Roles of fibroblasts from the interface zone in invasion, migration, proliferation and apoptosis of gastric adenocarcinoma.
Interface zone fibroblasts (INFs) are very important in the progression and metastasis of tumours but their effect on the invasion and migration of gastric cancer cells is still unclear. Primary fibroblasts were isolated from the distal normal zone (normal zone fibroblasts, NFs), interface zone (INFs) and tumour zone (cancer-associated fibroblasts, CAFs) of 60 human gastric carcinoma tissue samples. The crosstalk between these fibroblasts and human gastric cancer MGC-803 cells was evaluated using an indirect co-culture model in vitro. A high level of fibroblast activation protein (FAP) in the invasion front of gastric cancer was found in the gastric cancer tissue samples and no FAP expression was found in 20 normal gastric tissue samples by immunohistochemistry. High FAP expression was associated with Lauren classification, degree of differentiation, tumour node metastasis stage and depth of tumour invasion (p<0.05 or p<0.01). INFs promoted invasion and migration of MGC-803 cells. The number of invasions in INFs, CAFs and NFs were 120.10±27.53 (95% CI 102.12 to 138.10), 63.00±14.80 (95% CI 53.33 to 72.67) and 14.22±6.20 (95% CI 10.17 to 18.27), respectively; the number of invasions in INFs were 8.45-fold and 1.89-fold higher than those in NFs and CAFs, respectively (p<0.05). The number of migrations in INFs, CAFs and NFs were 118.00±16.83 (95% CI 107.00 to 129.00), 61.00±16.36 (95% CI 50.31 to 71.69) and 24.00±11.52 (95% CI 16.47 to 31.53), respectively; the number of migration in INFs were 4.91-fold and 1.92-fold higher than those in NFs and CAFs, respectively (p<0.05). INFs also significantly promoted cell proliferation and inhibited apoptosis in MGC-803 cells compared with NFs and CAFs (p<0.05). These findings indicate that INFs exhibit a more robust biological modulatory activity than CAFs and NFs. INFs may be a key factor leading to tumour progression and metastasis and may be of use as a tool for post-treatment surveillance.


The status of diabetic embryopathy.
Diabetic embryopathy is a theoretical enigma and a clinical challenge. Both type 1 and type 2 diabetic pregnancy carry a significant risk for fetal maldevelopment, and the precise reasons for the diabetes-induced teratogenicity are not clearly identified. The experimental work in this field has revealed a partial, however complex, answer to the teratological question, and we will review some of the latest suggestions.


Individual food-hoarding decisions in a nonterritorial coal tit population: the role of social context.
Among the Paridae, food hoarding is thought to be strongly associated with the exclusive use of territories by winter groups, although it has also been described in populations with loose social systems. However, detailed data on such populations are scarce. To identify the mechanisms underlying individual storing decisions, I studied hoarding behaviour in a nonterritorial, high-density coal tit, Parus ater, population in a subalpine forest. The presence of close neighbours (within 5 m) had the strongest, negative influence on caching probability, whereas more distant neighbours foraging in the same flock did not affect the probability of caching. Adults concentrated their stores in the centre of their home ranges. Caching location, but not caching intensity, was affected by the time of day. Coal tits took longer, and travelled further, to cache food in the inner parts of trees than in the outer parts. Resident adults stored in inner, safer caching locations more often than juvenile residents and transients. Differences in hoarding effort according to the storing substrate, and the daily storing location pattern of juvenile residents and transients, suggest that stores have a different use depending on where they are located. Therefore, my results show that hoarding is compatible with a nonterritorial, nonbreeding social system; hoarding could thus have originated in an ancient, nonterritorial, but sedentary, tit species. Copyright 2000 The Association for the Study of Animal Behaviour.


Studies on the sex-specific lethals of Drosophila melanogaster. IV. Gynandromorph analysis of three male-specific lethals, mle, msl-2(27) and mle(3)132.
Mutants at three male-specific lethal loci of Drosophila melanogaster (mle, msl-2(27) and mle(3)132) were examined by gynandromorph analysis. In all cases only a very few gynandromorphs with small X/O patches appeared. Most of these small X/O patches were in the abdomen, and the structures in these X/O regions were reduced in size. These results indicate that the primary effects of these mutants are not on any particular organs or tissues, but rather on individual cells, mle and msl-2 have been shown by BELOTE and LUCCHESI (1980a) to be defective in dosage compensation in X/Y males. We suggest that this dosage-compensation defect results in the expression of Minute-like phenotypes in X/O cells, and hence results in the death of X/O males and flies with large X/O tissue areas.


Phylogeography of the rice frog, Fejervarya multistriata (Anura: Ranidae), from China based on mtDNA D-loop sequences.
The rice frog, Fejervarya multistriata, is an amphibian widely distributed in China. In this study, we sampled the species across its distributional area in China and sequenced the mtDNA D-loop to investigate the genetic diversity and geographical pattern of the frog population. The results revealed 38 haplotypes in the population, with K2P values varying from 0.19% to 4.22%. Both a phylogenetic analysis and a nested clade analysis (NCA) detected two geographically isolated lineages respectively distributed around the Yangtze drainage (Yangtze lineage) and the south of China (southern lineage). NCA inferred a contiguous range expansion within the Yangtze lineage and allopatric fragmentation within the southern lineage, which might be partly due to the limited samples from this lineage. Accordingly, Fu's Fs test also indicated a population expansion after glacial movement. Therefore, we assumed that the species history responding to glacial events shaped the present population pattern of F. multistriata on the Chinese mainland.


The protein kinases TPL2 and EGFR contribute to ERK1/ERK2 hyperactivation in CFTRΔF508-expressing airway epithelial cells exposed to Pseudomonas aeruginosa.
Excessive inflammation and Pseudomonas aeruginosa infection are two major characteristics of cysticfibrosis (CF) lung disease. In this manuscript, we describe a novel mechanism of ERK1/ERK2 activationand CXCL8 expression in airway epithelial cells (AECs) lacking functional CFTR. In both non-CF and CFAECs, the protein kinase TPL2 is required for ERK1/ERK2 MAPK activation. However, we have found that EGFR is strongly phosphorylated in the airway epithelium of CF lung and contributes to ERK1/ERK2 MAPK activation in CF AECs exposed to P. aeruginosa diffusible material (PsaDM). Moreover, PsaDM stimulates the expression of the EGFR pro-ligand HB-EGF more strongly, and in a sustained manner, in CF AECs compared to non-CF cells. Finally, although both non-CF and CF AECs expresses CXCL8 in response to PsaDM, the levels of CXCL8 are higher and EGFR plays a more important role in regulating CXCL8 synthesis in CF AECs. Together, our finding shows that in addition to the TLR-mediated TPL2 activation of ERK1/ERK2, an additional pathway contributing to ERK1/ERK2 activation is triggered by infection of CF AECs: the EGFR signaling pathway. This second pathway may contribute to excessive inflammation observed in CF.


Antimicrobial Activity and Phytochemical Constituents of Leaf Extracts of Cassia auriculata.
Plants produce a wide variety of phytochemical constituents, which are secondary metabolites and are used either directly or indirectly in the pharmaceutical industry. 'For centuries, man has effectively used various components of plants or their extracts for the treatment of many diseases, including bacterial infections. In the present study methanol, chloroform and aqueous extracts of Cassia auriculata leaf were subjected for antimicrobial activity by well-diffusion method against six bacterial strains namely Bacillus cereus, Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa and Proteus mirabilis. The results revealed that the methanol and chloroform extracts exhibited strong inhibitory activity against all the tested organisms (zone of inhibition of 12-20 mm), except Pseudomonas aeruginosa (zone of inhibition 10 mm or nil). The aqueous extracts showed moderate activity by 'Zone of inhibition ≤12 or nil). The extracts were screened for their phytochemical constituents by standard protocols' and were shown to contain carbohydrates, proteins, alkaloids, flavonoids, steroids, saponins and tannins. The antibacterial activity of these extracts is possibly linked to the presence of flavonoids, steroid, saponins and/or tannins. Further studies are needed to determine the precise active principles from Cassia auriculata.


Plasmid transformation of Bacillus sphaericus 1593.
Plasmids pUB110 and pBC16 were introduced by protoplast transformation into the entomocidal bacterium Bacillus sphaericus 1593. Transformants expressed the antibiotic resistance determinants present on the plasmid and exhibited sporulation frequencies and larvicidal toxicities which were equivalent to those characteristic of the parent strain. These transformations constitute the first report of genetic transfer in B. sphaericus.


Evidence of an additional centre of apple domestication in Iran, with contributions from the Caucasian crab apple Malus orientalis Uglitzk. to the cultivated apple gene pool.
Divergence processes in crop-wild fruit tree complexes in pivotal regions for plant domestication such as the Caucasus and Iran remain little studied. We investigated anthropogenic and natural divergence processes in apples in these regions using 26 microsatellite markers amplified in 550 wild and cultivated samples. We found two genetically distinct cultivated populations in Iran that are differentiated from Malus domestica, the standard cultivated apple worldwide. Coalescent-based inferences showed that these two cultivated populations originated from specific domestication events of Malus orientalis in Iran. We found evidence of substantial wild-crop and crop-crop gene flow in the Caucasus and Iran, as has been described in apple in Europe. In addition, we identified seven genetically differentiated populations of wild apple (M. orientalis), not introgressed by the cultivated apple. Niche modelling combined with genetic diversity estimates indicated that these wild populations likely resulted from range changes during past glaciations. This study identifies Iran as a key region in the domestication of apple and M. orientalis as an additional contributor to the cultivated apple gene pool. Domestication of the apple tree therefore involved multiple origins of domestication in different geographic locations and substantial crop-wild hybridization, as found in other fruit trees. This study also highlights the impact of climate change on the natural divergence of a wild fruit tree and provides a starting point for apple conservation and breeding programmes in the Caucasus and Iran.


Pigs with the dominant white coat color phenotype carry a duplication of the KIT gene encoding the mast/stem cell growth factor receptor.
Comparative mapping data suggested that the dominant white coat color in pigs may be due to a mutation in KIT which encodes the mast/stem cell growth factor receptor. We report here that dominant white pigs lack melanocytes in the skin, as would be anticipated for a KIT mutation. We found a complete association between the dominant white mutation and a duplication of the KIT gene, or part of it, in samples of unrelated pigs representing six different breeds. The duplication was revealed by single strand conformation polymorphism (SSCP) analysis and subsequent sequence analysis showing that white pigs transmitted two nonallelic KIT sequences. Quantitative Southern blot and quantitative PCR analysis, as well as fluorescence in situ hybridization (FISH) analysis, confirmed the presence of a gene duplication in white pigs. FISH analyses showed that KIT and the very closely linked gene encoding the platelet-derived growth factor receptor (PDGFRA) are both located on the short arm of Chromosome (Chr) 8 at band 8p12. The result revealed an extremely low rate of recombination in the centromeric region of this chromosome, since the closely linked (0.5 cM) serum albumin (ALB) locus has previously been in situ mapped to the long arm (8q12). Pig Chr 8 shares extensive conserved synteny with human Chr 4, but the gene order is rearranged.


