Phototherapy in systemic sclerosis: Review.
Systemic scleroderma-also known as systemic sclerosis (SSc)-is a chronic systemic connective tissue disease characterized by collagen deposition in cutaneous and internal organs, leading to skin sclerosis and multiple organ fibrosis. The pathogenesis is complex and remains poorly understood. Treatment is based on organ involvement and requires a multidisciplinary approach. Skin sclerosis can cause disability, leading to decreasing quality of life. Various systemic antifibrotic therapies have been used; however, most have unsatisfactory results. Recently, phototherapy and in particular ultraviolet A (UVA) has been used to treat skin sclerosis in SSc patients with satisfactory results. The main mechanisms include lymphocyte apoptosis, cytokine alteration, inhibition of collagen synthesis and increased collagenase production, and neovascularization, leading to the breakdown of collagen fibrils resulting in skin softening or even healing digital ulcers. Most studies reported that psoralen plus UVA (PUVA) and UVA1 phototherapy improved clinical outcomes vis-à-vis skin sclerosis, joint mobility, ulcers, and histopathology. PUVA and UVA1 phototherapy therefore have potential as an alternative or adjunctive therapy for patients with SSc.


Helical magnetorotational instability in a Taylor-Couette flow with strongly reduced Ekman pumping.
The magnetorotational instability (MRI) is thought to play a key role in the formation of stars and black holes by sustaining the turbulence in hydrodynamically stable Keplerian accretion disks. In previous experiments the MRI was observed in a liquid metal Taylor-Couette flow at moderate Reynolds numbers by applying a helical magnetic field. The observation of this helical MRI (HMRI) was interfered with a significant Ekman pumping driven by solid end caps that confined the instability only to a part of the Taylor-Couette cell. This paper describes the observation of the HMRI in an improved Taylor-Couette setup with the Ekman pumping significantly reduced by using split end caps. The HMRI, which now spreads over the whole height of the cell, appears much sharper and in better agreement with numerical predictions. By analyzing various parameter dependencies we conclude that the observed HMRI represents a self-sustained global instability rather than a noise-sustained convective one.


Comparative effects of untreated and 3-methacryloxypropyltrimethoxysilane treated ZnO nanoparticle reinforcement on properties of polylactide-based nanocomposite films.
Polylactide (PLA) nanocomposites characterized by antimicrobial properties are gaining increasing attention for food packaging. In this contribution, the PLA based nanocomposite films with multifunctional end-use properties were achieved by incorporating ZnO nanoparticles (NPs) [untreated: ZnO(UT) and 3-methacryloxypropyltrimethoxysilane treated: ZnO(ST)] into polymer matrix via solvent casting method. The ZnO(ST) prevented the degradation of PLA at higher temperature and improved the mechanical property. Color, transparency, and anti-UV properties of composite films were influenced by the incorporation of ZnO NPs. Contrary to untreated ZnO, the treated NPs were more effective in enhancing the tortuosity of the diffusive path for the oxygen molecules to diffuse through the film. The glass transition (Tg) and crystallization (Tc) temperatures of composites were improved by the addition of ZnO, whereas a higher Tg was recorded for ZnO(ST) loaded films. XRD demonstrated the change in crystallinity of the films with NPs addition. Nanoparticles well distributed in the composite films as observed through SEM however spots of agglomeration were observed for PLA/ZnO(UT) films. Developed films especially incorporated with ZnO(ST) were found to be active against both Gram-negative (Salmonella Typhimurium) and Gram-positive (Listeria monocytogenes) bacteria. Therefore, PLA/ZnO nanocomposite films could be considered as environment-friendly active packaging material for food preservation.


A case report of pudendal arteries angioplasty with sirolimus drug-coated balloon and drug-eluting stent associated with intracavernous autologous peripheral blood mononuclear cells injection for untreatable vasculogenic erectile dysfunction.
Erectile dysfunction (ED) is a prevalent health problem that seriously impacts men's quality of life. The potential treatment of ED by percutaneous approach has emerged with valid angiographic results and a significant improvement in symptoms and quality of life. In addition, cell-based regenerative therapies aiming at enhancing neovascularization have been successfully performed with peripheral blood mononuclear cells (PBMNCs) in diabetic patients affected by critical limb ischaemia. We report a case of a young insulin dependent (ID) diabetic patients who suffered of severe vasculogenic erectile dysfunction associated with a poor response for more than 1 year to oral phosphodiesterase-5 inhibitors (PDE5i) and intracavernous (IC) phosphodiesterase type 1 (PDE1) therapy. At selective angiography of the pelvic district, a severe atherosclerotic disease of the internal iliac and pudendal artery was evident with absence of distal vascularization of the cavernous bodies. The patient was treated by mechanical revascularization with drug-coated balloon and drug-eluting stent placement associated with IC injection of autologous PBMNCs. Immediate and 1-year clinical and angiographic follow-up are described. Percutaneous revascularization with drug-coated balloon and drug-eluting stent associated with IC autologous PBMNCs cells injection is a safe and effective procedure to restore normal erectile function in diabetic patients affected by severe vasculogenic ED not responding to conventional oral drug therapies.


Intestinal absorption of calcium and phosphorus by horses.
Recent knowledge regarding the absorption of calcium and phosphorus from the intestine of the horse has been reviewed. Consideration has been given to sites, mechanisms and factors affecting absorption as well as to the availability of calcium and phosphorus from feedstuffs commonly used in Eastern North America. Although the anatomy of the digestive tract might appear to impose restrictions on the ability of the horse to assimilate minerals, studies of absorption show that the horse utilizes the calcium and phosphorus of many feeds very efficiently.


Thymosin α1 treatment reduces hepatic inflammation and inhibits hepatocyte apoptosis in rats with acute liver failure.
The present study aimed to evaluate whether thymosin α1 (Tα1) increases survival rates through the improvement of immunofunction and inhibition of hepatocyte apoptosis in rats with acute liver failure (ALF). A total of 25 rats were randomly divided into the control group (CG), the model group (MG) and the treatment group (TG). The CG received an intraperitoneal injection of saline (2 ml). The ALF rat model was established by the intraperitoneal injection of D-galactosamine (700 mg/kg) and lipopolysaccharide (10 µg/kg). The TG received an intraperitoneal injection of Tα1 (0.03 mg/kg) 1 h prior to and 30 min after modeling. The survival rates of the rats were recorded. An additional 63 rats were randomly divided into a CG (n=3), MG (n=30) and TG (n=30). Three rats were sacrificed at 3, 6, 9 and 12 h after establishment of the rat model to detect plasma alanine transaminase (ALT), aspartate transaminase (AST), total bilirubin (TBIL), tumor necrosis factor (TNF)-α and interleukin-10 (IL-10). Liver samples were stained with hematoxylin and eosin and TUNEL, and reverse transcription-quantitative polymerase chain reaction and western blot analysis were performed to detect B-cell lymphoma 2 (Bcl-2) and Bcl-2-associated X protein (Bax) in liver tissue. The results indicated that the survival rate of the TG was significantly higher compared with that of the MG at 24 h (P<0.05). Plasma ALT, AST and TBIL in the MG and TG increased over time (3-12 h), with ALT, AST and TBIL observed to be significantly lower in the TG compared with the MG at each time-point (P<0.05). Hepatocellular necrosis, hemorrhage and inflammatory cell infiltration of ALF were aggravated over time (3-12 h) in the MG and TG. Notably, in the Tα1-treated rats, the hepatocytes appeared healthier with fewer apoptotic cells compared with those from the MG at the same time-points. Hepatocyte apoptotic index increased in the TG and MG, but was significantly lower in the TG compared with the MG at each time-point (P<0.05) in TUNEL assays. Plasma TNF-α and IL-10 in the MG and TG increased over time (3-12 h), with TNF-α observed to be significantly lower in the TG compared with the MG at each time-point (P<0.05), however, IL-10 was observed to be significantly higher in the TG compared with the MG at each time-point (P<0.05). Bax mRNA expression was significantly lower in the TG compared with the MG at each time-point (P<0.05), whereas Bcl-2 was significantly higher (P<0.05). In conclusion, Tα1 improved survival rates in an ALF rat model by downregulating TNF-α and upregulating IL-10, leading to the attenuation of hepatic inflammation and hepatocyte apoptosis.


Comparison of the clinical results of STA-MCA anastomosis and the medical treatment in the cerebral low perfusion patients with viable brain tissue.
The long-term clinical results of STA-MCA anastomosis as well as the medical treatments were compared in cases that were confined as having a focal cerebral perfusion deficit with viable brain tissue, based on either the drug induced EEG and evoked potential test (DEE test) and/or by positron emission tomography (PET). The criteria for viable cerebral tissue was determined by the following four conditions: (1) functional reversibility could be confirmed by the DEE test; (2) a haemodynamic process could be found in the DEE test; (3) a haemodynamic compromise could be confirmed in the PET study; (4) misery perfusion could be confirmed in the PET study. From 1975 to 1989, 55 cases were confirmed as having viable brain tissue according to the DEE test and the PET study. Of the 55 cases, bypass surgery was performed on 35. Conservative treatment was given to the other 20 cases. There were 3 cases of perioperative neurological deterioration. One was permanent and the other 2 were transient. Results of the long-term follow up are as follows, Ipsilateral attack: 1 case (2.0%) received surgery, and 7 cases (35%) received conservative treatment. Re-attack in the contralateral or posterior circulation: 6 cases (17.2%) received surgery, and 1 case (5%) received conservative treatment. Seventy-seven per cent of the surgical cases improved or had no change in the final functional status, while only 55% of the conservative group either improved or showed no change. The incidence of ipsilateral cerebral ischaemia was significantly low in the surgical group. Contralateral and/or posterior circulation ischaemia tended to be high in this group, however.(ABSTRACT TRUNCATED AT 250 WORDS)


[Comparative normative on sanitary practices of cadaveric preservation in Spain].
In this paper the current regulations on cadaveric preservation practices required for the transfer of corpses in the different Autonomous Communities -Reglamentos de Policía Sanitaria Mortuoria- and national legislation are compared. The criteria taken into account have been: a) which sanitary practices are included in the regulations, b) which ones can be carried out in corpses posing a health risk, c) when they are compulsory to be carried out, d) when they can be carried out after death, and e) what professionals can carry them out and/or take responsibility for them. At the time of finishing the paper, a new mortuary regulation is being passed in Andalusia, as well as a decree from the Ministry of Health on technical and sanitary requirements concerning international transfer of corpses and human remains.


