[Reconstruction of laryngotracheal defect using the musculo-periosteum flap of the sternocleidomastoideus with clavicular periosteum].
To investigate the effect of the musculo-periosteum flap of the sternocleidomastoideus with clavicular periosteum on the reconstruction of extensiveness laryngotracheal defect. Retrospectively studied 49 patients, who admitted in our department from 1996 to 2005 years for severe laryngotracheal defect. There were 28 males and 21 females aged from 15 to 69 years old (mean age was 47 years old). The causes of laryngotracheal defect were laryngotracheal stenosis (31 cases) and surgery for thyroid carcinoma invading trachea (18 cases). All of 49 cases were treated with the graft of musculo-periosteum flap of the sternocleidomastoideus with clavicular periosteum and placed a silicon T-tube stenting for 3 to 6 months. All of 49 cases were successfully decannulated with recuperative normal airway patency and effective phonation. The follow up ranged from 2 to 10 years, and the effect of operation was steady. The musculo-periosteum flap of the sternocleidomastoideus with clavicular periosteum is an ideal graft for the reconstruction of cervical extensiveness tracheal defect.


[The effect of 4 different antacids on the gastrointestinal tract and mineral metabolism].
In a double-blind, randomized study, six healthy women were given four different antacids containing aluminium, magnesium or calcium, for a period of seven days, respectively. The antacids investigated were Trigastril 50 Del, Maaloxan Suspension, Kompensan-S forte Suspension and Solugastril 50 Gel. All the antacids tested led to a significant increase in the stool frequency and accelerated stool transit time. The sodium-containing agent produced a significantly greater acceleration as compared with the other antacids. No changes in the sodium, potassium or calcium blood levels were seen prior to and after administration of the various antacids. All preparations reduced phosphate concentrations (significant only with Solugastril an Trigastril). In the case of Maaloxan with a high content of magnesium, the magnesium concentration was increased mildly, but significantly. Irrespective of the dose of aluminium employed, all the antacids resulted in a significant increase in aluminium concentration of between 23 and 36 micrograms/l. All the antacids significantly reduced the excretion of phosphate in the urine. The preparation with a high level of magnesium produced the greatest excretion of magnesium, the preparation containing calcium the greatest excretion of calcium, in 24-hour urine. The results show that the effects on the weight of the stools, the transit time, the consistency of the stools, and on the mineral balance, depends upon the composition of the respective antacid.


Qingchang Wenzhong Decoction Alleviates DSS-Induced Inflammatory Bowel Disease by Inhibiting M1 Macrophage Polarization In Vitro and In Vivo.
An imbalance of macrophage M1/M2 polarization significantly influences the pathogenesis of inflammatory bowel disease. Qingchang Wenzhong decoction (QCWZD) has a proven therapeutic effect on patients with inflammatory bowel disease (IBD) and can significantly inhibit the inflammatory response in mice with colitis. However, its effect on macrophages during IBD treatment remains nebulous. Aim of the Study. Explore the mechanism underlying QCWZD effects in a dextran sulfate sodium (DSS)-induced colitis mouse model in vivo and RAW264.7 cell in vitro by observing macrophage polarization dynamics. The main active components of QCWZD were determined using high-performance liquid chromatography. Surface marker expression on M1-type macrophages was analyzed using flow cytometry and immunofluorescence. The effect on inducible nitric oxide synthase (iNOS), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) released by M1 type macrophages was determined using ELSA and RT-PCR. The expression of key proteins in the JAK2/STAT3 signaling pathway was analyzed using western blotting. QCWZD cytotoxicity in macrophages was measured using CCK8 and Annexin V-FITC/PI assays. The main active components of QCWZD were berberine chloride, coptisine chloride, epiberberine chloride, gallic acid, ginsenoside Rg1, ginsenoside Rb1, indigo, indirubin, notoginsenoside R1, palmatine chloride, and 6-curcumin. QCWZD markedly alleviated DSS-induced colitis in mice, as revealed by the rescued weight loss and disease activity index, attenuated the colonic shortening and mucosal injury associated with the inhibition of M1 macrophage polarization and expression of related cytokines, such as IL-6 and TNF-α, in vivo and in vitro. Furthermore, QCWZD decreased the iNOS, JAK2, and STAT3 levels in vivo and in vitro, regulating the JAK2/STAT3 signaling pathway. QCWZD administration improves intestinal inflammation by inhibiting M1 macrophage polarization. The JAK2/STAT3 signaling pathway may mediate the effects of QCWZD on M1 macrophage polarization in colitis treatment. This study presents a novel macrophage-mediated therapeutic strategy for the treatment of IBD.


Kerker Conditions upon Lossless, Absorption, and Optical Gain Regimes.
The directionality and polarization of light show peculiar properties when the scattering by a dielectric sphere can be described exclusively by electric and magnetic dipolar modes. Particularly, when these modes oscillate in phase with equal amplitude, at the so-called first Kerker condition, the zero optical backscattering condition emerges for nondissipating spheres. However, the role of absorption and optical gain in the first Kerker condition remains unexplored. In this work, we demonstrate that either absorption or optical gain precludes the first Kerker condition and, hence, the absence of backscattered radiation light, regardless of the particle's size, incident wavelength, and incoming polarization. Finally, we derive the necessary prerequisites of the second Kerker condition of the zero forward light scattering, finding that optical gain is a compulsory requirement.


Influence of trace substances on methanation catalysts used in dynamic biogas upgrading.
The aim of this work was to study the possible deactivation effects of biogas trace ammonia concentrations on methanation catalysts. It was found that small amounts of ammonia led to a slight decrease in the catalyst activity. A decrease in the catalyst deactivation by carbon formation was also observed, with ammonia absorbed on the active catalyst sites. This was via a suppression of the carbon formation and deposition on the catalyst, since it requires a higher number of active sites than for the methanation of carbon oxides. From the paper findings, no special pretreatment for ammonia removal from the biogas fed to a methanation process is required.


Optimism and well-being in older adults: the mediating role of social support and perceived control.
To investigate how psychosocial resources may improve well-being for older adults, this study explored the relationship among questionnaire measures of optimism, social support and perceptions of control in predicting subjective well-being (measured with the positive affect subscale of the Affect Balance Scale) (Bradburn, 1969) and psychological well-being (measured with the purpose in life scale of the Ryff Psychological Well-being scales) (Ryff, Lee, Essex, & Schmutte, 1994) among older adults. The potential mediating roles of perceived social support and perception of control were also explored. Participants were 225 adults aged from 65 to 94 years. Optimism was found to be a predictor of both subjective and psychological well-being, and perceived social support was found to mediate the relationship between optimism and subjective well-being, but not psychological well-being. In contrast, perception of control was found to mediate the relationship between optimism and psychological well-being, but not subjective wellbeing. Longitudinal research is needed to confirm these pathways.


[Field testing of new WHO growth standards: assessment of anthropometric outcomes of children from 0 to 5 years from Rosario city, Argentina].
The field testing of the preliminary WHO child growth standards was conducted in Rosario, Argentina. The objective of the article is to analyze the anthropometrical outcomes based on the national and international growth references. POPULATION, MATERIALS AND METHODS: Descriptive, cross-sectional study. Healthy children born at term, aged 0 to 5 years, and users of the health care network of the municipality from January to May 2005 were included. A data collection form was designed for the study. The weight (kg) was measured with an electronic scale. The length/height (cm) was taken with instruments constructed locally. The measurements techniques were based on national guidelines. The NUTRI 1.3: 5 and ANTHRO 2005 software were used. A sample of 1.804 boys and girls was analyzed. The prevalence of underweight was 1,7 times higher in children less than 6 months with the application of the new standards compared to the national reference. For the rest of the age groups, the situation was the opposite. A major prevalence of stunting was observed after 6 months of age based on the new standards compared to the national reference. The prevalence of overweight, in comparison with the old growth international reference, increased with the use of the new standards. Differences in underweight, stunting and overweight were found based on the tool used. The prevalence of stunting and overweight may increase with the application of the new growth standard.


[Several clinical aspects of a piloted Martian flight].
The authors consider factors and risk sources in long and superlong (interplanetary) missions, conceivable effects of extended exposures in microgravity, and probability of diseases in the crew. They also lay down the basic principles of medical care, including surgery, to be applied in the interplanetary mission, and propose a nomenclature of key means and equipment for the therapeutic and emergency medical care, and a configuration of a medical compartment.


Live-cell fluorescence imaging of microgametogenesis in the human malaria parasite Plasmodium falciparum.
Formation of gametes in the malaria parasite occurs in the midgut of the mosquito and is critical to onward parasite transmission. Transformation of the male gametocyte into microgametes, called microgametogenesis, is an explosive cellular event and one of the fastest eukaryotic DNA replication events known. The transformation of one microgametocyte into eight flagellated microgametes requires reorganisation of the parasite cytoskeleton, replication of the 22.9 Mb genome, axoneme formation and host erythrocyte egress, all of which occur simultaneously in <20 minutes. Whilst high-resolution imaging has been a powerful tool for defining stages of microgametogenesis, it has largely been limited to fixed parasite samples, given the speed of the process and parasite photosensitivity. Here, we have developed a live-cell fluorescence imaging workflow that captures the entirety of microgametogenesis. Using the most virulent human malaria parasite, Plasmodium falciparum, our live-cell approach captured early microgametogenesis with three-dimensional imaging through time (4D imaging) and microgamete release with two-dimensional (2D) fluorescence microscopy. To minimise the phototoxic impact to parasites, acquisition was alternated between 4D fluorescence, brightfield and 2D fluorescence microscopy. Combining live-cell dyes specific for DNA, tubulin and the host erythrocyte membrane, 4D and 2D imaging together enables definition of the positioning of newly replicated and segregated DNA. This combined approach also shows the microtubular cytoskeleton, location of newly formed basal bodies, elongation of axonemes and morphological changes to the erythrocyte membrane, the latter including potential echinocytosis of the erythrocyte membrane prior to microgamete egress. Extending the utility of this approach, the phenotypic effects of known transmission-blocking inhibitors on microgametogenesis were confirmed. Additionally, the effects of bortezomib, an untested proteasomal inhibitor, revealed a clear block of DNA replication, full axoneme nucleation and elongation. Thus, as well as defining a framework for broadly investigating microgametogenesis, these data demonstrate the utility of using live imaging to validate potential targets for transmission-blocking antimalarial drug development.


