The effect of a novel movement strategy in decreasing ACL risk factors in female adolescent soccer players.
There is a need to investigate the effect of specific movement strategies in reducing biomechanical risk factors for anterior cruciate ligament injury in young female athletes. The purpose of this study was (a) to determine the feasibility of implementing a novel movement strategy (Core-PAC) into a team warm-up before soccer training based on subject compliance and integration of the Core-PAC into the warm-up and (b) to determine whether the Core-PAC would improve peak knee flexion angles and peak abduction moments at the knee during a side cut (SC) and an unanticipated side cut (USC) before kicking a soccer ball, and a side hop (SH) task after immediate instruction and after a 4-week training program. A convenience sample of ten 14- to 16-year-old female soccer players were instructed in the Core-PAC immediately after baseline testing and during a training program consisting of a 20-minute warm-up, 2 times per week. The Core-PAC was understood and accepted by the subjects and incorporated into their warm-up activities with good compliance. After the immediate instruction, there were significant increases in peak knee flexion angles of a mean 6.4° during the SC (p = 0.001), 3.5° during the USC (p = 0.007), and 5.8° during the SH (p < 0.001) tasks. Peak knee abduction moments decreased by a mean of 0.25 N·m·kg(-1) during the SC (p < 0.03), 0.17 N·m·kg(-1) during the USC (p = 0.05), and 0.27 N·m·kg(-1) during the SH (p = 0.04) tasks. After the 4-week training program, some individuals showed improvement. The results of this study suggest that the Core-PAC may be 1 method of modifying high-risk movements for ACL injury such as side cutting and single-leg landing.


Adult presentation of Caroli's syndrome treated with orthotopic liver transplantation.
When Caroli's disease, defined as a congenital dilation and ectasia of segmental intrahepatic bile ducts in the absence of other histological abnormalities, is associated with periportal fibrosis, it is termed Caroli's syndrome. We describe the case of a 35-yr-old woman with Caroli's syndrome without clinical manifestation of portal hypertension despite diffuse involvement of the liver who was successfully treated with orthotopic liver transplantation after recurrent nearly fatal episodes of cholangitis.


Synthesis of palladium(II) complexes containing a new alpha-D-xylofuranose-modified diphosphine and their application as catalyst precursors in the co- and terpolymerization of CO-ethene and propene.
The diphosphine 3,5-dideoxy-1,2-O-isopropylidene-3,5-bis(di(2-methoxyphenyl)phosphanyl)-alpha-D-xylofuranose (o-MeO-xylophos), which differs from the known 3,5-dideoxy-1,2-O-isopropylidene-3,5-bis(diphenylphosphanyl)-alpha-D-xylofuranose (xylophos) by the presence of 2-methoxy substituents on the P-aryl rings, has been synthesized and characterized. These two ligands have been employed to stabilize the Pd(II) complexes [PdCl2(o-MeO-xylophos)] (1a), [PdCl2(xylophos)] (2a), [PdClMe(o-MeO-xylophos)] (1b), [PdClMe(xylophos)] (2b), [Pd(OTs)(H2O)(o-MeO-xylophos)](OTs) (1c) and [Pd(OTs)(H2O)(xylophos)](OTs) (2c). All complexes have been characterized by multinuclear-NMR spectroscopy. The solid-state structure of 1a has been determined by a single crystal X-ray analysis. The Pd-aqua complexes 1c and 2c have been employed to catalyse the CO-ethene and CO-propene copolymerization as well as the CO-ethene-propene terpolymerization reaction in MeOH. The catalytic activity and the molecular weight of the polyketones have been compared to those of the products obtained with analogous catalysts, [Pd(H2O)2(o-MeO-dppp)](OTs)2 (3c) and [Pd(H2O)(OTs)(dppp)](OTs) (4c), bearing the classical 1,3-bis(diphenylphoshino)propane ligand (dppp). Under comparable catalytic conditions, all catalysts produce structurally similar polymeric materials, with 1c yielding the largest propene incorporation as well as the highest productivity of low-molecular-weight terpolymers.


Future of Medicare system on the table as forums spark debate across country.
Society needs to reach some conclusions about cost-efficient primary care and how medicare dollars should be spent, panelists told a recent conference in Vancouver. The discussion covered a wide range of subjects, including the use of alternate providers and the principle of universality.


Nanoscale dynamic behavior of surface magnetic domains on a La0.7Sr0.3MnO3 thin film.
An oscillating magnetic tip can be used to induce the striped magnetic ripple pattern with alternating up-and-down striped magnetic domains on a ferromagnetic La0.7Sr0.3MnO3 (LSMO) thin film surface. Magnetic force microscopy (MFM) images show that the surface magnetic domains (SMDs) can be aligned in a well-ordered alternating up-and-down c(2 x 2) structure on the stripe magnetic domains, indicating that the oscillating magnetic tip turns the ferromagnetic LSMO surface into a canted antiferromagnetic state. The orientation of the SMDs is determined by their discrete phase distribution. A three-dimensional (3D) SMD orientation model is built to understand dynamic behavior of the SMDs.


[Effective application of therapeutic plasma exchange in a case of acute dermatomyositis].
We present a case of 22-year-old male with acute dermatomyositis who did not respond to a standard immunosuppressive therapy. Due to rapidly deteriorating clinical status a series of plasmapheresis was performed subsequent to which a quick clinical improvement was observed.


A group of genome-based biomarkers that add to a Kattan nomogram for predicting progression in men with high-risk prostate cancer.
The three main treatment options for primary prostate cancer are surgery, radiation, and active surveillance. Surgical and radiation intervention for prostate cancer can be associated with significant morbidity. Therefore, accurate stratification predictive of outcome for prostate cancer patients is essential for appropriate treatment decisions. Nomograms that use clinical and pathologic variables are often used for risk prediction. Favorable outcomes exist even among men classified by nomograms as being at high risk of recurrence. Previously, we identified a set of DNA-based biomarkers termed Genomic Evaluators of Metastatic Prostate Cancer (GEMCaP) and have shown that they can predict risk of recurrence with 80% accuracy. Here, we examined the risk prediction ability of GEMCaP in a high-risk cohort and compared it to a Kattan nomogram. We determined that the GEMCaP genotype alone is comparable with the nomogram, and that for a subset of cases with negative lymph nodes improves upon it. Thus, GEMCaP shows promise for predicting unfavorable outcomes for negative lymph node high-risk cases, where the nomogram falls short, and suggests that addition of GEMCaP to nomograms may be warranted.


[SIRS (systemic inflammatory response syndrome): clinical entity, definitions, and the significance].
The clinical entity, definitions, and the significance of SIRS (systemic inflammatory response syndrome) were reviewed. The term, SIRS was proposed to define sepsis and its sequelae clearly in 1991, in order to make early detection of the disease possible, and to improve the ability to compare innovative potential diagnostic and therapeutic modalities by standardizing terms. Although the criteria of SIRS is not strict and too sensitive, SIRS has been shown to be useful as a warning sign of severe condition in clinical setting. We also discussed about a new concept, CARS (compensatory anti-inflammatory response syndrome), which was characterized as anti-inflammatory mediators-dominant condition, in this issue.


Extending the IOI to significant others and to non-hearing-aid-based interventions.
Two extensions of the International Outcome Inventory for Hearing Aids are described: the first is designed for the significant other (SO) (IOI-HA-SO), and the second for alternative interventions for hearing difficulties (IOI-AI). A feature of the IOI-HA-SO is that several items are modified to inquire about effects of the partner's hearing loss on the SO. The IOI-AI is designed to cover effects of use of listening aids other than personally worn hearing aids, use of hearing tactics, and aural surgery.


A Critical Review of the Performance and Soil Biodegradability Profiles of Biobased Natural and Chemically Synthesized Polymers in Industrial Applications.
This review explores biobased polymers for industrial applications, their end fate, and most importantly, origin and key aspects enabling soil biodegradation. The physicochemical properties of biobased synthetic and natural polymers and the primary factors governing degradation are explored. Current and future biobased systems and factors allowing for equivalent comparisons of degradation and possible sources for engineering improved biodegradation are reviewed. Factors impacting ultraviolet (UV) stability of biopolymers have been described including methods to enhance photoresistance and impact on biodegradation. It discusses end-fate of biopolymers in soil and impact of residues on soil health. A limited number of studies examine side effects (e.g., microbial toxicity) from soil biodegradation of composites and biopolymers. Currently available standards for biodegradation and composting have been described with limitations and scope for improvements. Finally, design considerations and implications for sustainable polymers used, under consideration, and to be considered within the context of a rational biodegradable strategy are elaborated.


Parameters for a model of an oscillating neuronal network in the cochlear nucleus defined by genetic algorithms.
Chopper neurons in the cochlear nucleus are characterized by intrinsic oscillations with short average interspike intervals (ISIs) and relative level independence of their response (Pfeiffer, Exp Brain Res 1:220-235, 1966; Blackburn and Sachs, J Neurophysiol 62:1303-1329, 1989), properties which are unattained by models of single chopper neurons (e.g., Rothman and Manis, J Neurophysiol 89:3070-3082, 2003a). In order to achieve short ISIs, we optimized the time constants of Rothman and Manis single neuron model with genetic algorithms. Some parameters in the optimization, such as the temperature and the capacity of the cell, turned out to be crucial for the required acceleration of their response. In order to achieve the relative level independence, we have simulated an interconnected network consisting of Rothman and Manis neurons. The results indicate that by stabilization of intrinsic oscillations, it is possible to simulate the physiologically observed level independence of ISIs. As previously reviewed and demonstrated (Bahmer and Langner, Biol Cybern 95:371-379, 2006a), chopper neurons show a preference for ISIs which are multiples of 0.4 ms. It was also demonstrated that the network consisting of two optimized Rothman and Manis neurons which activate each other with synaptic delays of 0.4 ms shows a preference for ISIs of 0.8 ms. Oscillations with various multiples of 0.4 ms as ISIs may be derived from neurons in a more complex network that is activated by simultaneous input of an onset neuron and several auditory nerve fibers.


Accomplishments in 2008 in the adjuvant treatment of colon cancer.
Overview of the Disease IncidencePrognosisCurrent General Therapy Standards StagingLymph Node ExcisionStage III DiseaseStage II DiseaseMolecular MarkersAccomplishments During the Year Therapy Cytotoxic ChemotherapyChemotherapy Plus Targeted TherapySpecial PopulationsBasic Science-BiomarkersMethodologyWhat Needs to Be Done Application of the AccomplishmentsControversies and DisagreementsFuture Directions Comments on ResearchObstacles to Progress.