Why have drug treatments been so disappointing?
The title of this contribution involves two consecutive questions: have the effects of medication in autism indeed been disappointing? And if so, why? The answer to the first question depends on whether one focuses on the core social and communicative deficits of autism, or on various complicating behaviour problems. Attempts over the past decades to develop drugs that specifically improve social and communicative functioning have failed. Among the most ambitious attempts were medical interventions in the endogenous opioid system that were motivated from animal models on the involvement of this system in various aspects of social behaviour. By contrast, medications such as the newer antipsychotics, psychostimulants, presynaptic noradrenergic blocking agents (clonidine and guanfacine) and selective serotonin reuptake inhibitors were shown to reduce impairing complicating symptoms of affective instability, irritability, hyperactivity and inattentiveness, aggression, self-injury and stereotypies. The explanation for the medication-refractory status of social and communicative deficits should be sought in at least two related factors: (1) the as yet unidentified neurochemical basis of autism, and (2) the obvious lack of involvement of the main neurotransmitter systems (dopamine, noradrenaline and serotonin) in the pathophysiology of social and communicative behaviour.


Mandibular form in a rabbit model of familial nonsyndromic coronal suture synostosis.
Nonsyndromic coronal suture synostosis produces predictable and well-documented morphologies of the cranial vault with anteroposterior growth restrictions and mediolateral compensatory growth. The potential effects of nonsyndromic coronal suture synostosis on mandibular form are not as clear, however. This study was designed to evaluate whether coronal suture synostosis is associated with alterations in mandibular form by using a familial rabbit model of coronal suture synostosis. To assess this potential relation, the following hypothesis was tested: mandibular form in rabbits with coronal suture synostosis is significantly (P < 0.05) different from that seen in normal rabbits. The cleaned and dried mandibles of 33 adult New Zealand white rabbits were used (12 from normal rabbits, 13 from rabbits with delayed-onset synostosis, and 8 from rabbits with complete coronal suture synostosis). Seven anatomical landmarks on the mandible were located and digitized in three dimensions: anterior molar on the alveolus, posterior molar on the alveolus, coronoid process, anterior pole of the condyle, condylar process, angular process, and mandibular angle. To describe the mandibular condyle, the distance from the anterior pole to the posterior pole of the condyle was measured with digital sliding calipers, as was the distance between the medial and lateral poles. A shape ratio was then created using the dividend of these sums. Statistical analyses of mean form differences between mandibles were executed using Euclidean distance matrix analysis. Statistical analyses of the mandibular condyle linear and shape measurements were analyzed using one-way ANOVA in the three groups. Results showed that complete coronal suture synostosis is associated with significant (P < 0.05) differences in mandibular form compared with that of normal rabbits but that mandibular form in rabbits with delayed-onset synostosis does not differ from that of normal rabbits (P > 0.05). In particular, distances involving the coronoid process in rabbits with coronal suture synostosis were significantly different, paralleling previous work in human patients with coronal synostosis. There are no intrinsic condylar linear or shape differences between any of these groups, however. The form difference noted is most likely secondary to the synostosed coronal suture and may reflect alterations in the cranial base or masticatory musculature in this rabbit model.


[The contemporary view of the cardiac conduction system].
Cardiac conduction system was described in its complete form in homeotherm vertebrates 110 years ago. Despite this fact, many new findings concerning its specification and development that have an impact on its pacemaking and conducting function appeared in the past decade. Conduction system disorders are associated with arrhythmias, and some of which have a developmental origin. Evolutionary view on this area is particularly useful for better understanding of the atrioventricular canal remodelling.


Disruption of the NAD(P)H:quinone oxidoreductase 1 (NQO1) gene in mice causes myelogenous hyperplasia.
NAD(P)H:quinone oxidoreductase1 (NQO1) is a cytosolic protein that reduces and detoxifies quinones and their derivatives, thus protecting cells against redox cycling and oxidative stress. Disruption of the NQO1 gene in mice caused myeloid hyperplasia of bone marrow and highly significant increases in blood neutrophils, eosinophils, and basophils. NQO1-null mice also showed a decrease in lymphocytes and WBCs as compared with wild-type mice. Various techniques also demonstrated an increase in megakaryocytes without an increase in blood platelets. Histological analysis of liver, kidney, spleen, and thymus did not demonstrate a difference between wild-type and NQO1-null mice or a sign of infection. Blood cultures and urine analysis also did not demonstrate any sign of infection in NQO1-null and wild-type mice. Additional analysis of the bone marrow from NQO1-null mice revealed that loss of NQO1 alters the intracellular redox status because of accumulation of NAD(P)H, cofactors for NQO1. This causes a reduction in the levels of pyridine nucleotides and tumor suppressor proteins p53 and p73, and a decrease in apoptosis. The decrease in apoptosis causes myelogenous hyperplasia in NQO1-null mice. These results demonstrate that NQO1 acts as an endogenous factor in the protection against myelogenous hyperplasia. This is significant because 2-4% of human individuals without known abnormalities, and >25% of individuals with benzene poisoning and acute myelogenic leukemia are homozygous for a mutant allele (P187S) of NQO1 and lack NQO1 protein/activity.


Urban air pollution increases plasma fibrinogen and plasminogen activator inhibitor-1 levels in susceptible patients.
The cardiovascular effects on fibrinolytic activity by urban air pollution are still unknown. Paired fasting blood samples during high and low air pollution days in Taipei were taken from a panel of 49 patients with coronary heart disease or multiple risk factors to study their fibrinolytic and inflammatory response to urban air pollution. Paired t-tests and mixed-effects models were used to determine the air pollution effects. Patients' plasma plasminogen activator inhibitor-1 levels were significantly increased when hourly concentrations of particulate matter with diameters less than 10 microm (PM10) were greater than 100 microg/m during the period 0800 to 1800 h. Urban air pollution has an adverse effect on plasma fibrinolytic function in a susceptible population.


Enhancement of the solubility and efficacy of poorly water-soluble drugs by hydrophobically-modified polysaccharide derivatives.
This work was intended to develop and evaluate a new polymeric system based on amphiphilic carboxymethylpullulans (CMP(49)C(8) and CMP(12)C(8)) that can spontaneously self-assemble in aqueous solutions and efficiently solubilize hydrophobic drugs. The self-assembling properties of CMP(49)C(8) and CMP(12)C(8) were characterized by fluorescence spectroscopy and surface tension measurements. The solubilization of benzophenone and docetaxel was assessed from surface tension measurements, UV spectrometry and HPLC assays. The in vitro cytoxicity of CMP(49)C(8) solutions and the docetaxel commercial vehicle (Tween 80/Ethanol-water) were evaluated in the absence and in the presence of docetaxel. Compared to CMP(12)C(8), CMP(49)C(8) in aqueous solutions appeared to self-organize into monomolecular aggregates containing hydrophobic nanodomains, and to significantly increase the apparent solubility of benzophenone. Docetaxel solubility could also be improved in the presence of CMP(49)C(8) but to a lower extent due to the surface properties of the drug. Nevertheless, in vitro, the cytotoxicity studies revealed that against cancer cells, the CMP(49)C(8)-docetaxel formulation was equipotent to the commercial docetaxel one. Furthermore, in the absence of the drug, CMP(49)C(8) appeared less cytotoxic against macrophages than the Tween 80/Ethanol-water. CMP(49)C(8) is a good candidate for solubilizing hydrophobic drugs and could be applied to docetaxel formulations.


TBX20 loss-of-function variants in families with left ventricular non-compaction cardiomyopathy.
TBX20 encodes a cardiac transcription factor that is associated with atrial septal defects. Recent studies implicate loss-of-function TBX20 variants with left ventricular non-compaction cardiomyopathy (LVNC), although clinical and genetic data in families are limited. We report four families with TBX20 loss-of-function variants that segregate with LVNC. Genetic testing using genome or exome sequencing was performed in index cases, variants were validated with Sanger sequencing, and cascade genetic testing was performed in family members. A multi-exon deletion, small deletion, essential splice site variant and nonsense variant in TBX20 were found in four families. The index cases in two families were symptomatic children with identical congenital heart diseases and LVNC who developed different cardiomyopathy phenotypes with one developing heart failure requiring transplantation. In another family, the child index case had LVNC and congestive heart failure requiring heart transplantation. In the fourth family, the index case was a symptomatic adult with LVNC. In all families, the variants segregated in relatives with isolated LVNC, or with congenital heart disease or cardiomyopathy. Family members displayed a clinical spectrum from asymptomatic to severe presentations including heart failure. Our data strengthen TBX20 loss-of-function variants as a rare cause of LVNC and support TBX20 inclusion in genetic testing of LVNC.


Noise exposure and hearing loss among sand and gravel miners.
The objectives of this study were to describe workplace noise exposures, risk factors for hearing loss, and hearing levels among sand and gravel miners, and to determine whether full shift noise exposures resulted in changes in hearing thresholds from baseline values. Sand and gravel miners (n = 317) were interviewed regarding medical history, leisure-time and occupational noise exposure, other occupational exposures, and use of hearing protection. Audiometric tests were performed both before the work shift (following a 12-hour noise-free interval) and immediately following the work shift. Full shift noise dosimetry was conducted. Miners' noise exposures exceeded the Recommended Exposure Limit (REL) of the National Institute for Occupational Safety and Health (NIOSH) for 69% of workers, and exceeded the Mine Safety and Health Administration's action level for enrollment in a hearing conservation program for 41% of workers. Significantly higher noise exposures occurred among employees of small companies, among workers with a job classification of truck driver, among males, and among black workers. Hearing protection usage was low, with 48% of subjects reporting that they never used hearing protection. Hearing impairment, as defined by NIOSH, was present among 37% of 275 subjects with valid audiograms. Black male workers and white male workers had higher hearing thresholds than males from a comparison North Carolina population unexposed to industrial noise. Small but statistically significant changes in hearing thresholds occurred following full shift noise exposure among subjects who had good hearing sensitivity at baseline. In a logistic regression model, age and history of a past noisy job were significant predictors of hearing impairment. Overall, sand and gravel workers have excessive noise exposures and significant hearing loss, and demonstrate inadequate use of hearing protection. Well-designed hearing conservation programs, with reduction of noise exposure, are clearly needed.


