The effects of ovariectomy and stretch on the regulatory profile and activity of the uterus.
Following ovariectomy of five New Zealand white rabbits at day 25 of pregnancy, the intrauterine pressure (IUP) and uterine progesterone (P) and prostaglandin (PG) levels were measured sequentially at days 25, 26 and 27. At day 25, when the uterine P and PGE and PGF were high, massive intrauterine treatment with 500 microng PGF2alpha provoked only a sustained contracture on which only low level oscillation in IUP was superimposed. At day 26, when the P levels had decreased significantly (P less than 0.001) and the PG levels had not changed significantly, 50 microng PGF2alpha significantly increased cyclic IUP as compared with the day 25 value (P less than 0.001). At day 27, when the P levels decreased further, as little as 5 microng PGF2alpha provoked still higher cyclic IUP, in spite of a significant reduction in PG levels (P less than o.05). Stretching the uterus of six post partum and six 26 days pregnant rabbits (after removing the uterine contents) significantly increased the uterine PGF levels (P less than o.001). However, stretch increased only cyclic IUP of the post partum uterus and was without effect on the pregnant uterus, which still had high P levels. These results indicate that the myometrium is activated by exogenous PG or stretch, regardless of whether the uterine PG levels increase, remain unchanged or even moderately decrease, provided that the uterine P levels are reduced to a critical value.


Does Long-Term High Fat Diet Always Lead to Smaller Hippocampi Volumes, Metabolite Concentrations, and Worse Learning and Memory? A Magnetic Resonance and Behavioral Study in Wistar Rats.
Obesity is a worldwide epidemic with more than 600 million affected individuals. Human studies have demonstrated some alterations in brains of otherwise healthy obese individuals and elevated risk of neurodegenerative disease of old age; these studies have also pointed to slightly diminished memory and executive functions among healthy obese individuals. Similar findings were obtained in animal models of obesity induced by high fat diet. On the other hand, low carbohydrate high fat diets are currently promoted for losing weight (e.g., Atkin's style diets). However, the long-term effects of such diets are not known. Additionally, high fat diets leading to (mild) ketonemia were shown to improve brain function in elderly humans and in some animal models. To evaluate the hypothesis that long-term use of a high fat diet was associated with decreases in spatial memory, smaller hippocampi and hippocampi metabolite concentrations in Wistar rats. Twenty five male Wistar rats were put on high fat diet (HFD; 60% calories from fat, 30% from carbohydrates) on their 55th day of life, while 25 control male rats (CONs) remained on chow. Adequate levels of essential nutrients were provided. Both groups underwent memory tests in 8-arm radial maze at 3rd, 6th, 9th, and 12th month. 1H magnetic resonance spectroscopy was employed to measure concentrations of tNAA (marker of neuronal integrity) at one month and one year, whereas MRI was used to evaluate hippocampal volumes. Obese rats (OBRs) consumed similar amount of calories as CONs, but less proteins. However, their protein intake was within recommended amounts. Throughout the experiment OBRs had statistically higher concentrations of blood ketone bodies than CONs, but still within normal values. At post-mortem assessment, OBRs had 38% larger fat deposits than CONs (p<0.05), as evaluated by volume of epididymis fat, an acknowledged marker of fat deposits in rats. Contrary to our expectations, OBRs had better scores of memory behavioral tasks than CONs throughout the experiment. At one year, their hippocampi were by 2.6% larger than in CONs (p = 0.05), whereas concentration of tNAA was 9.8% higher (p = 0.014). Long-term HFD in our study resulted in better memory, larger hippocampal volumes, as well as higher hippocampal metabolite concentrations, possibly due to increased levels of blood ketone bodies. The results should be interpreted with caution, as results from animal models do not necessarily directly translate in human condition.


Fluorescence polarization measurement system using a liquid crystal layer and an image sensor.
The detection system which enables simultaneous fluorescence polarization (FP) measurement of multiple samples was proposed and proven by a proof-of-concept experiment on the viscosity dependence of FP of fluorescein sample in water-ethylene glycol solution and another experiment on the FP immunoassay of prostaglandin E2 sample. The measurement principle of FP is based on the synchronization between the orientation of the liquid crystal molecules and the sampling frequency of a CCD. This report is the first description of the simultaneous FP measurement of multiple samples. This system has a great potential for equipment miniaturization and price reduction as well as providing simultaneous FP measurement of multiple samples.


Is thrombopenia in cord blood indicative of intra-uterine sensitization?
The relation between platelet counts (PCT) and IgE was studied in cord blood from 136 European newborns. PCT was significantly lower (P = 0.0014) when cord-IgE was superior to 1.20 IU/ml (n = 29; 245,000/microliter) than when it was inferior to this value (n = 107; 284,080/microliter) which resulted in a significant negative Spearman rank correlation between PCT and cord-IgE (P = 0.002; rs = -0.25). A follow-up by questionnaire in 97 of the newborns revealed that those newborns who had developed definite atopy within 18 months of age had significantly (P = 0.002) lower PCT at birth (n = 8; 196,000/microliter) than those free of atopic symptoms (n = 61; 286,000/microliters). Further newborns to atopic mothers (n = 23; 245,000/microliters) had significantly (P = 0.014) lower PCT than newborns to non-atopic mothers (n = 74; 286,000/microliters). The lowest PCT was recorded when both the mother was atopic and the newborn had developed definite or probable atopy by the age of 18 months (n = 7; 175,000/microliters) as compared to atopy alone in mothers (n = 16; 276,000/microliters; P = 0.005), to atopy alone in infants (n = 9; 281,000/microliters; P = 0.005) and to non-atopic infants of non-atopic mothers (n = 65; 286,000/microliters; P = 0.0007). Significantly (P = 0.03) lower PCT amongst boys (n = 49; 259,000/microliters) compared with girls (n = 48; 294,000/microliters) was attributed to the higher incidence of elevated cord-IgE and infant atopy among boys.(ABSTRACT TRUNCATED AT 250 WORDS)


Primary invasive ovarian adenocarcinoma with brain and placental metastases: a case report.
A case of primary ovarian adenocarcinoma during pregnancy with both placental and central nervous system metastases is reported.


Relative frequency of ultrasound diagnoses in patients referred for ophthalmic ultrasound.
An ultrasound diagnostic coding system was developed that permitted entry of diagnoses into a programmable calculator, thus permitting rapid information retrieval of patients with a specific diagnosis or diagnoses as well as the number of patients with a specific diagnosis. Cataract, vitreous opacity, trauma, choroidal disease, and retinal detachment were the most common diagnoses made. Only 7.2% of the patients had a normal ultrasound, indicating that ultrasound examination is a test probably underutilized by ophthalmologists.


Stereochemistry of hydrolysis by snake venom phosphodiesterase.
[18O]Adenosine 5'-O-phosphorothioate-O-p-nitrophenyl ester was prepared by saponification of the bis (-O,O-p-nitrophenyl ester) with K18OH. Only the diastereoisomer with the Rp configuration si a substrate for snake venom phosphodiesterase. The asymmetrically labeled [18O]adenosine 5'-O-phosphorothioate formed in this reaction was converted enzymatically to [18O]adenosine 5'-(1-thiodiphosphate) with the Sp configuration. The position of the 18O label, either bridging [1,2-mu-18O] or nonbridging [1-18O] was then determined. The results show that the reaction catalyzed by snake venom phosphodiesterase takes place with retention of configuration at phosphorus. This indicates that the hydrolysis proceeds via a covalent nucleotide enzyme intermediate.


Outdoor recreational activity experiences improve psychological wellbeing of military veterans with post-traumatic stress disorder: Positive findings from a pilot study and a randomised controlled trial.
The authors confirm that all ongoing and related trials for this intervention are registered. The studies reported in this manuscript are registered as clinical trials at ISRCTN: Pilot ID- ISRCTN15325073 RCT ID- ISRCTN59395217.


Discovery of N-benzyl-2-[(4S)-4-(1H-indol-3-ylmethyl)-5-oxo-1-phenyl-4,5-dihydro-6H-[1,2,4]triazolo[4,3-a][1,5]benzodiazepin-6-yl]-N-isopropylacetamide, an orally active, gut-selective CCK1 receptor agonist for the potential treatment of obesity.
We describe the design, synthesis, and structure-activity relationships of triazolobenzodiazepinone CCK1 receptor agonists. Analogs in this series demonstrate potent agonist activity as measured by in vitro and in vivo assays for CCK1 agonism. Our efforts resulted in the identification of compound 4a which significantly reduced food intake with minimal systemic exposure in rodents.


[The promotion of health of the Brazilian female and healthy eating: discourses and opinions printed in the Brazilian newspaper Folha de São Paulo].
The study identifies the discourse and opinions about women's health in relation to their eating habits by means of qualitative research using the journalistic discourse analysis method of the Folha de São Paulo newspaper. Based on the selection of texts on health, women's health and nutrition published throughout the year 2013, the sample resulted in seven journalistic texts, in which voices from the scientific universe related to research, quotes from journals, scientific associations and the opinion of health professionals and researchers were predominantly identified. However, the discourse of women in general about their health rarely appears in the sample analyzed. The main topics were related to health risks and the connection with diet or supplements, as well as pregnancy. The predominant content discourse related to health risk and its relationship with eating habits, nutrition or supplements, as well as pregnancy and/or the manner of delivery; health as a commodity associated with products or procedures, such as diets, dietary supplements, drugs and bariatric surgery, with no room for the promotion of health and healthy eating.


SENP1 in the retrosplenial agranular cortex regulates core autistic-like symptoms in mice.
Autism spectrum disorder (ASD) is a highly heritable neurodevelopmental disorder, causing defects of social interaction and repetitive behaviors. Here, we identify a de novo heterozygous gene-truncating mutation of the Sentrin-specific peptidase1 (SENP1) gene in people with ASD without neurodevelopmental delay. We find that Senp1+/- mice exhibit core autistic-like symptoms such as social deficits and repetitive behaviors but normal learning and memory ability. Moreover, we find that inhibitory and excitatory synaptic functions are severely affected in the retrosplenial agranular (RSA) cortex of Senp1+/- mice. Lack of Senp1 leads to increased SUMOylation and degradation of fragile X mental retardation protein (FMRP), also implicated in syndromic ASD. Importantly, re-introducing SENP1 or FMRP specifically in RSA fully rescues the defects of synaptic function and autistic-like symptoms of Senp1+/- mice. Together, these results demonstrate that disruption of the SENP1-FMRP regulatory axis in the RSA causes autistic symptoms, providing a candidate region for ASD pathophysiology.