Can online self-reports assist in real-time identification of influenza vaccination uptake? A cross-sectional study of influenza vaccine-related tweets in the USA, 2013-2017.
The Centers for Disease Control and Prevention (CDC) spend significant time and resources to track influenza vaccination coverage each influenza season using national surveys. Emerging data from social media provide an alternative solution to surveillance at both national and local levels of influenza vaccination coverage in near real time. This study aimed to characterise and analyse the vaccinated population from temporal, demographical and geographical perspectives using automatic classification of vaccination-related Twitter data. In this cross-sectional study, we continuously collected tweets containing both influenza-related terms and vaccine-related terms covering four consecutive influenza seasons from 2013 to 2017. We created a machine learning classifier to identify relevant tweets, then evaluated the approach by comparing to data from the CDC's FluVaxView. We limited our analysis to tweets geolocated within the USA. We assessed 1 124 839 tweets. We found strong correlations of 0.799 between monthly Twitter estimates and CDC, with correlations as high as 0.950 in individual influenza seasons. We also found that our approach obtained geographical correlations of 0.387 at the US state level and 0.467 at the regional level. Finally, we found a higher level of influenza vaccine tweets among female users than male users, also consistent with the results of CDC surveys on vaccine uptake. Significant correlations between Twitter data and CDC data show the potential of using social media for vaccination surveillance. Temporal variability is captured better than geographical and demographical variability. We discuss potential paths forward for leveraging this approach.


Broadening the Spectrum of Ehlers Danlos Syndrome in Patients With Congenital Adrenal Hyperplasia.
The contiguous gene deletion syndrome (CAH-X) was described in a subset (7%) of congenital adrenal hyperplasia (CAH) patients with a TNXA/TNXB chimera, resulting in deletions of CYP21A2, encoding 21-hydroxylase necessary for cortisol biosynthesis, and TNXB, encoding the extracellular matrix glycoprotein tenascin-X (TNX). This TNXA/TNXB chimera is characterized by a 120-bp deletion in exon 35 and results in TNXB haploinsufficiency, disrupted TGF-β signaling, and an Ehlers Danlos syndrome phenotype. The objective of the study was to determine the genetic status of TNXB and resulting protein defects in CAH patients with a CAH-X phenotype but not the previously described TNXA/TNXB chimera. Design, Settings, Participants, and Intervention: A total of 246 unrelated CAH patients were screened for TNXB defects. Genetic defects were investigated by Southern blotting, multiplex ligation-dependent probe amplification, Sanger, and next-generation sequencing. Dermal fibroblasts and tissue were used for immunoblotting, immunohistochemical, and coimmunoprecipitation experiments. The genetic and protein status of tenascin-X in phenotypic CAH-X patients was measured. Seven families harbor a novel TNXB missense variant c.12174C>G (p.C4058W) and a clinical phenotype consistent with hypermobility-type Ehlers Danlos syndrome. Fourteen CAH probands carry previously described TNXA/TNXB chimeras, and seven unrelated patients carry the novel TNXB variant, resulting in a CAH-X prevalence of 8.5%. This highly conserved pseudogene-derived variant in the TNX fibrinogen-like domain is predicted to be deleterious and disulfide bonded, results in reduced dermal elastin and fibrillin-1 staining and altered TGF-β1 binding, and represents a novel TNXA/TNXB chimera. Tenascin-X protein expression was normal in dermal fibroblasts, suggesting a dominant-negative effect. CAH-X syndrome is commonly found in CAH due to 21-hydroxylase deficiency and may result from various etiological mechanisms.


Intralitter variation of neonatal rat lung morphology following prenatal maternal hypervitaminosis A.
Prenatal exposure to excess vitamin A (160,000 USP units/day) from days 15 through 19 of gestation results in altered lung morphology, characterized by thickened septal walls and/or large areas of atelectasis and an associated high neonatal mortality. Marked variability in both morphological and physiological expression from this prenatal insult is commonly seen between litters and littermates, making analyses difficult. The present study documents morphological intralitter variation observed in vitamin A-exposed 2-day-old rats as compared to controls. Representative midhilar coronal histological sections of each lung were examined by two methods and the results compared. The first method, although less sensitive, demonstrated that five out of eight experimental rat lungs had a significantly greater percentage of tissue to airway space as compared with undisturbed controls (greater than 43%). The second method, using several morphological criteria and a grid system to score parenchyma into classifications based on the degree of morphological variation and projected functional capability, clearly found significantly increased percentages of poor or nonfunctional lung tissue (P greater than 0.01) in seven out of eight pups exposed to excess vitamin A. This method of ranking the severity of adverse effects on tissue morphology allowed identification of drug-affected newborn and provided a means to quantify the alterations. Such a means for identifying affected individuals from littermates is essential to research methodologies for detecting substances which, when administered during fetal life, produce decrements of postnatal function but no gross structural abnormalities.


Epitopes associated with the MHC restriction site of T cells. II. Somatic generation of Iat epitopes on T cells in radiation bone marrow chimeras.
We described in this paper systematic alterations in the expression of unique I region controlled epitopes on helper T cells (Th) in chimeras according to the changes in their H-2 restriction specificity. Taking advantage of the reactivity of monoclonal antibodies (anti-Iat) putatively specific for the epitopes indirectly controlled by I region and expressed in association with the Iak restriction site of Th, we examined the alterations of these epitopes on Th cells from various bone marrow chimeras. Iatk epitopes were physiologically expressed on Iak-restricted but not on Iab-restricted Th cells in (H-2k X H-2b)F1 mice. In the chimeric condition, the H-2k-restricted Th of B6----F1 chimera acquired the expression of Iatk even though B6 Th is unable to express Iatk when developed under the physiologic condition. Iatk are also found on Th of fully allogeneic chimera of B6----C3H, whereas Th cells of C3H----B6 completely lost the Iatk expression. These results indicate that Iat epitopes originally defined as unique I region-controlled determinants selectively expressed on T cells are not encoded by the I region genes but are associated with the T cell receptor that sees the self Ia. The epitopes undergo the adaptive alterations according to the acquisition of a new MHC restriction. This is the first example to demonstrate the epitope associated with T cell receptor which undergo the systematic adaptive differentiation.


Effects of dietary phosphorus concentration during the transition period on plasma calcium concentrations, feed intake, and milk production in dairy cows.
Our aim was to evaluate the effects of a low or high dietary phosphorus (P) concentration during the dry period, followed by either a high or low dietary P concentration during the first 8 wk of lactation, on plasma Ca concentrations, feed intake, and lactational performance of dairy cattle. Sixty pregnant multiparous Holstein Friesian dairy cows were assigned to a randomized block design with repeated measurements and dietary treatments arranged in a 2 × 2 factorial fashion. The experimental diets contained 3.6 (Dry-HP) or 2.2 (Dry-LP) g of P/kg of dry matter (DM) during the dry period, and 3.8 (Lac-HP) or 2.9 (Lac-LP) g of P/kg of DM during 56 d after calving period. In dry cows, plasma Ca concentrations were 3.3% greater when cows were fed 2.2 instead of 3.6 g of P/kg of DM. The proportion of cows being hypocalcemic (plasma Ca concentrations <2 mM) in the first week after calving was lowest with the low-P diets both during the dry period and lactation. Plasma Ca concentrations in wk 1 to 8 after calving were affected by dietary P level in the dry period and in the lactation period, but no interaction between both was present. Feeding Dry-LP instead of Dry-HP diets resulted in 4.1% greater plasma Ca values, and feeding Lac-LP instead of Lac-HP diets resulted in 4.0% greater plasma Ca values. After calving, plasma inorganic phosphate (Pi) concentrations were affected by a 3-way interaction between sampling day after calving, and dietary P levels during the dry period and lactation. From d 1 to d 7 postpartum, cows fed Lac-HP had increased plasma Pi concentrations, and the rate appeared to be greater in cows fed Dry-LP versus Dry-HP. In contrast, plasma Pi concentrations decreased from d 1 to d 7 postpartum in cows fed Lac-LP, and this decrease was at a higher rate for cows fed Dry-HP versus Dry-LP. After d 7, plasma Pi concentrations remained rather constant at 1.5 to 1.6 mM when cows received Lac-HP, whereas with Lac-LP plasma Pi concentrations reached stable levels (i.e., 1.3-1.4 mM) at d 28 after calving. Milk production, DM intake, and milk concentrations of P, Ca, fat, protein, and lactose were not affected by any interaction nor the levels of dietary P. It is concluded that the feeding of diets containing 2.2 g of P/kg of DM during the last 6 wk of the dry period and 2.9 g of P/kg of DM during early lactation increased plasma Ca levels when compared with greater dietary P levels. These low-P diets may be instrumental in preventing hypocalcemia in periparturient cows and do not compromise DM intake and milk production. Current results suggest that P requirements in dairy cows during dry period and early lactation can be fine-tuned toward lower values than recommended by both the National Research Council and the Dutch Central Bureau for Livestock Feeding. Caution however is warranted to extrapolate current findings to entire lactations because long-term effects of feeding low-P diets containing 2.9 of g/kg of DM on production and health needs further investigation.


AF automatic classification based on different time-delay values of the recurrence plot.
Recurrence plot (RP) has been widely used to transform 1D ECG waveforms into 2D images and explore the recurrence patterns of the electrical signals generated by the cardiac system. However, selecting the critical parameter time-delay τ for creating an RP has not been well-reported. In this work, we investigated the influence of different τ values on the RP-based AF prediction. And the results illustrated that the best classification performance could be achieved at τ=1 with full characters of the dynamic system.Clinical Relevance-This work established the AF classification system based on recurrence features and found the optimal parameters of the recurrence plot improving the ECG-based classification performance.


