Oxygen utilisation in patients on prolonged parenteral nutrition; a case-controlled study.
Parenteral nutrition (PN) deficient in mitochondrial substrates and thiamine may lead to acidosis. This, combined with fatigue seen in patients with intestinal failure (IF), may suggest suboptimal oxidative metabolism. We therefore studied oxygen utilisation in otherwise apparently well-nourished individuals with intestinal failure receiving long term PN. This was a retrospective analysis conducted in a tertiary IF institution, from 2010 to 2019, comparing treadmill/bicycle cardiopulmonary exercise test (CPET) derived variables including peak oxygen consumption (VO2 peak), anaerobic threshold (AT) and ventilatory efficiency (minute ventilation (VE)/CO2 output (VCO2) of patients with IF (cases) to those without (controls), matched in a 1:2 ratio for age ( ± 3 years), gender, use of beta-blockers and physiology parameters of p-POSSUM score ( ± 5). All subjects were free of sepsis and metastatic malignancy. Mann-Whitney or Student's t-test for continuous and Fisher's exact or chi-squared test for categorical variables were used as appropriate. Data shown represent mean or median values. Participants (31 cases, 62 controls) were comparable in age (65.4 vs. 65.3, p = 0.98); p-POSSUM parameters (18.0 vs. 17.0, p = 0.45); gender (p = 1.00); smoking status (p = 0.52); use of beta-blockers (p = 1.00) and ≤10 mg/day of oral steroids (p = 0.34). Participants had been on PN for 11.0 (6.0-24.0) months and were adequately nourished (requirements 27.6 kcal/kg/day, replacement 23.5 kcal/kg/day). No differences were found between VO2 peak (15.2 vs. 14.6 ml/kg/min, p = 0.96), AT (10.4 vs. 11.0 ml/kg/min, p = 0.44) and VE/VCO2 (33.0 vs. 33.0, p = 0.96) of the examined groups. Patients with intestinal failure receiving PN who are apparently well-nourished also appear to have normal oxygen utilisation, suggesting alternative causes for fatigue. More studies will be required to determine whether CPET could reliably be used to assess perioperative risk in this group of patients.


In-plane chemical pressure essential for superconductivity in BiCh2-based (Ch: S, Se) layered structure.
BiCh2-based compounds (Ch: S, Se) are a new series of layered superconductors, and the mechanisms for the emergence of superconductivity in these materials have not yet been elucidated. In this study, we investigate the relationship between crystal structure and superconducting properties of the BiCh2-based superconductor family, specifically, optimally doped Ce1-xNdxO0.5F0.5BiS2 and LaO0.5F0.5Bi(S1-ySey)2. We use powder synchrotron X-ray diffraction to determine the crystal structures. We show that the structure parameter essential for the emergence of bulk superconductivity in both systems is the in-plane chemical pressure, rather than Bi-Ch bond lengths or in-plane Ch-Bi-Ch bond angle. Furthermore, we show that the superconducting transition temperature for all REO0.5F0.5BiCh2 superconductors can be determined from the in-plane chemical pressure.


Accuracy and precision of depth-resolved estimation of attenuation coefficients in optical coherence tomography.
Parametric imaging of the attenuation coefficient μOCT using optical coherence tomography (OCT) is a promising approach for evaluating abnormalities in tissue. To date, a standardized measure of accuracy and precision of μOCT by the depth-resolved estimation (DRE) method, as an alternative to least squares fitting, is missing. We present a robust theoretical framework to determine accuracy and precision of the DRE of μOCT. We derive and validate analytical expressions for the accuracy and precision of μOCT determination by the DRE using simulated OCT signals in absence and presence of noise. We compare the theoretically achievable precisions of the DRE method and the least-squares fitting approach. Our analytical expressions agree with the numerical simulations for high signal-to-noise ratios and qualitatively describe the dependence on noise otherwise. A commonly used simplification of the DRE method results in a systematic overestimation of the attenuation coefficient in the order of μOCT2×Δ, where Δ is the pixel stepsize. When μOCT·|AFR|≲1.8, μOCT is reconstructed with higher precision by the depth-resolved method compared to fitting over the length of an axial fitting range |AFR|. We derived and validated expressions for the accuracy and precision of DRE of μOCT. A commonly used simplification of this method is not recommended as being used for OCT-attenuation reconstruction. We give a rule of thumb providing guidance in the choice of estimation method.


Investigation of thermodynamic and kinetic parameters of Albizia lebbeck seed pods using thermogravimetric analysis.
Thermodynamic and kinetic studies are very necessary to evaluate the conversion efficiency of biomass to energy. Therefore, this current work reported the thermodynamic and kinetic parameters of Albizia lebbeck seed pods through thermogravimetric analysis, which was carried out at temperatures from 25 °C to 700 °C, and heating rates of 5, 10, 15, and 20 °C/min. Apparent activation energies were determined by applying three iso-conversional model-free methods including Kissinger-Akahira-Sunose (KAS), Ozawa-Flynn-Wall (OFW), and Starink. Resultantly, average apparent activation energy values for the three models of KAS, OFW, and Starink were found to be 155.29, 156.14, and 155.53 kJ/mol, respectively. In addition, thermodynamic triplets such as enthalpy, Gibbs free energy, and entropy were obtained as 151.16 kJ/mol, 150.64 kJ/mol, and -7.57 J/mol·K, respectively. The above results suggest Albizia lebbeck seed pods could become a potential source for bioenergy production aiming to achieve the sustainable goal and waste-to-energy strategy.


Metastatic disease from untreated uveal melanomas.
Few ophthalmologists or pathologists have observed uveal melanomas that metastasized before they were recognized and treated. In an effort to characterize those melanomas that have produced metastatic disease before the tumor-containing eye was enucleated, we have collected a series of 29 cases for review. These have generally involved older subjects (median age 65 years) who had large tumors that had been symptomatic for long periods before being recognized. A disproportionately large percentage showed extraocular extension. Although the data support the thesis that uveal melanomas are typically slow-growing tumors that show local infiltrative properties but little tendency to produce metastatic disease unless treated by enucleation of the eye, it is possible that the available information is possibly biased by our methods of acquisition of data. Much pertinent information is lost because the cases usually do not come to the attention of ophthalmologists or ophthalmic pathologist. This missing link in our knowledge of the natural course of untreated uveal melanomas is one of several factors that make it impossible to determine whether the overall effects of enucleation have been beneficial or harmful in the management of this disease.


ATR-FTIR combined with machine learning for the fast non-targeted screening of new psychoactive substances.
Due to the diversity and fast evolution of new psychoactive substances (NPS), both public health and safety are threatened around the world. Attenuated total reflection-Fourier transform infrared spectroscopy (ATR-FTIR), which serves as a simple and rapid technique for targeted NPS screening, is challenging with the rapid structural modifications of NPS. To achieve the fast non-targeted screening of NPS, six machine learning (ML) models were constructed to classify eight categories of NPS, including synthetic cannabinoids, synthetic cathinones, phenethylamines, fentanyl analogues, tryptamines, phencyclidine types, benzodiazepines, and "other substances" based on the 1099 IR spectra data items of 362 types of NPS collected by one desktop ATR-FTIR and two portable FTIR spectrometers. All these six ML classification models, including k-nearest neighbor (KNN), support vector machine (SVM), random forest (RF), extra trees (ET), voting, and artificial neural networks (ANNs) were trained through cross validation, and f1-scores of 0.87-1.00 were achieved. In addition, hierarchical cluster analysis (HCA) was performed on 100 synthetic cannabinoids with the most complex structural variation to investigate the structure-spectral property relationship, which leads to a summary of eight synthetic cannabinoid sub-categories with different "linked groups". ML models were also constructed to classify eight synthetic cannabinoid sub-categories. For the first time, this study developed six ML models, which were suitable for both desktop and portable spectrometers, to classify eight categories of NPS and eight synthetic cannabinoids sub-categories. These models can be applied for the fast, accurate, cost-effective, and on-site non-targeted screening of newly emerging NPS with no reference data available.


Synthesis and biochemical evaluation of N-(1-substituted-cycloalkyl)-beta-(3,4-dimethoxy; or dihydroxy) phenethylamines: potential dopaminergic agents.
The design and synthesis of some hybrid-structures comprising the dopamine framework on one hand and an N-(1-substituted-cycloalkyl) moiety on the other have been elaborated. Selective members of the new series were biochemically assayed to determine their effects on the levels of dopamine and its metabolite norepinephrine in brains of Albino-rats. The brain MAO activity was also estimated. The results were compared with those displayed by apomorphine, metoclopramide and PCP.


Uniform Manifold Approximation and Projection for Clustering Taxa through Vocalizations in a Neotropical Passerine (Rough-Legged Tyrannulet, Phyllomyias burmeisteri).
Vocalizations from birds are a fruitful source of information for the classification of species. However, currently used analyses are ineffective to determine the taxonomic status of some groups. To provide a clearer grouping of taxa for such bird species from the analysis of vocalizations, more sensitive techniques are required. In this study, we have evaluated the sensitivity of the Uniform Manifold Approximation and Projection (UMAP) technique for grouping the vocalizations of individuals of the Rough-legged Tyrannulet Phyllomyias burmeisteri complex. Although the existence of two taxonomic groups has been suggested by some studies, the species has presented taxonomic difficulties in classification in previous studies. UMAP exhibited a clearer separation of groups than previously used dimensionality-reduction techniques (i.e., principal component analysis), as it was able to effectively identify the two taxa groups. The results achieved with UMAP in this study suggest that the technique can be useful in the analysis of species with complex in taxonomy through vocalizations data as a complementary tool including behavioral traits such as acoustic communication.


Are international patients the answer to American hospitals' problems?
American hospitals hoping to capitalize on the lucrative market for international patients may be in for some surprises. Not only is this market limited, but also the drawbacks may outweigh the potential benefits for hospitals seeking to enter this business.


Management of metastatic pancreatic cancer: Current treatment options and potential new therapeutic targets.
Pancreatic ductal adenocarcinoma is a malignancy with a poor prognosis, with the majority of patients diagnosed with advanced disease on presentation. Treatment options remain limited with little progress over the last 40 years. This review will focus on the current management of metastatic pancreatic ductal adenocarcinoma, with a discussion of new and future treatment strategies based on an improved understanding of tumour biology and mechanisms of pathogenesis.