2,3-migration in Rh(II)-catalyzed reactions of beta-trifluoroacetamido alpha-diazocarbonyl compounds.
[Structure: see text] The hydroxy group was directly converted into the trifluoroacetamido group by reacting beta-hydroxy-alpha-diazo carbonyl compounds with trifluoroacetimidoyl chloride in the presence of DBU. Rh(II)-catalyzed reactions of these diazo compounds gave 2,3-migration products in high yields.


Global exponential stability of neutral high-order stochastic Hopfield neural networks with Markovian jump parameters and mixed time delays.
In this paper, a class of neutral high-order stochastic Hopfield neural networks with Markovian jump parameters and mixed time delays is investigated. The jumping parameters are modeled as a continuous-time finite-state Markov chain. At first, the existence of equilibrium point for the addressed neural networks is studied. By utilizing the Lyapunov stability theory, stochastic analysis theory and linear matrix inequality (LMI) technique, new delay-dependent stability criteria are presented in terms of linear matrix inequalities to guarantee the neural networks to be globally exponentially stable in the mean square. Numerical simulations are carried out to illustrate the main results.


Effect of protein kinase C activation and depletion on insulin stimulation of glycogen synthesis in cultured hepatoma cells.
Insulin stimulation of glycogen synthesis was nearly abolished in hepatoma cells shortly treated with 4 beta-phorbol 12 beta-myristate, 13 alpha-acetate (protein kinase C activation) but remained unmodified in cells chronically treated with the phorbol ester (protein kinase C depletion). Thus, although exogenous activation of protein kinase C results in an inhibition of insulin action, protein kinase C depletion has no influence on this process. The results suggest that, in hepatoma cells, no endogenous activation of protein kinase C may occur in response to the signal triggered by insulin.


C. elegans DAF-12, Nuclear Hormone Receptors and human longevity and disease at old age.
In Caenorhabditis elegans, DAF-12 appears to be a decisive checkpoint for many life history traits including longevity. The daf-12 gene encodes a Nuclear Hormone Receptor (NHR) and is member of a superfamily that is abundantly represented throughout the animal kingdom, including humans. It is, however, unclear which of the human receptor representatives are most similar to DAF-12, and what their role is in determining human longevity and disease at old age. Using a sequence similarity search, we identified human NHRs similar to C. elegans DAF-12 and found that, based on sequence similarity, Liver X Receptor A and B are most similar to C. elegans DAF-12, followed by the Pregnane X Receptor, Vitamin D Receptor, Constitutive Andosteron Receptor and the Farnesoid X Receptor. Their biological functions include, amongst others, detoxification and immunomodulation. Both are processes that are involved in protecting the body from harmful environmental influences. Furthermore, the DAF-12 signalling systems seem to be functionally conserved and all six human NHRs have cholesterol derived compounds as their ligands. We conclude that the DAF-12 signalling system seems to be evolutionary conserved and that NHRs in man are critical for body homeostasis and survival. Genomic variations in these NHRs or their target genes are prime candidates for the regulation of human lifespan and disease at old age.


Preparation of solid organic fertilizer by co-hydrothermal carbonization of peanut residue and corn cob: A study on nutrient conversion.
With continuous recognition of green, organic and pollution-free products, the organic fertilizer plays an increasingly important role in agricultural production. Hydrothermal carbonization (HTC) is an efficient and environmentally friendly biomass treatment technology that can achieve value-added utilization of solid wastes. This study evaluated the potential of two typical agricultural and forestry wastes (corn cob and peanut residue) in preparing as solid organic fertilizers through HTC. The effects of reaction temperature, residence time, and the raw material composition on hydrochar yield, total nutrient content (TNC), nitrogen recovery, and nutrient elements transformation in HTC were investigated. Corn cob was proven to be not an ideal raw material for the preparation of organic fertilizers because of the low TNC and the high C/N ratio of its hydrochar. On the contrary, peanut residue was suitable for preparing organic fertilizers due to its high TNC and appropriate C/N ratio. The co-HTC of corn cob and peanut residue could further improve the N recovery rate from 8.52% (for peanut residue only) to 19.51% due to the synergistic effect between them. Under the optimal hydrothermal conditions of 240 °C, 120 min, and mixing ratio of 1:1, the hydrochar yield was as high as 27.86%, and the C/N value (11.98) and TNC (6.331%) were both appropriate as fertilizer. Furthermore, the potential migration and transformation paths of nutrients including N, P, K and metal elements in the co-HTC were analyzed. The thermodynamic conditions and raw materials composition significantly affect the migration and transformation of N, P and K between solid and liquid. N dissolved into process water (mainly ammonia) would migrate into hydrochar and bio-oil with increasing of reaction temperature. P was fixed in hydrochar through precipitation and adsorption reaction with metal ions. Further, adjusting pH or adding metal salts can promote the fixation of N and P in solid.


Interrater reliability and accuracy in identifying ischemic strokes using computed tomography scans in people with dementia.
To assess the reliability and interobserver agreement of stroke identification on neuroimaging in patients presenting with dementia. Comparison study between neurologists, radiology reports, and autopsy. Dementia registry within a health maintenance organization. Dementia patients with computed tomography (CT) scans obtained near the time of diagnosis and postmortem neuropathological examinations (N=99). Three neurologists independently read CT scans for the presence and locations of strokes. Radiology reports from these scans were reviewed. The results from neurologists, radiologists, and autopsies were compared. The positive predictive value for CT-observed strokes compared with their presence on autopsy was 0.44 to 0.49, regardless of the specialty of the observer. Strokes were present at autopsy in 46 of 99 cases. Agreement between neurologists on the presence of strokes was fair to moderate (kappa=0.27-0.56). Less agreement was found between neurologists and radiologists (kappa=0.00-0.11). Results improved slightly when each case was evaluated as any stroke present versus no stroke on imaging (kappa=0.34-0.75) or for the presence of multiple strokes (kappa=0.17-0.69). There is only fair to moderate agreement between observers regarding the identification of strokes on CT scans in patients presenting with dementia. Furthermore, strokes identified on imaging were present on pathology only half the time.


In vivo corneal confocal microscopy and prediction of future-incident neuropathy in type 1 diabetes: a preliminary longitudinal analysis.
In vivo corneal confocal microscopy (IVCCM) has been established in cross-sectional studies as a valid measure for the identification of diabetic sensorimotor polyneuropathy (DSP). We aimed to determine the predictive validity of a baseline IVCCM measure in identifying future DSP onset in patients with type 1 diabetes. We followed 65 patients with type 1 diabetes without DSP at baseline. They were followed longitudinally for a mean of 3.5±0.9 years and underwent IVCCM, clinical and electrophysiologic examinations at baseline and follow up. At the end of follow up, participants were assigned as new-onset cases of DSP or as controls. Predictive validity was assessed using receiver operating characteristic curves. At baseline, participants were 34±15 years of age with mean diabetes duration of 18±12 years. The 11 (17%) new-onset cases of DSP were similar to the 54 (83%) controls in baseline age, diabetes duration, gender, glycated hemoglobin levels and electrophysiologic parameters (p≥0.20). However, cases of new onset had significantly lower baseline corneal nerve fibre length (CNFL) and branch density (p<0.05). For identification of new-onset cases, area under the receiver operating characteristic curve for CNFL was 0.78 with an optimal threshold of 14.9 mm/mm(2) (sensitivity=0.82, specificity=0.69). Despite similar clinical and electrophysiologic parameters, participants with type 1 diabetes at risk for future DSP had significantly lower baseline IVCCM measures. CNFL may have applicability in identifying high-risk patients for therapeutic intervention in clinical research and practice.


Comparing a thyroid prognostic nomogram to the existing staging systems for prediction risk of death from thyroid cancers.
Thyroid prognostic nomogram can be applied across different histological types for predicting the individualized risk of death from thyroid cancer. The objective of this study was to compare the strength of our recently published thyroid prognostic nomogram with 12 existing staging systems to predict the risk of death from thyroid cancer. This study included 1900 thyroid cancer patients, from a population based cohort of 2296 patients, on whom adequate staging information was available. Competing risk sub-hazard models were used to compare 12 pre-existing prognostic models with the nomogram model. Their relative strengths for prediction of patients' individualized risks of death from thyroid cancer were compared using Akaike information criterion (AIC), delta AIC, and concordance index. R version 3.2.2 was used to analyze the data. Our cohort of 450 males and 1450 females included 1796 (93.4%) differentiated thyroid cancers. Amongst the compared models, thyroid prognostic nomogram model appeared to be better than other models for predicting the risk of death from all non-anaplastic thyroid cancer (concordance index = 94.4), differentiated thyroid cancer (concordance index = 94.1) and papillary thyroid cancer (concordance index = 94.7). The difference from next best staging systems was most pronounced in non-anaplastic thyroid cancer (delta AIC = 114.8), followed by differentiated thyroid cancer (delta AIC = 35.6) and papillary thyroid cancer (delta AIC = 8.4). Thyroid prognostic nomogram model was found to be better than the other models compared for predicting risk of death from thyroid cancer.


Antenatal screening for Group B Streptococcus: a diagnostic cohort study.
A range of strategies have been adopted to prevent early onset Group B Streptococcal (EOGBS) sepsis, as a consequence of Group B Streptococcal (GBS) vertically acquired infection. This study was designed to provide a scientific basis for optimum timing and method of GBS screening in an Australian setting, to determine whether screening for GBS infection at 35-37 weeks gestation has better predictive values for colonisation at birth than screening at 31-33 weeks, to examine the test characteristics of a risk factor strategy and to determine the test characteristics of low vaginal swabs alone compared with a combination of perianal plus low vaginal swabs per colonisation during labour. Consented women received vaginal and perianal swabs at 31-33 weeks gestation, 35-38 weeks gestation and during labour. Swabs were cultured on layered horse blood agar and inoculated into selective broth prior to analysis. Test characteristics were calculated with exact confidence intervals for a high risk strategy and for antenatal screening at 31-33 and 35-37 weeks gestation for vaginal cultures alone, perianal cultures alone and combined low vaginal and perianal cultures. The high risk strategy was not informative in predicting GBS status during labour. There is an unequivocal benefit for the identification of women colonised with GBS during labour associated with delaying screening until 36 weeks however the results for method of screening were less definitive with no clear advantage in using a combined low vaginal and perianal swabbing regimen over the use of a low vaginal swab alone. This study can contribute to the development of prevention strategies in that it provides clear evidence for optimal timing of swabs. The addition of a perianal swab does not confer clear benefit. The quantification of advantages and disadvantages provided in this study will facilitate communication with clinicians and pregnant women alike.