Chemical test for mammalian feces in ground black pepper: collaborative study.
A collaborative study for determining mammalian feces in ground black pepper was conducted, using a modified version of the AOAC Official Method 986.28 for mammalian feces in grain products. With the proposed method, the presence of alkaline phosphatase, an enzyme found in mammalian feces, was determined by using phenolphthalein diphosphate as the enzyme substrate in a test agar medium containing 1% agar in a borate buffer, pH 9.5. Ground black pepper was stirred in water to extract interfering color. The mixture was filtered and the residue was scattered on plates of liquid test agar. The alkaline phosphatase cleaved phosphate radicals from phenolphthalein diphosphate, generating free phenolphthalein, which appeared as pink to red-purple around the fecal particles in the previously colorless medium. For the 10- and 20-particle spike level, collaborators recovered averages of 12.3 and 24.1 particles, respectively. The experimental background was zero. Collaborators reported that the method was clear and easy to perform.


Plasma Biomarkers and Incident CKD Among Individuals Without Diabetes.
Biomarkers of kidney disease progression have been identified in individuals with diabetes and underlying chronic kidney disease (CKD). Whether or not these markers are associated with the development of CKD in a general population without diabetes or CKD is not well established. Prospective observational cohort. In the Atherosclerosis Risk in Communities) study, 948 participants were studied. The baseline plasma biomarkers of kidney injury molecule-1 (KIM-1), monocyte chemoattractant protein-1 (MCP-1), soluble urokinase plasminogen activator receptor (suPAR), tumor necrosis factor receptor 1 (TNFR-1), tumor necrosis factor receptor 2 (TNFR-2), and human cartilage glycoprotein-39 (YKL-40) measured in 1996-1998. Incident CKD after 15 years of follow-up defined as ≥40% estimated glomerular filtration rate decline to <60 mL/min/1.73 m2 or dialysis dependence through United States Renal Data System linkage. Logistic regression and C statistics. There were 523 cases of incident CKD. Compared with a random sample of 425 controls, there were greater odds of incident CKD per 2-fold higher concentration of KIM-1 (OR, 1.49; 95% CI, 1.25-1.78), suPAR (OR, 2.57; 95% CI, 1.74-3.84), TNFR-1 (OR, 2.20; 95% CI, 1.58-3.09), TNFR-2 (OR, 2.03; 95% CI, 1.37-3.04). After adjustment for all biomarkers, KIM-1 (OR, 1.42; 95% CI, 1.19-1.71), and suPAR (OR, 1.86; 95% CI, 1.18-2.92) remained associated with incident CKD. Compared with traditional risk factors, the addition of all 6 biomarkers improved the C statistic from 0.695-0.731 (P < 0.01) and using the observed risk of 12% for incident CKD, the predicted risk gradient changed from 5%-40% (for the 1st-5th quintile) to 4%-44%. Biomarkers and creatinine were measured at one time point. Higher levels of KIM-1, suPAR, TNFR-1, and TNFR-2 were associated with higher odds of incident CKD among individuals without diabetes. For people with diabetes or kidney disease, several biomarkers have been shown to be associated with worsening kidney disease. Whether these biomarkers have prognostic significance in people without diabetes or kidney disease is less studied. Using the Atherosclerosis Risk in Communities study, we followed individuals without diabetes or kidney disease for an average of 15 years after biomarker measurement to see if these biomarkers were associated with the development of kidney disease. We found that elevated levels of KIM-1, suPAR, TNFR-1, and TNFR-2 were associated with the development of kidney disease. These biomarkers may help identify individuals who would benefit from interventions to prevent the development of kidney disease.


Design of microdrop concentrating processes.
Concentrating solutes within aqueous microdrops is one of the processes that have been investigated recently in microfluidic systems. In order to design the process of concentrating solutes within microdrops more precisely, thermodynamic investigation of the process plays an important role. By knowing the equilibrium concentration and size of the drop, the magnitude of the driving force toward equilibrium will be determined which will help researchers to design such processes more accurately. Here, we have investigated the thermodynamic equilibrium of microdrop concentrating processes involving two kinds of solutes: glycerol as a solute with no solubility limit and sodium chloride as a solute with a solubility limit. It is found that the presence of a solubility limit affects the equilibrium of the process significantly in terms of trends in equilibrium concentration and size.


Structure-based Discovery of Novel CK2α-Binding Cyclic Peptides with Anti-cancer Activity.
Protein kinase CK2 is considered as an emerging target in cancer therapy, and recent efforts have been made to develop its ATP-competitive inhibitors, but achieving selectivity with respect to related kinases remains challenging because of the highly conserved ATP-binding pocket of kinases. Non-ATP competitive inhibitors might solve this challenge; one such strategy is to identify compounds that target the CK2α/CK2β interface as CK2 holoenzyme antagonists. Here we improved the binding affinity to CK2α and cell-based anti-cancer activity of a CK2β-derived cyclic peptide (Pc) by combining structure-based computational design with experimental evaluation. By analyzing molecular dynamics simulations of Pc bound to CK2α, a series of Pc-derived peptides was rationally designed and synthesized to evaluate their binding affinity to CK2α, as well as anti-proliferative and pro-apoptotic effects against HepG2 cancer cell line. One amino acid substitutions on Pc, I192F, exhibited over 10-fold improvement in the predicted binding affinity to CK2α when compared to Pc, and a cell-permeable version, I192F-Tat, also demonstrated more potent anti-proliferative and pro-apoptotic effects against HepG2 compared to Pc. A second modification of Pc, H193W, also led to more potent cell-based activity, despite having weaker binding affinity (∼5×) to CK2α. The discovery of the I192F and H193W peptides provides new insights for further optimization of CK2 antagonist candidates as anti-cancer leads.


Profiling a soft solid layer to passively control the conduit shape in a compliant microchannel during flow.
The shape of a microchannel during flow through it is instrumental to understanding the physics that govern various phenomena ranging from rheological measurements of fluids to separation of particles and cells. Two commonly used approaches for obtaining a desired channel shape (for a given application) are (i) fabricating the microchannel in the requisite shape and (ii) actuating the microchannel walls during flow to obtain the requisite shape. However, these approaches are not always viable. We propose an alternative, passive approach to a priori tune the elastohydrodynamics in a microsystem toward achieving a predetermined (but not prefabricated) flow geometry when the microchannel is subjected to flow. That is, we use the interaction between a soft solid layer, the viscous flow beneath it, and the shaped rigid wall above it to tune the fluid domain's shape. Specifically, we study a parallel-wall microchannel whose top wall is a slender soft coating of arbitrary thickness attached to a rigid platform. We derive a nonlinear differential equation for the soft coating's fluid-solid interface, which we use to infer how to achieve specific conduit shapes during flow. Using this theory, we demonstrate the tuning of four categories of microchannel geometries, which establishes, via a proof-of-concept, the viability of our modeling framework. We also explore slip length patterning on the rigid bottom wall of the microchannel, a common technique in microfluidics, as an additional "handle" for microchannel shape control. However, we show that this effect is much weaker in practice.


Enteric continence and the ileal pouch-anal procedure.
The ileal pouch-anal procedure maintains enteric continence by preserving critical physiological mechanisms. The reservoir, although possessing somewhat different physiologic characteristics than the rectum, provides sufficient storage capacity to enable the patient to resume most daily activities. The intact anorectal angle continues to perform its pivotal role in the maintenance of gross fecal continence, while the functioning anal sphincter muscles fine-tune the system. The success of the procedure has shown that certain widely held "principles" of continence may be less important than previously believed. These include the requirement for a long rectal stump, the preservation of the rectosphincteric inhibitory reflex, and the maintenance of sensation to the upper half of the anal canal. Yet, results are not perfect, and it is possible that while these mechanisms are not required for gross fecal continence, their transgression results in a subtle reduction in function from that of the normal state. When one considers, however, that the only other curative procedure for patients with familial polyposis is total proctocolectomy with permanent ileostomy, the ileal pouch-anal operation represents an important advance. The disease is removed, yet reasonably effective control of enteric continence is restored such that quality of life appears to be enhanced when compared to that achieved after proctocolectomy and Brook ileostomy.


Youth Resilience Corps: An Innovative Model to Engage Youth in Building Disaster Resilience.
Despite the growing awareness that youth are not just passive victims of disaster but can contribute to a community's disaster resilience, there have been limited efforts to formally engage youth in strengthening community resilience. The purpose of this brief report was to describe the development of a Youth Resilience Corps, or YRC (ie, a set of tools to engage young people in youth-led community resilience activities) and the findings from a small-scale pilot test. The YRC was developed with input from a range of government and nongovernmental stakeholders. We conducted a pilot test with youth in Washington, DC, during summer 2014. Semi-structured focus groups with staff and youth surveys were used to obtain feedback on the YRC tools and to assess what participants learned. Focus groups and youth surveys suggested that the youth understood resilience concepts, and that most youth enjoyed and learned from the components. The YRC represent an important first step toward engaging youth in building disaster resilience, rather than just focusing on this group as a vulnerable population in need of special attention.


Structure of the carboxypeptidase B complex with N-sulfamoyl-L-phenylalanine - a transition state analog of non-specific substrate.
Carboxypeptidase B (EC 22.214.171.124) (CPB) is commonly used in the industrial insulin production and as a template for drug design. However, its ability to discriminate substrates with hydrophobic, hydrophilic, and charged side chains is not well understood. We report structure of CPB complex with a transition state analog N-sulfamoyl-L-phenylalanine solved at 1.74Å. The study provided an insight into structural basis of CPB substrate specificity. Ligand binding is affected by structure-depended conformational changes of Asp255 in S1'-subsite, interactions with Asn144 and Arg145 in C-terminal binding subsite, and Glu270 in the catalytic center. Side chain of the non-specific substrate analog SPhe in comparison with that of specific substrate analog SArg (reported earlier) not only loses favorable electrostatic interactions and two hydrogen bonds with Asp255 and three fixed water molecules, but is forced to be in the unfavorable hydrophilic environment. Thus, Ser207, Gly253, Tyr248, and Asp255 residues play major role in the substrate recognition by S1'-subsite.


