[Amniotic band syndrome].
Amniotic band syndrome is a well-described clinical entity, which includes several congenital deformities. Hand malformations and limb defects represent the most frequent clinical characteristics, gathering, with variable localization, constriction rings, acrosyndactylies and amniotic amputations. Other anomalies of skull, face, body wall and internal organs, sometimes complex and lethal, are significantly associated with this syndrome. The syndrome is then included in the larger entity of limb body wall complex (LBWC). Congenital ring constriction, amniotic band disruption complex, or congenital transverse defect are some of the numerous synonyms defining this malformative syndrome, showing either its clinical variability, or the uncertainties surrounding its etiology. Indeed, several pathogenic theories have been successively opposed, bringing about a certain degree of confusion. Recent experimental genetic studies could unify the different fetal malformations. The surgical treatment actually applies only to the aftereffects of the intrauterine phenomenon, until antenatal diagnosis followed by in utero surgery will be perfected.


The effect of aging on VEGF/VEGFR2 signal pathway genes expression in rat liver sinusoidal endothelial cell.
Liver sinusoidal endothelial cells (LSECs) play a key role in the initiation and neoangiogenesis of liver regeneration. We presume that the abnormity of the VEGF/VEGFR2 and its pathway gene Id1, Wnt2 and HGF expression in aged LSECs may be an important mechanism to affect liver regeneration of the elderly. LSECs from two different groups (adult and old) were isolated in a rodent model, and observed by SEM and TEM. The adult and old rats were underwent 70% partial hepatectomy. The proliferation of hepatocytes and LSECs were analyzed by Immunofluorescence staining. The expression of VEGF/VEGFR2 and its pathway gene in isolated LSECs and liver tissue after hepatectomy were detected by qRT-PCR and Western blot. There is a decreased number of endothelial fenestrae in the LSECs of the old group, compared to the adult group. The old group had a lower expression of VEGF/VEGFR2 and its pathway gene than the adult groups (p < 0.01). The results of western blot were consistent with those of qRT-PCR. The hepatocytes had a high proliferation rate at first 4 days after hepatectomy, and a significantly higher proliferation rate in the adult group. The LSECs began to proliferate after 4 days of hepatectomy, and showed a quantity advantage in the adult group. The adult group had a significantly higher expression of VEGF/VEGFR2 and its pathway gene after hepatectomy than the old group (p < 0.01). LSCEs turn to be defenestration in structure and have a low expression of VEGF/VEGFR2 and its pathway gene with aging.


Oxovanadium(IV) complex formation by simple sugars in aqueous solution.
The binding of oxovanadium(IV) to simple sugars in neutral or basic aqueous solution, as studied by EPR and electronic absorption spectroscopy, is reported. The complexation is favored in basic media and involves the coordination of the metal ion to couples of adjacent deprotonated hydroxyls of the sugar molecule. However, only the ligands provided with cis couples can adopt this chelating ligand behavior. The ability of the cis hydroxyl couples to yield chelated complexes has been related to the structural rearrangement (decrease of the O-C-C-O torsion angle in the five-membered chelated ring) needed to permit the oxovanadium(IV) coordination by the sugar molecule.


Importance of adipocyte cyclooxygenase-2 and prostaglandin E2-prostaglandin E receptor 3 signaling in the development of obesity-induced adipose tissue inflammation and insulin resistance.
We examined the involvement of adipocyte cyclooxygenase-2 (COX-2) and prostaglandin E2 (PGE2)-prostaglandin E receptor (EP)3-mediated signaling during hypertrophy and hypoxia in the development of obesity-associated adipose tissue (AT) inflammation and insulin resistance. The experiments were conducted with high-fat diet (HFD)-induced obese rats, db/db mice, human subjects, and 3T3-L1 and the human Simpson-Golabi-Behmel syndrome (SGBS) adipocytes; the groups were treated with selective inhibitors of COX-2 [celecoxib 30 mg/kg, half maximal inhibitory concentration (IC50) ≈ 0.04 µM] and EP3 (L-798106 100 µg/kg, IC50 ≈ 0.5 µM) or a short interfering RNA. There were strong, positive correlations between adipocyte COX-2 and EP3 gene expressions and the AT TNF-α and monocyte chemotactic protein-1 contents and the homeostatic model assessment for insulin resistance in HFD-induced obese rats, as well as body mass index in human subjects. Treatment with COX-2 and EP3 inhibitors significantly reversed AT inflammatory gene and protein expressions (-50%) and impaired glucose and insulin tolerance in db/db mice. COX-2 inhibition diminished the chemotaxis of adipocytes isolated from HFD rats to macrophages and T cells. Targeting inhibition of adipocyte COX-2 and EP3 during hypertrophy and hypoxia reversed the release of the augmented proinflammatory adipokines and the diminished adiponectin and also suppressed NF-κB and hypoxia-inducible factor-1α transcription activation. These findings suggest that adipocyte COX-2 PGE2-EP3-mediated signaling is crucially involved in the development of obesity-associated AT inflammation and insulin resistance.-Chan, P.-C., Hsiao, F.-C., Chang, H.-M., Wabitsch, M., Hsieh, P. S. Importance of adipocyte cyclooxygenase-2 and prostaglandin E2-prostaglandin E receptor 3 signaling in the development of obesity-induced adipose tissue inflammation and insulin resistance.


