Systemic therapies for psoriasis: understanding current and newly emerging therapies.
The treatment of moderate to severe psoriasis is a rapidly expanding area. Recent insights into the pathogenesis of this disease as a T-cell mediated process has led to a greater understanding of the mechanisms of action of conventional FDA-approved systemic therapies such as methotrexate, cyclosporine, acitretin, and psoralen with ultraviolet A phototherapy. It has also led to the development of rationally targeted therapies against key components of the immune process critical in the generation of the psoriatic plaque. Safety and efficacy data from clinical studies of 4 biologic agents furthest along in their development are reviewed. These results are promising, adding to the armamentarium for treating this disease.


Pulsatile distention of the nondiseased and stenotic aortic valve annulus: analysis with electrocardiogram-gated computed tomography.
Knowledge of the dynamic changes of the aortic valve (AV) annulus may aid in the sizing and design of transcatheter valve prostheses. We assessed AV annulus distention in patients without AV disease and with severe AV stenosis (AS) using computed tomography (CT). Electrocardiogram-gated multislice CT scans of 15 patients without AV disease (age 53±12 years) and 20 patients with severe AS (age 81±6 years) were analyzed. Images in plane with the AV annulus were reconstructed for every 10% to 12.5% of the cardiac cycle. With the use of dedicated software the annulus was segmented. In all phases of the cardiac cycle the area was measured, as were the maximum radius (Rmax) and minimum radius (Rmin) of an ellipse fitted around the segmented lumen. The asymmetry ratio was defined as Rmax/Rmin. Direct comparison of both groups was not possible because age and scan protocols were confounding factors. The mean change of the area, Rmax, and Rmin was 122±33 mm2, 1.8±0.7 mm, and 2.4±0.5 mm in the patients with nondiseased annulus and 98±52 mm2, 1.4±0.7 mm, and 1.9±0.8 mm in those with AS. The mean asymmetry ratio was 1.3±0.1, indicating an elliptic annulus. Both the asymmetry ratio and the area changed significantly over the cardiac cycle (p<0.001). With the use of CT and postprocessing software, significant area and radius changes during the cardiac cycle were demonstrated in both the nondiseased annulus and the stenotic annulus. This finding may help selection of the optimal size in patients undergoing AV implantation and also aid in prosthesis design.


Complications of macular hole surgery.
Macular hole is a serious vision-threatening disease for which, until the early 1990s, no effective treatment was available. However, with advanced techniques in microsurgical vitrectomy surgery, effective and successful closure of macular holes now can be obtained. Many complications can occur after any ocular surgery. Some of the specific complications associated with macular hole surgery are RPE alterations, retinal detachments, CME, subretinal neovascular membrane, endophthalmitis, hypopyon, late re-opening of macular holes, increased intraocular pressure, visual field defects, and cataract formation. Because macular hole surgery is a relatively recent operation devised in the last 8 years, data on complications still are being compiled and studied to understand and minimize the rates of complications after such surgery. We hope that, in the future, the rate of complications after macular hole surgery will be no higher than that for any other ophthalmic procedure.


Padel an increasing cause of sport-related eye injuries in Sweden.
The objective of this study was to determine the current Swedish epidemiology of sport-related eye injuries and to analyse the effect of the increased popularity of the racquet sport padel. This was a retrospective, register-based, cohort study of medical records in the county of Jönköping, Sweden. All individuals with a sports-related eye injury needing healthcare between January 2017 and December 2021 were included. For these individuals, data about background, consequences and treatment of the injuries were obtained. During the 5-year study period, 255 patients sought care for sports-related eye injuries at the ophthalmological clinics in Jönköping County. Floorball caused the largest proportion of eye injuries (39%) followed by padel (20%) and football (15%). However, the proportion of injuries caused by padel increased during the study period to be the dominating cause in 2021. Compared to floorball, patients with eye injuries from padel were older and had female gender to a higher extent. The ball caused almost all injuries from padel; the majority occurred in the right eye. Most the eye injuries from padel were mild or moderate but 4% had severe consequences with an imminent risk of long-term complications. In a short time period, padel has become the leading cause of sports-related eye injuries in Sweden. To reduce the number of eye injuries, protective eyewear could be recommended.


In situ Synthesis of Biomimetic Silica Nanofibrous Aerogels with Temperature-Invariant Superelasticity over One Million Compressions.
Resilient and compressible three-dimensional nanomaterials comprising polymers, carbon, and metals have been prepared in diverse forms. However, the creation of thermostable elastic ceramic aerogels remains an enormous challenge. We demonstrate an in situ synthesis strategy to develop biomimetic silica nanofibrous (SNF) aerogels with superelasticity by integrating flexible electrospun silica nanofibers and rubber-like Si-O-Si bonding networks. The stable bonding structure among nanofibers is in situ constructed along with a fibrous freeze-shaping process. The resultant SNF aerogels exhibit integrated properties of ultralow density (>0.25 mg cm-3 ), temperature-invariant superelasticity up to 1100 °C, and robust fatigue resistance over one million compressions. The ceramic nature also endows the aerogels with fire resistance and ultralow thermal conductivity. The successful synthesis of the SNF aerogels opens new pathways for the design of superelastic ceramic aerogels in a structurally adaptive and scalable form.


Exact analytic solutions for a Dirac electron moving in graphene under magnetic fields.
Exact analytical solutions for the bound states of a graphene Dirac electron in various magnetic fields with translational symmetry are obtained. In order to solve the time-independent Dirac-Weyl equation the factorization method used in supersymmetric quantum mechanics is adapted to this problem. The behavior of the discrete spectrum, probability and current densities are discussed.


Non discrimination on the basis of disability in air travel. Final rule.
The Department of Transportation (DOT or Department) is amending its rules implementing the Air Carrier Access Act of 1986 (ACAA) and section 504 of the Rehabilitation Act of 1973 to require airports and air carriers to provide boarding assistance to individuals with disabilities by using ramps, mechanical lifts, or other suitable devices where level-entry boarding by loading bridge or mobile lounge is not available on any aircraft with a seating capacity of 31 or more passengers. This final rule parallels the 1996 final rule for aircraft with a seating capacity of 19 through 30 passengers


Metal-based nanotoxicity and detoxification pathways in higher plants.
The potential risks from metal-based nanoparticles (NPs) in the environment have increased with the rapidly rising demand for and use of nanoenabled consumer products. Plant's central roles in ecosystem function and food chain integrity ensure intimate contact with water and soil systems, both of which are considered sinks for NPs accumulation. In this review, we document phytotoxicity caused by metal-based NPs exposure at physiological, biochemical, and molecular levels. Although the exact mechanisms of plant defense against nanotoxicity are unclear, several relevant studies have been recently published. Possible detoxification pathways that might enable plant resistance to oxidative stress and facilitate NPs detoxification are reviewed herein. Given the importance of understanding the effects and implications of metal-based NPs on plants, future research should focus on the following: (1) addressing key knowledge gaps in understanding molecular and biochemical responses of plants to NPs stress through global transcriptome, proteome, and metablome assays; (2) designing long-term experiments under field conditions at realistic exposure concentrations to investigate the impact of metal-based NPs on edible crops and the resulting implications to the food chain and to human health; and (3) establishing an impact assessment to evaluate the effects of metal-based NPs on plants with regard to ecosystem structure and function.


[The "Écoute Défense" helpline, a new care tool within the military health service].
The "Écoute Défense" helpline was launched on 23rd January 2013. This freephone number, available 24/7, is aimed at soldiers, former soldiers and their families. The main objective of the service is to listen, provide information and guide those suffering from psychological traumas which have arisen during service. Carried out by clinical psychologists from the military health service, the mission raises discussion around the challenges of this new channel for accessing care for soldiers.


Follicular Bronchiolitis: Two Cases with Varying Clinical and Radiological Presentation.
Follicular bronchiolitis (FB) is a rare bronchiolar disorder associated with hyperplasia of the bronchial-associated lymphoid tissue (BALT). It is characterized by the development of lymphoid follicles with germinal centers in the walls of small airways. It falls under the category of lymphoproliferative pulmonary diseases (LPDs) and commonly occurs in relation to connective tissue disease, immunodeficiency, infections, interstitial lung disease (ILD), and inflammatory airway diseases. Computerized tomography (CT) findings include centrilobular nodules with patchy ground glass infiltrate, tree-in-bud findings, and air trapping. It can very rarely present as diffuse cystic lung disease. We present two cases of FB. The first case is associated with Human Immunodeficiency Virus (HIV) infection and asthma with diffuse cystic changes on the CT. The second case is associated with reactive airway disease and gastroesophageal reflux disease (GERD) with the classic centrilobular nodules and ground glass opacities on the CT.


Structure and dynamics of the human pleckstrin DEP domain: distinct molecular features of a novel DEP domain subfamily.
Pleckstrin1 is a major substrate for protein kinase C in platelets and leukocytes, and comprises a central DEP (disheveled, Egl-10, pleckstrin) domain, which is flanked by two PH (pleckstrin homology) domains. DEP domains display a unique alpha/beta fold and have been implicated in membrane binding utilizing different mechanisms. Using multiple sequence alignments and phylogenetic tree reconstructions, we find that 6 subfamilies of the DEP domain exist, of which pleckstrin represents a novel and distinct subfamily. To clarify structural determinants of the DEP fold and to gain further insight into the role of the DEP domain, we determined the three-dimensional structure of the pleckstrin DEP domain using heteronuclear NMR spectroscopy. Pleckstrin DEP shares main structural features with the DEP domains of disheveled and Epac, which belong to different DEP subfamilies. However, the pleckstrin DEP fold is distinct from these structures and contains an additional, short helix alpha4 inserted in the beta4-beta5 loop that exhibits increased backbone mobility as judged by NMR relaxation measurements. Based on sequence conservation, the helix alpha4 may also be present in the DEP domains of regulator of G-protein signaling (RGS) proteins, which are members of the same DEP subfamily. In pleckstrin, the DEP domain is surrounded by two PH domains. Structural analysis and charge complementarity suggest that the DEP domain may interact with the N-terminal PH domain in pleckstrin. Phosphorylation of the PH-DEP linker, which is required for pleckstrin function, could regulate such an intramolecular interaction. This suggests a role of the pleckstrin DEP domain in intramolecular domain interactions, which is distinct from the functions of other DEP domain subfamilies found so far.