MISCAN: estimating lead-time and over-detection by simulation.
To estimate the mean lead-time and rate of over-detection associated with screening for prostate cancer with prostate-specific antigen. Simulation models, fitted to the results of the Rotterdam section of the European Randomized Study of Screening for Prostate Cancer, were used to predict the mean lead-time and over-detection rate in population-based screening programmes. The mean lead-time is estimated to be 11-12 years and over-detection to occur in half the cases found by population screening. The estimates are compared with published estimates. The effect of lead-time and over-detection on the balance of positive and negative consequences of screening cannot be neglected.


Longitudinal serum lipoprotein changes in white males during adolescence: the Bogalusa Heart Study.
Determinants of follow-up levels of low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C) and the ratio of LDL-C to HDL-C were analyzed in a longitudinal study. White boys (n = 81) aged 11 to 12 years, when examined in 1973-1974 (year 1) were reexamined in 1978-1979 (year 6) at ages 16 to 17 years. During follow-up, mean levels of LDL-C increased from 87.6 mg/dL to 89.8 mg/dL, mean levels of HDL-C decreased from 67.0 mg/dL to 48.4 mg/dL and the mean LDL-C/HDL-C ratio increased from 1.45 to 2.12. Cross-sectional associations between the serum lipoproteins and weight, triceps skinfold thickness, and ponderosity (wt/ht3) were stronger in year 6 than in year 1. A persistence of ranks was observed between year 1 and year 6 for LDL-C (r = 0.61), HDL-C (r = 0.51), and LDL-C/HDL-C (r = 0.50). Multiple linear regression indicated that year 6 LDL-C levels were positively related to year 1 LDL-C, year 1 Tanner stage (an indication of sexual maturation), and the change in skinfold thickness during follow-up. Follow-up LDL-C/HDL-C was related both to change in height (negatively) and to change in weight (positively), after controlling for year 1 LDL-C/HDL-C. These longitudinal findings were similar to those obtained from earlier cross-sectional analyses and were further verified on an independent cohort of white boys also followed for five years (1976-1977 through 1981-1982).(ABSTRACT TRUNCATED AT 250 WORDS)


Increased GABA B receptor subtype expression in the nucleus of the solitary tract of the spontaneously hypertensive rat.
Expression of GABA(B) receptor messenger RNA (mRNA) in the central nervous system was compared between the spontaneously hypertensive (SHR) and normotensive Wistar Kyoto (WKY) rat. Polymerase chain reaction (PCR) revealed all the isoforms except B1e in cortex, hypothalamus, and medulla oblongata. In the nucleus of the solitary tract (NTS) and ventrolateral medulla (VLM), the B1a-c and 1 g isoforms were present as well as B2. Real-time PCR detected significantly higher levels of B1a (p < 0.01) and B2 (p < 0.05) mRNA in the NTS of SHR compared to WKY. A significant increase in B1a expression (p < 0.05) was detected in VLM. Immunolabeling suggested presynaptic and postsynaptic expression of B1a, B1b, and B2 subtypes throughout the NTS, with significant differences in distribution patterns and labeling between subtypes and between SHR and WKY. These findings suggest that GABA(B) receptors expressed by neurones in NTS may be involved in cardiovascular regulation and that changes in GABA(B) mRNA expression levels may contribute to the hypertensive state in SHR.


Label-free detection of DNA by a dielectric modulated armchair-graphene nanoribbon FET based biosensor in a dual-nanogap setup.
A Double-Gate Armchair-Graphene Nanoribbon FET is proposed to realize a high-sensitive and small-size biosensor in order to detect DNA without high-cost and time-consuming labeling process. Two nanogap cavities open inside the top and bottom gate oxides by the method of sacrificed layer etching. When the DNA biomolecule is introduced to the nanogap cavity, the hybridization event which is actually the formation of a double-strand of DNA will occur thus electrically modulating the GNR channel leading to a change in the drain current. The important report of this research is about attained high sensitivity of the proposed biosensor for a vast spectrum of the DNA biological samples. It is worth noting that a DNA sequence by 23 nucleotides extracted from Neisseria gonorrhoeae can be detected as a special case. An extensive numerical approach has been applied in order to characterize the proposed biosensor. The suggested biosensor has been evaluated by solving Schrödinger equation )SE( with Non-Equilibrium Green Function (NEGF) method in the mode-space coupled into Poisson solver in a self-consistent manner assuming ballistic limit. Two different expressions of sensitivity in terms of the threshold voltage and current have been defined giving a good metric for the sensitivity analysis. The results revealed a relative sensitivity of 1 mV/nm2 by a filled area by the DNA about 120 nm2 showing the excellent superiority for the proposed biosensor as compared to other counterparts. The effective area of the proposed biosensor obtains 240 nm2 which is very small in comparison with other reports highlighting high capability of the biosensor in the detection. It has been shown that the proposed biosensor can be implemented in ultra-scaling domain resulting in considerable increase in the sensitivity promising a potent and reliable candidate for high-sensitive and small-size biosensors. Also, the technical issues on designing the suggested biosensor have been investigated to achieve a useful guideline in detection and identification of the target DNAs.


In-situ hybridization as a methodological tool for the neuroscientist.
The technique of in-situ hybridization is now well established for the identification and localization of both DNA and mRNA in cells in the nervous system. For the nonspecialist neuroscientist, use of the technique has been greatly facilitated by the availability of convenient commercial kits for producing isotopically labelled cDNA and cRNA probes. Additionally, the development of synthetic oligonucleotide probes and nonradioactive detection for DNA or RNA has greatly contributed to accessibility of the technique.


Body image disturbance in young North European and East Asian women with and without eating disorders in Australia and in Singapore.
To investigate body image disturbance in young women with and without an eating disorder (ED) across two different ethnic groups in Australia and Singapore. The relationship of body image disturbance to cultural orientation and socio-cultural factors was analysed in 154 women with and without an ED. Participants were from the following backgrounds: North European Australian, East Asian Australian, Singaporean Chinese (SC) and North European expatriates in Singapore. Irrespective of cultural group, women with an ED had similar body dissatisfaction. Among those without an ED, SC women reported greater body dissatisfaction than all other cultural groups. Finally, within each cultural group, ED participants reported significantly higher body dissatisfaction than their non-ED counterparts with the exception of SC women where there was no difference. Socio-cultural factors other than body image may play more important roles in SC women's ED psychopathology.


[Comparative study between an easy coagglutination test and traditional cultures for the detection of group A beta-hemolytic streptococci in the oropharynx].
The authors make a comparative study of the conventional culture media and a commercially available coagglutination test for detection of streptococcus beta-haemolyticus. They draw attention to the simplicity and quickness of the coagglutination test and to their high value of prediction.


Novel zebrafish model reveals a critical role for MAPK in lymphangiogenesis.
Lymphatic disorders are poorly understood with few animal models. We designed a novel assay to measure lymphatic development using transgenic zebrafish with fluorescently labeled endothelial cells. Two major branches of the vascular endothelial growth factor receptor (VEGFR) signaling pathway were examined: the MAPK and PI3K pathways. Direct visualization of lymphatic development was performed in control embryos or under chemical inhibition. Treatment involved a 6-hour pulse of inhibitor at 3 days postfertilization. Fish were analyzed for the presence of the thoracic duct (TD) at 4 days postfertilization (n > 100 specimens). Thoracic duct formation was prevented using selective inhibitors against kinases (MAPK, PI3K/TOR, or VEGFR). These kinases were important for TD formation because the lymphatic vessel failed to form in most of treated animals. Remarkably, MAPK pathway inhibition most robustly reduced lymphangiogenesis, demonstrated by a lack of lymphatic endothelial cells. We conclude that MAPK pathway function downstream of the VEGFRs is crucial at the early stages of TD development. This study provides a novel animal model and a potential target pathway for further investigation. We suggest further examination of MAPK pathway deregulation as a potential mechanism underlying lymphatic disease in humans.


Performance analysis of univariate and multivariate EEG measurements in the diagnosis of ADHD.
To investigate the performance of univariate and multivariate EEG measurements in diagnosing ADHD subjects in a broad age range. EEG from eight cortical regions were recorded at rest during eyes open and eyes closed in 22 male ADHD subjects of combined type and 21 healthy male controls (age range 4-15 years). Univariate and interdependence measurements calculated from the frequency domain and from the reconstructed state spaces of EEG signals were computed, and their performance in discriminating ADHD from healthy subjects was analyzed. Significant between-group differences in univariate measures were age-dependent. However, certain interdependence inter-hemispheric measures during eyes closed showed significant, age-independent between-groups differences. Among them, coherence in the beta band between inter-occipital regions and between left/occipital-right/central regions provided an overall accuracy classification rate of 74.4%. Even greater accuracy (86.7%) was obtained by an interdependence index of generalized synchronization between left/occipital-right/central regions and left/central-right/temporal regions. EEG beta coherence and especially the degree of generalized synchronization between a few inter-hemispheric regions during resting state with eyes closed allow a high accuracy classification rate of ADHD subjects. Changes in inter-hemispheric EEG functional brain connectivity at rest are useful for ADHD diagnosis in a broad age range.


A theory on the control of arbitrary movements.
A theory dealing with the control of human, arbitrary movements is proposed. A schema is set up to suggest how the relevant information flows and what kind of operations affect it. A number of successive steps are distinguished in the production of a movement. It is assumed that the intended movement is carried out in the imagination, and that this imaginary movement is composed of a spatial trajectory and an intensity course, which are considered to be independent features of the intended movement. The spatial trajectory will be encoded in a special coding, which is related to the lengths of the muscles that effect the movement. From this special coding of the intended movement static and dynamic control signals can be derived. Because afferent and efferent signals are encoded in the same way in this schema, the evaluation and correction of the performed movement is quite simple. The higher levels in the control schema may function in an abstract way, i.e. the signals at these levels are barely concerned with details of the peripheral motor system. This abstract functioning of the higher levels is based on the numerous feedback mechanisms involved at all levels of control and in the peripheral motor system. Nevertheless, it is possible to incorporate specific peripheral properties in the generation of the control signals. The assumptions in this theory will be discussed and aspects of the proposed control schema will be compared with general control principles.