The behavior of organic components in copper recovery from electroless plating bath effluents using 3D electrode systems.
An electrochemical method was applied for the recovery of copper both from the spent solutions and from the rinse waters of electroless copper plating baths, containing copper sulfate, formaldehyde, quadrol, and NaOH. Experiments were conducted in a rotating packed cell (Rollschichtzelle) to investigate the effects of current density, electrolyte composition, temperature, and pH on the copper recovery. All the copper (final CCu=0.1 ppm) was recovered from the waste and rinse waters of chemical copper plating plants with 70% current efficiency by the electrochemical treatment in a rotating packed cell at 130 A/m2 current density, room temperature, with 5mm diameter cathode granules, with the presence of formaldehyde, and with a specific energy consumption of 3.2-3.5 kW h/kg Cu. On the other hand, final copper concentrations of 5 ppm were reached with 62% current efficiency and 5.5-5.8 kW h/kg Cu specific energy consumption, with electrolytes containing no formaldehyde.


Neuropsychological patterns and language deficits in 20 consecutive cases of autopsy-confirmed Alzheimer's disease.
A retrospective chart review of clinical symptoms was done for 20 consecutive patients in whom postmortem examination had revealed senile plaques and neurofibrillary tangles in a distribution consistent with Alzheimer's disease. All patients had met clinical diagnostic criteria for probable Alzheimer's disease. On initial examination, 1 to 14 years beyond putative onset of the dementia, all patients displayed at least some memory impairment. In 16 patients, disturbances of attention or recent memory were among the most salient features. In two patients, language disturbances, and in two others, visuospatial deficits, were more prominent than difficulties with memory and attention. On initial examination, 17 of the 20 patients displayed word-finding difficulties, characteristically in the context of a fluent, anomic aphasia. All of the 12 reexamined patients demonstrated progressive, although variable, deterioration. In general, the initial salient deficit remained salient during much of the disease course. Language comprehension was spared in the earlier stages but eventually deteriorated. Severe deficits emerged in all major cognitive domains as the disease reached the terminal stages. Nonfluent aphasias (eg, Broca's aphasia) were not observed even in the advanced stages of the disease.


Single center experience of endoscopic submucosal dissection (ESD) in early Barrett's adenocarcinoma.
Endoscopic mucosal resection (EMR) or radical surgical resection are the standard treatment options for patients with early Barrett's adenocarcinoma (EBAC). Endoscopic submucosal dissection (ESD) is a new endoscopic technique, which allows--in contrast to EMR--endoscopic en-bloc resection of neoplastic lesions greater than 2 cm with complete histological evaluation of the resected specimen. In contrast to Western countries, Barrett's esophagus is less common in Asia indicating the low volume of published data of ESD in EBAC in Japanese series. Therefore, the aim of the present study is to describe the results of ESD in patients with EBAC performed in a German tertiary referral center. Between November 2009 and April 2014 ESDs were performed in 22 patients with histologically proven EBAC. Data were given for the en-bloc, the R0, the R0 en-bloc, and the curative resection rate as well as for the complication and the local recurrence rate. ESD was technically possible in all of the 22 patients. 20 of the resected EBAC were mucosal carcinomas, whereas in two patients the tumor showed submucosal invasion. The en-bloc, R0, R0 en-bloc, and curative resection rates were 95.5, 81.8, 81.8 %, and 77.3 %, resp. Complication rate was 27.3 % (perforation n = 1, bleeding n = 2, stenosis n = 3). In case of curative tumor resection, only one local tumor recurrence (5.9 %) occurred after a medium follow-up of 1.6 years. Despite the small number of patients and a relatively short follow-up, the present data underline the value of ESD, especially in case of curative resections in the definite and less invasive therapy of EBAC. Attention should be drawn toward subsquamous extension of EBAC requiring a sufficient safety margin as an obligate condition for curative R0 resections. Due to the required learning curve and the management of potential complications, ESD should be restricted to greater endoscopic centers.


Transport of acetate and butyrate in the hind-gut of rabbits.
1. Everted sacs of colonic mucosa from the wild rabbit did not transport acetate against a concentration gradient, but permeation down a concentration gradient did occur. 2. Butyrate was shown to permeate sheets of caecal mucosa with some conversion into ketone bodies during the passage. More ketone bodies were released from the serosal surface of the sheet than from the epithelial surface, regardless of the side to which the butyrate was added. 3. During absorption in vivo of [1-(14)C]butyrate from the caecum the ratio of [(14)C]butyrate to (14)C-labelled ketone bodies in the blood collected from the appropriate caecal vein was 13. The extent of conversion of butyrate into ketone bodies during absorption in vivo was less than that observed during transport in vitro. Possible explanations of these differences are discussed. 4. The relative concentrations of the individual volatile fatty acids in blood collected from the caecal vein during absorption in vivo were similar to those present in contents from the caecum. 5. The results are compared with similar transport and absorption studies on the ruminant fore-stomach.


Cingulum bundle diffusivity and delusions of reference in first episode and chronic schizophrenia.
The goal of this study was to assess integrity of the cingulum bundle in patients diagnosed with first episode schizophrenia, chronic schizophrenia, and matched controls as well as to determine the relationship between diffusion measures of cingulum bundle integrity and severity of patients' delusions of reference. Participants, who comprised 18 first episode patients, 20 chronic patients, and two groups of matched controls (20 subjects in each), underwent 3 T MRI diffusion tensor imaging. Patients diagnosed with schizophrenia (chronic+first episode) showed decreased fractional anisotropy in the right cingulum bundle compared with controls. First episode patients exhibited higher trace bilaterally, compared with matched controls, and on the left compared with chronic patients. Axial diffusivity was increased in first episode patients, bilaterally, compared with matched controls and chronic patients. Radial diffusivity was also higher, bilaterally, in first episode patients compared with matched controls, and on the right compared with chronic patients. Trace diffusity and radial diffusivity in first episode patients were significantly correlated with increased severity of delusions of reference. Given that the abnormalities were present only in first episode patients and were not observed in chronic cases, it appears that they normalize over time. These abnormalities in first episode patients involved diffusivity measures in all directions (trace, radial and axial), suggesting a likely acute, partially reversible process in which there is an increase in brain water content, i.e., swelling, edema, or inflammation, that may reflect an early neuroinflammatory response in first episode patients.


SWIMMY: Free Software for Teaching Neurophysiology of Neuronal Circuits.
To circumvent the many problems in teaching neurophysiology as a "wet lab," we developed SWIMMY, a virtual fish that swims by moving its virtual tail by means of a virtual neural circuit. SWIMMY diminishes the need for expensive equipment, troubleshooting, and manual skills that require practice. Also, SWIMMY effectively replaces live preparations, which some students find objectionable. Using SWIMMY, students (1) review the basics of neurophysiology, (2) identify the neurons in the circuit, (3) ascertain the neurons' synaptic interconnections, (4) discover which cells generate the motor pattern of swimming, (5) discover how the rhythm is generated, and finally (6) use an animation that corresponds to the activity of the motoneurons to discover the behavioral effects produced by various lesions and explain them in terms of their neural underpinnings. SWIMMY is a genuine inquiry-based exercise producing data that requires individual thought and interpretation. It is neither a cookbook exercise nor a demonstration. We have used SWIMMY for several terms with great success. SWIMMY solidifies students' understanding of material learned in traditional lecture courses because they must apply the concepts. Student ratings of SWIMMY have been very positive, particularly ratings from students who have also been exposed to a "wet" neurophysiology lab. Because SWIMMY requires only computers for implementation and makes minimal demands on instructional resources, it provides for a great deal of flexibility. Instructors could use SWIMMY as part of a traditional lab course, as a classroom exercise, in distance learning, or in blended instructional formats (internet with classroom). SWIMMY is now available for free online complete with student and instructor manuals at http://mdcune.psych.ucla.edu.


Hypogastric artery aneurysm: survival after rupture into the rectum.
We have described a 70-year-old man with rupture of a previously ligated hypogastric aneurysm. The first operation for multiple abdominal aneurysms was an aorto-bifemoral bypass with endoaneurysmorrhaphy of bilateral iliac aneurysms and proximal ligation of a right hypogastric artery aneurysm. Five months later, after the previously ligated hypogastric artery aneurysm ruptured into the rectum, endoaneurysmorrhaphy and suture ligation of all feeding orifices, creation of a Hartmann's pouch, and end-on colostomy were done. The patient is doing well at nine months' follow-up. We recommend aggressive surgical ablation of hypogastric artery aneurysms, with endoaneurysmorrhaphy and suture ligation of all "feeding" orifices.


Rabbit antithymocyte globulin (thymoglobulin) impairs the thymic output of both conventional and regulatory CD4+ T cells after allogeneic hematopoietic stem cell transplantation in adult patients.
Rabbit antithymocyte globulin-Genzyme™ is used to prevent graft-versus-host disease after allogeneic hematopoietic stem cell transplantation. Common disadvantages of treatment are infectious complications. The effects of rabbit antithymocyte globulin-Genzyme™ on thymic function have not been well-studied. Multicolor flow cytometry was used to analyze the kinetics of conventional and regulatory T cells in adult patients treated (n=12) or not treated (n=8) with rabbit antithymocyte globulin-Genzyme™ during the first 6 months after allogeneic hematopoietic stem cell transplantation. Patients treated with rabbit antithymocyte globulin-Genzyme™ had almost undetectable levels of recent thymic emigrants (CD45RA(+)CD31(+)) of both conventional and regulatory CD4T cells throughout the 6 months after allogeneic hematopoietic stem cell transplantation whereas CD4(+)CD45RA-memory T cells were less affected, but their levels were also significantly lower than in patients not treated with rabbit antithymocyte globulin-Genzyme™. In vitro, rabbit antithymocyte globulin-Genzyme™ induced apoptosis and cytolysis of human thymocytes, and its cytotoxic effects were greater than those of rabbit antithymocyte globulin-Fresenius™. Rabbit antithymocyte globulin-Genzyme™ in combination with a conditioning regimen strongly impairs thymic recovery of both conventional and regulatory CD4(+) T cells. The sustained depletion of conventional and regulatory CD4(+)T cells carries a high risk of both infections and graft-versus-host disease. Our data indicate that patients treated with rabbit antithymocyte globulin-Genzyme™ could benefit from thymus-protective therapies and that trials comparing this product with other rabbit antithymocyte globulin preparations or lymphocyte-depleting compounds would be informative.