Measuring single-cell density.
We have used a microfluidic mass sensor to measure the density of single living cells. By weighing each cell in two fluids of different densities, our technique measures the single-cell mass, volume, and density of approximately 500 cells per hour with a density precision of 0.001 g mL(-1). We observe that the intrinsic cell-to-cell variation in density is nearly 100-fold smaller than the mass or volume variation. As a result, we can measure changes in cell density indicative of cellular processes that would be otherwise undetectable by mass or volume measurements. Here, we demonstrate this with four examples: identifying Plasmodium falciparum malaria-infected erythrocytes in a culture, distinguishing transfused blood cells from a patient's own blood, identifying irreversibly sickled cells in a sickle cell patient, and identifying leukemia cells in the early stages of responding to a drug treatment. These demonstrations suggest that the ability to measure single-cell density will provide valuable insights into cell state for a wide range of biological processes.


Mechanistic studies on the addition of dihydrogen to tantalocene complexes.
The mechanism of dihydrogen addition to Cp(2)Ta(CH(2))(H) was examined using parahydrogen-induced polarization (PHIP), (13)C labeling, and comparison to the related complex Cp(2)Ta(CH(2))(CH(3)). The reaction of para-enriched hydrogen with Cp(2)Ta(CH(2))(H) leads to polarized resonances for both Cp(2)Ta(CH(3))(H)(2) and Cp(2)TaH(3), even at the earliest reaction times. Use of the labeled compound Cp(2)Ta((13)CH(2))(H) shows that the polarized resonances of Cp(2)Ta(CH(3))(H)(2) correspond to the two hydride ligands. The results thus support a mechanistic pathway of H(2) addition to an unsaturated Ta(III) intermediate, [Cp(2)Ta(CH(3))], rather than addition directly across the Ta=C bond. In a same sample comparison, the rates of initial H(2) addition and subsequent C-H reductive elimination for both Cp(2)Ta(CH(2))(H) and Cp(2)Ta(C(6)H(4))(H) were examined. The methylene complex exhibits greater reactivity than the benzyne complex, with the major difference due to the C-H coupling step, in which formation of methane is more facile than that of benzene. The reactivity of the related ethylene hydride complex, Cp(2)Ta(C(2)H(4))(H), with hydrogen was also examined. The PHIP study of this system leads to unusual and unexpected polarization, which is found to be due to a minor impurity in the sample.


Surviving in the Electronic Era: My Top EMR Hacks.
With many pediatric orthopaedic surgeons spending 3 or even more days a week in clinic, a thorough understanding of the ever-changing electronic medical record is paramount to providing excellent clinical care, overall job satisfaction, and minimizing clinician burnout. Here we provide 5 tips to optimize clinic workflow for the busy pediatric orthopaedic surgeon in the electronic medical record era.


[Diversity of soil archaea in Tibetan Mila Mountains].
In order to study the diversity of archaea and ammonia-oxidizing archaea (AOA) of the alp prairie soil in Mila Mountain of Tibet. Total microbial DNA was directly extracted from the alp prairie of Mila Mountain. The clone library of 16S rRNA genes and amoA genes were amplified by PCR with universal primer sets. The sequences of archaea and AOA were defined into operational taxonomic units (OTUs) according to the 97% similarity threshold for OTU assignment was performed using the software program DOTUR. Phylogenetic analysis revealed archaea in the soil of Mila Mountain including the Crenarchaeota (71.7%) and unclassified-Archaea (28.3%) phyla. All the Crenarchaeota belong to the Thermoprotei. Phylogenetic analysis revealed AOA in the alp prairie soil of Mila Mountain belonged to the kingdom Crenarchaeota. Archaea and AOA species composition from Mila Mountain included 64 OTUs and 75 OTUs. These findings show prolific archaeal diversity in the alp prairie soil of Mila Mountain, where they may be actively involved in nitrification.


The society of genes: networks of functional links between genes from comparative genomics.
Comparative genomics provides at least three methods beyond traditional sequence similarity for identifying functional links between genes: the examination of common phylogenetic distributions, the analysis of conserved proximity along the chromosomes of multiple genomes, and observations of fusions of genes into a multidomain gene in another organism. We have previously generated the links according to each of these methods individually for 43 known microbial genomes. Here we combine these results to construct networks of functional associations. We show that the functional networks obtained by applying these methods have different topologies and that the information they provide is largely additive. In particular, the combined networks of functional links contain an average of 57% of an organism's complete genetic complement, uncover substantial portions of known pathways, and suggest the function of previously unannotated genes. In addition, the combined networks are qualitatively different from the networks obtained using individual methods. They have a dominant cluster that contains approximately 80%-90% of the genes, independent of genome size, and the dominant clusters show the small world behavior expected of a biological system, with global connectivity that is nearly random, and local properties that are highly ordered. When the information on functional linkage provided by three emerging computational methods is combined, the integrated network uncovers large numbers of conserved pathways and identifies clusters of functionally related genes. It therefore shows considerable utility and promise as a tool for understanding genomic structure, and for guiding high throughput experimental investigations.


Ultrafine particle deposition and clearance in the healthy and obstructed lung.
Numerous epidemiologic studies have shown associations between exposure to particulate air pollution and acute increases in morbidity and mortality, particularly in persons with chronic obstructive pulmonary disease. The dosimetry of ultrafine particles in the human lung is poorly characterized. We studied the deposition and clearance of an ultrafine technetium-99m-labeled aerosol in 10 patients with chronic obstructive pulmonary disease and in 9 healthy subjects. Particle retention was followed for 2 hours after inhalation and again at 24 hours by gamma scintigraphy. Central-to-peripheral ratios indexed airway deposition. Particle accumulation in the liver was examined by quantifying activity below the right lung. The dose rate for an aerosol exposure of 10 micro g/m(3) was calculated. Patients had a significantly greater dose rate than healthy subjects (2.9 +/- 1.0 versus 1.9 +/- 0.4 micro g/h, p = 0.02). Central-to-peripheral ratios were slightly greater in patients than in healthy subjects (1.11 +/- 0.10 versus 1.01 +/- 0.11, p = 0.05). Clearance did not statistically differ between health and disease. On average, 24-hour retention was 85 +/- 8% (corrected for isotope dissolution). No accumulation in the liver's vicinity was observed. Data suggest that relative to healthy subjects, patients with moderate-to-severe airways obstruction receive an increased dose from ultrafine particle exposure.


Evaluation of atropine in acute pancreatitis.
A prospective randomized clinical trial was carried out to evaluate the efficacy of atropine in the treatment of acute pancreatitis. Fifty-one patients with elevated amylase levels, and with the clinical signs and symptoms of acute pancreatitis, were included in the study. All were treated with fluids intravenously and analgesics, and a nasogastric tube if needed. In addition, on a random basis, 19 were given atropine intramuscularly and 32 were not. The clinical courses of the two groups of patients did not differ significantly.


Malignant melanoma in Taiwan: a prognostic study of 181 cases.
This study was performed to determine the characteristics and clinical outcome of patients with cutaneous malignant melanoma in Taiwan. The medical records of patients with primary cutaneous melanoma between 1992 and 2001 at Chang Gung Memorial Hospital (CGMH) were retrieved from the cancer registry. Survival was analysed by the Kaplan-Meier method. Univariate and multivariate analyses of factors associated with survival were performed using the Cox proportional hazard model. One hundred and eighty-one cases were retrieved from the cancer registry of CGMH. The male to female ratio was 1 : 1.13. The most common age of onset was the sixth decade. The median age of onset was 61 years (2-95 years). There were 105 cases (58%) of acral lentiginous melanoma (ALM), 55 cases (30.4%) of nodular melanoma (NM), 19 cases (10.5%) of superficial spreading melanoma (SSM) and two cases (1.1%) of lentigo maligna melanoma. The median survival of the 181 patients was 3.71 years, and the 5-year survival rate was 45.63%. Five-year survival rates of patients with stages I, II, III and IV disease were 84.39%, 56.03%, 34.7% and 0%, respectively. Sex, Breslow thickness, Clark's level, pathological type and age were significant prognostic factors. There were no survival differences between ALM and NM. Both ALM and NM were associated with a poor prognosis when compared with SSM. In conclusion, ALM is the most common type of cutaneous malignant melanoma in Taiwan. The prognostic factors in Taiwan are similar to those in melanoma-prevalent countries.


Para-hydrogen induced polarization of amino acids, peptides and deuterium-hydrogen gas.
Signal Amplification by Reversible-Exchange (SABRE) is a method of hyperpolarizing substrates by polarization transfer from para-hydrogen without hydrogenation. Here, we demonstrate that this method can be applied to hyperpolarize small amounts of all proteinogenic amino acids and some chosen peptides down to the nanomole regime and can be detected in a single scan in low-magnetic fields down to 0.25 mT (10 kHz proton frequency). An outstanding feature is that depending on the chemical state of the used catalyst and the investigated amino acid or peptide, hyperpolarized hydrogen-deuterium gas is formed, which was detected with (1)H and (2)H NMR spectroscopy at low magnetic fields of B(0) = 3.9 mT (166 kHz proton frequency) and 3.2 mT (20 kHz deuterium frequency).


Association Between Cannabis and Violence in Community-Dwelling Patients With Severe Mental Disorders: A Cross-sectional Study Using Machine Learning.
The objective of this cross-sectional study was to identify cannabis-related features and other characteristics predictive of violence using a data-driven approach in patients with severe mental disorders (SMDs). A Least Absolute Shrinkage and Selection Operator regularization regression model was used on the database consisting of 97 patients with SMD who completed questionnaires measuring substance use and violence. Cannabis use, particularly related to patients' decision to consume or time spent using, was a key predictor associated with violence. Other patterns of substance use and personality traits were identified as strong predictors. Regular patterns of cannabis use and interpersonal issues related to cannabis/stimulant abuse were inversely correlated to violence. This study identified the effect of several predictors correlated to violence in patients with SMD using a regularization regression model. Findings open the door to better identify the profiles of patients that may be more susceptible to perpetrate violent behaviors.