Maternal C-reactive protein and cytokine levels during pregnancy and the risk of selected neuropsychiatric disorders in offspring: A systematic review and meta-analysis.
The pathophysiology of neuropsychiatric disorders is unclear. Increasing evidence has suggested maternal immune system dysregulation may be implicated in offspring's early brain development and related to an increased risk of neuropsychiatric disorders in offspring. The primary objective of this meta-analysis was to investigate the association of maternal CRP and cytokine levels with offspring's neuropsychiatric disorders. We identified relevant studies following a search of PubMed, Web of Science, EMbase database between January 1971 and February 2018. A meta-analysis was performed on studies which reported the association of prenatal maternal peripheral blood concentrations of CRP and cytokines with offspring's neuropsychiatric disorders. Results were reported according to PRISMA statement. Fifteen studies (six for maternal CRP, nine for maternal cytokines) were included in the meta-analysis, of which 80% were of high methodological quality. Random-effect meta-analysis showed that increasing maternal CRP (OR = 1.31, 95% CI 1.11-1.55, SMD = 0.15, 95% CI 0.06-0.24, P < 0.01), pro-inflammatory cytokine interleukin (IL)-8 (OR = 1.64, 95% CI 1.06-2.55, SMD = 0.27, 95% CI 0.03-0.52, P = 0.03) and anti-inflammatory cytokine IL-10 (OR = 2.16, 95% CI 1.30-3.59, SMD = 0.43, 95% CI 0.14-0.71, P < 0.01) were significantly associated with schizophrenia in offspring. The finding of our meta-analysis has identified significantly altered maternal CRP and cytokine concentrations in schizophrenia, strengthening evidence of maternal immune system dysregulation in neuropsychiatric disorders where inflammatory signals dominate.


Mechanical recanalization of subacute vessel occlusion in peripheral arterial disease with a directional atherectomy catheter.
To retrospectively examine the technical feasibility and safety of directional atherectomy for treatment of subacute infrainguinal arterial vessel occlusions. Five patients (one woman, four men, age range 51-81 years) with peripheral arterial disease who experienced sudden worsening of their peripheral arterial disease-related symptoms during the last 2-6 weeks underwent digital subtraction angiography, which revealed vessel occlusion in native popliteal artery (n = 4) and in-stent occlusion of the superficial femoral artery (n = 1). Subsequently, all patients were treated by atherectomy with the SilverHawk (ev3 Endovascular, USA) device. The mean diameter of treated vessels was 5.1 ± 1.0 mm. The length of the occlusion ranged 2-14 cm. The primary technical success rate was 100%. One patient experienced a reocclusion during hospitalization due to heparin-induced thrombocytopenia. There were no further periprocedural complications, in particular no peripheral embolizations, until hospital discharge or during the follow-up period of 1 year. The recanalization of infrainguinal arterial vessel occlusions by atherectomy with the SilverHawk device is technically feasible and safe. In our limited retrospective study, it was associated with a high technical success rate and a low procedure-related complication rate.


Involvement of DNA replication in phage lambda Red-mediated homologous recombination.
Crosses between a non-replicating linear bacteriophage lambda chromosome and a replicating plasmid bearing a short cloned segment of lambda DNA were monitored by extracting DNA from infected cells, and analysing it via restriction endonuclease digestion and Southern blots. Recombinant formation resulting from the action of the Red homologous recombination system, observed directly in this way, was found to be fast, efficient, independent of the bacterial recA function and highly dependent upon replication of the target plasmid. These features of the experimental system faithfully model Red-mediated recombination in a lytically infected cell in which phage DNA replication is occurring. Neither of the previously established mechanisms by which the Red system can operate--strand annealing or strand invasion--accounts well for these findings. A third mechanism, replisome invasion, involving replication directly in the recombination mechanism, is invoked as an alternative.


[Efficacy of esophagus protection in complex treatment of erosive gastroesophageal reflux disease: a systematic review and meta-analysis of controlled trials].
To review the data about the efficacy of esophagus protective agent based on the fixed combination of hyaluronic acid and chondroitin sulfate dissolved in the bioadhesive carrier (poloxamer 407) in the complex therapy of patients with erosive gastroesophageal reflux disease (GERD). A search in MEDLINE/PubMed, EMBASE, Cochrane, and Russian Science Citation Index of Scientific Electronic Library electronic databases was performed. Relevant original controlled studies of a fixed combination of hyaluronic acid and chondroitin sulfate as an esophagus protective agent in a population of patients with erosive GERD were included. The final analysis included three studies that enrolled 181 patients with erosive GERD. All the studies had a uniform design with the assessment of the primary endpoints (complete epithelialization of esophageal erosions and complete resolution of heartburn) 28 days after the start of therapy. Meta-analysis of the three controlled trials has demonstrated that combination therapy with proton pump inhibitors (PPIs) and esophagus protective agents is significantly more effective than PPI monotherapy for complete epithelialization of esophageal erosions at 28 days of treatment (relative risk 1.267, 95% confidence interval 1.082-1.483, p=0.003; I2=21.19%), but did not differ for complete resolution of heartburn on the day 28 of treatment (relative risk 1.638, 95% confidence interval 0.660-4.067, p=0.287; I2=92.59%). Combined therapy with PPI and Alfasoxx is significantly more effective than PPI monotherapy for the epithelialization of esophageal erosions in patients with erosive GERD.


Influence of age, gender, education and dexterity on upper limb motor performance in Parkinsonian patients and healthy controls.
Finger tapping, the most widely used test for evaluating motor dysfunction in Parkinson's disease (PD), was found to react sensitively to disease specific factors like disease severity and changes in medication. A possible interference caused by disease unrelated demographic factors--age, gender, education and dexterity--however has not yet been studied systematically. Various components of tapping performance of 187 healthy subjects and 200 PD patients were assessed by means of the BRAIN TEST, a digitalized test battery. The effects of demographic factors--above all education and age--were found to be significant. These influences generally affect different aspects of movement to a different extent, with speed and akinesia being affected more severely than dysmetria and arrhythmokinesis. Our study suggests that whenever precise assement of upper limb motor performance is needed, specific corrections for these demographic factors in both healthy controls and PD patients are necessary.


FDG-PET predictors of response to behavioral therapy and pharmacotherapy in obsessive compulsive disorder.
In subjects with obsessive-compulsive disorder (OCD), lower pre-treatment metabolism in the right orbitofrontal cortex (OFC) and anterior cingulate gyrus (AC) has been associated with a better response to clomipramine. We sought to determine pre-treatment metabolic predictors of response to behavioral therapy (BT) vs. pharmacotherapy in subjects with OCD. To do this, [18F]fluorodeoxyglucose positron emission tomography scans of the brain were obtained in subjects with OCD before treatment with either BT or fluoxetine. A Step-Wise Variable Selection was applied to normalized pre-treatment glucose metabolic rates in the OFC, AC, and caudate by treatment response (change in Yale-Brown Obsessive-Compulsive Scale) in the larger BT group. Left OFC metabolism (normalized to the ipsilateral hemisphere) alone was selected as predicting treatment response in the BT-treated group (F = 6.07, d.f. = 1,17, P = 0.025). Correlations between normalized left OFC metabolism and treatment response revealed that higher normalized metabolism in this region was associated with greater improvement in the BT-treated group (tau = 0.35, P = 0.04), but worse outcome (tau = -0.57, P = 0.03) in the fluoxetine-treated group. These results suggest that subjects with differing patterns of metabolism preferentially respond to BT vs. medication.


Photocatalytic reduction of vanadium(V) in TiO₂ suspension: chemometric optimization and application to wastewaters.
The photocatalytic reduction of V(V) to V(IV) over TiO₂ in aqueous solution is presented. Experiments were undertaken on air-equilibrated water spiked with V(V) (0.6-20 mgL(-1)), under UV-A or solar light. A chemometric study was performed to optimize the reduction yield, by considering the most important variables recognized to affect the photocatalytic process. Among pH, irradiation time and catalyst concentration, the two latter proved to be determinant. The good yields achieved (up to 98%), along with the possibility of working in aerated solution, make this procedure simple, rapid and efficient. Although a deep insight on the photochemical mechanisms was beyond our scope, the role of electron donors was investigated, proving the efficiency of 2-propanol, citric acid and formic acid in the acceleration and improvement of V(V) conversion. After irradiation, total vanadium and aqueous V(V) and V(IV) after solid-phase separation on Chelex-100 resin, were determined by inductively coupled plasma optical emission spectroscopy (ICP-OES). The procedure was applied to contaminated wastewaters, combining remediation and possible vanadium recovery as V(IV).


Rumen cannulation: procedure and use of a cannulated bovine.
Rumen cannulation can be done on a healthy animal currently in the herd with minimal expense. The surgery is no more difficult than most other routine surgical procedures performed by bovine practitioners. A cannulated animal provides a long-term, readily available source of rumen content that can be used to transfaunate herd mates that have suffered various digestive upsets.


Assessment of Construct Validity of the Oswestry Disability Index and the Scoliosis Research Society-30 Questionnaire (SRS-30) in Patients With Degenerative Spinal Disease.
Observational cohort study. To measure and compare the structural validity of the Oswestry Disability Index (ODI) and the Scoliosis Research Society-30 (SRS-30) questionnaire in an adult population with prolonged degenerative thoracolumbar disease. The ODI and the SRS-30 are commonly used patient-reported outcome instruments to assess back-specific disability and symptoms related to scoliosis. Still, these instruments have not been validated for degenerative spinal disease with different stages of deformity. Altogether, 637 consecutive adult patients with degenerative spinal pathologies were included. The patients completed the ODI (version 2.0), the 23 preoperative items of the SRS-30, a general health survey, the Kasari Frequency Intensity Time (FIT) index, the Depression Scale (DEPS), the RAND-36, and visual analog scales for leg and back pain instruments. Psychometric statistical and illustrative analyses were conducted. Deformity groups were analyzed to assess how well the two instruments reflect deformity-related back problems. Both instruments reflected good coverage and targeting. Correlation between the ODI and the SRS-30 was high (r = 0.70; p < .001). Both measures could distinguish between different general health states. The SRS-30 strongly reflected mental state and social well-being. The SRS-30 was less sensitive for pain and function. Furthermore, the principal component of pain/function explained more variance in the SRS-30 compared with the ODI score. The ODI was more sensitive for variance of disability among different age and deformity groups. Both the ODI and the the SRS-30 provide valid scores in evaluating health-related quality of life and/or level of disability among patients with prolonged degenerative thoracolumbar disease. The ODI has slightly higher correlation with physical functioning. The SRS-30 seems to be better when evaluating the emotional and psychological functions. Level III.