"If somebody could just understand what I am going through, it would make all the difference": Conceptualizations of trauma in homeless populations experiencing severe mental illness.
Exposure to violence, vulnerability due to lack of shelter, alienation due to stigma, the experiences of severe mental illness (SMI) and subsequent institutionalization, make homeless persons with SMI uniquely susceptible to trauma exposure and subsequent mental health consequences. This study aims to contribute to the development of culturally sensitive interventions for identifying and treating trauma in a population of homeless persons with SMI in Tamil Nadu, India by understanding the manifestations of trauma and its associated consequences in this population. Free-listing exercises followed by in-depth interviews were conducted with a convenience sample of 26 user-survivors who have experienced homelessness or were at risk of homelessness, and suffered from SMI. Topics explored included events considered to be traumatic, pathways to trauma, associated emotional, physical and social complaints, and coping strategies. Results indicate discrepancies in classification of traumatic events between user-survivors and the Diagnostic and Statistical Manual of Mental Disorders. Traumatic experiences, particularly relating to social relationships and poverty, mentioned by user-survivors did not match traditional conceptualizations of trauma. Positive coping strategies for trauma included being mentally strong, knowledge and awareness, whereas the main negative coping strategy is avoidance. User-survivors attributed their experiences of homelessness and SMI to past traumas. Differing views of trauma between user-survivors and mental health professionals can lead to misdiagnosis and under-recognition of trauma in this population of homeless persons with SMI.


Plasmodium falciparum population dynamics during the early phase of anti-malarial drug treatment in Tanzanian children with acute uncomplicated malaria.
This study aimed to explore Plasmodium falciparum population dynamics during the early phase of anti-malarial drug treatment with artemisinin-based combination therapy in children with clinical malaria in a high transmission area in Africa. A total of 50 children aged 1-10 years with acute uncomplicated P. falciparum malaria in Bagamoyo District, Tanzania, were enrolled. Participants were hospitalized and received supervised standard treatment with artemether-lumefantrine according to body weight in six doses over 3 days. Blood samples were collected 11 times, i.e. at time of diagnosis (-2 h) and 0, 2, 4, 8, 16, 24, 36, 48, 60 and 72 h after initiation of treatment. Parasite population dynamics were assessed using nested polymerase chain reaction (PCR)-genotyping of merozoite surface protein (msp) 1 and 2. PCR-analyses from nine sequential blood samples collected after initiation of treatment identified 20 and 21 additional genotypes in 15/50 (30%) and 14/50 (28%) children with msp1 and msp2, respectively, non-detectable in the pre-treatment samples (-2 and 0 h combined). Some 15/20 (75%) and 14/21 (67%) of these genotypes were identified within 24 h, whereas 17/20 (85%) and 19/21 (90%) within 48 h for msp1 and msp2, respectively. The genotype profile was diverse, and varied considerably over time both within and between patients, molecular markers and their respective families. PCR analyses from multiple blood samples collected during the early treatment phase revealed a complex picture of parasite sub-populations. This underlines the importance of interpreting PCR-outcomes with caution and suggests that the present use of PCR-adjustment from paired blood samples in anti-malarial drug trials may overestimate assessment of drug efficacy in high transmission areas in Africa.The study is registered at http://www.clinicaltrials.gov with identifier NCT00336375.


Antithrombotic therapy for venous thromboembolism in myeloproliferative neoplasms.
In myeloproliferative neoplasms (MPNs) the incidence of venous thromboembolism (VTE) is 0.6-1.0 per 100 pt-years, and the rate of recurrence after VTE is 6.0-6.5 per 100 pt-yrs. Vitamin K-antagonists (VKA) reduces the risk of recurrence after VTE at usual sites (i.e., deep venous thrombosis (DVT) of the legs and pulmonary embolism (PE)) by 48-69%, with a rate of recurrent thrombosis per 100 pt-yrs of 3.4-4.7 on VKA and 8.9-9.6 off VKA; VKA discontinuation produces a 2.2-fold increased risk of novel thrombotic events with respect to continuation. However, the rate of both recurrent thrombosis and major bleeding on VKA is higher in MPN patients than in non-MPN patients, and the risk-benefit balance of long-term VKA treatment is challenging. In the absence of strong evidence, the tailored management of MPN-related VTE should operatively consider the risk categories for recurrence and bleed well established in the non-MPN setting. In summary, MPN patients with VTE are candidates for life-long VKA treatment, especially after unprovoked proximal DVT and PE. Aspirin can offer a moderate benefit in those patients who stop anticoagulation. The use of direct oral anticoagulants should be explored aiming to ameliorate the rate of bleeding.


Direct effects of thymopentin (Arg-Lys-Asp-Val-Tyr) on cholinergic agonist-induced slow inactivation of nicotinic acetylcholine receptor function.
The effects of thymopentin (TP-5) on the cholinergic agonist-induced inactivation of function (desensitization) of the nicotinic acetylcholine receptor (nAChR) were explored using two systems, 1) Torpedo californica electroplax nAchR reconstituted into phospholipid vesicles and 2) T. californica nAChR expressed, in Xenopus laevis oocytes, from in vitro synthesized RNA transcripts. The pentapeptide did not modify the equilibrium binding of 125I-alpha-bungarotoxin, but toxin rate binding assays in the presence of the cholinergic agonist carbamylcholine (Carb) revealed that it shortened the time course of the Carb-induced nAchR transition to the high affinity, desensitized state. Thymopentin (but not thymosins alpha 1 and beta 4) accelerated the slow inactivation of nAchR-mediated 86Rb+ influx, as measured by the first-order decrease in the Carb-induced 86Rb+ transport into the reconstituted vesicles. The decay of the acetylcholine-induced current from Torpedo receptor expressed in oocytes was also accelerated by TP-5. The pentapeptide had no ion channel-blocking or agonist activity of its own and exhibited a requirement for Ca2+ to express its effects. On the basis of these results, it is proposed that TP-5 has a direct effect on the nAChR, resembling that of noncompetitive blockers, as opposed to an indirect mechanism of action via the activation of specific metabolic pathways.


A fluorescent reporter model for the visualization and characterization of TDC.
TDC are hematopoietic cells that combine dendritic cell (DC) and conventional T-cell markers and functional properties. They were identified in secondary lymphoid organs (SLOs) of naïve mice as cells expressing CD11c, major histocompatibility molecules (MHC)-II, and the T-cell receptor (TCR). Despite thorough characterization, a physiological role for TDC remains to be determined. Unfortunately, using CD11c as a marker for TDC has the caveat of its upregulation on different cells, including T cells, upon activation. Here, we took advantage of Zbtb46-GFP reporter mice to explore the frequency and localization of TDC in different tissues at steady state and upon viral infection. RNA sequencing analysis confirmed that TDC sorted from Zbtb46-GFP mice have a gene signature that is distinct from conventional T cells and DC. In addition, this reporter model allowed for identification of TDC in situ not only in SLOs but also in the liver and lung of naïve mice. Interestingly, we found that TDC numbers in the SLOs increased upon viral infection, suggesting that TDC might play a role during viral infections. In conclusion, we propose a visualization strategy that might shed light on the physiological role of TDC in several pathological contexts, including infection and cancer.


Exercise hyperemia and vasoconstrictor responses in humans with cystic fibrosis.
ATP released from circulating erythrocytes is a potential signal regulating muscle blood flow during exercise (exercise hyperemia), and intravascular ATP appears to blunt sympathetic vasoconstriction during exercise. Erythrocytes from patients with cystic fibrosis (CF) do not release ATP. The goal of the present study was to determine whether increases in forearm blood flow during exercise are blunted in CF patients and whether CF patients exhibit greater vasoconstrictor responsiveness during exercise. Nine control subjects and 10 CF patients who were free of other disease complications (approximately 96% O2 saturation) performed incremental rhythmic forearm exercise at 5, 10, and 15% of maximum handgrip strength for 21 min (7 min at each workload). We used a cold pressor test to evoke sympathetic vasoconstriction under resting conditions and at each exercise workload. As a control, subjects performed a second exercise bout without the cold pressor test. Continuous brachial artery blood velocity was monitored beat-to-beat, and vessel diameter was assessed by Doppler ultrasound. Artery diameter, as well as blood pressure, heart rate, and O2 saturation, was measured at steady-state exercise and at 1 min into the cold pressor stimulus. Blood pressure and heart rate responses to the forearm exercise and each cold pressor test were similar in both groups (P > 0.05). Contrary to our hypothesis, forearm blood flow (P = 0.91) and forearm vascular conductance (P = 0.82) were similar at rest and at each level of exercise between CF patients and controls. Additionally, there was no difference in the degree of sympathetic vasoconstriction between groups at rest and at each level of exercise (P = 0.22). Our results suggest that ATP released from the deformation of erythrocytes is not an obligatory signal for exercise hyperemia in human skeletal muscle.


Effect of anesthesia combined with intercostal nerve block on analgesia for esophageal cancer after operation.
To discuss the effect of combined with intercostal nerve block on analgesia for esophageal cacer after operation. The total of 80 patients with esophageal cancer as the research object in our hospital from June 2012 to June 2013 were randomly grouped as epidural anesthesia (control group) and general anesthesia and intercostal nerve block combined with application (observation group), whose prognoses were compared. We compared the control group at each time point and the observation group at time T1-T4 with T0. Mean arterial pressure (MAP) had significantly lower performance (mean p < 0.05); at T4, central venus pressure (CVP) of the control group improved significantly (mean p < 0.05), MAP value of the observation group at T3, T4 was significantly lowerthan the control group (mean p < 0.05). The degree of pain 24-48 h after operation of the observation group was lower than the control group, and the difference was statistically significant (p < 0.05). Application of general anesthesia combined with intercostal nerve block analgesia in esophageal surgery can obtain satisfactory postoperative analgesia.


Mechanisms of membrane binding of small GTPase K-Ras4B farnesylated hypervariable region.
K-Ras4B belongs to a family of small GTPases that regulates cell growth, differentiation and survival. K-ras is frequently mutated in cancer. K-Ras4B association with the plasma membrane through its farnesylated and positively charged C-terminal hypervariable region (HVR) is critical to its oncogenic function. However, the structural mechanisms of membrane association are not fully understood. Here, using confocal microscopy, surface plasmon resonance, and molecular dynamics simulations, we observed that K-Ras4B can be distributed in rigid and loosely packed membrane domains. Its membrane binding domain interaction with phospholipids is driven by membrane fluidity. The farnesyl group spontaneously inserts into the disordered lipid microdomains, whereas the rigid microdomains restrict the farnesyl group penetration. We speculate that the resulting farnesyl protrusion toward the cell interior allows oligomerization of the K-Ras4B membrane binding domain in rigid microdomains. Unlike other Ras isoforms, K-Ras4B HVR contains a single farnesyl modification and positively charged polylysine sequence. The high positive charge not only modulates specific HVR binding to anionic phospholipids but farnesyl membrane orientation. Phosphorylation of Ser-181 prohibits spontaneous farnesyl membrane insertion. The mechanism illuminates the roles of HVR modifications in K-Ras4B targeting microdomains of the plasma membrane and suggests an additional function for HVR in regulation of Ras signaling.