Immune checkpoint inhibitors and tyrosine kinase inhibitors in patients with advanced hepatocellular carcinoma: Does the sequence matter?
Combination therapy with immune checkpoint inhibitor (ICI) and antivascular endothelial growth factor (anti-VEGF) is currently the first line treatment for advanced hepatocellular carcinoma (aHCC). However, there are many patients who may not be able to receive combination therapy due to underlying comorbidities or resource limitations. For these patients, systemic treatment options include single agent tyrosine kinase inhibitors (TKIs) or ICI monotherapy. However, whether an optimal sequence of systemic therapy exists remains unknown. We aim to explore the impact of sequencing of TKI and ICI therapy in terms of response rates and to examine the safety of their use in sequential order. Patients with aHCC treated with both ICI and TKI between December 30, 2013 and June 13, 2018 were retrospectively identified. Patients were classified into two groups: those who received TKI in the first-line (TKI1), followed by ICI (ICI2) and those who received ICI (ICI1) in the first-line followed by TKI (TKI2). The primary objective of the study was to identify differences in objective response rate (ORR) and disease control rate (DCR), as evaluated based on response evaluation criteria in solid tumor v1.1 for TKI1, TKI2, ICI1, and ICI2. Secondary objectives included comparison of progression free survival (PFS) for each line of therapy, overall survival (OS) and adverse events (AEs). Twenty-seven and 23 patients were classified into group 1 and 2, respectively. Objective response rates of TKI1 and TKI2 were 3.8% and 17.6%, respectively (p = .28); DCR to TKI1 versus TKI2 was 23.1% versus 35.3% (p = .49). ORRs of ICI1 and ICI2 were 8.7% and 14.3%, respectively (p = .66); DCR to ICI2 versus ICI1 was 56.5% versus 42.9% (p = .37). Median PFS was not significant between TKI1 and TKI2 (PFS 3.06 versus 1.61 months, p = .097) as well as between ICI2 and ICI1 (PFS 1.84 versus 2.37 month, p = .32). Median OS was also not significantly different between both groups (OS 20.63 versus 13.93 months, p = .20) on univariable and multivariable analysis (OS adjusted hazard ratio [HR] 2.07, 95% CI .83-5.18, p = .118). The proportion of patients who experienced adverse events of any grade was similar in both groups (TKI1 59.3% versus TKI2 52.2%; ICI1 78.3% versus ICI2 70.4%). Our study suggests that the sequence of TKI versus ICI therapy in patients with aHCC may not matter, given similar efficacy and toxicity profile when either agent is received in the first or second-line setting. This finding is of value in the real-world setting, where patients may be frail or have comorbidities that render them unable to tolerate combination therapy (ICI and TKI/anti-VEGF). For these patients, sequential exposure to both classes of drugs (ICI and TKI) may be a suitable option.


Home Sleep Apnea Test to Screen Patients With Atrial Fibrillation for Sleep Apnea Prior to Catheter Ablation.
Whether all atrial fibrillation (AF) patients should be evaluated for sleep apnea before catheter ablation (CA) remains controversial. Watch-type peripheral arterial tonometry (W-PAT) is a home sleep testing device and an easier tool for diagnosing sleep apnea than polysomnography. We investigated the prevalence and predictors of sleep apnea using W-PAT in unscreened sleep apnea patients with AF before CA.Methods and Results:The study was conducted under a retrospective, single-center, observational design. We included 776 consecutive patients who underwent both W-PAT and AF ablation. Sleep apnea assessments were successfully performed in 774 patients (99.7%; age 65±11 years, 73.3% male; body mass index [BMI] 24.1±3.5, 56.8% paroxysmal AF). The mean apnea-hypopnea index (AHI) was 20.1±15.6. Although 81.7% of the patients had normal Epworth sleepiness scores (mean 6.5), only 88 (11.4%) had a normal AHI (AHI <5) and 412 (53.2%) had moderate-severe sleep apnea (AHI ≥15). Obesity, male sex, nonparoxysmal AF, hypertension, and a left atrial diameter (LAd) ≥40 mm were predictors of moderate-severe sleep apnea. However, the prevalence of moderate-severe sleep apnea in patients without those predictors (i.e., non-obesity (44.2%), female sex (43.0%), paroxysmal AF (43.9%), no hypertension (45.5%)), and LAd <40 mm (41.0%) was considerably high. Almost all patients successfully underwent W-PAT to diagnose sleep apnea. Patients undergoing AF ablation had a high prevalence of sleep apnea, and screening for sleep apnea was important in those patients even if they did not have sleepiness or risk factors.


Endotracheal tube perforation of the hypopharynx.
Perforation of the hypopharynx or esophagus is a serious though not often reported complication of endotracheal intubation. Only 12 cases had been reported before the eight which are presented here to emphasize this hazard of intubation. The early symptoms of perforation, which occurred during insertion of the tube, were: subcutaneous emphysema (seven patients), mediastinal emphysema (six), pneumothorax (two), cardiac arrest (one). One patient had no recognized early signs of perforation, but presented with an abscess of the mediastinum six weeks later. The site of perforation, determined by endoscopy in six patients, was the lateral hypopharynx in four, and the vallecula in two. The outcome of the eight perforations was as follows: two patients recovered on conservative management; in two, abscesses of the neck and in one an abscess of the mediastinum developed. All three recovered after drainage of the abscesses. Three patients died. Two outstanding characteristics of these eight cases were that in all of them intubation was attempted by physicians relatively inexperienced in the technique, and in all but one it was done in emergency. Since the use of intubation in emergency situations is increasing, all physicians in training should receive formal instruction in technique.


The development of the Edinburgh modular arm system.
Modularity has not been investigated in any significant way in the development of upper-limb prostheses. The components currently available are the results of different research programmes conducted at different times by a variety of academic and commercial teams. The result is a historical hodge-podge of systems which are largely mutually exclusive in terms of compatibility. The Edinburgh work seeks to solve this problem by designing components which are neutral in structural terms so that left- and right-handed prostheses can be configured from the same basic parts. Currently, child and adult components are separate items; this does not need to be the case and the design presented here allows adult elbow parts to be used as children's shoulders. This paper will cover the rationale behind the design values and the technical aspects of the development.


17 β-estradiol and 17 α-ethinylestradiol mineralization in sewage sludge and biosolids.
Natural steroid estrogens (e.g., 17 β-estradiol, E2), synthetic steroid estrogens (e.g., 17 α-ethinylestradiol, EE2) and pharmaceutical antibiotics (e.g., ciprofloxacin) are chemicals detected in biosolids and sewage sludges because they partition into the solids fraction during the wastewater treatment process. This research utilized a three-way factorial design (six media × two estrogens × three antibiotic treatments) to quantify cumulative E2 and EE2 mineralization over 133 d (MAX) in a range of sewage sludge and biosolid samples in the presence (4 and 40 mg kg(-1)) and absence of ciprofloxacin. The same three-way factorial design was utilized to quantify the impact of the six media, E2 or EE2, and ciprofloxacin on cumulative soil respiration over 133 d (RESP). Minimal ciprofloxacin mineralization was observed (<0.05% over 133 d), but despite its persistence, ciprofloxacin had no significant effect on MAX of E2 or EE2, and, in general, no significant effect on RESP. MAX ranged from 38.38% to 48.44% for E2 but from only 0.72% to 24.27% for EE2 although RESP was relatively similar, ranging from 101.00 to 866.54 mg CO2 in the presence of E2 and from 69.55 to 893.95 mg CO2 in the presence of EE2. The sorption-limited bioavailability of EE2, which is inherently resistant to biodegradation due to chemical structure, as MAX and Freundlich sorption coefficients (Kf) were negatively correlated. As such, the Kf values of EE2 were largest in composted biosolids in which EE2 was particularly resistant to microbial degradation as the MAX of EE2 was <3%. In contrast, the MAX of E2 showed a positive association with the Kf values of E2 because some steps in the E2 transformation process have been found to occur in the sorbed phase. The MAX of E2 was significantly greater in the biosolid and composted biosolid media than in any other media, whereas the MAX of E2 decreased in the following order: secondary sewage sludge > primary sewage sludge > biosolid = composted biosolid. This suggests that sewage sludges in municipal lagoons and pre-treatment holding lagoons are a more favorable media for mineralization of EE2, whereas biosolids in post-treatment storage lagoons are a more favorable media for the mineralization of E2. The presence of ciprofloxacin will have no impact on the potential E2 or EE2 mineralization rates in these cases.


Serum protein biomarkers screening in patients with ischemic stroke by LC-MS/MS.
The purpose of this study was to investigate the serum proteins biomarkers by label-free liquid chromatography coupled to tandem mass spectrometry quantification methods in the Chinese patients with acute ischemic stroke (AIS). In the study period, sera from 40 AIS patients and 40 normal cases were selected for screening study. The selected protein associations with disease risk were further evaluated by enzyme-linked immunosorbent assay (ELISA) testing of the remaining stroke cases and controls. Its value for biomarkers diagnosis was appreciated through receiver operating characteristic (ROC) curve. Patients versus control levels differences were suggested for 19 proteins (nominal P < 0.05) for stroke, with three proteins having a false discovery rate <0.05. The association of mannose-binding lectin (MBL) with stroke (P < 0.001) was confirmed using ELISA in replication studies. Based on the ROC curve, the optimal serum concentration of MBL as a surrogate marker to support the diagnosis of ischemic cerebral injury was found to be 1050 ug/L, which yielded a sensitivity of 81.8% and a specificity of 80.2%, the area under the curve was 0.812 (95% CI: 0.724-0.876). In multivariate analysis, there was an increased risk of AIS associated with MBL levels ≥1050 ug/L (OR: 4.76, 95% CI: 1.59-10.12) after adjusting for possible confounders. The discovery and replication studies presented here show MBL to be a risk marker for AIS in the Chinese population, which appears to be a novel finding.


Transcatheter aortic valve intervention in patients with cancer.
The prevalence of concurrent cancer and severe aortic stenosis (AS) is increasing due to an ageing population. In addition to shared traditional risk factors for AS and cancer, patients with cancer may be at increased risk for AS due to off-target effects of cancer-related therapy, such as mediastinal radiation therapy (XRT), as well as shared non-traditional pathophysiological mechanisms. Compared with surgical aortic valve replacement, major adverse events are generally lower in patients with cancer undergoing transcatheter aortic valve intervention (TAVI), especially in those with history of mediastinal XRT. Similar procedural and short-to-intermediate TAVI outcomes have been observed in patients with cancer as compared with no cancer, whereas long-term outcomes are dependent on cancer survival. Considerable heterogeneity exists between cancer subtypes and stage, with worse outcomes observed in those with active and advanced-stage disease as well as specific cancer subtypes. Procedural management in patients with cancer poses unique challenges and thus requires periprocedural expertise and close collaboration with the referring oncology team. The decision to ultimately pursue TAVI involves a multidisciplinary and holistic approach in assessing the appropriateness of intervention. Further clinical trial and registry studies are needed to better appreciate outcomes in this population.


