Aptamers as Functional Modules for DNA Nanostructures.
Watson-Crick base-pairing of DNA allows the nanoscale fabrication of biocompatible synthetic nanostructures for diagnostic and therapeutic biomedical purposes. DNA nanostructure design elicits exquisite control of shape and conformation compared to other nanoparticles. Furthermore, nucleic acid aptamers can be coupled to DNA nanostructures to allow interaction and response to a plethora of biomolecules beyond nucleic acids. When compared to the better-known approach of using protein antibodies for molecular recognition, nucleic acid aptamers are bespoke with the underlying DNA nanostructure backbone and have various other stability, synthesis, and cost advantages. Here, we provide detailed methodologies to synthesize and characterize aptamer-enabled DNA nanostructures. The methods described can be generally applied to various designs of aptamer-enabled DNA nanostructures with a wide range of applications both within and beyond biomedical nanotechnology.


Strategy for purifying maltose binding protein fusion proteins by affinity precipitation.
The maltose binding protein (MBP) affinity tag has been extensively used for protein purification. A commercial grade cationic starch could precipitate MBP or an MBP-tagged protein quantitatively by simultaneous addition of 10% (w/v) polyethylene glycol (PEG) and 50 mM calcium chloride. The precipitated MBP or MBP-tagged protein could be selectively dissociated by suspending the precipitate in 1 M NaCl. In the case of a soluble MBP fusion with a fragment of human immunodeficiency virus protein gp120, 38% of the contaminating proteins could be removed by precipitation with PEG/CaCl(2) and 100% of the fusion protein was recovered. In all cases, the purified proteins showed a single band on sodium dodecyl sulfate-polyacrylamide gel electrophoresis and the expected changes in fluorescence emission spectra upon binding to maltose.


Inhibition of chymase activity by phosphoglycerides.
The activity of chymase was markedly inhibited by phosphoglycerides such as phosphatidic acid, phosphatidylserine, and phosphatidylinositol, but was not affected by acylglycerides, phosphoglyceroserine, serine, inositol, or glycerol. These results suggest that both the nonpolar hydrophobic hydrocarbon tails and the polar hydrophilic head are essential for the inhibitory effects of phosphoglycerides. Binding of a primary amine to an anionic polar head of phosphatidic acid, such as in phosphatidylserine and phosphatidylethanolamine, slightly decreased the inhibitory effect of phosphatidic acid and, conversely, binding of a strong cation to the head, such as in phosphatidylcholine, resulted in its activation of chymase. Phosphatidic acid containing an unsaturated fatty acid, such as dioleoyl phosphatidic acid, caused the same extent of inhibition as natural phosphatidic acid from bovine brain, but was 20 times more inhibitory than phosphatidic acid containing a saturated fatty acid, such as distearoyl phosphatidic acid. The inhibition by phosphatidylserine was noncompetitive and pseudoirreversible, and the Ki value was 0.54 microM. The inhibition of chymase by phosphatidylserine was pH dependent, being strong at pH 8.5 to 9.5 but weak below pH 7.5. Phosphatidylserine specifically inhibited chymase and elastase; it did not inhibit the other chymotrypsin-type serine endopeptidases tested, trypsin, papain, collagenase, carboxypeptidase A, or cathepsin D.


Dietary advanced glycation endproducts and oxidative stress: in vivo effects on endothelial function and adipokines.
Advanced glycation endproducts (AGEs) and oxidative stress (OS) contribute to the development and progression of diabetic complications. We have reported that dietary AGEs and OS induce acute endothelial dysfunction in vivo, but little is known about their effects on adipokines. Twenty inpatients with type 2 diabetes mellitus (mean age: 55.9; range: 32-71 years), received a standard diabetes diet for 6 days. On days 4 and 6, the acute effects of a high-AGE (HAGE) or a low-AGE (LAGE) meal (15.100 vs. 2.750 kU AGE) were studied in a randomized, cross-over, investigator-blinded design. Measurements were performed after an overnight fast, at baseline (B) and at 2, 4, and 6 h after the HAGE or LAGE meals. Both meals had the same ingredients and differed only by the cooking method. Two h following HAGE, a significant decrease from baseline occurred in adiponectin (-10%*double dagger vs. +0%) and leptin (-22%*double dagger vs. -13%*), and a significant increase occurred in vascular cell adhesion molecule 1 (+19%*double dagger vs. -5%) and thiobarbituric acid reactive substances (+23%*double dagger vs. +6%). These changes did not occur, or occurred to a lesser extent, following LAGE. At 4 h following HAGE, an increase in methylglyoxal (+20%double dagger vs. -5%) and E-selectin (+54%*double dagger vs. -3%) occurred. Urinary AGEs increased only after HAGE (+51%*double dagger vs. -2%; values presented as HAGE vs. LAGE; *P < 0.05 vs. baseline, double daggerP < 0.05 vs. LAGE). The postprandial excursions in glucose, insulin, and triglycerides were similar between both meals. A meal rich in AGEs induces acute endothelial and adipocyte dysfunction. These effects were prevented by changing the cooking method.


ProS-GNN: Predicting effects of mutations on protein stability using graph neural networks.
Predicting protein stability change upon variation through a computational approach is a valuable tool to unveil the mechanisms of mutation-induced drug failure and develop immunotherapy strategies. Some previous machine learning-based techniques exhibit anti-symmetric bias toward destabilizing situations, whereas others struggle with generalization to unseen examples. To address these issues, we propose a gated graph neural network-based approach to predict changes in protein stability upon mutation. The model uses message passing to encode the links between the molecular structure and property after eliminating the non-mutant structure and creating input feature vectors. While doing so, it also incorporates the coordinates of the raw atoms to provide spatial insights into the chemical systems. We test the model on the Ssym, Myoglobin, Broom, and p53 datasets to demonstrate the generalization performance. Compared to existing approaches, our proposed method achieves improved linearity with symmetry in less time. The code for this study is available at: https://github.com/HongzhouTang/Pros-GNN.


Decision criteria do not shift: commentary on Mueller and Weidemann (2008).
The effects of base rates and payoffs on the shapes of rating receiver operating characteristic curves are inconsistent with the basic assumptions of signal detection theory (SDT), in particular the notion of a shifting decision criterion. Mueller and Weidemann (2008) propose that these unexpected phenomena are not due to problems with the decision-criterion construct but are instead due to two compounded effects: instability of the decision criterion across trials, and even greater instability in the flanking criteria that determine which confidence rating will be reported. There are several problems with the authors' decision-noise hypothesis. First, even if their hypothesis about decision noise were taken for granted, the key feature of the ratings data that rejects the SDT model would remain a mystery. Second, the same violations of SDT that are exhibited in the ratings paradigm are also exhibited in the yes-no detection task when response time is substituted for confidence as a basis for analysis. Finally, the decision-noise hypothesis predicts that sensitivity will increase when one source of this variation-the response on a previous trial-is controlled for. This prediction was consistently violated in both the yes-no and ratings conditions of Mueller and Weidemann's experiment. In an Addendum, we respond to Weidemann and Mueller's (2008) reply to this Comment.


Quality of Life, Self-Esteem, and Depression Among Thai Transgender Women Before and After Male-to-Female Gender Confirmation Surgery: A Prospective Cohort Observational Study.
Previous studies have reported low quality of life scores and a high prevalence of depression among transgender women in Thailand; however, there is still little research on the effects of gender confirmation surgery among this population. This study aims to prospectively evaluate the overall quality of life, self-esteem, and depression status among male-to-female transgender individuals in Thailand. This prospective observational cohort study was conducted between January 2018 and December 2020 and included 41 participants who underwent gender confirmation surgery. All participants underwent a psychiatric evaluation and received 3 sets of questionnaires preoperatively and 6 months postoperatively to evaluate quality of life, self-esteem, and depression: the Thai abbreviated version of the World Health Organization quality of life questionnaire, the Rosenberg Self-Esteem Scale, and the Patient Health Questionnaire-9, respectively. We examined scores from each questionnaire and depression status before and after gender confirmation surgery, with P < .05 considered significant. This study's primary outcomes measured quality of life, depression, and self-esteem before and after gender confirmation surgery. Thirty-seven participants completed all sets of questionnaires (response rate 90.2%). The mean age of the participants was 26.2 ± 4.7 years at the time of surgery. Five (13.5%) participants met the criteria for mild depression preoperatively, but none did postoperatively. There were no signs of major depressive disorder, suicidal ideation, or suicidal attempts in any of the participants. There was a significant improvement in quality of life (P < .001) and self-esteem (P < .001), as well as lower depression (P < .001) after gender confirmation surgery. The greatest quality of life improvement was related to participants' sexual relationships. Male-to-female gender confirmation surgery significantly contributes to improving quality of life, self-esteem, and depression in Thai transgender women. Persons diagnosed with gender dysphoria who intend to undergo gender confirmation surgery should be supported by healthcare providers in accessing the medical facilities and treatment needed to improve their quality of life. Chaovanalikit T, Wirairat K, Sriswadpong P. Quality of Life, Self-Esteem, and Depression Among Thai Transgender Women Before and After Male-to-Female Gender Confirmation Surgery: A Prospective Cohort Observational Study. Sex Med 2022;10:100533.


Interferon assay in patients suspected of viral infections as a tool for rapid diagnosis. Brief report.
Significantly elevated interferon titers were found in sera and cerebrospinal fluids of patients suspected of viral infection, as compared to healthy controls. In most patients interferon was detected before serological confirmation or virus isolations.


Istradefylline Improves Impaired Smooth Pursuit Eye Movements in Parkinson's Disease.
Patients with Parkinson's disease (PD) exhibit alterations in eye movement control, primarily diverse oculomotor deficits which include hypometric saccade and impaired smooth pursuit with reduced pursuit-gain necessitating catch-up saccades. The effects of dopaminergic treatment of PD on eye movements are controversial. Previous studies suggest that smooth pursuit eye movements (SPEMs) are not directly influenced by the dopaminergic system. The nondopaminergic drug istradefylline, a selective adenosine A2A receptor antagonist, reduces the OFF time and improves somatomotor function in levodopa-treated PD. Here, we investigated whether istradefylline improves SPEMs in PD, and determined whether oculomotor performance is associated with somatomotor performance. Using an infrared video eye tracking system, we quantified horizontal SPEMs in six patients with PD before and 4-8 weeks after initiation of istradefylline administration. A further five patients with PD were tested before and after a 4-week interval without istradefylline to control for practice effects. We evaluated smooth pursuit gain (eye velocity/target velocity), accuracy of smooth pursuit velocity, and saccade rate during pursuit before and after istradefylline administration during the ON state. Patients received istradefylline by single daily oral administration at 20 to 40 mg. Eye tracking data were obtained 4-8 weeks after initiation of istradefylline administration. Istradefylline increased smooth pursuit gain and the accuracy of smooth pursuit velocity, and tended to decrease saccade rates during pursuit. Istradefylline ameliorated the oculomotor deficit in SPEM of patients with PD, although differences in somatomotor performance before and after istradefylline treatment were not significant during ON periods. The discrepancy observed between the oculomotor and somatomotor responses to istradefylline supports previous findings that SPEM is at least partially under nondopaminergic control.