Elucidating the role of maternal environmental exposures on offspring health and disease using two-sample Mendelian randomization.
There is considerable interest in estimating the causal effect of a range of maternal environmental exposures on offspring health-related outcomes. Previous attempts to do this using Mendelian randomization methodologies have been hampered by the paucity of epidemiological cohorts with large numbers of genotyped mother-offspring pairs. We describe a new statistical model that we have created which can be used to estimate the effect of maternal genotypes on offspring outcomes conditional on offspring genotype, using both individual-level and summary-results data, even when the extent of sample overlap is unknown. We describe how the estimates obtained from our method can subsequently be used in large-scale two-sample Mendelian randomization studies to investigate the causal effect of maternal environmental exposures on offspring outcomes. This includes studies that aim to assess the causal effect of in utero exposures related to fetal growth restriction on future risk of disease in offspring. We illustrate our framework using examples related to offspring birthweight and cardiometabolic disease, although the general principles we espouse are relevant for many other offspring phenotypes. We advocate for the establishment of large-scale international genetics consortia that are focused on the identification of maternal genetic effects and committed to the public sharing of genome-wide summary-results data from such efforts. This information will facilitate the application of powerful two-sample Mendelian randomization studies of maternal exposures and offspring outcomes.


Susceptibility pattern and molecular type of species-specific Candida in oropharyngeal lesions of Indian human immunodeficiency virus-positive patients.
A study of oropharyngeal candidiasis (OPC) in Indian human immunodeficiency virus (HIV)/AIDS patients was conducted over a period of 15 months. This study revealed that 75% of the HIV/AIDS patients had OPC. MIC testing revealed that 5% of the Candida isolates were fluconazole resistant. A correlation between CD4(+)-T-cell counts and development of OPC in HIV/AIDS patients was also observed. Molecular typing of C. albicans isolates showed that all were genetically unrelated.


Clinical and laboratory aspects of disseminated intravascular coagulation (DIC): a study of 118 cases.
The medical records of 118 cases who met laboratory criteria of DIC were studied. The most frequent etiologies were: Generalized infection (39.8%), trauma (16.9%), malignancy (6.8%) and surgical cases (6.8%). The main clinical manifestations which appeared to be related solely to DIC were (in a decreasing order of frequency): Bleeding (64.4%), renal dysfunction (24.6%), liver dysfunction (18.6%), respiratory dysfunction (16.1%), shock (14.4%), thromboembolic phenonmena (6.8%) and central nervous system involvement (1.7%). In 26 patients none of these manifestations were observed. In patients with infection, liver and renal dysfunction were frequent and respiratory dysfunction rare, whereas in trauma cases, liver and renal dysfunctions were rare and respiratory dysfunction frequent. This variability indicates that the clinical manifestations are affected not only by the process of intravascular coagulation but also by the underlying clinical disorders. The most impaired coagulation tests were prothrombin time, partial thromboplastin time, platelet count and thrombin time. The degree of abnormality of these coagulation tests was found to be related to the extensiveness of organ involvement. The mortality (overall 54.7%) increased independently with age, with the number of clinical manifestations and with the degree of abnormality of the above-mentioned four most impaired coagulation tests. In addition, older patients were more likely to have an increased number of clinical manifestations and more impaired coagulation tests. Mortality was similar in the various etiologies except for trauma patients in whom it was lower (30%).


Progressive irreversible hearing loss is caused by stria vascularis degeneration in an Slc26a4-insufficient mouse model of large vestibular aqueduct syndrome.
Hearing loss of patients with enlargement of the vestibular aqueduct (EVA) can fluctuate or progress, with overall downward progression. The most common detectable cause of EVA is mutations of SLC26A4. We previously described a transgenic Slc26a4-insufficient mouse model of EVA in which Slc26a4 expression is controlled by doxycycline administration. Mice that received doxycycline from conception until embryonic day 17.5 (DE17.5; doxycycline discontinued at embryonic day 17.5) had fluctuating hearing loss between 1 and 6 months of age with an overall downward progression after 6 months of age. In this study, we characterized the cochlear functional and structural changes underlying irreversible hearing loss in DE17.5 mice at 12 months of age. The endocochlear potential was decreased and inversely correlated with auditory brainstem response thresholds. The stria vascularis was thickened and edematous in ears with less severe hearing loss, and thinned and atrophic in ears with more severe hearing loss. There were pathologic changes in marginal cell morphology and gene expression that were not observed at 3 months. We conclude that strial dysfunction and degeneration are the primary causes of irreversible progressive hearing loss in our Slc26a4-insufficient mouse model of EVA. This model of primary strial atrophy may be used to explore the mechanisms of progressive hearing loss due to strial dysfunction.


Low incidence of minor BRAF V600 mutation-positive subclones in primary and metastatic melanoma determined by sensitive and quantitative real-time PCR.
BRAF V600 mutation is an important biological marker for therapeutic guidance in melanoma, where mutation-positive cases are candidates for therapy targeting mutant B-Raf. Recent studies showing intratumor variation in BRAF mutation status have caused concern that sensitive mutation analysis can lead to mutation-positive results in patients with melanomas with small subsets of mutation-positive cells who may not benefit from therapy targeting mutant B-Raf. Mutation analysis with high analytical sensitivity is generally preferred, to reduce the risk of false-negative results. In this study, sensitive and quantitative BRAF V600E and V600K mutation-specific real-time quantitative PCR was used to study the occurrence of small subsets of mutation-positive cells in primary melanomas and melanoma metastases. The BRAF V600E mutation was detected in 39 of 82 melanoma patients. We observed a highly dichotomous pattern, with most samples either testing mutation positive in a high fraction of alleles (median, 51%) or negative with a high sensitivity (median, 0.06%). This finding demonstrates that the occurrence of small subsets of mutation-positive cells was rare in our study population and indicates that sensitive mutation analysis can generally be expected to produce clinically relevant results in melanoma patients.


Effects of drying methods and solvent extraction on quantification of major bioactive compounds in pomegranate peel waste using HPLC.
Bioactive compound characterization is an essential step for utilizing pomegranate peel waste as food and nutraceuticals ingredients. In the present investigation, the effects of different drying methods (freeze, tray-oven, and sun) and extraction solvents such as methanol, ethanol, water, acetone, and hexane were investigated on the extraction and recovery of major bioactive compounds (ellagic acid, gallic acid, quercetin, and punicalagin) of pomegranate peel for two pomegranate varieties (i.e., Bhagwa and Ganesh) using high-performance liquid chromatography (HPLC). The results indicated that the freeze dried pomegranate peel powder of both pomegranate varities potential to extraction higher amount of bioactive compounds with methanol as extraction solvent as compared to other drying methods and solvents. Freeze-dried peel powder of Bhagwa pomegranate showed a higher amount of gallic acid (32.2 mg/g), ellagic acid (13.6 mg/g), punicalagin (15.2 mg/g), and quercetin (2.5 mg/g) with methanol solvent as compared to the other extract of Bhagwa and Ganesh varieties. The basis on the results of the current study, it can be concluded that the freeze-drying method of drying pomegranate peel powder and methanol as an extraction solvent are effective to recover higher amounts of bioactive compounds that can be utilized in food and pharmaceutical sectors at commercial scale.


Searching biomarker candidates in serum using multidimensional native chromatography. I. Enhanced separation method.
The microplate-based method developed by our group for non-denaturing multidimensional proteome separation was improved on using improved column arrays and a newly developed robot. Currently size exclusion, anion exchange and lectin affinity chromatography are combined orthogonally. Different samples run simultaneously to enhance reliability of intercomparison. LC-ESI (electro-spray ionization) MS/MS analysis of selected fractions identified 32,288 peptides matching 2,669 serum proteins. The present contribution (I) shows the characteristics of the method, whereas "prove of principle" by applying it to search for biomarker candidates with model diseases is reported in an accompanying paper (II).


Gastrointestinal manifestations in symptomatic Coronavirus disease - 19 patients and its relevance in predicting severity and outcome.
Recent developments characterizing the pathophysiological basis of infection in the Coronavirus disease - 19 (COVID-19) have stirred great interest in studying this disease outside the purview of respiratory involvement and especially focusing on the gastrointestinal (GI) system. The present study involving a large cohort of COVID-19-infected patients reports on the characteristics of GI manifestations in patients infected with COVID-19 as well as the predictive role in their association with disease severity and adverse outcomes. A retrospective cohort study was carried out in a tertiary care hospital in northern India. Descriptive analysis of GI symptoms was carried out followed by predictive analysis assessing COVID-19 severity and with the primary endpoint of 28-day in-hospital all-cause mortality. Of 3842 hospitalized COVID-19 patients, 2113 (55%) were symptomatic. GI symptoms were present in 163 (7.1%) patients. Common GI symptoms were diarrhea 65 (3.1%), anorexia 61 (2.9%) and vomiting 37 (1.8%). Mild and moderate-to-severe disease was seen in 1725 (81.6%) and 388 (18.4%) patients, respectively. Logistic regression showed greater odds of moderate-to-severe disease in patients with any GI symptoms (odds ratio [OR] 1.849, 95% CI 1.289-2.651 [p = 0.001]) and anorexia in particular (OR 2.797, 95% CI 1.647-4.753 [p = 0.001]); however, on multivariable-analysis, this association lost its significance. A total of 172 patients succumbed to illness. In the Cox proportional hazards model for mortality, patients with any GI symptom (HR 2.184, 95 CI 1.439-3.317 [p < 0.001]) and anorexia (HR 3.556, 95% CI 2.155-5.870 [p < 0.001]) had higher risk. In multi-variable analysis after adjustment to age, sex, oxygen saturation and comorbidities, the presence of any GI symptom was a significant predictor of mortality (hazard ratio adjusted [HRadj] 1.758, 95% CI 1.147-2.694 [p = 0.010]). GI symptoms were common among patients infected with COVID-19. The presence of any GI symptom was a significant predictor of the risk of mortality after adjustment to respiratory failure, age, sex and pre-existing comorbidities. The clinical and pathophysiological basis of these associations has been explored.


Restriction fragment length polymorphism analysis rules out cross-infection among renal patients with tuberculosis.
A cluster of five cases of tuberculosis occurred on a renal unit in 1993. The initial impression was that this was an outbreak, and cross-infection was suspected. Restriction fragment length polymorphism analysis was carried out on the strains of Mycobacterium tuberculosis isolated from these cases, using a DNA probe directed against the insertion sequence IS6110. DNA fingerprints obtained by this method differed for all the strains tested, ruling out cross-infection as a cause of the outbreak. This technique is a useful adjunct to standard epidemiological investigations in outbreaks of tuberculosis.