Inhibitory effect of Paeonia lactiflora Pallas extract (PE) on poly (I:C)-induced immune response of epidermal keratinocytes.
Epidermal keratinocytes provide protective role against external stimuli by barrier formation. In addition, kertinocytes exerts their role as the defense cells via activation of innate immunity. Disturbance of keratinocyte functions is related with skin disorders. Psoriasis is a common skin disease related with inflammatory reaction in epidermal cells. We attempted to find therapeutics for psoriasis, and found that Paeonia lactiflora Pallas extract (PE) has an inhibitory potential on poly (I:C)-induced inflammation of keratinocytes. PE significantly inhibited poly (I:C)-induced expression of crucial psoriatic cytokines, such as IL-6, IL-8, CCL20 and TNF-α, via down-regulation of NF-κB signaling pathway in human keratinocytes. In addition, PE significantly inhibited poly (I:C)-induced inflammasome activation, in terms of IL-1β and caspase-1 secretion. Finally, PE markedly inhibited poly (I:C)-increased NLRP3, an important component of inflammasome. These results indicate that PE has an inhibitory effect on poly (I:C)-induced inflammatory reaction of keratinocytes, suggesting that PE can be developed for the treatment of psoriasis.


Switch From Originator to Equivalent Drug in the Era of Generic Antiepileptic Drugs: Study of Keppra Versus Epitiram Clinical Equivalence.
Generic antiepileptic drugs represent a measure to maximize cost saving. Levetiracetam (LEV) is one of most commonly used and effective antiepileptic drugs. The objective of our work was to demonstrate the effectiveness and safety of overnight switch from monotherapy with Keppra (original drug) to epitiram (generic drug) at the same dose. In our observational study, we consecutively enrolled 37 seizure-free patients with epilepsy who expressed the wish to switch to a generic drug for economic reasons. During the 6-month evaluation period, we assessed treatment efficacy, tolerability, compliance, and intersubject variability of LEV serum concentration. At each visit, clinical and neurological examination, scales, video-electroencephalogram, and blood sample analysis to evaluate LEV plasma level were performed. A total of 36 of 37 enrolled patients switched from Keppra to epitiram, which was administered at the same dose in monotherapy. Three of 36 patients dropped out during follow-up for adverse events. The other 33 subjects had neither seizures nor adverse events. No significant differences in electroencephalogram features and scale scores were revealed; the intersubject variability of LEV serum concentration did not differ significantly at follow-up evaluation (P = 0.53). All the patients expressed good clinical personal impression and continued to take epitiram. The switchback rate was 8 %. The switch from Keppra to epitiram was easy and safe in our population, and epitiram can be considered as effective and tolerable as Keppra. Only a slight, non-statistically significant variability in LEV serum concentration was documented after the switch from Keppra to epitiram. Larger epileptic populations should be studied to confirm these results.


Comparison of 2 Exercise Rehabilitation Programs for Multidirectional Instability of the Glenohumeral Joint: A Randomized Controlled Trial.
The recommended initial treatment for multidirectional instability (MDI) of the shoulder is a rehabilitation program, yet there is very low-quality evidence to support this approach. Purpose/Hypothesis: The purpose was to compare the Watson MDI program and Rockwood Instability program among patients with nontraumatic, nonstructural MDI. The hypothesis was that the Watson MDI program would produce clinically and statistically superior outcomes over the Rockwood Instability program. Randomized controlled trial; Level of evidence, 2. Forty-one participants with MDI were randomly allocated to the Watson MDI or Rockwood Instability program. Participants attended 12 weekly physiotherapy sessions for exercise prescription. Outcomes were assessed at baseline and 6, 12, and 24 weeks after randomization. Primary outcomes were the Melbourne Instability Shoulder Score (MISS) and the Western Ontario Shoulder Index (WOSI). Secondary outcomes included the Orebro Musculoskeletal Pain Questionnaire, pain, muscle strength, scapular upward rotation, scapular coordinates, global rating of change, satisfaction scales, limiting angle in abduction range, limiting factor in abduction range, and incidence of dislocation. Primary analysis was by intention to treat based on linear mixed models. Between-group differences showed significant effects favoring the Watson program for the WOSI (effect size [ES], 11.1; 95% CI, 1.9-20.2; P = .018) and for the limiting factor in abduction (ES, 0.1; 95% CI, 0.0-1.6; P = .023) at 12 weeks, and for the WOSI (ES, 12.6; 95% CI, 3.4-21.9; P =. 008), MISS (ES, 15.4; 95% CI, 5.9-24.8; P = .002), and pain (ES, -2.0; CI: -2.3 to -0.7, P = .003) at 24 weeks. For people with MDI, 12 sessions of the Watson MDI program were more effective than the Rockwood program at 12- and 24-week follow-up. Registration: ACTRN12613001240730 (Australian New Zealand Clinical Trials Registry).


[In silico identification of molecular mimicry between T-cell epitopes of Neisseria meningitidis B and the human proteome].
The objective of the study was to determine the T-cell epitopes of four of the most frequent antigenic proteins of the outer membrane of Neisseria meningitidis B, and to identify the most relevant sites for molecular mimicry with T-cell epitopes in humans. In order to do so, an in silico study -a type of study that uses bioinformatic tools- was carried out using SWISS-PROT/TrEMBL, SYFPEITHI and FASTA databases, which helped to determine the protein sequences, CD4 and CD8 T-cell epitope prediction, as well as the molecular mimicry with humans, respectively. Molecular similarity was found in several human proteins present in different organs and tissues such as: liver, skin and epithelial tissues, brain, lymphatic system and testicles. Of these, those found in testicles were more similar, showing the highest frequency of mimetic sequences. This finding shed light on the success of N. meningitidis B to colonize human tissues and the failure of certain vaccines against this bacterium, and it even helps to explain possible autoimmune reactions associated with the infection or vaccination.


Leveraging medical thesauri and physician feedback for improving medical literature retrieval for case queries.
This paper presents a study of methods for medical literature retrieval for case queries, in which the goal is to retrieve literature articles similar to a given patient case. In particular, it focuses on analyzing the performance of state-of-the-art general retrieval methods and improving them by the use of medical thesauri and physician feedback. The Kullback-Leibler divergence retrieval model with Dirichlet smoothing is used as the state-of-the-art general retrieval method. Pseudorelevance feedback and term weighing methods are proposed by leveraging MeSH and UMLS thesauri. Evaluation is performed on a test collection recently created for the ImageCLEF medical case retrieval challenge. Experimental results show that a well-tuned state-of-the-art general retrieval model achieves a mean average precision of 0.2754, but the performance can be improved by over 40% to 0.3980, through the proposed methods. The results over the ImageCLEF test collection, which is currently the best collection available for the task, are encouraging. There are, however, limitations due to small evaluation set size. The analysis shows that further refinement of the methods is necessary before they can be really useful in a clinical setting. Medical case-based literature retrieval is a critical search application that presents a number of unique challenges. This analysis shows that the state-of-the-art general retrieval models are reasonably good for the task, but the performance can be significantly improved by developing new task-specific retrieval models that incorporate medical thesauri and physician feedback.


Gastroparesis Symptoms Associated with Intestinal Hypomotility: An Explorative Study Using Wireless Motility Capsule.
Gastric emptying measurements are mandatory in gastroparesis diagnostics, but the association between delayed emptying and symptoms is questionable. It is imperative to find biomarkers better correlated to symptom generation. Hence, we examined the association between symptom severity and gastrointestinal motility measured by wireless motility capsule. In this prospective single-centre study, patients with gastroparesis symptoms were simultaneously investigated with gastric emptying scintigraphy and wireless motility capsule, measuring regional transit times and contractility parameters. Symptom severity was assessed with the Patient Assessment of Upper Gastrointestinal Symptom Severity Index (PAGI-SYM), including the Gastroparesis Cardinal Symptom Index (GCSI). We included 107 patients (70% women). In the whole patient group, nausea correlated with the gastric (rs = -0.31, p = 0.007), small bowel (rs = -0.41, p < 0.001) and colonic (rs = -0.33, p = 0.012) motility indices. In patients with idiopathic etiology, nausea correlated with small bowel motility index (rs = -0.81, p < 0.001) and mean stomach pressure (rs = -0.64, p = 0.013). We also found negative correlations between total GCSI score and maximum pressure of the small bowel (rs = -0.77, p < 0.001) and colon (rs = -0.74, p = 0.002). In diabetes patients, total PAGI-SYM score correlated with colonic motility index (rs = -0.34, p = 0.012), and mean pressure of the colon correlated with upper abdominal pain (rs = -0.37, p = 0.007). We found no association between symptoms, gastric emptying nor any other transit times. In patients with gastroparesis symptoms, we found that symptom severity was associated with intestinal hypomotility. Based on these results, gastroparesis diagnostics should also include an evaluation of the small bowel and colon.


Midfacial volumetric and upper lip soft tissue changes after Le Fort I advancement of the cleft maxilla.
To analyze, using 3-dimensional photogrammetric data, midfacial soft tissue and volumetric changes in the cleft maxilla after 1- or 2-piece Le Fort I (LF1) advancement. This was a retrospective study of patients with cleft and maxillary hypoplasia who underwent LF1 advancement. The primary predictor variable was the type of advancement (1 piece vs 2 pieces). Outcome measurements were changes in soft tissue linear measurements (subnasale [Sn], labium superius [LS], and stomion [SO]) and midfacial volume after maxillary advancement. Eleven patients (7 male, 4 female) underwent LF1 advancements (4 underwent 2-piece advancement). The mean maxillary advancement was 6.2 ± 1.7 mm. Soft tissue changes at the Sn, LS, and SO were 5.2 ± 2.0, 5.8 ± 2.5, and 5.2 ± 1.8 mm, respectively. The average volume change was 12.2 ± 5.7 cm(3). The mean ratios of soft tissue change to the amount of maxillary advancement (millimeters per millimeter) at the Sn, LS, and SO were 0.89 ± 0.49, 0.97 ± 0.44, and 0.89 ± 0.34, respectively. Volume increased by 2.1 ± 1.3 cm(3)/mm. Patients undergoing 1-piece advancement had greater mean advancement and greater soft tissue changes at the LS and SO (P < .03). After controlling for the amount of advancement, 1-piece LF1 osteotomy showed significantly greater improvements at the LS and SO (P < .04). Midface advancement at the LF1 level in patients with cleft consistently expands upper lip soft tissue and midfacial volume. Greater changes at the LS and SO were seen with 1-piece than with 2-piece osteotomy.