Enhancement of aerobic degradation of benzoate and 2-chlorobenzoate by adapted activated sludge.
Activated sludge from the Stickney Water Reclamation Plant of the Metropolitan Water Reclamation District of Greater Chicago was adapted in the laboratory to either benzoate or 2-chlorobenzoate as the sole carbon source in sequencing batch reactors with a 48-h feed-aerate-settle-draw cycle and a mean cell residence time (MCRT) of 10 days. Benzoate degradation increased by more than 80-fold after 7 MCRTs compared to unadapted activated sludge. A greater than 15-fold increase in 2-chlorobenzoate metabolism occurred after adaptation for about 5-7 MCRTs. For each substrate the maximum rate measured for adapted cultures was near or above the highest previously reported in the literature. For both adapted and unadapted sludges, benzoate metabolism was considerably faster than that of 2-chlorobenzoate, and for both substrates the rate of metabolism increased incrementally with time of adaptation. As expected, addition of the benzoate-adapted sludge to unadapted sludge enhanced the latter's ability to degrade benzoate.


[Nuclear DNA analysis of benign skin tumor and carcinoma in site developed from keratinocyte].
To know the variation of DNA contents of seborrheic keratosis, keratoacanthoma, actinic keratosis, and Bowen's disease, cytophotometric assay was used. As the results, following findings were obtained. 1. DNA index of actinic keratosis was higher than those of seborrheic keratosis and keratoacanthoma. 2. DNA index of Bowen's disease was higher than that of seborrheic keratosis. 3. Polyploid cell population (greater than 6C) of keratoacanthoma was higher than that of seborrheic keratosis. 4. Polyploid cell populations (greater than GC) of carcinoma in site (actinic keratosis, Bowen's disease) were higher than that of keratoacanthoma . These date suggested that polyploid cell population and DNA index reflect grade of malignancy of tumor developed from keratinocytes. A clinic keratosis and Bowen's disease revealed almost the same DNA pattern. And the difference of polyploid cell population of keratoacanthoma++ ++ and seborrheic keratosis suggested the difference of the biological activity of them.


Detection of Pathological Voice Using Cepstrum Vectors: A Deep Learning Approach.
Computerized detection of voice disorders has attracted considerable academic and clinical interest in the hope of providing an effective screening method for voice diseases before endoscopic confirmation. This study proposes a deep-learning-based approach to detect pathological voice and examines its performance and utility compared with other automatic classification algorithms. This study retrospectively collected 60 normal voice samples and 402 pathological voice samples of 8 common clinical voice disorders in a voice clinic of a tertiary teaching hospital. We extracted Mel frequency cepstral coefficients from 3-second samples of a sustained vowel. The performances of three machine learning algorithms, namely, deep neural network (DNN), support vector machine, and Gaussian mixture model, were evaluated based on a fivefold cross-validation. Collective cases from the voice disorder database of MEEI (Massachusetts Eye and Ear Infirmary) were used to verify the performance of the classification mechanisms. The experimental results demonstrated that DNN outperforms Gaussian mixture model and support vector machine. Its accuracy in detecting voice pathologies reached 94.26% and 90.52% in male and female subjects, based on three representative Mel frequency cepstral coefficient features. When applied to the MEEI database for validation, the DNN also achieved a higher accuracy (99.32%) than the other two classification algorithms. By stacking several layers of neurons with optimized weights, the proposed DNN algorithm can fully utilize the acoustic features and efficiently differentiate between normal and pathological voice samples. Based on this pilot study, future research may proceed to explore more application of DNN from laboratory and clinical perspectives.


A very feasible alternative in patients with feeding difficulties from gastrostomy: Jejunal tube advanced through the gastrostomy.
Our aim is to share our experiences regarding patients who cannot be fed effectively through the gastrostomy tube, but were inserted feeding jejunostomy through the gastrostomy orifice using scopic fluoroscopic techniques utilised by the interventional radiology. Between January 2010 and May 2013 the patients that were inserted jejunostomy tube through the gastrostomy orifice using fluoroscopic techniques were retrospectively analysed. Data including primary indication for gastrostomy, sex, concomitant disease and the requirement for gastroesophageal reflux disease (GERD) were all recorded. There were five patients with these criteria. They all received either medical or surgical GERD therapy; nevertheless enteral feeding failed to reach an effective level, they all had vomiting and did not gain any weight. Following conversion, all the patients gained minimum 2 kg in 2-5 months; all the patients tolerated enteral feeding and were discharged in the early period. There were neither procedure related complications such as perforation, bleeding nor sedation related complications. Procedure took no more than 30 min as a whole. There was no need for surgical intervention. However in one patient re-intervention was required due to accidental removal of the catheter. In case of feeding difficulties following the gastrostomy; instead of an invasive surgical intervention; physicians should consider jejunal feeding that is advanced through the gastrostomy, which does not require any anaesthesia.


Origin of muscle action potentials evoked by transcranial magnetic stimulation in cats.
We studied the effects of transcranial magnetic stimulation on ipsilateral and contralateral forelimb extensor muscles in anesthetized cats. A magnetic stimulator, operating at 100% intensity, was used through a circular coil, which was placed tangentially over the midline scalp. Bilateral activation of extensor muscles was readily obtained in all animals. The onset latencies were 7.3 +/- 1.1 and 7.07 +/- 0.8 msec for the contralateral and ipsilateral muscles, respectively. The amplitude of muscle response was unstable in magnitude, nevertheless, it did not show any significant difference between the two sides. The latency of response for ipsilateral and contralateral muscles was similar, which suggests simultaneous activation of motor pathways servicing forelimb muscles. Lesioning or ablation of the motor cortex and decerebration at mid-colliculi level did not abolish the evoked responses elicited at high intensity magnetic stimulation. Stereotactic electrical stimulation of the vestibular nuclei complex was performed, and satisfactory ipsilateral motor responses were obtained. Subsequently, a stereotactic radiofrequency lesion was made at the vestibular nuclei complex, with morphological confirmation. After this lesion, the motor evoked potentials (MEPs) were significantly diminished in amplitude. This finding strongly suggests that the generator of the MEPs resides in the brainstem, mainly at the vestibular nuclei complex.


Laparoscopic Management of Dermoid Cyst of Ovary is a Safe Procedure.
Dermoid cyst, a common benign neoplasm of ovary in women, needs treatment because of the risk of torsion, rupture, and malignant change. Laparoscopic surgery nowadays is the preferred treatment modality, but the only issue is its safety in case of rupture and spillage of its contents with the risk of chemical peritonitis and malignant dissemination. Aim of the study was to find out the safety of laparoscopic surgery for dermoid cyst of ovary. It was a retrospective study done from January 2017 to December 2019. All the women with diagnosis of dermoid cyst of ovary managed laparoscopically either salpingoophorectomy or cystectomy were taken into study. Analysis of size of the cyst operated, the time taken, spillage rate, duration of hospital stay, and post-operative complications especially chemical peritonitis was done. There were 61 women who had undergone laparoscopic surgery. Laparoscopic cystectomy was done in 68.9% (n=42), laparoscopic salpingoophorectomy in 29.5% (n=18). Mean age of the patient was 31.74±8.38 years. Mean size was 6.21±1.99 cm. Rupture and spillage were observed in 21.3% (n=13) that were > 5cm in diameter (X2= 3.62, p=0.05). Larger the size of the cyst, more the surgical time was noted (X2=6.26, p=0.04). Significant difference in mean operating time in case of cyst rupture and spillage (p=0.004) was observed. Mean hospital stay was 53.5±1.3 hours. No case of chemical peritonitis was observed with spillage. All cases had histopathology of mature cystic teratoma. Laparoscopic surgery is safe for dermoid cyst of ovary even with rupture and spillage of its contents.


Fine particles are more strongly associated than coarse particles with acute respiratory health effects in schoolchildren.
Numerous studies have reported associations between airborne particles and a range of respiratory outcomes from symptoms to mortality. Current attention has been focused on the characteristics of these particles responsible for the adverse health effects. We have reanalyzed three recent longitudinal diary studies to examine the relative contributions of fine and coarse particles on respiratory symptoms and peak expiratory flow in schoolchildren. In the Harvard Six Cities Diary Study, lower respiratory symptoms in a two-pollutant model were associated with an interquartile range increment in fine particles [(for 15 microg/m3 particulate matter (PM) <2.5 microm in aerodynamic diameter (PM2.5), odds ratio = 1.29, 95% confidence limits (CL) = 1.06, 1.57] but not coarse particles (for 8 microg/m3 PM2.5-10, odds ratio = 1.05, 95% CL = 0.90, 1.23). In Uniontown, PA, we found that peak flow was associated with fine particles (for 15 microg/m3 PM2.1, peak flow = -0.91 liters/minute, 95% CL = -0.14, -1.68), especially fine sulfate particles, but not with coarse particles (for 15 microg/m3 PM2.1-10, +1.04 liters/minute, 95% CL = -1.32, +3.40). We found similar results for an equivalent children's cohort in State College, PA. We conclude that fine particles, especially fine sulfate particles, have much stronger acute respiratory effects than coarse particles.


Ammonium tunnel levels and spin-rotational wavefunctions in (NH4)2S2O8.
Proton spin-lattice relaxation in a single crystal of (NH4)2S2O8 was studied as a function of resonance frequency at various constant temperatures between 4.2 and 30 K. Two T1 minima were found, one at 8.6 MHz and the other at 4.3 MHz. They are related to the splitting between the lowest T level and the A level, equal to 8.6 MHz nearly independently of temperature below 25 K. Together with the large tunnel splitting of 269 MHz, determined earlier by Clough et al. (Chem. Phys. 152, 343 (1991)) our results define the spin-rotational wavefunction of the lowest T level very accurately, although those of the two higher T levels remain largely undetermined.


Characteristics of the Flash-induced 515 Nanometer Absorbance Change of Intact Isolated Chloroplasts.
In intact (type A) chloroplasts isolated from mesophyll protoplasts of maize (Zea mays L. convar. KSC 360) the flash-induced 515 nanometer absorbance change was much higher than in conventionally prepared (types B and C) chloroplasts. The 515 nanometer signal of type A chloroplasts exhibited a biphasic rise: the initial very fast rise (rise time <<1 millisecond) was followed by a slow increase of absorbance (rise time 10 to 20 milliseconds). With decreasing degree of envelope retention the slow phase disappeared. Thus the biphasic rise of the flash-induced 515 nanometer absorbance change can be regarded as an attribute of intact chloroplasts.The 515 nanometer signal of intact chloroplasts was studied at various pH values of the external medium, with various dark intervals between the flashes and at different temperatures. The absorbance change was probed with electron transport inhibitors and ionophores. The data show that the fast phase of the absorbance increase was similar in chloroplasts isolated from protoplasts and in conventional chloroplast preparations. The slow rise, which has not been hitherto recognized in isolated chloroplasts, can be due to a contribution of the proton pump to the electric field which is generated across the thylakoid membranes.