LA Sprouts: A 12-Week Gardening, Nutrition, and Cooking Randomized Control Trial Improves Determinants of Dietary Behaviors.
To evaluate the effect of an exploratory 12-week nutrition, cooking, and gardening trial (LA Sprouts) on preference for fruit and vegetables (FV); willingness to try FV; identification of FV; self-efficacy to garden, eat, and cook FV; motivation to garden, eat, and cook FV; attitudes toward FV; nutrition and gardening knowledge; and home gardening habits. Randomized controlled trial. Four elementary schools. Three hundred four predominately Hispanic/Latino third- through fifth-grade students were randomized to either the LA Sprouts group (n = 167 students) or control group (n = 137 students). Twelve-week after-school nutrition, cooking, and gardening intervention. Determinants of dietary behavior as measured by questionnaire at baseline and postintervention. Analyses of covariance. After the 12-week program, compared with controls, LA Sprouts participants improved scores for identification of vegetables (+11% vs +5%; P = .001) and nutrition and gardening knowledge (+14.5% vs -5.0%; P = .003), and were more likely to garden at home (+7.5% vs -4.4%; P = .003). The LA Sprouts program positively affected a number of determinants of dietary behaviors that suggest possible mechanisms by which gardening and nutrition education act to improve dietary intake and health outcomes.


Evaluating the Accumulation of Antioxidant and Macro- and Trace Elements in Vaccinium myrtillus L.
This study was conducted in order to characterise the accumulation ability of Vaccinium myrtillus L for trace elements such as Al, Cd, Cu, Fe, Mn, Pb and Zn and selected macroelements Ca, K, Mg, Na and P. The accumulation of nutrient elements and trace elements (ANE and ATE) and changes in the ecophysiological responses in bilberry in differently polluted areas were compared. The accumulation of the elements in the roots, stems and leaves of bilberry from four sites (in the nearest vicinity of a zinc smelter, a Mining and Metallurgical Plant, a main road with a high traffic volume and an unprotected natural forest community) were measured using optical emission spectrometry with excitation using inductively coupled argon plasma after wet acid digestion. The highest Cd, Cu, Pb and Zn concentrations were found in the V. myrtillus samples that were growing under the influence of the emissions from the zinc smelter. Moreover, the level of the total accumulated trace metals (ATE-17.09 mmolc kg-1) was also highest for the bilberry at this site. However, in the same area, the sum of the accumulated macronutrients (ANE-296.92 mmolc kg-1) was lower than at the other sampling sites. An EF > 2 was found for Cd, Pb, Zn and Mn, which suggests that bilberries may be enriched in these metals. According to the translocation factor, V. myrtillus was an accumulator of Cd, Zn and Mn. An analysis of the ecophysiological responses showed that the greatest concentration of ascorbic acid was found in the leaves of V. myrtillus at the most contaminated site (3.32 mg g-1 fresh weight). There were no significant differences in the total phenols between the contaminated and non-contaminated sites. However, the lowest value of the total phenolic content (490.77 mg g-1 dry weight) was recorded at the site where the highest Fe concentration was detected in the leaves. A significantly positive correlation between the Cd, Pb and Zn concentrations and a strong negative correlation between the Mn concentration and ascorbic acid content in the leaves of bilberry was also observed. The results provide evidence that the ANE method, which is used to interpret the chemical composition of bilberry has made determining the impact of toxic trace metals on the mineral composition of V. myrtillus significantly easier and also that a non-enzymatic antioxidant such as ascorbic acid can be a good biomarker for determining the oxidative stress that is caused by toxic trace metals.


Carnosine-like immunoreactivity in the olfactory bulb of the rat: an electron microscopic study.
Carnosine-immunoreactive primary olfactory nerve terminals are demonstrated in the glomerular layer of the rat olfactory bulb by immunoelectron microscopy. Asymmetrical synapses between dendrites of mitral/tufted cells and that of periglomerular cells could be observed. In the accessory olfactory system, carnosine-like immunoreactivity is also detected in the vomeronasal neurons.


Guanidine-containing double-network silks with enhanced tensile and antibacterial property.
The bacterial infection of surgical wounds results in prolonged hospitalization and even death of patients, calling for antibacterial function in modern suture products. To tackle this challenge, cationic guanidine-containing copolymer was synthesized, exhibiting antibacterial potency over 5 log reduction against both Gram-positive S. aureus and Gram-negative E. coli. Furthermore, we developed a double-network silk suture by integrating a guanidine-containing copolymer network into the silk fibroin network. This suture exhibited biocidal activity against S. aureus and E. coli, and superior strength compared to the commercial product in both dry and wet conditions. These results may bring general benefits to public health and medical equipment sustainability.


Immunogenicity and safety of the quadrivalent human papillomavirus vaccine in Chinese females aged 9 to 26 years: A phase 3, open-label, immunobridging study.
The quadrivalent human papillomavirus (qHPV; HPV6/11/16/18) vaccine was approved for use in Chinese women aged 20-45 years in 2017. This Phase 3, open-label study (NCT03493542) aimed to assess immunogenicity and safety of the qHPV vaccine in Chinese girls aged 9-19 years versus Chinese young women aged 20-26 years; we report results from Day 1 through Month 7. The study will continue through Month 60 to assess antibody persistence in Chinese girls aged 9-19 years. Participants aged 9-26 years received three doses of the qHPV vaccine (Day 1, Month 2, Month 6). Geometric mean titers (GMTs) and seroconversion percentages for anti-HPV6/11/16/18 antibodies were determined by competitive Luminex immunoassay (cLIA) in serum samples obtained on Day 1 and at Month 7. Injection-site adverse events (AEs) and systemic AEs within 30 days post-vaccination, and serious AEs (SAEs) occurring at any time during the study, were recorded. In total, 766 participants (383 aged 9-19 years; 383 aged 20-26 years) were enrolled and received ≥1 vaccine dose. All participants in the per-protocol immunogenicity population of both age groups seroconverted to each of the vaccine HPV types at Month 7. Anti-HPV6/11/16/18 antibody GMTs at Month 7 in participants aged 9-19 years were non-inferior to those in participants aged 20-26 years. Injection-site AEs and systemic AEs were reported by 36.6% and 49.3% of 9-19-year-olds, and 40.7% and 54.8% of 20-26-year-olds, respectively. There were no vaccine-related SAEs. No participants discontinued the vaccine due to an AE and no deaths were reported. Antibody responses induced by the 3-dose qHPV vaccination regimen in Chinese girls aged 9-19 years were non-inferior to those in Chinese young women aged 20-26 years. The vaccine was generally well tolerated in the study population. ClinicalTrials.gov Identifier: NCT03493542.


[Diagnosis of the active phase of periodontal disease. 1. Clinical parameters].
Review of the literature shows that the common clinical parameters used in practice are inaccurate in assessing periodontal disease activity. Radiographs and probings are, instead, relatively accurate in retrospectively assessing periodontal disease activity. Currently more sophisticated radiographic techniques are being developed to diagnose ongoing periodontal disease activity.


Multilineage polyclonal engraftment of Cal-1 gene-modified cells and in vivo selection after SHIV infection in a nonhuman primate model of AIDS.
We have focused on gene therapy approaches to induce functional cure/remission of HIV-1 infection. Here, we evaluated the safety and efficacy of the clinical grade anti-HIV lentiviral vector, Cal-1, in pigtailed macaques (Macaca nemestrina). Cal-1 animals exhibit robust levels of gene marking in myeloid and lymphoid lineages without measurable adverse events, suggesting that Cal-1 transduction and autologous transplantation of hematopoietic stem cells are safe, and lead to long-term, multilineage engraftment following myeloablative conditioning. Ex vivo, CD4+ cells from transplanted animals undergo positive selection in the presence of simian/human immunodeficiency virus (SHIV). In vivo, Cal-1 gene-marked cells are evident in the peripheral blood and in HIV-relevant tissue sites such as the gastrointestinal tract. Positive selection for gene-marked cells is observed in blood and tissues following SHIV challenge, leading to maintenance of peripheral blood CD4+ T-cell counts in a normal range. Analysis of Cal-1 lentivirus integration sites confirms polyclonal engraftment of gene-marked cells. Following infection, a polyclonal, SHIV-resistant clonal repertoire is established. These findings offer strong preclinical evidence for safety and efficacy of Cal-1, present a new method for tracking protected cells over the course of virus-mediated selective pressure in vivo, and reveal previously unobserved dynamics of virus-dependent T-cell selection.


Cognitive function before and after dialysis initiation in adults with chronic kidney disease-a new perspective on an old problem?
The impact of dialysis on cognitive trends is uncertain. Kurella Tamura et al. evaluated cognitive trajectories in 212 participants from the Chronic Renal Insufficiency Cohort study and found that dialysis initiation was associated with a decline in executive function. This is consistent with a cerebrovascular basis for cognitive impairment in patients with renal disease. However, larger corroborative studies are needed while targets for intervention are identified to ameliorate dialytic effects on cognitive function.


[Effect of visual deprivation on the cytochemical differentiation of neurons in the separate laminae of the rabbit superior colliculus].
The neurons of lamina II, III, VII of the superior colliculus are interferometrically shown to develop features of cytochemical underdevelopment in response to the exclusion of specific visual impulsation. Of the neurons of the lamina studied, lower protein contents in their cytoplasm and nuclei are characteristic, in addition to smaller sizes in comparison with normal ones. A definite specificity of these changes is revealed, which is explained by morphofunctional peculiarities of the neurons of the lamina of the superior colliculus studied.


Inorganic ion chemistry of local particulate matter in a populated city of North China at light, medium, and severe pollution levels.
Twenty-six pairs of PM2.5 and PM10 samples were collected during haze episodes in Zhengzhou (113°28' E, 34°37' N), a highly populated city in North China. The samples were used to examine the inorganic ion chemistry of particulate matter (PM) of local origin at light (PM2.5 < 60 μg m-3 and PM10 < 135 μg m-3), medium (PM2.5: 60-170 μg m-3 and PM10: 135-325 μg m-3), and severe (PM2.5 > 170 μg m-3 and PM10 > 325 μg m-3) pollution levels. At the light and severe pollution levels, the increase of PM10 was accounted for by the increase of PM2.5, and the variation of PM10-2.5 was small. In contrast, the increase of PM10 at the medium pollution level was caused by the increase in both PM2.5 and PM10-2.5. Sulfate (SO42-), nitrate (NO3-), ammonium (NH4+), and chloride in the form of ammonium chloride (Cl-S) accounted for 47.8% and 60.3% of the PM2.5 mass at the light and severe levels, respectively. These values indicate a large contribution of secondary inorganic species to the PM2.5 growth. As the pollution level changed from light to medium, the contribution of SO42- to the growth of PM2.5 decreased from 49.0% to 15.1%, while those of NO3- and Cl-S increased from 25.1% and 0.6% to 32.5% and 2.8%, respectively, indicating the substantial production of nitrate and chloride. At the severe level, the contribution of SO42- was 30.1%, while those of NO3- and Cl-S were 5.9% and 0.5%, respectively, suggesting a hindering effect of sulfate on the production of nitrate and chloride. These results indicate that the production of secondary species with the increase of PM2.5 was dominated by sulfate-associated conversions at the light and severe pollution levels and was substantially influenced by nitrate- and chloride-associated conversions at the medium pollution level. The estimation of carbonate presence in the PM indicates that part of the carbonate in coarse particles (PM10-2.5) of crustal origin enhanced sulfate production via heterogeneous surface reactions. Quantification of the contribution of primary and secondary species to PM2.5 showed that it was dominated by both primary and secondary particles at the light pollution level, and it was mainly composed of secondary species at the severe pollution level.