Chymopapain-induced reduction of proinflammatory phospholipase A2 activity and amelioration of neuropathic behavioral changes in an in vivo model of acute sciatica.
The mechanism of action underlying chymopapain (Chymodiactin) chemonucleolysis remains obscure. Radiographic studies suggest that chymopapain does not alter disc fragment size acutely; nonetheless, patients often report symptom resolution within a few days, even hours, of treatment. The authors postulate that, in addition to its chemonucleolytic action, chymopapain may possess antiinflammatory properties. To test this hypothesis, the authors assessed the ability of chymopapain to modulate the activity of the proinflammatory enzyme phospholipase A2 (PLA2) and to ameliorate behavioral changes associated with inflammatory neuropathy in an in vivo model of sciatica. Thirty-nine male Fischer rats were randomly assigned to one of three treatment groups: 1) saline, 2) betamethasone, or 3) chymopapain. All of the rats underwent unilateral sciatic nerve ligation with loose chromic gut suture to induce inflammatory mononeuropathy. The animals were tested for thermal and mechanical hyperalgesia on Days 0 (preoperation), 7 (pretreatment), and 14 (prior to death). Three animals were killed on Day 0 to determine the baseline PLA2 activity within unmanipulated rat sciatic nerves. On Day 7, three animals from each group were killed to assess PLA2 activity prior to treatment. The remainder were given a single infusion of saline, betamethasone (0.3 mg/kg), or chymopapain (100 pKat U) around the inflamed nerve. On Day 14, the remaining animals were killed and their sciatic nerves were removed. The tissue was homogenized and the PLA2 activity was determined using [14C]arachidonate-labeled Escherichia coli phospholipid membrane as a substrate. Lipids were extracted and separated by thin-layer chromatography. All animals developed behavioral changes consistent with inflammatory mononeuropathy 24 to 72 hours postoperatively; these included gait disturbance, flexion deformity, and hyperalgesia of the involved hindlimb. The degree of mechanical and thermal hyperalgesia was comparable between groups at Day 7. By Day 14, the thermal hyperalgesia had resolved; the mechanical hyperalgesia was less evident in the betamethasone- and chymopapain-treated groups than in the saline-treated controls (p = 0.003; saline- vs. chymopapain-treated groups p = 0.004; saline- vs. betamethasone-treated groups p = 0.008). The mean PLA2 activity at baseline (Day 0) was 11.6 +/- 4.9 nmol phospholipid hydrolyzed per minute per milligram of protein. The PLA2 activity at Day 7 was 74.4 +/- 18.2 (ligated side) and 21.2 +/- 11.7 (nonligated side). At Day 14, PLA2 activity was reduced in the chymopapain- (47.8 +/- 12.3) and betamethasone- (39.7 +/- 9.5) treated groups compared with the saline control group (62.3 +/- 11.2), (saline- vs. chymopapain-treated groups p < 0.05; saline- vs. betamethasone-treated groups p < 0.01). The PLA2 activity in nonligated specimens was 18.6 +/- 10.1. These data indicate that chymopapain exhibits antiinflammatory properties in vivo, reducing PLA2 activity and ameliorating mechanical hyperalgesia in this model of inflammatory sciatic neuropathy.


Drug delivery from structured porous inorganic materials.
Structured porous inorganic materials show high chemical and mechanical stability under an array of physiological conditions. Their hydrophilic character and porous structure can in principle be tailored to control the diffusion rate of an adsorbed or encapsulated drug, gene, or protein. This organized porosity has been used to achieve a sustained, controlled, or pulsed release in drug delivery applications. Their large surface areas together with their large pore volumes have been used to improve the solubility of poorly soluble drugs. Their low density allows them to float in the gastrointestinal tract and prolong the gastric retention of oral drugs. In addition, their easy surface functionalization allows their grafting with bioadhesive and targeting moieties, and their interior pore volume protects biological payloads from physiological degradation. Some of those porous inorganic materials can be synthesized or microfabricated to form deposits thus acting as drug reservoirs. Finally, diffusion-controlling porous membranes or coatings of those materials can be tailored with specific pore sizes to control drug release in eluting devices. Current research is focused on designing on demand targeted drug delivery systems using those inorganic porous materials as reservoirs together with triggering systems on their pore entrances to be externally activated to release the encapsulated therapeutic moiety. All of the previous scenarios will be overviewed to demonstrate the numerous possibilities of structured porous inorganic materials in drug delivery applications.


Digital radiography for clinical applications.
In the field of radiological research methods, digital imaging is becoming increasingly prevalent. Apart from computerised tomography, magnetic resonance tomography and angiography, also in projection radiography, traditional film/screen imaging is more and more being replaced by digital imaging using digital image-intensifier and storage phosphor technology. Digital imaging offers various new possibilities in image processing, storage and transmission. This may yield additional diagnostic information, dose reduction and fast availability of images. However, an inappropriate parameter selection for imaging and post-processing as well as a lack of integration in the entire organisation may lead to a rejection of this innovative technology.


Oryzacystatin I expressed in transgenic potato induces digestive compensation in an insect natural predator via its herbivorous prey feeding on the plant.
We observed recently that the rice cysteine proteinase inhibitor, oryzacystatin I (OCI) expressed in transgenic potato does not affect growth and development of the two-spotted stinkbug predator (Perillus bioculatus) via its herbivorous prey feeding on the plant. Here we monitored the inhibitory activity of recombinant OCI along this potato --> herbivore --> predator continuum, to determine if the absence of effect was associated with a digestive compensatory response of the predator following inhibition of its proteinases by the recombinant cystatin. After confirming that OCI is present in the plant, and ingested in an active form by potato beetle larvae, quantitative and electrophoretic assays allowed us to determine that the recombinant cystatin (representing about 0.8% of total soluble proteins in leaves) was entirely bound to a approximately 30-kDa target proteinase in the prey's midgut, forming a sodium dodecyl sulphate (SDS)-stable complex detected on immunoblots with an anti-OCI polyclonal antibody. Despite the apparent absence of free, residual OCI in the beetle's midgut, digestive protease activity in the predator, known to include OCI-sensitive activity, was altered negatively when the prey was fed the modified plant. This inhibitory process at the third trophic level was accompanied by a compensatory response in the predator, by which serine-type proteinases were synthesized de novo. Overall, our data suggest that the affinity between OCI and the predator's OCI-sensitive proteinases is: (i) as strong as (or stronger than) the affinity between OCI and the potato beetle 30-kDa-sensitive proteinase; and (ii) stronger than the affinity between these enzymes and the plant endogenous homologue of OCI, potato multicystatin, induced in the plant by potato beetle feeding. Our results also show that predatory organisms can adapt their digestive metabolism to the presence of plant antidigestive proteins ingested by their herbivorous preys. In a broader context, this study stresses the need to monitor the inhibitory effects of PI-expressing plants not only on the herbivorous insects targeted, but also on the organisms likely to consume these pests in the environment.


The Aurora-B-dependent NoCut checkpoint prevents damage of anaphase bridges after DNA replication stress.
Anaphase chromatin bridges can lead to chromosome breakage if not properly resolved before completion of cytokinesis. The NoCut checkpoint, which depends on Aurora B at the spindle midzone, delays abscission in response to chromosome segregation defects in yeast and animal cells. How chromatin bridges are detected, and whether abscission inhibition prevents their damage, remain key unresolved questions. We find that bridges induced by DNA replication stress and by condensation or decatenation defects, but not dicentric chromosomes, delay abscission in a NoCut-dependent manner. Decatenation and condensation defects lead to spindle stabilization during cytokinesis, allowing bridge detection by Aurora B. NoCut does not prevent DNA damage following condensin or topoisomerase II inactivation; however, it protects anaphase bridges and promotes cellular viability after replication stress. Therefore, the molecular origin of chromatin bridges is critical for activation of NoCut, which plays a key role in the maintenance of genome stability after replicative stress.


[Nose and sinus: anatomo-pathologic relations].
The relationship between rhinitis and chronic sinusitis is close and complex and may perhaps show many points of view, anatomical and physiological, epidemiological (by comparing the prevalence of an ailment in carriers of another ailment), experimental (by making nasal allergen provocation tests and studying the sinus anomalies induced) and physiopathological (by phenotyping and comparison of the inflammation present with one another and other ailments). If the results of these studies are convincing, there is still lack of formal proof that confirms the fundamental role of nasal inflammation in general and in particular allergic inflammation in the genesis of sinusitis.


Broad-Spectrum Antibiotics and Risk of Graft-versus-Host Disease in Pediatric Patients Undergoing Transplantation for Acute Leukemia: Association of Carbapenem Use with the Risk of Acute Graft-versus-Host Disease
Variation in the gastrointestinal (GI) microbiota after hematopoietic cell transplantation (HCT) has been associated with acute graft-versus-host disease (aGVHD). Because antibiotics induce dysbiosis, we examined the association of broad-spectrum antibiotics with subsequent aGVHD risk in pediatric patients undergoing HCT for acute leukemia. We performed a retrospective analysis in a dataset merged from 2 sources: (1) the Center for International Blood and Marrow Transplant Research, an observational transplantation registry, and (2) the Pediatric Health Information Services, an administrative database from freestanding children's hospitals. We captured exposure to 3 classes of antibiotics used for empiric treatment of febrile neutropenia: (1) broad-spectrum cephalosporins, (2) antipseudomonal penicillins, and (3) carbapenems. The primary outcome was grade II-IV aGVHD; secondary outcomes were grade III-IV aGVHD and lower GI GVHD. The adjusted logistic regression model (full cohort) and time-to-event analysis (subcohort) included transplantation characteristics, GVHD risk factors, and adjunctive antibiotic exposures as covariates. The full cohort included 2550 patients at 36 centers; the subcohort included 1174 patients. In adjusted models, carbapenems were associated with an increased risk of grade II-IV aGVHD in the full cohort (adjusted odds ratio [aOR], 1.24; 95% confidence interval [CI], 1.02 to 1.51) and subcohort (sub hazard ratio [HR], 1.31; 95% CI, 0.99 to 1.72), as well as with an increased risk of grade III-IV aGVHD (subHR, 1.77; 95% CI, 1.25 to 2.52). Early carbapenem exposure (before day 0) especially impacted aGVHD risk. For antipseudomonal penicillins, the associations with aGVHD were in the direction of increased risk but were not statistically significant. There was no identified association between broad-spectrum cephalosporins and aGVHD. Carbapenems, more than other broad-spectrum antibiotics, should be used judiciously in pediatric HCT recipients to minimize aGVHD risk. Further research is needed to clarify the mechanism underlying this association.