4 Day in dry immersion reproduces partially the aging effect on the arteries as observed during 6 month spaceflight or confinement.
The objectives of this study were to determine whether 4 days of dry immersion (DI) induced similar arterial aging as spaceflight and to test the impact of thigh cuffs. Eighteen subjects underwent DI; nine wore thigh cuffs. Cardiac and arterial targets were assessed by ultrasound. No significant differences were found between the groups. The left ventricle volume, stroke volume (SV), and ejection fraction decreased with DI (p < 0.001). Carotid distensibility reduced (p < 0.05), carotid to femoral arterial tree became stiffer in 33% of the subjects, and femoral artery intima media thickness increased (p < 0.05). A reduction in plasma volume is likely to have caused the observed cardiac changes, whereas the arterial wall changes are probably best explained by hypokinesia and/or environmental stress. These changes are similar but lower in amplitude than those observed in spaceflight and mimic the natural aging effect on earth. The daytime-worn thigh cuffs had no acute or chronic impact on these arterial-focused measurements.


Antibodies against haptens in the study of structure and biological activity of growth hormone.
The alpha-amino group of bovine Growth Hormone was selectively modified with TNBS with no detectable changes in growth promoting activity. TNP was used as hapten for the production of antibodies against the end terminal region of bGH. The region near the alpha-amino group is not involved in the binding of bGH to rat liver cells, and it seems to be away from the part of the molecule that interacts with the cell binding sites.


Oblique dipole layer potentials applied to electrocardiology.
We study the properties of the potential field generated by an oblique dipole layer. This field arises, for instance, in describing the potential elicited by a depolarization wavefront spreading in the myocardium when a dependence of the potential on the cardiac fiber orientation is introduced. The representation of cardiac bioelectric sources by means of an oblique dipole layer leads to a mathematical structure which generalizes the classical solid angle theory used in electrocardiology, which has been challenged by recent experimental evidence, and links models previously proposed with a view to adequately reproduce the potential observed in experiments. We investigate also the relationship between our model and an intracellular current model and we derive potential jump formulae for some models which account for the anisotropic structure of the myocardium. The potential generated by an oblique dipole layer is considered both for unbounded and bounded domains. In the latter case an integral boundary equation is derived and we study its solvability. A numerical procedure for solving this integral equation by means of the finite element method with collocation is outlined.


Solid-State Radical C-H Trifluoromethylation Reactions Using Ball Milling and Piezoelectric Materials.
The application of piezoelectricity for the generation of trifluoromethyl (CF3 ) radicals is reported together with the development of a method for the mechanochemical C-H trifluoromethylation of aromatic compounds. As compared to conventional solution-based approaches, this mechanoredox C-H trifluoromethylation enables cleaner and more sustainable access to a wide range of trifluoromethylated N-heterocycles and peptides, which are important structural motifs in modern drug discovery. This study thus represents an important milestone for future applications of mechanoredox systems to medicinal and pharmaceutical science.


[Evaluation of potentiality of combined SHF- and glow discharge in intensification of carbon dioxide and hydrogen processing within life support system].
The article reports an experimental carbon dioxide hydration process in combined SHF- and glow discharge, and describes a design of SHF plasmatrones for CO2 processing at air pressure and in an integrated unit. Maximal transformation of 80% CO2 per a run was reached with the total input power of no more than 0.9 kW. Thermal zero lag of plasma forming, essentially instant and timely engagement and disengagement of thermal action on CO2-H2 mixture renders SHF-energy applicable to intensification of next generation life support technologies, processing of these gases within atmosphere regeneration system specifically.


Extracellular calcium as an integrator of tissue function.
The past several decades of research into calcium signaling have focused on intracellular calcium (Ca(i)(2+)), revealing both exquisite spatial and dynamic control of this potent second messenger. Our understanding of Ca(i)(2+) signaling has benefited from the evolution of cell culture methods, development of high affinity fluorescent calcium indicators (both membrane-permeant small molecules and genetically encoded proteins), and high-resolution fluorescence microscopy. As our understanding of single cell calcium dynamics has increased, translational efforts have attempted to push calcium signaling studies back into tissues, organs and whole animals. Emerging results from these more complicated, diffusion-limited systems have begun to define a role for extracellular calcium (Ca(o)(2+)) as an agonist, spurred by the cloning and characterization of a G protein-coupled receptor activated by Ca(o)(2+) (the calcium sensing receptor, CaR). Here, we review the current state-of-the art for measurement of Ca(o)(2+) fluctuations, and the evidence that fluctuations in Ca(o)(2+) can act as primary signals regulating cell function. Current results suggest that Ca(o)(2+) in bone and epidermis may act as a chemotactic homing signal, targeting cells to the appropriate tissue locations prior to initiation of the differentiation program. Ca(i)(2+) signaling-mediated Ca(o)(2+) fluctuations in interstitial spaces may integrate cell signaling responses in multicellular networks through activation of CaR. Appreciation of the importance of Ca(o)(2+) fluctuations in coordinating cell function will likely spur identification of additional, niche-specific Ca(2+) sensors, and provide unique insights into the regulation of multicellular signaling networks.


Elevated serum caeruloplasmin level in a patient with adult Still's disease.
We report the case of a woman with a characteristic transient skin rash, fever, severe polyarthritis, hepatosplenomegaly, lymphadenopathy and myalgia. The clinical and laboratory data led to a diagnosis of adult-onset Still's disease. The elevated levels of serum ferritin and caeruloplasmin could be important as diagnostic indicators.


Association of acanthosis nigricans with insulin resistance in patients with polycystic ovary syndrome.
This study was designed to explore the association of insulin resistance and acanthosis nigricans (AN) in patients with polycystic ovary syndrome (PCOS). Fifty women, 18-37 years old, were included in the study, and divided into five groups consisting of: (I) 10 women with PCOS, abnormal body mass index (BMI) and AN; (II) 10 women with PCOS and abnormal BMI, but without AN; (III) 10 women with PCOS, normal BMI, and no AN; (IV) 10 women with abnormal BMI, but without PCOS or AN; and (V) 10 healthy women with normal BMI. Measurement of fasting glucose and insulin levels before and after oral glucose challenge was performed. Fasting serum insulin levels were found to be significantly lower in groups III, IV and V than in groups I and II, with no significant difference between groups I and II, or between groups III, IV and V. Total insulin response following administration of glucose did not differ significantly between the groups. These findings support the view that obese PCOS patients with AN do not have significantly higher insulin resistance than obese patients without AN. Insulin resistance is a necessary, but not the only, factor leading to the development of AN in patients with PCOS. Other factors should also be considered in the pathogenesis of this cutaneous reaction.


Effect of amino acids on cell proliferation and protein p53 expression in organotypic culture of lymphoid tissue from neonatal rats.
The effect of the larger molecular weight l-amino acids on the development of spleen explants from 1- and 21-day rats in organotypic tissue culture was studied. The amino acids asparagine, lysine, arginine, and glutamic acid inhibited the growth zone of explants of immature tissue from 1-day animals but had an opposite, stimulating, effect on mature spleen tissue of 21-day rats. Immunohistochemical analysis revealed a reciprocal correlation between the expression of the proapoptotic protein, p53, and T-cell proliferation in response to lysine, asparagine, and glutamic acid. Interestingly only arginine reduced the area of p53 expression both in explants of mature and immature spleen tissue. The ability of arginine to reduce p53 expression can be suggested as one of the mechanisms of the tumor growth stimulation.


Redox regulation of wound healing? NF-kappaB activation in cultured human keratinocytes upon wounding and the effect of low energy HeNe irradiation.
The complex process of wound healing as well as the signaling systems orchestrating this intricate process remain incompletely defined. Using human keratinocytes in primary culture, we sought to characterize their NF-kappaB responses to wounding alone or in combination with other treatments. We initially characterized these cultured human keratinocytes responses to known NF-kappaB activators (PMA, TNF-alpha and IL-1) using two different assays, immunohistochemistry and electrophoretic mobility shift (EMSA). After eliciting the expected NF-kappaB responses, we applied these same assays to assess responses to either wounding or HeNe irradiation alone. The results obtained indicated that only a modest/sporadic activation of NF-kappaB was elicited by these which was only detectable using immunohistochemistry. When the combination of wounding and HeNe irradiation on NF-kappaB status was assessed, a marked, localized activation of NF-kappaB in keratinocytes along the wound edge was found. Treatment induced NF-kappaB activation (e.g., wounding, HeNe irradiation and combined wounding and HeNe irradiation) was abrogated by pyrrolidine dithiocarbamate (PDTC) which inhibits NF-kappaB activation through an as yet incompletely understood (antioxidant?) mechanism. These data therefore suggest that NF-kappaB and oxidation mediated changes in its activation state likely play important roles in normal cutaneous wound healing.


Dithiol-Activated Bioorthogonal Chemistry for Endoplasmic Reticulum-Targeted Synergistic Chemophototherapy.
The controlled intracellular release of nitrite is still an unmet challenge due to the lack of bio-friendly donors, and the antitumor effect of nitrite is limited by its physiologically inert activity. Herein, we designed benzothiadiazole-based organic nitrite donors that are stable against bio-relevant species but selectively respond to dithiol species through SN Ar/intramolecular cyclization tandem reactions in the aqueous media. The bioorthogonal system was established to target the endoplasmic reticulum (ER) of liver cancer HepG2 cells. The nitrite and nonivamide were coupled to induce elevation of intracellular levels of calcium ions as well as reactive oxygen/nitrogen species, which resulted in ER stress and mitochondrial dysfunction. We demonstrated that a combination of photoactivation and "click to release" strategy could enhance antitumor effect in cellular level and show good potential for cancer precision therapy.