Physicochemical, functional, and nutritional characteristics of stabilized rice bran form tarom cultivar.
Extrusion is a multistep thermal process which has been utilized in a wide spectrum of food preparations. The effect of extrusion processing on the physicochemical, nutritional, and functional properties of Tarom cultivar rice bran was studied. However, the color of rice bran was improved by extrusion processing, but the protein content was reduced in the stabilized rice bran, which can be related to the denaturation of protein. Extrusion had also a reduction significant effect on the phytic acid as well as vitamin E in rice bran. However, the content of niacin, riboflavin, pantothenic acid, and folic acid remained unchanged, but the dietary fiber was enhanced which has beneficial health effect on human consumption. In comparison with unstabilized rice bran, water holding capacity was enhanced, but the oil absorption capacity was reduced. Foaming capacity and foaming stability of extruded rice bran was more than that of untreated rice bran, although they were less than that of rice bran protein concentrate/isolate. In general, the extrusion process improves some functional and nutritional properties of rice bran which are valuable to industrial applications and have potential as ingredient in food to improve consumer health.


[Effects of N-acetylcysteine on apoptosis induced by myocardial ischemia reperfusion injury in rats' heart transplantation].
To investigate the effect of N-acetylcysteine (NAC) on the apoptosis during myocardial ischemia reperfusion injury in rats' heart transplantation, and to explore the possible role of NAC in myocardial apoptosis. Sixty healthy male Lewis rats (weighing, 200-220 g) were randomly divided into 3 groups, 20 rats each group (10 donors and 10 recipients). In control group, 1 mL normal saline was infused via inferior vena cava at 30 minutes before donor harvesting; in donor preconditioning group, NAC (300 mg/kg) was infused via inferior vena cava at 30 minutes before donor harvesting, but no treatment in recipients; and in recipient preconditioning group, NAC (300 mg/kg) was infused via inferior vena cava at 30 minutes before recipient transplantation, but no treatment in donors. Heart transplantation was established in each group. Blood was drawn at 6 and 24 hours after reperfusion for analysis of aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH) as markers of graft injury; myocardial tissue was harvested to determine the superoxide dismutase (SOD) and lipid hydroperoxide (LPO) activity at 24 hours after reperfusion and to observe the histology and ultrastructural changes. Graft active Caspase-3 protein expression was measured by immunohistochemistry staining, and apoptosis index (AI) was calculated by TUNEL. The heart transplantation operation was successfully completed in all groups, and the rats survived to the end of the experiment. The serum levels of AST, ALT, and LDH in donor and recipient preconditioning groups were significantly lower than those in control group at 6 hours after reperfusion (P < 0.05); the levels of AST and ALT in donor preconditioning group and the levels of AST and LDH in recipient preconditioning group were significantly lower than those in control group at 24 hours (P < 0.05); and no significant difference was found between donor and recipient perconditioning groups (P > 0.05). The levels of AST, ALT, and LDH at 24 hours were significantly lower than those at 6 hours in each group (P < 0.05) except the level of ALT in recipient preconditioning group (P > 0.05). SOD activity and SOD/LPO in donor and recipient preconditioning groups were significantly higher than those in control group (P < 0.05), but no significant difference between donor and recipient preconditioning groups (P > 0.05); there was no significant difference in LPO activity among 3 groups (P > 0.05). Histological staining and transmission electron microscope showed that myocardial injury in recipient preconditioning group was obviously lighter than that in donor preconditioning group and control group. Active Caspase-3 in recipient pretreatment group was significantly higher than that in donor preconditioning group and control group (P < 0.05). AI of donor and recipient preconditioning groups was significantly lower than that of control group (P < 0.05), but no significant difference was found between donor and recipient preconditioning groups (P > 0.05). NAC can relieve ischemia reperfusion injury in rats' heart transplantation by improving myocardial SOD content, and reducing active Caspase-3 activity and AI, which has a protective effect on myocardial cell of donor heart.


The promise of science-based training and application in psychological clinical science.
Baker, McFall, and Shoham (2008) analyzed and critiqued the state of training in clinical psychology, asserting that much of this training is not sufficiently influenced by science. They asserted that the emergent demands of health care, with its attendant costs and resource constraints, require that mental and behavioral health care become increasingly efficient, effective, and cost-effective. Baker et al. (2008) then offered examples of how science-based evidence and methods could influence training in clinical psychology to achieve those goals. Laska, Gurman, and Wampold (2014, pp. 467-481) critiqued aspects of the Baker et al. (2008) paper. In the current paper, we argue that Laska et al. (2014) misconstrued points made in the early Baker paper. We also assert that evidence of common factors in psychological interventions is in no way antithetical or problematic to a science-based approach to clinical training and application. Further, we argue for a multidimensional approach to evaluating intervention performance, one that involves an evaluation of efficacy, effectiveness, cost-effectiveness, translation potential, and so on. Finally, we discuss how researchers can most efficiently develop intervention methods and delivery systems that are superior to the induction of common factors per se.


The use of the 2-iminobiotin-avidin interaction for the selective retrieval of labeled plasma membrane components.
A general method for the selective retrieval of surface labeled plasma membrane components had been devised. The basis of the technique is the covalent attachment of compounds containing 2-iminobiotin, the cyclic guanidino analog of biotin, onto the cell surface proteins and the use of immobilized avidin to recover the labeled components uncontaminated by other cytosolic and membrane components. The pH-dependent interaction of 2-iminobiotin with avidin makes recovery possible. At high pH the free base form of 2-iminobiotin retains the high affinity specific binding to avidin characteristic of biotin, whereas at acidic pH values, the salt form of the analog interacts poorly with avidin. Model studies on the interaction of 2-iminobiotinylated proteins with avidin-Sepharose 4B show that for tight binding to the affinity matrix, the pH of the column must be 9.5 or higher, that a single 2-iminobiotin group is sufficient for binding, and that proteins with different extents of labeling behave similarly when the low pH buffer is applied. When intact human erythrocytes were sequentially labeled with periodate and 2-iminobiotin hydrazide and the Triton X-100-solubilized plasma membrane proteins were subjected to affinity isolation, the major sialoglycoproteins, periodic acid-Schiff (PAS) 1, PAS 2, and PAS 3, plus two proteins with apparent molecular weights higher than band 3 were retrieved. The recovery of these proteins is not due to a nonspecific adsorption to the affinity matrix.


Endoscope-Assisted Microsurgery in Pediatric Cases With Pineal Region Tumors: A Study of 18 Cases Series.
Background: An endoscope-assisted technique was recently introduced to microsurgery (MS) and may compensate for the disadvantages of MS for deep-seated lesions. This study was performed to identify the effectiveness and safety of endoscopic-assisted microsurgery (EAM) and share our experience of EAM for pediatric cases with pineal region tumors. Method: We retrospectively analyzed the clinical data of consecutive pediatric cases with pineal region tumors treated by EAM or MS from January 2016 to June 2020. These data included the patient population, clinical manifestations, preoperative examination findings, surgical approach, pathological results, and clinical outcomes. The clinical outcomes were analyzed in the EAM group and MS group with a focus on the gross total resection (GTR) rate, postoperative hydrocephalus remission rate, and Karnofsky performance score (KPS). Studies on the surgical management of children with pineal region tumors in the last decade were reviewed. Result: Eighteen children successfully underwent tumor resection via MS (n = 8) or EAM (n = 10). The children's mean age was 11.4 ± 4.7 years, and the male to female ratio was 7:2. Seventeen patients (94.4%) complicated preoperative hydrocephalus, and 16 (88.9%) presented headache with nausea and/or vomiting. The pathological examination revealed germ cell tumors in 11 (61.1%) patients, neuroepithelial tumors in 4 (22.2%) patients, and a pineoblastoma, arachnoid cyst, and atypical teratoid rhabdoid tumor in 1 (5.6%) patient each. GTR was more commonly achieved in the EAM than MS group (80.0 vs. 50.0%, respectively), and the postoperative hydrocephalus remission rate was higher in the EAM than MS group (87.5 vs. 50.0%, respectively). At a mean follow-up time of 23.6 ± 11.5 weeks, the mean improvement of the KPS 6 months postoperatively was greater in the EAM than MS group (24.0 ± 9.7 vs. 17.5 ± 7.1 points, respectively). Conclusion: EAM combines endoscopic and microsurgical techniques and can be safely and effectively performed to achieve GTR of pineal region tumors in pediatric patients. In children with pineal region tumors who have obstructive hydrocephalus, EAM could improves hydrocephalus remission rates by checking and clearing the midbrain aqueduct under visualization.


School clinics for adolescents with asthma.
Adolescents with asthma often have a poor attendance record at primary care review clinics. A school-based asthma clinic project was set up to see whether this service could improve adherence with treatment and clinic attendance.


Aluminum enhancement of plant growth in acid rooting media. A case of reciprocal alleviation of toxicity by two toxic cations.
The generally rhizotoxic ion Al3+ often enhances root growth at low concentrations. The hypothesis that Al3+ enhances growth by relieving H+ toxicity was tested with wheat seedlings (Triticum aestivum L.). Growth enhancement by Al3+ only occurred under acidic conditions that reduced root elongation. Al3+ increased cell membrane electrical polarity and stimulated H+ extrusion. Previous investigations have shown that Al3+ decreases solute leakage at low p H and that the alleviation of H+ toxicity by cations appears to be a general phenomenon with effectiveness dependent upon charge (C3+ >C2+ >Cl+ ). Alleviation of one cation toxicity by another toxic cation appears to be reciprocal so that Al3+ toxicity is relieved by H+ . It has been argued previously that this latter phenomenon accounts for the apparent toxicity of ALOH2+ and Al(OH)+2 . Reduction of cell-surface electrical potential by the ameliorative cation may reduce the cell-surface activity of the toxic cation.


[One in five surgeons do not wash hands after visiting a toilet - an ethnographic field study].
Non-compliance with regard to hand hygiene is a major problem in the health-care system especially among surgeons and anaesthetists. The purpose of this study was to examine the hand hygiene routines after toilet visits among participants attending an international surgical congress. An observational study was conducted at the American College of Surgeons (ACS) Clinical Congress 2012 and at the American Medical Writers Association (AMWA) Congress 2012 as comparison. The study was performed as an ethnographic field study. A standardized observational matrix was developed for observing whether hand washing (as a surrogate measure of hand hygiene) was performed after toilet visits by observers. Frequencies were compared using Fisher's exact test. A total of 100 persons were observed (80% males). Of the 50 males observed at the ACS meeting, ten males did not use hand hygiene in relation to toilet visits (20%), while only one person at the AMWA meeting out of the 50 observed did not use hand hygiene (2%), p = 0.008. At both congresses only males did not use hand hygiene in relation to toilet visits. One in five surgeons did not wash hands after visiting a toilet. Even though the observed surgeons were not observed in an operating theatre or in a setting that required a distinct degree of hand hygiene, it does reveal a worrying behaviour. It is not known whether this was a conscious act, the result of business, or if it was due to lack of knowledge about the effects of hand hygiene on bacterial transmission. not relevant. This study was neither registered at the National Committee of Health Research nor at Clinical Trials since it did not meet the requirements of registration.