Reference genes for proximal femoral epiphysiolysis expression studies in broilers cartilage.
The use of reference genes is required for relative quantification in gene expression analysis and the stability of these genes can be variable depending on the experimental design. Therefore, it is indispensable to test the reliability of endogenous genes previously to their use. This study evaluated nine candidate reference genes to select the most stable genes to be used as reference in gene expression studies with the femoral cartilage of normal and epiphysiolysis-affected broilers. The femur articular cartilage of 29 male broilers with 35 days of age was collected, frozen and further submitted to RNA extraction and quantitative PCR (qPCR) analysis. The candidate reference genes evaluated were GAPDH, HMBS, HPRT1, MRPS27, MRPS30, RPL30, RPL4, RPL5, and RPLP1. For the gene stability evaluation, three software were used: GeNorm, BestKeeper and NormFinder, and a global ranking was generated using the function RankAggreg. In this study, the RPLP1 and RPL5 were the most reliable endogenous genes being recommended for expression studies with femur cartilage in broilers with epiphysiolysis and possible other femur anomalies.


Alcohol use in severely injured trauma patients.
Alcohol is a major risk factor for several types of injuries, and it is associated with almost all types and mechanisms of injury. The focus of the study was to evaluate alcohol use in severely injured trauma patients with New Injury Severity Score (NISS) of 16 or over, and to compare mortality, injury severity scores and mechanisms and patterns of injury between patients with positive and negative blood alcohol levels (BAL). Medical histories of all severely injured trauma patients (n = 347 patients) enrolled prospectively in Trauma Register of Tampere University Hospital (TAUH) between January 2016 to December 2017 were evaluated for alcohol/substance use, injury mechanism, mortality and length of stay in Intensive Care Unit (ICU). A total of 252 of 347 patients (72.6%) were tested for alcohol with either direct blood test (50.1%, 174/347), breathalyser (11.2%, 39/347), or both (11.2%, 39/347). After untested patients were excluded, 53.5% of adult patients (18-64 years), 20.5% of elderly patients (above 65 years) and 13.3% of paediatric patients (0-17 years) tested BAL positive. The mean measured BAL for the study population was 1.9 g/L. The incidence of injuries was elevated in the early evenings and the relative proportion of BAL positive patients was highest (67.7%) during the night. Injury severity scores (ISS or NISS) and length of stay in ICU were not adversely affected by alcohol use. Mortality was higher in patients with negative BAL (18.2% vs. 7.7%, p = 0.0019). Falls from stairs, and assaults were more common in patients with positive BAL (15.4% vs. 5.4% and 8.7% vs. 2.7%, p < 0.006, respectively). There were no notable differences in injury patterns between the two groups. Alcohol use among severely injured trauma patients is common. Injury mechanisms between patients with positive and negative BAL have differences, but alcohol use will not increase mortality or prolong length of stay in ICU. This study supports the previously reported findings that BAL is not a suitable marker to assess patient mortality in trauma setting.


Surface acoustic wave (SAW) real-time interaction analysis of influenza A virus hemagglutinins with sialylated neoglycolipids.
Real-time interaction analysis of H1 hemagglutinin from influenza A H1N1 (A/New York/18/2009) and H7 hemagglutinin from influenza A H7N7 (A/Netherlands/219/03) with sialylated neoglycolipids (neoGLs) was performed using the surface acoustic wave (SAW) technology. The produced neoGLs carried phosphatidylethanolamine (PE) as lipid anchor and terminally sialylated lactose (Lc2, Galβ1-4Glc) or neolactotetraose (nLc4, Galβ1-4GlcNAcβ1-3Galβ1-4Glc) harboring an N-acetylneuraminic acid (Neu5Ac). Using α2-6-sialylated neoGLs, H1 and H7 exhibited marginal attachment toward II6Neu5Ac-Lc2-PE, whereas Sambucus nigra lectin (SNL) exhibited strong binding and Maackia amurensis lectin (MAL) was negative in accordance with their known binding preference toward a distal Neu5Acα2-6Gal- and Neu5Acα2-3Gal-residue, respectively. H1 revealed significant binding toward IV6Neu5Ac-nLc4-PE when compared to weak interaction of H7, whereas SNL showed strong and MAL no attachment corresponding to their interaction specificities. Additional controls of MAL and SNL with α2-3-sialylated II3Neu5Ac-Lc2-PE and IV3Neu5Ac-nLc4-PE underscored the reliability of the SAW technology. Pre-exposure of model membranes spiked with α2-6-sialylated neoGLs to Vibrio cholerae neuraminidase substantially reduced the binding of the hemagglutinins and the SNL reference. Collectively, the SAW technology is capable of accurate measuring binding features of hemagglutinins toward neoGL-spiked lipid bilayers, which can be easily loaded to the functionalized biosensor gold surface thereby simulating biological membranes and suggesting promising clinical application for influenza virus research.


Population drinking and fatal injuries in Eastern Europe: a time-series analysis of six countries.
To estimate to what extent injury mortality rates in 6 Eastern European countries are affected by changes in population drinking during the post-war period. The analysis included injury mortality rates and per capita alcohol consumption in Russia, Belarus, Poland, Hungary, Bulgaria and the former Czechoslovakia. Total population and gender-specific models were estimated using auto regressive integrated moving average time-series modelling. The estimates for the total population were generally positive and significant. For Russia and Belarus, a 1-litre increase in per capita consumption was associated with an increase in injury mortality of 7.5 and 5.5 per 100,000 inhabitants, respectively. The estimates for the remaining countries ranged between 1.4 and 2.0. The gender-specific estimates displayed national variations similar to the total population estimates although the estimates for males were higher than for females in all countries. The results suggest that changes in per capita consumption have a significant impact on injury mortality in these countries, but the strength of the association tends to be stronger in countries where intoxication-oriented drinking is more common.


Gustatory neural coding in the monkey cortex: mixtures.
1. Psychophysicists have shown that the intensity and quality of a taste stimulus, as perceived by humans, is modified by including that stimulus in a mixture. Gustatory neurons in the primary taste cortex (anterior insula and frontal operculum) of the cynomolgus macaque are involved with the coding of stimulus intensity and quality, and so should reflect the impact of these stimulus interactions. 2. We recorded the activity of 48 neurons in primary taste cortex in response to the oral application of each of the four basic stimuli, their six possible dyads, the four triads, and the tetrad of all four. Stimuli were maintained at a constant intensity in all mixtures by increasing their concentrations as the number of components rose. 3. Glucose was the most effective basic stimulus, followed by quinine HCl, NaCl, and HCl. The mean response to dyads was suppressed by 50% from the sum of responses to the two unmixed components. The response to triads was 62% lower than the sum of responses to their three components, and activity evoked by the tetrad was suppressed by 74% from the sum of all four individual responses. Therefore there was nearly total suppression in the sense that the responses to the mixtures were approximately 1/2, 1/3, and 1/4 the sums of responses to two, three, and four components, respectively. 4. Neurons could be divided into four subtypes: those that responded best to each of the basic stimuli. All subtypes except HCl cells were about equally suppressed when their preferred stimulus was included in a mixture. HCl was a particularly ineffective stimulus, such that this subtype responded poorly and so was less susceptible to mixture suppression. 5. Taste quality, as indexed by correlation coefficients among profiles of activity, was quite predictable for dyads. If the mixture included HCl, the profile it generated correlated poorly (about +0.20) with that of HCl and rather well (about +0.60) with that of the other component. If HCl was not included, the mixture's profile correlated about +0.40 with that of each component. 6. The profile generated by the mixture of three stimuli was predictable only if one of the components was HCl. In that case, the triad elicited a profile midway between those of the other two components, i.e., the contribution of HCl was largely ignored. When HCl was not involved, or when all four basic stimuli were combined, the resulting profiles were poorly correlated with those of all basic stimuli. 7. The contribution made by each basic taste to human perception and to the macaque's neurophysiological response was compared for all mixtures. The contribution was often quite similar for human and macaque, but when differences occurred, they were typically due to lower activity from HCl cells in the macaque, a loss that was replaced mainly by larger responses from glucose neurons. 8. The magnitude of responses to mixtures in the macaque taste cortex matches well with expectations from human psychophysical studies. The presumed quality of the response to mixtures is also similar, except that HCl is less effective in monkeys and sugars more so.


Genetic characterization of fall armyworm (Spodoptera frugiperda) in Ecuador and comparisons with regional populations identify likely migratory relationships.
Fall armyworm, Spodoptera frugiperda (J. E. Smith), is an important agricultural pest native to the Americas that has recently been introduced into the Eastern Hemisphere where it has spread rapidly through most of Africa and much of Asia. The long-term economic consequences of this invasion will depend on how the species and important subpopulations become distributed upon reaching equilibrium, which is expected to be influenced by a number of factors including climate, geography, agricultural practices, and seasonal winds, among others. Much of our understanding of fall armyworm movements have come from mapping genetically defined subpopulations in the Western Hemisphere, particularly in North America where annual long-distance migrations of thousands of kilometers have been documented and modeled. In contrast, fall armyworm mapping in much of the rest of the hemisphere is relatively incomplete, with the northern portion of South America particularly lacking despite its potential importance for understanding fall armyworm migration patterns. Here we describe the first genetic description of fall armyworm infesting corn in Ecuador, which lies near a likely migration conduit based on the location of regional trade winds. The results were compared with populations from corn habitats in select locations in the Caribbean and South America to investigate the possible migratory relationship between these populations and was further assessed with respect to prevailing wind patterns and the distribution of locations with climate favorable for fall armyworm population establishment and growth.


Evaluation of optical quality of corneas using corneal topographers.
To review the evaluation of the optical quality of the cornea by corneal topography. Color-coded maps show qualitatively the characteristics and severity of irregular astigmatism at the entrance pupil. Topographic indices such as the surface regularity index and predicted corneal acuity are derived from computation of the corneal power distribution, and they are highly correlated with high-contrast visual acuity. Fourier analysis can be used to represent the irregular and regular astigmatism components simultaneously. Zernike polynomials can be used to calculate higher-order wavefront aberrations due to the corneal surface. Evaluation of the optical properties of the cornea using a corneal topographer is useful for assessing quality of vision.


Clinical Impact of Plasma Metagenomic Next-generation Sequencing in a Large Pediatric Cohort.
Plasma metagenomic next-generation sequencing (mNGS) has the potential to detect thousands of different organisms with a single test. There are limited data on the real-world impact of mNGS and even less guidance on the types of patients and clinical scenarios in which mNGS testing is beneficial. A retrospective review of patients who had mNGS testing as part of routine clinical care at Texas Children's Hospital from June 2018-August 2019 was performed. Medical records were reviewed for pertinent data. An expert panel of infectious disease physicians adjudicated each unique organism identified by mNGS for clinical impact. There were 169 patients with at least one mNGS test. mNGS identified a definitive, probable or possible infection in 49.7% of patients. mNGS led to no clinical impact in 139 patients (82.2%), a positive impact in 21 patients (12.4%), and a negative impact in 9 patients (5.3%). mNGS identified a plausible cause for infection more often in immunocompromised patients than in immunocompetent patients (55.8% vs. 30.0%, P = 0.006). Positive clinical impact was highest in patients with multiple indications for testing (37.5%, P = 0.006) with deep-seated infections, overall, being most often associated with a positive impact. mNGS testing has a limited real-world clinical impact when ordered indiscriminately. Immunocompromised patients with well-defined deep-seated infections are likely to benefit most from testing. Further studies are needed to evaluate the full spectrum of clinical scenarios for which mNGS testing is impactful.