Isthmic origin of neurons of the rat substantia nigra.
This study provides new data on the time of origin, the generation site and the migration route of the young neurons of the substantia nigra of the rat during embryogenesis. The neurons of the substantia nigra are generated on day 12, 13, 14 and 15 of gestation. They settle following a light spatiotemporal rostrocaudal gradient from day 12 to 15. The neurons of the substantia nigra are generated at two different points of the basal plate at the level of the fovea isthmi (meso-isthmic junction) and migrate in radial pattern as two definite streams toward the ventral mesencephalon. From this point they move rostralwards along the surface towards their final site. The main findings of this work are the disclosure that the neurons of the substantia nigra are generated in the region of the isthmus rhombencephali and that its cells do not migrate between existing cells of the mesencephalic tegmentum but first migrate ventralwards in a radial pattern and then rostrally towards their definite site. Numerous neurons of the basal mesencephalon and of the midline structures of the caudal mesencephalon are apparently derived from the region of the fovea isthmi.


Evidence of cytosolic iron release during post-ischaemic reperfusion of isolated rat hearts. Influence on spin-trapping experiments with DMPO.
Previous studies of oxygen-derived free radical generation based on spin-trapping methods have shown a signal formed of six bands (sextet) using electron spin resonance spectrometry (ESR) of coronary effluents collected during post-ischaemic reperfusion of isolated hearts perfused with 5,5-dimethyl-1-pyrroline N-oxide (DMPO). The origin of this signal has recently become controversial. In the present study we show that, in the rat, this sextet and cytosolic iron release occur simultaneously, and that this signal can be inhibited by the iron chelator desferrioxamine. It also appears that the iron release is not protein bound, and could therefore have a marked catalytic activity. This may be responsible for the production of an artefactural signal observed as the sextet.


Surgical outcome of isolated total anomalous pulmonary venous connection in adults: a 14-year experience.
To investigate the surgical result of adult total anomalous pulmonary venous connection (TAPVC). From March 1997 to March 2011, 12 adult cases of isolated TAPVC, with an average age of 24.9 ± 6.7 years (from 18 to 41 years), underwent surgical repair in our department. All patients suffered from right-sided volume overload with clinical manifestations varying from mild cyanosis to severe heart failure. According to Darling's classification, eight cases were classified as supracardiac type, four as cardiac type. Unobstructed connections were established between the left atrium and the pulmonary common vein in all patients with external cardiac approach in four supracardiac cases, and internal cardiac approach in four cardiac and three supracardiac cases, and Warden technique in one supracardiac patient. Concomitant operations included De Vega's tricuspid annuloplasty in six patients, patent arteriosus ductus closure in two. All patients survived the operation, and postoperative follow-up was 100% complete with a period ranging from 10 months to 14 years. NYHA grade decreased from 2.33 ± 0.49 to 1.08 ± 0.29 (p < 0.01). Three patients had postoperative tricuspid insufficiency. Five patients had cardiac arrhythmia, among two symptomatic cases; one controlled with medication, another received a successful radiofrequency ablation for incision-related atrial flutter. Surgical correction of isolated adult TAPVC can be carried out safely with acceptable long-term outcome. Postoperative tricuspid insufficiency and cardiac arrhythmias may have a negative long-term impact, which should be evaluated preoperatively and managed individually during surgery.


Cognitive, behavioral, and brain functional connectivity correlates of fatigue in amyotrophic lateral sclerosis.
Fatigue is defined as a symptom of exhaustion unexplained by drug effects or psychiatric disorders and comprises two main components (i.e., central or "mental" and peripheral or "physical" components), both influencing global disability in amyotrophic lateral sclerosis (ALS). We aim at investigating the clinical correlations between "physical" and "mental" components of fatigue, measured by the Multidimensional Fatigue Inventory scale, and motor and cognitive/behavioral disability in a large sample of patients with ALS. We also investigated the correlations between these measures of fatigue and resting-state functional connectivity of brain functional magnetic resonance imaging (RS-fMRI) large-scale networks in a subset of patients. One hundred and thirty ALS patients were assessed for motor disability, cognitive and behavioral dysfunctions, fatigue, anxiety, apathy, and daytime sleepiness. Moreover, the collected clinical parameters were correlated with RS-fMRI functional connectivity changes in the large-scale brain networks of 30 ALS patients who underwent MRI. Multivariate correlation analysis revealed that "physical" fatigue was related to anxiety and respiratory dysfunction, while "mental" fatigue was related to memory impairment and apathy. Moreover, the mental fatigue score was directly related to functional connectivity in the right and left insula (within the salience network), and inversely related to functional connectivity in the left middle temporal gyrus (within the default mode network). Although the "physical" component of fatigue may be influenced by the disease itself, in ALS the "mental" component of fatigue correlates with cognitive and behavioral impairment, as well as with alterations of functional connectivity in extra-motor networks.


Complete Genome Sequence of Streptomyces ambofaciens DSM 40697, a Paradigm for Genome Plasticity Studies.
The sequence of Streptomyces ambofaciens DSM 40697 was completely determined. The genome consists of an 8.1-Mbp linear chromosome with terminal inverted repeats of 210 kb. Genomic islands were identified, one of which corresponds to a new putative integrative and conjugative element (ICE) called pSAM3.


Comparison of sodium chloride hopper cubes grown under microgravity and terrestrial conditions.
Sodium chloride (NaCl) grown in terrestrial conditions form hopper cubes under diffusion controlled mass transport (Péclet number: ≪ 1), high supersaturations (S > 1.45), and fast growth rates (10-110 µm/s) over periods only maintainable for seconds to minutes yielding hopper cubes typically <250 µm. Here we report on NaCl hopper cubes grown in microgravity on the International Space Station (ISS) by evaporation of brine. They grew under diffusion limited mass transport (Péclet number: ~4 × 10-4 - 4) at low supersaturation (S < 1.002) and slow growth rates (0.34-1 µm/min) over periods of days to weeks. Due to the lack of sedimentation, symmetrical hopper cubes, 2-8 mm were produced. The most striking differences between microgravity and terrestrial gravity hopper growth conditions are low supersaturation and slow growth rates over long periods of time. Large, 1-20 cm naturally occurring symmetrical NaCl hopper cubes are found suspended in brine soaked mud, hypothesized to be produced in a slow growth, diffusion dominated environment. We speculate these geologic conditions allow for hopper growth similar to that of microgravity.


Percutaneous internal ring suturing as a first choice laparoscopic inguinal hernia repair method in girls: a single-center study in 148 patients.
We sought to retrospectively assess the operative findings and clinical outcomes of 148 girls who underwent laparoscopic inguinal hernia repair with the percutaneous internal ring suturing (PIRS) technique. Between 2010 and 2014, girls with inguinal hernia underwent surgery using the laparoscopic PIRS technique described by Patkowski. Demographic and perioperative findings, complications, and recurrences were evaluated. A total of 205 inguinal hernia repairs were performed in 148 children with a mean age of 5.83 years (1 month-16 years). In 57 girls (38.5 %), the hernias were bilaterally repaired, while in 91 girls (61.5 %) hernias were unilaterally repaired. The mean follow-up time was 3.6 years (range 2.5-6.1 years). No serious complications or recurrence were noted. Granuloma occurred in one patient. The PIRS technique is a safe, simple and effective procedure for girls. Excellent cosmetic results and reduced recurrence rates are associated with this method. This procedure is particularly suitable for girls because they lack a spermatic cord and vascular structures that can cause complications with this technique in boys. Based on our experience and others in the literature, we suggest that the PIRS procedure might be considered a gold standard for inguinal hernia operations in girls.


Applications of nanoparticles for treating cutaneous infection.
Today, nanotechnology is finding applications in medicine. The unique physical and chemical properties of nanoparticles can overcome barriers and allow them to gain access to biological systems. Because of the increasing prevalence of microbial resistance to conventional therapies, the development of novel antimicrobials is imperative. Creating nanotechnology-based drug delivery systems with antibacterial and immunomodulatory activities may lead to novel treatments for cutaneous pathogens.


Solubility and Thermodynamic Analysis of Antihypertensive Agent Nitrendipine in Different Pure Solvents at the Temperature Range of 298.15 to 318.15°K.
The aim of the present study was to ascertain the solubility of nitrendipine (NP), an antihypertensive drug in six different pure solvents such as water, ethyl acetate (EA), ethanol, isopropyl alcohol (IPA), polyethylene glycol-400 (PEG-400), and Transcutol at temperature from 298.15 to 318.15 K under atmospheric pressure (p) of 0.1 MPa. Experimental solubility data of NP was fitted with Apelblat and ideal models. The mole fraction solubility of NP was found maximum in PEG-400 (6.85 × 10-2 at 318.15 K) followed by Transcutol (4.65 × 10-2 at 318.15 K), EA (1.68 × 10-2 at 318.15 K), ethanol (2.83 × 10-3 at 318.15 K), IPA (2.69 × 10-3 at 318.15 K), and water (1.29 × 10-7 at 318.15 K). The dissolution activity of NP was observed as an endothermic, spontaneous, and an entropy-driven in most of studied pure solvents. The solubility data of NP obtained in the present study could be useful in purification, recrystallization, and dosage forms design of NP.


Genome analysis of Pseudomonas chlororaphis subsp. aurantiaca mutant strains with increased production of phenazines.
Genomes of three strains-phenazine producers-Pseudomonas chlororaphis subsp. aurantiaca (B-162 (wild type), mutant strain B-162/255, and its derivative B-162/17) were sequenced and compared. Comparison of a wild-type strain and B-162/255 mutant genomes revealed 32 mutations. 19 new mutations were detected in the genome of B-162/17. Further bioinformatics analysis allowed us to predict mutant protein functions and secondary structures of five gene products, mutations which might potentially influence phenazine synthesis and secretion in Pseudomonas bacteria. These genes encode phenylalanine hydroxylase transcriptional activator PhhR, type I secretion system permease/ATPase, transcriptional regulator MvaT, GacA response regulator, and histidine kinase. Amino acid substitutions were found in domains of studied proteins. One deletion in an intergenic region could affect a potential transcription factor binding site that participates in the regulation of gene that encodes ABC transporter.


Concurrent Hepatic Tuberculosis and Hepatic Graft-versus-host Disease in an Allogeneic Hematopoietic Stem Cell Transplant Recipient: A Case Report.
Infection and graft-versus-host disease (GVHD) are among the most common complications after hematopoietic stem cell transplantation (HSCT). With well-known risk factors including allogeneic HSCT and GVHD, tuberculosis (TB) has a higher incidence and shorter survival rate in HSCT recipients than in the general population. A 55-year-old Indonesian female with a history of latent TB was found to have acute myeloid leukemia 3 months after allogeneic HSCT. She presented with fever, abdominal pain, and predominant cholestatic-type liver function tests derangement. Computed tomography scans showed a relatively unremarkable liver. Liver biopsy specimens revealed multiple necrotizing granulomas with numerous acid-fast bacilli shown using Ziehl-Neelsen histochemical stain. No fungal organisms are detected by Grocott's methenamine silver and periodic acid-Schiff stains. There was also mild portal hepatitis with prominent bile duct injury and scattered apoptotic bodies, compatible with GVHD. In addition, the patient was also discovered to have cutaneous and intestinal TB as well as cutaneous and colonic GVHD during investigation. She was started on anti-TB treatment and adjusted immunosuppression scheme accordingly. Unfortunately, our patient died of spontaneous intracranial haemorrhage approximately 2 months after the diagnosis of post-transplantation TB and GVHD. We report a case of concurrent hepatic TB and GVHD in an allogeneic HSCT recipient. Recognition of the dual pathology in the biopsy results aids proper treatment.