mu-Opiate receptor agonist loperamide blocks bethanechol-induced gallbladder contraction, despite higher cholecystokinin plasma levels in man.
mu-Opiate receptor agonists, such as loperamide, influence biliary excretion and suppress cholecystokinin (CCK)-induced gallbladder contraction. Loperamide decreases cholinergic mechanisms, like pancreatic polypeptide (PP) release, while muscarinic agonist (bethanechol)-induced PP release remains unaffected. The effects of loperamide on gallbladder contraction and peptide release were performed to resolve this discrepancy. Six subjects (27.6 +/- 2.0 years) received bethanechol (12.5, 25 and 50 microg kg(-1) h(-1) continuously over 40 min) after oral 16 mg loperamide (vs placebo) in a crossover design. Gallbladder volume and plasma levels of CCK, PP, motilin, gastrin, neurotensin, cholylglycine were measured regularly. Bethanechol significantly reduced gallbladder volume (26.7 +/- 1.9 to a nadir of 15.3 +/- 2.2 mL, P < or = 0.05), and this action was inhibited by loperamide. Basal CCK levels increased significantly after loperamide. Incremental integrated CCK release after bethanechol was higher under loperamide (P < or = 0.05), as placebo CCK release was significantly decreased under bethanechol (2.0 +/- 0.4-0.8 +/- 0.3 pmol L(-1)). In both settings, PP levels were significantly increased after bethanechol, while release of neurotensin, motilin, gastrin and cholylglycine was unaffected. The mu-opiate receptor agonist loperamide inhibits bethanechol-induced gallbladder contraction. This effect is not mediated by inhibition of CCK release, as loperamide even enhances basal CCK plasma levels. As cholinergic mechanisms, like bethanechol-induced incremental PP release, were unaffected, mu-opiate agonists might influence gallbladder contraction via vagal-cholinergic pathways.


Monophasic synovial sarcoma of spindle-cell type. Epithelial differentiation as revealed by ultrastructural features, content of prekeratin and binding of peanut agglutinin.
Monophasic synovial sarcomas of spindle-cell type and fibrosarcomas were studied by electron and immunofluorescence microscopy for their intermediate filament expression and the binding of peanut agglutinin (PNA). In monophasic synovial sarcomas of spindle-cell type (two cases), frequent cell-to-cell junctions, irregular cytoplasmic processes, and occasional cytoplasmic, tonofilament-like bundles of intermediate filaments were seen by electron microscopy. These features were absent from fibrosarcomas. Immunohistologically, the monophasic synovial sarcomas showed arrays of prekeratin-positive cells in the midst of the vimentin-positive spindle cells. By double fluorescence microscopy, the prekeratin-positive cells also bound PNA, like the epithelial-like cells of the classical biphasic synovial sarcoma. In contrast to monophasic synovial sarcomas, prekeratin-positive cells and arrays of PNA-binding cells, were not seen by immunofluorescence microscopy in fibrosarcomas (seven cases). Thus the prekeratin-content, the binding of PNA lectin, and certain ultrastructural features suggesting early epithelial differentiation, help to distinguish monophasic synovial sarcomas of spindle-cell type from other spindle cell sarcomas.


[Electronic mechanisms of molecular oxygen bioactivation].
Electronic mechanisms of reductive activation of O2 by oxidases coenzymes (K) are considered. Activation is induced by triplet-singlet (T-S)-transitions at the charge-transfer stage and K+...O2- radical pair (RP) formation. For flavoproteins the spin reversion is induced by spin-orbit coupling (SOC) in superoxide ion, for metal-oxidases--by exchange interaction with paramagnetic metal ion. Another type of spin activation is connected with the singlet peroxide ion O(2)2- formation in cytochromes (structures of the type Fe(3+)-O- -O-Cu2+).


Adventitial contributions of the extracellular signal-regulated kinase and Akt pathways to neointimal hyperplasia.
We recently reported that the efficacy of nitric oxide (NO) appears to be based on both sex and hormone status. The mechanism responsible for this differential efficacy is unknown. The aim of this study was to characterize the effect of sex, hormones, and NO on the extracellular signal-regulated kinase (ERK) and Akt signaling pathways after arterial injury. Male and female Sprague-Dawley rats underwent castration or sham surgery. Two weeks later, they underwent carotid artery balloon injury. Treatment groups included the following: control, injury, and injury + 1-[2-(carboxylato)pyrrolidin-1-yl]diazen-1-ium-1,2-diolate (PROLI/NO) (n = 5 per group). Arteries were harvested 2 weeks after injury and assessed for phospho-ERK (pERK) and phospho-Akt (pAkt) expression. After injury, more pERK and pAkt activity was seen in the adventitia than media in both sexes, regardless of hormone status (P < .05). In hormonally intact males, NO further increased pERK (44%) and pAkt (120%) after injury (P < .001). Castration attenuated the effects of NO. In hormonally intact females, NO caused the opposite pattern with pERK activity but did not affect pAkt activity. After arterial injury, ERK and Akt activity is significantly greater in the adventitia than the media, and depends on sex, hormone status, and NO. Understanding adventitial regulation of proliferative signaling pathways will allow the development of targeted therapies for neointimal hyperplasia.


The neuroendocrine circuitry controlled by POMC, MSH, and AGRP.
Obesity is one of the most challenging health problems worldwide. Over the past few decades, our knowledge concerning mechanisms of weight regulation has increased tremendously leading to the identification of the leptin-melanocortin pathway. The filling level of energy stores is signaled to the brain, and the information is integrated by hypothalamic nuclei, resulting in a well-orchestrated response to food intake and energy expenditure to ensure constant body weight. One of the key players in this system is proopiomelanocortin (POMC), a precursor of a variety of neuropeptides. POMC-derived alpha- and beta-MSH play an important role in energy homeostasis by activating melanocortin receptors expressed in the arcuate nucleus (MC3R) and in the nucleus paraventricularis (MC4R). Activation of these two G protein-coupled receptors is antagonized by agouti-related peptide (AgRP). Naturally occurring mutations in this system were identified in patients suffering from common obesity as well as in patients demonstrating a phenotype of severe early-onset obesity, adrenal insufficiency, red hair, and pale skin. Detailed understanding of the complex system of POMC-AgRP-MC3R-MC4R and their interaction with other hypothalamic as well as peripheral signals is a prerequisite to combat the obesity epidemic.


Phage tailspike modularity and horizontal gene transfer reveals specificity towards E. coli O-antigen serogroups.
The interaction between bacteriophages and their hosts is intricate and highly specific. Receptor-binding proteins (RBPs) of phages such as tail fibers and tailspikes initiate the infection process. These RBPs bind to diverse outer membrane structures, including the O-antigen, which is a serogroup-specific sugar-based component of the outer lipopolysaccharide layer of Gram-negative bacteria. Among the most virulent Escherichia coli strains is the Shiga toxin-producing E. coli (STEC) pathotype dominated by a subset of O-antigen serogroups. Extensive phylogenetic and structural analyses were used to identify and validate specificity correlations between phage RBP subtypes and STEC O-antigen serogroups, relying on the principle of horizontal gene transfer as main driver for RBP evolution. We identified O-antigen specific RBP subtypes for seven out of nine most prevalent STEC serogroups (O26, O45, O103, O104, O111, O145 and O157) and seven additional E. coli serogroups (O2, O8, O16, O18, 4s/O22, O77 and O78). Eight phage genera (Gamaleya-, Justusliebig-, Kaguna-, Kayfuna-, Kutter-, Lederberg-, Nouzilly- and Uetakeviruses) emerged for their high proportion of serogroup-specific RBPs. Additionally, we reveal sequence motifs in the RBP region, potentially serving as recombination hotspots between lytic phages. The results contribute to a better understanding of mosaicism of phage RBPs, but also demonstrate a method to identify and validate new RBP subtypes for current and future emerging serogroups.


Significance of upfront cytoreductive nephrectomy stratified by IMDC risk for metastatic renal cell carcinoma in targeted therapy era - a multi-institutional retrospective study.
This retrospective multicenter study aimed to evaluate the survival benefit of upfront cytoreductive nephrectomy (CN) in metastatic renal cell carcinoma (RCC) patients stratified by International Metastatic RCC Database Consortium (IMDC) risk criteria. We reviewed the medical records in the Michinoku Database between 2008 and 2019. Patients who received upfront CN, systemic therapy without CN (no CN) and CN after drug therapy (deferred CN) were analyzed. To exclude selection bias due to patient characteristics, baseline clinical data were adjusted by inverse probability of treatment weighting (IPTW). Overall survival (OS) was compared between upfront CN and non-upfront CN (no CN plus deferred CN). Associations between time-varying covariates including systemic therapies and OS stratified by IMDC risk criteria were analyzed by IPTW-adjusted Cox regression method. Of 259 patients who fulfilled the selection criteria, 107 were classified in upfront CN and 152 in non-upfront CN group. After IPTW-adjusted analysis, upfront CN showed survival benefit compared to non-upfront CN in patients with IMDC intermediate risk (median OS: 52.5 versus 31.3 months, p < 0.01) and in patients with IMDC poor risk (27.2 versus 11.4 months, p < 0.01). In IPTW-adjusted Cox regression analysis of time-varying covariates, upfront CN was independently associated with OS benefit in patients with IMDC intermediate risk (hazard ratio 0.52, 95% confidence interval 0.29-0.93, p = 0.03) and in patients with IMDC poor risk (0.26, 0.11-0.59, p < 0.01). Upfront CN may confer survival benefit in RCC patients with IMDC intermediate and poor risk.


Endogenous antioxidants predicted outcome and increased after treatment: A benzoate dose-finding, randomized, double-blind, placebo-controlled trial for Alzheimer's disease.
Previous pilot studies suggest that sodium benzoate may be a potential cognitive enhancer for patients with Alzheimer's disease (AD), schizophrenia, or late-life depression. Especially for AD treatment, a confirmatory trial with predictive biomarkers is urgently needed. This study aimed to confirm benzoate as a novel treatment for AD and to discover its optimal dose and biomarkers. A 24-week, dose-finding, randomized, double-blind, placebo-controlled trial, with clinical measurements at weeks 0, 8, 16, and 24, was conducted in three major medical centers in Taiwan. Among 154 patients screened for AD, 149 were eligible and randomized to one of the four treatments: (i) benzoate 500 group (fixed 500 mg/day); (ii) benzoate 750 (500 mg/day for the first 4 weeks, 750 mg/day from the 5th week); (iii) benzoate 1000 (500 mg/day for the first 4 weeks, 1000 mg/day from the 5th week); and (iv) placebo. The primary outcome measure was AD assessment scale-cognitive subscale (ADAS-cog). The benzoate 1000 group performed best in improving ADAS-cog (P = 0.026 at week 24), with female advantage. Higher plasma catalase at baseline predicted better outcome. Benzoate receivers tended to have higher catalase and glutathione than placebo recipients after treatment. The four intervention groups showed similar safety profiles. By enhancing two vital endogenous antioxidants, catalase and glutathione, sodium benzoate therapy improved cognition of patients with AD, with higher baseline catalase predicting better response. Supporting the oxidative stress theory, the results show promise for benzoate as a novel treatment for AD.