Effect of ouabain in pressurized middle cerebral arteries from normotensive and hypertensive rats.
The aim of the present study was to assess the ability of ouabain to induce vasomotor responses and interfere with the myogenic tone in isolated segments of middle cerebral arteries from male Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR) subjected to different pressures and no-flow conditions using a pressure myograph. At 60 mmHg, ouabain (1 nM-1 mM) caused relaxations at concentrations of 10 microM and up in segments from WKY while 1 nM ouabain produced a relaxation that was unaltered by the remaining concentrations in SHR segments. The relaxations were higher in SHR than in WKY arteries. Endothelium removal practically abolished the relaxation in arteries from both strains, whereas 10 microM L-NAME (an inhibitor of nitric oxide synthase) had no effect. When arteries were pressurized from 20-120 mmHg, myogenic activity developed in 3 out of 10 WKY arteries while SHR arteries did not show myogenic tone. Endothelium removal did not alter the effects of pressure increase in both strains, and incubation of segments in a Ca(2+)-free medium to abolish myogenic tone, shifted the pressure-response curve of WKY segments to the left; pressure-response curves from SHR were not modified. Although ouabain (0.1 mM) did not alter the pressure-response curve from WKY segments, curves obtained from SHR were shifted to the left. These results suggest that: 1) ouabain produces vasodilation in pressurized middle cerebral arteries of WKY and SHR which is positively modulated by an endothelial factor distinct from nitric oxide; and 2) only WKY arteries develop myogenic activity while the diameter of SHR arteries is passively enhanced with increases in intraluminal pressure. This passive increase is facilitated by ouabain. Therefore, hypertension modifies the mechanical properties of cerebral arteries resulting in a loss in the capacity for autoregulation.


Diagnostic imaging in gynecology.
Ultrasound (US), computed tomography (CT) and magnetic resonance imaging (MRI) are the "gold standard" among gynecological imaging methods. They are important diagnostic tools used to determine the site of origin of a pelvic mass and to characterize the adnexal lesions. This paper summarizes the diagnostic performance of ultrasound, computed tomography, and magnetic resonance imaging in various gynecological diseases and tumours diagnostics.


Quantitative evaluation of rotaviral antigenemia in children with acute rotaviral diarrhea.
Rotaviral antigen and RNA have recently been identified in the serum of patients with rotaviral gastroenteritis, but the roles they play in disease remains undetermined. Rotaviral antigen and RNA were quantified by enzyme-linked immunosorbant assay and by quantitative reverse-transcription polymerase chain reaction in stool and serum specimens from children with rotaviral diarrhea (n=102), children with nonrotaviral diarrhea (n=40), and nondiarrheal control children (n=30). Rotaviral antigenemia was detected in 64%, 3%, and 0% of the children with rotaviral diarrhea, the children with nonrotaviral diarrhea, and the nondiarrheal control children, respectively. The level of rotaviral antigen in serum was approximately 2x10(2) -fold lower than that in stool, and a moderate correlation was observed between the 2 levels. Rotaviral RNA was detected in 93% of the antigen-positive serum specimens. The median number of RNA copies in serum was approximately 1 x 10(5) -fold lower than that in stool, and no correlation was observed between the 2 levels. Serum levels of both antigen and RNA were inversely associated with baseline titers of rotaviral serum immunoglobulin G (P<.01). Antigenemia was also associated with G1 serotype. Rotaviral antigenemia and viremia were common in children with rotaviral diarrhea, but antigen and RNA levels in serum were substantially lower than those in stool. Antigenemia was associated with infection with G1 strains and with low baseline titers of rotaviral serum antibody.


Inforna 2.0: A Platform for the Sequence-Based Design of Small Molecules Targeting Structured RNAs.
The development of small molecules that target RNA is challenging yet, if successful, could advance the development of chemical probes to study RNA function or precision therapeutics to treat RNA-mediated disease. Previously, we described Inforna, an approach that can mine motifs (secondary structures) within target RNAs, which is deduced from the RNA sequence, and compare them to a database of known RNA motif-small molecule binding partners. Output generated by Inforna includes the motif found in both the database and the desired RNA target, lead small molecules for that target, and other related meta-data. Lead small molecules can then be tested for binding and affecting cellular (dys)function. Herein, we describe Inforna 2.0, which incorporates all known RNA motif-small molecule binding partners reported in the scientific literature, a chemical similarity searching feature, and an improved user interface and is freely available via an online web server. By incorporation of interactions identified by other laboratories, the database has been doubled, containing 1936 RNA motif-small molecule interactions, including 244 unique small molecules and 1331 motifs. Interestingly, chemotype analysis of the compounds that bind RNA in the database reveals features in small molecule chemotypes that are privileged for binding. Further, this updated database expanded the number of cellular RNAs to which lead compounds can be identified.


Depolarization-induced influx of sodium in response to phenylephrine in rat atrial heart muscle.
1. The effects of alpha 1-adrenoceptor stimulation on transmembrane potential, currents and ion fluxes were investigated in multicellular preparations and/or single cells obtained from the left atrium of rat hearts. 2. In multicellular preparations, phenylephrine caused a concentration-dependent positive inotropic effect, an increase in action potential duration, and a decrease in resting potential; the effects were antagonized by phentolamine. 3. In the presence of phenylephrine (100 mumol/1), two levels of resting potential were observed when the preparations were, alternately, electrically stimulated or kept at rest (-74 +/- 1 mV during activity and -62 +/- 4 mV at rest; mean +/- S.E.M.; n = 9). 4. In resting preparations, the depolarization in response to phenylephrine was eliminated in low-Na+ solution (12 mmol/l) and antagonized by tetrodotoxin (10 mumol/l). 5. The phenylephrine-induced depolarization was also seen in nominally Ca(2+)-free solution and in the presence of (-)-devapamil (1 mumol/l). 6. The alkylating agent N-ethyl-maleimide (30 mumol/l) abolished the depolarizing effect of phenylephrine. 7. Phorbol 12,13-dibutyrate (10 mumol/l) also abolished the depolarizing effect of phenylephrine. 8. Phenylephrine caused a significant increase of 22Na+ uptake in resting preparations and of 45Ca2+ uptake in beating preparations. 9. The depolarizing effect of phenylephrine was also observed in single atrial myocytes. Steady-state membrane currents in response to 500 ms depolarizing and hyperpolarizing voltage clamp steps were decreased. The cross-over of I-V curves under control and test conditions was at about -70 mV. The effects of phenylephrine were antagonized in the presence of phentolamine. 10. After suppression of potassium currents by substitution of CsCl for internal and external KCl ([KCl]o), phenylephrine had no effect on membrane currents. 11. In conclusion, we presume the following sequence of events in response to phenylephrine in rat atrial heart muscle. First, the stimulation of alpha 1-adrenoceptors decreases the K+ conductance thereby producing a depolarization in the presence of an inward current. Second, the change of the membrane potential in the depolarizing direction induces a TTX-sensitive Na+ window current which further propels the depolarization. Third, the increase in Na+ influx may increase Ca2+ influx by activating the Na(+)-Ca2+ exchange in mechanism. The greater influx of Ca2+ may contribute to the positive inotropic effect in response to phenylephrine.


High-resolution micropatterned Teflon AF substrates for biocompatible nanofluidic devices.
We describe a general photolithography-based process for the microfabrication of surface-supported Teflon AF structures. Teflon AF patterns primarily benefit from superior optical properties such as very low autofluorescence and a low refractive index. The process ensures that the Teflon AF patterns remain strongly hydrophobic in order to allow rapid lipid monolayer spreading and generates a characteristic edge morphology which assists directed cell growth along the structured surfaces. We provide application examples, demonstrating the well-controlled mixing of lipid films on Teflon AF structures and showing how the patterned surfaces can be used as biocompatible growth-directing substrates for cell culture. Chinese hamster ovary (CHO) cells develop in a guided fashion along the sides of the microstructures, selectively avoiding to grow over the patterned areas.


Transient receptor potential family members PKD1L3 and PKD2L1 form a candidate sour taste receptor.
Animals use their gustatory systems to evaluate the nutritious value, toxicity, sodium content, and acidity of food. Although characterization of molecular identities that receive taste chemicals is essential, molecular receptors underlying sour taste sensation remain unclear. Here, we show that two transient receptor potential (TRP) channel members, PKD1L3 and PKD2L1, are coexpressed in a subset of taste receptor cells in specific taste areas. Cells expressing these molecules are distinct from taste cells having receptors for bitter, sweet, or umami tastants. The PKD2L1 proteins are accumulated at the taste pore region, where taste chemicals are detected. PKD1L3 and PKD2L1 proteins can interact with each other, and coexpression of the PKD1L3 and PKD2L1 is necessary for their functional cell surface expression. Finally, PKD1L3 and PKD2L1 are activated by various acids when coexpressed in heterologous cells but not by other classes of tastants. These results suggest that PKD1L3 and PKD2L1 heteromers may function as sour taste receptors.


Macrophages from BALB/c and CBA/Ca mice differ in their cellular responses to Streptococcus pneumoniae.
In a mouse model of pneumonia caused by Streptococcus pneumoniae, differences in the timing and vigor of the host inflammatory response have been associated with susceptibility to invasive disease. BALB/c and CBA/Ca mice are known to be resistant and susceptible to acute pneumococcal disease, respectively. In this study, we have demonstrated that BMM from BALB/c and CBA/Ca mice differ in their expression and regulation of TLR9 in response to S. pneumoniae. We have also shown that BMM from CBA/Ca mice failed to fully activate p38, NF-kappaB, and ERK 1/2 signaling pathways, resulting in reduced secretion of TNF-alpha and CCL5 in response to this pathogen. In addition, we have established that S. pneumoniae induced significant cell death in BMM from CBA/Ca mice. These findings indicate that variations between the two strains are likely to reflect differences in macrophage responses to the pathogen.


Taurine-Modified Boehmite Nanoparticles for GFRP Wind Turbine Rotor Blade Fatigue Life Enhancement.
Advanced nanoparticle-reinforced glass fibre composites represent a promising approach to improving the service life of fatigue-loaded structures such as wind turbine rotor blades. However, processing particle-reinforced resins using advanced infusion techniques is problematic due to, for example, higher viscosity as well as filtering effects. In this work, the effects of boehmite nanoparticles on viscosity, static properties and fatigue life are investigated experimentally. Whereas rheological analysis reveals a significant increase of viscosity in the case of pristine boehmite particles, an additional taurine surface modification of the particles can effectively reduce viscosity increase. As regards mechanical properties, significant improvements of both static as well as fatigue properties are found. The addition of 15 wt.% of boehmite particles increases fatigue life by a maximum of 270% compared to the unmodified fibre-reinforced epoxy. Transmitted light-based investigation of the damage mechanisms shows delayed initiation and smaller growth rates for laminates containing boehmite particles. At the same time, the observed mechanisms and their accumulation along the relative cycle number do not change significantly. In addition, by characterising autonomous heating, the so-called Risitano fatigue limit is determined. The results reveal that with increasing particle content there is an increase in the fatigue limit.