[Psychological factors and male reproductive health].
Reproductive health is a focus of the 21st century medical sciences. Researches on the correlation between psychological factors and male reproductive health may help discover the rules of the development of male diseases. This paper analyzes the social root-cause of the adverse psychological factors of men, discusses how psychological factors affect male reproductive health, and proposes some remedial measures for related psychological problems.


Development of AMOEBA Polarizable Force Field for Rare-Earth La3+ Interaction with Bioinspired Ligands.
Rare-earth metals (REMs) are crucial for many important industries, such as power generation and storage, in addition to cancer treatment and medical imaging. One promising new REM refinement approach involves mimicking the highly selective and efficient binding of REMs observed in relatively recently discovered proteins. However, realizing any such bioinspired approach requires an understanding of the biological recognition mechanisms. Here, we developed a new classical polarizable force field based on the AMOEBA framework for modeling a lanthanum ion (La3+) interacting with water, acetate, and acetamide, which have been found to coordinate the ion in proteins. The parameters were derived by comparing to high-level ab initio quantum mechanical (QM) calculations that include relativistic effects. The AMOEBA model, with advanced atomic multipoles and electronic polarization, is successful in capturing both the QM distance-dependent La3+-ligand interaction energies and experimental hydration free energy. A new scheme for pairwise polarization damping (POLPAIR) was developed to describe the polarization energy in La3+ interactions with both charged and neutral ligands. Simulations of La3+ in water showed water coordination numbers and ion-water distances consistent with previous experimental and theoretical findings. Water residence time analysis revealed both fast and slow kinetics in water exchange around the ion. This new model will allow investigation of fully solvated lanthanum ion-protein systems using GPU-accelerated dynamics simulations to gain insights on binding selectivity, which may be applied to the design of synthetic analogues.


Fission-neutron-induced expression of a tumour-associated antigen in human cell hybrids (HeLa x skin fibroblasts): evidence for increased expression at low dose rate.
The induction of a tumour-associated antigen in a human cell hybrid line (HeLa x skin fibroblast) following exposure to fission neutrons of average energy 0.85 MeV (Janus reactor, Argonne National Laboratory) at two dose rates, 0.086 and 10.3 cGy/min, has been examined. The dose-response data obtained indicate the lower dose rate to be 2.9-fold more effective than the higher in inducing expression of the tumour-associated antigen, while there was no significant dose-rate effect in terms of cell killing. These results are qualitatively in agreement with previous observations using neutrons from the Janus reactor for the neoplastic transformation of C3H10T1/2 cells and Syrian hamster embryo cells.


Epidural space identification: a meta-analysis of complications after air versus liquid as the medium for loss of resistance.
The best method for identifying the epidural space for neuraxial blocks is controversial. We conducted this meta-analysis to test the hypothesis that loss of resistance with liquid reduces complications with epidural placement. The MEDLINE, EMBASE, and Cochrane databases were searched for prospective, randomized studies comparing air versus liquid as the medium for loss of resistance during epidural space identification in adults. Data were abstracted from 5 studies (4 obstetric and 1 nonobstetric) (n = 4422 patients) that met inclusion criteria and analyzed for the following 6 outcomes: difficult catheter insertion, paresthesia, intravascular catheter insertion, accidental dural puncture, postdural puncture headache, and partial block. The overall risk differences for adverse outcome between the different mediums were not statistically different for the obstetric population. A small, but statistically significant, risk difference for postdural puncture headache was observed when fluid was used during epidural placement for chronic pain management. Larger studies that overcome limitations of heterogeneity across studies and a relatively infrequent occurrence of complications are required to determine the optimal medium for loss of resistance during epidural block.


Antiproliferative and teratogenic activities of the bishemisuccinates of 7 alpha-hydroxycholesterol and 7 beta-hydroxycholesterol.
1. The bishemisuccinates of 7 alpha-hydroxycholesterol and 7 beta-hydroxycholesterol induced a dose-dependent decrease in the incorporation of [3H]thymidine into fibroblast cell line (3T3), macrophage-like cell line (P388D1) and rat hepatoma cell line (H35). Concomitantly there was a reduction in cell viability. 2. The 3T3 cells were less susceptible than P388D1 and H35 cells. 3. The aforementioned derivatives of 7 alpha-hydroxycholesterol and 7 beta-hydroxycholesterol produced malformations in cultured embryos including abnormalities in yolk sac circulation, heartbeat, body axis, otic vesicle, branchial apparatus, cranial neural tube and forelimb bud. Axial length and somite number were reduced.


Genetic susceptibility loci for Chlamydia trachomatis endometrial infection influence expression of genes involved in T cell function, tryptophan metabolism and epithelial integrity.
Identify genetic loci of enhanced susceptibility to Chlamydial trachomatis (Ct) upper genital tract infection in women. We performed an integrated analysis of DNA genotypes and blood-derived mRNA profiles from 200 Ct-exposed women to identify expression quantitative trait loci (eQTL) and determine their association with endometrial chlamydial infection using a mediation test. We further evaluated the effect of a lead eQTL on the expression of CD151 by immune cells from women with genotypes associated with low and high whole blood expression of CD151, respectively. We identified cis-eQTLs modulating mRNA expression of 81 genes (eGenes) associated with altered risk of ascending infection. In women with endometrial infection, eGenes involved in proinflammatory signaling were upregulated. Downregulated eGenes included genes involved in T cell functions pivotal for chlamydial control. eGenes encoding molecules linked to metabolism of tryptophan, an essential chlamydial nutrient, and formation of epithelial tight junctions were also downregulated in women with endometrial infection. A lead eSNP rs10902226 was identified regulating CD151, a tetrospanin molecule important for immune cell adhesion and migration and T cell proliferation. Further in vitro experiments showed that women with a CC genotype at rs10902226 had reduced rates of endometrial infection with increased CD151 expression in whole blood and T cells when compared to women with a GG genotype. We discovered genetic variants associated with altered risk for Ct ascension. A lead eSNP for CD151 is a candidate genetic marker for enhanced CD4 T cell function and reduced susceptibility.


Dehydration of UO2Cl2·3H2O and Nd(NO3)3·6H2O with a Soft Donor Ligand and Comparison of Their Interactions through X-ray Diffraction and Theoretical Investigation.
We investigated whether the relatively Lewis basic imidazole-2-thiones could be used to substitute water ligands bound to f-element cations and generate f-element soft donor complexes. Reactions of 1,3-diethylimidazole-2-thione (C2C2ImT) with Nd(NO3)3·6H2O and UO2Cl2·3H2O led to the isolation of the anhydrous thione complexes Nd(NO3)3(C2C2ImT)3 and UO2Cl2(C2C2ImT)2, characterized by single crystal X-ray diffraction. Differences in the strength of metal-thione interactions have been examined by means of the crystal structure analysis and density functional theory (DFT) calculations. The C2C2ImT ligands were found to be affected by both coordination and noncovalent interactions, making it impossible to deconvolute the effects of one from the other. Calculated partial atomic charges indicated greater ligand-to-metal charge transfer in the [UO2]2+ complex, indicative of a stronger interaction. The reactivity of C2C2ImT demonstrates its usefulness in the preparation of f-element soft donor complexes from readily available hydrates that could be useful intermediates for promoting the coordination and studying the effects of soft donor anions.


Exertional syncope and presyncope: faint signs of underlying problems.
Physicians often see patients who have syncope or presyncope, but episodes associated with exercise are uncommon. Transient syncopal episodes usually require minimal evaluation and intervention. Most cases of exercise-associated syncope have neurocardiogenic origins and are benign, but fainting may signal a potentially fatal underlying problem. More serious causes of exertional syncope include structural cardiovascular abnormalities and cardiac arrhythmias. All physicians who care for active patients should be aware of the potential seriousness of this early warning sign and evaluate patients accordingly. Familiarity with the Bethesda guidelines will help clinicians decide when it is safe for an athlete to return to play following a syncopal episode.


Neuropsychological effects among workers exposed to organic solvents.
To assess neuropsychological performance among workers at a paint factory in Mexico City. During 2004 and 2005 we assessed the neuropsychological performance of 208 workers who were exposed to organic solvents at a paint factory, mainly toluene and xylene. We categorized workers into low and high exposure groups using a cumulative index for toluene, based on times spent in different tasks. We evaluated cognitive and motor functions with 13 neuropsychological tests. We found lower attention, longer time to complete the test β=5.5 (R2=12.3%), and a lower score in the motor-cognitive test β=-15.7 (R2=19.5%) in the high exposure group through multiple linear regression model analysis, with adjustment for age and education. Our results are similar to the ones reported in the literature, but the effects are less severe, probably due to lower exposure to organic solvents.


Intimate partner violence: psycho-physio-pathological sequelae for defining a holistic enriched treatment.
Intimate partner violence (IPV) is a health priority, which worldwide, mainly affects women. The consequences of IPV include several psychophysiological effects. These range from altered levels of hormones and neurotrophins to difficulties in emotion regulation and cognitive impairment. Mounting evidence from preclinical studies has shown that environmental enrichment, a form of sensory-motor, cognitive, and social stimulation, can induce a wide range of neuroplastic processes in the brain which consistently improve recovery from a wide variety of somatic and psychiatric diseases. To support IPV survivors, it is essential to ensure a safe housing environment, which can serve as a foundation for environmental enrichment-based interventions. However, some concerns have been raised when supportive housing interventions focus on the economic aspects of survivors' lives instead of the emotional ones. We thus propose a holistic intervention in which supportive housing is integrated with evidenced-based psychotherapies which could constitute an enriched therapeutic approach for IPV survivors.


Heat shock proteins in the human eye.
Heat shock proteins (Hsps) are believed to primarily protect and maintain cell viability under stressful conditions such as those occurring during thermal and oxidative challenges chiefly by refolding and stabilizing proteins. Hsps are found throughout the various tissues of the eye where they are thought to confer protection from disease states such as cataract, glaucoma, and cancer. This minireview summarizes the placement, properties, and roles of Hsps in the eye and aims to provide a better comprehension of their function and involvement in ocular disease pathogenesis.