Detection of HCV RNA in saliva of patients with hepatitis C virus infection by using a highly sensitive test.
Hepatitis C virus (HCV) is transmitted primarily by direct percutaneous exposures to blood. Since HCV RNA has been found in saliva, it has been suggested that saliva might also be a source of infection. HCV RNA in saliva from plasma HCV RNA positive patients was tested by a highly sensitive PCR method. HCV RNA was detected in 32 out of 61 saliva specimens (52.4%). No correlation was found between the presence of HCV in saliva and age, sex, identified risk factors for HCV infection, time lapsed since the diagnosis, transaminases and alkaline phosphatase values and stimulated salivary flow. A statistically significant relation between plasma HCV RNA viral load and saliva HCV RNA detection was observed (P<0.001). In conclusion, HCV RNA is often present in saliva of HCV infected patients, with plasma viral load being the only known predictable factor. Further studies on salivary HCV RNA are needed.


Interferon-inducible MyD88 protein inhibits hepatitis B virus replication.
Myeloid differential primary response protein (MyD88) is a critical component in the signaling cascade through Toll-like receptors (TLRs) and is induced by alpha interferon (IFN-alpha). To examine the role of MyD88 in the antiviral activity of IFN-alpha against hepatitis B virus (HBV), we established MyD88 stably expressing cell lines and studied HBV replication in these lines after transient transfection. The levels of HBV proteins and viral replicative intermediates were effectively reduced in MyD88-expressing cells. A significant reduction of total and cytoplasmic viral RNAs in MyD88 stably expressing cells was also observed. Using a nuclear factor-kappaB (NF-kappaB) dependent reporter assay, it was shown that activation of NF-kappaB was moderately increased in the presence of expression of MyD88, and further significantly increased by co-expression of HBV. These results suggest a novel mechanism for the inhibition of HBV replication by IFN-alpha via expression of MyD88 protein involving activation of NF-kappaB signaling pathway and downregulation of viral transcription.


Translocation mapping exposes the risky lifestyle of B cells.
Recurrent chromosomal translocations can drive oncogenesis, but how they form has remained elusive. Now, Chiarle et al. (2011) and Klein et al. (2011) characterize the genome-wide spectrum of translocations that form from a single double-stranded break, revealing that specific loci have an intrinsic predisposition for frequent chromosomal rearrangements.


Identification method and application of critical load contribution areas based on river retention effect.
For the entire watershed, the critical source areas (CSAs) and the critical load contribution areas (CLCAs) are two completely different concepts. The CLCAs can reflect the impact of river retention effects on pollutant transmission. In this study, an integrated modelling approach was developed for those complex watersheds by combining two models: MECM (modified export coefficient model) and SWAT (Soil and Water Assessment Tool). A case study was performed in a typical rural area-Miyun Reservoir watershed, China. The simulated results indicated that anthropogenic pollution is the main source of pollutants in most townships, including livestock breeding, rural activities, and crop cultivation. It spreads upstream with the outlet of the basin as the center, and the transport efficiency decays regularly, so the location of the pollution source is closely related to its transport efficiency. The river retention effect has a significant retardation effect on the transportation of pollutants, more than half of the pollutant load will be deposited in the river network. Generally, the CLCAs are concentrated in the area where the transport efficiency and pollutant load are relatively high, which is quite different from the spatial distribution of the CSAs. The research results fully excavated the transmission path and process of pollutants, especially the process of river migration, which helps to improve the scientific configuration of management practices.


Kinetics of monensin complexation with sodium ions by 23NaNMR spectroscopy.
The kinetics of the sodium binding to the ionophore monensin (Mon) in methanol has been studied by 23NaNMR spectroscopy. Fast quadrupole relaxation of the bound sodium affected the relaxation rate of the free sodium through an exchange process between these two species. The exchange was found to be dominated by the reaction: Na+ + Mon-in equilibrium MonNa. The dissociation rate constant at 25 degrees C is 63 s(-1), with an activation enthalpy of 10.3 kcal/mol and activation centropy of -15.8 cal/mol deg. These results indicate that the specificity of the binding of sodium ions to monensin is reflectied in the relatively slow dissociation process. The entropy changes indicate that the activated monensin-sodium complex undergoes a conformational change, but the existence of a conformational change in monensin anion prior to complexation is excluded.


In vitro antimicrosporidial activity of gold nanoparticles against Heterosporis saurida.
Worldwide, there is a need to expand the number of drugs available to treat parasitic infections in aquaculture. One of the new materials being tested is metal nanoparticles, which have unique chemical and physical characteristics owing to their extremely small size and high surface area to volume ratio. We examined the effectiveness of gold nanoparticles against the microsporidian parasite Heterosporis saurida, which causes severe economic losses in lizard fish, Saurida undosquamis aquaculture. We synthesized gold nanoparticles by chemical reduction of tetrachloroauric acid as a metal precursor. We assessed the antimicrosporidial efficacy of the nanoparticles against H. saurida using an in vitro screening approach, which we had developed previously using the eel kidney cell line EK-1. The number of H. saurida spores produced in EK-1 cells was reduced in a proportional manner to the dosage of gold nanoparticles administered. A cell metabolic activity test (MTT) indicated that the gold nanoparticles did not appear to be toxic to the host cells. Gold nanoparticles can act as an effective antimicrosporidial agent and hold promise to reduce disease in lizardfish aquaculture. Metal nanoparticles should be considered as an alternate choice for development of new antimicrosporidial drugs to combat disease problems in aquaculture.


Exploring in-hospital death from myocardial infarction in Eastern Europe: from the International Registry of Acute Coronary Syndromes in Transitional Countries (ISACS-TC); on the Behalf of the Working Group on Coronary Pathophysiology & Microcirculation of the European Society of Cardiology.
The aim of the current study was to investigate the outcomes of coronary reperfusion therapies and ST-segment elevation myocardial infarction (STEMI) in patients of Eastern countries with economies in transition. Federation, and Serbia. The overall population consisted of 23,486 consecutive patients admitted to hospitals from January 1(st) to December 31(st) 2009. Registry data and statistics from the Organization for Economic Cooperation and Development (OECD) countries for the same period were used for comparison (2009-2010). In-hospital mortality was between 4% and 5% in the Western countries. In comparison mortality data were significantly larger in Serbia (10.8%) and Bosnia and Herzegovina (11.2%), intermediate in Russian Federation (7.2%) and similar in Hungary (5.0%). The rates of primary percutaneous coronary intervention (primary PCI) were very low in Bosnia and Herzegovina (18.3%), low in Russian Federation (20.6%) and Serbia (22%), and high in Hungary (70%). Major risk factors for death appear to be lack of reperfusion therapy, longer time delay from symptoms onset to hospital presentation as well as the higher percentage of patients with clinical presentation in Killip class III/IV. In-hospital STEMI case-fatality rates ranges widely in the former Eastern Bloc countries. Beyond the quality of care provided in hospitals, differences in time delay from symptoms onset to hospital admission may strongly influence STEMI patients' outcome.


Attitudes of affiliate faculty members toward medical student summative evaluation for clinical clerkships: a qualitative analysis.
Summative evaluation of medical students is a critical component of the educational process. Despite extensive literature on evaluation, few studies have centered on affiliate faculty members' attitudes toward summative evaluation of students, though it has been suggested that these attitudes influence their effectiveness as evaluators. The objective is to examine affiliate faculty members' attitudes toward clinical clerkship evaluation using primarily qualitative research methods. The study used a nonexperimental research design and employed mixed methods. Data were collected through interviews, focus groups, and a questionnaire from 11 affiliate faculty members. Themes emerging from the data fell into three broad categories: (a) factors that influence grading, (b) consequences of negative evaluations, and (c) disconnections in the grading process. The quantitative portion of the study revealed important discrepancies supporting the use of qualitative methods. The study highlights faculty members' struggles with the evaluative process and emphasizes the need for improvements in evaluation tools and faculty development.


Fabrication Characterization of 1Ce10ScSZ Electrolyte Prepared by Co-Precipitation and Hydrothermal Treatment for Solid Oxide Fuel Cells.
Nanocrystallite ceria-doped scandia-stabilized zirconia (1Ce10ScSZ) powders are prepared using a combination of co-precipitation and hydrothermal treatments. Power density of 1.0 W cm(-2) is obtained at 1.6 A cm(-2) and 800 °C due to the drastic reduction of ohmic and polarization resistance in the SOFC cell.


Solid and liquid state characterization of tetrahydrocurcumin using XRPD, FT-IR, DSC, TGA, LC-MS, GC-MS, and NMR and its biological activities.
Tetrahydrocurcumin (THC) is one of the major metabolites of curcumin (CUR), an ancient bioactive natural polyphenolic compound. This research article describes both the solid and liquid state characterization of THC using advanced spectroscopic and thermo-analytical techniques. Anti-inflammatory, anti-oxidant, and neuroprotective activities of THC were investigated using in vitro cell lines. Liquid chromatography-mass spectrometry analysis revealed that our sample comprised 95.15% THC, 0.51% tetrahydrodemethoxycurcumin (THDC), 3.40% hexahydrocurcumin, and 0.94% octahydrocurcumin. Gas chromatography-mass spectrometry analysis indicated the presence of 96.68% THC and 3.32% THDC. THC in solution existed as keto-enol tautomers in three different forms at different retention time, but the enol form was found to be dominant, which was also supported by nuclear magnetic resonance analysis. THC was thermally stable up to 335.55 °C. THC exhibited more suppression of cytokines (TNF-α, IL-1β, and MIP-1α) than CUR in a concentration-dependent manner in mouse splenocytes, while NK-cell and phagocytosis activity was increased in macrophages. THC showed a significant reduction of free radicals (LPO) along with improved antioxidant enzymes (SOD and catalase) and increased free radical scavenging activity against ABTS+ radicals in HepG2 cells. THC displayed higher protection capability than CUR from oxidative stress and neuronal damage by improving cell viability against H2O2 induced HepG2 cells and MPP+ induced SH-SY5Y cells, respectively, in a concentration-dependent manner. Thus, a variation of the biological activities of THC might rely on its keto-enol form and the presence of other THC analogs as impurities. The present study could be advantageous for further research on THC for better understanding its physicochemical properties and biological variation.