Gut and Cutaneous Microbiome Featuring Abundance of Lactobacillus reuteri Protected Against Psoriasis-Like Inflammation in Mice.
Psoriasis is a chronic autoinflammatory skin disease, and its aetiology remains incompletely understood. Recently, gut microbial dysbiosis is found to be tightly associated with psoriasis. We sought to reveal the causal role of gut microbiota dysbiosis in psoriasis pathogenesis and investigate the protective effect of healthy commensal bacteria against imiquimod -induced psoriasis-like skin response. By using fecal microbial transplantation (FMT), 16S rRNA gene-based taxonomic profiling and Lactobacillus supplement, we have assessed the effect of FMT from healthy individuals on psoriasis-like skin inflammation and associated immune disorders in imiquimod-induced psoriasis mice. Here, by using psoriasis mice humanized with the stools from healthy donors and psoriasis patients, the imiquimod-induced psoriasis in mice with psoriasis patient stool was found to be significantly aggravated as compared to the mice with healthy donor stools. Further analysis showed fecal microbiota of healthy individuals protected against Treg/Th17 imbalance in psoriasis. Moreover, we found the gut and skin microbiome in mice receipted with gut microbiota of healthy individuals (HD) differed from those of mice receipted with gut microbiota of psoriasis patients (PSD). 16S rRNA sequencing revealed that Lactobacillus reuteri was greatly enriched in fecal and cutaneous microbiome of HD mice as compared to PSD mice. Intriguingly, supplement with Lactobacillus reuteri was sufficient to increase the expression of anti-inflammatory gene IL-10, reduce Th17 cells counts and confer resistance to imiquimod-induced inflammation on the mice with gut microbiota dysbiosis. Our results suggested that the gut microbiota dysbiosis is the potential causal factor for psoriasis and the gut microbiota may serve as promising therapy target for psoriasis patients.


Extrathyroidal Extension Is Associated with Compromised Survival in Patients with Thyroid Cancer.
Patients with thyroid cancer who have extrathyroidal extension (ETE) are considered to have more advanced tumors. However, data on the impact of ETE on patient outcomes remain limited. The purpose of this study was to evaluate the association between ETE and survival in patients with thyroid cancer. The National Cancer Database (1998-2012) was queried for all adult patients with differentiated thyroid cancer and medullary thyroid cancer. Patients were divided into three groups: no ETE (T1 and T2 tumors), minimal ETE (T3 tumors <4 cm), and extensive ETE (T4 tumors <4 cm). Patient demographic, clinical, and pathologic factors were evaluated for all patients. A Cox proportional hazards model was developed for each histology to identify factors associated with survival. In total, 241,118 patients with differentiated thyroid cancer met the inclusion criteria; 86.9% had no ETE, 9.1% minimal ETE, and 4.0% extensive ETE. Compared with patients with no ETE, patients with minimal and extensive ETE were more likely to have larger tumors (1.4 cm vs. 1.8 cm and 2.0 cm, respectively), lymphovascular invasion (8.6% vs. 28.0% and 35.1%, respectively), positive margins after thyroidectomy (6.1% vs. 35.2% and 45.9%, respectively), and regional lymph node metastases (32.5% vs. 67.0% and 74.6%, respectively; all p < 0.01). After adjustment, minimal ETE (hazard ratio [HR] = 1.13; p < 0.01) and extensive ETE (HR = 1.74; p < 0.01) were associated with compromised survival for patients with differentiated thyroid cancer. In total, 3415 patients with medullary thyroid cancer met the inclusion criteria; 87.9% had no ETE, 7.1% minimal ETE, and 5.0% extensive ETE. Compared with patients with no ETE, patients with minimal and extensive ETE were more likely to have larger tumors (1.7 cm vs. 2.2 cm and 2.2 cm, respectively), lymphovascular invasion (19.2% vs. 68.9% and 79.3%, respectively), positive margins after thyroidectomy (5.8% vs. 44.1% and 51.9%, respectively), and regional lymph node metastases (39.0% vs. 90.5% and 94.4%, respectively; all p < 0.01). After adjustment, extensive ETE (HR = 1.63; p = 0.01) was associated with compromised survival for patients with medullary thyroid cancer. In patients with differentiated and medullary thyroid cancers, ETE is associated with compromised survival. Given these findings, ETE should be included in the thyroid cancer treatment guidelines.


Aspirin-Based Organoiron Dendrimers as Promising Anti-Inflammatory, Anticancer, and Antimicrobial Drugs.
Designing nanocarriers with actions directed at a specific organ or tissue is a very promising strategy since it can significantly reduce the toxicity of a bioactive drug. In this study, an organometallic dendrimer was used to synthesize a biocompatible drug delivery system by attaching aspirin to the periphery of the dendrimer. Our goal is to enhance the bioavailability and anticancer activity of aspirin and reduce its toxicity through successive generations of organoiron dendrimers. The biological activity of aspirin-based dendrimer complexes was evaluated. The result of antimicrobial activity of the synthesized dendrimers also demonstrated an increase in their antimicrobial activity with increased generation of the dendrimers for most types of microorganisms. This study reveals for the first time that organoiron dendrimers linked with aspirin exhibit an excellent Gram-negative activity comparable to the reference drug Gentamicin. All synthesized dendrimers were tested for their anticancer activity against breast cancer cell lines (MCF-7), hepatocellular cell lines (Hep-G2), and a non-cancer cell line, Human Embryonic Kidney (HEK293), using the MTT cell viability assay and compared against a standard anticancer drug, Doxorubicin. Compounds G3-D9-Asp and G4-D12-Asp exhibited noticeable activity against both cell lines, both of which were more effective than aspirin itself. In addition, the in vivo anti-inflammatory activity and histopathology of swollen paws showed that the designed aspirin-based dendrimers displayed significant anti-inflammatory activity; however, G2-D6-Asp showed the best anti-inflammatory activity, which was more potent than the reference drug aspirin during the same period. Moreover, the coupling of aspirin to the periphery of organoiron dendrimers showed a significant reduction in the toxicity of aspirin on the stomach.


Detection of vitronectin mRNA in tissues and cells of the mouse.
Mouse vitronectin (Vn) was isolated from serum by heparin affinity chromatography. The purified protein (Mr 71,000) supported adhesion of mouse and human cells in an Arg-Gly-Asp-dependent manner and bound to type 1 plasminogen activator inhibitor with kinetics similar to those observed using human and bovine Vn. To further characterize murine Vn and its biosynthesis in vivo, a mouse Vn cDNA was isolated from a liver cDNA library. The amino acid sequence of mouse Vn was deduced from the cDNA and was aligned with that of human Vn. Based on this alignment, mouse Vn was inferred to be 457 amino acids long and to have extensive (82%) homology with human Vn. Northern blot hybridization analysis of RNA from mouse tissues, using the mouse Vn cDNA as a hybridization probe, revealed the presence of a single transcript of 1.7 kilobases in mouse liver. Vn mRNA was not detectable in heart, lung, kidney, spleen, muscle, brain, thymus, testes, uterus, skin, adipose tissue, and aorta. The cellular localization of liver Vn mRNA was studied by in situ hybridization. Strong staining was observed only in hepatocytes, suggesting that these cells are the primary source of Vn in vivo.


Health status at entry to methadone maintenance treatment using the SF-36 health survey questionnaire.
This study used the SF-36 general health questionnaire to measure the health status of heroin users at entry to a public methadone maintenance programme. Their results were compared to those from the general population and from three clinical groups: patients with minor medical, major medical and psychiatric problems. One hundred consecutive clients were interviewed in the first week on the programme using the SF-36 health questionnaire. Data were also gathered on their drug use, use of medical services and HIV risk behaviour. The results showed that heroin users at entry to the methadone maintenance programme had significantly worse physical and psychological health than the general population. Their scores were most similar to the psychiatrically depressed patients, although they had worse physical health than this comparison group. The greater the amount of heroin used by clients before entering the programme, the more pain they reported. Alcohol and marijuana use were associated with better social and physical health. The relationship between general health status and amount or frequency of drug use is not a clear one. Heroin users experience severe emotional and physical problems at the time of entering methadone maintenance treatment.


Primary Care Patients' Willingness to Participate in Comprehensive Weight Loss Programs: From the WWAMI Region Practice and Research Network.
In the United States, 69% of adults are overweight or obese, as defined by a body mass index (BMI) ≥25 kg/m(2). The US Preventive Services Task Force recommends screening all adult patients for obesity and referring obese patients to intensive, multicomponent behavioral weight loss programs comprising 12 to 26 yearly sessions. The objective of this study is to determine the degree to which overweight and obese primary care patients report willingness to participate in these intensive weight loss programs and to identify the patient factors associated with reported willingness to participate. This 2013 cross-sectional survey was offered to all adult patients seen for an office visit at 1 of 12 primary care clinics in the Washington, Wyoming, Alaska, Montana and Idaho (WWAMI) Region Practice and Research Network (WPRN). Patients self-reported both their health information and their willingness to participate in a comprehensive weight loss program. Respondents were characterized by descriptive statistics. We compared reported rates of willingness to participate by patient factors and assessed which patient factors were independently associated with reported willingness using bivariate analysis and logistic regression, respectively. Of overweight and obese respondents, 63% reported willingness to participate in comprehensive weight loss programs. Age, sex, race/ethnicity, insurance status, BMI, and reason for wanting to lose weight were all significantly and independently associated with reported willingness to participate. Reported willingness to participate in comprehensive weight loss programs suggests that additional resources are needed to understand strategies for disseminating and implementing effective comprehensive weight loss programs.


Motion sickness in migraine sufferers.
Motion sickness commonly occurs after exposure to actual motion, such as car or amusement park rides, or virtual motion, such as panoramic movies. Motion sickness symptoms may be disabling, significantly limiting business, travel and leisure activities. Motion sickness occurs in approximately 50% of migraine sufferers. Understanding motion sickness in migraine patients may improve understanding of the physiology of both conditions. Recent literature suggests important relationships between the trigeminal system and vestibular nuclei that may have implications for both motion sickness and migraine. Studies demonstrating an important relationship between serotonin receptors and motion sickness susceptibility in both rodents and humans suggest possible new motion sickness prevention therapies.