Review of safety and mobility issues among older pedestrians.
Although old people make up an extremely vulnerable road-user group, older pedestrians' difficulties have been studied less extensively than those of older drivers, and more knowledge of this issue is still required. The present paper reviews current knowledge of older-adult problems with the main components of pedestrian activity, i.e., walking and obstacle negotiation, wayfinding, and road crossing. Compared to younger ones, old pedestrians exhibit declining walking skills, with a walking speed decrease, less stable balance, less efficient wayfinding strategies, and a greater number of unsafe road crossing behaviors. These difficulties are linked to age-related changes in sensorial, cognitive, physical, and self-perception abilities. It is now known that visual impairment, physical frailty, and attention deficits have a major negative impact on older pedestrians' safety and mobility, whereas the roles of self-evaluation and self-regulation are still poorly understood. All these elements must be taken into consideration, not only in developing effective safety interventions targeting older pedestrians, but also in designing roads and cars. Recent initiatives are presented here and some recommendations are proposed.


Bone formation in rabbit cancellous bone explant culture model is enhanced by mechanical load.
When studying and designing an artificial bone in vitro with similar features and functionality of natural bone by tissue engineering technology, the culturing environment, especially the mechanical environment is supposed to be an important factor, because a suitable mechanical environment in vitro may improve the adaptability of the planted-in tissue engineering bone in the body. Unfortunately, up to now, the relationship between mechanical stimuli and natural bone growth has not yet been precisely determined, and it is so imperative for a prior study on effect of mechanical loading on growth of the natural bone cultured in vitro. Under sterile conditions, explant models of rabbit cancellous bone with 3 mm in thickness and 8 mm in diameter were prepared and cultured in a dynamic loading and circulating perfusion bioreactor system. By Micro-CT scanning, a 3D model for finite element (FEM) analysis was achieved. According to the results of FEM analysis and physiological load bearing capacity of the natural bone, these models were firstly subjected to mechanical load with 1Hz frequency causing average apparent strain of 1000 με, 2000 με, 3000 με and 4000 με respectively for 30 min every day, activities of alkaline phosphatase (AKP) were detected on the 5th and the 14th loading day and on the 14th and the 21st day, mechanical properties, tissue mineral density (TMD) of the bone explant models were investigated and Von-kossa staining and fluorescence double labeling assays were conducted to evaluate whether there were fresh osteoid in the bone explant models. In addition, Western blot, Elisa and Real-time PCR were employed to analyze expression of Collagen-I (COL-1), bone morphogenetic protein-2 (BMP-2) and osteoprotegerin (OPG) protein and RNA. The explant models of rabbit cancellous bone prepared under sterile conditions grew well in the bioreactor system. With the increasing culturing time and load levels, bone explant models in groups with 1000 με and 2000 με average apparent strain experienced improving mechanical properties and TMD (P<0.05), and results of Von-kossa staining and fluorescence double labeling also showed apparent fresh osteoid formation. Under the same loading conditions, a up-regulations in protein and RNA of COL-1, BMP-2 and OPG were detected, especially, relative genes notably expressed after 21 days. Our study demonstrated that mechanical load could improve function and activity of osteoblasts in explant models of cancellous bone. Through regulations of COL-1, OPG and BMP-2 secreted by osteoblasts, the mechanical load could improve the tissue structural density and stiffness due to formation of fresh osteoid.