Lower C-reactive protein and better hemodialysis survival are associated with regular exercise activity: Longitudinal outcomes from the ACTIVE-ADIPOSE special study.
Introduction Cross-sectional and longitudinal studies in the general population have shown that a physically active lifestyle may have anti-inflammatory properties, but evidence from studies conducted with maintenance hemodialysis (HD) patients is limited. Methods A multicenter prospective cohort of 755 HD participants aged 20-92 was evaluated in a USRDS special study 2009-2013. Kilocalories/week (kcal/week) of leisure time physical activity (LTPA) was estimated from the Minnesota Leisure Time Activity questionnaire. Predialysis serum samples were obtained concurrent with LTPA report date. Generalized estimating equations (GEE) examined association of participants' LTPA and log-normalized CRP across 24 months. Cox proportional hazards models investigated LTPA and survival over a median follow-up of 718 days. Findings Baseline median CRP concentration was lower for participants with 500+ kcal/week LTPA vs. those with <500 kcal/week LTPA (3.4 mg/L vs. 4.6 mg/L; P = 0.03). Participants who reported lower LTPA (<500 kcal/week) at both baseline and 12 months had a borderline significant increase in CRP concentration (within-group change 4.8 [1.9-10.4] to 5.8 [1.6-15.7]; P = 0.08). Lower LTPA was associated with higher log CRP over 24 months in adjusted GEE analyses (β coefficient = 0.16 [95% CI 0.02-0.31]; P = 0.03). 67/364 (18%) and 43/391 (11%) deaths occurred, respectively, among participants reporting <500 vs. 500+ kcal/week LTPA [adjusted mortality hazard ratio 1.63 (CI, 1.07, 2.47)]. Discussion The data suggest that increased estimated levels of LTPA, a physical activity/exercise opportunity widely applicable to HD patients, may be associated with lower CRP concentration as well as better survival outcome.


Left ventricular mass and diastolic function in normotensive young adults with autosomal dominant polycystic kidney disease.
Left ventricular hypertrophy is often found very early in the course of autosomal dominant polycystic kidney disease (ADPKD). Diastolic dysfunction has been shown in hypertensive adult patients with ADPKD with increased left ventricular mass (LVM), but there are no data about diastolic function in the young ADPKD population without hypertension and with normal renal function. To evaluate very early alterations in cardiac structure and diastolic function in young normotensive patients with ADPKD, color Doppler echocardiography was performed in 46 young normotensive patients with ADPKD and 35 healthy subjects. LVM, transmitral pulsed Doppler flow (diastolic function), and valvular abnormalities were studied. Patients with ADPKD showed higher LVM indices (LVMIs) than controls (89.7+/-17.3 v 68.5+/-17.2 g/m2; P < 0.0001). Peak early diastolic velocity (E wave) deceleration time and isovolumic relaxation time were significantly prolonged in patients with ADPKD compared with controls (E wave deceleration time, 182.5+/-51.3 v 149.4+/-34 msec; P=0.002; isovolumic relaxation time, 97.7+/-17.5 v 79+/-15 msec; P=0.0001). No differences were found in valvular abnormalities in the two groups. In conclusion, young normotensive patients with ADPKD showed increased LVMIs and Doppler abnormalities consistent with early diastolic dysfunction.


The infection and treatment method of vaccination against heartwater.
The history of vaccination techniques against heartwater and the development of the infection and treatment method are reviewed briefly. Present techniques and their shortcomings are defined and possible areas of improvement discussed.


Enhancing the decolorization activity of Bacillus pumilus W3 CotA-laccase to Reactive Black 5 by site-saturation mutagenesis.
Reactive Black 5 (RB5) is a typical refractory azo dye. Widespread utilization of RB5 has caused a variety of environmental and health problems. The enzymatic degradation of RB5 can be a promising solution due to its superiority as an eco-friendly and cost-competitive process. Bacterial CotA-laccase shows great application prospect to eliminate hazardous dyes from wastewater. However, efficient decolorization of RB5 CotA-laccase generally requires the participation of costly, toxic mediators. In the present study, we modified the amino acids Thr415 and Thr418 near the type 1 copper site and the amino acid Gln442 at the entrance of the substrate-binding pocket of Bacillus pumilus W3 CotA-laccase to boost its RB5 decolorization activity based on molecular docking analysis and site-saturation mutagenesis. Through the strategies, two double site mutants T415D/Q442A and T418K/Q442A obtained demonstrated 43.94 and 52.64% RB5 decolorization rates in the absence of a mediator at pH 10.0, respectively, which were about 3.70- and 4.43-fold higher compared with the wild-type CotA-laccase. Unexpectedly, the catalytic efficiency of the T418K/Q442A to ABTS was enhanced by 5.33-fold compared with the wild-type CotA-laccase. The mechanisms of conferring enhanced activity to the mutants were proposed by structural analysis. In summary, the mutants T415D/Q442A and T418K/Q442A have good application potentials for the biodegradation of RB5. KEY POINTS: • Three amino acids of CotA-laccase were manipulated by site-saturation mutagenesis. • Decolorization rate of two mutants to RB5 was enhanced 3.70- and 4.43-fold, respectively. • The mechanisms of awarding enhanced activity to the mutants were supposed.


Comparative expression analysis of aquaporin-5 (AQP5) in keratoconic and healthy corneas.
Keratoconus (KC) is a common progressive corneal disease characterized by excessive stromal thinning, central or paracentral conical protrusion, and disruptions in Bowman's layer. The etiology of KC is largely unknown, and a combination of genetic and environmental factors is believed to play a role in the origin of the disease. Recently, the absence of transcripts of the water channel, aquaporin-5 (AQP5), was demonstrated by reverse-transcription polymerase chain reaction (RT-PCR) in KC tissues and was proposed as a possible marker for KC. In this study, we sought to evaluate AQP5 mRNA and protein expression in KC and non-KC corneal tissues using a combination of techniques. A total of 69 samples of corneal tissue were analyzed including 39 corneal buttons from patients with advanced KC, 16 samples of non-KC corneal epithelium belonging to patients who underwent surface refractive surgery, 12 sclerocorneal rims obtained from healthy donor subjects, and two healthy corneal buttons. Determination of AQP5 transcript and protein expression patterns was performed by means of real time RT-PCR, immunohistochemistry, immunocytochemistry, and flow cytometry methods. Cell culture was performed to identify AQP5 protein expression in KC epithelial cells. AQP5 mRNA was expressed with no significant differences between KC and non-KC tissues. Moreover, AQP5 protein expression analysis did not reveal differences in protein levels and/or cell location among KC and non-KC tissues. Interestingly, AQP5 expression continues for up to 21 days in the isolated KC corneal epithelial cells. Our results do not support a role for AQP5 in KC etiopathogeny or as a disease marker. Genetic background differences or a distinct pathogenetic KC cascade specific to the analyzed population could account for the dissimilarities observed in KC-related AQP5 expression.


The role of hepatitis B infection in anti-tuberculosis drug-induced liver injury: a meta-analysis of cohort studies.
Drug-induced liver injury (DILI) is a common adverse drug reaction leading to the interruption of tuberculosis (TB) therapy. We aimed to identify whether the hepatitis B virus (HBV) infection would increase the risk of DILI during first-line TB treatment. A meta-analysis of cohort studies searched in PubMed, Web of Science and China National Knowledge Infrastructure was conducted. Effect sizes were reported as risk ratios (RRs) and 95% confidence intervals (CIs) and calculated by R software. Sixteen studies with 3960 TB patients were eligible for analysis. The risk of DILI appeared to be higher in TB patients co-infected with HBV (RR 2.66; 95% CI 2.13-3.32) than those without HBV infection. Moreover, patients with positive hepatitis B e antigen (HBeAg) were more likely to develop DILI (RR 3.42; 95% CI 1.95-5.98) compared to those with negative HBeAg (RR 2.30; 95% CI 1.66-3.18). Co-infection with HBV was not associated with a higher rate of anti-TB DILI in latent TB patients (RR 4.48; 95% CI 0.80-24.99). The effect of HBV infection on aggravating anti-TB DILI was independent of study participants, whether they were newly diagnosed with TB or not. Besides, TB and HBV co-infection patients had a longer duration of recovery from DILI compared to non-co-infected patients (SMD 2.26; 95% CI 1.87-2.66). To conclude, the results demonstrate that HBV infection would increase the risk of DILI during TB therapy, especially in patients with positive HBeAg, and close liver function monitoring is needed for TB and HBV co-infection patients.


Simple equation for earthquake distribution.
The earthquake distribution, the Gutenberg-Richter law, is obtained postulating a connection through a diffusion process between the kinetic energy of the active zone and the radiated energy. A link between the value of the critical exponent and the stress release is proposed.


Ethnoveterinary remedies of diseases among milk yielding animals in Kathua, Jammu and Kashmir, India.
The triangle of relationship between human beings, animals and plants has existed for ages, and has given rise to intense-relationships and consequently rich traditions of ethnoveterinary knowledge throughout the world. The predominantly rural population and the strong agricultural base have provided unique situation for rich ethnoveterinary practices in the study area. The present study was conducted in the Kathua district of Jammu and Kashmir between 2007 and 2009 to provide list of the important plants of the region for further phytochemical and pharmacological studies, and to prepare inventory of the ethnoveterinary practices for the future generations. Direct interview of 78 informants was conducted and the information gathered was analyzed for two quantitative methods viz. informant consensus factor (ICF) and use-value (UV). The characteristics of ethnoveterinary plants and practices were also documented. A total of 72 plants were used to cure 33 common ailments of milk yielding animals of Kathua district. Fabaceae (7 species) was the most represented family, along with Poaceae (6 species). Leaves (27.2%) were the most frequently used plant parts, herbs (48.6%) the most frequently used life-form and wild flora (58.3%) the most used source for the ethnoveterinary practices. The highest ICF was reported for urological disorders (0.95) and lowest for nutritional diseases (0.80). The values of ICF were generally on the higher side which shows that the informants share the knowledge about the ailment among themselves. The important ethnoveterinary plant species on the basis of use-values were: Brassica campestris, Saccharun officinarum, Emblica officinalis, Trachyspermum ammi, Asparagus adscendens, Musa paradisica, Oryza sativa, Curcuma longa, Azadirachta indica, Tinospora cordifolia and Tamarindus indica. High diversity of ethnoveterinary plants were found to cure the common milk yielding animals of Kathua district. Further phytochemical and pharmacological studies are required to ascertain their chemical nature for the betterment of the locals and farmers, and commercial utilization of this knowledge.