A novel SHAPE reagent enables the analysis of RNA structure in living cells with unprecedented accuracy.
Due to the mounting evidence that RNA structure plays a critical role in regulating almost any physiological as well as pathological process, being able to accurately define the folding of RNA molecules within living cells has become a crucial need. We introduce here 2-aminopyridine-3-carboxylic acid imidazolide (2A3), as a general probe for the interrogation of RNA structures in vivo. 2A3 shows moderate improvements with respect to the state-of-the-art selective 2'-hydroxyl acylation analyzed by primer extension (SHAPE) reagent NAI on naked RNA under in vitro conditions, but it significantly outperforms NAI when probing RNA structure in vivo, particularly in bacteria, underlining its increased ability to permeate biological membranes. When used as a restraint to drive RNA structure prediction, data derived by SHAPE-MaP with 2A3 yields more accurate predictions than NAI-derived data. Due to its extreme efficiency and accuracy, we can anticipate that 2A3 will rapidly take over conventional SHAPE reagents for probing RNA structures both in vitro and in vivo.


Comprehensive analysis of common and rare mitochondrial DNA variants in elite Japanese athletes: a case-control study.
The purpose of the present study was to identify mitochondrial DNA (mtDNA) polymorphisms and rare variants that associate with elite Japanese athletic status. Subjects comprised 185 elite Japanese athletes who had represented Japan at international competitions (that is, 100 endurance/middle-power athletes: EMA; 85 sprint/power athletes: SPA) and 672 Japanese controls (CON). The entire mtDNA sequences (16 569 bp) were analyzed by direct sequencing. Nucleotide variants were detected at 1488 sites in the 857 entire mtDNA sequences. A total of 311 variants were polymorphisms (minor allele frequency 1% in CON), and the frequencies of these polymorphisms were compared among the three groups. The EMA displayed excess of seven polymorphisms, including subhaplogroup D4e2- and D4g-specific polymorphisms, compared with CON (P<0.05), whereas SPA displayed excess of three polymorphisms and dearth of nine polymorphisms, including haplogroup G- and subhaplogroup G2a-specific polymorphisms, compared with CON (P<0.05). The frequencies of 10 polymorphisms, including haplogroup G- and subhaplogroup G2a-specific polymorphisms, were different between EMA and SPA (P<0.05): although none of these polymorphisms differed significantly between groups after correcting for multiple comparison (false discovery rate q-value 0.05). The number of rare variants in the 12S ribosomal RNA and NADH dehydrogenase subunit I genes were also higher in SPA than in CON (P<0.05). Analysis of the entire mtDNA of elite Japanese athletes revealed several haplogroup- and subhaplogroup-specific polymorphisms to be potentially associated with elite Japanese athletic status.


Estimation of the diffusion rate and crossing probability for biased edge movement between two different types of habitat.
One of the fundamental goals of ecology is to examine how dispersal affects the distribution and dynamics of insects across natural landscapes. These landscapes are frequently divided into patches of habitat embedded in a matrix of several non-habitat regions, and dispersal behavior could vary within each landscape element as well as the edges between elements. Reaction-diffusion models are a common way of modeling dispersal and species interactions in such landscapes, but to apply these models we also need methods of estimating the diffusion rate and any edge behavior parameters. In this paper, we present a method of estimating the diffusion rate using the mean occupancy time for a circular region. We also use mean occupancy time to estimate a parameter (the crossing probability) that governs one type of edge behavior often used in these models, a biased random walk. These new methods have some advantages over other methods of estimating these parameters, including reduced computational cost and ease of use in the field. They also provide a method of estimating the diffusion rate for a particular location in space, compared to existing methods that represent averages over large areas. We further examine the statistical properties of the new method through simulation, and discuss how mean occupancy time could be estimated in field experiments.


A realistic computational model for the formation of a Place Cell.
Hippocampal Place Cells (PCs) are pyramidal neurons showing spatially localized firing when an animal gets into a specific area within an environment. Because of their obvious and clear relation with specific cognitive functions, Place Cells operations and modulations are intensely studied experimentally. However, although a lot of data have been gathered since their discovery, the cellular processes that interplay to turn a hippocampal pyramidal neuron into a Place Cell are still not completely understood. Here, we used a morphologically and biophysically detailed computational model of a CA1 pyramidal neuron to show how, and under which conditions, it can turn into a neuron coding for a specific cue location, through the self-organization of its synaptic inputs in response to external signals targeting different dendritic layers. Our results show that the model is consistent with experimental findings demonstrating PCs stability within the same spatial context over different trajectories, environment rotations, and place field remapping to adapt to changes in the environment. To date, this is the only biophysically and morphologically accurate cellular model of PCs formation, which can be directly used in physiologically accurate microcircuits and large-scale model networks to study cognitive functions and dysfunctions at cellular level.


Effects of isoflavone supplement on healthy women.
Effects of the isoflavone supplement on hormonal states in young premenopausal women were studied by cross-over study design. Administration of 20 mg or 40 mg isoflavones (IF) by tablets, of which 1 g contained 43.5 mg daidzein, 6.0 mg genistein, 24.0 mg glycitein, to 40 young female students for one month caused a prolonged menstruation in 60% of young women, shortened menstruation in 20% of young women, 17% remained unchanged and 3% became irregular. Larger dose tended to elongate more, but 17beta-estradiol levels in both follicular and luteal phages were not different between 20 mg and 40 mg isoflavone intake. Equor excreters tended to show low plasma progesteron level in the luteal phase. Detailed hormonal analysis on 3 of students by a cross over study design showed decreased level of 17beta-estradiol throughout the menstruation cycle. SHBG significantly increased about 10% in all three. DEAS, androstendione, and testosterone showed different responses according to the follicular or luteal phase. T3 and T4 increased as a result of isoflavone tablet administration in the follicular phase, but it decreased in the luteal phase. These changes suggest that isoflavones influence not only estrogen receptor-related functions but the hypothalamo-hypophysis-gonadal axis.


Effects of topical honey on post-operative wound infections due to gram positive and gram negative bacteria following caesarean sections and hysterectomies.
The possible therapeutic effect of topical crude undiluted honey in the treatment of severe acute postoperative wound infections was studied. Fifty patients having postoperative wound infections following caesarean sections or total abdominal hysterectomies with gram positive or gram negative bacterial infections were allocated in two groups. Twenty-six patients (group A) were treated with 12 hourly application of crude honey and 24 patients (group B) were treated with local antiseptics: spirit (70% Ethanol) and povidone-iodine. Both groups received systemic antibiotics according to culture and sensitivity. Results showed that eradication of bacterial infections was obtained after 6 +/- 1.9 days (mean +/- SD) in group A and after 14.8 +/- 4.2 days in group B (p <0.05). Period for antibiotics use was 6.88 +/- 1.7 days in-group A and 15.45 +/- 4. 37 in-group B (p <0.05). Complete wound healing was evident after 10. 73 +/- 2.5 days in group A and after 22.04 +/- 7.33 in group B (p <0. 05). Size of postoperative scar was 3.62 +/- 1.4 mm after using topical honey and was 8.62 +/- 3.8 mm after local antiseptics (p <0. 05). The mean hospital stay was 9.36 +/- 1.8 days in group A and 19. 91 +/- 7.35 days in group B (p <0.05). After using honey, 22/26 patients (84.4%) showed complete wound healing without wound disruption or need for re-suturing and only 4 patients showed mild dehiscence. In group B, 12/24 patients (50%) showed complete wound healing and 12 patients showed wound dehiscence, six of them needed re-suturing under general anesthesia. We concluded that topical application of crude undiluted honey could (1) faster eradication of bacterial infections, (2) reduce period of antibiotic use and hospital stay, (3) accelerate wound healing, (4) prevent wound dehiscence and need for re-suturing and (5) result in minimal scar formation.


[Diversity and quality in medical training].
Ethnocultural diversity among medical students is important in order to guarantee a true reflection of society in the medical profession. It is known that students from ethnic minority groups perform less well in assessments during medical training. This is partly due to language problems but also to differences in culture. In order to keep these students in medical training, assessments should ideally be free of ethnocultural prejudice. Furthermore, it is important to ensure that there is no discrimination. To get a valid impression of these students it is important that multiple assessments be performed by several assessors. Then the real problems can be exposed and students from ethnic minority groups can get the support they need to become good physicians.


Changes in Lid Crease Measurements in Levator Advancement for Ptosis.
Although previous reports addressed the differences in marginal reflex distance 1 (MRD-1) measurements based on various techniques of levator advancement, eyelid crease measurements have not been studied as markers in perioperative planning. In addition to possible benefits in optimal results for improvement of visual field defects and functional impairment, recent work has suggested that eyelid crease is important in the perception of attractiveness. Therefore, the aims of this study were to determine the change in eyelid crease measurements in levator advancement and to further expand on numerical correlation of levator advancement in preoperative planning to avoid overcorrection or undercorrection. The authors performed a retrospective analysis of preoperative and postoperative eye measurements in patients who underwent levator advancement for ptosis between August 2016 and April 2019. This study included 13 patients, all of whom had recorded preoperative and postoperative measurements of MRD-1, whereas 8 of 13 patients had additional preoperative and postoperative measurements of the mid pupil to crease and lateral limbus to crease at the level of mid pupil. All patients had increased in MRD-1, mid pupil to crease, and lateral limbus to crease measurements postoperatively. The average advancement of 4.8 mm led to an elevation of MRD-1 to 2.6 mm (n = 25) and an improvement in mid pupil to crease distance of 1.9 mm (n = 15) and lateral limbus to crease distance of 2.6 mm (n = 15). No cases of undercorrection or overcorrection were found. All patients reported satisfaction with the results, including improvement in function and quality of life. No infections, hematomas, or other complications were noted postoperatively in any of the patients. Marginal reflex distance 1 is a consistently reliable planning tool in preoperative assessment of levator advancement, with beneficial patient outcomes including improvement of visual field defects caused by ptosis and satisfaction with cosmetic results. This study is the first to report use of crease measurements (mid pupil to crease and lateral limbus to crease), which may provide additional understanding to the aesthetic value of to the levator advancement.