[Otitis media with effusion: expectant management]
OBJECTIVE: Despite the fact that chronic otitis media with effusion (OME) is an entity with a high prevalence among children, the real effectiveness of most treatments in use nowadays has not been completely established. Based on its natural course, we defend an expectant management as the initial treatment. METHODS: We undertook a review of the available data taking into consideration the natural history, epidemiology and therapeutic options for OME. We looked for a guideline concerning the best treatment for OME in children. RESULTS: The treatment of OME still remains controversial, in spite of many therapeutic options. In children, the best management still seems to be the observation, probably for a period of three to six months. However, interventionist treatment should be done earlier on those patients considered as high risk or in which a problem happened with their development, due to hearing loss secondary to OME. CONCLUSIONS: The understanding of the several factors involved in the pathogenesis of OME, as well as of the features in its evolutive course, encourage the idea of a conservative expectant approach at first or up to the moment in which an interventionist approach (clinical or surgical) is justified.


Relationship between LDL, HDL, blood pressure and atheroma progression in the coronaries.
To highlight clinical trials that have employed coronary artery imaging to evaluate the impact of medical therapies that target established cardiovascular risk factors. High resolution imaging of the entire vessel wall permits assessment of changes in the full extent of coronary atherosclerosis. Intensive lowering of LDL cholesterol and systolic blood pressure are associated with the greatest benefit in terms of slowing disease progression. Therapeutic approaches that promote the biological activity of HDL have the potential to promote regression of atherosclerotic plaque. Targeting inflammatory cascades may also have a beneficial effect on the extent and composition of coronary plaque. Intensive modification of established risk factors has a profound impact on the natural history of atheroma progression.


Synchronization of developmental, molecular and metabolic aspects of source-sink interactions.
Plants have evolved a multitude of strategies to adjust their growth according to external and internal signals. Interconnected metabolic and phytohormonal signalling networks allow adaption to changing environmental and developmental conditions and ensure the survival of species in fluctuating environments. In agricultural ecosystems, many of these adaptive responses are not required or may even limit crop yield, as they prevent plants from realizing their fullest potential. By lifting source and sink activities to their maximum, massive yield increases can be foreseen, potentially closing the future yield gap resulting from an increasing world population and the transition to a carbon-neutral economy. To do so, a better understanding of the interplay between metabolic and developmental processes is required. In the past, these processes have been tackled independently from each other, but coordinated efforts are required to understand the fine mechanics of source-sink relations and thus optimize crop yield. Here, we describe approaches to design high-yielding crop plants utilizing strategies derived from current metabolic concepts and our understanding of the molecular processes determining sink development.


Combined effects of alcohol and caffeine on the late components of the event-related potential and on reaction time.
The effects of .7 ml/kg alcohol and 200 mg caffeine on the P200, N200, P300 and N500 difference wave components of the event-related potential and on reaction time (RT) were examined in 16 females who performed both simple and choice RT tasks. Alcohol slowed the decision time (DT) component of reaction time, lengthened the latency of the P200 and P300 components, reduced N200 amplitude, increased P300 amplitude at parietal sites, and modified the effect of sagittal site on N500 difference wave peak amplitude. Caffeine shortened DT in the choice RT task, shortened N200 latency at right hemisphere sites, and shortened N200 latency in the choice RT task in combination with alcohol compared to when alcohol was administered alone. Caffeine also increased P300 amplitude in the choice RT task and reduced the integral of the N500 difference wave at most sites when combined with alcohol. It was concluded that whereas alcohol slows attention allocation and impairs working memory, caffeine accelerated response-related decisions and enhanced cortical arousal.


The human rhinovirus internal cis-acting replication element (cre) exhibits disparate properties among serotypes.
It has been reported previously that the Human rhinovirus 14 (HRV-14) RNA genome contains a cis-acting replication element (cre) that maps to the capsid coding (P1) sequence [19]. Further characterization of the HRV-14 cre in the present study established that by moving the cre stem-loop structure downstream, adjacent to the 3'NCR, that its position is not critical for function. When the P1 sequences of two closely related serotypes of HRV-14 were analyzed for the presence of a cre, both HRV-3 and HRV-72 were found to contain similar sequence at the same positions as HRV-14. Moreover, sequence at these positions produced structures from MFOLD analysis that closely resembled the HRV-14 cre. It was also discovered that neither HRV serotypes 1a or 16 harbor replication elements that map to the P1 segments of their genomes. Computer and mutational analyses suggest that the cre in these latter HRV serotypes map instead to the 2A gene, as has been reported for HRV-2. The putative HRV-3 cre was determined to be unable to support replication when placed in an HRV-14 replicon background. Similarly, the previously identified HRV-2 cre was unable to support replication of the HRV-14 genome. This finding is in contrast to the cardiovirus cre, which has been shown to be functionally active between two members of its family, and further suggests that there is a close link between the evolution of the human rhinoviruses and the mechanisms of RNA replication.


Synthesis of highly functionalized bicyclo[m.n.1]alkanones via a cationic reaction cascade.
[reaction: see text] The acid-mediated Prins/pinacol and the triple domino reactions Diels-Alder/Prins/pinacol were used to construct highly functionalized bicyclo[m.n.1]alkanones 19-29 and 33a-c possessing various ring sizes from ketals 8-18 and 31a-c in 44-96% yields. This approach proves to be highly efficient and reliable to generate high molecular complexity in a single step.


Sociocultural correlates of eating pathology in college women from US and Iran.
The buffering role of the hijab as a protective factor against eating pathology has been questioned in countries where wearing the hijab is compulsory, such as Iran; and, cross-cultural comparisons of body image in Iranian and Western women are sparse. Consequently, we examined sociocultural correlates of eating pathology in US and Iranian women. College women from the US (n = 709) and Iran (n = 331) completed the Eating Disorder Examination-Questionnaire (EDE-Q) and the Sociocultural Attitude Toward to Appearance Questionnaire-4 (SATAQ-4). Prior to examining main hypotheses, we evaluated whether the scales perform similarly (i.e., establish measurement invariance) by culture. The EDE-Q and SATAQ-4 were not invariant by culture indicating that the scales performed differently across groups, so separate analyses were conducted in each sample. Thin-ideal internalization and pressures for thinness were significant positive predictors of eating pathology in both US and Iranian women. Both pressures for thinness and thin-ideal internalization appear to be relevant to eating pathology in women from both cultures. However, there may be important cross-cultural differences in the interpretation or experience of these constructs. Further understanding of this measurement non-invariance and the ways in which Iranian women may be uniquely impacted by Western values of appearance is a critical next step.


A scanning tunneling microscopy study of self-assembled nickel(II) octaethylporphyrin deposited from solutions on HOPG.
The adsorption of nickel(II) octaethylporphyrin (NiOEP) from benzene and chloroform solutions on highly ordered pyrolytic graphite (HOPG) was investigated with a scanning tunneling microscope (STM) operated in ambient conditions. STM images show that NiOEP self-assembles on the graphite surface and that the molecules lie flat and form 2D lattices with spacings of 1.58 +/- 0.03 nm by 1.46 +/- 0.06 nm with a lattice angle of 69 degrees +/- 4 degrees averaged over both solvents. We were unable to eliminate the possibility that one unit cell distance is twice the above-reported distance. The corresponding molecular packing density, 4.5 +/- 0.3 x 10(13) molecules/cm(2), was essentially the same for benzene and chloroform solution deposition. These results differ somewhat from the structure revealed by high-resolution STM images of NiOEP on Au (111). The lack of apparent height (image intensity) in the constant current STM image of the alkane region of alkane-substituted metal porphyrins is attributed to a combination of changes in alkane configuration relative to the ring and associated changes in electronic coupling with HOMO and LUMO.


3D high resolution clonogenic survival measurement of xrs-5 cells in low-dose region of carbon ion plans.
In this study, we performed biological verification measurements of cell survival of a 12C ion irradiation plan employing a high-resolution 3D culture setup. This allowed, in particular, to access the cell inactivation in the low-dose regions close to the target area. We established the protocol for a 3D culture setup where xrs-5 cells were grown inside a layered matrigel structure in 384-well plates. Their radiosensitivity to conventional and 12C ion radiation was evaluated by irradiating them either with 250 kV X-rays at GSI or with monoenergetic 12C beams of 110 MeV/u at MIT, and compared with those of monolayers. A treatment plan for a rectangular target was prepared using the GSI research treatment planning system TRiP98. xrs-5 cells were seeded in the matrigel-based setup and irradiated in dose fall-off regions using active scanning 12C ion beams. In addition, film dosimetry utilizing radiochromic EBT3 film has been performed to assess the field homogeneity downstream of 384-well V-bottom plates with or without additional agarose coating of the well plate bottom. Dose response curves following X-ray and 12C ion irradiation had linear shape and showed a significant decrease in survival fraction at even moderate doses. Survival measurements in the low-dose regions of the plan for the extended target showed good agreement to the predicted survival fraction. The irradiated film profiles yielded a flat dose distribution without apparent artifacts or inhomogeneities for well plates both with and without agarose coating, confirming the suitability of the experimental setup. We conclude that the V-bottom 384-well plates in combination with the radiation-sensitive xrs-5 cell line constitute a suitable radiobiological verification tool which can be used especially for low doses. Furthermore, the measured survival of xrs-5 cells show a good agreement with the expected survival in the low-dose out-of-field regions, both laterally and downstream of the target.


Crystallization and preliminary X-ray analysis of gene product 44 from bacteriophage Mu.
Bacteriophage Mu baseplate protein gene product 44 (gp44) is an essential protein required for the assembly of viable phages. To investigate the roles of gp44 in baseplate assembly and infection, gp44 was crystallized at pH 6.0 in the presence of 20% 2-methyl-2,4-pentanediol. The crystals belong to space group R3, with unit-cell parameters a = b = 127.47, c = 63.97 A. The crystals diffract X-rays to at least 2.1 A resolution and are stable in the X-ray beam and are therefore appropriate for structure determination. Native data have been collected to 2.1 A resolution using a DIP6040 image-plate system at beamline BL44XU at the SPring-8 facility in Japan.


Structure of ABCA tetrablock copolymer vesicles and their formation in selective solvents: a Monte Carlo study.
Vesicles formed by ABCA tetrablock copolymers in solvents that are selective for block A are studied using the Monte Carlo simulation. Simulation results show that the chain length ratio and hydrophobicity of blocks B and C are key factors determining the hydrophobic layer structure of the vesicles. If the B and C blocks are of the same hydrophobicity, the longer block C tends to form the closed hydrophobic layer, whereas the shorter block B is located on the outer surface of the closed hydrophobic layer. However, if the hydrophobicity difference between blocks B and C is high enough, the reverse will occur given that block B has a higher hydrophobicity and block C has a lower hydrophobicity. The kinetics of vesicle formation is also studied. Simulation results reveal that the hydrophobic layer structure is formed through the migration of the polymer chain within the vesicle membrane after the formation of the vesicle profile. This migration is independent of the differences in chain length ratio and the hydrophobicity between the blocks B and C. The packing mode and the migration of polymer chains within the vesicle membrane are also presented and discussed.