Intra-unit patient transports: time, motion, and cost impact on hospital efficiency.
The costly and inefficient movement of patients within the hospital challenges health systems across the country as they strive to simultaneously contain rising costs and provide high-quality patient care. Solid evidence to support the improvement of hospital and patient care efficiency through the identification and suggested elimination of waste patterns within the transport process is presented.


Analytical expressions for the homotropic binding of ligand to protein dimers and trimers.
Cooperative binding of a ligand to multiple subsites on a protein is a common theme among enzymes and receptors. The analysis of cooperative binding data (either positive or negative) often relies on the assumption that free ligand concentration, L, can be approximated by the total ligand concentration, L(T). When this approximation does not hold, such analyses result in inaccurate estimates of dissociation constants. Presented here are exact analytical expressions for equilibrium concentrations of all enzyme and ligand species (in terms of K(d) values and total concentrations of protein and ligand) for homotropic dimeric and trimeric protein-ligand systems. These equations circumvent the need to approximate L and are provided in Excel worksheets suitable for simulation and least-squares fitting. The equations and worksheets are expanded to treat cases where binding signals vary with distinct site occupancy.


Environmental tobacco smoke and mortality in Chinese women who have never smoked: prospective cohort study.
To evaluate the association of environmental exposure to tobacco smoke from husbands and from work, as well as from family members in early life, with all cause mortality and mortality due to cancer or cardiovascular disease in Chinese women. Ongoing prospective cohort study in Shanghai, China. Of 72,829 women who had never smoked, 65,180 women provided information on smoking by their husbands, and 66,520 women provided information on exposure to tobacco smoke at work and in early life from family members. All cause mortality and cause specific mortality with the main focus on cancer and cardiovascular disease. Cumulative mortality according to exposure status, and hazard ratios. Exposure to tobacco smoke from husbands (mainly current exposure) was significantly associated with increased all cause mortality (hazard ratio 1.15, 95% confidence interval 1.01 to 1.31) and with increased mortality due to cardiovascular disease (1.37, 1.06 to 1.78). Exposure to tobacco smoke at work was associated with increased mortality due to cancer (1.19, 0.94 to 1.50), especially lung cancer (1.79, 1.09 to 2.93). Exposure in early life was associated with increased mortality due to cardiovascular disease (1.26, 0.94 to 1.69). In Chinese women, exposure to environmental tobacco smoke is related to moderately increased risk of all cause mortality and mortality due to lung cancer and cardiovascular disease.


Effects of exercise mode, energy, and macronutrient interventions on inflammation during military training.
Load carriage (LC) exercise may exacerbate inflammation during training. Nutritional supplementation may mitigate this response by sparing endogenous carbohydrate stores, enhancing glycogen repletion, and attenuating negative energy balance. Two studies were conducted to assess inflammatory responses to acute LC and training, with or without nutritional supplementation. Study 1: 40 adults fed eucaloric diets performed 90-min of either LC (treadmill, mean ± SD 24 ± 3 kg LC) or cycle ergometry (CE) matched for intensity (2.2 ± 0.1 VO2peak L min(-1)) during which combined 10 g protein/46 g carbohydrate (223 kcal) or non-nutritive (22 kcal) control drinks were consumed. Study 2: 73 Soldiers received either combat rations alone or supplemented with 1000 kcal day(-1) from 20 g protein- or 48 g carbohydrate-based bars during a 4-day, 51 km ski march (~45 kg LC, energy expenditure 6155 ± 515 kcal day(-1) and intake 2866 ± 616 kcal day(-1)). IL-6, hepcidin, and ferritin were measured at baseline, 3-h post exercise (PE), 24-h PE, 48-h PE, and 72-h PE in study 1, and before (PRE) and after (POST) the 4-d ski march in study 2. Study 1: IL-6 was higher 3-h and 24-h post exercise (PE) for CE only (mode × time, P < 0.05), hepcidin increased 3-h PE and recovered by 48-h, and ferritin peaked 24-h and remained elevated 72-h PE (P < 0.05), regardless of mode and diet. Study 2: IL-6, hepcidin and ferritin were higher (P < 0.05) after training, regardless of group assignment. Energy expenditure (r = 0.40), intake (r = -0.26), and balance (r = -0.43) were associated (P < 0.05) with hepcidin after training. Inflammation after acute LC and CE was similar and not affected by supplemental nutrition during energy balance. The magnitude of hepcidin response was inversely related to energy balance suggesting that eating enough to balance energy expenditure might attenuate the inflammatory response to military training.


Strabismus in pediatric pseudophakia.
To evaluate strabismus associated with pediatric pseudophakia. Retrospective case series. Charts of 94 pediatric patients who underwent cataract extraction with primary intraocular lens implantation from 1990 to 2003 at Indiana University School of Medicine were reviewed. Only those patients who had pre-cataract extraction and post-cataract extraction alignment measurements were included. Data were collected on gender, race, age at presentation, age at time of cataract surgery, and type of cataract. Pre-cataract extraction and post-cataract extraction data on visual acuity (VA), alignment, and amblyopia were recorded. Results of strabismus surgery were also evaluated. Frequency, type and amount of strabismus, and results of strabismus surgery. Ninety-four pediatric pseudophakia patients were identified, and 37 (39%) had strabismus. Exotropia (46%) was more common than esotropia (41%). Factors not associated with the development of strabismus included age at presentation, interval between diagnosis and cataract extraction, race, and type of cataract. Factors statistically associated with the development of strabismus include pre-cataract extraction and post-cataract extraction VA, type of strabismus, and post-cataract extraction amblyopia. The mean pre-cataract extraction deviation of the group that had strabismus surgery was 22 prism diopters, and 75% were aligned at the last examination (mean follow up, 24 months). Strabismus occurs more frequently in pseudophakic pediatric patients than in the general pediatric population. Pseudophakic children should be monitored carefully for the development of strabismus, which in many cases can be successfully treated.


A correlative study of the antiulcer effects of zinc sulphate in stressed rats.
The effects on zinc sulphate pretreatment of rats on stress-induced gastric ulcers and on changes in mast cell counts were studied and correlated with changes in gastric mucosal microcirculation. The effects on zinc sulphate on blood pressure responses and on growth were also examined. Stress (2 h restraint at 4 degrees C) produced marked glandular mucosal ulceration, lowered the stomach wall mast cell counts and increased the microcirculatory blood volume in the superficial glandular mucosa. Zinc sulphate (22, 44 or 88 mg/kg; injected i.p. 48 h before stress) reversed all these changes in a dose-related manner. Blood pressure responses to i.v. acetylcholine, adrenaline or histamine were unaffected and growth of the rats as observed for 7 days after injection was not impaired. On the basis of these findings the mechanism of the antiulcer action of zinc sulphate is the following: inhibition of the stress-induced release of vasoactive agents from gastric mast cells and thus prevention of the subsequent microciculatory changes known to produce mucosal ulceration. Interference with vascular responses through direct blockade or toxicity is unlikely.


[Osteomyelitis. First experiences with P.M.M.A. chains and balls (author's transl)].
A new therapeutic principle in the treatment of osteomyelitis is introduced-as an alternative to "Suction Drainage"-, i.e. "Gentamycine P.M.M.A. chains". After exact surgical debridement a local therapy with high concentrations of antibiotic is possible. Results of the performed operations on 51 patients are encouraging after 14 months. Long term results are as yet not known.


D-cycloserine improves sociability and spontaneous stereotypic behaviors in 4-week old mice.
Balb/c mice are a model of impaired sociability and social motivation relevant to autism spectrum disorders (ASDs). Impaired sociability of 8-week old Balb/c mice is attenuated by agonists of the glycine(B) site on the NMDA receptor, such as d-cycloserine. Although ASDs are often recognized in toddlerhood, there is interest in earlier identification (e.g., before 6 months) and disease-modifying interventions to improve functional outcomes. Thus, we wondered if d-cycloserine could improve sociability in 4-week old Balb/c mice, similar to its effects in 8-week old mice. d-Cycloserine improved measures of impaired sociability in 4-week old (i.e., one-week post-weanling) Balb/c mice. Moreover, because stereotypies can compete with the salience of social stimuli, we compared Balb/c and Swiss Webster mice on several spontaneous stereotypic behaviors emerging during social interaction with a social stimulus mouse. Interestingly, similar to 8-week old mice, spontaneous stereotypic behaviors during social interaction were more intense in the 4-week old Swiss Webster mice; furthermore, d-cycloserine reduced their intensity. Thus, d-cycloserine improves both sociability and stereotypic behaviors, but these effects may lack strain-selectivity. A prosocial effect of d-cycloserine was observed at a dose as low as 32.0mg/kg in Balb/c mice. d-cycloserine has the therapeutic properties of a desired medication for ASDs; specifically, a medication should not improve stereotypic behaviors at the expense of worsening sociability and vice versa. The data suggest that targeting the NMDA receptor can have promising therapeutic effects on two prominent domains of psychopathology in ASDs: impaired sociability and spontaneous stereotypic behaviors.


Alkaline extraction: An optimal approach for extracting methylmercury from paddy soils.
Accurately measuring the concentration of methylmercury (MeHg) is a critical part of Hg research. While analytical methods of MeHg have not been validated for paddy soils, which are one of the most important and active sites of MeHg production. Here we compared two methods most widely used to extract MeHg from paddy soils, i.e., CuSO4/KBr/H2SO4-CH2Cl2 (referred to as acid extraction) and KOH-CH3OH (referred to as alkaline extraction). By evaluating the formation of MeHg artifact using Hg isotope amendments and quantifying the extraction efficiency using the standard spike in 14 paddy soils, we propose that alkaline extraction is an optimal choice for paddy soils, with negligible MeHg artifact (accounting for 0.62-8.11 % of the background MeHg) and consistently high extraction efficiency (81.4-114.6 % for alkaline extraction compared with 21.3-70.8 % for acid extraction). Our finding highlights the importance of suitable pretreatment and appropriate quality controls during the measurement of MeHg concentrations.