Novelty and spatio-temporal heterogeneity in the bacterial diversity of hypersaline Lake Tebenquiche (Salar de Atacama).
Lake Tebenquiche is one of the largest saline water bodies in the Salar de Atacama at 2,500 m above sea level in northeastern Chile. Bacteria inhabiting there have to deal with extreme changes in salinity, temperature and UV dose (i.e., high environmental dissimilarity in the physical landscape). We analyzed the bacterioplankton structure of this lake by 16S rRNA gene analyses along a spatio-temporal survey. The bacterial assemblage within the lake was quite heterogeneous both in space and time. Salinity changed both in space and time ranging between 1 and 30% (w/v), and total abundances of planktonic prokaryotes in the different sampling points within the lake ranged between two and nine times 10(6) cells mL(-1). Community composition changed accordingly to the particular salinity of each point as depicted by genetic fingerprinting analyses (denaturing gradient gel electrophoresis), showing a high level of variation in species composition from place to place (beta-diversity). Three selected sites were analyzed in more detail by clone libraries. We observed a predominance of Bacteroidetes (about one third of the clones) and Gammaproteobacteria (another third) with respect to all the other bacterial groups. The diversity of Bacteroidetes sequences was large and showed a remarkable degree of novelty. Bacteroidetes formed at least four clusters with no cultured relatives in databases and rather distantly related to any known 16S rRNA sequence. Within this phylum, a rich and diverse presence of Salinibacter relatives was found in the saltiest part of the lake. Lake Tebenquiche included several novel microorganisms of environmental importance and appeared as a large unexplored reservoir of unknown bacteria.


Enhancement of immunogenic activity of ribosomal preparations from Haemophilus influenzae by various adjuvants.
Ribosomes from Haemophilus influenzae type b have been reported to have immunoprotective activity in animals that can be enhanced by adjuvants. In this report we evaluated the adjuvant activity of several compounds in conjunction with ribosomes from the b and c serotypes of H. influenzae. Alhydrogel, saponin, and DPT were found to significantly enhance the immunoprotective response in mice, equalling or exceeding the activity of Freund's incomplete adjuvant. All of these adjuvants also enhanced significantly the IgM response of mice to sheep red blood cells. Ribosomes were also found to enhance this response. Among the compounds failing to provide adjuvant activity for ribosomes were poly(A:U), muramyl dipeptide, mycobacterial extract, dimethylglycine, methylated bovine serum albumin, sodium diethylthiocarbamate, and cetyltrimethylammonium bromide.


Association of sleep apnea and type II diabetes: a population-based study.
Cross-sectional association has been reported between sleep-disordered breathing (SDB) and insulin resistance, but no prospective studies have been performed to determine whether SDB is causal in the development of diabetes. The purpose of our study was to investigate the prevalence and incidence of type II diabetes in subjects with SDB and whether an independent relationship exists between them. A cross-sectional and longitudinal analysis was performed in 1,387 participants of the Wisconsin Sleep Cohort. Full polysomnography was used to characterize SDB. Diabetes was defined in two ways: (1) physician-diagnosis alone or (2) for those with glucose measurements, either fasting glucose > or = 126 mg/dl or physician diagnosis. There was a greater prevalence of diabetes in subjects with increasing levels of SDB. A total of 14.7% of subjects with an apnea-hypopnea index (AHI) of 15 or more had a diagnosis of diabetes compared with 2.8% of subjects with an AHI of less than 5. The odds ratio for having a physician diagnoses of diabetes mellitus with an AHI of 15 or greater versus an AHI of less than 5 was 2.30 (95% confidence interval, 1.28-4.11; p = 0.005) after adjustment for age, sex, and body habitus. The odds ratio for developing diabetes mellitus within 4 yr with an AHI of 15 or more compared with an AHI of less than 5 was 1.62 (95% confidence interval, 0.67-3.65; p = 0.24) when adjusting for age, sex, and body habitus. Diabetes is more prevalent in SDB and this relationship is independent of other risk factors. However, it is not clear that SDB is causal in the development of diabetes.