Pathology and morphometry of Hystrichis acanthocephalicus (Nematoda) from Phimosus infuscatus (Pelecaniformes) in southern Brazil.
Species of Hystrichis are parasite nematodes of the digestive tract of aquatic birds in South America, Europe and Asia. In Brazil, Hystrichis acanthocephalicus has been reported in Phimosus infuscatus. There are few data on the morphometry of this species and there are no reports on pathological conditions that it causes. Therefore, the purpose of this study was to report morphometric data from H. acanthocephalicus and describe the pathological effects of this parasite on the Phimosus infuscatus proventriculus. Thirty gastrointestinal tracts of P. infuscatus were examined to search for nematodes and H. acanthocephalicus occurred in 83% of hosts. Were measured the total length and body width of males and females, and of their respective cuticular spines, esophagus, spicules and eggs, and the internal and external diameter of copulatory bursa. Histopathological examination revealed parasitic structures in the proventriculus from the lumen (anterior end) to the outer layers of the organ (intermediate and posterior parts), in which we observed inflammatory reaction with infiltration of heterophils, hemorrhage and hemosiderin. The results of this study of histopathology, morphometry and parasitological indices are the first ones reported to H. acanthocephalicus and should contribute to the identification and recognition in cases of outbreaks in the Neotropical region.


Obesity is related to increased menopausal symptoms among Spanish women.
To assess the metabolic syndrome (METS) and its components in postmenopausal women using updated diagnostic criteria and explore their relation to menopausal symptom severity. Medical records of the first visit of 574 postmenopausal Caucasian Spanish women attending a menopause clinic were retrospectively reviewed. Recorded information included general demographic data, type of menopause, menopausal symptom intensity (Kupperman index) and baseline hormonal and metabolic parameters. METS was established if three or more of the following criteria were met: body mass index (BMI) >28.8 kg/m(2), fasting glycaemia ≥100 mg/dL, high-density lipoprotein cholesterol (HDL-C) <50 mg/dL, triglycerides ≥150 mg/dL and blood pressure ≥130/85 mmHg. Mean ± SD age of the whole cohort was 49.9 ± 6.1 years, 66% had natural menopause and 38.9% were obese. In all, 23.1% met diagnostic criteria for METS who were significantly older and displayed higher rates of being married, obesity and abnormal glucose, triglyceride, HDL-C, low-density lipoprotein cholesterol and blood pressure values, when compared with those without the syndrome. The mean Kupperman index score for the whole sample was 26.4±10.6, with 73.8% displaying moderate to severe scores (20 or more). Logistic regression analysis determined that obesity and marriage status were independent risk factors related to more severe menopausal symptoms (Kupperman index scores of 20 or more). Although METS was observed in a lower frequency than previous reports, obesity was associated with more severe menopausal symptoms among postmenopausal Spanish women.


Lipid and fatty acid analysis of fresh and frozen-thawed immature and in vitro matured bovine oocytes.
The lipid content and fatty acid composition of fresh immature and in vitro matured bovine oocytes cultured in media with or without serum, and also those of frozen-thawed immature oocytes were analysed. All oocytes were ranked (A or B) on the basis of their cytoplasmic quality. Fatty acid composition (mol %; w/w) in the total lipid fraction was analysed by gas chromatography. Triglyceride, total cholesterol, phospholipid (phosphocholine-containing phospholipid) and non-esterified fatty acid contents of immature and in vitro matured oocytes were determined using lipid analysis kits. Phosphocholine-containing phospholipid and non-esterified fatty acid contents were determined in frozen-thawed immature bovine oocytes. Palmitic acid was the most abundant fatty acid in immature oocytes (A: 35%, B: 36%), and in in vitro matured oocytes cultured in the medium containing serum (A: 36%, B: 35%) or polyvinyl alcohol (A: 33%, B: 36%). Oleic acid was the second most abundant fatty acid in all A ranked oocytes, whereas stearic acid was the second most abundant fatty acid in all B ranked oocytes. There were significant differences (P < 0.05) in linoleic and arachidonic acid fractions between A and B ranked immature oocytes. In vitro matured oocytes had significantly (P < 0.05) lower proportions of linoleic and arachidonic acids, and significantly (P < 0.01) lower contents of triglyceride and total cholesterol compared with those of immature oocytes. The fatty acid composition of in vitro matured oocytes cultured in medium containing fetal calf serum or polyvinyl alcohol was similar, but significant differences (P < 0.01) in triglyceride and the total cholesterol content were observed. There was a significant decrease (P < 0.05) in the arachidonic acid proportion in frozen-thawed immature oocytes compared with that in fresh immature oocytes. In addition, significant (P < 0.05) decreases in both phospholipid (15.8--10.6 pmol) and non-esterified fatty acid (11.0--4.1 pmol) were found in frozen--thawed immature oocytes. The results indicate that lipids are available for use as an energy source for maturation and that serum lipids are incorporated into the oocyte cytoplasm during in vitro maturation. The changes in the lipid content (mainly phospholipid) and fatty acid composition were also observed in frozen--thawed immature oocytes. The study indicates that the alteration of fatty acid composition in bovine oocytes might improve maturation and cryopreservation.


Complementation group assignments of moderately UV-sensitive CHO mutants isolated by large-scale screening (FAECB).
The complementation group (CG) assignment is presented for 74 moderately sensitive (approximately 2-4x sensitivity of parental line based on ratio of D10s) UV-sensitive mutants of Chinese hamster ovary (CHO) cells from the Facility for Automated Experiments in Cell Biology (FAECB) collection. The distribution of mutants within the first five rodent UV CGs was similar to that of previously reported highly sensitive (> 4x wild-type UV sensitivity) mutants from this collection. This analysis nearly completes the identification of this large collection of over 200 mutant lines isolated after screening an estimated 3 million total colonies of mutagenized CHO cells from approximately 20 mutant hunts with up to about 400,000 colonies screened. Only eight lines with less than about 2x parental line UV sensitivity remain unassigned. One CG of UV mutants (CG6), which now has five identified representatives in the collection, has only been found among moderately UV-sensitive CHO cells. Mutant UV40, a mitomycin C (MMC)- and X-ray-sensitive line with moderate UV cross-sensitivity, is not in CGs 1-6 and apparently is not a nucleotide excision repair mutant. Also identified were new alleles of CG1 and CG4 mutants with profoundly deficient unscheduled DNA synthesis and moderate UV sensitivity but low sensitivity to MMC. The first CG5 mutant derived from MMC-sensitive MC5 cells has been identified as the second CG5 mutant in the collection. No representatives of rodent CGs 7-11 were found, suggesting that AA8 cells have a chromosomal makeup that precludes easy isolation of mutants in these CGs.


Rare, functional, somatic variants in gene families linked to cancer genes: GPCR signaling as a paradigm.
Oncodriver genes are usually identified when mutations recur in multiple tumours. Different drivers often converge in the activation or repression of key cancer-relevant pathways. However, as many pathways contain multiple members of the same gene family, individual mutations might be overlooked, as each family member would necessarily have a lower mutation frequency and thus not identified as significant in any one-gene-at-a-time analysis. Here, we looked for mutated, functional sequence positions in gene families that were mutually exclusive (in patients) with another gene in the same pathway, which identified both known and new candidate oncodrivers. For instance, many inactivating mutations in multiple G-protein (particularly Gi/o) coupled receptors, are mutually exclusive with Gαs oncogenic activating mutations, both of which ultimately enhance cAMP signalling. By integrating transcriptomics and interaction data, we show that the Gs pathway is upregulated in multiple cancer types, even those lacking known GNAS activating mutations. This suggests that cancer cells may develop alternative strategies to activate adenylate cyclase signalling in multiple cancer types. Our study provides a mechanistic interpretation for several rare somatic mutations in multi-gene oncodrivers, and offers possible explanations for known and potential off-label cancer treatments, suggesting new therapeutic opportunities.


Evidence-Based ACL Reconstruction.
There is controversy in the literature regarding a number of topics related to anterior cruciate ligament (ACL) reconstruction. The purpose of this article is to answer the following questions: 1) Bone-patellar tendon-bone reconstruction (BPTB-R) or hamstrimg reconstruction (H-R); 2) Double bundle or single bundle; 3) Allograft or authograft; 4) Early or late reconstruction; 5) Rate of return to sports after ACL reconstruction; 6) Rate of osteoarthritis after ACL reconstruction. A Cochrane Library and PubMed (MEDLINE) search of systematic reviews and meta-analysis related to ACL reconstruction was performed. The key words were: ACL reconstruction, systematic reviews and meta-analysis. The main criteria for selection were that the articles were systematic reviews and meta-analyses focused on the aforementioned questions. Sixty-nine articles were found, but only 26 were selected and reviewed because they had a high grade (I-II) of evidence. BPTB-R was associated with better postoperative knee stability but with a higher rate of morbidity. However, the results of both procedures in terms of functional outcome in the long-term were similar. The double-bundle ACL reconstruction technique showed better outcomes in rotational laxity, although functional recovery was similar between single-bundle and double-bundle. Autograft yielded better results than allograft. There was no difference between early and delayed reconstruction. 82% of patients were able to return to some kind of sport participation. 28% of patients presented radiological signs of osteoarthritis with a follow-up of minimum 10 years.


Achieving pH control in the critically ill patient: the role of continuous infusion of H2-receptor antagonists.
Stress-related gastric mucosal damage is a common occurrence in intensive care unit (ICU) patients. Because of the significant morbidity and mortality associated with this mucosal damage, many ICU patients routinely receive prophylactic therapy, usually with histamine H2-receptor antagonists (H2RAs). Gastric acid secretion occurs in a circadian pattern, with late afternoon and evening surges. H2RAs by continuous infusion may control this uneven pattern of secretion more effectively than H2RAs given by bolus injection. More studies are needed to identify the target ICU population for prophylactic treatment.