End-plate channels behave as neutral site channels.
The voltage sensitivity and concentration dependence of single channel conductance at the motor end-plate in the presence of different alkali cations have been compared with the predictions of different permeation models. The models have been developed, using the diffusional approach, to cater for three cations and anion permeability has been assumed to be insignificant. It was found that a neutral site channel model provided the best fit to the experimental data. The analyses also implied a high field strength sequence for the equilibrium selectively of the sites.


Structural and energetic understanding of novel natural inhibitors of Mycobacterium tuberculosis malate synthase.
Persistent infection by Mycobacterium tuberculosis requires the glyoxylate shunt. This is a bypass to the tricarboxylic acid cycle in which isocitrate lyase (ICL) and malate synthase (MS) catalyze the net incorporation of carbon during mycobacterial growth on acetate or fatty acids as the primary carbon source. To identify a potential antitubercular compound, we performed a structure-based screening of natural compounds from the ZINC database (n = 1 67 740) against the M tuberculosis MS (MtbMS) structure. The ligands were screened against MtbMS, and 354 ligands were found to have better docking score. These compounds were assessed for Lipinski and absorption, distribution, metabolism, excretion, and toxicity prediction where 15 compounds were found to fit well for redocking studies. After refinement by molecular docking and drug-likeness analysis, four potential inhibitors (ZINC1483899, ZINC1754310, ZINC2269664, and ZINC15729522) were identified. These four ligands with phenyl-diketo acid were further subjected to molecular dynamics simulation to compare the dynamics and stability of the protein structure after ligand binding. The binding energy analysis was calculated to determine the intermolecular interactions. Our results suggested that the four compounds had a binding free energy of -201.96, -242.02, -187.03, and -169.02 kJ·mol-1 , for compounds with IDs ZINC1483899, ZINC1754310, ZINC2269664, and ZINC15729522, respectively. We concluded that two compounds (ZINC1483899 and ZINC1754310) displayed considerable structural and pharmacological properties and could be probable drug candidates to fight against M tuberculosis parasites.


Beyond the hand and upper extremity: The role of hand therapists in care of people with rheumatic diseases.
Invited Clinical Commentary BACKGROUND: Arthritis is one of the most frequently reported causes of disability in the United States and the prevalence is expected to increase in the coming decades. While many rheumatic diseases involve hand impairments, most are systemic and involve more than the musculoskeletal system. Functional and work disability are high and people would benefit from the services of occupational and physical therapists. This paper reviews concepts of self-management, and symptoms that contribute to limitations and restrictions to participation in daily life in people with rheumatic diseases and suggests roles for hand therapists beyond the immediate hand impairments. The impact of selected rheumatic diseases on functional and work disability are reviewed along with strategies for symptom management and self-management. Upper extremity impairments of selected rheumatic diseases are also discussed. The role for hand therapists in evaluating and addressing the complex needs of persons with rheumatic diseases, including less common diseases, is discussed. Outcome measures for fatigue, muscle involvement, ergonomics and computer use, and work disability are introduced. Finally, strategies for self-management and prevention of work and functional disability, along with symptom management for fatigue and pain are presented. Hand therapists can play a vital role in chronic rheumatic disease management to improve self-management and increase participation in meaningful activities. Patients, primary care and rheumatology providers need to be educated about the scope of services occupational and physical therapists provide beyond the hand impairments.


Oncologic outcome in surgical management of jugular paraganglioma and factors influencing outcomes.
The purpose of this study was to identify the factors that may influence the management outcome in patients with jugular paragangliomas. The surgical records of 121 cases of jugular paraganglioma (Fisch classifications C and D) were reviewed. The average follow-up was 88 months. Intracranial extension (ICE; Fisch classification De and Di) constitutes 55.4% of the cases. Two cases had a malignant jugular paraganglioma. Complete tumor resection was achieved in 81.8% of the cases, and there was evidence of recurrence in 4.0% from this group. Surgical tumor control was achieved in 96% of cases. Perioperative complications consisted mainly of cerebrospinal fluid leakage in 1.6% of the cases. The lower cranial nerve (CN) was preserved in 63% of the patients mainly in the cases without ICE. The infratemporal fossa approach type A allows for complete tumor resection with low perioperative morbidity and recurrence rates. The significant influential factors were the severity of ICE and internal carotid artery involvement.


In the normal repertoire of CD4+ T cells, a single class II MHC/peptide complex positively selects TCRs with various antigen specificities.
In the thymus, immature T cells are positively and negatively selected by multiple interactions between their Ag receptors (TCRs) and self MHC/peptide complexes expressed on thymic stromal cells. Here we show that in the milieu of negative selection on physiological self class II MHC/peptide complexes (Abwt), a single class II/peptide complex AbEp52-68 positively selects a number of TCRs with various Ag specificities. This TCR repertoire is semidiverse and not biased toward Ep-like Ags. Our finding implies that the degeneracy of positive selection for peptide ligands exceeds peptide-specific negative selection and is essential to increase the efficiency and diversity of the repertoire so that T cells with the same Ag specificity can be selected by different self MHC/ peptide complexes.


A reply to: "Response to Comment on "Density Functional Theory and 3D-RISM-KH molecular theory of solvation studies of CO2 reduction on Cu-, Cu2O-, Fe-, and Fe3O4-based nanocatalysts"".
In response (Kovalenko and Neburchilov, J. Mol. 28:33, 1) to the comment (Gusarov, J. Mol. 27:344-354, 2), the authors avoided answering the main question about the incorrect intermediate state of CO2 + H2 reduction reaction studied by Kovalenko and Neburchilov (J. Mol. 26:267-276, 3). The intermediate products of this reaction are well known and presented in the literature including the studies of Li and Kanan (J. Am. Chem. Soc. 134:7231-7234, 4); Feaster et al. (ACS Catal. 7:4822-4827, 5); Choi et al. (Sci. Rep. 7:41,207-41,210, 6); Kuhl et al. (Am. Chem. Soc. 136:14,107-14,113, 7); Kuhl et al. (Energy Environ. Sci. 5:7050-7059, 8); and Hatsukade et al. (Phys. Chem. Chem. Phys. 16:13,814-13,819, 9) referenced by Kovalenko and Neburchilov (J. Mol. 26:267-276, 3). In particular, in Figs. 2(d), 3(d), 4(d), and 5(d) (Kovalenko and Neburchilov, J. Mol. 26:267-276, 3), the orientation of carbon monoxide is opposite to Fig. 4 (Feaster et al., ACS Catal. 7:4822-4827, 5), Fig. 6(a) (Choi et al., Sci. Rep. 7:41,207-41,210, 6), Fig. 7 (Kuhl et al., Energy Environ. Sci. 5:7050-7059, 8), Fig. 7 (Hatsukade et al., Phys. Chem. Chem. Phys. 16:13,814-13,819, 9), and Fig. 2 (Gusarov, J. Mol. 27:344-354, 2). This obvious fact which also comes from chemical properties of components should not be ignored.


Optimization of a medium composition for the heterologous production of Alcaligenes faecalis penicillin G acylase in Bacillus megaterium.
Penicillin G acylase (PGA) is a strategic enzyme in the production processes of beta-lactam antibiotics. High demand for β-lactam semisynthetic antibiotics explain the genetic and biochemical engineering strategies devoted towards novel ways for PGA production and application. This work presents a fermentation process for the heterologous production of PGA from Alcaligenes faecalis in Bacillus megaterium with optimization. The thermal stability from A. faecalis PGA is considerably higher than other described PGA and the recombinant enzyme is secreted to the culture medium by B. megaterium, which facilitates the separation and purification steps. Media optimization using fractional factorial design experiments was used to identify factors related to PGA activity detection in supernatant and cell lysates. The optimized medium resulted in almost 6-fold increased activity in the supernatant samples when compared with the basal medium. Maximum enzyme activity in optimized medium composition achieves values between 135 and 140 IU/ml. The results suggest a promising model for recombinant production of PGA in B. megaterium with possible extracellular expression of the active enzyme.


Prevalence and risk factors for enterobiasis among preschool children in a metropolitan city in Korea.
The infection rate of Enterobius vermicularis was investigated in 1,191 preschool children in 25 daycare centers in Seoul, Korea by cellotape anal swab from July to August 1999. Both the directors of the daycare centers and the children's parents were asked to complete questionnaires that inquired about the potential risk factors involved. The overall egg positive rate for E. vermicularis was 9.5%, and the prevalence in the daycare centers ranged from 0 to 31.1%. Children aged 6-7 years showed a significantly higher egg positive rate than younger children, but the infection rate was similar for boys and girls. The socioeconomic status of the family and personal hygiene were not associated with enterobiasis, but anthelmintic medication significantly reduced the infection rate. The daycare centers in residential areas showed significantly lower egg positive rates than those situated near traditional markets. The environment of daycare centers is an important factor in enterobiasis, and the mass screening and treatment of children at high risk is recommended.


Overcoming the learning curve of laparoscopic Roux-en-Y gastric bypass: a 12-year experience.
Surgical treatment of morbid obesity with laparoscopic Roux-en-Y gastric bypass (LRYGB) is technically challenging and involves high-risk patients. In this study, the short-term outcome of LRYGB in a large population of patients has been evaluated, and morbimortality before and after overcoming the learning curve has been assessed. The objective of this study was to establish the learning curve for laparoscopic Roux-en-Y gastric bypass. This retrospective study involved 2281 patients submitted to LRYGB at São José do Avaí Hospital between August 1999 and December 2011. The parameters analyzed were operating time, rates of short-term postoperative complications, mortality, and conversion. The study population was predominantly female (71.3%) and presented a mean age of 37.5 years and mean body mass index (BMI) of 45.15 kg/m(2). The average time in surgery was 119 minutes, and average hospital stay was 4.3 days. The incidence of postoperative complications (hemorrhage, fistula, and bowel obstruction) was 1.75%. The relative risk of complications diminished in line with the increased experience of the surgical team and tended to stabilize at<2.5% after the first 500 procedures. The mortality rate was .43%, and the main causes of death were pulmonary embolism and leaks (.14% each). The conversion rate was .17%. Operating time and risks of adverse outcome were significantly reduced after a long learning curve of 500 consecutive procedures. The number of surgeries performed and the standardization of the laparoscopic technique used were the main factors contributing to the low rates of postoperative complications, mortality, and conversion.


Survey shows who is sharing which services.
An AHA survey shows overall growth in shared services from 1975 to 1978 and participation according to type of hospital, bed-size category, type of service, and other specifics.