Functional magnetic stimulation of the spinal cord--a urodynamic study in healthy humans.
To study the effects of functional magnetic stimulation of the spinal cord in healthy subjects on somatic and autonomic pathways innervating the anal and the external urethral sphincter, bladder, bladder neck, and rectum. Eight healthy male volunteers gave their written informed consent and underwent functional magnetic stimulation of the thoracolumbar and sacral spinal cord. A two-channel microtip pressure transducer catheter was placed rectally measuring the abdominal and anal sphincter pressure. A three-channel microtip pressure transducer catheter was inserted into the urethra measuring the bladder, the bladder neck, and the external urethral sphincter pressure. A comprehensive protocol of single and repetitive magnetic stimulations was performed. Frequency, location, and duration of stimulation were varied while the intensity of stimulation was adapted to the maximum the subjects could tolerate. In four subjects, the degree of bladder filling was changed and the protocol was repeated when the subjects reported a full bladder and desire to void. Continuous magnetic stimulation of the thoracolumbar spinal cord and the sacral roots applied with different frequencies (5, 15, 30, 60, 100 Hz) and different duration of stimulation (10, 30, 120 sec) evoked sphincter contraction of both anal and urethral sphincters. The stimulation could not evoke contractions of the bladder, the bladder neck, or the rectum. Also with filled bladder and present desire to void, the magnetic stimulation could not activate autonomic pathways innervating these structures. Considering our results, we suggest that in individuals with preserved sensibility magnetic stimulation of the spinal cord with intensities below the pain threshold is ineffective in activating autonomic nerve fibres innervating bladder, bladder neck, and rectum.


The role of inflammation in core features of depression: Insights from paradigms using exogenously-induced inflammation.
A wealth of evidence has implicated inflammation in the development of depression. Yet, the heterogeneous nature of depression has impeded efforts to understand, prevent, and treat the disease. The purpose of this integrative review is to summarize the connections between inflammation and established core features of depression that exhibit more homogeneity than the syndrome itself: exaggerated reactivity to negative information, altered reward processing, decreased cognitive control, and somatic syndrome. For each core feature, we first provide a brief overview of its relevance to depression and neurobiological underpinnings, and then review evidence investigating a potential role of inflammation. We focus primarily on findings from experimental paradigms of exogenously-induced inflammation. We conclude that inflammation likely plays a role in exaggerated reactivity to negative information, altered reward reactivity, and somatic symptoms. There is less evidence supporting an effect of inflammation on cognitive control as assessed by standard neuropsychological measures. Finally, we discuss implications for future research and recommendationsfor how to test the role of inflammation in the pathogenesis of heterogeneous psychiatric disorders.


Spinal hydatid cyst initially diagnosed as spinal tumor: A case report and review of the literature.
The spinal hydatid cyst is a benign pathology but has considerable morbidity. It should be considered as a differential diagnosis in patients having signs and symptoms of spinal compression, particularly in endemic areas.


Response characteristics of neurons in the cat vestibular nuclei during slow and constant velocity off-vertical axes rotations in the clockwise and counterclockwise rotations.
The responses to slow constant velocity rotations in the clockwise (CW) and counterclockwise (CCW) directions about an axis tilted 10 degrees from the earth's vertical were studied in static tilt-sensitive neurons in the vestibular nuclei of decerebrate cats. Each unit responded to any 360 degrees unidirectional rotation with a position-dependent discharge maximum. The location of the maximum, obtained by rotation in one direction, differed from that obtained by an oppositely directed rotation (phase difference). In about 80% of the units such phase difference (up to 160 degrees in second-order neurons) in response to oppositely directed rotations was unaffected by different amplitudes of head displacement (5-25 degrees). Units were thus classified into two groups depending on the location of the CW discharge maximum relative to the CCW counterpart. The direction of rotation had no influence on the response gains of these units.


Severity of acute kidney injury is associated with decreased survival after fenestrated and branched endovascular aortic aneurysm repair.
Acute kidney injury (AKI) occurs frequently in complex aortic surgery and has been implicated in perioperative and long-term survival. This study sought to characterize the relationship between AKI severity and mortality after fenestrated and branched endovascular aortic aneurysm repair (F/B-EVAR). Consecutive patients enrolled by the US Aortic Research Consortium in 10, prospective, nonrandomized, physician-sponsored investigational device exemption studies evaluating F/B-EVAR, between 2005 and 2023, were included in this study. Perioperative AKI during hospitalization was defined by and staged using the 2012 Kidney Disease Improving Global Outcomes criteria. Determinants of AKI were evaluated with backward stepwise mixed effects multivariable ordinal logistic regression. Survival was analyzed with conditionally adjusted survival curves and backward stepwise mixed effects Cox proportional hazards modelling. In the study period, 2413 patients with a median (interquartile range [IQR]) age of 74 years (IQR, 69-79 years) underwent F/B-EVAR. The median follow-up duration was 2.2 years (IQR, 0.7-3.7 years). The median baseline estimated glomerular filtration rate (eGFR) and creatinine were 68 mL/min/1.73 m2 (IQR, 53-84 mL/min/1.73 m2) and 1.1 mg/dL (IQR, 0.9-1.3 mg/dL), respectively. Stratification of AKI identified 316 patients (13%) with stage 1 injury, 42 (2%) with stage 2 injury, and 74 (3%) with stage 3 injury. Renal replacement therapy was initiated during the index hospitalization in 36 patients (1.5% of cohort, 49% of stage 3 injuries). Thirty-day major adverse events were associated with AKI severity (all P ≤ .0001). Multivariable predictors of AKI severity included baseline eGFR (proportional odds ratio, 0.9 per 10 mL/min/1.73 m2 [95% confidence interval (CI), 0.85-0.95 per 10 mL/min/1.73 m2]; P < .0001), baseline serum hematocrit (0.58 per 10% [95% CI, 0.48-0.71 per 10%]; P < .0001), renal artery technical failure during aneurysm repair (3 [95% CI,1.61-5.72]; P = .0006), and total operating time (1.05 per 10 minutes [95% CI, 1.04-1.07 per 10 minutes]; P < .0001). One-year unadjusted survivals for AKI severity strata were 91% (95% CI, 90%-92%) for no injury, 80% (95% CI, 76%-85%) for stage 1 injury, 72% (95% CI, 59-87%) for stage 2 injury, and 46% (95% CI, 35-59%) for stage 3 injury (P<.0001). Multivariable determinants of survival included AKI severity (stage 1, hazard ratio [HR], 1.6 [95% CI, 1.3-2]); stage 2, HR, 2.2 [95% CI, 1.4-3.4]); stage 3 HR, 4 [95% CI, 2.9-5.5]; P < .0001), decreased eGFR (HR, 1.1 [95% CI, 0.9-1.3]; P = .4), patient age (HR, 1.6 per 10 years [95% CI, 1.4-1.8 per 10 years]; P < .0001), baseline chronic obstructive pulmonary disease (HR, 1.5 [95% CI, 1.3-1.8]; P < .0001), baseline congestive heart failure (HR, 1.7 [95% CI, 1.6-2.1]; P < .0001), postoperative paraplegia (HR, 2.1 [95% CI, 1.1-4]; P = .02), and procedural technical success (HR, 0.6 [95% CI, 0.4-0.8]; P = .003). AKI, as defined by the 2012 Kidney Disease Improving Global Outcomes criteria, occurred in 18% of patients after F/B-EVAR. Greater severity of AKI after F/B-EVAR was associated with decreased postoperative survival. The predictors of AKI severity identified in these analyses suggest a role for improved preoperative risk mitigation and staging of interventions in complex aortic repair.


Removal of lens material dropped into the vitreous cavity during cataract surgery using an optical fiber-free intravitreal surgery system.
We describe a technique for removing lens fragments dropped into the vitreous cavity during cataract surgery using an optical fiber-free intravitreal surgery system (OFFISS) that was developed for bimanual vitrectomy. The dropped nucleus was removed by 2-port corneal vitrectomy using the OFFISS in 3 patients during complicated cataract surgery. No complications occurred, and good visual recovery was achieved. The OFFISS provided a good view of the fundus without fiber optics and allowed the use of 2 ports for vitrectomy through the corneal wound. This technique is suitable for cataract surgeons who have not been trained in 3-port pars plana vitrectomy.


The obstetric consequences of uterovaginal anomalies.
Congenital uterovaginal anomalies can have adverse effects on pregnancy outcome. Early diagnosis and an aggressive evaluation of any patient presenting with mid-trimester abortion, premature labor, malpresentation, or retained placenta may prevent additional pregnancy wastage and maternal morbidity. With more timely and accurate diagnosis, appropriate management is likely to provide the best possible outcome for all such patients.


A Randomized Controlled Clinical Trial of Dialogical Exposure Therapy versus Cognitive Processing Therapy for Adult Outpatients Suffering from PTSD after Type I Trauma in Adulthood.
Although there are effective treatments for posttraumatic stress disorder (PTSD), there is little research on treatments with non-cognitive-behavioural backgrounds, such as gestalt therapy. We tested an integrative gestalt-derived intervention, dialogical exposure therapy (DET), against an established cognitive-behavioural treatment (cognitive processing therapy, CPT) for possible differential effects in terms of symptomatic outcome and drop-out rates. We randomized 141 treatment-seeking individuals with a diagnosis of PTSD to receive either DET or CPT. Therapy length in both treatments was flexible with a maximum duration of 24 sessions. Dropout rates were 12.2% in DET and 14.9% in CPT. Patients in both conditions achieved significant and large reductions in PTSD symptoms (Impact of Event Scale - Revised; Hedges' g = 1.14 for DET and d = 1.57 for CPT) which were largely stable at the 6-month follow-up. At the posttreatment assessment, CPT performed statistically better than DET on symptom and cognition measures. For several outcome measures, younger patients profited better from CPT than older ones, while there was no age effect for DET. Our results indicate that DET merits further research and may be an alternative to established treatments for PTSD. It remains to be seen whether DET confers advantages in areas of functioning beyond PTSD symptoms.


Real-time ultrasound evaluation of CORE muscle activity in a simultaneous contraction in subjects with non-specific low back pain and without low-back pain. Protocol of an observational case-control study.
Non-specific low back pain represents 90-95% of all cases of low back pain and it has a prevalence of 18% in the adult population, assuming a great socioeconomic impact. The main objective of this observational case-control study study is to evaluate if there are differences in the simultaneous contraction of the core muscles between nonspecific low back pain and healthy subjects. This study will be carried out in the Physiotherapy department of the University of Alcalá. Eighty-two participants <18 years old, will be recruited, paired with NSLBP (n = 41) and healthy (n = 41). The main outcome will be the onset muscle contraction of lateral abdominal wall (internal oblique, external oblique and transversus abdominis), pelvic floor, lumbar multifidus and respiratory diafragm. The maneuvers that the subjects will perform will be abdominal drawing in maneouver, contralateral arm lift, valsalva, and voluntary pelvic floor contraction in sitting and standing. As a secondary objective, to analyze the amount of contraction of each muscle group and the capacity of the diaphragms to be excreted in both groups of subjects. Finally, to relate pain and disability.


