eulemur albifrons) in Spain and response to treatment derived from a human pediatric protocol.
Baylisascaris procyonis is a well-known ascaridoid nematode that causes larva migrans in humans and many other animal species. The North American raccoon (Procyon lotor) is the definitive host, which has been successfully introduced in the past decades to other geographical regions around the world. Two white-headed lemurs (Eulemuralbifrons) from a Zoological Park in Lugo, Spain, developed severe neurological signs within a brief period after being transferred from exhibit and placed in close contact with three captive raccoons from the same zoo. One lemur was euthanized due to the severity of disease progression and histopathology revealed granulomatous inflammation and ascaridoid larvae in kidneys, lung, spleen and brain. Larvae were identified as B. procyonis larvae by real time PCR. In light of the results, the cage mate with similar neurological signs was put on an albendazole treatment regimen adapted from a human pediatric protocol. The aggressive anthelmintic treatment likely contributed to the arrest of clinical signs and recovery of some motor skills. Importantly, Baylisascaris procyonis infection might occur in wild raccoon populations in Spain.


Microwave assisted micellar extraction coupled with solid phase microextraction for the determination of organochlorine pesticides in soil samples.
Microwave assisted micellar extraction (MAME) coupled with solid phase microextraction (SPME) and HPLC-UV determination have been used for the determination of five organochlorine pesticides from agricultural soil samples. A non-ionic surfactant, Polyoxyethlylene 10 Lauryl Ether was used, and the different variables for the optimization of MAME and SPME procedures were studied. This method was applied successfully to the determination of these pesticides in several kinds of agricultural soil samples with different characteristics. Most of the compounds studied can be recovered in good yields with R.S.D. lower than 9% and detection limit ranged between 56-96 ng g(-1) for the pesticides studied.


Insights into high-solids anaerobic digestion of food waste concomitant with sorbate: Performance and mechanisms.
High-solids anaerobic digestion (HS-AD) of food waste is increasingly applied commercially. Sorbate, a food preservative extensively used in the food industry, induces potential environmental risks. Results indicated sorbate at 0-10 mg/g volatile solids (VS) slightly inhibited methane production, and the cumulative methane yield suggested a negative correlation with 25 mg/g VS sorbate, with a reduction of 15.0% compared to the control (from 285.7 to 253.6 mL CH4/g VS). The reduction in methane yield could be ascribed to the promotion of solubilization and inhibition of acidogenesis and methanogenesis with sorbate addition. Excessive sorbate (25 mg/g VS) resulted in the inhibition of aceticlastic metabolism and the key enzymes activities (e.g., acetate kinase and coenzyme F420). This study deeply elucidated the response mechanism of HS-AD to sorbate, supplemented the potential ecological risk assessment of sorbate, and could provide insights to further prevent the potential risk of sorbate in anaerobic digestion of food waste.


DNA methylation analysis of BDNF gene promoters in peripheral blood cells of schizophrenia patients.
Accumulating evidence suggests that epigenetic alterations in brain-derived neurotrophic factor (BDNF) promoters are associated with the pathophysiology of psychiatric disorders. Epigenetic changes in BDNF were reported not only in brain tissues but also in other tissues, including peripheral blood cells (PBC) and saliva. We examined DNA methylation levels of BDNF promoters I and IV using genomic DNA derived from PBC of healthy controls (n=100), and patients with schizophrenia (n=100), all from the Japanese population, by pyrosequencing. The examined CpG sites were chosen based on previous epigenetic studies that reported altered DNA methylation. We found a significantly higher level of methylation at BDNF promoter I in patients with schizophrenia compared to controls, although the difference was small. Subsequent analysis revealed that in controls, the methylation level of BDNF promoters was associated with sex, and the methylation difference observed in promoter I was more prominent in male patients with schizophrenia. Epigenetic alteration of BDNF in the PBC might reflect the pathophysiology of schizophrenia, and could be a potential biomarker.


The effect of L-Dopa on the spinal monosynaptic mass reflex.
After i.v. injection of reserpine, the monosynaptic mass reflex (MSMR) is depressed in spinalized cats. However, the complete recovery of MSMR was obtained 30 min after L-Dopa application. Pimozide, a dopamine-receptor blocking agent, blocked this action of L-Dopa. It is presumed that dopaminergic receptors are involved in the action of L-Dopa on spinal MSMR.


Relation of dyspnea to left ventricular wall motion disturbances in a population of 67-year-old men.
Dyspnea, a potential early symptom of coronary artery disease and congestive heart failure, was evaluated to establish its relation to left ventricular wall motion abnormalities. A group of 67-year-old men, drawn from the general population of Gothenburg, Sweden, was studied. Acceptable studies by 2-dimensional echocardiography were obtained from 42 of 49 men with dyspnea of presumed cardiac origin, and from 45 randomly selected nondyspneic control subjects. Both groups originated from a random population sample of 644 men. All men with akinesia, not limited to the basal inferolateral segment, were dyspneic. Akinesia (inferolateral segment only) was found in 4 of 45 control subjects (9%). Six of 20 men (30%) with low-grade dyspnea and 5 of 5 men with the most severe grade of dyspnea had 1 or more akinetic segments. The severity of dyspnea was related to regional wall motion disturbances (as classified in 11 anatomic segments [p less than 0.02 to p less than 0.0001]) and to presence and number of akinetic segments (p less than 0.0001). The degree of dyspnea was correlated to anterior (p less than 0.0001) but not inferior akinesia. The regional wall motion disturbances measured by echocardiography still contributed significantly to the explanation of dyspnea when taking into account the presence or absence of clinical coronary artery disease determined from a 12-lead electrocardiogram, the history of angina pectoris and myocardial infarction, and the findings on chest x-ray films. Thus, presumed cardiac dyspnea is a sensitive marker of regional wall motion disturbances. Furthermore, the location of these disturbances may be of importance for the hemodynamic changes leading to cardiac dyspnea.