Hydrogenation of Pt/TiO₂{101} nanobelts: a driving force for the improvement of methanol catalysis.
Single-crystalline anatase TiO2 nanobelts with a dominant surface of the {101} facet were hydrogenated and used as substrates of platinum for methanol oxidation reaction (MOR). The hydrogenated TiO2 anatase{101} supporting Pt exhibits a 228% increase of current density for methanol oxidation compared with the same system without hydrogenation under dark conditions. The synergetic interactions of hydrogenated anatase{101} with the Pt cluster were investigated through first principles calculations, and found that the hydrogenation shifts the conduction band minimum to the Fermi level of pristine TiO2, and reduces the activation barrier for methanol dissociation considerably. Thus, this work provides an experimental and theoretical basis for developing non-carbon substrates with high electro-catalytic activity toward MOR.


Probabilistic design analysis of the influence of material property on the human cervical spine.
Studies reported previously in the literature have described the importance of material variation on the cervical responses and have examined some effects by varying the material properties, but there is no systematic approach using statistical methods to understand the influence of material variation on a cervical spine model under a full range of loading conditions, especially under compression and anterior and posterior shear. A probabilistic design system based on Monte Carlo simulation methods using Latin hypercube sampling techniques is used to analyze the material sensitivity of a C4-C6 cervical spine model involving 13 uncertain input parameters on the biomechanical responses and disc annulus stresses under compression, anterior shear, posterior shear, flexion, extension, lateral bending, and axial rotation. The loading types and range of values were as follows: compression, 0-1 mm; anterior shear, 0-2 mm; posterior shear, 0-3.5 mm; flexion, extension, lateral bending, and axial rotation. 0-1.8 Nm with 73.6-N preload. For each case, the load-deflection and key stress values at various spinal components were captured after each load step. The model was also validated under the same conditions. The minimum and maximum predicted responses were within the range of the experimental data. Ignoring compression loading, the combined effects on the biomechanical responses of the cervical ligaments under the remaining loads are enormous. Their total impacts are almost equal to or slightly less than the influence of disc annulus. Results show that the fiber mechanical properties did not have a significant effect on the compressive stiffness. This study reveals important features that help us identify the critical input parameters and enable us to reduce the development time of a patient-specific biomechanical model.


The action of probiotic microorganisms on chemical contaminants in milk.
Consumption of milk and its derivatives is an important food habit in the diet of all age groups. However, there has been increasing concern about physical, biological (pathogenic or spoilage microorganisms) and chemical (metals, pesticides and mycotoxins) contaminants in milk and dairy products. Considering the high levels of consumption, it is important that milk and dairy products are free from toxic compounds. Microbial degradation as a strategy for chemical decontamination is an emerging biotechnological approach that is considered a safe and inexpensive practice. The decontaminant activity of probiotic microorganisms is associated with fermentation, antibiosis and the ability of the microbial cell wall to bind to the contaminant. Exploiting the potential of microorganisms for chemical decontamination will further leverage its application in the food industry.


Volume replacement with Ringer-lactate is detrimental in severe hemorrhagic shock but protective in moderate hemorrhagic shock: studies in a rat model.
To date, there are insufficient data demonstrating the benefits of preclinically administered Ringer-lactate (RL) for the treatment of hemorrhagic shock following trauma. Recent animal experiments have shown that lactate tends to have toxic effects in severe hemorrhagic shock. This study aimed to compare the effects of RL administered in a rat model of severe hemorrhagic shock (mean arterial blood pressure (MAP): 25 to 30 mmHg) and moderate hemorrhagic shock (MAP: 40 to 45 mmHg). Four experimental groups of eight male Wistar rats each (moderate shock with Ringer-saline (RS), moderate shock with RL, severe shock with RS, severe shock with RL) were established. After achieving the specified depth of shock, animals were maintained under the shock conditions for 60 minutes. Subsequently, reperfusion with RS or RL was performed for 30 minutes, and the animals were observed for an additional 150 minutes. All animals with moderate shock that received RL survived the entire study period, while six animals with moderate shock that received RS died before the end of the experiment. Furthermore, animals with moderate shock that received RL exhibited considerable improvements in their acid-base parameters and reduced organ damage. The preclinical use of RL for volume replacement has different effects depending on the severity of hemorrhagic shock. RL exhibits detrimental effects in cases of severe shock, whereas it has pronounced protective effects in cases of moderate shock.


How a 7-Week Food Literacy Cooking Program Affects Cooking Confidence and Mental Health: Findings of a Quasi-Experimental Controlled Intervention Trial.
Obesity and mental health disorders are rising simultaneously with shifting dietary behavior away from home cooking, toward typically nutrition-poor and energy-dense convenience meals. Food literacy strongly influences nutrition choices. Community-based cooking interventions target barriers to healthy eating and facilitate development of food literacy skills, thereby potentially increasing preparation of home-cooked meals and positively influencing health. This study of 657 healthy Australian adults explored the efficacy of a 7-week cooking program in improving cooking confidence, whether this transferred to behavior surrounding food, and/or affected mental health. Significant post-program improvements in cooking confidence and satisfaction (all p < 0.001, η p 2 1.12 large), ability to change eating habits (p < 0.001) and overcome lifestyle barriers (p = 0.005) were observed for the intervention group but not control. Participation also improved mental and general health (all p < 0.05, η p 2 0.02 small). No changes were observed for acquisition and consumption of food, or nutrition knowledge in either group. This 7-week cooking program built cooking confidence and improved general and mental health but did not change dietary behavior. To further improve nutrition related behaviors associated with better mental health, more effort is needed to recruit those with below-average nutrition knowledge and interest in cooking.


Angiotensin Receptor-Neprilysin Inhibitors in Patients With Heart Failure With Reduced Ejection Fraction and Advanced Chronic Kidney Disease: A Retrospective Multi-Institutional Study.
Data regarding using angiotensin receptor-neprilysin inhibitor (ARNI) in patients with both heart failure with reduced ejection fraction (HFrEF) and advanced chronic kidney disease (CKD) are limited. Between January 2016 and December 2018, patients with HFrEF and advanced CKD (estimated glomerular filtration rate [eGFR] ≤ 30 mL/min/1.73 m2) were identified from a multi-institutional database in Taiwan. Patients who had never been prescribed with an ARNI, angiotensin-converting enzyme inhibitor (ACEI), or angiotensin receptor blocker (ARB) were excluded. We used inverse probability of treatment weighting (IPTW) to balance baseline covariates, and compared outcomes between ARNI and ACEI/ARB users. There were 206 patients in the ARNI group and 833 patients in the ACEI/ARB group. After IPTW adjustment, the mean ages (65.1 vs. 66.6 years), male patients (68.3 vs. 67.9%), left ventricular ejection fraction (30.5 vs.31.2%), eGFR (20.9 vs. 20.3 mL/min/1.73 m2) were comparable in the ARNI and ACEI/ARB groups. Over 85% of the patients had beta-blockers prescriptions in both groups (86.2 vs. 85.5%). After IPTW adjustment, the mean follow-up durations were 7.3 months and 6.6 months in the ARNI and ACEI/ARB groups, respectively. ARNI and ACEI/ARB users had a comparable risk of the composite clinical event (all-cause mortality or heart failure hospitalization) (hazard ratio [HR], 1.31; 95% confidence interval (CI) 0.91-1.88) and progression to dialysis (HR 1.04; 95% CI 0.54-2.03). In subgroup analysis, dialysis patients who used ARNIs were associated with higher incidence of heart failure hospitalization (subdistribution HR, 1.97; 95% CI 1.36-2.85). Compared with ACEIs or ARBs, ARNIs were associated with comparable clinical and renal outcomes in patients with HFrEF and advanced CKD (eGFR ≤ 30 mL/min/1.73 m2). In short-term, HF hospitalization may occur more frequently among ARNI users, especially in patients on dialysis.


Synthesis and Structural Characterization of Novel Trihalo-sulfone Inhibitors of WNK1.
With No lysine (K) [WNK] kinases are structurally unique serine/threonine protein kinases that have therapeutic potential for blood pressure regulation and cancer. A novel class of trihalo-sulfone compounds was identified by high-throughput screening. Trihalo-sulfone 1 emerged as an effective inhibitor of WNK1 with an IC50 value of 1.6 μM. Herein, we define chemical features necessary for inhibition of WNK1 using chemical synthesis and X-ray crystallography. Analogues that probed the role of specific functional groups to the inhibitory activity were synthesized. X-ray structures of trihalo-sulfone 1 and a second trihalo-sulfone 23 bound to WNK1 revealed active site binding to two of the three previously defined canonical inhibitor binding pockets as well as a novel binding site for the trihalo-sulfone moiety. The elucidation of these novel interaction sites may allow for the strategic design of even more selective and potent WNK inhibitors.


[Risk analysis and preventive strategies of implant placement in patients with hypertension].
Recently, among the edentulous patients who undergo dental implants, the proportion of hypertensive patients remains high, which poses a greater challenge for clinicians to operate and to maintain the therapeutic effect. The present review comprehensively summarized clinical researches about the adverse effects on dental implants, outlined molecular mechanisms of the positive effects of various antihypertensive drugs on bone metabolism, and proposed that clinicians should select preventive strategies during preoperative and intraoperative procedures according to the blood pressure of patients with hypertension.


Nasal-cardiopulmonary reflexes: a role of the larynx.
A brief review of the literature from otorhinolaryngology and the basic sciences shows the existence and role of nasal-cardiopulmonary reflexes in animals and man. There is ample evidence that odors, fluids and mechanical stiumlation of the nasal mucosa will induce changes in the lungs and cardiovascular system. The proposition that nasal obstruction also produces cardiopulmonary changes is briefly reviewed. The suggestion is made that one of the functions of the nose is to act as an expiratory brake. the removal of this brake could result in changes in laryngeal resistance that lead to poor ventilation.