Development of an individual fitness score (IFS) based on the depression treatment guidelines of in the Japanese Society of Mood Disorders.
Treatment guidelines are designed to assist patients and health care providers and are used as tools for making treatment decisions in clinical situations. The treatment guidelines of the Japanese Society of Mood Disorders establish treatment recommendations for each severity of depression. The individual fitness score (IFS) was developed as a simple and objective indicator to assess whether individual patients are practicing treatment by the recommendations of the depression treatment guidelines of the Japanese Society of Mood Disorders. The EGUIDE project members determined the IFS through the modified Delphi method. In this article, the IFS was calculated based on the treatment of depressed patients treated and discharged between 2016 and 2020 at facilities participating in the EGUIDE project. In addition, we compared scores at admission and discharge. The study included 428 depressed patients (mild n = 22, moderate/severe n = 331, psychotic n = 75) at 57 facilities. The mean IFS scores by severity were statistically significantly higher at discharge than at admission with moderate/severe depression (mild 36.1 ± 34.2 vs. 41.6 ± 36.9, p = 0.49; moderate/severe 50.2 ± 33.6 vs. 55.7 ± 32.6, p = 2.1 × 10-3; psychotic 47.4 ± 32.9 versus 52.9 ± 36.0, p = 0.23). We developed the IFS based on the depression treatment guideline, which enables us to objectively determine how close the treatment is to the guideline at the time of evaluation in individual cases. Therefore, the IFS may influence guideline-oriented treatment behavior and lead to the equalization of depression treatment in Japan, including pharmacotherapy.


Gut microbiota alterations promote traumatic stress susceptibility associated with p-cresol-induced dopaminergic dysfunctions.
Mounting evidence suggests a link between gut microbiota abnormalities and post-traumatic stress disorder (PTSD). However, whether and how the gut microbiota influences PTSD susceptibility is poorly understood. Here using the arousal-based individual screening model, we provide evidence for pre-trauma and post-trauma gut microbiota alterations in susceptible mice exhibiting persistent PTSD-related phenotypes. A more in-depth analysis revealed an increased abundance of bacteria affecting brain processes including myelination, and brain systems like the dopaminergic neurotransmission. Because dopaminergic dysfunctions play a key role in the pathophysiological mechanisms subserving PTSD, we assessed whether these alterations in gut microbiota composition could be associated with abnormal levels of metabolites inducing dopaminergic dysfunctions. We found high levels of the l-tyrosine-derived metabolite p-cresol exclusively in the prefrontal cortex of susceptible mice. We further uncovered abnormal levels of dopamine and DOPAC, together with a detrimental increase of dopamine D3 receptor expression, exclusively in the prefrontal cortex of susceptible mice. Conversely, we observed either resilience mechanisms aimed at counteracting these p-cresol-induced dopaminergic dysfunctions or myelination-related resilience mechanisms only in the prefrontal cortex of resilient mice. These findings reveal that gut microbiota abnormalities foster trauma susceptibility and thus it may represent a promising target for therapeutic interventions.


Iontophoretic study of skin vessel reactivity in atopic dermatitis and its correlation to serum IgE levels.
Skin vessel reactivity was studied by means of an iontophoretic technique in 19 adult patients with atopic dermatitis. Fifteen patients were available for reinvestigation some 6 months later in winter. Compared with a control group, we found a significantly increased sensitivity in summer of dermal skin vessels toward the alpha 1-agonist phenylephrine. Patients with elevated serum IgE levels seemed to be more sensitive to phenylephrine. However, the difference was not significant. Isoproterenol, the beta-adrenoceptor agonist, induced blanching (as opposed to erythema) in 7 of 19 (37%) atopic dermatitis patients in summer and in 9 of 15 (60%) in winter compared with 1 of 36 in the control groups. This blanching was antagonized by the alpha-blocker phentolamine. From the results we concluded that there may be an increased alpha-adrenoceptor reactivity and/or a decreased beta-adrenoceptor reactivity in atopic dermatitis patients, which might be a primary defect.


Myocardial protection during ischemic cardiac arrest. The importance of magnesium in cardioplegic infusates.
The increasing use of coronary infusates for the protection of the human heart drug ischemic cardiac arrest has placed great emphasis on the need for a rational and safe formulation of any infusion solution. Using a rat heart model of cardiopulmonary bypass and ischemic cardiac arrest, we have found magnesium to be a highly effective component of protective infusates which can be additive to hypothermia and other protective agents. However, the concentration of magnesium bears a complex relationship to the degree of protection, a fact which stresses the need for the establishment of the correct concentration for optimal protection.


Identifying the contingencies of self-worth associated with eating disorder symptoms: The use of choice-based conjoint analysis.
Self-worth contingent on shape/weight is a diagnostic criterion and key maintaining factor for eating disorders. However, the role of other contingencies of self-worth (i.e., domains in which self-worth is invested) is largely unknown. Moreover, research has relied on self-ratings of contingency strength, which are subject to distortion through socially desirable responding and limited self-awareness, and may have limitations in terms of ecological validity. To overcome these limitations, the present study investigated a broad range of contingencies of self-worth in relation to eating disorder pathology and employed a choice-based conjoint (CBC) approach for assessing these contingencies. Young women and men from the community (N = 428) completed a CBC task to assess the domains in which self-worth is invested, the Eating Disorder Examination Questionnaire (EDE-Q) to assess eating disorder symptomatology, and the Balanced Inventory of Desirable Responding to assess socially desirable responding. Beta regression analyses showed that CBC thinness and athletic competence predicted higher scores on all EDE-Q scales. CBC muscularity and facial attractiveness predicted higher scores, while coping ability and quality of relationships predicted lower scores, on various aspects of eating disorder symptoms. CBC social acceptance predicted lower eating disorder symptoms in males only. The findings suggest that a broader range of contingencies of self-worth beyond shape/weight are relevant to eating disorder pathology and should be considered as potential underlying mechanisms and treatment targets. In addition, this first use of the CBC method in eating disorder research provides initial support for its validity and utility.


Women's cognitive and affective reactions to breast cancer survivor stories: a structural equation analysis.
Compare the immediate affective and cognitive reactions to cancer survivor stories about mammography and breast cancer vs. a didactic, informational approach. Participants (N=489) were African American women age 40 years and older (mean=61). Most had ≤high school education (67%), annual household income ≤$20,000 (77%), and a prior mammogram (89%). Participants completed surveys before and after watching the narrative or informational video. We used structural equation modeling to examine the large number of inter-related latent constructs. Women who watched the narrative video experienced more positive and negative emotions, found it easier to understand the video, had more positive evaluations of the video, reported stronger identification with the message source (i.e., perceived similarity, trust, liking), and were more engaged with the video. Narratives elicited immediate reactions consistent with theorized pathways of how communication affects behavior. Future studies should examine whether and how these immediate outcomes act as mediators of the longer term effects of narratives on affect, cognitions, and behavior. Stories of other women's experiences may be more powerful than a didactic presentation when encouraging African American women to get a mammogram.


Emerging Therapeutic Promise of Ketogenic Diet to Attenuate Neuropathological Alterations in Alzheimer's Disease.
Alzheimer's disease (AD) is a multifactorial and chronic neurodegenerative disorder that interferes with memory, thinking, and behavior. The consumption of dietary fat has been considered a vital factor for AD as this disease is related to blood-brain barrier function and cholesterol signaling. The ε4 allele of apolipoprotein E (APOE4) is a primary genetic risk factor that encodes one of many proteins accountable for the transport of cholesterol and it is deemed as the leading cholesterol transport proteins in the brain. In case of AD development, the causative factor is the high level of serum/plasma cholesterol. However, this statement is arguable and, in the meantime, the levels of brain cholesterol in individuals with AD are extremely inconstant and levels of cholesterol in the brain and serum/plasma of AD individuals do not reflect cholesterol as a risk factor. In fact, APOE4 is neither fundamental nor sufficient for the advancement of AD; it just acts as a synergistic and increases the danger of AD. Another noticeable characteristic of AD is area-specific decreases in the metabolism of brain glucose. It has been found that the brain cells cannot efficiently metabolize fats; hence, they totally rely upon glucose as a vitality substrate. Thus, suppression of glucose metabolism can possess an intense effect on brain actions. Hypometabolism is frequently found in AD and has quite recently achieved impressive consideration as a plausible target for interfering in the progression of the disease. One promising approach is to keep up the normal supply of glucose to the brain with ketone bodies from the ketogenic diet signifies a potential therapeutic agent for AD. Therefore, this review represents the role of ketogenic diets to combat AD pathogenesis by considering the influence of APOE.


Prognostic outcomes of treatment naïve oral tongue squamous cell carcinoma (OTSCC): a comprehensive analysis of 14 years.
To analyze the factors predicting survival outcomes in treatment naïve oral tongue squamous cell carcinoma (OTSCC). A comprehensive review of 531 oral tongue carcinoma patients treated with upfront surgery followed by adjuvant radiotherapy or chemoradiotherapy was conducted from 2004-2018. The mean age of presentation was 53 years (11-86) with a male to female ratio of 1.3:1. The associated risk factors were smoking (21%), betel nut (16%), naswar (9%) and alcohol (1%). Most of the cases were either well (45.1%) or moderately (46.2%) differentiated. Surgery was performed in 164 patients alone while 368 were treated with surgery in combination with adjuvant modalities. Overall (OS) and disease free survival (DFS) were 66 and 71%, respectively, with a median follow up of 2.5 years. Cox regression analysis showed nodal positivity, increased depth of invasion (DOI) and higher lymph node ratio (LNR) as significant prognosticators impacting OS and DSS. Nodal volume, DOI and LNR are the most consistent predictors of poor outcome in OTSCC. Nodal positivity, depth of invasion > 5 mm and lymph node ratio > 0.04 adversely affect OS and DSS.


Immunologic tolerance: self-nonself discrimination versus costimulatory factors and second signals.
An attempt is made to assess the total number of the theoretically possible antigenic epitopes, the number of lymphocyte clones and the number of epitopes on cell surface antibody of a clone may be able to recognize. We suggest that the structures of recognizing antibody sites of a human are far from random and derived from a limited number of structures adapted to the recognition of pathogenic agents. The probability of recognition for a random epitope-like structure is likely to be very small. Discriminative power of BCR and TCR binding sites, together with T-helper control, should be sufficient for prevention of peripheral autoimmune response, but second-signal-type controls should not be neglected as supplementary mechanisms to prevent such response.


Saliva control issues in the neurologically challenged. A 30 year experience in team management.
The objective of this paper is to report the experience of a multidisciplinary team (otolaryngologist, speech-language pathologists, pediatric dentist, and social worker) functioning at a pediatric rehabilitation center have had in the management of 1487 neurologically challenged individuals with saliva control issues assessed from 1976 to the end of 2004. The role of each team member is outlined. Management decisions have consisted of no treatment, utilization of oral-motor training program, elimination of contributing situational factors, utilization of medication, surgery and Botox injections of the major salivary glands. Oral-motor programs to improve oral-motor function is essential initially if there is patient compliance. Surgery was recommended in the majority of patients. Submandibular duct relocation with simultaneous sublingual gland excision remains the procedure of first choice for persistent significant drooling. Aspiration is much less common than drooling and is more problematic to treat. Simultaneous ligation of the submandibular and parotid ducts (aka 4-duct ligation) is promising. A recent initiative to inject the major salivary glands with Botox is being evaluated. Team evaluation with consensus decision making has worked well in this patient population with complex medical conditions.