A Value-Added Health Systems Science Intervention Based on My Life, My Story for Patients Living with HIV and Medical Students: Translating Narrative Medicine from Classroom to Clinic.
In 2018-2019, at the Keck School of Medicine of the University of Southern California (KSOM), we developed and piloted a narrative-based health systems science intervention for patients living with HIV and medical students in which medical students co-wrote patients' life narratives for inclusion in the electronic health record. The pilot study aimed to assess the acceptability of the "life narrative protocol" (LNP) from multiple stakeholder positions and characterize participants' experiences of the clinical and pedagogical implications of the LNP. Students were recruited from KSOM. Patients and staff were recruited from the Maternal, Child, and Adolescent/Adult Center for Infectious Disease and Virology (MCA) at Los Angeles County+USC Medical Center. Ten patients, seventeen students, and ten MCA staff participated in the pilot study. Qualitative methods were used to gather data from students', patients', and staff's perspectives. Three themes emerged from the thematic analysis: (1) patients' life narratives conveyed their unique life experiences and voices; (2) the protocol could result in wide-ranging effects on HIV care; (3) the LNP enabled students to contribute value to patients' healthcare. Across groups, participants considered the LNP an acceptable intervention. The LNP, its limitations, and implications for HIV care, narrative medicine, and health information technology are presented.


My Approach to Preservation Rhinoplasty.
Preservation rhinoplasty entails the preservation of the supportive ligaments, preservation of the cartilage structure, and preserving the anatomy of the nasal dorsum. The preservation methods I use are described in this article.


CONUT Score: A New Tool for Predicting Prognosis in Patients with Advanced Thyroid Cancer Treated with TKI.
(1) Background: The Controlling Nutritional Status (CONUT) score is an immuno-nutritional screening tool based on serum albumin, total cholesterol, and lymphocyte count. The aim of the study was to assess the CONUT score as a potential prognostic factor of response to therapy in patients with advanced thyroid cancer treated with tyrosine kinase inhibitors (TKIs). (2) Methods: We retrospectively evaluated 42 metastatic thyroid cancer patients (54.8% female). The median age at the time of TKI treatment was 69 years. Histological diagnosis was differentiated thyroid cancer in 66.7%, poorly differentiated thyroid cancer in 21.4%, and medullary thyroid cancer in 11.9% of patients. CONUT score was assessed before starting TKI therapy. (3) Results: Progression-free survival (PFS) and overall survival (OS) were significantly influenced by baseline CONUT score. The best CONUT cut-off able to predict the response to treatment was 3. Both PFS and OS were better in patients with CONUT score <3 than in those with CONUT score ≥3 (p < 0.0001). CONUT score was the only independent prognostic factor associated with PFS (p = 0.021) and OS (p = 0.007). (4) Conclusions: CONUT score represents a relatively new screening tool, easily applicable in clinical practice and potentially useful in predicting prognosis in thyroid cancer patients treated with TKIs.


Dizziness and Loss of Balance in Individuals With Diabetes: Relative Contribution of Vestibular Versus Somatosensory Dysfunction.
The authors studied patients with diabetes and complaints of dizziness to determine whether peripheral neuropathy or inner ear dysfunction was more likely to disturb balance. Quantitative testing showed that the majority failed to maintain balance in vestibular-related conditions and had normal equilibrium scores in conditions relying on somatosensory input. Vestibular dysfunction should be an immediate consideration in patients with diabetes and complaints of dizziness regardless of the presence of peripheral neuropathy.


Individual cases of autochthonous malaria in Evros Province, northern Greece: serological aspects.
From 1994 to 1995 four presumably autochthonous malaria cases were diagnosed by blood smear microscopy in Evros Province, northern Greece. Alarmed by these unexpected infections a serological survey was performed from 1997 to 1999 in ten rural villages, including those where the malaria cases had occurred. Among the 1,102 blood samples examined, nine turned out to contain specific antibodies against plasmodial parasites as detected by indirect fluorescent antibody test, including two of the former patients. The remaining seven samples were taken from healthy individuals with no history of recent infection or of having travelled to endemic areas. A further 21 sera showed borderline reactivity with Plasmodium falciparum antigen. Although no retrospective examination of the blood specimens could be performed to confirm the serological results by direct parasite detection, we can conclude that at least the seropositive persons have actually undergone infection with malaria parasites but developed no or only mild clinical symptoms which went unnoticed. It is becoming obvious that even in European countries where climatic and vector conditions are favourable for the development of the parasite there is a potential risk of incidental malaria transmission by indigenous Anopheles mosquitoes.


Two sesquiterpene pyridine alkaloids and a triterpenoid saponin from the root barks of Tripterygium hypoglaucum.
Two new sesquiterpene pyridine alkaloids hypoglaunines E (1) and F (2) and a new triterpenoid saponin hypoglaside A (3), together with a known diterpenoid glucoside11-O-β-D-glucopyranosyl neotriptophenolide (4) and two known triterpenoids 23-noroxopristimerol(5) and 2,3-dihydroxy-6-oxo-D:A-froedo-24 nor-1,3,5(10),7-oleanatetraen-29-oic acid (6), have been isolated from the root barks of Tripterygiumhypoglaucum. Their structures were elucidated by NMR spectroscopy and MS analysis.Compounds 1–3 were screened for their cytotoxic activities against five cancer celllines, but all of them were inactive.


Severe acute respiratory syndrome coronavirus 2 infection reaches the human nervous system: How?
Without protective and/or therapeutic agents the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection known as coronavirus disease 2019 is quickly spreading worldwide. It has surprising transmissibility potential, since it could infect all ages, gender, and human sectors. It attacks respiratory, gastrointestinal, urinary, hepatic, and endovascular systems and can reach the peripheral nervous system (PNS) and central nervous system (CNS) through known and unknown mechanisms. The reports on the neurological manifestations and complications of the SARS-CoV-2 infection are increasing exponentially. Herein, we enumerate seven candidate routes, which the mature or immature SARS-CoV-2 components could use to reach the CNS and PNS, utilizing the within-body cross talk between organs. The majority of SARS-CoV-2-infected patients suffer from some neurological manifestations (e.g., confusion, anosmia, and ageusia). It seems that although the mature virus did not reach the CNS or PNS of the majority of patients, its unassembled components and/or the accompanying immune-mediated responses may be responsible for the observed neurological symptoms. The viral particles and/or its components have been specifically documented in endothelial cells of lung, kidney, skin, and CNS. This means that the blood-endothelial barrier may be considered as the main route for SARS-CoV-2 entry into the nervous system, with the barrier disruption being more logical than barrier permeability, as evidenced by postmortem analyses.


Barium chloride injures myofibers through calcium-induced proteolysis with fragmentation of motor nerves and microvessels.
Local injection of BaCl2 is an established model of acute injury to study the regeneration of skeletal muscle. However, the mechanism by which BaCl2 causes muscle injury is unresolved. Because Ba2+ inhibits K+ channels, we hypothesized that BaCl2 induces myofiber depolarization leading to Ca2+ overload, proteolysis, and membrane disruption. While BaCl2 spares resident satellite cells, its effect on other tissue components integral to contractile function has not been defined. We therefore asked whether motor nerves and microvessels, which control and supply myofibers, are injured by BaCl2 treatment. The intact extensor digitorum longus (EDL) muscle was isolated from male mice (aged 3-4 months) and irrigated with physiological salt solution (PSS) at 37 °C. Myofiber membrane potential (Vm) was recorded using sharp microelectrodes while intracellular calcium concentration ([Ca2+]i) was evaluated with Fura 2 dye. Isometric force production of EDL was measured in situ, proteolytic activity was quantified by calpain degradation of αII-spectrin, and membrane disruption was marked by nuclear staining with propidium iodide (PI). To test for effects on motor nerves and microvessels, tibialis anterior or gluteus maximus muscles were injected with 1.2% BaCl2 (50-75 μL) in vivo followed by immunostaining to evaluate the integrity of respective tissue elements post injury. Data were analyzed using Students t test and analysis of variance with P ≤ 0.05 considered statistically significant. Addition of 1.2% BaCl2 to PSS depolarized myofibers from - 79 ± 3 mV to - 17 ± 7 mV with a corresponding rise in [Ca2+]i; isometric force transiently increased from 7.4 ± 0.1 g to 11.1 ± 0.4 g. Following 1 h of BaCl2 exposure, 92 ± 3% of myonuclei stained with PI (vs. 8 ± 3% in controls) with enhanced cleavage of αII-spectrin. Eliminating Ca2+ from PSS prevented the rise in [Ca2+]i and ameliorated myonuclear staining with PI during BaCl2 exposure. Motor axons and capillary networks appeared fragmented within 24 h following injection of 1.2% BaCl2 and morphological integrity deteriorated through 72 h. BaCl2 injures myofibers through depolarization of the sarcolemma, causing Ca2+ overload with transient contraction, leading to proteolysis and membrane rupture. Motor innervation and capillarity appear disrupted concomitant with myofiber damage, further compromising muscle integrity.


[Investigation on the gene expression pattern in cervical squamous cell carcinoma of uygur].
To investigate the differentially expressed gene in cervical squamous cell carcinoma of uygur and normal cervical tissue using gene chip. Gene chips containing 2,048 human genes were used to investigate the gene expression pattern of 3 samples of cervical cancer. By applying this gene chip we identified 64 differentially expressed genes in all 3 clinical cervical cancer samples, and we further identified 53 upregulated and 11 downregulated genes for functional analysis. The analysis of gene expression pattern of tumor based on gene chip can realize high-throughput screening of the genes associated with the cervical cancer.


Bovine cesarean section in the field.
Cesarean section is perhaps one of the more challenging surgical procedures performed on the farm; the veterinarian often has far less control over the patient, availability of assistance, and environmental contaminants. A number of variables may affect the successful outcome of this procedure for both the calf and cow; case selection is the most important and often overlooked variable. In addition, patient and surgeon preparation, surgical technique, calf viability at the time of surgery, and exteriorizing the uterus can affect outcome. Good surgical technique including gentle tissue handling, appropriate suture materials and patterns, adequate infolding of the uterine incision to prevent leakage, combined with antibiotics and anti-inflammatory medication when indicated can help minimize detrimental adhesions that may adversely affect the future reproductive efficiency of the cow.