Tuberculosis genotyping--United States, 2004-2010.
Tuberculosis (TB) genotyping is a laboratory-based genetic analysis of the bacteria that cause TB disease (i.e., any of the organisms in the Mycobacterium tuberculosis complex). When combined with epidemiologic data, TB genotyping has sufficient discriminatory power to help find TB cases likely to be in the same chain of transmission or determine that cases are not related. Since 2004, >70,000 M. tuberculosis isolates have been genotyped through partnerships between CDC, national genotyping laboratories, and state and local public health departments, with a goal to genotype at least one M. tuberculosis isolate for each case of culture-positive TB in the United States. National genotype surveillance coverage, or the proportion of culture-positive TB cases with a genotyped isolate, increased from 51.2% in 2004 to 88.2% in 2010. The TB Genotyping Information Management System (TB GIMS), accessible to public health departments through a secure, online web portal, was launched in 2010. TB GIMS enables systematic collection of genotyping results, which have been available since 2004, and integrates those results with epidemiologic, geographic, demographic, and clinical data collected by the National TB Surveillance System (NTSS) since 1993. Genotyping timeliness, represented by the median time from specimen collection until linked genotyping results and surveillance data are available to TB GIMS users, improved from 22 weeks in July 2010 to 11 weeks in December 2010. These improvements in genotype surveillance coverage and timeliness will improve outbreak detection efforts and enable more in-depth studies of TB epidemiology, leading to better use of limited public health resources.


Topological Dirac states in transition-metal monolayers on graphyne.
Realizing topological Dirac states in two-dimensional (2D) magnetic materials is particularly important to spintronics. Here, we propose that such states can be obtained in a transition-metal (Hf) monolayer grown on a 2D substrate with hexagonal hollow geometry (graphyne). We find that the significant orbital hybridizations between Hf and C atoms can induce sizable magnetism and bring three Dirac cones at/around each high-symmetry K(K') point in the Brillouin zone. One Dirac cone is formed by pure spin-up electrons from the dz2 orbital of Hf, and the remaining two are formed by crossover between spin-up electrons from the dz2 orbital and spin-down electrons from the hybridization of the dxy/x2-y2 orbitals of Hf atoms and the pz orbital of C atoms. We also find that the spin-orbit coupling effect can open sizable band gaps for the Dirac cones. The Berry curvature calculations further show the nontrivial topological nature of the system with a negative Chern number C = -3, which is mainly attributed to the Dirac states. Molecular dynamics simulations confirm the system's thermodynamic stability approaching room temperature. The results provide a new avenue for realizing the high-temperature quantum anomalous Hall effect based on 2D transition-metals.


A data-driven approach to clinical decision support in tinnitus retraining therapy.
Tinnitus, known as "ringing in the ears", is a widespread and frequently disabling hearing disorder. No pharmacological treatment exists, but clinical management techniques, such as tinnitus retraining therapy (TRT), prove effective in helping patients. Although effective, TRT is not widely offered, due to scarcity of expertise and complexity because of a high level of personalization. Within this study, a data-driven clinical decision support tool is proposed to guide clinicians in the delivery of TRT. This research proposes the formulation of data analytics models, based on supervised machine learning (ML) techniques, such as classification models and decision rules for diagnosis, and action rules for treatment to support the delivery of TRT. A knowledge-based framework for clinical decision support system (CDSS) is proposed as a UI-based Java application with embedded WEKA predictive models and Java Expert System Shell (JESS) rule engine with a pattern-matching algorithm for inference (Rete). The knowledge base is evaluated by the accuracy, coverage, and explainability of diagnostics predictions and treatment recommendations. The ML methods were applied to a clinical dataset of tinnitus patients from the Tinnitus and Hyperacusis Center at Emory University School of Medicine, which describes 555 patients and 3,000 visits. The validated ML classification models for diagnosis and rules: association and actionable treatment patterns were embedded into the knowledge base of CDSS. The CDSS prototype was tested for accuracy and explainability of the decision support, with preliminary testing resulting in an average of 80% accuracy, satisfactory coverage, and explainability. The outcome is a validated prototype CDS system that is expected to facilitate the TRT practice.


Extensive outcrossing and androdioecy in a vertebrate species that otherwise reproduces as a self-fertilizing hermaphrodite.
The mangrove killifish (Kryptolebias marmoratus) is the only vertebrate known to be capable of self-fertilization. Its gonad is typically an ovotestis that simultaneously produces eggs and sperm, and fertilization is internal. Although most populations of this species consist primarily or exclusively of hermaphroditic individuals, gonochoristic males occur at approximately 20% frequency in a natural population at Twin Cays, Belize. Here we use a battery of 36 microsatellite loci to document a striking genetic pattern (high intraspecimen heterozygosities and low within-population linkage disequilibria) that differs qualitatively from the highly homozygous (or "clonal") genetic architecture characteristic of killifish populations previously studied in Florida, where males are much rarer. These findings document that outcrossing (probably between gonochoristic males and hermaphrodites) is common at the Belize site, and, more importantly, they demonstrate the dramatic impact that functional androdioecy can have on the population genetic architecture of this reproductively unique vertebrate species.


Congenital infections and preconception counseling.
Given the risks of congenital infections, the frequent occurrence of unintended pregnancy, and the lack of prenatal care in the first trimester, physicians should seek opportunities to discuss immunizations and disease prevention with women of childbearing age. Discussions of the following topics would be beneficial: 1. Encourage women to seek medical care at the first missed period. 2. Discuss safe sex and abstinence for prevention of sexually transmitted diseases. (See "Clinical Prevention Guidelines" in the CDC's 1998 Guidelines for Treatment of Sexually Transmitted Diseases.) 3. Encourage early medical care for vaginal discharge, pelvic pain, or possible exposure to sexually transmitted diseases. 4. Encourage good handwashing, especially before and after handling food or changing diapers. 5. Encourage the use of universal precautions when exposed to body fluids or blood. 6. Educate the patient on the importance of cooking food thoroughly and avoiding raw meat and unpasteurized dairy products. 7. Ensure vaccination against hepatitis B, rubella, and varicella.


Homozygous CRISPR/Cas9 Knockout Generated a Novel Functionally Active Exon 1 Skipping XPA Variant in Melanoma Cells.
Defects in DNA repair pathways have been associated with an improved response to immune checkpoint inhibition (ICI). In particular, patients with the nucleotide excision repair (NER) defect disease Xeroderma pigmentosum (XP) responded impressively well to ICI treatment. Recently, in melanoma patients, pretherapeutic XP gene expression was predictive for anti-programmed cell death-1 (PD-1) ICI response. The underlying mechanisms of this finding are still to be revealed. Therefore, we used CRISPR/Cas9 to disrupt XPA in A375 melanoma cells. The resulting subclonal cell lines were investigated by Sanger sequencing. Based on their genetic sequence, candidates from XPA exon 1 and 2 were selected and further analyzed by immunoblotting, immunofluorescence, HCR and MTT assays. In XPA exon 1, we established a homozygous (c.19delG; p.A7Lfs*8) and a compound heterozygous (c.19delG/c.19_20insG; p.A7Lfs*8/p.A7Gfs*55) cell line. In XPA exon 2, we generated a compound heterozygous mutated cell line (c.206_208delTTG/c.208_209delGA; p.I69_D70delinsN/p.D70Hfs*31). The better performance of the homozygous than the heterozygous mutated exon 1 cells in DNA damage repair (HCR) and post-UV-C cell survival (MTT), was associated with the expression of a novel XPA protein variant. The results of our study serve as the fundamental basis for the investigation of the immunological consequences of XPA disruption in melanoma.


Aortic Dissection and COVID-19 Pneumonia in a Pregnant Woman at 34 Weeks of Gestation.
Between 0.1% and 0.3% of all aortic dissections occur during pregnancy. Arterial hypertension, connective tissue disorders, and congenital cardiovascular anomalies-including bicuspid aortic valves-are well-known risk factors. The causality between pregnancy and aortic dissection is unclear, but there have been some observations that COVID-19 illness may increase the risk. This report describes a pregnant woman at 34 weeks of gestation who had a bicuspid aortic valve and experienced an acute aortic dissection while ill with COVID-19 pneumonia. Computed tomography confirmed a type A aortic dissection and bilateral patchy pulmonary opacities. Cesarean delivery was performed, followed by replacement of the aortic valve with a mechanical aortic prosthesis and reconstruction of the ascending aorta and hemiarch. The intraoperative course was uneventful, and the patient was successfully weaned from mechanical ventilation after 51 hours. COVID-19 during pregnancy seems to increase the risk for aortic dissection, although there is no evidence base for an association. Because guidelines for diagnosis and treatment in such complex cases are lacking, care from a multidisciplinary team is crucial for successful outcomes.


Women Gerontologists' Personal Experiences with Aging: Results From the Women in Gerontology Legacy Project.
The Women in Gerontology Legacy (WIGL) Project involved interviewing 46 older women gerontologists between 2014 and 2015. The current study focuses on the WIGL interview questions regarding the interactions between participants' experiences as gerontologists and their own aging. Emergent themes focus on the direction of influence: professional lives influencing personal lives, personal lives informing professional lives and mutuality between personal and professional lives. Thematic findings expand our current understanding of how professional knowledge and experiences contribute to personal aging experiences and the role personal aging experiences can have on the professional lives of women gerontologists. There is a potential for disconnect to occur between our personal experiences and the experiences of others. The current study contributes to our understanding of when and how this occurs, so we can then ensure our messages fall on receptive ears by overcoming the natural tendency to distort or ignore messages that may create anxiety.


Identification of succinic semialdehyde reductases from Geobacter: expression, purification, crystallization, preliminary functional, and crystallographic analysis.
Succinic semialdehyde reductase (SSAR) is an important enzyme involved in γ-aminobutyrate (GABA) metabolism. By converting succinic semialdehyde (SSA) to γ-hydroxybutyrate (GHB), the SSAR facilitates an alternative pathway for GABA degradation. In this study, we identified SSARs from Geobacter sulfurreducens and Geobacter metallireducens (GsSSAR and GmSSAR, respectively). The enzymes were over-expressed in Escherichia coli and purified to near homogeneity. Both GsSSAR and GmSSAR showed the activity of reducing SSA using nicotinamide adenine dinucleotide phosphate as a co-factor. The oligomeric sizes of GsSSAR and GmSSAR, as determined by analytical size exclusion chromatography, suggest that the enzymes presumably exist as tetramers in solution. The recombinant GsSSAR and GmSSAR crystallized in the presence of NADP(+), and the resulting crystals diffracted to 1.89 Å (GsSSAR) and 2.25 Å (GmSSAR) resolution. The GsSSAR and GmSSAR crystals belong to the space groups P2(1)22(1) (a= 99.61 Å, b= 147.49 Å, c= 182.47 Å) and P1 (a= 75.97 Å, b= 79.14 Å, c= 95.47 Å, α = 82.15°, β = 88.80°, γ = 87.66°), respectively. Preliminary crystallographic data analysis suggests the presence of eight protein monomers in the asymmetric units for both GsSSAR and GmSSAR.