Cardiogenic embolism as the main cause of ischemic stroke in a city hospital: an interdisciplinary study.
It is essential to understand the pathogenesis of ischemic stroke to ensure rational acute therapy and secondary prevention. We wanted to know the distribution of pathogenesis in patients of a city hospital and the differences in risk factors, neurologic deficits, disability, and delay in clinical admittance. During a period of one year, 222 patients (mean age 76.6 years; 59% women) with complete acute ischemic stroke were admitted and underwent complete clinical and diagnostic procedures: CCT/MRI; Doppler- and color-coded duplex and transcranial sonography; echocardiography; use of the NINCDS stroke scale and the Oxford disability scale; study of risk factors, and exploration of delay in admittance. The following percentages of etiologies were evident: 31% cardiogenic embolism (60% with atrial fibrillation), 13% microangiopathy, 9% macroangiopathy, 11% cerebellar or brain stem infarction, 18% more than one cause and 18% no cause found. The patients with cardiogenic embolism showed significantly the highest scores on the stroke scale and the disability scale and had the shortest delay in admittance (57% were admitted within 3 hours). In a city hospital, cardiogenic embolism is the main cause of ischemic stroke. These patients suffer significantly the most severe neurologic deficits, dependence, and requirement of daily nursing care. These patients have the shortest delay in clinical admittance and the best chance of benefitting from acute therapy and early secondary prevention.


Female Same-Sex Bidirectional Intimate Partner Violence in China.
Although there exists a growing body of research on female same-sex intimate partner violence (FSSIPV) as well as bidirectional intimate partner violence (BIPV) among lesbian women, much of this literature focuses on the IPV experience of women living in Western societies such as the United States. The current study represents the very first to explore BIPV among lesbian women in China. In this study, we analyze a survey sample of 225 self-identified lesbian women in China to examine FSSBIPV patterns, pattern-specific rates, and risk factors of FSSBIPV. Using the Latent Class Analysis technique, we discover three main patterns of partner abuse, including bidirectional psychological violence (60%), bidirectional violence multiple types with physical abuse (79.1%), and minimal violence (20.9%). Logistic regressions show that there is no significant demographic, socioeconomic, or attitudinal difference between the bidirectional psychological violence group and the minimal violence group while being younger, cohabitating, and holding pro-IPV attitudes significantly predicted higher odds of experiencing multiple types of bidirectional violence. Contributions to the literature, as well as policy implications, are also discussed.


Increased clusterin (apolipoprotein J) expression in human and mouse brains infected with transmissible spongiform encephalopathies.
Clusterin (apolipoprotein J), a multifunctional protein involved in amyloidogenesis in Alzheimer's disease, was studied immunohistochemically in both human transmissible spongiform encephalopathies (TSEs) and a mouse model of human TSE. Clusterin immunoreactivity was co-localized with plaque-type deposits but not with punctate-type prion protein (PrP) deposits in human TSEs. On the other hand, clusterin-positive astrocytes were readily demonstrated in the regions of punctate PrP deposits, but not around plaque PrP deposits despite the presence of surrounding astrocytes. Clusterin expression in astrocytes was not disease specific, but the punctate immunoreactivity for clusterin was more prominently demonstrated in TSEs with punctate PrP deposits. Serial analysis in the mouse model of human TSE revealed that clusterin expression in astrocytes was enhanced in the lesions with punctate-type PrP deposits during the disease progression. Thus, the induction of clusterin expression in astrocytes could be more enhanced by punctate-type PrP deposits than by plaque-type deposits. The clusterin molecules co-localized in plaque PrP deposits might be derived not from surrounding astrocytes but from other resources such as cerebrospinal fluid and blood plasma, both of which contain clusterin in significant amounts. Taken together with previously reported findings of the anti-amyloidogenic property in clusterin, our findings suggest that clusterin may be induced as one of the important molecules participating in the neurodegeneration caused by abnormally deposited PrP.


Device-specific outcomes after endovascular abdominal aortic aneurysm repair.
Over the last decade, endovascular aneurysm repair (EVAR) has been used extensively for the elective treatment of infra-renal abdominal aneurysms. However, it remains unclear how specific devices perform and how they compare to others. We provide an overview of currently used endografts, and discuss the current evidence regarding device-specific outcomes. Published literature confirms differences in results according to endograft selection. These differences were more pronounced with older generations of devices, in comparison to newer models. Contemporary results are generally good and one should remember that no randomized data exist regarding individual device performance. Moreover, by the time there is enough follow-up to draw conclusions, the data is relatively obsolete due to constant improvements in endograft technology and design. Results from EVAR have been steadily improving and individualized device selection has shown to be valuable. It appears that patients with favorable anatomy do well with most modern endografts. Those with challenging anatomies may benefit more from a particular design, delivery and deployment feature requiring greater knowledge and experience for adequate device selection.


The use of pulmonary function testing and questionnaires as epidemiologic tools in the study of occupational lung disease.
Pulmonary function testing and questionnaires are valuable tools in epidemiologic studies of occupational lung disease. Accurate equipment and standardized methodology are vital to obtain reproducible responses. For spirometry, the FVC and FEV show the least intrasubject variability and on questionnaires, occupational and smoking history are more reproducible than symptoms. The limitations of any method used to define a lower limit of normal should be kept in mind and, whenever possible, groups should be compared by use of the distribution of observations in the two groups--not just the prevalence of "abnormal" findings.


Inhibitory effects of nitroglycerin on contractile responses to methoxamine and clonidine in isolated rabbit renal and femoral arteries.
The inhibitory effect of nitroglycerin (NG) on contractile responses to methoxamine (MO) and clonidine (CL) was investigated in isolated rabbit renal and femoral arteries. NG (10(-7)-10(-5) mol/l) inhibited the responses to MO and CL in a noncompetitive manner and its inhibitory effect on CL-responses was much greater than that on the MO-responses. In the presence of phenoxybenzamine, however, NG (10(-5) mol/l) markedly inhibited the residual response to MO. Contractile responses to KCl or added Ca2+ in a Ca2+-free medium containing KCl were slightly inhibited by NG. In the presence of nifedipine, NG (10(-5) mol/l) markedly inhibited residual responses to CL but it only slightly inhibited the response to MO. In a Ca2+-free medium with EGTA, MO (10(-5) mol/l) or CL (10(-5) mol/l) induced a phasic contraction. NG had a greater inhibitory effect on the response to CL than MO. In a Ca2+-free medium with EGTA, nifedipine and MO (10(-5) mol/l) or CL (10(-5) mol/l), Ca2+ induced a tonic contraction. NG inhibited the Ca2+-response in the presence of CL, but it had little or no effect on the Ca2+-response in the presence of MO. These results suggest that in rabbit renal and femoral arteries, the potent inhibitory effect of NG on the responses to CL as compared to MO may be due to differences in the amount of receptor reserves that exist for both the agonists. In addition, the inhibition of voltage-dependent Ca2+ channels may not play a major role in the vasoinhibitory action of NG. Further, NG inhibits contractile responses due to mobilization of intracellular Ca2+ much more than the responses due to receptor-activated, nifedipine-insensitive Ca2+-movement.


The physiology of idiopathic dystonia.
Dystonia is mysterious and its pathophysiology is uncertain. The fundamental motor abnormality is an abnormality of muscle command signals, such that the wrong agonists may be activated for too long, there is abnormal co-contraction of agonist and antagonists, and there is excessive and misdirected action of synergists and postural fixators. The result is action dystonia. In addition, muscle spasms may occur spontaneously. The peripheral motor apparatus, the corticomotoneurone pathway, and (as far as is known) the proprioceptive feedback machinery, are all intact in primary dystonia. However, a defect of interneuronal machinery has been identified in both the brainstem and spinal cord. In blepharospasm there is hyperexcitability of the lower brainstem interneurones responsible for the R2 component of the blink reflex. In the dystonic arm there is loss of the later phases of Ia reciprocal inhibition from extensors to flexors. Both deficits may be due to loss of normal basal ganglia inputs onto interneurones. The known sites of focal lesions that may cause symptomatic dystonia all impair basal ganglia output. However, whether such abnormal interneuronal function is sufficient to explain dystonia is not known. Among many unanswered questions are 1) are the cortical instructions for movement specified correctly, and 2) what is responsible for the spontaneous dystonic spasms?


Occlusal interferences related to dental panoramic radiographic changes in subjects treated with fixed prosthesis.
Because of contradictory reports between clinical and radiographic findings, occlusal analysis correlated to dental panoramic findings was completed in 147 patients treated with fixed prosthesis. Both occlusal interferences and radiographic changes in the TMJ area and/or in dentition were frequently discovered. Dysfunction and occlusal indices gave statistically significant correlations to radiographic changes (P less than 0.01 and P less than 0.05, respectively) in the TMJ area. Periodontal changes with vertical bone pocket formation and sclerotic lamina dura seem to be early radiographic findings and occlusal interferences were the only means to give a clear-cut correlation to the radiographic changes (P less than 0.001). However, if periodontal tissues with supporting bone structure fail to respond to occlusal trauma, changes in the TMJ area will probably appear. From the clinical changes the deviation on mouth opening, tenderness to palpation of TMJ, and slide from retrusion to intercuspidation (RP-IP) explained most of the radiological TMJ changes when tested by the discriminant analysis. The value of radiographic follow-up of subjects following prosthetic treatment is emphasized.