WATERSHED INFARCTION IN HYPEREOSINOPHILIC SYNDROME: A DIAGNOSTIC DILEMMA IN FIP1L1-PDGFR ALPHA-ASSOCIATED MYELOID NEOPLASM.
The FIP1L1-PDGFR alpha-positive, hypereosinophilic syndrome (HES) is a new category of hematological entities. Various clinical symptoms may occur, with no specific characteristics in either the clinical picture or the neuroimaging findings, and this may give rise to a diagnostic dilemma. A report on a long follow-up period (10 years) in a case of HES that presented with neuropsychiatric symptoms appears to be unique. Besides the complexity of the diagnostic process, the successful treatment is discussed. The HES was diagnosed in a male patient at the age of 33 years, with involvement of the central nervous system and the myocardium. After the onset of the clinical signs, the MRI indicated bilateral cerebral and cerebellar cortico-subcortical lesions involving the watershed areas, mainly in the parieto-occipital regions. High-dose intravenous steroid (methylprednisolone 500 mg/day) alleviated the neurological symptoms within a few weeks, and the administration of imatinib (200 mg/day) resulted in an impressive regression of the hypereosinophilia and splenomegaly within 6 weeks. During the follow-up, the patient has continued to receive imatinib. The molecular remission has persisted, no new complaints have developed and the condition of the patient has remained stable. The timely recognition of the HES and identification of the disease subtype which led to the administration of imatinib may be the key to successful treatment. The long stable follow-up period gives rise to a new dilemma in the treatment of the HES in these special cases: for how long should a patient receive a tyrosine kinase inhibitor, and may the treatment be suspended?


Theoretical investigation of non-Förster exciton transfer mechanisms in perylene diimide donor, phenylene bridge, and terrylene diimide acceptor systems.
The rates of exciton transfer within dyads of perylene diimide and terrylene diimide connected by oligophenylene bridge units have been shown to deviate significantly from those of Förster's resonance energy transfer theory, according to single molecule spectroscopy experiments. The present work provides a detailed computational and theoretical study investigating the source of such a discrepancy. Electronic spectroscopy data are calculated by time-dependent density functional theory and then compared with experimental results. Electronic couplings between the exciton donor and the acceptor are estimated based on both the transition density cube method and transition dipole approximation. These results confirm that the delocalization of the exciton to the bridge parts contributes to significant enhancement of donor-acceptor electronic coupling. Mechanistic details of exciton transfer are examined by estimating the contributions of the bridge electronic states, vibrational modes of the dyads commonly coupled to both donor and acceptor, inelastic resonance energy transfer mechanism, and dark exciton states. These analyses suggest that the contribution of common vibrational modes serves as the main source of deviation from Förster's spectral overlap expression.


The therapeutic management of back pain with and without sciatica in the emergency department: a systematic review.
An increasing number of patients are attending the Emergency Department (ED) with back pain with or without sciatica. There is evidence to suggest that medical management is varied and inconsistent. The purpose of this study was to review the literature to determine the evidence base for the therapeutic management of adults presenting with back pain with or without sciatica in the ED. A systematic review of the literature included the therapeutic management of patients presenting in the ED. Articles published in peer review journals in English language up to August 2018 were searched for in the following data-bases: MEDLINE, EMBASE, SCOPUS, CINAHL, ZETOC, PubMed, The Cochrane Library (Cochrane Database of Systematic Reviews), Web of Science, Open Grey and ETHOS. A narrative synthesis approach was followed. Twenty two studies, including 17 randomised control trials, one randomised control pilot study, two cohort studies, one cohort pilot study and one retrospective audit were included. The Downs and Black methodological quality scores ranged from 16 to 31 with a mean score of 24 out of a possible 32. Evidence suggests that Naproxen alone should be considered as first line management in cases of back pain without sciatica. Intra-venous corticosteroids should be considered in the management of cases of severe sciatica. More high quality trials are needed to determine an evidence-based management protocol for the treatment of acute low back pain in the ED, specifically focusing on non-pharmacological management and the first line management of patients presenting with LBP with sciatica. Systematic Review Registration Number PROSPERO CRD42016042087.


[Postoperative angioedema induced by angiotensin-converting enzyme inhibitor: case report].
Angioedema is a potentially fatal condition that may occur at any time in the perioperative period. It may result from histamine release, hypersensitivity reaction to drugs, or be triggered by bradykinin, in non-allergic reactions of hereditary or acquired etiology. The aim of this report is to report a case of angioedema in the early postoperative period in a patient on antihypertensive medication involving angiotensin-converting enzyme inhibitors. A 67-year-old male, Afro-descendant, hypertensive, and taken enalapril maleate underwent orthopedic shoulder surgery under general anesthesia combined with brachial plexus block. The procedure lasted 3hours uneventfully. After discharge from the post-anesthesia care unit, the patient presented with angioedema and severe airway impairment. Tracheal intubation was attempted but it was impossible due to edema affecting the lips, tongue, and oropharyngeal region Emergency cricothyroidotomy was performed. The onset of angioedema had no causal relationship with the administration of any medication; there were no cutaneous manifestations and also not response to therapy for hypersensitivity reaction to drugs, such as antihistamines, corticoid, and adrenaline. It was considered to be mediated by bradykinin, as the patient had already had two similar episodes and was on regular medication (enalapril). The evolution was satisfactory. Angioedema is a potentially fatal condition when it affects the airway, and should be recognized by anesthesiologists and physicians working in the emergency departments.


Polynomial modal analysis of lamellar diffraction gratings in conical mounting.
An efficient numerical modal method for modeling a lamellar grating in conical mounting is presented. Within each region of the grating, the electromagnetic field is expanded onto Legendre polynomials, which allows us to enforce in an exact manner the boundary conditions that determine the eigensolutions. Our code is successfully validated by comparison with results obtained with the analytical modal method.


Effects of T142 phosphorylation and mutation R145G on the interaction of the inhibitory region of human cardiac troponin I with the C-domain of human cardiac troponin C.
Cardiac troponin I (cTnI) is the inhibitory component of the troponin complex, and its interaction with cardiac troponin C (cTnC) plays a critical role in transmitting the Ca(2+) signal to the other myofilament proteins in heart muscle contraction. The switch between contraction and relaxation involves a movement of the inhibitory region of cTnI (cIp) from cTnC to actin-tropomyosin. This region of cTnI is prone to missense mutations in heart disease, and a specific mutation, R145G, has been associated with familial hypertrophic cardiomyopathy. It also contains the unique cardiac PKC phosphorylation site at residue T142. To determine the structural consequences of the mutation R145G and the T142 phosphorylation on the interaction of cIp with cTnC, we have utilized 2D [(1)H, (15)N]-HSQC NMR spectroscopy to monitor the binding of native cIp, cIp-R (R145G), and cIp-P (phosphorylated T142), respectively, to the Ca(2+)-saturated C-domain of cTnC (cCTnC.2Ca(2+)). We also report a strategy for cloning, expression, and purification of cTnI peptide, and both synthetic and recombinant peptides are used in this study. NMR chemical shift mapping indicates that the binding epitope of cIp on cCTnC.2Ca(2+) is not greatly affected, but the affinity is reduced by approximately 14-fold by the T142 phosphorylation and approximately 4-fold by the mutation R145G, respectively. This suggests that these modifications of cIp have an adverse effect on the binding of cIp to cCTnC.2Ca(2+). These perturbations may correlate with the impairment or loss of cTnI function in heart muscle contraction.


The evolution of an academic-community partnership in the design, implementation, and evaluation of experience corps® Baltimore city: a courtship model.
Experience Corps Baltimore City (EC) is a product of a partnership between the Greater Homewood Community Corporation (GHCC) and the Johns Hopkins Center on Aging and Health (COAH) that began in 1998. EC recruits volunteers aged 55 and older into high-impact mentoring and tutoring roles in public elementary schools that are designed to also benefit the volunteers. We describe the evolution of the GHCC-COAH partnership through the "Courtship Model." We describe how community-based participatory research principals, such as shared governance, were applied at the following stages: (1) partner selection, (2) getting serious, (3) commitment, and (4) leaving a legacy. EC could not have achieved its current level of success without academic-community partnership. In early stages of the "Courtship Model," GHCC and COAH were able to rely on the trust developed between the leadership of the partner organizations. Competing missions from different community and academic funders led to tension in later stages of the "Courtship Model" and necessitated a formal Memorandum of Understanding between the partners as they embarked on a randomized controlled trial. The GHCC-COAH partnership demonstrates how academic-community partnerships can serve as an engine for social innovation. The partnership could serve as a model for other communities seeking multiple funding sources to implement similar public health interventions that are based on national service models. Unified funding mechanisms would assist the formation of academic-community partnerships that could support the design, implementation, and the evaluation of community-based public health interventions.


Business plan development: a door to the future.
The face of the American health care delivery system is changing, and change means opportunity. A business plan--the medical entrepreneur's tool to create future opportunities--can be introduced, described, and explained in terms of a positive contribution to an organization's financial viability.


Modified chemical vapor deposition synthesis of ultralong V2O5 nanobelt and its electronic properties.
The fascinating properties and wide applications of the V2O5 nanostructures have attracted significant attention over the past decades. In this paper, ultralong (centimeter-scale) single-crystal V2O5 nanobelts are successfully fabricated by modified chemical vapor deposition. The wide of the V2O5 nanobelts are 20-500 nm. The aspect ratio exceeds 10(5). The structure and crystal orientation of the nanobelts are investigated. X-ray diffractometer (XRD) patterns and Raman spectrum show the substrate temperature affecting the size and morphology of the V2O5 nanobelts. And the growth mechanism and electronic properties of the ultralong V2O5 nanobelt are studied in detail. The activation energy 0.12 eV is calculated. The fastest growth orientation along the [010] direction has been observed. Our work demonstrates that the single-crystal V2O5 nanobelt has potential applications in field-emitters, lithium-ion batteries, photodetectors, interconnect, and optoelectronic devices, etc.


Writing waveguides inside monolithic crystalline silicon with nanosecond laser pulses.
Direct three-dimensional (3D) laser writing of waveguides is highly advanced in a wide range of bandgap materials, but has no equivalent in silicon so far. We show that nanosecond laser single-pass irradiation is capable of producing channel micro-modifications deep into crystalline silicon. With an appropriate shot overlap, a relative change of the refractive index exceeding 10-3 is obtained without apparent nonuniformity at the micrometer scale. Despite the remaining challenge of propagation losses, we show that the created structures form, to the best of our knowledge, the first laser-written waveguides in the bulk of monolithic silicon samples. This paves the way toward the capability of producing 3D architectures for the rapidly growing field of silicon photonics.