Exploratory analysis of cold, heat, deficiency, or excess pattern distribution in women with dysmenorrhea.
To understand the impact and implications of cold, heat, deficiency, or excess pattern identification in relation to dysmenorrhea, comparing the prevalence of these patterns between women with and without dysmenorrhea is needed. We gathered data from the Korea Constitutional Multicenter Bank. A total of 508 patients were recruited and provided with cold, heat, deficiency, or excess pattern and dysmenorrhea questionnaires. On the basis of their responses, they were divided into the dysmenorrhea group (moderate or severe dysmenorrheic pain; n = 90) and non-dysmenorrhea group (no dysmenorrheic pain; n = 155). We analyzed the characteristics of the groups and compared the cold, heat, deficiency, or excess pattern scores. Comparisons were performed using the independent t-test. We also performed multiple comparisons of each individual symptom between the groups to explore which symptoms appear with dysmenorrhea using the Bonferroni adjustment method. There was a high positive correlation between deficiency pattern scores and excess pattern scores (p < 0.001). The cold, deficiency, and excess pattern scores were significantly higher in the dysmenorrhea group than in the non-dysmenorrhea group (p < 0.001). Twenty among the 76 pattern items showed significant differences between the groups (p < 0.001). Among all items, there was a large effect size only in sleep quality (mean difference 1.07, 95% confidence interval 0.75-1.39, p < 0.001). Women with dysmenorrhea have higher cold, deficiency, and excess pattern scores than those without dysmenorrhea. The longitudinal observation of these symptoms needs to be evaluated using a clinical prospective study design in accordance with pattern differentiation in the future.


Effects of geldanamycin on hatching and juvenile motility in Caenorhabditis elegans and Heterodera glycines.
Several Streptomyces species are known to produce metabolites that inhibit plant pathogens. One such compound is geldanamycin (GA), a benzoquinone ansamycin originally isolated from Streptomyces hygroscopicus. We examined the effect of geldanamycin on egg hatch and juvenile motility in Caenorhabditis elegans and in two populations of the plant-parasitic nematode Heterodera glycines. When C. elegans eggs were exposed to geldanamycin, both hatch and motility were reduced by GA doses between 2 and 50 microg/ml. The H. glycines inbred populations TN17 and TN18 exhibited low dose stimulation of hatch and motility, whereas levels occurring at higher GA doses were at or below control levels. These experiments represent the first demonstration of geldanamycin effects in C. elegans and H. glycines and suggest that the heat shock chaperone Hsp90, the known molecular target of geldanamycin, may be involved in nematode egg hatch and motility. This study also indicates that geldanamycin-producing strains of Streptomyces may be useful as biocontrol agents for nematodes.


Bombesin-like immunoreactivity in female rat genito-urinary tract.
The quantitative distribution and localization of bombesin-like immunoreactivity (BLI), by antiserum which cross-reacted fully with gastrin-releasing peptide (GRP), was determined by radioimmunoassay and immunocytochemistry in various regions of female rat urogenital tract. The highest concentration of BLI was found in the vagina, with lower but significant concentrations in the uterus and bladder. Bombesin-like immunoreactive nerve fibres were localized by immunocytochemistry in the smooth muscle layer, around blood vessels and in the submucosa of the vagina and bladder. BLI was separable into two immunoreactive peaks on both gel permeation chromatography and reverse phase HPLC. The major peak emerged exactly in the position of neuromedin C (C-terminal decapeptide of GRP) in both chromatographic systems, while the remaining immunoreactivity emerged close to the position of porcine GRP on gel permeation chromatography, but was easily distinguishable from this on HPLC. This suggests a significant species difference between rat and porcine GRP. Amphibian bombesin and mammalian neuromedin C have previously been shown to have potent biological actions in the rat urogenital tract. The presence of mammalian bombesin-like peptides in nerve fibres of the urogenital tract suggests that they may have a regulatory role in these organs.