Predictability of lower incisor tip using clear aligner therapy.
Uprighting incisors is particularly important with clear aligner therapy as incisor tip determines the mesio-distal space needed in the arch, and consequently the fit of the aligner. The objective of this study was to investigate the accuracy of ClinCheck® software to predict lower incisor tip by comparing digitally prescribed movements with actual clinical outcomes and to determine whether the presence of a vertically orientated rectangular composite attachment influences the efficacy of incisor tip. This retrospective study included 66 lower incisors from 42 non-extraction adult patients treated using the Invisalign® appliance. Twenty-one incisors had vertical attachments, while 45 incisors did not have any attachments. Lower incisor tip was measured at T0 (pre-treatment), T1 (predicted post-treatment) and T2 (achieved post-treatment) on digital models using metrology software. The change in position from T0 to T1 and T0 to T2 was measured from the estimated centre of resistance (CRes) of each tooth. The estimated centre of rotation was plotted relative to the CRes to describe the type of orthodontic tooth movement (OTM) predicted and achieved. Predicted incisor tip and achieved incisor tip were positively correlated (R2 = 0.55; p < 0.001). For every degree of tip planned 0.4 degrees of tip was achieved. The presence of an attachment resulted in 1.2 degrees greater tip (F = 3.7; p = 0.062) and 0.5 mm greater movement of the predicted apex of the tooth (F = 4.3; p = 0.042) compared with the no attachment group. The type of OTM achieved differed from the type predicted. Sixty-seven percent of incisors investigated were predicted to move by root movement, while 46% achieved this type of movement. The amount of lower incisor tip achieved was on average substantially less than the ClinCheck® displayed. Vertically orientated rectangular attachments are recommended where large root movement is planned, and their presence slightly improves apex movement.


Comparative Pharmacokinetics of Commercially Available Cannabidiol Isolate, Broad-Spectrum, and Full-Spectrum Products.
A wide variety of products containing cannabidiol (CBD) are available on the commercial market. One of the most common products, CBD oil, is administered to self-treat a variety of conditions. These oils are available as CBD isolate, broad-spectrum [all terpenes and minor cannabinoids except Δ-9-tetrahydrocannabinol (THC)], or full-spectrum (all terpenes and minor cannabinoids with THC < 0.3% dried weight) products. A systematic pharmacokinetic study was performed to determine whether there are differences in the pharmacokinetic parameters and systemic exposure of CBD after oral dosing as an isolate, broad-spectrum, or full-spectrum product. Male and female Sprague Dawley rats were treated with a single, equivalent oral dose of CBD delivered as isolate, broad-spectrum, or full-spectrum product. An additional study using an in-house preparation of CBD isolate plus 0.2% THC was performed. A permeability assay was also conducted to investigate whether the presence of THC alters the intestinal permeability of CBD. There was an increase in the oral bioavailability of CBD (12% and 21% in male and female rats, respectively) when administered as a full-spectrum product compared with the isolate and broad-spectrum products. There was no difference in the bioavailability of CBD between the commercially available full-spectrum formulation (3.1% CBD; containing 0.2% THC plus terpenes and other minor cannabinoids) versus the in-house preparation of CBD full-spectrum (CBD isolate 3.2% plus 0.2% THC isolate). In vitro permeability assays demonstrated that the presence of THC increases permeability of CBD while also decreasing efflux through the gut wall. The presence of 0.2% THC increased the oral bioavailability of CBD in male and female rats, indicating that full-spectrum products may produce increased effectiveness of CBD due to a greater exposure available systemically.


Women with fibromyalgia syndrome in New Zealand: the symptom experience.
Diagnosis and treatment of fibromyalgia syndrome (FMS) currently focuses on the experience of widespread pain. However, the symptom experience described by patients with FMS in clinical practice is far more diverse. This study aims identify the most common and severe symptoms in female patients diagnosed with FMS. This study interviewed 56 patients diagnosed with fibromyalgia syndrome about their symptoms using the Clinical Interview Schedule--Revised. The most frequent and disabling symptoms reported by participants were fatigue, sleep disturbance and cognitive difficulties. These findings highlight the need for a range of symptoms to be considered in the assessment and treatment of FMS to help improve patient outcomes.


Purification of isoacceptor transfer RNA by affinity coupling to aldehyde-containing matrix.
A method has been developed for the affinity coupling of aminoacyl-tRNA to an aldehyde-containing polymer by means of reduction with sodium cyanoborohydride. Sephadex dialdehyde obtained from periodate oxidation of Sephadex G-50, and Enzacryl polyaldehyde obtained from hydrolysis of Enzacryl polyacetal, were found to provide the requisite polymeric matrix. This coupling reaction permitted the rapid purification of isoacceptor tRNAs of Escherichia coli for the alpha-amino acids glycine, valine, and arginine, as well as the alpha-imino acid proline.


The effect of cyclical intravenous pamidronate in children and adolescents with osteogenesis imperfecta type V.
Intravenous treatment with pamidronate is beneficial in children and adolescents with moderate to severe forms of osteogenesis imperfecta (OI) types I, III and IV, but there is little information on the effects of this treatment on the newly described OI type V. Here, we describe the results of 2 years of pamidronate treatment in 11 children and adolescents with OI type V (age at start of therapy 1.8 to 15.0 years; 6 girls). Pamidronate was given in intravenous cycles at a cumulative yearly dose of 9 mg/kg. The first infusion cycle was associated with fever and mild hypocalcemia in most patients, but no other short-term side effects were noted. Two years of pamidronate treatment led to a decrease in the urinary excretion of N-terminal telopeptide of type I collagen to 50% of baseline levels. Both the size and volumetric bone mineral density of lumbar vertebrae increased compared to age- and sex-matched reference data (P < 0.05 in both cases). Histomorphometry of transiliac bone samples showed an average increase of 86% in cortical thickness (N = 7; P = 0.005). No significant changes with treatment were observed in the age-related z scores of isometric maximal grip force and height. Fracture incidence decreased from 1.5 fractures per year before treatment to 0.5 fractures per year during the fist 2 years of treatment. Ambulation status improved in four patients and remained unchanged in the others. In conclusion, the intravenous pamidronate therapy has a similar effect in OI type V as it has in the other OI types.


Paroxysmal events during prolonged video-video electroencephalography monitoring in refractory epilepsy.
Given that epileptic seizures and non-epileptic paroxysmal events have similar clinical manifestations, using specific diagnostic methods is crucial, especially in patients with drug-resistant epilepsy. Prolonged video electroencephalography monitoring during epileptic seizures reveals epileptiform discharges and has become an essential procedure for epilepsy diagnosis. The main purpose of this study is to characterise paroxysmal events and compare patterns in patients with refractory epilepsy. We conducted a retrospective analysis of medical records from 91 patients diagnosed with refractory epilepsy who underwent prolonged video electroencephalography monitoring during hospitalisation. During prolonged video electroencephalography monitoring, 76.9% of the patients (n=70) had paroxysmal events. The mean number of events was 3.4±2.7; the duration of these events was highly variable. Most patients (80%) experienced seizures during wakefulness. The most common events were focal seizures with altered levels of consciousness, progressive bilateral generalized seizures and psychogenic non-epileptic seizures. Regarding all paroxysmal events, no differences were observed in the number or type of events by sex, in duration by sex or age at onset, or in the number of events by type of event. Psychogenic nonepileptic seizures were predominantly registered during wakefulness, lasted longer, started at older ages, and were more frequent in women. Paroxysmal events recorded during prolonged video electroencephalography monitoring in patients with refractory epilepsy show similar patterns and characteristics to those reported in other latitudes.


Higenamine regulates Nrf2-HO-1-Hmgb1 axis and attenuates intestinal ischemia-reperfusion injury in mice.
Intestinal ischemia and reperfusion (IR) syndrome is a life-threatening dilemma caused by diverse events. Higenamine (HG), an active ingredient of Aconiti Lateralis Radix Praeparata, has been traditionally used as a heart stimulant and anti-inflammatory agent in oriental countries. But the function of HG on intestine IR injury has never been investigated. Mice underwent a 2 cm midline laparotomy, and the superior mesenteric artery (SMA) was obstructed by micro-vascular clamp to induce intestinal ischemia. In our current study, HG increases mouse intestinal epithelial (IEC-6) cell viability through induced heme oxygenase-1 (HO-1) production in vitro. In our in vivo murine intestinal IR injury model, the increased HO-1 protein level and activity, decreased intestinal injury score, Myeloperoxidase (MPO) activity, and inflammatory cytokine expression induced by HG were all abolished with additional treatment of HO-1 inhibitor zinc protoporphyrin IX (ZnPPIX). Furthermore, HG reduced high mobility group box-1 (Hmgb1) expression in IR injury-performed intestine which was inhibited by additional administration of ZnPPIX. And HG treatment significantly decreased HO-1 expression in nuclear factor erythroid 2-related factor (Nrf-2) SiRNA-transfected cells but not in control SiRNA-transfected cells. Our study provides evidence HG regulates Nrf2-HO-1-Hmgb1 axis and attenuates intestinal IR injury in mice.


Suicidal ideation among the long-term unemployed: a 5-year follow-up.
Suicidal ideation was monitored in a 5-year follow-up of a representative sample of long-term unemployed Norwegians. Four items from the General Health Questionnaire-28 were used as a Suicidal Ideation Index, which showed a prevalence of 17% in the present sample of unemployed subjects, higher than the value of 11% in a sample of Australian students used to construct the Index. Five years later, suicidal ideation was found in 6% of those who had been re-employed and 22% of those still unemployed, indicating that the high prevalence of suicidal ideation may be due to unemployment. Routine clinical examination was also tried for preventive purposes. In total, 8% of the unemployed subjects showed clinically significant suicidal ideation. They were referred to a psychologist or their GP, and were given the standard advice about suicide prevention. A Resource Centre, which many employees at the Labour Office have missed, has now been set up in the area under the National Plan for Suicide Prevention.


Activator proteins which regulate immunoglobulin heavy chain gene transcription in B lymphocytes.
While our results do not completely explain the B-cell specificity or other regulated aspects of IgH transcription, they show that IgH transcriptional factors belong to several different DNA-binding families which are capable of dimerization. It may be that formation of heteromultimers provides an additional level of regulation which might confer functional tissue specificity. Our results also suggest that enhancers and promoters may interact through protein-protein interactions, looping out the intervening DNA. Finally, we have shown that the same protein may regulate several genes including IgH and c-myc, indicating that transcriptional regulatory mechanisms for different genes are both complex and interconnected.