A Comparative Metabolomic Analysis Reveals Difference Manufacture Suitability in "Yinghong 9" and "Huangyu" Teas (Camellia sinensis).
"Yinghong 9" is a widely cultivated large-leaf variety in South China, and the black tea made from it has a high aroma and strong sweet flavor. "Huangyu" is a light-sensitive tea variety with yellow leaves. It was cultivated from the bud-mutation of "Yinghong 9" and has a very low level of chlorophyll during young shoot development. Due to chlorophyll being involved in carbon fixation and assimilation, the changes in photosynthesis might potentially affect the accumulation of flavor metabolites, as well as the quality of "Huangyu" tea. Although "Huangyu" has a golden yellow color and high amino acid content, the mechanism underlying the formation of leaf color and drinking value remains unclear. The widely targeted metabolomics and GC-MS analysis were performed to reveal the differences of key metabolites in fresh and fermented leaves between "Yinghong 9" and "Huangyu." The results showed that tea polyphenols, total chlorophyll, and carotenoids were more abundant in "Yinghong 9." Targeted metabolomics analysis indicated that kaempferol-3-glycoside was more abundant in "Yinghong 9," while "Huangyu" had a higher ratio of kaempferol-3-glucoside to kaempferol-3-galactoside. Compared with "Yinghong 9" fresh leaves, the contents of zeaxanthin and zeaxanthin palmitate were significantly higher in "Huangyu." The contents of α-farnesene, β-cyclocitral, nerolidol, and trans-geranylacetone, which were from carotenoid degradation and involved in flowery-fruity-like flavor in "Huangyu" fermented leaves, were higher than those of "Yinghong 9." Our results indicated that "Huangyu" was suitable for manufacturing non-fermented tea because of its yellow leaf and flowery-fruity-like compounds from carotenoid degradation.


Features of lateral cephalograms associated with difficult laryngoscopy in Japanese children undergoing oral and maxillofacial surgery.
Difficult laryngoscopy and tracheal intubation are occasionally encountered in children with congenital anomalies or micrognathia. However, no study has elucidated anatomical etiology in relation to craniofacial development. Two hundred ten patients aged 8 months-18 years were analyzed. We analyzed the lateral cephalograms of: (i) eight patients in whom laryngoscopy was anticipated as difficult before anesthesia and who were unable to be intubated by direct laryngoscopy and needed fiberoptic bronchoscopy (group A); (ii) 11 patients in whom laryngoscopy was anticipated as difficult before anesthesia but who were able to be intubated by direct laryngoscopy (group B); and (iii) 191 patients in whom laryngoscopy was anticipated as easy before anesthesia and was actually found to be easy (group C). Eight cephalometric parameters were measured and age-parameter relationships were plotted. Logistic regression analysis was performed to characterize group A children for each of the cephalometric variables. Apparently insufficient growth of the mandible was observed in the group A children. Furthermore, the group A children of aged <4 years had undeveloped maxilla, longer mandibular plane-hyoid distances (≥1.3 cm), and deeper depth of the oropharynx; those of aged ≥4 years showed increased inclination of the mandible (sella-nasion plane to mandibular plane angle of ≥46.5°). Difficult laryngoscopy and tracheal intubation are expected in children aged <4 years with lower-positioned hyoid bone caused by caudal larynx as well as undeveloped maxilla and mandible, and in those aged ≥4 years with increased inclination of the mandible as well as undeveloped mandible.


Purification of fusion ferritin from recombinant E. coli using two-step sonications.
Fusion ferritin, combined by heavy chain ferritin (21 kDa) and light chain ferritin (19 kDa), was expressed in recombinant E. coli. The fusion ferritin was easily purified by two-step sonications as well as gel filtration chromatography. SDS-gel electrophoresis showed a single band of 38 kDa with heavy and light chains. MALDI-TOF MS gave a molecular weight of fusion ferritin was 38 kDa. The specific activity and yield of purified fusion ferritin are 0.41 Fe3+ mg mg(-1) of protein and 66%. Those values are larger than the previous ones of 0.2 Fe3+ mg mg(-1) (Kim et al. 2001).


Mechanism of action of therapeutic monoclonal antibodies: promises and pitfalls of in vitro and in vivo assays.
Therapeutic monoclonal antibodies (mAbs) are mostly used in cancer, as anti-infectious agents and as immunomodulatory drugs, and are amongst the most active area of research and development in the pharmaceutical industry. This class of drugs comprises unconjugated antibodies or antibody fragments, antibody-drug conjugates, radio-immunoconjugates and bispecific/trispecific molecules. A better understanding of the mechanism of action of successful mAbs is fundamental for the selection of more active and less toxic mAbs of new generation. Furthermore reliable screening of new compounds at an early stage of preclinical development, for both efficacy and toxicity, should allow the selection of the best molecules at an early stage, and improve the rate of success of this class of drugs. Here we review the major methods that are employed for testing the activity of therapeutic mAbs in vitro and in vivo in small animal models and point out to some of the pitfalls in these assays.


Studies on pig serum lipoproteins. VI. Surface charge of very low density lipoprotein.
The surface electric charge of pig serum very low density lipoprotein (VLDL) is described. By isoelectric focusing VLDL was separated into at least 3 fractions having different isoelectric points and polypeptide distributions. The ultracentrifugal and electron microscopic results indicate that the VLDL was not drastically denatured by Ampholine.


Anomalous Origin of the Right Coronary Artery from the Left Main Coronary Artery in the Setting of Critical Bicuspid Aortic Valve Stenosis.
Anomalous origin of the right coronary artery (ARCA) is an extremely rare cardiac pathology. The coronary artery can potentially course between the aorta and the pulmonary artery, putting the patient at risk for sudden cardiac death. Even rarer is an ARCA that arises from the left main coronary artery (LMCA). To our knowledge, this is the first case where an ARCA arising entirely from the LMCA is associated with critical bicuspid aortic valve stenosis.


Stimulation of mouse resistance to bacterial infection with muramyl dipeptide glycoside.
We studied the capacity of 9 new muramyl dipeptide glycosides to stimulate mouse resistance to experimental sepsis induced by intraperitoneal injection of salmonella typhimurium culture. Preventive intraperitoneal injections of muramyl dipeptide beta-glycosides better improved survival of infected animals compared to the original (unmodified) muramyl dipeptide and muramyl dipeptide alpha-glycosides. The most effective drug muramyl dipeptide beta-heptylglycoside injected during sepsis development also reduced animal mortality, decreased bacterial contamination of the viscera, and increased phagocytic activity of peritoneal macrophages in infected animals.


Clinical efficacy and compliance of sublingual immunotherapy with Dermatophagoides farinae drops in patients with atopic dermatitis.
The oral route for administration of allergen immunotherapy has been explored since the 1900s. We attempted to evaluate the efficacy and safety of sublingual immunotherapy (SLIT) with Dermatophagoides farinae drops in patients with atopic dermatitis (AD) and investigate related factors influencing the patients' compliance. A total of 107 patients with AD were randomized to receive either D. farinae drops plus pharmacotherapy (treatment group, n = 58) or only pharmacotherapy (control group, n = 49). Patients' compliance, the total effective rate, daily drug scores, visual analogue scale (VAS) scores, and IgG4 level were compared respectively between two groups at different time points. Twenty-three cases have withdrawn from the study. The total effective rate in the treatment group (77.78%) was significantly higher than the control group (53.85%) (P < 0.05). The treatment group was significantly reduced in daily drug scores and VAS scores compared with the control group at 12 months follow-up. Meanwhile, at the end of therapy, a significant difference was found in the change in average daily drug scores (difference from 1 month) between two groups (P < 0.01); The treatment group evidently had a higher level of serum-specific IgG4 than the control group at 6 and 12 month of treatment (P < 0.05). Dermatophagoides farinae drops are a safe and effective SLIT for patients with AD, which was proven to reduce the need for medicine. In addition, SLIT could induce a tolerogenic IgG4 response to mite allergen correlated with favorable clinical efficacy. Standardization of specific immunotherapy is essential to ensure therapeutic efficacy and compliance.


Cellular delivery and enhanced anticancer activity of berberine complexed with a cationic derivative of γ-cyclodextrin.
A cationic derivative of γ-cyclodextrin (GCD) modified with propylenediamine (PDA) was synthesized. It was shown that the derivative (GCD-PDA) is mucoadhesive and resistant to the digestion with ∝-amylase indicating that it may constitute an efficient oral delivery vehicle. GCD-PDA formed an inclusion complex with berberine (BBR), an alkaloid displaying a multitude of beneficial physiological effects. The complexed BBR penetrates a lipid membrane easier than the free one. Both uncomplexed BBR and that complexed with GCD-PDA was delivered to normal (NMuMG) and cancerous (4T1) murine mammary gland cells. In the normal cells both free and complexed BBR was homogeneously dispersed in the cytoplasm and was nontoxic up to 131 μM. In the cancerous cells uncomplexed BBR was also homogeneously dispersed but it was toxic to about 25% of cells at 131 μM, while the GCD-PDA/BBR complex was preferably localized in lysosomes and its toxicity doubled at this concentration compared to that of free BBR. Moreover, free BBR and GCD-PDA/BBR showed even more efficient inhibitory effect against murine melanoma (B16-F10) cells than against 4T1 cells.


Current Role and Indications for the Use of Indocyanine Green in Robot-assisted Urologic Surgery.
This mini review article summarizes the many clinical applications of near-infrared fluorescence with indocyanine green in urologic robotic-assisted surgery with a focus on robotic partial nephrectomy.


Rapid measurement of binding constants and heats of binding using a new titration calorimeter.
A new titration calorimeter is described and results are presented for the binding of cytidine 2'-monophosphate (2'CMP) to the active site of ribonuclease A. The instrument characteristics include very high sensitivity, rapid calorimetric response, and fast thermal equilibration. Convenient software is available for instrument operation, data collection, data reduction, and deconvolution to obtain least-squares estimates of binding parameters n, delta H degree, delta S degree, and the binding constant K. Sample through-put for the instrument is high, and under favorable conditions binding constants as large as 10(8) M-1 can be measured. The bovine ribonuclease A (RNase)/2'CMP system was studied over a 50-fold range of RNase concentration and at two different temperatures. The binding constants were in the 10(5) to 10(6) M-1 range, depending on conditions, and heats of binding ca. -15,000 cal/mol. Repeat determinations suggested errors of only a few percent in n, delta H degree, and K values over the most favorable concentration range.


Pulpal survival in replanted and autotransplanted apicoectomized mature teeth of dogs with prepared nutritional canals.
In the present study, an attempt was made to improve the possibilities for rapid revascularization and original pulp tissue survival in replanted and autotransplanted mature dog teeth by increasing the contact area between the pulp and the vascularized periradicular tissues. In 12 teeth, the root tip was resected and 3 additional nutritional canals were prepared in the apical 1/3 of the root at the time of the operation. Another 12 teeth were replanted or autotransplanted with intact roots. After an observation time of 120 days, the teeth were studied with microangiographic and histologic techniques. 11 of the teeth that were replanted or autotransplanted with intact roots showed total pulpal necrosis. Partial or total pulpal revascularization and repair was seen in all apicoectomized teeth with nutritional canals. The revascularized area of the pulp was somewhat larger in the replanted compared to the autotransplanted group of teeth. Signs of survival of the original pulp tissue were not seen. A comparison of the findings with those of previous studies on replanted and autotransplanted teeth with apicoectomized roots but without additional canals shows that the revascularization of the pulp did not proceed more rapidly in the apicoectomized teeth in the present study, although the contact area between the pulp and the periradicular tissues was enlarged through the preparation of the 3 artificial nutritional canals.