Cu(OAc)2-promoted reaction of [60]fullerene with primary amines or diamines.
The Cu(OAc)2-promoted reaction of C60 with easily available primary amines allows the concise preparation of aziridinofullerenes. Both alkyl and aryl amines are suitable in this reaction. Moreover, the Cu(OAc)2-promoted reaction of C60 with diamines affords C60-fused cyclic 1,2-diaminated fullerenes.


Negative control of epithelial cell proliferation by prostatic stroma.
The influence of prostatic fibroblasts on the growth of the prostatic carcinoma cell lines PC-3 and LNCaP was examined. In a double layer soft agar system, clonal growth of both cell lines was inhibited by all prostatic fibroblasts tested, irrespective of whether they were derived from malignant or non malignant prostate tissue. Irradiated fibroblasts and quiescent fibroblasts showed similar effects. The finding that growth was also inhibited in the presence of fibroblasts conditioned medium suggests that the observed effects were mediated by a diffusable growth inhibiting factor. Organ-specific production was suggested by the observation that skin fibroblasts stimulated rather than inhibited PC-3 cell growth. These findings indicate a negative control of epithelial cell proliferation by prostatic stroma.


Assessment and management of children aged 1-59 months presenting with wheeze, fast breathing, and/or lower chest indrawing; results of a multicentre descriptive study in Pakistan.
Using current WHO guidelines, children with wheezing are being over prescribed antibiotics and bronchodilators are underutilised. To improve the WHO case management guidelines, more data is needed about the clinical outcome in children with wheezing/pneumonia overlap. In a multicentre prospective study, children aged 1-59 months with auscultatory/audible wheeze and fast breathing and/or lower chest indrawing were screened. Response to up to three cycles of inhaled salbutamol was recorded. The responders were enrolled and sent home on inhaled bronchodilators, and followed up on days 3 and 5. A total of 1622 children with wheeze were screened from May 2001 to April 2002, of which 1004 (61.8%) had WHO defined non-severe and 618 (38.2%) severe pneumonia. Wheeze was audible in only 595 (36.7%) of children. Of 1004 non-severe pneumonia children, 621 (61.8%) responded to up to three cycles of bronchodilator. Of 618 severe pneumonia children, only 166 (26.8%) responded. Among responders, 93 (14.9%) in the non-severe and 63 (37.9%) children in the severe pneumonia group showed subsequent deterioration on follow ups. No family history of wheeze, temperature >100 degrees F, and lower chest indrawing were identified as predictors of subsequent deterioration. Two third of children with wheeze are not identified by current WHO ARI (acute respiratory infections) guidelines. Antibiotics are over prescribed and bronchodilators under utilised in children with wheeze. Children with wheeze constitute a special ARI group requiring a separate management algorithm. In countries where wheeze is common it would be worthwhile to train health workers in use of the stethoscope to identify wheeze.


[Clinical observation on human alpha glucosidase in treatment of five patients with glycogen storage disease Ⅱ].
Objective: To evaluate the effect of enzyme replacement therapy (ERT) on glycogen storage disease typeⅡ(GSDⅡ). Method: The clinical data of three juvenile onset and two infant onset GSDⅡpatients were collected from First Affiliated Hospital of Sun Yat-sen University in October 2015 to July 2016.Patient 1 was female, the age of onset was 15 months. Patient 2 was male, the age of onset was 20 months. Patient 3 was female, the sister of patient 2, the age of onset was 47 months. Patient 4 was male, the age of onset was 5 months. Patient 5 was male, the age of onset was 1 month.The age at the start of ERT of the 5 patients was 32, 31, 56, 34, and 3 months respectively and the duration of ERT was 19, 9, 4, 5, 5 doses respectively.ERT was administered at 20 mg/kg every 2 weeks.Dexamethasone was regularly given before each infusion. Result: ERT was well tolerated, only one time, Patient 1 developed tachycardia and hypertension without using dexamethasone.Patient 2 underwent successfully ventilator weaning.Patient 1 underwent a tracheotomy, also needed mechanical ventilation treatment.Patient 4 noninvasive ventilation was tried. Conclusion: Recombinant human alpha-glucosidase treatment was effective and well tolerated in patients with GSDⅡ.


The immunoregulatory role of CD4⁺ FoxP3⁺ CD25⁻ regulatory T cells in lungs of mice infected with Bordetella pertussis.
The identification of regulatory T (Treg) cells was originally based on CD25 expression; however, CD25 is also expressed by activated effector T cells. FoxP3 is a more definitive marker of Treg cells, and CD4(+) FoxP3(+) CD25(+) T cells are considered the dominant natural Treg (nTreg) population. It has been suggested that certain CD4(+) FoxP3(+) Treg cells do not express CD25. In this study, we used a murine model of respiratory infection with Bordetella pertussis to examine the role of Treg cells in protective immunity in the lung. We first demonstrated that CD4(+) FoxP3(+) CD25(-) cells are the dominant Treg population in the lung, gut and liver. Pre-activated lung CD4(+) FoxP3(+) CD25(-) cells suppressed CD4(+) effector T cells in vitro, which was partly mediated by IL-10 and not dependent on cell contact. Furthermore, CD4(+) FoxP3(+) CD25(-) IL-10(+) T cells were found in the lungs of mice at the peak of infection with B. pertussis. The rate of bacterial clearance was not affected by depletion of CD25(+) cells or in IL-10-deficient (IL-10(-/-) ) mice, but was compromised in CD25-depleted IL-10(-/-) mice. Our findings suggest that IL-10-producing CD4(+) FoxP3(+) CD25(-) T cells represent an important regulatory cell in the lung.


Medications in the first trimester of pregnancy: most common exposures and critical gaps in understanding fetal risk.
To determine which medications are most commonly used by women in the first trimester of pregnancy and identify the critical gaps in information about fetal risk for those medications. Self-reported first-trimester medication use was assessed among women delivering liveborn infants without birth defects and serving as control mothers in two large case-control studies of major birth defects. The Teratology Information System (TERIS) expert Advisory Board ratings of quality and quantity of data available to assess fetal risk were reviewed to identify information gaps. Responses from 5381 mothers identified 54 different medication components used in the first trimester by at least 0.5% of pregnant women, including 31 prescription and 23 over-the-counter medications. The most commonly used prescription medication components reported were progestins from oral contraceptives, amoxicillin, progesterone, albuterol, promethazine, and estrogenic compounds. The most commonly used over-the-counter medication components reported were acetaminophen, ibuprofen, docusate, pseudoephedrine, aspirin, and naproxen. Among the 54 most commonly used medications, only two had "Good to Excellent" data available to assess teratogenic risk in humans, based on the TERIS review. For most medications commonly used in pregnancy, there are insufficient data available to characterize the fetal risk fully, limiting the opportunity for informed clinical decisions about the best management of acute and chronic disorders during pregnancy. Future research efforts should be directed at these critical knowledge gaps.


Drug-induced hair disorders.
Drugs may induce hair loss, stimulate hair growth or, more rarely, induce changes in the hair shape and colour. Drug-induced hair loss is usually completely reversible and is, in most cases, a consequence of a toxic effect of the drug on the hair follicle matrix. In rare cases alopecia may be permanent. Depending on type of drug, dosage and patient susceptibility, hair loss presents as telogen effluvium, anagen effluvium or both. Telogen effluvium is also commonly observed after discontinuation of drugs that prolong anagen, such as topical minoxidil and oral contraceptives. Although a large number of drugs have been occasionally reported to produce hair loss, only for a few drugs the relation between drug intake and hair loss has been proven.


Moheibacter stercoris sp. nov., isolated from an input sample of a biogas plant.
A Gram-stain-negative, rod-shaped bacterium, strain 784B1_12E-CasoT, was isolated from a mixed manure sample used as input material of a German biogas plant. Phylogenetic identification based on the nearly full-length 16S rRNA gene sequence placed the strain within the family Flavobacteriaceae(Bacteroidetes) with highest sequence similarity to the type strain of Moheibacter sediminis (93.7 %) followed by Empedobacter brevis(90.7 %). Major cellular fatty acids of strain 784B1_12E-CasoT were iso-C15 : 0 and iso-C17 : 0 3-OH. The polyamine pattern contained predominantly sym-homospermidine and the quinone system consisted exclusively of menaquinone MK-6. Major polar lipids were phosphatidylethanolamine and an unidentified polar lipid only detectable after staining for total lipids. The DNA G+C content was 34.5 mol%. Based on phylogenetic, chemotaxonomic and physiological analyses, a novel species of the genus Moheibacter is proposed, Moheibacterstercoris sp. nov. (type strain 784B1_12E-CasoT=CIP 110830T=LMG 28502T).


The predictive value of mean platelet volume, plateletcrit and red cell distribution width in the differentiation of autoimmune gastritis patients with and without type I gastric carcinoid tumors.
Autoimmune gastritis is an autoimmune and inflammatory condition that may predispose to gastric carcinoid tumors or adenocarcinomas. The early diagnosis of these tumors is important in order to decrease morbidity and mortality. Platelet indices such as mean platelet volume and plateletcrit levels increase in inflammatory, infectious and malign conditions. The primary aim of this study was to explore wheter platelet indices and red cell distribution width have any predictive role in the discrimination of autoimmune gastritis patients with and without gastric carcinoid tumors. Also secondary aim of this study was to investigate whether any changes exist betwenn autoimmune gastritis and functional dyspepsia patients by means of platelet indices. Plateletcrit (0.22 ± 0.06 vs. 0.20 ± 0.03%, p < 0.001) and red cell distribution width (16.11 ± 3.04 vs. 13.41 ± 0.95%, p < 0.001) were significantly higher in autoimmune gastritis patients compared to control group. Receiver operating curve analysis suggested that optimum plateletcrit cut-off point was 0.20% (AUC: 0.646), and 13.95% as the cut off value for red cell distribution width (AUC: 0.860). Although plateletcrit (0.22 ± 0.06 vs. 0.21 ± 0.04%, p = 0.220) and mean platelet volume (8.94 ± 1.44 vs. 8.68 ± 0.89 fl, p = 0.265) were higher in autoimmune gastritis patients without carcinoid tumor compared to patients with carcinoid tumors, these parameters were not statistically significant. Changes in plateletcrit and red cell distribution width values may be used as a marker in the discrimination of autoimmune gastritis and fucntional dyspepsia patients but not useful in patients with gastric carcinoid tumor type I.