Functional effects of expression of wolframin-antisense transcripts in BRIN-BD11 beta-cells.
Wolfram syndrome is a rare condition in which the pancreatic beta-cells of patients are selectively deleted during the early years of life by a non-autoimmune-mediated mechanism. The condition is associated with mutations in the gene encoding wolframin, suggesting that this protein exerts a critical, but currently unknown, function in beta-cells. We have used an antisense strategy to modulate the expression of wolframin in insulin-secreting BRIN-BD11 cells to study its function. Stably transfected clones were established expressing full-length human wolframin antisense transcripts. These cells exhibited a dramatic reduction in cell proliferation rate and changes in morphology, although insulin secretion was not modified. The results imply that wolframin expression is required to sustain normal rates of beta-cell proliferation.


Esophageal atresia: new guidelines in management.
Esophageal atresia is the most common congenital anomaly of the esophagus in newborns. This review article discusses the incidence, embryological classification, diagnosis and associated anomalies of esophageal atresia. Emphasis is placed in the current guidelines of standard surgical management of this congenital condition.


Development and implementation of a single-chain Fv antibody for specific detection of Bacillus anthracis spores.
A single-chain Fv (scFv) antibody was developed and applied for efficient and specific detection of Bacillus anthracis spores. The antibody was isolated from a phage display library prepared from spleens of mice immunized with a water-soluble extract of the outer membrane of the B. anthracis spore (exosporium). The library (7 x 10(6) PFU) was biopanned against live, native B. anthracis ATCC delta14185 spores suspended in solution, resulting in the isolation of a unique soluble scFv antibody. The antibody was affinity purified and its affinity constant (3 x 10(8) +/- 1 x 10(8) M(-1)) determined via flow cytometry (FCM). Preliminary characterization of scFv specificity indicated that the scFv antibody does not cross-react with representatives of some phylogenetically related Bacillus spores. The potential use of scFv antibodies in detection platforms was demonstrated by the successful application of the soluble purified scFv antibody in enzyme-linked immunosorbent assays, immunofluorescence assays, and FCM.


Cultural and Cognitive Determinants of Personal Control in Older African Americans with Diabetes.
The study was funded by Pennsylvania Department of Health's Commonwealth Universal Research Enhancement (CURE) Program (SAP#4100051727). To describe the determinants of personal control over diabetes complications in older African Americans (N=123) with type 2 diabetes. We administered structured instruments to assess perceptions of personal control, time orientation, religiosity, depression, and cognition in this cross-sectional study. More years of education (p ≤ .001), better Clock Drawing (p ≤ .001), higher levels of Religiosity (p ≤ .04), and lower Present Time Orientation (p ≤ .01 ) were independent predictors of higher levels of Personal Control. Risk perceptions of control over diabetes complications vary among older African Americans according to cultural constructs, executive function, and education. This finding highlights the cultural diversity in this population and the potential impact of culturally-determined views and cognitive function on health behaviors. Cognitive screening of older persons with diabetes and interventions that incorporate perceptions of time and religion to increase rates of eye examinations are needed.


Direct induction of Dictyostelium prestalk gene expression by DIF provides evidence that DIF is a morphogen.
We have isolated a gene that is very rapidly induced at the transcriptional level by DIF--a low molecular weight, diffusible factor necessary for stalk cell differentiation in Dictyostelium cells developing in vitro. The gene encodes a protein containing an N-terminal signal peptide preceding approximately 70 tandem repeats of a highly conserved 24 amino acid sequence with a high cysteine content. These features suggest it is an extracellular structural protein. During normal development, the gene is maximally expressed in the slug, in which the mRNA is very highly enriched in prestalk over prespore cells. The gene is not detectably expressed until the tipped aggregate stage, several hours later than prespore genes, suggesting that prespore cell differentiation precedes prestalk cell differentiation. The demonstration that DIF induces a gene normally only expressed in the prestalk zone of the slug provides strong evidence that DIF is a Dictyostelium morphogen.


How useful are vibrational frequencies of isotopomeric O2 fragments for assessing local symmetry? Some simple systems and the vexing case of a galactose oxidase model.
The tendency for mixed-isotope O2 fragments to exhibit different stretching frequencies in asymmetric environments is examined with various levels of electronic structure theory for simple peroxides and peroxyl radicals, as well as for a variety of monocopper-O2 complexes. The study of the monocopper species is motivated by their relevance to the active site of galactose oxidase. Extensive theoretical work with an experimental model characterized by Jazdzewski et al. (J. Biol. Inorg. Chem. 8:381-393, 2003) suggests that the failure to observe a splitting between 16O18O and 18O16O isotopomers cannot be taken as evidence against end-on O2 coordination. Conformational analysis on an energetic basis, however, is complicated by biradical character inherent in all of the copper-O2 singlet structures.


Erectile function post robotic radical prostatectomy: technical tips to improve outcomes?
Robotic surgery is becoming more and more commonplace. At the same time, so are complications, especially related to erectile function. The population being diagnosed with cancer is younger, with more aggressive cancers and higher expectations for good erectile function postoperatively. We conduct a retrospective analysis of literature over 20 years for Embase and Medline. Search terms used include (Robotic) AND (prostatectomy) AND (erectile function). There are a variety of multifactorial causes, resulting in worsening ED post-robotic radical prostatectomy; however, there are a number of treatments that can support this. There is much we can do to help prevent patients getting postoperative erectile dysfunction post-radical surgery. However, part of this is management of realistic patient expectations.