Interaction of protein kinase C with filamentous actin: isozyme specificity resulting from divergent phorbol ester and calcium dependencies.
The mechanism of activation of protein kinase C isoforms by filamentous actin (F-actin) was investigated with respect to isozyme specificity and phorbol ester and Ca(2+) dependencies. It was found that the "conventional" (cPKC), alpha, betaI, betaII, and gamma, "novel" (nPKC) delta and epsilon, and "atypical" (aPKC) zeta isoforms were each activated by F-actin with varying potencies. The level of activity along with the affinity for binding to F-actin was further potentiated by the phorbol ester 4beta-12-O-tetradecanoylphorbol 13-acetate (TPA), the potency of which again varied for each isoform. By contrast to the other cPKC isoforms, the level of cPKC-gamma activity was unaffected by TPA, as was also the case for aPKC-zeta. It was found that whereas in the absence of F-actin the soluble form of cPKC-betaI contained two phorbol ester binding sites of low and high affinity, respectively, as previously reported for cPKC-alpha [Slater et al. (1998) J. Biol. Chem. 273, 23160-23168], the F-actin-bound form of the isozyme contained only a single site of relatively low affinity. The level of TPA required to induce cPKC-alpha, -betaI, and -betaII activity and the binding of these isozymes to F-actin was reduced in the presence of Ca(2+). By contrast, the activity of cPKC-gamma was unaffected by Ca(2+), as were the activities of nPKC-delta and -epsilon and aPKC-zeta, as expected. Thus, the interaction with F-actin appears to be a general property of each of the seven PKC isozymes tested. However, isoform specificity may, in part, be directed by differences in the phorbol ester and Ca(2+) dependences, which, with the notable exception of cPKC-gamma, appear to resemble those observed for the activation of each isoform by membrane association. The observation that cPKC isoforms may translocate to F-actin as well as the membrane as a response to an elevation of Ca(2+) levels may allow for the functional coupling of fluctuations of intracellular Ca(2+) levels through cPKC to F-actin cytoskeleton-mediated processes.


Deletion of chromosome 2 (p11-p13): case report and review.
The case of a young man with del(2) (p11.2p13) is reported. Accounts of previous cases of deletion of the short arm of chromosome 2 are reviewed. Common features include mental retardation, proportional short stature and weight, dysmorphic facial features (a prominent nose, abnormal ears), and abnormal hands. Growth and developmental delay are present during the postnatal period.


Ultrasound for the assessment of the embolic risk of carotid plaques.
In a prospective study we compared duplex-ultrasound characteristics of symptomatic internal carotid artery (ICA) stenoses with cranial computerized tomographic (CCT) findings in 82 patients suffering from completed or transient middle cerebral artery symptoms. The aim was to assess the pathogenic role of ICA plaque morphology and the potential embolic risk of ICA plaques. The degree of carotid stenosis was estimated by spectral analysis of the pulsed Doppler signal. The CCT findings were classified as being either normal, lacunar lesions, hemodynamically induced low-perfusion infarctions, or territorial embolic infarctions. According to their ultrasonic features we characterized the ICA plaque surface as smooth or irregular and their structure as homogeneous or heterogeneous. Plaques with an irregular surface and heterogeneous echogenicity dominated significantly in CCT-territorial infarctions (p < 0.01), whereas hemodynamically induced low-perfusion infarctions showed no relationship with any plaque characteristic. High degree ICA stenoses (> 50%) dominated in both territorial infarctions and low-perfusion infarctions, as compared to ipsilateral normal CCT or lacunes (p < 0.05). Normal CCT and lacunar infarctions were associated with homogeneous and smooth plaques (both p < 0.05). We conclude that > 50% ICA stenoses can cause both hemodynamically induced low-perfusion infarctions as well as thromboembolic territorial infarctions, whereas ulcerated and heterogeneous plaques constitute a high risk factor for arterio-arterial embolic stroke. Furthermore, carotid ultrasound may help to estimate the clinical significance of carotid lesions.


'Through privation to knowledge': unknown documents from Freud's university years.
The paper is centred on three hitherto unknown grants, two of them donated by different Jewish Foundations to the medical student Freud shortly before the end of his studies. It furthermore turned out that Freud's salary as a demonstrator in Brücke's Laboratory had been a grant too, donated by the University of Vienna. Aspects of the contemporary background by means of the private foundations and their donors as well as of the aspiring tendencies at the University of Vienna are described. Documentary evidence demonstrates that Brücke promoted Sigmund Freud continuously, more than hitherto known in the biography. The significance of Brücke and Charcot as identification-figures, on the one hand, and for Freud's development as a scientist, on the other, is elaborated. Contemporary quotations shed light on Freud's poverty in his youth as well as the arising anti-Semitism at the University of Vienna.


Expanding functions of intracellular resident mono-ADP-ribosylation in cell physiology.
Poly-ADP-ribosylation functions in diverse signaling pathways, such as Wnt signaling and DNA damage repair, where its role is relatively well characterized. Contrarily, mono-ADP-ribosylation by for example ARTD10/PARP10 is much less understood. Recent developments hint at the involvement of mono-ADP-ribosylation in transcriptional regulation, the unfolded protein response, DNA repair, insulin secretion and immunity. Additionally, macrodomain-containing hydrolases, MacroD1, MacroD2 and C6orf130/TARG1, have been identified that make mono-ADP-ribosylation reversible. Complicating further progress is the lack of tools such as mono-ADP-ribose-specific antibodies. The currently known functions of mono-ADP-ribosylation are summarized here, as well as the available tools such as mass spectrometry to study this modification in vitro and in cells.


Mucinous adenocarcinoma of the prostatic urethra following a remote history of primary brachytherapy for prostate cancer.
Secondary malignancies are a known, albeit uncommon, complication of radiation for prostate cancer, either in the form of external beam radiotherapy or seed-implant brachytherapy. Of these secondary malignancies, mucinous adenocarcinoma of the prostatic urothelium is an extremely rare clinical entity that has only once been reported in the literature. We report the case of an 80-year-old gentleman who initially underwent low-dose brachytherapy for low-risk prostate cancer 18 years ago. He subsequently developed recurrent gross hematuria and obstructive voiding symptoms. He underwent cystoscopy and transurethral resection of a large tumor from within the prostate. Final pathology of the tumor revealed a mucinous adenocarcinoma. Further immunostaining revealed this is likely to have originated from the prostatic urothelium. Given his age, comorbidities, and no clear data demonstrating that aggressive extirpative surgery provides a clinical benefit, we elected to undergo surveillance. Clinicians should be aware of mucinous adenocarcinoma of the prostatic urethra as an extremely rare, radiation-induced malignancy. Once a diagnosis is made, extirpative surgery is an option for localized disease, although prognosis remains poor.


Comparing shoulder maneuvers to magnetic resonance imaging and arthroscopic findings in patients with supraspinatus tears.
Shoulder maneuvers and magnetic resonance imaging (MRI) are performed to diagnose supraspinatus tendon tears regardless of arthroscopy exam. Although there are many studies on this subject, there is a lack of studies comparing the sensitivity (Se) and specificity (Sp) of shoulder maneuvers and MRI to arthroscopic findings (intact, partial, or full thickness supraspinatus tendon tear). To compare the diagnostic values of shoulder maneuvers with MRI for supraspinatus tendon tears in patients undergoing shoulder arthroscopy. A total of 199 consecutive patients from four orthopedic centers met the eligibility criteria of shoulder pain persisting for at least four weeks. They were prospectively enrolled in this study from April 2017 to April 2019. Seven clinical tests (full can, empty can, drop arm, Hawkins', painful arc, Neer's sign and resisted external rotation) and MRI were performed, and all were compared with surgical findings. Full can, empty can and resisted external rotation tests were interpreted as positive in the case of pain and/or weakness. We assessed the Se, Sp, accuracy, positive predictive value (PPV) and negative predictive value (NPV), positive and negative likelihood ratio and diagnostic odds ratio for overall, partial and full-thickness supraspinatus tears. MRI had the highest Se for overall (0.97), partial (0.91) and full-thickness (0.99) tears; moreover, MRI had the highest NPV: 0.90, 0.88 and 0.98 for overall, partial and full-thickness tears, respectively. For overall supraspinatus tears, the Se and PPV were: Painful arc (Se = 0.85/PPV = 0.91), empty can (pain) (Se = 0.80/PPV = 0.89), full can (pain) (Se = 0.78/PPV = 0.90), resisted external rotation (pain) (Se = 0.48/PPV = 0.87), drop arm (Se = 0.19/PPV = 0.97), Neer's sign (Se = 0.78/PPV = 0.93) and Hawkins' (Se = 0.80/PPV = 0.88). MRI had the highest PPV (0.99). The Hawkin's test had the highest false positive rate in patients with intact tendons (0.36). The Sp of the empty can and full can (both tests positive for pain and weakness), drop arm and MRI were: 0.93, 0.91, 0.98 and 0.96, respectively. For partial and full-thickness tears, the empty can test (positive for pain and weakness) had a Sp of 0.93, and the drop arm and MRI had the same Sp (0.98). Physical examination demonstrated good diagnostic value, the drop arm test had a Sp as good as MRI for supraspinatus tears; however, MRI was more accurate in ruling out tears. The Hawkins' test had high false-positive findings in patients with intact tendons.


Down-regulation of p27 is associated with malignant transformation and aggressive phenotype of cervical neoplasms.
p27Kip1 (p27) is a member of the cyclin-dependent kinase inhibitor family. The level of p27 protein expression decreases during tumor development and progression in some epithelial tumors. To identify the potential implications of the p27 gene in the development of cervical carcinoma and explore the clinical importance of change in gene expression, we assessed the level of p27 protein in precancerous lesions and carcinomas of the cervix. In our study, 20 low-grade squamous intraepithelial lesions (LSIL), 35 high-grade squamous intraepithelial lesions (HSIL), 12 microinvasive carcinomas, and 103 invasive carcinomas were evaluated. The expression of p27 was studied by immunohistochemistry using a monoclonal antibody specific for the protein. p27 was expressed in all samples of normal epithelium, LSIL, and HSIL, and the mean values of expression were 55.1, 52.8, and 45.4%, respectively. Conversely, the expression of p27 was significantly reduced in microinvasive (15.9%) and invasive carcinomas (11.2%). Furthermore, loss of p27 expression was significantly associated with lymph node metastasis (P = 0.009). However, p27 down-regulation had no influence on overall survival using univariate analysis. The trend of reduced p27 expression in microinvasive and invasive carcinomas suggests that down-regulation of p27 expression is strongly linked to neoplastic transformation of cervical epithelium, and inactivation of p27 may be an early event in cervical carcinogenesis. Moreover, loss of p27 expression was related to lymph node metastasis in cervical carcinoma. These results imply that inactivation of p27 is associated with highly aggressive phenotype of cervical carcinoma.