Pharmacokinetics and effects of ribavirin following intraventricular administration for treatment of subacute sclerosing panencephalitis.
Ribavirin is a broad-spectrum antiviral drug with inhibitory activity against many RNA viruses, including measles virus. Five patients with subacute sclerosing panencephalitis (SSPE) were treated with ribavirin by intraventricular administration. Although there were transient side effects attributed to ribavirin, such as drowsiness, headache, lip and gingival swelling, and conjunctival hyperemia, intraventricular ribavirin therapy was generally safe and well tolerated. The cerebrospinal fluid (CSF) ribavirin concentration decreased, as described by a monoexponential function, after a single intraventricular dose. There was considerable interindividual variability, however, in the peak level and half-life. We aimed to adjust the individual dose and frequency of intraventricular administration based on the peak level and half-life of ribavirin in the CSF in order to maintain the CSF ribavirin concentration at the target level. Clinical effectiveness (significant neurologic improvement and/or a significant decrease in titers of hemagglutination inhibition antibodies against measles virus in CSF) was observed for four of five patients. For these four patients, CSF ribavirin concentrations were maintained at a level at which SSPE virus replication was almost completely inhibited in vitro and in vivo, whereas the concentration was lower in the patient without clinical improvement. These results suggest that intraventricular administration of ribavirin is effective against SSPE if the CSF ribavirin concentration is maintained at a high level. Intraventricular ribavirin therapy should be pursued further for its potential use for patients with SSPE and might be applied in the treatment of patients with encephalitis caused by other RNA viruses.


The N-terminal fragment of GRP94 is sufficient for peptide presentation via professional antigen-presenting cells.
The chaperone glucose-regulated protein 94 (GRP94) has long been used to augment peptide presentation to T cells. This chaperone binds antigenic peptides, binds to receptors on professional antigen-presenting cells (APCs), activates these cells and after internalization, transfers the peptides to MHC class I for activation of T cells. Here we show that all these activities reside within amino acids 1-355 of GRP94. This small fragment is sufficient to bind peptides, to bind and be taken up by the receptors CD91 and scavenger receptor type A on either dendritic cells or macrophages. The minimal construct can augment peptide presentation in culture and induce antigen-specific CTL in naive mice only because it loads APCs with the relevant peptide. Thus, the sequence 1-355 is the immunologically sufficient module of GRP94 and we propose that this 'mini-chaperone' can be used in immunotherapy of tumors and vaccine development.


Immunomodulatory Role of Stem Cells from Human Exfoliated Deciduous Teeth on Periodontal Regeneration.
Periodontitis is initiated by the infection of periodontal bacteria and subsequent tissue inflammation due to immunoreaction, eventually leading to periodontal apparatus loss. Stem cells from human exfoliated deciduous teeth (SHEDs) have exhibited beneficial characteristics in dental tissue regeneration. However, the immunomodulatory functions of SHEDs have not been elucidated in the context of periodontitis treatment. In this study, we investigated the potential immunomodulatory effects of SHEDs on experimental periodontitis and demonstrated that multidose delivery of SHEDs led to periodontal tissue regeneration. SHEDs and monocytes/macrophages were cocultured in transwell systems and SHEDs were found to be capable of promoting monocyte/macrophage conversion to CD206+ M2-like phenotype. Bioluminescence imaging (BLI) was employed to assess the survival and distribution of SHEDs after delivery in periodontal tissues in an induced periodontitis model, and BLI revealed that SHEDs survived for ∼7 days in periodontal tissues with little tissue diffusion. Then, multidose SHED delivery was applied to treat periodontitis at 7-day intervals. Results showed that mutidose SHEDs altered the cytokine expression profile in gingival crevicular fluid, reduced gum bleeding, increased new attachment of periodontal ligament, and decreased osteoclast differentiation. Micro-computed tomography analysis showed SHED administration significantly increased periodontal regeneration and alveolar bone volume, and decreased distance of cementoenamel junction to alveolar bone crest. Furthermore, an increase in the number of CD206+ M2 macrophages was observed in periodontal tissues following the delivery of SHEDs, which aligned well with the promoted conversion to CD206+ M2-like cells from monocytes/macrophages in vitro after stimulation by SHEDs. This study demonstrated in a rat periodontitis model that local delivery of SHEDs attributed to the induction of M2 macrophage polarization, reduction of periodontal tissue inflammation, and enhancement of periodontal regeneration.


No involvement of nitric oxide in the limitation of beta-adrenergic inotropic responsiveness during ischemia.
We tested whether or not endogenous nitric oxide (NO) attenuates beta-adrenergic inotropic responsiveness during normoperfusion or moderate myocardial ischemia. In 13 anesthetized pigs with a cannulated left anterior descending (LAD) coronary artery, the maximal contractile responses to intracoronary dobutamine and calcium were assessed during normoperfusion and at the end of a 90-min period of moderate ischemia (50% reduction in coronary arterial inflow) without (group 1, n = 6) and with (group 2, n = 7) prior inhibition of NO synthesis [30 mg/kg iv N(omega)-nitro-L-arginine (L-NNA)]. Contractile function was assessed by a regional work index (sonomicrometry, micromanometry, mm. mmHg). In groups 1 and 2 during normoperfusion, the maximal increase of the work index was greater with calcium than with dobutamine. At the end of ischemia in group 1, the baseline work index was decreased by approximately 50%, and the subsequent maximal increase of the work index with dobutamine, but not with calcium, was reduced compared with normoperfusion. In group 2 during normoperfusion, L-NNA did not alter the maximal increases of the work index with dobutamine or calcium. At the end of ischemia, the baseline work index was reduced by 64%, and the subsequent maximal increases of the work index with both dobutamine and calcium were reduced compared with normoperfusion; however, the response to calcium was still greater than that to dobutamine. We conclude that endogenous NO does not limit beta-adrenergic inotropic responsiveness in normoperfused or moderately ischemic porcine myocardium.


Comparison of Mechanical Properties of PMMA Disks for Digitally Designed Dentures.
In this study, the physical properties of a custom block manufactured using a self-polymerizing resin (Custom-block), the commercially available CAD/CAM PMMA disk (PMMA-disk), and a heat-polymerizing resin (Conventional PMMA) were evaluated via three different tests. The Custom-block was polymerized by pouring the self-polymerizing resin into a special tray, and Conventional PMMA was polymerized with a heat-curing method, according to the manufacturer's recommended procedure. The specimens of each group were subjected to three-point bending, water sorption and solubility, and staining tests. The results showed that the materials met the requirements of the ISO standards in all tests, except for the staining tests. The highest flexural strength was exhibited by the PMMA-disk, followed by the Custom-block and the Conventional PMMA, and a significant difference was observed in the flexural strengths of all the materials (p < 0.001). The Custom-block showed a significantly higher flexural modulus and water solubility. The water sorption and discoloration of the Custom-block were significantly higher than those of the PMMA-disk, but not significantly different from those of the Conventional PMMA. In conclusion, the mechanical properties of the three materials differed depending on the manufacturing method, which considerably affected their flexural strength, flexural modulus, water sorption and solubility, and discoloration.


Continuous subcortical motor evoked potential stimulation using the tip of an ultrasonic aspirator for the resection of motor eloquent lesions.
Resection of a motor eloquent lesion has become safer because of intraoperative neurophysiological monitoring (IOM). Stimulation of subcortical motor evoked potentials (scMEPs) is increasingly used to optimize patient safety. So far, scMEP stimulation has been performed intermittently during resection of eloquently located lesions. Authors of the present study assessed the possibility of using a resection instrument for continuous stimulation of scMEPs. An ultrasonic surgical aspirator was attached to an IOM stimulator and was used as a monopolar subcortical stimulation probe. The effect of the aspirator's use at different ultrasound power levels (0%, 25%, 50%, 75%, and 100%) on stimulation intensity was examined in a saline bath. Afterward monopolar stimulation with the surgical aspirator was used during the resection of subcortical lesions in the vicinity of the corticospinal tract in 14 patients in comparison with scMEP stimulation via a standard stimulation electrode. During resection, the stimulation current at which an MEP response was still measurable with subcortical stimulation using the surgical aspirator was compared with the corresponding stimulation current needed using a standard monopolar subcortical stimulation probe at the same location. The use of ultrasound at different energy levels did result in a slight but irrelevant increase in stimulation energy via the tip of the surgical aspirator in the saline bath. Stimulation of scMEPs using the surgical aspirator or monopolar probe was successful and almost identical in all patients. One patient developed a new permanent neurological deficit. Transient new postoperative paresis was observed in 28% (4 of 14) of cases. Gross-total resection was achieved in 64% (9 of 14) cases and subtotal resection (> 80% of tumor mass) in 35% (5 of 14). Continuous motor mapping using subcortical stimulation via a surgical aspirator, in comparison with the sequential use of a standard monopolar stimulation probe, is a feasible and safe method without any disadvantages. Compared with the standard probe, the aspirator offers continuous information on the distance to the corticospinal tract.


Galangin Activates the ERK/AKT-Driven Nrf2 Signaling Pathway to Increase the Level of Reduced Glutathione in Human Keratinocytes.
Previously, we demonstrated that galangin (3,5,7-trihydroxyflavone) protects human keratinocytes against ultraviolet B (UVB)-induced oxidative damage. In this study, we investigated the effect of galangin on induction of antioxidant enzymes involved in synthesis of reduced glutathione (GSH), and investigated the associated upstream signaling cascades. By activating nuclear factor-erythroid 2-related factor (Nrf2), galangin treatment significantly increased expression of glutamate-cysteine ligase catalytic subunit (GCLC) and glutathione synthetase (GSS). This activation of Nrf2 depended on extracellular signal-regulated kinases (ERKs) and protein kinase B (AKT) signaling. Inhibition of GSH in galangin-treated cells attenuated the protective effect of galangin against the deleterious effects of UVB. Our results reveal that galangin protects human keratinocytes by activating ERK/AKT-Nrf2, leading to elevated expression of GSH-synthesizing enzymes.