Murine homologues of the Drosophila gustavus gene are expressed in ovarian granulosa cells.
Mammalian homologues of genes that control oogenesis in other organisms may play similar roles in mammalian ovarian development. In Drosophila melanogaster, GUSTAVUS (GUS) protein physically interacts with and is necessary for the proper posterior localization of VASA protein, and thus is required for specification of germ cells. We identified two mouse genes, SSB-1 and SSB-4 (SPRY domain SOCS box protein), whose protein products share 75% identity and are each approximately 70% identical to Drosophila GUS. Both SSB-1 and SSB-4 mRNA were detectable in mouse ovaries by Northern blotting of total and poly(A) + RNA, but were expressed in few other tissues. SSB-1 was detectable in testes, although the 3'-untranslated region of the mRNA was considerably shorter than the ovarian mRNA. In situ hybridization and RT-PCR analysis of ovaries revealed that both genes were expressed in granulosa cells at all stages of follicular development. In contrast, expression was barely detectable in in oocytes. Immunoblotting analysis revealed that SSB-1 protein was present in follicles at different stages of growth, and immunocytochemistry confirmed that SSB-1 and SSB-4 were detectable in granulosa cells of primary and subsequent stage follicles and that they were present in both mural and cumulus granulosa cells of antral follicles. These results establish that GUS-related proteins, which in Drosophila are restricted to the germ cells, are in the mouse instead expressed in the granulosa cells and are present throughout folliculogenesis. Based on their tissue-restricted pattern of expression and apparent abundance in granulosa cells, we propose that SSB-1 and SSB-4 play key roles in regulating granulosa cell physiology.


Mutational analysis of the primary substrate specificity pocket of complement factor B. Asp(226) is a major structural determinant for p(1)-Arg binding.
Factor B is a serine protease, which despite its trypsin-like specificity has Asn instead of the typical Asp at the bottom of the S(1) pocket (position 189, chymotrypsinogen numbering). Asp residues are present at positions 187 and 226 and either one could conceivably provide the negative charge for binding the P(1)-Arg of the substrate. Determination of the crystal structure of the factor B serine protease domain has revealed that the side chain of Asp(226) is within the S(1) pocket, whereas Asp(187) is located outside the pocket. To investigate the possible role of these atypical structural features in substrate binding and catalysis, we constructed a panel of mutants of these residues. Replacement of Asp(187) caused moderate (50-60%) decrease in hemolytic activity, compared with wild type factor B, whereas replacement of Asn(189) resulted in more profound reductions (71-95%). Substitutions at these two positions did not significantly affect assembly of the alternative pathway C3 convertase. In contrast, elimination of the negative charge from Asp(226) completely abrogated hemolytic activity and also affected formation of the C3 convertase. Kinetic analyses of the hydrolysis of a P(1)-Arg containing thioester by selected mutants confirmed that residue Asp(226) is a primary structural determinant for P(1)-Arg binding and catalysis.


Oxidation in the complementarity-determining regions differentially influences the properties of therapeutic antibodies.
Therapeutic antibodies can undergo a variety of chemical modification reactions in vitro. Depending on the site of modification, either antigen binding or Fc-mediated functions can be affected. Oxidation of tryptophan residues is one of the post-translational modifications leading to altered antibody functionality. In this study, we examined the structural and functional properties of a therapeutic antibody construct and 2 affinity matured variants thereof. Two of the 3 antibodies carry an oxidation-prone tryptophan residue in the complementarity-determining region of the VL domain. We demonstrate the differences in the stability and bioactivity of the 3 antibodies, and reveal differential degradation pathways for the antibodies susceptible to oxidation.


Mediators of the Jak/STAT signaling pathway in human spermatozoa.
In their journey to acquire the ability to fertilize the egg, numerous intracellular signaling systems are activated in spermatozoa, leading to an increase in protein tyrosine phosphorylation. Although the JAK/STAT signaling pathway is usually associated with the activation of transcription of specific genes, our laboratory previously demonstrated the presence of the IL6 receptor (IL6R) and the Janus kinase 1 (JAK1) in human spermatozoa, a cell that is mostly transcriptionally inactive. In order to determine the importance of the JAK/STAT signaling pathway, our objectives were to identify and characterize the mediators of this system in human sperm. Cell fractionation and surface biotinylation assays clearly demonstrated that IL6R is expressed at the sperm membrane surface. The kinase JAK1 is enriched in membrane fractions and is activated during human sperm capacitation as suggested by its increase in phosphotyrosine content. Many signal transducer and activator of transcription (STAT) proteins are expressed in human sperm, including STAT1, STAT3, STAT4, STAT5, and STAT6. Among them, only STAT1 and STAT5 were detected in the cytosolic fraction. All the detected STAT proteins were enriched in the cytoskeletal structures. STAT4 was present in the perinuclear theca, whereas JAK1, STAT1, and STAT5 were detected in the fibrous sheath. Indirect immunofluorescence studies showed that JAK1 and STAT1 colocalized in the neck region and that STAT4 is present at the equatorial segment and flagella. The presence of STAT proteins in sperm structural components suggests that their role is different from their well-known transcription factor activity in somatic cells, but further investigations are required to determine their role in sperm function.


An oligodeoxyribonucleotide N3'--> P5' phosphoramidate duplex forms an A-type helix in solution.
The solution conformations of the dinucleotide d(TT) and the modified duplex d(CGCGAATTCGCG)2 with N3'--> P5' phosphoramidate internucleoside linkages have been studied using circular dichroism (CD) and NMR spectroscopy. The CD spectra indicate that the duplex conformation is similar to that of isosequential phosphodiester RNA, a A-type helix, and is different from that of DNA, a B-type helix, NMR studies of model dimers d(TpT) and N3'--> P5' phosphoramidate d(TnpT) show that the sugar ring conformation changes from predominantly C2'-endo to C3'-endo when the 3'-phosphoester is replaced by a phosphoramidate group. Two-dimensional NMR (NOESY, DQF-COSY and TOCSY spectra) studies of the duplex provide additional details about the A-type duplex conformation of the oligonucleotide phosphoramidate and confirm that all furanose rings of 3'-aminonucleotides adopt predominantly N-type sugar puckering.


Relapse of Graves' disease after medical therapy: predictive value of thyroidal technetium-99m uptake and serum thyroid stimulating hormone receptor antibody levels.
In 49 patients with Graves' disease, the 20-min thyroidal uptake of 99mTc and serum levels of thyroid stimulating hormone (TSH) receptor antibody were estimated at presentation and at intervals during a 1-yr course of carbimazole and triiodothyronine. In the 12 mo after cessation of therapy, 29 patients developed recurrent thyrotoxicosis. Thyroidal 99mTc uptake had a poor predictive value for recurrence of thyrotoxicosis, both at presentation and during therapy. A very high level of TSH receptor antibody was present in seven patients at presentation, all of whom relapsed on withdrawing therapy. An abnormal value of TSH receptor antibody at the end of the course of medical therapy was present in 24/29 (83%) patients who relapsed and in 1/20 (5%) patients who remained euthyroid 1 yr after stopping antithyroid drugs.


The use of computed radiography for routine linear accelerator and simulator quality control.
Computed radiography (CR) systems were originally developed for the purpose of clinical imaging, and there has been much work published on its effectiveness as a film replacement for this end. However, there has been little published on its use for routine linear accelerator and simulator quality control, and therefore we have evaluated the use of the Kodak 2000RT system with large Agfa CR plates as a replacement for film for this function. A prerequisite for any such use is a detailed understanding of the system behaviour, hence characteristics such as spatial uniformity of response, reproducibility of spatial accuracy, plate signal decay with time and the dose-response of plates were investigated. Finally, a comparison of results obtained using CR for the measurement of radiation field dimensions was made against those from radiographic film, and found to be in agreement within 0.1 mm (mean difference for high-resolution images, 0.3 mm root mean square difference) for megavoltage images and 0.3 mm (maximum difference) for simulator images. In conclusion, the CR system has been shown to be a good alternative to radiographic film for routine quality control of linear accelerators and simulators.


Chronological observation on the energy metabolism of skin flaps by 31P-MRS: a novel approach to evaluate the state of a flap.
Although much has been reported on the energy metabolism of various flaps, at present there is no practical noninvasive and nondestructive method to demonstrate chronologically the changes in phosphate compounds in the same subject during the healing process. A skin island flap was obtained from the dorsal side of the posterior extremities in each of 18 Wistar female rats, and a skin arterial island flap (vein included in the pedicle was ligated and divided) also was obtained from the same area in each of 15 Wistar female rats. Chronological changes of ATP, phosphocreatine, and inorganic phosphate were observed by 31P-MRS (magnetic resonance spectroscopy) using surface coils at various intervals ranging from 2 hours to 1 week after the operation. And pH was calculated based on the chemical shift values. The results showed that the PCr/Pi ratio recovered at 4 to 8 hours postoperatively in the survival group, whereas the PCr/Pi ratio lasted at the low level after the operations in the necrosis group. Magnetic resonance spectroscopy is used extensively in studies of brain, heart, and muscle, but we have found only a few papers dealing with magnetic resonance spectroscopy and none with in vivo study in the field of plastic and reconstructive surgery. Since nuclear magnetic resonance imaging is becoming a "bedside" test in the general hospitals, we consider that the PCr/Pi ratio obtained from 31P-MRS can be an effective, noninvasive, and simple method for clinical use in predicting and observing the viability of flaps at an early stage.


Salvage Therapy After Regorafenib or Trifluridine/Tipiracil Treatment of Metastatic Colorectal Cancer: A Conditional Landmark Analysis.
This study aimed to describe the chemotherapy effects after trifluridine/tipiracil (TFTD) and/or regorafenib treatment in colorectal cancer (CRC) patients. Patients receiving regorafenib or TFTD for metastatic CRC during 2013-2018 were selected and divided into two groups: one with additional chemotherapy after regorafenib or TFTD (CTX group) and one without additional chemotherapy (Non-CTX group). Patients were followed up from a landmark point (90 days from the last day of administration of regorafenib or TFTD). We compared overall survival (OS) between the groups. The median OS was 7.7 months in the CTX group and 4.1 months in the non-CTX groups. Several sensitivity analyses did not negate the survival advantage detected in the CTX group. The chemotherapy after regorafenib or TFTD was associated with prolonged OS in advanced CRC patients. Further study is required to determine appropriate treatment choice.