Sodium accumulation promotes diastolic dysfunction in end-stage heart failure following Serca2 knockout.
Alterations in trans-sarcolemmal and sarcoplasmic reticulum (SR) Ca(2+) fluxes may contribute to impaired cardiomyocyte contraction and relaxation in heart failure. We investigated the mechanisms underlying heart failure progression in mice with conditional, cardiomyocyte-specific excision of the SR Ca(2+)-ATPase (SERCA) gene. At 4 weeks following gene deletion (4-week KO) cardiac function remained near normal values. However, end-stage heart failure developed by 7 weeks (7-week KO) as systolic and diastolic performance declined. Contractions in isolated myocytes were reduced between 4- and 7-week KO, and relaxation was slowed. Ca(2+) transients were similarly altered. Reduction in Ca(2+) transient magnitude resulted from complete loss of SR Ca(2+) release between 4- and 7-week KO, due to loss of a small remaining pool of SERCA2. Declining SR Ca(2+) release was partly offset by increased L-type Ca(2+) current, which was facilitated by AP prolongation in 7-week KO. Ca(2+) entry via reverse-mode Na(+)-Ca(2+) exchange (NCX) was also enhanced. Up-regulation of NCX and plasma membrane Ca(2+)-ATPase increased Ca(2+) extrusion rates in 4-week KO. Diastolic dysfunction in 7-week KO resulted from further SERCA2 loss, but also impaired NCX-mediated Ca(2+) extrusion following Na(+) accumulation. Reduced Na(+)-K(+)-ATPase activity contributed to the Na(+) gain. Normalizing [Na(+)] by dialysis increased the Ca(2+) decline rate in 7-week KO beyond 4-week values. Thus, while SERCA2 loss promotes both systolic and diastolic dysfunction, Na(+) accumulation additionally impairs relaxation in this model. Our observations indicate that if cytosolic Na(+) gain is prevented, up-regulated Ca(2+) extrusion mechanisms can maintain near-normal diastolic function in the absence of SERCA2.


Grafting Hypercrosslinked Polymers on TiO2 Surface for Anchoring Ultrafine Pd Nanoparticles: Dramatically Enhanced Efficiency and Selectivity toward Photocatalytic Reduction of CO2 to CH4.
Metal deposition with photocatalyst is a promising way to surmount the restriction of fast e- /h+ recombination to improve the photocatalytic performance. However, the improvement remains limited by the existing strategies adopted for depositing metal particles due to the serious aggregation and large unconnected area on photocatalyst surface. Here, a strategy is proposed by directly grafting hypercrosslinked polymers (HCPs) on TiO2 surface to construct Pd-HCPs-TiO2 composite with uniform dispersion of ultrafine Pd nanoparticles on HCPs surface. This composite with surface area of 373 m2 g-1 exhibits improved photocatalytic CO2 conversion efficiency to CH4 with an evolution rate of 237.4 µmol g-1 h-1 and selectivity of more than 99.9%. The enhancement can be ascribed to the grafted porous HCPs with high surface area and N heteroatom on TiO2 surface for the stabilization of Pd nanoparticles, favoring the electron transfer and CO2 adsorption for selective CH4 production. This strategy may hold the promise for design and construction of porous organic polymer with semiconductor for efficient photocatalytic conversion.


Next-Generation Sequencing Enables Spatiotemporal Resolution of Human Centromere Replication Timing.
Centromeres serve a critical function in preserving genome integrity across sequential cell divisions, by mediating symmetric chromosome segregation. The repetitive, heterochromatic nature of centromeres is thought to be inhibitory to DNA replication, but has also led to their underrepresentation in human reference genome assemblies. Consequently, centromeres have been excluded from genomic replication timing analyses, leaving their time of replication unresolved. However, the most recent human reference genome, hg38, included models of centromere sequences. To establish the experimental requirements for achieving replication timing profiles for centromeres, we sequenced G₁- and S-phase cells from five human cell lines, and aligned the sequence reads to hg38. We were able to infer DNA replication timing profiles for the centromeres in each of the five cell lines, which showed that centromere replication occurs in mid-to-late S phase. Furthermore, we found that replication timing was more variable between cell lines in the centromere regions than expected, given the distribution of variation in replication timing genome-wide. These results suggest the potential of these, and future, sequence models to enable high-resolution studies of replication in centromeres and other heterochromatic regions.


Immune-driven alterations in mucin sulphation is an important mediator of Trichuris muris helminth expulsion.
Mucins are heavily glycosylated proteins that give mucus its gel-like properties. Moreover, the glycans decorating the mucin protein core can alter the protective properties of the mucus barrier. To investigate whether these alterations could be parasite-induced we utilized the Trichuris muris (T. muris) infection model, using different infection doses and strains of mice that are resistant (high dose infection in BALB/c and C57BL6 mice) or susceptible (high dose infection in AKR and low dose infection in BALB/c mice) to chronic infection by T. muris. During chronicity, within the immediate vicinity of the T. muris helminth the goblet cell thecae contained mainly sialylated mucins. In contrast, the goblet cells within the epithelial crypts in the resistant models contained mainly sulphated mucins. Maintained mucin sulphation was promoted by TH2-immune responses, in particular IL-13, and contributed to the protective properties of the mucus layer, making it less vulnerable to degradation by T. muris excretory secretory products. Mucin sulphation was markedly reduced in the caecal goblet cells in the sulphate anion transporter-1 (Sat-1) deficient mice. We found that Sat-1 deficient mice were susceptible to chronic infection despite a strong TH2-immune response. Lower sulphation levels lead to decreased efficiency of establishment of T. muris infection, independent of egg hatching. This study highlights the complex process by which immune-regulated alterations in mucin glycosylation occur following T. muris infection, which contributes to clearance of parasitic infection.


Prevalence and location of bone bruises associated with anterior cruciate ligament injury and implications for mechanism of injury: a systematic review.
Bone bruising is commonly observed on magnetic resonance imaging (MRI) after non-contact anterior cruciate ligament (ACL) injury. The primary objective of this study was to determine if the location and prevalence of tibial and femoral bone bruises after ACL injury can be explained by specific injury mechanism(s). The secondary objective was to determine whether the bone-bruise literature supports sex-specific injury mechanism(s). We hypothesized that most studies would report bone bruising in the lateral femoral condyle (LFC) and on the posterior lateral tibial plateau (LTP). MEDLINE, PubMed, and SCOPUS were searched for studies that reported bone bruise prevalence and location in ACL-injured subjects. Sex differences in bone-bruise patterns were assessed. Time from injury to imaging was assessed to account for confounding effects on bone-bruise size and location. Thirty-eight studies met the inclusion/exclusion criteria. Anterior-posterior location of bone bruises within the tibiofemoral compartment was assessed in 11 studies. Only five of these studies reported bone-bruise locations on both the tibia and the femur. The most common bone-bruise combination in all five studies was on the LFC and the posterior LTP. Sex differences were only assessed in three studies, and only one reported significantly greater prevalence of LTP bruising in females. Bone-bruise patterns in the current literature support a valgus-driven ACL injury mechanism; however, more studies should report the specific locations of tibial and femoral bone bruises. There is insufficient evidence in the literature to determine whether there are sex-specific bone-bruise patterns in ACL-injured subjects.


Analysis of acidic oligosaccharides and glycopeptides by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.
2,5-Dihydroxybenzoic acid (DHB) is the most commonly used matrix for matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI/TOF) of oligosaccharides. Because acidic, sialylated oligosaccharides are detected at only the low picomole level with DHB, alternative matrices were screened to identify a matrix with a lower limit of detection. Negative-ion spectra of pure mono-, di-, and trisialylated oligosaccharides were acquired with either 6-aza-2-thiothymine or 2',4',6'-trihydroxyacetophenone (THAP) in the linear mode. Detection limits of less than 50 fmol with signal-to-noise ratios of better than 5:1 were achieved with both matrices. THAP was the preferred matrix because it provided a lower limit of detection and gave less prompt fragmentation. Incorporation of ammonium citrate into the matrix, along with vacuum drying of the sample, was required in order to obtain maximum sensitivity with THAP. No evidence of competition for ionization was found when a mixture of mono-, di-, and trisialylated oligosaccharides was analyzed with THAP. These findings suggest that MALDI/TOF analysis may provide a rapid means to identify changes in carbohydrate composition in glycoproteins. In addition, THAP offered improved sensitivity for detection of acidic glycopeptides over alpha-cyano-4-hydroxycinnamic acid.


Roseibium limicola sp. nov., isolated from tidal mudflat.
A novel bacterium, designated strain CAU 1637T, was isolated from a tidal mudflat. Cells of strain CAU 1637T were Gram-stain-negative, aerobic, motile with single flagellum and rod-shaped. The optimum conditions for growth were observed at 30 °C, pH 6.0 and in the presence of 2 % (w/v) NaCl. The respiratory quinone was ubiquinone-10. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain CAU 1637T was closely related to the genus Roseibium, with the highest similarity to Roseibium aestuarii NRBC 112946T (97.4 %), followed by Roseibium hamelinense NRBC 16783T (96.8 %), Roseibium aquae JCM 19310T (96.4 %), Roseibium sediminis KCTC 52373T (95.8 %) and Roseibium denhamense JCM 10543T (95.3 %). The predominant cellular fatty acids were C18 : 1 ω7c 11-methyl and summed feature 8 (C18 : 1 ω7c and/or C18 : 1 ω6c). The major polar lipids consisted of diphosphatidylglycerol and phosphatidylglycerol. The average nucleotide identity values between the novel isolate and related strains ranged from 71.0 to 76.4 %, and the DNA-DNA hybridization values ranged from 19.3 to 20.3 %. The G+C content was 58.4 mol% and the whole-genome size was 4.6 Mb, which included 17 contigs and 3931 protein-coding genes. Based on the taxonomic data, strain CAU 1637T represents a novel species of the genus Roseibium, for which the name Roseibium limicola sp. nov. is proposed. The type strain is CAU 1637T (=KCTC 82429T=MCCC 1K06080T).


Computer aided assignment of motile Aeromonas strains to genospecies level by standard biochemical tests.
A procedure is given for differentiation of motile Aeromonas spp. Based on nine to 12 biochemical properties it allows an assignment of isolated Aeromonas strains first to phenotypes and, in the second step, to hybridization groups (HGs) 1-13 as well as to the genotypically defined species Aer. allosaccharophila and Aer. encheleia. The computer aided classification is carried out according to the principles of numerical taxonomy. Using this differentiation scheme 23 Aeromonas strains, which were isolated from food, and two reference strains were speciated. A total of 16 strains were assigned to Aer. hydrophila, six strains to Aer. caviae and one strain to Aer. sobria. Of the 16 Aer. hydrophile strains, 11 were attached to HG 1, one to HG 2 and four could not be classified clearly as HG 3 or HG 1. All six Aer. caviae isolated were assigned to HG 5 and the Aer. sobria strain was ranked among HG 8. The reference strains were assigned to the same genotypes by this method than by DNA-DNA hybridization assays.


Leukemic leptomeningeal involvement in stage 0 and stage 1 chronic lymphocytic leukemia.
Central nervous system (CNS) involvement in early (Rai Stage 0 and Stage 1) chronic lymphocytic leukemia (CLL) is rare, with only five cases reported. We present the sixth reported case, a 77-year-old male with a 4 year history of Stage 0 CLL who presented with sudden onset of diplopia and headache. Workup revealed a leukemic involvement of his CNS and he responded well to treatment with intrathecal (IT) methotrexate. After his third IT treatment, he developed a change in his mental status, consistent with a chemotherapy induced encephalopathy, which was effectively treated with IT hydrocortisone. In addition to the case presentation, we review the previously reported cases in an effort to determine any characteristics common among the Stage 0/1 CLL patients with reported CNS involvement.