Spectrum of MR imaging findings in Wernicke encephalopathy: are atypical areas of involvement only present in nonalcoholic patients?
Although MR imaging is considered the most effective method to confirm a diagnosis of WE, MR imaging studies designed to distinguish WE between NA and AL patients have yielded controversial results. The purpose of this study was to determine potential differences in MR imaging features between AL and NA patients with WE and to compare neurologic symptoms with MR imaging findings. This retrospective study included 24 consecutive patients (male/female, 15:9; mean age, 54 years) diagnosed with WE in a university hospital (AL = 13, NA = 11). Clinical manifestations and MR imaging findings between AL and NA patients were evaluated. Classic WE symptom triad and consciousness level and MR imaging findings were scored and compared with each other. Statistical analyses were performed with χ(2), Fisher exact, and Spearman tests. No differences were observed regarding the areas of hyperintense signal intensity on FLAIR imaging and enhancement of the mammillary bodies between AL and NA patients (P > .05). Frequent sites of involvement were the medial thalami (86%), dorsal medulla (82%), tectal plate (77%), and the periaqueductal gray matter (75%). A positive association was found between the consciousness levels of the patients and the involvement of atypical sites (P = .01). Only 4 of the 24 patients (17%) had all 3 symptoms of the classic WE symptom triad. MR imaging features of WE may not be different between AL and NA patients. The medulla is 1 of the most frequently involved sites, and consciousness level is also associated with atypical site involvement.


Investigation and verification of GIMAP6 as a robust biomarker for prognosis and tumor immunity in lung adenocarcinoma.
According to previous reports, GTPase of immunity-associated protein 6 (GIMAP6) is essential for autophagy. However, it is unclear how GIMAP6 affects the development and tumor immunity of lung adenocarcinoma (LUAD). In the present study, the role of GIMAP6 in vivo and in vitro was examined using reverse transcription-quantitative PCR, western blotting, and Cell Counting Kit-8, colony formation and Transwell assays. Datasets from The Cancer Genome Atlas and Genotype-Tissue Expression databases were thoroughly analyzed using R software. A nomogram was created using GIMAP6 and prognostic characteristics. Gene Ontology, Kyoto Encyclopedia of Genes and Genomes and Gene Set Enrichment Analysis were applied to explore the potential mechanism of GIMAP6 in lung cancer. The link between GIMAP6 and the immunological landscape was studied using single-cell RNA sequencing datasets from Tumor Immune Estimation Resource (TIMER) 2.0 and Tumor Immune Single-cell Hub. Patients with high GIMAP6 expression had improved overall and disease-specific survival compared with those patients with low GIMAP6 expression. According to the receiver operating characteristic and calibration curve, the nomogram based on T stage, N stage and GIMAP6 had predictive value for prognosis. According to functional enrichment analysis, GIMAP6 was primarily involved in T-cell receptor signaling pathway, chemokine signaling pathway, cytokine and cytokine receptor interaction. GIMAP6 was shown to be favorably linked with the infiltration of immune cells and immune-related molecules, including cytotoxic T-lymphocyte associated protein 4, programmed death-ligand 1, and T cell immunoreceptor with Ig and ITIM domains, by single-cell sequencing and TIMER2.0 analysis. The role of GIMAP6 in lung cancer cell proliferation, invasion, migration and immunity was experimentally verified. These findings confirmed that GIMAP6 was an effective prognostic molecule that was involved in the regulation of the immune microenvironment of LUAD, and may become a predictor for the efficacy of immunotherapy.


Grafting improves tomato drought tolerance through enhancing photosynthetic capacity and reducing ROS accumulation.
Drought is the main meteorological threat to plants and limits plant growth, development, and adaptation to environmental changes. However, root-shoot communication plays a vital role in improving tomato plant drought tolerance, especially when cultivars are grafted onto drought-tolerant rootstock. In this study, the relationship between photosynthetic capacity and reactive oxygen species (ROS) in response to drought stress was studied in tomato grafted with different drought-resistant tomato seedlings. To determine the drought-relieving effect of drought-tolerant rootstocks, we measured the effects of grafting on plant growth, net photosynthetic rate (Pn), ROS accumulation, and antioxidant enzyme activities in tomato leaves and roots under drought stress. Plant growth and Pn were significantly inhibited by drought, but ROS accumulation and antioxidant enzyme activities were significantly increased. Treatment with drought-tolerant tomato seedlings significantly increased plant growth and increased Pn under water-deficit conditions compared with those grafted with drought-susceptible rootstock. In addition, the plants grafted with drought-tolerant seedlings had increased activities of partial antioxidant enzymes, leading to decreased ROS production. Our results indicate that tomato grafted with drought-tolerant seedlings alleviated the phytotoxicity and oxidative damage caused by drought by regulating antioxidant enzymes under drought stress.


Echolocating bats rely on audiovocal feedback to adapt sonar signal design.
Many species of bat emit acoustic signals and use information carried by echoes reflecting from nearby objects to navigate and forage. It is widely documented that echolocating bats adjust the features of sonar calls in response to echo feedback; however, it remains unknown whether audiovocal feedback contributes to sonar call design. Audiovocal feedback refers to the monitoring of one's own vocalizations during call production and has been intensively studied in nonecholocating animals. Audiovocal feedback not only is a necessary component of vocal learning but also guides the control of the spectro-temporal structure of vocalizations. Here, we show that audiovocal feedback is directly involved in the echolocating bat's control of sonar call features. As big brown bats tracked targets from a stationary position, we played acoustic jamming signals, simulating calls of another bat, timed to selectively perturb audiovocal feedback or echo feedback. We found that the bats exhibited the largest call-frequency adjustments when the jamming signals occurred during vocal production. By contrast, bats did not show sonar call-frequency adjustments when the jamming signals coincided with the arrival of target echoes. Furthermore, bats rapidly adapted sonar call design in the first vocalization following the jamming signal, revealing a response latency in the range of 66 to 94 ms. Thus, bats, like songbirds and humans, rely on audiovocal feedback to structure sonar signal design.


Correlation between semen adenosine triphosphate and sperm fertilizing capacity.
The concentration of ATP was determined in a large number of semen samples from fertile men and infertility clinic patients. Results were correlated with routine semen characteristics, in vitro sperm fertilizing capacity, and functional integrity of the sperm membrane. The results confirm the findings of Comhaire et al. and Irvine and Aitken that there are positive correlations between semen ATP concentration and sperm count and sperm motility. In routine laboratory examination of semen specimen, the results agree with those of Irvine and Aitken that semen ATP determination does not appear to be useful as a biochemical marker for sperm fertilizing capacity, as assessed by the in vitro zona-free HEPA.


Dendritic Spine Instability in a Mouse Model of CDKL5 Disorder Is Rescued by Insulin-like Growth Factor 1.
CDKL5 (cyclin-dependent kinase-like 5) is mutated in many severe neurodevelopmental disorders, including atypical Rett syndrome. CDKL5 was shown to interact with synaptic proteins, but an in vivo analysis of the role of CDKL5 in dendritic spine dynamics and synaptic molecular organization is still lacking. In vivo two-photon microscopy of the somatosensory cortex of Cdkl5(-/y) mice was applied to monitor structural dynamics of dendritic spines. Synaptic function and plasticity were measured using electrophysiological recordings of excitatory postsynaptic currents and long-term potentiation in brain slices and assessing the expression of synaptic postsynaptic density protein 95 (PSD-95). Finally, we studied the impact of insulin-like growth factor 1 (IGF-1) treatment on CDKL5 null mice to restore the synaptic deficits. Adult mutant mice showed a significant reduction in spine density and PSD-95-positive synaptic puncta, a reduction of persistent spines, and impaired long-term potentiation. In juvenile mutants, short-term spine elimination, but not formation, was dramatically increased. Exogenous administration of IGF-1 rescued defective rpS6 phosphorylation, spine density, and PSD-95 expression. Endogenous cortical IGF-1 levels were unaffected by CDKL5 deletion. These data demonstrate that dendritic spine stabilization is strongly regulated by CDKL5. Moreover, our data suggest that IGF-1 treatment could be a promising candidate for clinical trials in CDKL5 patients.


Growth inhibitory activities of kalopanaxsaponins A and I against human pathogenic fungi.
Antifungal activities of the compounds isolated from Kalopanax pictus against representative fungi of dermatomycosis were investigated using paper disc diffusion method. It was found that kalopanaxsaponins A and I were effective in inhibiting the growth of Candida albicans KCTC 1940 and Cryptococcus neoformans KCTC 7224 with minimum inhibitory concentration (MIC) of 25 micrograms/ml. It showed that antifungal activity of both compounds have strong selectivity against the fungi of dermatomycosis.


Eye movements during reading in aphasics.
In 40 normal subjects and in 21 patients with anomic, Wernicke's, and Broca's aphasia, eye movements were registered with DC-EOG during reading of two standardized texts and analysed with respect to the number of fixations and regressions and reading time. Patients with these aphasic syndromes developed different internal strategies of their saccadic construction: Patients with Wernicke's aphasia showed increasing difficulty in overcoming the text with a tendency to make smaller leaps over the line, with almost a complete disintegration of the saccadic structure ("strategy of small and smallest steps"). The saccadic pattern in Broca's aphasics was clearly better preserved. During oral reading there was a characteristic increase in fixation times and number of regressions ("motor waiting and searching behaviour"). Patients with anomic aphasia showed alterations most similar to the reading behaviour of unskilled normal readers.


Investigations on metabolism and carcinogenicity of 1,1,2-trichloroethane.
Two groups of male and female Sprague-Dawley rats (50 animals/group per sex) were treated with either 15.37 or 46.77 mumole of 1,1,2-TCE in DMSO/rat for 2 years. The animals were treated once a week by s.c. injection of test compound in the skin of neck. Two groups of controls received either DMSO or no treatment at all. The incidence of benign mesenchymal and epithelial tumors was not significant when compared with either DMSO-treated or untreated controls. The animals treated with 46.77 mumole 1,1,2-TCE significantly developed sarcomas when compared with the untreated controls. In a further experiment, either 40 mumole or 160 mumole 1,1,2-TCE was injected into male Wistar rats and the metabolites, TdGA and HEMA, were determined in 24-h urine samples. Comparative studies were carried out giving equimolar amounts of chloroethanol and 2-chloroacetaldehyde diethyl acetal. Analysis of the metabolites showed that no detectable HEMA was excreted in urine after treatment of rats with 1,1,2-TCE or chloroethanol. TdGA was excreted in urine much more among chloroacetaldehyde-treated animals than among 1,1,2-TCE- or chloroethanol-treated rats.