Motility and the polar flagellum are required for Aeromonas caviae adherence to HEp-2 cells.
Aeromonas caviae is increasingly being recognized as a cause of gastroenteritis, especially among the young. The adherence of aeromonads to human epithelial cells in vitro has been correlated with enteropathogenicity, but the mechanism is far from well understood. Initial investigations demonstrated that adherence of A. caviae to HEp-2 cells was significantly reduced by either pretreating bacterial cells with an antipolar flagellin antibody or by pretreating HEp-2 cells with partially purified flagella. To precisely define the role of the polar flagellum in aeromonad adherence, we isolated the A. caviae polar flagellin locus and identified five polar flagellar genes, in the order flaA, flaB, flaG, flaH, and flaJ. Each gene was inactivated using a kanamycin resistance cartridge that ensures the transcription of downstream genes, and the resulting mutants were tested for motility, flagellin expression, and adherence to HEp-2 cells. N-terminal amino acid sequencing, mutant analysis, and Western blotting demonstrated that A. caviae has a complex flagellum filament composed of two flagellin subunits encoded by flaA and flaB. The predicted molecular mass of both flagellins was approximately 31,700 Da; however, their molecular mass estimated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis was approximately 35,500 Da. This aberrant migration was thought to be due to their glycosylation, since the proteins were reactive in glycosyl group detection assays. Single mutations in either flaA or flaB did not result in loss of flagella but did result in decreased motility and adherence by approximately 50%. Mutation of flaH, flaJ, or both flagellin genes resulted in the complete loss of motility, flagellin expression, and adherence. However, mutation of flaG did not affect motility but did significantly reduce the level of adherence. Centrifugation of the flagellate mutants (flaA, flaB, and flaG) onto the cell monolayers did not increase adherence, whereas centrifugation of the aflagellate mutants (flaH, flaJ, and flaA flaB) increased adherence slightly. We conclude that maximum adherence of A. caviae to human epithelial cells in vitro requires motility and optimal flagellar function.


Development and Validation of the Short Healthy Eating Index Survey with a College Population to Assess Dietary Quality and Intake.
Because diet quality (DQ) is associated with risk of chronic disease and is a common construct assessed in health-related research, validated tools to assess DQ are needed that have low respondent and researcher burden. Thus, content experts develop the Short Healthy Eating Index (sHEI) tool and an associated scoring system. The sHEI scoring system was then refined using a classification and regression tree (CRT) algorithm methodology with an iterative feedback process with expert review and input. The sHEI scoring system was then validated using a concurrent criterion validation process that included the sHEI DQ scores (calculated from responses from 50 participants) being compared to the participants' Healthy Eating Index scores derived from 24 h recalls. The total HEI score from the CRT algorithm highly correlated with the 24 h recall HEI score (0.79). For individual food group items, the correlation between the CRT algorithm scoring and the 24 h recall data scoring ranged from 0.44 for refined grains to 0.64 for whole fruits. The sHEI appears to be a valid tool for estimating overall dietary quality and individual items (with correlations > 0.49) for fruits, vegetables, dairy, added sugar, sugar from sugar-sweetened beverages, and calcium.


Using bioinformatics for drug target identification from the genome.
Genomics and proteomics technologies have created a paradigm shift in the drug discovery process, with bioinformatics having a key role in the exploitation of genomic, transcriptomic, and proteomic data to gain insights into the molecular mechanisms that underlie disease and to identify potential drug targets. We discuss the current state of the art for some of the bioinformatic approaches to identifying drug targets, including identifying new members of successful target classes and their functions, predicting disease relevant genes, and constructing gene networks and protein interaction networks. In addition, we introduce drug target discovery using the strategy of systems biology, and discuss some of the data resources for the identification of drug targets. Although bioinformatics tools and resources can be used to identify putative drug targets, validating targets is still a process that requires an understanding of the role of the gene or protein in the disease process and is heavily dependent on laboratory-based work.


Characterization of Protein Nanocrystals Based on the Reversibility of Crystallization.
A new approach is described to screen for protein nanocrystals based on the reversibility of crystallization. Methods to characterize nanocrystals are in strong need to facilitate sample preparation for serial femtosecond X-ray nanocrystallography (SFX). SFX enables protein structure determination by collecting X-ray diffraction from nano- and microcrystals using a free electron laser. This technique is especially valuable for challenging proteins as for example membrane proteins and is in general a powerful method to overcome the radiation damage problem and to perform time-resolved structure analysis. Nanocrystal growth cannot be monitored with common methods used in protein crystallography, as the resolution of bright field microscopy is not sufficient. A high-performance method to screen for nanocrystals is second order nonlinear imaging of chiral crystals (SONICC). However, the high cost prevents its use in every laboratory, and some protein nanocrystals may be "invisible" to SONICC. In this work using a crystallization robot and a common imaging system precipitation comprised of nanocrystals and precipitation caused by aggregated protein can be distinguished.


Muscle Activation Differences During Eccentric Hamstring Exercises.
The hamstring muscles play a critical role in the prevention of lower limb injuries. However, it is still unclear which exercises are more effective in terms of muscle activation. In healthy individuals, there are differences between muscular activations of the biceps femoris (BF), semitendinosus (ST), and semimembranosus (SM) muscles during eccentric hamstring exercises. Cross-sectional. Level 2. A total of 31 healthy participants (18 male; mean age, 22.5 years; SD, 3.1) were included in this study. The maximum voluntary isometric contraction of the hamstring muscles was measured using an isokinetic dynamometer. The participants were asked to perform one of the following exercises randomly (3 repetitions each): stiff-leg deadlift (SLDL), unilateral stiff-leg deadlift (USLDL), Nordic hamstring exercise (NHE), and ball leg curl (BLC). Activation of the BF, ST, and SM muscles was measured using surface electromyography during the exercises. In the statistical analysis of this study, factorial analysis of variance was used to compare the effects of each exercise on the muscle groups and to analyze which exercise type was more effective for each muscle group. The NHE led to higher muscle activation than the other exercises (P < 0.001). When exercise type and muscle interaction were examined, SM activation was lower than BF (P = 0.04) and ST (P = 0.001) during NHE (P < 0.05). The highest level of muscular activation was recorded during the NHE in both male and female participants. The NHE may be the most effective exercise for the hamstring muscles as it leads to greater muscle activation. SLDL, USLDL, and BLC exercises may be preferred at the beginning of strength training programs since they lead to lower muscular activation compared with the NHE. To select the optimum hamstring exercise, it is important to know the activation levels of the hamstring muscles during different eccentric exercises.


Low protein supplemented diet corrects altered serum thyroid hormone and TSH concentrations in patients with chronic nephrotic syndrome.
Creatinine clearance, daily urinary protein excretion, serum concentrations of thyroid hormones (TT4, TT3, fT4, fT3), TSH and parathyroid hormone (PTH), have been measured before and after 2 or 6 months of a low protein diet supplemented with aminoacids and ketoanalogues in 18 patients affected by chronic nephrotic syndrome without significant impairment of renal function. Mean creatinine clearance and mean serum protein concentration (79.5 +/- 13.8 ml/min and 5.4 +/- 0.6 g/dl, mean +/- S.D., respectively) did not significantly change (79.1 +/- 17.3 ml/min and 5.5 +/- 0.6 g/dl) after the diet. Mean daily urinary protein excretion (7.1 +/- 2.2 g/day basally) significantly decreased (5.5 +/- 1.9 g/day) after the diet (p less than 0.05). Mean serum TT4 concentration (5.6 +/- 1.8 micrograms/dl basally) significantly increased (6.7 +/- 2 micrograms/dl, p less than 0.05) after the diet. Mean serum TT3 concentration (106.7 +/- 28.5 ng/dl, basally) significantly increased (126.7 +/- 22.6 ng/dl) after the diet (p less than 0.01). Mean serum fT4 and fT3 concentrations (8.0 +/- 2.9 pg/ml and 4.5 +/- 1.6 pg/ml, respectively) did not significantly change (9.4 +/- 2.7 pg/ml, and 4.9 +/- 1.9 pg/ml, respectively) after the diet. In some patients low basal serum concentration values of TT4, TT3, fT4, fT3 became normal after the diet. Mean serum TSH concentration (3.1 +/- 2.3 microU/ml basally), significantly decreased (1.5 +/- 1.3 microU/ml) after the diet (p less than 0.05). Mean serum PTH concentration (0.7 +/- 0.3 ng/ml basally) significantly decreased (0.4 +/- 0.2 ng/ml) after the diet (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)


[The two faces of autophagy in the nervous system].
Autophagy is a cellular mechanism for degrading proteins and organelles. It was first described as a physiological process essential for maintaining homeostasis and cell survival, but understanding its role in conditions of stress has been complicated by the recognition of a new type of cell death ("type 2") characterized by deleterious autophagic activity. This paradox is important in the central nervous system where the activation of autophagy seems to be protective in certain neurodegenerative diseases but deleterious in cerebral ischemia. The development of new therapeutic strategies based on the manipulation of autophagy will need to take into account these opposing roles of autophagy.


Three hundred patients referred for lung transplantation. Experiences of the Dutch Lung Transplantation Program. Groningen Lung Transplantation Group.
In November 1990, a lung transplantation program began at the University Hospital in Groningen, the Netherlands. As of April 1994, 300 patients were referred for lung transplantation and we investigated the decisions that have been made concerning these referrals up to January 1, 1995. The patients were evaluated according to a stepwise procedure. In stage 1, written information about the referred patients was discussed during the weekly, multidisciplinary lung transplantation meeting. In this stage, 14% of the patients were rejected and 2% were postponed. If no major objections for transplantation were identified, the patient was invited for a visit to the outpatient clinic, stage 2. The newly acquired information from that visit was discussed again at the transplantation meeting. In this stage, 11% of the patients were rejected and 18% postponed. The remaining patients underwent an (partial or complete) inpatient evaluation, stage 3. From all patients about whom a decision was made in this stage, only 5% were rejected, respectively 35% after partial evaluation and only 1.5% after complete evaluation. A total of 110 patients (37% of all referred patients) were listed for lung transplantation, stage 4. Of the listed patients, 20% died while awaiting an appropriate donor. The group of patients with COPD/emphysema had by far the lowest death rate on the waiting list. Patients with short stature (< or = 1.65 m) had a much higher risk to die on the waiting list compared with patients with longer stature, 42% vs 13%. As of January 1, 1995, 55 patients have undergone transplantation, which is 50% of all patients on the waiting list and 18% of all referred patients. The stepwise selection procedure identifies patients with potential contraindications at an early stage. In this way, unrealistic expectations and unnecessary examinations, expense, and/or hospital admissions may be prevented. Donor shortage, and thus waiting list problems, still remains a significant drawback in the further development of lung transplantation.