Comodulation masking release in subjects with unilateral and bilateral hearing impairment.
Three subjects with unilateral cochlear hearing loss and three subjects with bilateral cochlear hearing loss were tested in three experiments. In the first, their auditory filter shapes were measured for center frequencies of 700 and 2000 Hz, using the notched-noise method. The auditory filters were generally broader for the impaired than for the normal ears. In experiment 2, the threshold for detecting a 2000-Hz signal centered in a band of noise was measured as a function of the noise bandwidth for a Gaussian noise, and for that same noise multiplied (modulated) by a second noise low-pass filtered at 12.5 Hz. For the Gaussian noise, thresholds increased up to a certain noise bandwidth and then flattened off. This bandwidth was usually greater for the impaired than for the normal ears, consistent with the broader auditory filters of the impaired ears. For the modulated noise, thresholds tended to decrease when the noise bandwidth was increased beyond a certain value, indicating comodulation masking release (CMR). The decrease occurred at wider bandwidths for the impaired than for the normal ears. For the unilaterally impaired subjects, the amount of decrease was smaller for the impaired than for the normal ears when tested at equal SPL, but not when tested at equal SL. In experiment 3, the threshold for detecting a 700-Hz signal centered in a 20-Hz-wide band of noise (the on-frequency band, ONB) was measured in the presence of eight flanking bands (FBs) whose envelopes were either identical with that of the ONB (correlated condition) or were uncorrelated. CMR was defined as the difference in threshold between the correlated and uncorrelated conditions. The ONB and the FBs were presented either to the same ear (monaural condition) or to opposite ears (dichotic condition). CMRs tended to be greatest at high levels of the ONB and the FBs. CMRs in the monaural condition were smaller for hearing-impaired than for normal ears. However, at high levels, CMRs in the dichotic condition were similar for normal, bilaterally impaired, and unilaterally impaired subjects. In the latter case, CMRs were similar when the ONB was presented to the normal ear and to the impaired ear of each subject.(ABSTRACT TRUNCATED AT 400 WORDS)


Hip resurfacing data from national joint registries: what do they tell us? What do they not tell us?
Current-generation metal-on-metal hip resurfacing implants (SRAs) have been in widespread global use since the 1990s, and in the United States, specific implants have recently been approved for clinical use. Many recent publications describe short-term survivorship achieved by either implant-designing surgeons or high-volume centers. National joint replacement registries (NJRRs) on the other hand report survivorship achieved from the orthopaedic community at large. We therefore reviewed SRA survivorship from national registry data and compared with that reported from individual centers. Additionally, we compared SRA survivorship reported by registries and compared prognosticators for failure with those of conventional total hip arthroplasty (THA). Although resurfacing was associated with an overall increased failure rate in comparison to THA (Australian registry 5-year cumulative revision rate [CRR], 3.7% and 2.7%, respectively), there were exceptions to this. Male patients younger than 65 years with primary osteoarthritis had equivalent results with SRA and THA (Australian registry 5-year CRR, 2.5% and 2.8%, respectively). Head size over 50 mm in diameter was a predictor of surface replacement arthroplasty survivorship and only females with a head diameter of 50 mm or greater (14% of females) had a comparable survivorship to males. Diagnoses other than primary osteoarthritis bear a higher risk of early revision of SRA as compared with THA. Revision of SRA does not lead to reproducible results with rerevision rates of 11% at 5 years. Given these predictors of failure, our review of data from the NJRR suggests stringent patient selection criteria might enhance the survival rates of SRA.


Catecholamine physiology and its implications in patients with COVID-19.
The risk factors for severe COVID-19 are diverse, yet closely resemble the clinical manifestations of catecholamine excess states (eg, hypertension, cardiovascular disease, immune dysregulation, and hyperglycaemia), suggesting a potentially common basis for disease. Unfortunately, severe illness (eg, respiratory failure, compromised cardiac function, and shock) incurred by COVID-19 hinders the direct study of catecholamines in these patients, especially among those on multiple medications or those on adrenaline or noradrenaline infusions, or both. Phaeochromocytoma and paraganglioma (PPGL) are tumours that secrete catecholamines, namely adrenaline and noradrenaline, often in excess. PPGL are well studied disease processes in which the effects of catecholamines are easily discernible and therefore their potential biochemical and physiological influences in patients with COVID-19 can be explored. Because catecholamines are expected to have a role in patients with critical illness, patients on vasopressor infusions, and patients who sustain some acute and chronic physical stresses, the challenges involved in the management of catecholamine excess states are directly relevant to the treatment of patients with COVID-19. In this Personal View, we discuss the complex interplay between catecholamines and COVID-19, and the management of catecholamine excess states, while referencing relevant insights derived from the study of PPGL.


Advising and limiting medical treatment during phone consultation: a prospective multicentre study in HEMS settings.
We investigated paramedic-initiated consultation calls and advice given via telephone by Helicopter Emergency Medical Service (HEMS) physicians focusing on limitations of medical treatment (LOMT). A prospective multicentre study was conducted on four physician-staffed HEMS bases in Finland during a 6-month period. Of all 6115 (mean 8.4/base/day) paramedic-initiated consultation calls, 478 (7.8%) consultation calls involving LOMTs were included: 268 (4.4%) cases with a pre-existing LOMT, 165 (2.7%) cases where the HEMS physician issued a new LOMT and 45 (0.7%) cases where the patient already had an LOMT and the physician further issued another LOMT. The most common new limitation was a do-not-attempt cardiopulmonary resuscitation (DNACPR) order (n = 122/210, 58%) and/or 'not eligible for intensive care' (n = 96/210, 46%). In 49 (23%) calls involving a new LOMT, termination of an initiated resuscitation attempt was the only newly issued LOMT. The most frequent reasons for issuing an LOMT during consultations were futility of the overall situation (71%), poor baseline functional status (56%), multiple/severe comorbidities (56%) and old age (49%). In the majority of cases (65%) in which the HEMS physician issued a new LOMT for a patient without any pre-existing LOMT, the physician felt that the patient should have already had an LOMT. The patient was in a health care facility or a nursing home in half (49%) of the calls that involved issuing a new LOMT. Access to medical records was reported in 29% of the calls in which a new LOMT was issued by an HEMS physician. Consultation calls with HEMS physicians involving patients with LOMT decisions were common. HEMS physicians considered end-of-life questions on the phone and issued a new LOMT in 3.4% of consultations calls. These decisions mainly concerned termination of resuscitation, DNACPR, intubation and initiation of intensive care.


Immobilization of lipases on polyethylene and application to perilla oil hydrolysis for production of alpha-linolenic acid.
The conditions of immobilization of lipase on the polyethylene powder were examined and the immobilized lipase was used for effective production of alpha-linolenic acid from perilla oil hydrolysis. Using the polyethylene powder containing micropores in its structure enabled immobilization of lipases. Ethanol pretreatment increased the immobilization efficiency. The efficiency of immobilization of six different lipases was 67-91%. On hydrolysis of perilla oil, the activity of the immobilized lipase was nearly the same as that of free lipase. Among the enzymes used, the Candida rugosa lipase hydrolyzed perilla oil most effectively. When the immobilized C. rugosa lipase was used 10 times for perilla oil hydrolysis by the batch reaction method (1 batch, 24-h reaction at 37 degrees C), there was little decrease in its activity. These results suggest that polyethylene-immobilized lipase can be used for the effective hydrolysis of perilla oil to produce alpha-linolenic acid.


A gene-environment-induced epigenetic program initiates tumorigenesis.
Tissue damage increases the risk of cancer through poorly understood mechanisms1. In mouse models of pancreatic cancer, pancreatitis associated with tissue injury collaborates with activating mutations in the Kras oncogene to markedly accelerate the formation of early neoplastic lesions and, ultimately, adenocarcinoma2,3. Here, by integrating genomics, single-cell chromatin assays and spatiotemporally controlled functional perturbations in autochthonous mouse models, we show that the combination of Kras mutation and tissue damage promotes a unique chromatin state in the pancreatic epithelium that distinguishes neoplastic transformation from normal regeneration and is selected for throughout malignant evolution. This cancer-associated epigenetic state emerges within 48 hours of pancreatic injury, and involves an 'acinar-to-neoplasia' chromatin switch that contributes to the early dysregulation of genes that define human pancreatic cancer. Among the factors that are most rapidly activated after tissue damage in the pre-malignant pancreatic epithelium is the alarmin cytokine interleukin 33, which recapitulates the effects of injury in cooperating with mutant Kras to unleash the epigenetic remodelling program of early neoplasia and neoplastic transformation. Collectively, our study demonstrates how gene-environment interactions can rapidly produce gene-regulatory programs that dictate early neoplastic commitment, and provides a molecular framework for understanding the interplay between genetic and environmental cues in the initiation of cancer.


The Living Experience of Suffering: A Parse Method Study.
The purpose of this study was to investigate the humanuniverse living experience of suffering. The Parse method was used to answer the question: What is the structure of the living experience of suffering? The participants were 10 adults living in the community. The finding of the study, the structure of the living experience of suffering, was found to be as follows: Suffering is anguishing desolation with varied alliances arising with envisioning anew. The living experience of suffering is discussed in relation to the principles of the humanbecoming paradigm and in relation to further research inquiries.


Predictors of Successful Yield of Transbronchial Lung Biopsy in Patients With Sarcoidosis.
Transbronchial lung biopsy (TBLB) is an important bronchoscopic procedure used in the diagnosis of sarcoidosis. Only a few studies have evaluated determinants associated with successful diagnostic yield of TBLB. Herein, we evaluate the factors predicting successful yield of TBLB in subjects with sarcoidosis. Consecutive subjects with a clinical suspicion of sarcoidosis who underwent TBLB were enrolled. We evaluated the association between symptoms, spirometric lung function, radiologic stage of sarcoidosis, number of specimens, presence of floating biopsies, number of alveoli, and successful diagnostic yield (presence of granuloma) on TBLB. Of the 223 subjects, sarcoidosis was diagnosed in 209 [mean (SD) age, 43.9 (12.6) y; 50.7% men] individuals. A total of 1021 TBLB specimens were obtained. Granulomas were demonstrated in 123 (58.9%) subjects on TBLB. On a multivariate analysis, there was no association between successful diagnostic yield and the presence of dyspnea, spirometric lung function, radiologic stage of sarcoidosis, presence of floating biopsies, presence of at least 50 alveoli, or crush artifacts during histopathologic examination. Complications were encountered in 25 (11.9%) subjects. There were no deaths. TBLB is a reasonably safe procedure with a good diagnostic yield. The present study did not identify any predictors associated with successful diagnostic yield of TBLB in sarcoidosis.