Integrative analysis workflow for the structural and functional classification of C-type lectins.
It is important to understand the roles of C-type lectins in the immune system due to their ubiquity and diverse range of functions in animal cells. It has been observed that currently confirmed C-type lectins share a highly conserved domain known as the C-type carbohydrate recognition domain (CRD). Using the sequence profile of the CRD, an increasing number of putative C-type lectins have been identified. Hence, it is highly needed to develop a systematic framework that enables us to elucidate their carbohydrate (glycan) recognition function, and discover their physiological and pathological roles. Presented herein is an integrated workflow for characterizing the sequence and structural features of novel C-type lectins. Our workflow utilizes web-based queries and available software suites to annotate features that can be found on the C-type lectin, given its amino acid sequence. At the same time, it incorporates modeling and analysis of glycans - a major class of ligands that interact with C-type lectins. Thereafter, the results are analyzed together with context-specific knowledge to filter off unlikely predictions. This allows researchers to design their subsequent experiments to confirm the functions of the C-type lectins in a systematic manner. The efficacy and usefulness of our proposed immunoinformatics workflow was demonstrated by applying our integrated workflow to a novel C-type lectin -CLEC17A - and we report some of its possible functions that warrants further validation through wet-lab experiments.


Quantifying the dosimetric effects of neck contour changes and setup errors on the spinal cord in patients with nasopharyngeal carcinoma: establishing a rapid estimation method.
The purpose of this study was to quantify the effect of neck contour changes and setup errors on spinal cord (SC) doses during the treatment of nasopharyngeal carcinoma (NPC) and to establish a rapid dose estimation method. The setup errors and contour changes in 60 cone-beam computed tomography (CBCT) images of 10 NPC patients were analysed in different regions of the neck (C1-C3, C4-C5 and C6-C7). The actual delivered dose to the SC was calculated using the CBCT images, and univariate simulations were performed using the planning CT to evaluate the dose effects of each factor, and an index ${\mathrm{Dmax}}_{\mathrm{displaced}}$ was introduced to estimate the SC dose. Compared with the planned dose, the mean (maximum) Dmax increases in the C1-C3, C4-C5 and C6-C7 regions of the SC were 2.1% (12.3%), 1.8% (8.2%) and 2.5% (9.2%), respectively. The simulation results showed that the effects of setup error in the C1-C3, C4-C5 and C6-C7 regions were 1.5% (9.7%), 0.9% (8.2%) and 1.3% (6.3%), respectively, and the effects of contour change were 0.4% (1.7%), 0.7% (2.5%) and 1.5% (4.9%), respectively. The linear regression model can be used to estimate the dose effect of contour changes (R2 > 0.975) and setup errors (R2 = 0.989). Setup errors may lead to a significant increase in the SC dose in some patients. This study established a rapid dose estimation method, which is of great significance for the daily dose evaluation and the adaptive re-planning trigger of the SC.


Adhesion tunes speed and persistence by coordinating protrusions and extracellular matrix remodeling.
Cell migration through 3D environments is essential to development, disease, and regeneration processes. Conceptual models of migration have been developed primarily on the basis of 2D cell behaviors, but a general understanding of 3D cell migration is still lacking due to the added complexity of the extracellular matrix. Here, using a multiplexed biophysical imaging approach for single-cell analysis of human cell lines, we show how the subprocesses of adhesion, contractility, actin cytoskeletal dynamics, and matrix remodeling integrate to produce heterogeneous migration behaviors. This single-cell analysis identifies three modes of cell speed and persistence coupling, driven by distinct modes of coordination between matrix remodeling and protrusive activity. The framework that emerges establishes a predictive model linking cell trajectories to distinct subprocess coordination states.


Correlations between Majorana fermions through a superconductor.
We consider a model of ballistic quasi-one-dimensional semiconducting wire with intrinsic spin-orbit interaction placed on the surface of a bulk s-wave superconductor (SC), in the presence of an external magnetic field. This setup has been shown to give rise to a topological superconducting state in the wire, characterized by a pair of Majorana-fermion (MF) bound states formed at the two ends of the wire. Here, we demonstrate that besides the well-known direct-overlap-induced energy splitting, the two MF bound states may hybridize via elastic tunneling processes through virtual quasiparticle states in the SC, giving rise to an additional energy splitting between MF states from the same as well as from different wires.


Dihydropyridine binding of the calcium channel complex from skeletal muscle is modulated by subunit interaction.
The dihydropyridine-binding subunit alpha 1 of the calcium channel complex from rabbit skeletal muscle can be partially depleted from the alpha 2 delta beta-complex using wheat germ agglutinin-affinity chromatography. This depletion of the alpha 1 from the other subunits leads to a loss of dihydropyridine-binding, which can be fully reconstituted by repletion of the alpha 1 with the other subunits. Reassembly of these subunits results in an increase in the Kd and Bmax of the dihydropyridine-binding indicating that the non-dihydropyridine-binding subunits influence dihydropyridine-binding. The affinity of the alpha 1 subunit for the other subunits was determined to be approximately 35 nM. Since the free alpha 1 subunit will not bind to the beta subunit alone, there is evidence, given the selective partitioning of the beta subunit to the lectin-bound subunit pool, that either beta binds with higher affinity to the alpha 2 delta-complex than to the free alpha 1 subunit or that the bound alpha 1 creates or modulates beta-binding. This indicates a functional high affinity interaction between the dihydropyridine-binding alpha 1 subunit and the alpha 2 delta beta-complex.


Depletion-interaction-driven assembly of golf ball-like particles for development of colloidal macromolecules.
Colloidal molecules created by clustering monodisperse particles are a significant model system of atoms and molecules in colloidal scale. To attain modelling of complex or high-molecular-weight molecules such as hyper-branched polymers and proteins, it is required to develop a new assembling system which can prepare three-dimensionally designed colloidal molecules. In this study, we proposed an approach for complex colloidal molecules created by association between golf ball-like particles and spherical particles via depletion interaction. Several golf ball-like particles joined together, which formed joined particle assemblies at the spherical particles acting as their joints in a depletant solution. The number of golf ball-like particles in a particle assembly was increased by increasing the concentration of the depletant, leading to the formation of branched colloidal chains of the golf ball-like particles. Because the golf ball-like particles in the colloidal chain flexibly rotated at their joints, the conformation of the chains varied in the depletant solution. The present results demonstrated that the golf-ball like particle that can be joined to form colloidal macromolecules with high association number and high flexibility will be a promising building block for complex colloidal model systems.


Characterization of parotid gland tissue: a description of an MRI protocol set-up and results of in-vivo applications.
A reliable protocol for proton T2 mapping of the parotid region was set up for future characterization of parotid gland disease. A Carr-Purcell-Meiboom-Gill sequence, phase compensated, available on our 1.5 T imager, was selected and acquisition parameters were chosen on the basis of tests performed on phantoms (agarose-doped gels with T2 in the physiological range). Some experiments were carried out to evaluate the accuracy of T2 calculations for selective and nonselective refocussing pulses, for image uniformity corrections, and for different situations of slice shift and repetition times. The chosen protocol was then applied to in vivo evaluations to check the long-term precision by means of repeated measurements performed on the same subject over a 2-month period. Two or more reference gels were positioned both in the phantom and volunteer at the edge of the field-of-view (FOV). Image postprocessing consisted of an automatic procedure, written by the authors in Fortran 77, that selected the best fit for each pixel between mono- and biexponential decay models, and prepared four parametric images (T2 and Rho slow and fast contribution, Rho being a function of proton density and of T1) that may be used for future elaborations. The phantom experiment results showed an accuracy of 2.5% if a linear correction was performed using the reference gels at the edge of the FOV. No significant differences in accuracy were found between selective and nonselective refocussing pulse, and a homogeneity correction was not demonstrated necessary. The measurements performed on four volunteers showed that the best decaying model for healthy parotid tissue was monoexponential. Evaluated T2 resulted 80.18 +/- 6.11 ms (72.96 +/- 4.97 ms for uncorrected results). Long-term reproducibility of the group of measurements from one volunteer, summarizing all the measurement errors, ranged from 0.9 to 8.5%. The two-way ANOVA that was carried out considering the two classes of volunteers and of parotid positions (right or left) showed that differences found between the two parotids were not significant, while T2 differences among individuals are significant if a probability level higher than 1.1% is accepted. As in this case, the main source of error can be attributed to the biological variations among individuals. Future statistics collected on patients for the T2 evaluations of the pathologic tissue will clarify whether the T2 relaxation is a sufficient parameter for T2 discrimination of healthy and pathologic tissue.


Rituximab prevents an anamnestic response in patients with cryptic sensitization to HLA.
Some patients sensitized to HLA antigens do not have antibody present in serum specimens that are available before transplantation. However, such patients are at risk for an anamnestic response resulting from a proinflammatory response to the trauma of transplant surgery. Quantifying HLA-specific B cells provides a way to identify these patients and provide treatment to prevent an anamnestic response. B cells were isolated before transplantation from 59 patients, 20 of whom were treated with rituximab at the time of transplantation. Ninety-nine tests were performed to quantify HLA-specific B cells by staining with HLA tetramers. Patients were considered sensitized or nonsensitized based on the frequencies of HLA-specific B cells. Pretransplantation and posttransplantation sera were tested for the detection of antibody specific for the tetramer antigen. Of the 24 cases where patients were considered sensitized to HLA antigens but did not have antibody before transplantation, no posttransplantation antibody to the tetramer antigen was detected in 10 cases when patients were treated with rituximab, but antibody was detected in 13 of 16 cases when there was no rituximab treatment (P=0.00006). The mean frequencies of B cells specific for HLA-B7 were the same in rituximab-treated patients who did not make antibody and in nontreated patients who did make antibody (6.0% vs. 5.7%; P=0.8). Elimination of peripheral HLA-specific B cells in patients who are sensitized to HLA antigens but lacking detectable antibody abrogates an anamnestic response.


MIRVs and the strategic balance.
A quantitative treatment shows that the nuclear balance will not necessarily be upset if both the United States and the Soviet Union replace missile launchers with single warheads by multiple independently targetable re-entry vehicles.