Systemic osteoporosis--major complication of psoriatic arthritis.
Determination of bone mineral density in patients with psoriatic arthritis and its correlation with the development of the disease. Three groups of patients were recruited: group 1--patients with psoriasis arthritis; group 2--patients with rheumatoid arthritis, group 3--control group. Group 1 was divided into: group 1A--patients with disease duration < 5 years and group 1B--patients with disease duration > 5 years. Bone mineral density was determined for total hip by dual X-ray absorptiometry (DXA). In the group 1A BMD values of total femur were between -1.32 and -1.68 DS; in the group 1B BMD values of total femur were between 1B -1.58 and - 1.77DS; in the group 2 BMD values of total femur were between -2.51 and -3.41 DS and in the control group BMD values of total femur were between 0.29 and 1.3 DS. In patients with psoriatic arthritis, the duration of arthritis was negatively correlated with BMD values of total femur. In conclusion, psoriatic patients with longer duration of disease may be at a risk for osteoporosis, which can require preventative treatment efforts.


Gibbsite (100) and Kaolinite (100) Sorption of Cadmium(II): A Density Functional Theory and XANES Study of Structures and Energies.
Due to the potential toxicity of cadmium (Cd2+) and its presence in various waste products found in the environment, it is necessary to develop methods to attenuate and remediate Cd2+ waste. Sorption of Cd2+ to mineral surfaces is a potential route to accomplish this goal. This work focused on improving our molecular-scale understanding of the chemistry of Cd2+ interactions with gibbsite and kaolinite mineral surfaces. Plane-wave density functional theory (DFT) energy minimization calculations and molecular dynamics simulations were used to study the adsorption energies and the nature of the bonds between Cd2+ and the mineral surfaces for possible inner- and outer-sphere surface complexes. Models resulting from the DFT calculations were used to calculate theoretical XANES spectra that were compared with experimental Cd LIII XANES of aqueous Cd2+ as a proxy for outer-sphere Cd2+ hydrated complexes associated with the mineral surfaces. These studies suggest that Cd2+ would favorably bond to the (100) surfaces of both kaolinite and gibbsite through a bidentate mononuclear interaction. However, the results indicate that mixtures of surface complexes on these minerals are likely.


Resuscitation of the newly born infant: an advisory statement from the Pediatric Working Group of the International Liaison Committee on Resuscitation.
The International Liaison Committee on Resuscitation (ILCOR), with representation from North America, Europe, Australia, New Zealand, Africa, and South America, was formed in 1992 to provide a forum for liaison between resuscitation organizations in the developed world. This consensus document on resuscitation extends previously published ILCOR advisory statements on resuscitation to address the unique and changing physiology of the newly born infant within the first few hours following birth and the techniques for providing advanced life support.


Marked response to a cisplatin/docetaxel/temozolomide combination in a heavily pretreated patient with metastatic large cell neuroendocrine lung carcinoma.
At present, there is no clear consensus on the most appropriate treatment approach for large cell neuroendocrine carcinoma of the lung. Large cell neuroendocrine carcinoma lesions differ from other nonsmall cell lung carcinomas in that they have a particularly aggressive clinical behaviour and extremely poor prognosis. We report a 52-year-old woman large cell neuroendocrine carcinoma patient with progressive stage IV disease in the chest, liver, adrenal glands and, particularly, the brain, who achieved a marked response to a fourth-line combination of docetaxel, cisplatin and temozolomide. This regimen significantly improved her quality of life and survival. The good response obtained in this heavily pretreated patient adds to the evidence regarding the use of temozolomide in patients with lung cancer with brain metastases.


A Latent Profile Analysis of Affective Triggers for Risky and Impulsive Behavior.
Common theoretical models of risky and impulsive behaviors suggest that individuals engage in risky behavior to avoid negative affect or enhance positive affect. However, little research has been done to identify person-centered affective profiles of risky and impulsive behavior, and delineate the individual differences across these profiles. The present study used the Risky, Impulsive, and Self-destructive Behavior Questionnaire in community (N = 439) and incarcerated (N = 262) samples to examine latent affect profiles for risky and impulsive behavior. Four affective profiles emerged: low avoidance and low approach, average avoidance and average approach, high avoidance, and high approach. Conditional probability correlations revealed meaningful differences across these profiles in psychiatric symptomatology, personality characteristics, and behavior. Consideration of affective triggers provides an important framework for dissociating the underlying reasons why individuals engage in risky behavior.


Lanthanide-doped core-shell nanoparticles as a multimodality platform for imaging and photodynamic therapy.
We report a novel lanthanide-doped core-shell nanostructure NaYF4:Yb,Er@NaGdF4:Nd@SiO2-RB with a unique design feature that integrates luminescence imaging in biological window II, magnetic resonance imaging, and NIR-excited photodynamic antimicrobial chemotherapy, in a single nanoscale entity.


Comparison of sampling efficiency between simulated tempering and replica exchange.
We compared the sampling efficiency of simulated tempering and replica exchange. Our results indicate that simulated tempering is superior to replica exchange if the parameters for temperature transition in simulated tempering are adjusted to be proportional to the partition function. It is shown that, in simulated tempering, the rate of traversing energy space of different temperatures is much higher than that in replica exchange, especially in the case of low tempering frequency and/or larger temperature separations.


Changes in the Correlates for Intimate Partner Violence Against Women in Vietnam: Evidence From the 2010 and 2019 National Prevalence Surveys.
This study sought to understand whether the risk and protective factors associated with current partner violence changed in Vietnam using findings from two comparable surveys conducted in 2010 and 2019. Fifteen (2010) and 17 (2019) factors were significantly associated with violence, and the level of consistency was high-nonpartner sexual violence, respondent and partner prior abuse, men's expressions of masculinity, and indicators of low economic status continue to put women at risk. Gender-transformative approaches that address power inequalities, foster positive parenting, and promote the political and social influence of women are required and should be adapted to the Vietnam context.


Cultural malpractice during pregnancy, childbirth, and the postnatal period and its associated factors among women who gave birth once in Dire Dawa city administration, Eastern Ethiopia, in 2021.
Cultural practices are any experiences or beliefs that are socially shared views and behaviors practiced in a certain society at a certain time. Cultural malpractices are defined as socially shared views and traditionally accepted behaviors experienced in a certain society that harm maternal health. Worldwide, the period of pregnancy, labor, and delivery is embedded with different beliefs, customs, and rituals in different societies that contribute a lot to maternal death. They are responsible for the annual deaths of 303,000 mothers and 2.7 million newborns globally. In developing countries, it accounts for approximately 5%-15% of maternal deaths. In Ethiopia, approximately 18% of infant deaths occur due to cultural malpractice, and 52% of pregnant mothers give birth at home following cultural customs in Dire Dawa city. The objective of this study was to assess cultural malpractices during pregnancy, childbirth, and the postnatal period and its associated factors among women who gave birth once in Dire Dawa City in 2021. Community-based mixed study was conducted. A total of 624 study participants were selected through a systematic random sampling technique, and a purposive sampling method was used for qualitative data. The study was conducted in the randomly selected Kebeles of Dire Dawa City, Eastern Ethiopia, from November 1 to December 30, 2021. Data were entered into Epi Data version 4.1 and exported to SPSS version 24 for analysis. Bivariate and multivariate analyses were done, and the degree of association was measured by using the odds ratio with 95% CI and significance was declared at a p-value of <0.05. The qualitative data were analyzed thematically using ATLAS-ti version 7. The overall prevalence of cultural malpractice during pregnancy, childbirth, and the postnatal period was 74.6% [95% CI: 70.59%, 77.49%]. Women over the age of 35 were two times more likely [AOR 2.61, 95% CI, 1.45-4.72] to commit cultural malpractice than women aged 15-24 and 25-34. Those with no antenatal care (ANC) follow-up were three times more likely to commit cultural malpractice [AOR 3.57, 95% CI, 1.72-7.40], those who were absent from health education were nearly two times more likely to commit cultural malpractice [AOR 1.83, 95%CI, 1.25-2.67], and women whose culture allows harmful traditional practices were nearly two times more likely to commit cultural malpractices than their counterparts [AOR 1.69, 95%CI, 1.29-2.54]. In this study, nearly three-fourths of participants were involved in cultural malpractices. Therefore, strengthening community education and behavioral change messages on the importance of ANC and avoiding unhealthy care during pregnancy, childbirth, postnatal and neonatal periods, especially with pregnancy at old age (age > 35), may help to reduce cultural malpractices.


[Hysterosalpingography in the assessment of tubal patency].
A major cause of infertility in women is occlusion of fallopian tubes. Hysterosalpingography (HSG) and laparoscopic chemoperturbation are the two traditionnal diagnostic options for tubal assessment. Recently hysterosalpingo-contrast sonography (HyCoSy), an ultrasound-based technique that uses as a contrast agent fluid injected into the fallopian tubes via the uterine cavity, is gaining importance as an alternative procedure. The aim of this study is the analysis of several technic and semiologic aspects of HyCoSy. advantges and limits are discussed throughout a review of literature. HyCoSy is a well tolerated outpatient technique. When performed by experienced operators, it servs as a valable first line screening test of tubal patency in low fertility women. It can confirme that tubes are patent and permits to select patients who need more invasive procedures.


Psychometric identification of early Alzheimer disease in an elderly Chinese population with differing educational levels.
In this study, the authors (1) validated a concise neuropsychologic assessment battery to identify early Alzheimer disease (AD) in an elderly Chinese population, (2) studied how the level of literacy in this cohort influenced the psychometric test performance, (3) determined the best individual and combination of tests from the battery to detect AD, and (4) compared their results with parallel data from Western and other similar Chinese neuropsychologic studies. The psychometric battery was administered to 155 cognitively healthy elderly Chinese and 72 predominantly mild AD patients. Results showed that the majority of tests in this neuropsychologic battery validly identified early AD in the elderly Chinese subjects. Correct interpretation of test scores required adjustment for patients' educational attainments. Verbal memory, verbal fluency, and visuospatial functioning were the most important diagnostic domains, and this pattern has broad similarities with findings from the West, supporting the transcultural cognitive manifestation of AD.