Clinal variation in MHC diversity with temperature: evidence for the role of host-pathogen interaction on local adaptation in Atlantic salmon.
In vertebrates, variability at genes of the Major Histocompatibility Complex (MHC) represents an important adaptation for pathogen resistance, whereby high allelic diversity confers resistance to a greater number of pathogens. Pathogens can maintain diversifying selection pressure on their host's immune system that can vary in intensity based on pathogen richness, pathogen virulence, and length of the cohabitation period, which tend to increase with temperature. In this study, we tested the hypothesis that genetic diversity of MHC increases with temperature along a latitudinal gradient in response to pathogen selective pressure in the wild. A total of 1549 Atlantic salmon from 34 rivers were sampled between 46 degrees N and 58 degrees N in Eastern Canada. The results supported our working hypothesis. In contrast to the overall pattern observed at microsatellites, MHC class II allelic diversity increased with temperature, thus creating a latitudinal gradient. The observed temperature gradient was more pronounced for MHC amino acids of the peptide-binding region (PBR), a region that specifically binds to pathogens, than for the non-PBR. For the subset of rivers analyzed for bacterial diversity, MHC amino acid diversity of the PBR also increased significantly with bacterial diversity in each river. A comparison of the relative influence of temperature and bacterial diversity revealed that the latter could have a predominant role on MHC PBR variability. However, temperature was also identified as an important selective agent maintaining MHC diversity in the wild. Based on the bacteria results and given the putative role of temperature in shaping large-scale patterns of pathogen diversity and virulence, bacterial diversity is a plausible selection mechanism explaining the observed association between temperature and MHC variability. Therefore, we propose that genetic diversity at MHC class II represents local adaptation to cope with pathogen diversity in rivers associated with different thermal regimes. This study illuminates the link between selection pressure from the environment, host immune adaptation, and the large-scale genetic population structure for a nonmodel vertebrate in the wild.


Using the minimum data set 2.0 mood disturbance items as a self-report screening instrument for depression in nursing home residents.
Seeking to enhance nursing home residents' involvement in their care, the authors examined whether the Minimum Data Set, Version 2.0 (MDS) Mood Disturbance items could be administered by self-report. They compared the MDS to the Geriatric Depression Scale (GDS) in terms of its association with depression diagnosis. Subjects (N=204) were nursing home residents who were interviewed with a psychiatric diagnostic instrument, the GDS, and a self-report version of the MDS mood disturbance items. Analyses of variance and receiver operating characteristics analyses demonstrated that MDS items distinguished subjects with any versus no depression about as well as did the GDS. This pattern held within cognitive, gender, and ethnicity subgroups. The MDS Mood Disturbance items can be reliably and validly administered via self-report to persons scoring at least 12 on the Mini-Mental State Exam.


[Wilson disease - factors affecting clinical presentation].
Wilson disease (WD) is a genetic disorder with copper metabolism disturbances leading to copper accumulation in many organs with their secondary damage. It is caused by mutation in the ATP7B gene on chromosome 13, which encodes ATP-ase 7B involved in copper transport. The age of neurologic symptom onset in WD is 20-30 years, but there is a wide spectrum of disease including: age at onset, clinical signs and treatment efficacy. More than 500 mutations of ATP7B have been described so far, but the WD genotype does not explain the disease variability. Several other factors are suspected to influence WD presentation, including polymorphisms in the genes encoding: apolipoprotein E, prion-related protein, methyltenetetrahydrofolate reductase, Murr1, antioxidant-1, X-linked inhibitor of apoptosis as well as iron metabolism disturbances, gender impact, inflammatory reactions and oxidative stress. The explanation of their significance can change the therapy of WD. The aim of our study was to review and assess the clinical significance of the factors affecting WD presentation.


[Prognostic factors of cervical lymph metastases from squamous cell carcinomas the head and neck].
Cervical lymph node prognostic factors were investigated in 382 head and neck squamous cell carcinoma (SCC) patients including oral cavity cancer, oropharngeal cancer, hypopharyngeal cancer and laryngeal cancer. The overall five year survival rate of these patients was 46.1%, and the 5 year survival rate was 49.7%, 39.7%, 35.0% and 60.3% in carcinomas of oral cavity, oropharynx, hypopharynx and larynx, respectively. It was confirmed that clinical N staging, the size of lymph nodes, pathological conditions of neck nodes, numbers of positive areas and the lowest level of invasion are of prognostic value. Some suitable measures must be taken to cope with these factors to improve the five-year survival rate of patients with SCC of the head and neck.


Inhibition of plant protoporphyrinogen oxidase by the herbicide acifluorfen-methyl.
The effect of acifluorfen-methyl on tetrapyrrole synthesis in greening chloroplasts of Cucumis sativus was examined. Formation of Mg-proto-porphyrin IX from delta-aminolevulinate was reduced 98% by 10 micromolar acifluorfen-methyl. Conversion of protoporphyrin IX to Mg-protoporphyrin IX was unaffected, but protoporphyrin IX synthesis from delta-aminolevulinate was blocked, indicating a site of inhibition prior to the Mg-chelatase. The enzymic oxidation of protoporphyrinogen IX to protoporphyrin IX was highly sensitive to acifluorfen-methyl, indicating that the site of action of the herbicide is the protoporphyrinogen oxidase. ((c) 1989 FMC Corporation. All rights reserved.).


Multimetallic complexes and functionalized nanoparticles based on unsymmetrical dithiocarbamate ligands with allyl and propargyl functionality.
The new, unsymmetrical dithiocarbamate ligands, KS2CN(CH2CH═CH2)Me and KS2CN(CH2C≡CH)Me, are formed from the respective amines on reaction with KOH and carbon disulfide. The homoleptic complexes [Ni{S2CN(CH2CH═CH2)Me}2] and [M{S2CN(CH2C≡CH)Me}2] (M = Ni, Pd, Pt) are formed on reaction with suitable metal precursors. Conversion between the two pendant functionalities was confirmed by hydrogenation of [Ni{S2CN(CH2C≡CH)Me}2] to yield [Ni{S2CN(CH2CH═CH2)Me}2]. The monodithiocarbamate compounds of group 8, 10, and 11 metals, [Ru{S2CN(CH2CH═CH2)Me}(dppm)2](+), [Ru(CH═CHC6H4Me-4){S2CN(CH2CH═CH2)Me}(CO)(PPh3)2], [Ni{S2CN(CH2CH═CH2)Me}(dppp)](+), and [Au{S2CN(CH2CH═CH2)Me}(PPh3)] were formed successfully. Using KS2CN(CH2C≡CH)Me, the complex [Ru{S2CN(CH2C≡CH)Me}(dppm)2](+) was obtained from cis-[RuCl2(dppm)2]. One palladium example, [Pd{S2CN(CH2C≡CH)Me}(PPh3)2](+), was also isolated in low yield. However, under the typical conditions employed, a rearrangement reaction prevented isolation of further group 10 propargyl-dithiocarbamate products. Over the extended reaction time required, Me(HC≡CCH2)NCS2(-) was found to undergo a remarkable, atom-efficient cyclization to form the thiazolidine-2-thione, H2C═CCH2N(Me)C(═S)S, in high yield, with MeC═CHN(Me)C(═S)S as the minor product. The reactivity of the pendant triple bonds in [Ni{S2CN(CH2C≡CH)Me}2] was probed in the reaction with [RuH(CO)(S2P(OEt)2)(PPh3)2] to form the trimetallic example [Ni{S2CN(Me)CH2CH═CHRu(CO)(S2P(OEt)2)(PPh3)2}2], while the copper(I) catalyzed reaction with benzylazide yielded the triazole product, [Ni{S2CN(Me)CH2(C2HN3)Bz}2]. KS2CN(CH2C≡CH)Me was also used to prepare the gold nanoparticles, Au@S2CN(CH2C≡CH)Me. Structural studies are reported for [Ru(CH═CHC6H4Me-4){S2CN(CH2CH═CH2)Me}(CO)(PPh3)2] and [Ru{S2CN(CH2C≡CH)Me}(dppm)2]PF6.


Therapeutic vaccination with p24-VLP and zidovudine augments HIV-specific cytotoxic T lymphocyte activity in asymptomatic HIV-infected individuals.
This study evaluates the impact of therapeutic vaccination with p24-VLP and zidovudine on the induction or maintenance of HIV-specific cytotoxic lymphocyte activity in a cohort of asymptomatic patients with CD4 counts greater than 400 cells/microl. In a dummy, randomized, phase II clinical trial of the therapeutic vaccine, participants were randomized to one of three arms for 6 months: p24-VLP (500 microg) in alum monthly plus zidovudine 200 mg tds, alum adjuvant plus zidovudine, or p24-VLP plus placebo. Subjects were studied for a total of 52 weeks from baseline. Monitoring included viral load, CD4 and CD8 counts, markers of immune activation, delayed-type hypersensitivity (DTH) skin testing, and cytotoxic T lymphocyte (CTL) measurement. The nine subjects who received p24-VLP and zidovudine had an augmentation and/or broadening of their CTL response compared with baseline (p = 0.004). The eight subjects receiving p24-VLP and seven subjects receiving zidovudine did not have a statistically significant increase or broadening of CTL activity. The augmentation of the CTL response in the subjects who received p24-VLP and zidovudine was not associated with a decline in viral load or an increase in CD8 counts. This study suggests that HIV-specific CTL activity can be augmented in HIV-infected individuals receiving p24-VLP and zidovudine, supporting the hypothesis of therapeutic vaccination in the presence of antiretroviral therapy.


Hybrid Bilayer WSe2 -CH3 NH3 PbI3 Organolead Halide Perovskite as a High-Performance Photodetector.
A high-performance 2D photodetector based on a bilayer structure comprising a WSe2 monolayer and CH3 NH3 PbI3 organolead halide perovskite is reported. High performance is realized by modification of the WSe2 monolayer with laser healing and perovskite functionalization. After modification, the output of the device was three orders of magnitude better than the pristine device; the performance is superior to that of most of the 2D photodetectors based on transition-metal-dichalcogenides (TMDs). This result indicates that combinatory TMDs-halide perovskite hybrids can be promising building blocks in optoelectronics.


Emergence of new pathogens as a function of changes in host susceptibility.
A pathogen may emerge as an important public health problem because of changes in itself or its transmission pathways. Alternatively, a microorganism may emerge as a pathogen or acquire new public health importance because of changes in host susceptibility to infection. Factors influencing host susceptibility within the population as a whole include increases in the number of immunocompromised patients; increased use of immunosuppressive agents, particularly among persons receiving cancer chemotherapy or undergoing organ transplantation; aging of the population; and malnutrition. In considering the emergence of foodborne pathogens and designing interventions to limit their spread, the susceptibility of these population subgroups to specific infections should be taken into account.