Structural basis for dynamic mechanism of proton-coupled symport by the peptide transporter POT.
Proton-dependent oligopeptide transporters (POTs) are major facilitator superfamily (MFS) proteins that mediate the uptake of peptides and peptide-like molecules, using the inwardly directed H(+) gradient across the membrane. The human POT family transporter peptide transporter 1 is present in the brush border membrane of the small intestine and is involved in the uptake of nutrient peptides and drug molecules such as β-lactam antibiotics. Although previous studies have provided insight into the overall structure of the POT family transporters, the question of how transport is coupled to both peptide and H(+) binding remains unanswered. Here we report the high-resolution crystal structures of a bacterial POT family transporter, including its complex with a dipeptide analog, alafosfalin. These structures revealed the key mechanistic and functional roles for a conserved glutamate residue (Glu310) in the peptide binding site. Integrated structural, biochemical, and computational analyses suggested a mechanism for H(+)-coupled peptide symport in which protonated Glu310 first binds the carboxyl group of the peptide substrate. The deprotonation of Glu310 in the inward open state triggers the release of the bound peptide toward the intracellular space and salt bridge formation between Glu310 and Arg43 to induce the state transition to the occluded conformation.


Superior Hemimastectomy with Inferior Pedicle Nipple-Bearing Flap: A Five-Step Surgical Technique.
Oncoplastic breast surgery is an evolving field combining both breast aesthetic surgery and oncologic breast surgery. It aims to optimize cosmetic outcomes without interfering with oncologic safety. The superior hemimastectomy is a technique that can be considered for large upper-quadrant breast tumors or multifocal and multicentric breast tumors localized in the upper quadrants. As with mastectomy, axillary procedures can be performed through the same incision. The nipple-areola complex can be preserved and reimplanted. Superior hemimastectomy allows wide excision of the breast tissue, but its main disadvantage is the increased risk of necrosis of the free grafted nipple-areola complex. In this article, the authors present the surgical technique of superior hemimastectomy with an inferior pedicle nipple-bearing flap. This technique is presented as a simple five-step algorithm. A modified superior hemimastectomy with nipple-areola complex preservation using an inferior pedicle nipple-bearing flap is an alternative to the classic superior hemimastectomy technique. This modified technique decreases the risk of nipple-areola complex necrosis and preserves better nipple-areola complex sensitivity.


Removal of a mixture tetracycline-tylosin from water based on anodic oxidation on a glassy carbon electrode coupled to activated sludge.
The purpose of this study was first to examine the electrochemical oxidation of two antibiotics, tetracycline (TC) and tylosin (Tylo), considered separately or in mixture, on a glassy carbon electrode in aqueous solutions; and then to assess the relevance of such electrochemical process as a pre-treatment prior to a biological treatment (activated sludge) for the removal of these antibiotics. The influence of the working potential and the initial concentration of TC and Tylo on the electrochemical pre-treatment process was also investigated. It was noticed that antibiotics degradation was favoured at high potential (2.4 V/ saturated calomel electrode (SCE)), achieving total degradation after 50 min for TC and 40 min for Tylo for 50 mg L(-1) initial concentration, with a higher mineralization efficiency in the case of TC. The biological oxygen demand in 5 days (BOD5)/Chemical oxygen demand (COD) ratio increased substantially, from 0.033 to 0.39 and from 0.038 to 0.50 for TC and Tylo, respectively. Regarding the mixture (TC and Tylo), the mineralization yield increased from 10.6% to 30.0% within 60 min of reaction time when the potential increased from 1.5 to 2.4 V/SCE and the BOD5/COD ratio increased substantially from 0.010 initially to 0.29 after 6 h of electrochemical pre-treatment. A biological treatment was, therefore, performed aerobically during 30 days, leading to an overall decrease of 72% of the dissolved organic carbon by means of the combined process.


Droplet Jumping: Effects of Droplet Size, Surface Structure, Pinning, and Liquid Properties.
Coalescence-induced droplet jumping has the potential to enhance the efficiency of a plethora of applications. Although binary droplet jumping is quantitatively understood from energy and hydrodynamic perspectives, multiple aspects that affect jumping behavior, including droplet size mismatch, droplet-surface interaction, and condensate thermophysical properties, remain poorly understood. Here, we develop a visualization technique utilizing microdroplet dispensing to study droplet jumping dynamics on nanostructured superhydrophobic, hierarchical superhydrophobic, and hierarchical biphilic surfaces. We show that on the nanostructured superhydrophobic surface the jumping velocity follows inertial-capillary scaling with a dimensionless velocity of 0.26 and a jumping direction perpendicular to the substrate. A droplet mismatch phase diagram was developed showing that jumping is possible for droplet size mismatch up to 70%. On the hierarchical superhydrophobic surface, jumping behavior was dependent on the ratio between the droplet radius Ri and surface structure length scale L. For small droplets ( Ri ≤ 5 L), the jumping velocity was highly scattered, with a deviation of the jumping direction from the substrate normal as high as 80°. Surface structure length scale effects were shown to vanish for large droplets ( Ri > 5 L). On the hierarchical biphilic surface, similar but more significant scattering of the jumping velocity and direction was observed. Droplet-size-dependent surface adhesion and pinning-mediated droplet rotation were responsible for the reduced jumping velocity and scattered jumping direction. Furthermore, droplet jumping studies of liquids with surface tensions as low as 38 mN/m were performed, further confirming the validity of inertial-capillary scaling for varying condensate fluids. Our work not only demonstrates a powerful platform to study droplet-droplet and droplet-surface interactions but provides insights into the role of fluid-substrate coupling as well as condensate properties during droplet jumping.


Detecting epileptic seizures using hand-crafted and automatically constructed EEG features.
Epileptic seizure detection aims to replace unreliable seizure diaries by a model that automatically detects seizures based on electroencephalography (EEG) sensors. However, developing such a model is difficult and time consuming as it requires manually searching for relevant features from complex EEG data. Domain experts may have a partial understanding of the EEG characteristics that indicate seizures, but this knowledge is often not sufficient to exhaustively enumerate all relevant features. To address this challenge, we investigate how automated feature construction may complement hand-crafted features for epileptic seizure detection. By means of an empirical comparison on a real-world seizure detection dataset, we evaluate the ability of automated feature construction to come up with new relevant features. We show that combining hand-crafted and automated features results in more accurate models compared to using hand-crafted features alone. Our findings suggest that future studies on developing EEG-based seizure detection models may benefit from features constructed using a combination of hand-crafted and automated feature engineering.


Quantitative electron probe X-ray microanalysis of electrolyte elements within epithelial tissue compartments.
The electron probe X-ray microanalysis of 1-micron thick frozen-hydrated sections provides a method to measure local concentrations of electrolyte elements (and H2O) in and around the cells in situ with an analytical spatial resolution of better than 0.2 micron and a sensitivity limit better than 10 mM with a standard error of less than 10%. Our microprobe studies on several epithelia transporting isotonic fluids have provided strong evidence that the electrolyte concentration in the interspaces suspected to be the sites of solute-solvent coupling may, on average, be as much as 35% more than in the bathing fluid. There also appear to be distinct concentration gradients in interspaces, the profiles of which differ according to the tissue geometry but particularly according to the location of the leaky cell junctions, suggesting that the osmotic equilibration of the transported fluid may require substantial mass flow through the junctions. In addition, there is evidence a) that the major electrolytes in the cytoplasm of the epithelial cells are not uniformly distributed but may have distinct axial and radial concentration gradients that depend on active solute transport (e.g., that abolished by ouabain); b) that in some epithelia (e.g., rabbit ileum) there is a peripheral cytoplasmic zone that may support fast convective flow for transcellular fluxes; c) that the extracellular structures like the glycocalyx and basement membrane preferentially sequester potassium (and calcium) and could have a non-zero reflection coefficient; and d) that in normal cells, nuclei have ionic composition similar to that of the circumnuclear cytoplasm.


Oxidative stress in human immunodeficiency virus infection.
Infection by the human immunodeficiency virus (HIV-1) causes chronic ongoing inflammation in HIV-1 seropositive individuals as shown by high plasma levels of inflammatory cytokines and production of reactive oxygen intermediates (ROIs). One source of ROIs is provided from the very early stages of HIV infection by activated polymorphonuclear neutrophils. Tat, the viral protein, is also specifically responsible for an endogenous cellular increase of ROI. In this review we also evaluate the effects of this oxidative stress on various biological parameters such as immune response and survival of T lymphocytes, virus transcription and replication. It was clearly demonstrated in ex vivo experiments that the oxidative stress due to infection itself participates in CD4+ T lymphocyte depletion by increasing their rate of apoptosis and particularly of Fas-induced apoptosis. This oxidative stress also facilitates NF-kappa B-dependent activation of HIV transcription. In vitro studies suggest that the early steps of HIV activation from its quiescent state might be subsequently facilitated by this oxidative environment. Whereas already active replication is not influenced. The data presented here lead to a better understanding of the consequences of oxidative stress on the pathophysiology of HIV infection and also enable us to evaluate the potential use of antioxidant molecules as therapeutic agents against AIDS.


S-Palmitoylation during Retinoic Acid-Induced Neuronal Differentiation of SH-SY5Y Neuroblastoma Cells.
S-Palmitoylation is the covalent attachment of C14:0-C22:0 fatty acids (mainly C16:0 palmitate) to cysteines via thioester bonds. This lipid modification is highly abundant in neurons, where it plays a role in neuronal development and is implicated in neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, and Huntington's disease. The knowledge of S-palmitoylation in neurodevelopment is limited due to technological challenges in analyzing this highly hydrophobic protein modification. Here, we used two orthogonal methods, acyl-biotin exchange (ABE) and lipid metabolic labeling (LML), to identify S-palmitoylated proteins and sites during retinoic acid-induced neuronal differentiation of SH-SY5Y cells. We identified 2002 putative S-palmitoylated proteins in total, of which 650 were found with both methods. Significant changes in the abundance of S-palmitoylated proteins were detected, in particular for several processes and protein classes that are known to be important for neuronal differentiation, which include proto-oncogene tyrosine-protein kinase receptor (RET) signal transduction, SNARE protein-mediated exocytosis, and neural cell adhesion molecules. Overall, S-palmitoylation profiling by employing ABE and LML in parallel during RA-induced differentiation of SH-SY5Y cells revealed a subset of high confidence bona fide S-palmitoylated proteins and suggested an important role for S-palmitoylation in neuronal differentiation.