Mucosal administration of an altered CII263-272 peptide inhibits collagen-induced arthritis by suppression of Th1/Th17 cells and expansion of regulatory T cells.
Rheumatoid arthritis (RA) is a systemic autoimmune disease mediated by T cells. Collagen type II (CII) is one of the autoantigens associated with RA. CII263-272 is a predominant CII antigenic peptide that can induce T-cell activation upon binding to MHC and interaction with the appropriate T-cell receptor (TCR). Altered CII263-272 peptides with substitution of specific amino acids could bind to RA-associated HLA-DR4/1 with no T cell stimulating effects and could inhibit T cell activation in RA. We performed this study to evaluate the effect of mucosal administration and to explore the mechanism of the inhibitory effect of altered CII263-272 peptide (267Q-->A, 270K-->A and 271G-->A) on collagen induced arthritis (CIA). CIA was induced in Lewis rats by immunization with bovine CII. Altered CII263-272 peptide was given intranasally beginning from arthritis onset. Wild CII263-272 peptide or PBS was administered as controls. Therapeutic effects were evaluated by arthritis scores, body weight change, and joint pathologic scores. The anti-CII antibody and its subtypes and the cytokines, IFN-gamma, IL-10, and IL-17 were measured with ELISA. Foxp3+CD4+CD25+ regulatory T cell induction was assessed by FACS analysis. Following treatment with the altered CII263-272 peptide, arthiritis scores were reduced and body weight was increased. The altered CII263-272 peptide could retard the histologic lesion of the joints. The titers of anti-CII antibodies IgG2a in altered CII263-272 peptide treated rats decreased markedly compared to PBS-treated rats. The serum levels of IFN-gamma in rats treated with altered peptide was lower than that of rats treated with wild CII263-272 peptide and PBS. No differences were observed in the levels of serum IL-10 among the three groups. The altered CII263-272 peptide could decrease serum level of IL-17 and increase peripheral Foxp3+CD4+CD25+ T cells at early stage of CIA. Mucosal administration of altered CII263-272 peptide could effectively inhibit the progression of CIA. Altered CII263-272 peptide could suppress Th17 cells and expand regulatory T cells in the early stage of the disease. The IgG2a subtype of anti-CII antibodies and IFN-gamma were reduced and in vivo Th1 responses were inhibited as a result of altered CII peptide treatment. Altered CII peptide is likely therapeutic in RA.


Advances in adult non-Hodgkin's lymphoma. Current concepts of classification, diagnosis, and management.
In recent years, major advances in the knowledge of immunobiology of the malignant cell, changes in systems of histologic classification and staging procedures, and the development of new therapeutic regimens have considerably changed the approach to, and treatment of, patients with non-Hodgkin's lymphoma. Along with these developments has come the realization that close collaboration among the hematologist-oncologist, the hematopathologist, the radiotherapist, and the surgeon is critical in the successful treatment of these patients. Today, the possibility of cure exists for selected patients with non-Hodgkin's lymphoma; such patients must be identified and given appropriate initial therapy. In all patients, the selection of therapy is guided by the histologic type and stage of disease.


Selective decontamination of alimentary tract microbial flora in patients treated with bone marrow transplantation. A microbiological study.
14 patients undergoing bone marrow transplantation were studied regarding the oral and faecal microflora. Seven patients were given a multidrug regimen, directed against aerobic gram-negative rods and fungi, for local decontamination of the oral cavity and gastrointestinal tract. Seven other patients served as controls. The decontamination regimen was found to decrease the numbers of fungi in the oral cavity and to protect from new colonization. In the gastrointestinal tract aerobic gram-negative rods were eliminated in all patients and new colonization with acquired microorganisms was not observed even when the indigenous anaerobic flora had been disturbed by parenteral antibiotics. In the control group aerobic gram-negative rods and fungi were isolated from all patients during the observation period.


A comparison of the case-control and case-crossover designs for estimating medical costs of nonfatal fall-related injuries among older Americans.
Although the case-crossover design has been used widely in epidemiological and cost-offset studies as an alternative to the case-control design, it is rarely applied to cost-of-illness studies. In this study, costs for a series of hospitalized and nonhospitalized fall-related injuries were computed using the 2 approaches to allow for a direct comparison of the results. We used claims data from the Medicare fee-for-service 5% Standard Analytical Files. For the case-control design, those who sustained nonfatal fall-related injuries were tracked for 1 year after their first fall, and costs were compared, using regression analysis, to annual costs for a comparison sample of nonfallers. The case-crossover design used a modified regression approach that compared monthly costs of fallers before and after fall. We present unit costs for falls requiring (1) a hospitalization resulting in a live discharge, (2) an emergency department visit not resulting in an admission, and (3) falls requiring office-based or hospital outpatient visits only. Using the case-control design, these costs were $22,260, $3890, and $5040 respectively. Using the case-crossover design, these estimates were reduced to $20,920, $3230, and $4200. On average, estimates of the costs of fall injuries from the case-control design were between 6% and 17% greater than those from the case-crossover approach. These differences likely result from our inability to control for comorbidity differences between fallers and nonfallers in the case-control design. Under several scenarios, including unobserved heterogeneity between cases and controls, the case-crossover design, although computationally more intensive, produces more accurate results.


Monitoring tissue inflammation and responses to drug treatments in early stages of mice bone fracture using 50 MHz ultrasound.
Bone fracture induces moderate inflammatory responses that are regulated by cyclooxygenase-2 (COX-2) or 5-lipoxygenase (5-LO) for initiating tissue repair and bone formation. Only a handful of non-invasive techniques focus on monitoring acute inflammation of injured bone currently exists. In the current study, we monitored in vivo inflammation levels during the initial 2 weeks of the inflammatory stage after mouse bone fracture utilizing 50 MHz ultrasound. The acquired ultrasonic images were correlated well with histological examinations. After the bone fracture in the tibia, dynamic changes in the soft tissue at the medial-posterior compartment near the fracture site were monitored by ultrasound on the days of 0, 2, 4, 7, and 14. The corresponding echogenicity increased on the 2nd, 4th, and 7th day, and subsequently declined to basal levels after the 14th day. An increase of cell death was identified by the positive staining of deoxynucleotidyl transferase dUTP nick end-labeling (TUNEL) assay and was consistent with ultrasound measurements. The increases of both COX-2 and Leukotriene B4 receptor 1 (BLT1, 5-LO-relative receptor), which are regulators for tissue inflammation, in the immunohistochemistry staining revealed their involvement in bone fracture injury. Monitoring the inflammatory response to various non-steroidal anti-inflammatory drugs (NSAIDs) treatments was investigated by treating injured mice with a daily oral intake of aspirin (Asp), indomethacin (IND), and a selective COX-2 inhibitor (SC-236). The Asp treatment significantly reduced fracture-increased echogenicity (hyperechogenicity, p<0.05) in ultrasound images as well as inhibited cell death, and expression of COX-2 and BLT1. In contrast, treatment with IND or SC-236 did not reduce the hyperechogenicity, as confirmed by cell death (TUNEL) and expression levels of COX-2 or BLT1. Taken together, the current study reports the feasibility of a non-invasive ultrasound method capable of monitoring post-fracture tissue inflammation that positively correlates with histological findings. Results of this study also suggest that this approach may be further applied to elucidate the underlying mechanisms of inflammatory processes and to develop therapeutic strategies for facilitating fracture healing.


Scattering by a rigid sphere of audio sound generated by a parametric array loudspeaker.
This work investigates the scattering by a rigid sphere of audio sound generated by a parametric array loudspeaker (pal). A computationally efficient method utilizing a spherical harmonic expansion is developed to calculate the quasilinear solution of audio sound fields based on both Kuznetsov and Westervelt equations. The accuracy of using the Westervelt equation is examined, and the rigid sphere scattering effects are simulated with the proposed method. It is found the results obtained using the Westervelt equation are inaccurate near the sphere at low frequencies. Contrary to conventional loudspeakers, the directivity of the audio sound generated by a pal severely deteriorates behind a sphere, as the ultrasounds maintaining the directivity of the audio sound are almost completely blocked by the sphere. Instead, the ultrasounds are reflected and generate audio sound on the front side of the sphere. It means that a listener in front of the pal will hear the audio sound scattered back after introducing the sphere as if it is reflected by the sphere. The experiment results are also presented to validate the numerical results.


Children as passengers in automobiles: the neglected minority on the nation's highways.
The federal government is urging states to enact legislation requiring that safety belts be worn. Small children are excluded from this requirement. Following the neonatal period, the motor vehicle poses the greatest single threat to a child's life. Contrary to popular belief, more small children are killed and injured inside the vehicle than outside. The marjority of children now ride in cars unprotected or inadequately protected. Standard safety belts are unsuitable for small children. Special devices capable of distributing collision forces over a large body area should be used. Original children's car "safety" seats were not intended to protect their occupants in a crash. These seats became subject to a government safety standard in April 1971. Shortly after this standard came into effect it was shown to be grossly inadequate in ensuring crash protection. A proposal for revising current safety criteria was issued in March 1974--to be implemented in September 1975. A number of progressive companies have developed crashworthy devices. As public awareness is being awakened, manufacturers are begining to find that "safety" sells. Child crash protection has not escaped the attention of safety experts whose writings are reviewed, but it is shown that lack of parent awareness and concern can be directly related to sparse and often inaccurate and incomplete information available. Many popular child care books ignore the subject entirely. Because correct use of devices is of such critical importance, instructions detailing what parents must do should be prominently displayed on a permanent label attached to the device. Observation of car seats in use confirms that correct installation of the device itself and/or proper securement of the child within the device in the exception rather than the rule. The development of child restraints is of recent date. It is essential to keep abreast of advances made in the field. Earlier recommendations may be superseded by more recent research findings. It has been found that parents are most receptive to new ideas prior to and immediately following the birth of a new baby. In-hospital instruction of expectant and new parents is showing promising results. There is an urgent need for pediatricians to become involved in this vital area of "preventive medicine".


A bioethics for all seasons.
The last four decades have seen the emergence and flourishing of the field of bioethics and its incorporation into wide-ranging aspects of society, from the clinic or laboratory through to public policy and the media. Yet considerable debate still exists over what bioethics is and how it should be done. In this paper I consider the question of what makes good bioethics. Drawing on historical and contemporary examples, I suggest that bioethics encompasses multiple modes of responding to moral disagreement, and that an awareness of which mode is operational in a given context is essential to doing good bioethics.