Current practice of screening mammography in the United States: data from the National Survey of Mammography Facilities.
To describe the extent to which screening mammography (SCM) has been organized according to the public health concept of low-cost, high-quality, and population-based screening, selected indicators of U.S. mammography facilities were evaluated. Data from the National Cancer Institute's phase I of the National Survey of Mammography Facilities were analyzed. This data base consists of questionnaire information obtained in 1992 from a 10% random sample of U.S. mammography facilities. Of 1,057 facilities, 634 (60%) distinguished SCM from diagnostic mammography (DXM). In facilities providing SCM (n = 535), 477 (89%) used the mediolateral oblique (MLO) view and/or the craniocaudal (CC) view. While 898 (85%) of all facilities requested clinical follow-up of abnormal mammograms, only 285 (27%) facilities actually received this information. Only 137 (13%) facilities operated at high volume (> or = 15 mammograms per day per machine), and 211 (20%) used batch interpretation. Average cost of a screening mammogram was $89 (range, $10-$225). While more facilities are distinguishing SCM from DXM and obtain MLO and CC views, SCM does not appear to be organized for high volume and low cost.


Pseudogenes in Cancer: State of the Art.
Pseudogenes are duplicates of protein-coding genes that have accumulated multiple detrimental alterations, rendering them unable to produce the protein they encode. Initially disregarded as "junk DNA" due to their perceived lack of functionality, research on their biological roles has been hindered by this assumption. Nevertheless, recent focus has shifted towards these molecules due to their abnormal expression in cancer phenotypes. In this review, our objective is to provide a thorough overview of the current understanding of pseudogene formation, the mechanisms governing their expression, and the roles they may play in promoting tumorigenesis.


Minimally invasive heart valve surgery: how and why in 2012.
Cardiac surgical procedures via traditional sternotomy are safe and effective operations performed by cardiothoracic surgeons worldwide. However, postoperative limitations in upper extremity activity during bone healing are seen as undesirable by some. Percutaneous catheter-based attempts to emulate the outcomes of traditional cardiac surgical procedures have largely fallen short of established standards of efficacy and durability. The field of minimally invasive heart valve surgery thus developed out of a need to offer smaller, better-tolerated incisions to patients while maintaining high-quality clinical outcomes. These operations are safe and effective when performed by proficient surgical teams, allowing patients to resume normal activities more rapidly. We explore current evidence supporting the practice of minimally invasive heart valve surgery in 2012 and analyze the clinical impact of these nascent surgical platforms.


The arterial anatomy of the human carpus. Part II: The intraosseous vascularity.
The intraosseous vascular anatomy of the carpal bones of 25 fresh cadaver limbs was studied by injection and Spalteholz clearing techniques. The carpal bones were classified into three general groups based on the size and location of nutrient vessels, the presence or absence of intraosseous anastomoses, and the dependence of large areas of bone on a single intraosseous vessel. Group I included the scaphoid, capitate, and 20% of the lunates in this series. Each had large areas of bone dependent on a single intraosseous vessel and was considered at greater risk to develop avascular necrosis following fracture. Group II included the trapezoid and hamate, both of which have two areas of vessel entry but lack intraosseous anastomoses. Group III included the trapezium, triquetrum, pisiform, and 80% of the lunates in this series, which receive nutrient arteries through two nonarticular surfaces, have consistent intraosseous anastomoses, and have no large areas of bone dependent upon a single vessel. The clinical incidence of avascular necrosis in groups II and III is low.


Efficient communication: assessment-oriented oral case presentation.
To introduce and assess the time savings from and effectiveness of assessment-oriented (AO) oral case presentation as a model of interphysician communication. This was a prospective, interventional study of all 10 on-site faculty and 36 residents in a postgraduate year 1 to 3 format emergency medicine residency training program. Residents were requested to perform all oral case presentations in either the traditional or AO formats. Presentations were timed, and residents and faculty rated essential measures of oral case presentation effectiveness: data content, expression of decision making, organization, and overall satisfaction. A total of 199 oral case presentations were sampled-112 traditional and 87 AO. Mean length of presentation for traditional presentations was 117 seconds versus 71 seconds for AO presentations (p < 0.001), a clinically significant difference, without significant differences in the essential measures of case presentation effectiveness. AO oral case presentation may provide a means for emergency medicine residents to "get to the point" and to communicate effectively and efficiently.


A monoclonal antibody to the T-cell receptor increases IGF-I receptor content in normal T-lymphocytes: comparison with phytohemagglutinin.
The biological effects of the IGFs are mediated through interaction with specific cell surface receptors. It has been previously reported that mitogenic activation of T-lymphocytes by phytohemagglutinin (PHA) is associated with increased IGF-I receptor content. However, the mechanisms which regulate IGF-I receptor expression during T-lymphocyte activation are unknown. To explore further the regulation of IGF-I receptor expression in T-cells, we investigated IGF-I receptor content and mRNA abundance in T-lymphocytes after stimulation either by PHA or OKT-3, the latter being a monoclonal antibody directed against the CD-3 antigen of the T-cell receptor. IGF-I binding in T-cells demonstrated increased IGF-I receptor content after stimulation by both PHA and OKT-3. Peak binding was induced after 72 h of treatment with PHA and 48 h of treatment with OKT-3. Affinity cross-linking of 125I-IGF-I to T-cell membranes demonstrated a single approximately 130 kDa band which was increased after treatment with PHA or OKT-3. This band was inhibited by the addition of alpha-IR3, a monoclonal antibody to the IGF-I receptor. Both PHA and OKT-3 increased IGF-I receptor mRNA abundance with peak increases at 20 h and 60 h, respectively. Parallel increases in IGF-I receptor and beta-actin mRNA abundance were observed, consistent with previous studies demonstrating increased actin gene expression after T-cell activation. Thus, the increase in IGF-I receptor mRNA abundance markedly preceded the increase in IGF-I receptor content after PHA stimulation, but the increase in IGF-I receptor mRNA abundance followed the increase in IGF-I receptor content after OKT-3.(ABSTRACT TRUNCATED AT 250 WORDS)


Presence of gene expression of vitamin D receptor and 24-hydroxylase in OK cells.
We investigated the gene expression of 1,25-dihydroxy-vitamin D3 (1,25(OH)2D3) receptors (VDR) and 25-hydroxy-vitamin D3-24-hydroxylase (24-hydroxylase) in opossum kidney (OK) cells. Reverse transcription-polymerase chain reaction demonstrated the presence of VDR gene expression in OK cells. Northern hybridization, using rat VDR cDNA, also demonstrated a 4.4 kbp VDR mRNA expression which was affected by serum but not by 1,25(OH)2D3 and/or parathyroid hormone stimulation. Stimulation with 1,25(OH)2D3 induced 24-hydroxylase mRNA expression which peaked at 6 h. This study clearly demonstrates for the first time the presence of VDR and 24-hydroxylase gene expression in OK cells, suggesting that OK cells are a useful model for investigating the genetic action mechanisms of 1,25(OH)2D3.


Transcutaneous electric nerve stimulation (TENS) in the therapy of chronic facial pain. Preliminary report.
Chronic facial pain remains a therapeutic problem. We report on 29 patients (37 nerves involved), who were treated with transcutaneous electric nerve stimulation (TENS). Pain reduction was achieved in 27 patients (93%) while in 5 patients it was possible to stop the treatment because they were constantly free from pain. Two patients did not respond to TENS therapy. It was possible to reduce or discontinue the use of analgesics in 79% of the cases. There were no severe side effects. Therefore, TENS should be seen as a simple, safe and effective method of treatment for many forms of chronic facial pain, as opposed to other invasive surgical procedures.


Direct Photolithographic Patterning of Colloidal Quantum Dots Enabled by UV-Crosslinkable and Hole-Transporting Polymer Ligands.
Quantum dot (QD)-based displays call for nondestructive, high-throughput, and high-resolution patterning techniques with micrometer precision. In particular, self-emissive QD-based displays demand fine patterns of conductive QD films with uniform thickness at the nanometer scale. To meet these requirements, we functionalized QDs with photopatternable and semiconducting poly(vinyltriphenylamine-random-azidostyrene) (PTPA-N3-SH) ligands in which hole-transporting triphenylamine and UV-crosslinkable azide (-N3) groups are integrated. The hybridized QD films undergo chemical crosslinking upon UV irradiation without loss in the luminescence efficiency, enabling micrometer-scale QD patterns (pitch size down to ∼10 μm) via direct photolithography. In addition, the conjugated moieties in the ligands allow the crosslinked QD films to be used in electrically driven light-emitting diodes (LED). As the ultimate achievement, a patterned QD-LED was prepared with a maximum luminance of 11 720 cd m-2 and a maximum external quantum efficiency (EQE) of 6.25%. The present study offers a simple platform to fabricate conductive nanoparticle films with micrometer-scale patterns, and thus we anticipate that this system will expedite the realization of QD-based displays and will also be applicable to the manufacture of nanoparticles for other electronic devices.


A phase II study of ifosfamide in paediatric solid tumours.
A total of 20 children with recurrent or unresponsive tumours (10 Wilms' tumours, 3 rhabdomyosarcomas, 4 Ewing's sarcomas, 1 osteosarcoma, 1 hepatoblastoma, 1 hepatoma) were given ifosfamide as a 24-h infusion (5 g/m2), with mesna as a uroprotector. The number of courses ranged from 1 to 13 (median, 3), and the interval between them was 2-3 weeks. In all, 16 of these patients had previously received cyclophosphamide. Complete clinical responses (CRs) were seen in 3 cases (2 Wilms' tumours and 1 Ewing's sarcoma) and lasted 5, 7, and 9 months. Partial responses (PRs) were seen in 3 instances; mixed response or stable disease, in 4; and progressive disease, in 10. Treatment was well tolerated in most patients, with no cystitis or severe myelosuppression, but two children developed transient neurological symptoms and one became hypertensive. Nausea and vomiting were controlled by high-dose dexamethasone in most children.


Further evidence that phosphoprotein C23 (110 kD/pI 5.1) is the nucleolar silver staining protein.
Previously we demonstrated a similar distribution between nucleolar organizing region-(NOR)-specific silver staining and localization of nucleolar phosphoprotein C23 (MW 110 kD/pI 5.1) [1, 2]. We now report that under fixation conditions which allow for antibody binding and subsequent silver staining, monoclonal antibody against protein C23 blocks NOR silver staining as well as silver staining in interphase nucleoli. Monoclonal antibody against nucleolar phosphoprotein B23 (MW 37 kD/pI 5.1) did not block silver staining in either NORs or interphase nucleoli. These, along with earlier observations, provide evidence that nucleolar phosphoprotein C23 is the major silver staining protein of the nucleolus and that it is directly or indirectly associated with rDNA.