Misinformation, Fears and Adherence to Preventive Measures during the Early Phase of COVID-19 Pandemic: A Cross-Sectional Study in Poland.
The response to the pandemic requires access to accurate information and public understanding and adherence to preventive measures. This online cross-sectional study of adult Poles (n = 1337) assessed the frequency of COVID-19 preventive behaviors, fears related to the COVID-19 pandemic, and beliefs in COVID-19-related conspiracy theories during the early phase of the COVID-19 pandemic when the nationwide lockdown was imposed (April 2020). As shown, 22% of surveyed admitted not to wash their hands frequently, while 12% did not use disinfectants. These two behaviors were also less frequent in individuals with medical education. The highest levels of pandemic-related fears were associated with health loss in relatives, pandemic-induced economic crisis, and government using a pandemic to control citizens by the state. A significant share of surveyed individuals believed that the pandemic was intentional action to weaken non-Chinese economies (32%) or was deliberately induced for profits from selling vaccines (27%). Men, individuals with no children, and subjects with lower education were significantly less likely to adhere to sanitary measures (handwashing, disinfection, avoiding face touching, changes in greeting etiquette, face-covering when coughing or sneezing), and were less concerned over self and relatives' health. At the same time, men were less prone than women to the conspiracy theories related to the COVID-19 pandemic. The results indicate that adherence to sanitary measures during the pandemic can be a challenge also in developed countries, while misinformation campaigns (also concerning vaccines) have already affected the general public during the early phase of the epidemiological outbreak. The study provides observations that may be useful in the management of the public response to future epidemics.


Novel use of limited primer extension in detecting mutations in human iduronate 2-sulfatase gene.
Hunter syndrome is characterized by a deficiency of iduronate 2-sulfatase. A large number of mutations in the gene have been reported. We describe here the development of a limited primer method for the identification of mutations. In the reaction mixture designed for the limited primer extension, one or two deoxynucleotides from the four necessary deoxynucleotides are added as "selected nucleotides" and another deoxynucleotide which is radiolabeled is added as the "limited nucleotide". The absence of one or two of the deoxynucleotides limits the length of primer elongation, and the low concentration of the "limited nucleotide" causes an "extension-delay" effect and results in a banding pattern upon electrophoresis of the products thus making it possible to distinguish mutant and normal alleles. We have studied three novel mutations in exon IX, 407delTT (TTT to T), 423insCC (CCC to CCCCC), and W502X (TGG to TAG) of the iduronate 2-sulfatase gene by the limited primer extension method.


Bilobed testicle in children: diagnosis and management.
Bilobed testicle is an extremely rare testicular malformation in children. It may be presumed that this condition could be an incomplete expression of polyorchidism; however, the etiology of both entities remains unknown. In this report, a 3-year-old boy presented with a right bilobed testicle mimicking a testicular tumour. Since there are insufficient data in the pediatric literature presenting the ideal management of bilobed testicles, we believe it is important to report this case to provide more information about this condition. Although rare, bilobed testis should be considered in the differential diagnosis of a testicular mass. Surgical treatment is not mandatory, and conservative follow-up may play a role.


Father-to-father support: fathers of children with cancer share their experience.
Fathers are important to the stability of the family and to the coping of mothers and their children when there is a child in treatment with cancer. The vulnerability they experience is stupefying and causes self-doubt, general worry, and frustration with the medical care they receive. Fathers' experiences are relatively unreported in the literature, and even less so, the experiences of fathers with children who have cancer. This research is based on two focus groups of five men each who spoke unabashedly for more than 2 hours about their grief, their struggle to come to terms with the diagnosis and the role strain, and role confusion they experienced as fathers and husbands. The findings could be described as reflecting the following themes: (1) impact on the provider role, (2) the emotional impact: I cry privately, (3) it's the fight of our lives, (4) tag-team parenting, (5) hypervigilance, (6) that place is scary!, and (7) what happens next--coping and moving on. The group format was powerful in terms of what these men were willing to share of themselves and their experience. These groups could be characterized as the coming together of strangers, bound by the common experience of "cancer," who actively supported each other and each other's process. Implications for holistic nursing practice are provided.


Fabrication of electrocatalytic Ta nanoparticles by reactive sputtering and ion soft landing.
About 40 years ago, it was shown that tungsten carbide exhibits similar catalytic behavior to Pt for certain commercially relevant reactions, thereby suggesting the possibility of cheaper and earth-abundant substitutes for costly and rare precious metal catalysts. In this work, reactive magnetron sputtering of Ta in the presence of three model hydrocarbons (2-butanol, heptane, and m-xylene) combined with gas aggregation and ion soft landing was employed to prepare organic-inorganic hybrid nanoparticles (NPs) on surfaces for evaluation of catalytic activity and durability. The electrocatalytic behavior of the NPs supported on glassy carbon was evaluated in acidic aqueous solution by cyclic voltammetry. The Ta-heptane and Ta-xylene NPs were revealed to be active and robust toward promotion of the oxygen reduction reaction, an important process occurring at the cathode in fuel cells. In comparison, pure Ta and Ta-butanol NPs were essentially unreactive. Characterization techniques including atomic force microscopy (AFM), X-ray photoelectron spectroscopy (XPS), and transmission electron microscopy (TEM) were applied to probe how different sputtering conditions such as the flow rates of gases, sputtering current, and aggregation length affect the properties of the NPs. AFM images reveal the focused size of the NPs as well as their preferential binding along the step edges of graphite surfaces. In comparison, TEM images of the same NPs on carbon grids show that they bind randomly to the surface with some agglomeration but little coalescence. The TEM images also reveal morphologies with crystalline cores surrounded by amorphous regions for NPs formed in the presence of 2-butanol and heptane. In contrast, NPs formed in the presence of m-xylene are amorphous throughout. XPS spectra indicate that while the percentage of Ta, C, and O in the NPs varies depending on the sputtering conditions and hydrocarbon employed, the electron binding energies of the elements are similar for all of the NPs. The difference in reactivity between the NPs is attributed to their Ta/C ratios. Collectively, the findings presented herein indicate that reactive magnetron sputtering and gas aggregation combined with ion soft landing offer a promising physical approach for the synthesis of organic-inorganic hybrid NPs that have potential as low-cost durable substitutes for precious metals in catalysis.


Hepatectomy outcomes in patients with hepatitis C virus-related hepatocellular carcinoma with or without cirrhosis.
Hepatocellular carcinoma (HCC) is rare in HCV patients without cirrhosis, and little is known about the postoperative results of these patients. The present study compares the outcomes of cirrhotic and non-cirrhotic groups after liver resection (LR) in solitary HCV-related HCC patients and identifies risk factors for prognosis according to the presence or absence of cirrhosis in these patients. Two hundred and 7 adult hepatectomy patients with treatment-naïve solitary HCV-related HCC were identified prospectively at our institution between July 2005 and May 2019. The non-cirrhotic group had better liver function than the cirrhotic group based on platelet count, liver function tests, liver stiffness measurement, and indocyanine green retention rate at 15 minutes but were older than the cirrhotic group. Consistently, noninvasive markers in the cirrhotic group were significantly higher than in the non-cirrhotic group. The cumulative disease-free survival and overall survival in the non-cirrhotic group were significantly higher than in the cirrhotic group. HCC recurrence was related to major LR and α-FP of >40 ng/mL and death was related to long hospitalization and α-FP of >40 ng/mL in multivariate analysis. Noninvasive markers and the presence of cirrhosis were not related to HCC recurrence or death in multivariate analyses. The cirrhotic group showed poor prognosis due to poor liver function after LR compared to the non-cirrhotic group, but this was not sustained in multivariate analysis. The factors influencing HCC recurrence and death were different in the cirrhotic and non-cirrhotic groups.


Lymphonodular cryptococcosis diagnosed by fine needle aspiration cytology in hyper-IgM syndrome. A case report.
Most cases of cryptococcosis are diagnosed when signs of meningitis have appeared. We report a case of lymphonodular cryptococcosis that was diagnosed by fine needle aspiration cytology (FNAC), excisional biopsy of a cervical lymph node and culture of aspirated material. An 11-year-old boy presented with a history of fever and enlarged bilateral cervical lymph nodes of two weeks' duration. Past medical history included immunoglobulin replacement for hyper-IgM syndrome for the previous eight years. FNAC smears from a cervical lymph node showed numerous yeasts of various sizes, ranging from 5 to 15 microns in diameter, located in the cytoplasm of multinucleated giant cells and in the background. In air-dried, Diff-Quik-stained slides, the yeasts stained blue and were surrounded by clear halos. Aspirated material collected in the syringe was cultured, and Cryptococcus neoformans was isolated. This case report suggests that a combination of FNAC and culture is a simple and useful method of diagnosing fungal infections. Early diagnosis by FNAC makes possible the early initiation of treatment.


Stereotactic and computer-assisted neurosurgery at the Cleveland Clinic: review of 501 consecutive cases.
Stereotactic and computer-assisted techniques have revolutionized the diagnosis and treatment of many disorders of the brain by directing surgical instruments, the surgeon's hands, or focused radiation to an imaged target along predefined routes. This report reviews the basic principles and techniques of stereotactic and computer-assisted procedures in 501 consecutive procedures. Procedures performed include biopsy; decompression of cysts, hematomas, ventricles, and abscesses; "point," computer-assisted volumetric, and frameless stereotactic resection of brain lesions; placement of depth electrodes; treatment of movement or pain disorders; implantation of radioactive seeds in malignant tumors; and radiosurgery. Overall, image-directed stereotactic neurosurgery proved safe, accurate, and versatile.


The prevalence of dermatophytoses in Brazil: a systematic review.
Dermatophytosis is a common cutaneous mycosis worldwide whose prevalence in Brazil is still unknown. This systematic review has estimated the burden of dermatophytoses from updated literature data reported in the general Brazilian population. We used the following databases: Web of Science, Medline/PubMed, Embase, The Cochrane Library and Scopus for studies published between 2011 and 2020. Original articles with an emphasis on prevalence data for dermatophytosis in the Brazilian population, and diagnosed by culture exam or molecular biology were eligible. We also assessed the methodological quality of the studies. A total of 24 articles met the inclusion criteria and were reviewed. The occurrence of dermatophytoses found in the studies ranged from 4-88.50 %. The pooled prevalence of dermatophytosis for the population studies was 25 % (95 % CI: 24.7-25.3 %). The size of the samples used in the studies ranged from 45 to 36 446 participants, and ages ranged up to 98 years old. The populations studied involved mostly women. The presence of tinea unguium (toenail and fingernail) and tinea pedis were the most frequent dermatophytosis, and we observed a predominance of Trichophyton rubrum, T. interdigitale and T. mentagrophytes. The studies were primarily conducted in patient groups with suspected mycoses and were not entirely representative of the general population. Yet we believe that in the future, more collaborative strategies would improve both diagnostic capacity and epidemiological methodologies, associating the prevalence of dermatophytosis with social and environmental risk factors. This review helps to better understand future epidemiological trends in Brazil and the world.