Ethics manual: fifth edition.
Medicine, law, and social values are not static. Reexamining the ethical tenets of medical practice and their application in new circumstances is a necessary exercise. The fifth edition of the College's Ethics Manual covers emerging issues in medical ethics and revisits old ones. It reflects on many of the ethical tensions faced by internists and their patients and attempts to shed light on how existing principles extend to emerging concerns. In addition, by reiterating ethical principles that have provided guidance in resolving past ethical problems, the Manual may help physicians avert future problems. The Manual is not a substitute for the experience and integrity of individual physicians, but it may serve as a reminder of the shared obligations and duties of the medical profession.


The Effect of Salt Space on Clinical Findings and Peak Expiratory Flow in Children with Mild to Moderate Asthma: A Randomized Crossover Trial.
The asthma treatment and control might be associated with significant burden on family and community' thus exploring other therapeutic plans could be desirable. The aim of this study was to investigate the effect of salt space on clinical findings and peak expiratory flow rate among children with asthma. In this randomized crossover trial, 34 patients aged 6-14 years old with mild to moderate asthma were selected and randomly divided into two groups. The first group went through a period of salt therapy by staying in the salt room for one hour, three times a week for 3 consecutive weeks and then was under observation for three weeks. This process was reversed for the second group (three weeks under observation followed by salt therapy). The wash-out period was one week. During the study, the morning and evening peak expiratory flow (PEF), the frequency of coughing, wheezing, dyspnea and use of rescue medications were measured. Salt therapy had a significant effect on raising the morning and evening PEF in the second week in both groups (p=0.028 and p=0.032, respectively). However, there was no significant effect on PEF variabilities' cough' wheezing, dyspnea, and the frequency of rescue medication (p>0.05). No side effect was observed during salt therapy. This study showed the significant effect of salt therapy on PEF rate of the patients in the second week. However, further studies with different frequency and time of salt therapy on respiratory disorders are recommended.


Intraperitoneal chemotherapy in a pregnant woman with ovarian cancer.
Ovarian cancer diagnosed in pregnancy is rare. There is limited evidence to guide the choice of optimal chemotherapeutic management for treatment of disease during pregnancy. A 36-year-old primigravid woman was diagnosed with stage IIB grade III serous adenocarcinoma at 12 weeks of gestation. After extensive counseling, she opted for intraperitoneal chemotherapy. She received four cycles during the course of the pregnancy, and treatment was complicated by thrombocytopenia and mild preeclampsia. Delivery occurred by cesarean at 37 weeks of gestation, resulting in the birth of a live male neonate weighing 4 pounds 11 ounces with bilateral congenital talipes equinovarus. Pregnant women with ovarian cancer should be offered the opportunity to maximize their survival, including standard chemotherapeutic regimens used in nonpregnant patients.


Frameshift mutagenesis induced in Escherichia coli after in vitro treatment of double-stranded DNA with methylene blue plus white light: evidence for the involvement of lesion(s) other than 8-oxo-7,8-dihydro-2'-deoxyguanosine.
By means of specific mutation assays, we show here that in vitro treatment of double-stranded plasmid DNA with methylene blue and white light efficiently promotes frameshift mutagenesis in Escherichia coli. The assays detect either -1 or -2 frameshift mutations within previously characterized hot spot sequences for frameshift mutagenesis induced by the chemical carcinogen N-2-acetylaminofluorene, namely, short runs of contiguous guanines and alternating GpC sequences, respectively. The SOS and umuDC dependences of these mutagenic processes have been investigated. Both -1 and -2 frameshift mutagenesis are increased when the host SOS functions are induced. However, and although functional UmuDC proteins are required for maximal mutation induction, the inducibility of both -1 and -2 frameshift mutagenesis is partially independent upon the integrity of the umuDC operon. In addition, results obtained using plasmids with a site specifically located 7,8-dihydro-8-oxo-2'-deoxyguanosine (8-oxo-dGuo) residue show that this lesion, the major methylene blue plus light induced lesion characterized so far, is inefficient in promoting frameshift mutagenesis. Together, these results led us to conclude that methylene blue plus light treatment of DNA induces, at relatively high rates, lesion(s) other than 8-oxo-dGuo, that efficiently promote(s) frameshift mutagenesis in E. coli.


Acquired hepatocerebral degeneration and hepatic encephalopathy: correlations and variety of clinical presentations in overt and subclinical liver disease.
Acquired hepatocerebral degeneration (AHD) and hepatolenticular degeneration can have similar clinical presentations, but when a chronic liver disease and atypical motor findings coexist, the distinction between AHD and hepatic encephalopathy (HE) can be even more complicated. We describe three cases of AHD (two having HE) with different neuroimaging findings, distinct hepatic diseases and similar motor presentations, all presenting chronic arterial hypertension and weight loss before the disease manifestations. The diagnosis and physiopathology are commented upon and compared with previous reports. In conclusion, there are many correlations among HE, hepatolenticular degeneration and AHD, but the overlapping of AHD and HE could be more common depending on the clinical knowledge and diagnostic criteria adopted for each condition. Since AHD is not considered a priority that affects the liver transplant list, the prognosis in AHD patients remains poor, and flow interruption in portosystemic shunts must always be taken into account.


Virtual Reality Training With Three-Dimensional Video Games Improves Postural Balance and Lower Extremity Strength in Community-Dwelling Older Adults.
Avatar-based three-dimensional technology is a new approach to improve physical function in older adults. The aim of this study was to use three-dimensional video gaming technology in virtual reality training to improve postural balance and lower extremity strength in a population of community-dwelling older adults. The experimental group participated in the virtual reality training program for 60 min, twice a week, for 6 weeks. Both experimental and control groups were given three times for falls prevention education at the first, third, and fifth weeks. The experimental group showed significant improvements not only in static and dynamic postural balance but also lower extremity strength (p < .05). Furthermore, the experimental group was improved to overall parameters compared with the control group (p < .05). Therefore, three-dimensional video gaming technology might be beneficial for improving postural balance and lower extremity strength in community-dwelling older adults.


Hepatic leiomyosarcoma.
A case of hepatic leiomyosarcoma is reported and the literature on smooth muscle tumors of the liver is reviewed. All 15 patients with hepatic leiomyosarcoma presented initially with hepatic or abdominal mass. About half of these patients also had abdominal pain or weight loss or both. Elevated levels of serum alkaline phosphatase, SGOT, and lactic dehydrogenase were frequent but inconsistent findings. The prognoses appeared grave, but potentially curable. All but four patients died in less than 3 years. One patient was not followed. The three patients who were alive in follow-ups survived 8 months, 1 year, and 6.5 years, respectively, with no evidence of disease. All three surviving patients had resectable tumor and were surgically treated.


Swine industry stakeholders' perception on the use of water-based foam as an emergency mass depopulation method.
The U.S. pork supply chain is vulnerable to various internal and external threats and in need of prompt, comprehensive response plans. Under urgent circumstances, for example in the case of foreign disease incursions, swine farms will have to perform on-farm animal depopulation to prevent disease spread. Several animal depopulation methods including water-based foam (WBF) have been proposed and are under evaluation for feasibility in the field. However, the psychological/emotional impacts of applying depopulation methods for personnel managing and carrying on the tasks are not currently well understood. Thus, this study aimed to investigate WBF as an alternative for depopulation compared to existing methods approved by the American Veterinary Medical Association. Swine industry stakeholders were invited to voluntarily observe a WBF depopulation trial and to provide their self-reported perspectives before and after the observation. A survey was designed to explore key areas on expected and perceived method effectiveness, efficiency, and animal welfare considerations, as well as to evaluate short-term post-observation psychological impacts. Among 42 recruited stakeholders, 31.0% (13/42) were educators/researchers followed by animal health officials (26.2%, 11/42) and veterinarians (23.8%, 10/42), with an average of 11.7 ± 12.6 (n = 39) years of work experience. After the trial, respondents' positive perception of WBF depopulation increased specifically regarding the animal loading process being less stressful than restrained in-barn depopulation options (P = 0.003) and by the observation of fewer swine escape attempts and vocalizations than expected (P < 0.001). Respondents' positive perception of WBF also increased regarding to the time required to fill the trailer with foam, to stop hearing animal vocalization, and stop hearing animal movement, as the observed trial times were faster than their pre-observation estimates (P < 0.001). Additionally, 79.5% (31/39) of respondents agreed that the rapid destruction of animal populations had priority over animal welfare under urgent scenarios. Minor post-traumatic stress disorder-like (PTSD-like) symptoms from the observed trials were reported (26.7%, 4/15 respondents) one month after the observation. This study showed that the WBF depopulation process was perceived positively by swine stakeholders and may have limited short-term psychological impacts on personnel involved in animal depopulation.


Rates and determinants of seasonal influenza vaccination in pregnancy and association with neonatal outcomes.
There is growing evidence that seasonal influenza vaccination in pregnancy has benefits for mother and baby. We determined influenza vaccination rates among pregnant women during the 2 nonpandemic influenza seasons following the 2009 H1N1 pandemic, explored maternal factors as predictors of influenza vaccination status and evaluated the association between maternal influenza vaccination and neonatal outcomes. We used a population-based perinatal database in the province of Nova Scotia, Canada, to examine maternal vaccination rates, determinants of vaccination status and neonatal outcomes. Our cohort included women who gave birth between Nov. 1, 2010, and Mar. 31, 2012. We compared neonatal outcomes between vaccinated and unvaccinated women using logistic regression analysis. Overall, 1958 (16.0%) of 12,223 women in our cohort received the influenza vaccine during their pregnancy. Marital status, parity, location of residence (rural v. urban), smoking during pregnancy and maternal influenza risk status were determinants of maternal vaccine receipt. The odds of preterm birth was lower among infants of vaccinated women than among those of nonvaccinated women (adjusted odds ratio [OR] 0.75, 95% confidence interval [CI] 0.60-0.94). The rate of low-birth-weight infants was also lower among vaccinated women (adjusted OR 0.73, 95% CI 0.56-0.95). Despite current guidelines advising all pregnant women to receive the seasonal influenza vaccine, influenza vaccination rates among pregnant women in our cohort were low in the aftermath of the 2009 H1N1 pandemic. This study and others have shown an association between maternal influenza vaccination and improved neonatal outcomes, which supports stronger initiatives to promote vaccination during pregnancy.