Characterization of lesions in the temporal muscle and the male reproductive system (epididymis and testicle) of dogs experimentally infected with Leishmania infantum with different clinical stages.
Leishmaniosis is a zoonotic disease with a very complex pathogenesis modulated by the interaction between the parasite, the vector and the host. Although the pathological characteristics have been extensively studied in the typically affected organs, some locations such as muscles and reproductive organs have been less studied. The objective of this study was to evaluate the presence of lesions in the temporal muscle and the male reproductive organs (testicle and epididymis) and correlate their characteristics with the presence of the parasite and with the clinical status of the dogs. The temporal muscle was studied in 25 infected beagle dogs (nine females and 16 males) and five uninfected control dogs (two females and three males) and the testicle and epididymis in the 19 males. Dogs were euthanized one year after infection and clinical signs, anti-Leishmania serum antibodies, and lymph node parasite load were assessed. Muscular and reproductive lesions were characterized by H&E and immunohistochemistry (IHC). The presence of the parasite in the lesions was evaluated using IHC and molecular techniques. Myositis was observed in 72% (18/25) of the dogs and was characterized by lymphoplasmacytic or histiocytic lesions. Mild and severe lesions were detected, the latter being statistically associated with the presence of the parasite and with the clinical status of the dogs. Orchitis was observed in 50% (8/16) of the dogs and was mainly mild and lymphoplasmacytic. No statistical relationship was found between testicular lesions and the presence of the parasite or the clinical status. Epididymitis was observed in 87.5% (14/16) of the dogs, and the lesions were often infiltrated by numerous histiocytes and neutrophils. Epididymal lesions were statistically associated with the clinical status of the dogs and with the presence of the parasite in the lesions. IgG and IgM immunoglobulins were found in all lesions, suggesting a local immune response with reactivation of the infection. Leishmania was more frequently detected in severe and histiocytic lesions, although some lesions had no detectable parasites. These results have shown that lesions in the temporal muscle, epididymis, and testicles are common in dogs infected by Leishmania infantum and that dogs may show a different response to infection. This response is characterized by varying degrees of cellular and immune responses associated with a variable presence of the parasite.


Estimation of the size of the COVID-19 pandemic using the epidemiological wavelength model: results from OECD countries.
This study aimed to simplify the previously developed epidemiological wavelength model and to expand the scope of the model with additional variables to estimate the magnitude of the COVID-19 pandemic. The applicability of the extended wavelength model was tested in Organisation for Economic Cooperation and Development (OECD) member countries. The epidemiological wavelengths of OECD member countries for the years 2020, 2021 and 2022 were estimated comparatively, considering the cumulative number of COVID-19 cases. The size of the COVID-19 pandemic was estimated using the wavelength model. The scope of the wavelength model was expanded to include additional variables. The extended estimation model was improved by adding population density and human development index variables, in addition to the number of COVID-19 cases and number of days since the first case reported from the previous estimation model. According to the findings obtained from the wavelength model, the country with the highest epidemiological wavelength for the years 2020, 2021 and 2022 was the United States (We = 29.96, We = 28.63 and We = 28.86, respectively), and the country with the lowest wavelength was Australia (We = 10.50, We = 13.14 and We = 18.44, respectively). The average wavelength score of OECD member countries was highest in 2022 (We = 24.32) and lowest in 2020 (We = 22.84). The differences in the periodic wavelengths of OECD countries were analysed with the dependent t-test for paired samples in two periods, 2020-2021 and 2021-2022. There was a statistically significant difference between wavelengths in the 2020-2021 and 2021-2022 groups (t(36) = -3.670; P < 0.001). Decision-makers can use the extended wavelength model to easily follow the progress of the epidemic and to make quicker and more reliable decisions.


Using a Machine Learning Architecture to Create an AI-Powered Chatbot for Anatomy Education.
Artificial Intelligence chatbots allow interactive dialogue-driven teaching of medical sciences. Open-source tools allow educators to adapt existing technology to create intelligent learning systems. We utilised an open-source machine learning architecture and fine-tuned it with a customised database to train an AI dialogue system to teach medical students anatomy.


Increased metal tolerance and bioaccumulation of zinc and cadmium in Chlamydomonas reinhardtii expressing a AtHMA4 C-terminal domain protein.
The use of microalgal biomass for metal pollutant bioremediation might be improved by genetic engineering to modify the selectivity or capacity of metal biosorption. A plant cadmium (Cd) and zinc (Zn) transporter (AtHMA4) was used as a transgene to increase the ability of Chlamydomonas reinhardtii to tolerate 0.2 mM Cd and 0.3 mM Zn exposure. The transgenic cells showed increased accumulation and internalization of both metals compared to wild-type. AtHMA4 was expressed either as the full-length (FL) protein or just the C-terminal (CT) tail, which is known to have metal-binding sites. Similar Cd and Zn tolerance and accumulation was observed with expression of either the FL protein or CT domain, suggesting that enhanced metal tolerance was mainly due to increased metal binding rather than metal transport. The effectiveness of the transgenic cells was further examined by immobilization in calcium alginate to generate microalgal beads that could be added to a metal contaminated solution. Immobilization maintained metal tolerance, while AtHMA4-expressing cells in alginate showed a concentration-dependent increase in metal biosorption that was significantly greater than alginate beads composed of wild-type cells. This demonstrates that expressing AtHMA4 FL or CT has great potential as a strategy for bioremediation using microalgal biomass.


An Uncommon Case of Type III Endoleak Treated with a Custom-made Thoracic Stent Graft.
Endovascular aortic repair (EVAR) has been shown to be a valid and minimally invasive alternative to open abdominal aortic aneurysm repair. A major shortcoming for EVAR is the need to submit patients to regular follow-up to detect potential complications such as endoleak, limb occlusion, aneurysm expansion, aneurysm rupture, infection, structural failure, and migration. In this case report, we describe an uncommon case of late type III endoleak due to complete detachment of the stent-graft main body segment from its suprarenal uncovered fixation stent. It was treated with a custom-made Relay(®) NBS Plus (Bolton Medical, Barcelona, Spain) thoracic stent graft which also provided extra suprarenal fixation of the thoracic stent graft in the proximal neck. The postoperative period was uneventful and a computed tomography scan 1 year later revealed proper positioning of the stent graft and no signs of endoleak. The successful strategy chosen to correct this complication was at the same time original and infrequent, and also avoided potential complications related to open surgical repair and general anesthesia.


Dual-reverse-signal ratiometric fluorescence method for malachite green detection based on multi-mechanism synergistic effect.
The proposition of ratiometric detection mode has demonstrated great superiority in improving analysis accuracy by forming self-calibration. Herein, the novel dual-reverse-signal ratiometric fluorescence detection for malachite green (MG) was first achieved based on synergistic effect of fluorescence resonance energy transfer (FRET) and inner filter effect (IFE). The ratiometric fluorescence probe (B-RCDs) was self-assembled via electrostatic attraction between blue-emission carbon dots (BCDs) and red-emission carbon dots (RCDs), followed with FRET effect from BCDs to RCDs and exhibited dual-emission at 450 nm and 627 nm. In the presence of MG, the IFE effect between MG and RCDs quenched the fluorescence at 627 nm and restored the fluorescence at 450 nm, sending out two reverse signals along with an obvious color change from pink to purple (302 nm UV lamp). This ratiometric method not only simplified the preparation process, but also improved the detection sensitivity, showing a low limit of detection (LOD) of 41.8 nM, which exhibited superiority than that of single-signal RCDs (157.3 nM). This method held a rapid response of 10 min and represented satisfactory recoveries (99.14%-109.08%) in real water samples, revealing it was a promising candidate in the fast, sensitive and practical detection of MG. Moreover, the design of synergistic effect supplied a new perspective for the development of ratiometric sensing in the future.


Trans-sialidase from Trypanosoma cruzi epimastigotes is expressed at the stationary phase and is different from the enzyme expressed in trypomastigotes.
We have studied the trans-sialidase from insect forms of Trypanosoma cruzi growing in axenic culture. Log phase epimastigotes expressed little or no trans-sialidase activity, and were unable to incorporate exogenous sialic acid. Transsalidase started to be expressed at the late logarithmic phase, with specific activity increasing steadily as the culture reached the stationary phase. Trans-sialidase was purified from the late log phase epimastigote culture, which contained less than 2% of metacyclic forms, yielding a glycoprotein that migrated as a single 90-kDa band in sodium dodecyl sulfate gels. This enzyme features: (1) no reaction with antibodies against the peptide repeats present in the carboxy-terminal of trypomastigote trans-sialidase; (2) positive reaction with antibodies raised against a fragment of trypomastigote trans-sialidase that contains the active site; (3) similar kinetic properties and identical acceptor-donor specificity when compared to the trypomastigote enzyme; and (4) neuraminidase activity in the absence of acceptors. Upon differentiation into metacyclic forms, a trans-sialidase activity containing the carboxy-terminal repeats of the trypomastigote enzyme was released into the medium. These results suggest that epimastigotes express a developmentally regulated trans-sialidase that contains the same catalytic site but lacks the tandem amino acid repeats typical of trypomastigote trans-sialidase.


The Thai version of Effort-Reward Imbalance Questionnaire (Thai ERIQ): a study of psychometric properties in garment workers.
This study aimed to test the psychometric properties of the Thai version of the Effort-Reward Imbalance Questionnaire (T-ERIQ). The English version of the 23-item ERIQ was translated and back-translated. Content validity was examined by five experts and face validity was examined by twelve key informants before being tested for construct validity with 828 workers from six garment factories. Predictive validity was assessed through the relationship between the ERI constructs and psychological health outcomes including psychosomatic symptoms, state of anxiety, depression, and job satisfaction. The internal consistency of the Thai ERIQ was tested using the first survey (n=828), and test-retest stability was examined 2 to 4 wk later with a subsample (n=408). The results show that 2% of workers reported effort-reward imbalance (ERI ratio>/=1). The Thai ERIQ has good content validity with a Content Validity Index of 0.95. Cronbach's alpha coefficients for the effort, reward, and overcommitment scales were 0.77, 0.81, and 0.66, respectively. The 2-4 wk stability of these three constructs was moderate (r=0.496-0.576, p<0.001). Overall, the factorial validity was demonstrated as the best model fit, with high values of the goodness-of-fit indices, using confirmatory factor analysis, indicating accordance with the theoretical constructs of the ERI model. Logistic regression analyses supported significant associations of reward with all psychological health outcomes (p<0.05). The findings suggest that the Thai ERIQ has adequate reliability and validity to investigate the psychosocial work environment. The Thai ERIQ can be applied to the Thai working population, particularly industrial manufacturing workers.