Sevoflurane Preconditioning Confers Neuroprotection via Anti-apoptosis Effects.
Neuroprotection against cerebral ischemia afforded by volatile anesthetic preconditioning (APC) has been demonstrated both in vivo and in vitro, yet the underlying mechanism is poorly understood. We previously reported that repeated sevoflurane APC reduced infarct size in rats after focal ischemia. In this study, we investigated whether inhibition of apoptotic signaling cascades contributes to sevoflurane APC-induced neuroprotection. Male Sprague-Dawley rats were exposed to ambient air or 2.4 % sevoflurane for 30 min per day for 4 consecutive days and then subjected to occlusion of the middle cerebral artery (MCAO) for 60 min at 24 h after the last sevoflurane intervention. APC with sevoflurane markedly decreased apoptotic cell death in rat brains, which was accompanied by decreased caspase-3 cleavage and cytochrome c release. The apoptotic suppression was associated with increased ratios of anti-apoptotic Bcl-2 family proteins over pro-apoptotic proteins and with decreased activation of JNK and p53 pathways. Thus, our data suggest that suppression of apoptotic cell death contributes to the neuroprotection against ischemic brain injury conferred by sevoflurane preconditioning.


Comparison of four COVID-19 screening strategies to facilitate early case identification within the homeless shelter population: A structured summary of a study protocol for a randomised controlled trial.
1. To compare the effectiveness of four different surveillance strategies in detecting COVID-19 within the homeless shelter population. 2. To assess the participant adherence over time for each surveillance method. This is a prospective cluster-randomized study to compare the effectiveness of four different surveillance regimens across eight homeless shelters in the city of Hamilton. Participants will include both residents of, and the staff working within, the homeless shelters. All participants aged 18 or older who consent to the study and are able to collect a swab sample (where relevant) are eligible for the study. The study will take place across eight homeless shelters (four men-only and four women-only) in the City of Hamilton in Ontario, Canada. The comparator group will receive active daily surveillance of symptoms and testing will only be completed in symptomatic participants (i.e. those who fail screening or who seek care for potential COVID-19 related symptoms). The three intervention arms will all receive active daily surveillance of symptoms and testing of symptomatic participants (as in the comparator group) in addition to one of the following: 1. Once weekly self-collected oral swabs (OS) regardless of symptoms using written and visual instructions. 2. Once weekly self-collected oral-nares swab (O-NS) regardless of symptoms using written and visual instructions. 3. Once weekly nurse collected nasopharyngeal swab (NPS) regardless of symptoms. Participants will follow verbal and written instructions for the collection of OS and O-NS specimens. For OS collection, participants are instructed to first moisten the swab on their tongue, insert the swab between the cheek and the lower gums and rotate the swab three times. This is repeated on the other side. For O-NS collection, after oral collection, the swab is inserted comfortably (about 2-3 cm) into one nostril, parallel to the floor and turned three times, then repeated in the other nostril. NPS specimens were collected by the nurse following standard of care procedure. All swabs were placed into a viral inactivation medium and transported to the laboratory for COVID-19 testing. Briefly, total nucleic acid was extracted from specimens and then amplified by RT-PCR for the UTR and Envelope genes of SARS-CoV-2 and the human RNase P gene, which is used as a sample adequacy marker. 1. COVID-19 detection rate, i.e. the number of new positive cases over the study period of 8 weeks in each arm of the study. 2. Qualitative assessment of study enrollment over 8 weeks. Percentage of participants who performed 50% or more of the weekly swabs in the intervention arms in the 8 week study period. We will use a computer-generated random assignment list to randomize the shelters to one of four interventions. Shelters were stratified by gender, and the simple randomization scheme was applied within each stratum. The randomization scheme was created using WinPEPI. This is an open-label study in which neither participants nor assessors are blinded. Since we are including our total sample frame, a sample size estimation at the cluster level is not required. However, if we succeed to enroll 50 participants per shelter from 8 shelters (n=400), and the detection rate is 3 times higher in the intervention groups (0.15) than in the comparator groups (0.05), we will have 90% power to detect a statistically significant and clinically important difference at a type I error rate of alpha=0.05 (one tailed), assuming an intraclass correlation of ~0.008. These computations were done using WinPEPI, and informed by conservative estimates from other studies on respiratory illness in the homeless (see Full protocol). The protocol version number is 3.0. Recruitment began on April 17, 2020 and is ongoing. Due to low numbers of COVID cases in the community and shelter system during the initial study period, the trial was extended. The estimated date for the end of the extended recruitment period is Feb 1, 2021. The trial was registered with ClinicalTrials.gov on June 18, 2020 with the identifier NCT04438070 . The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.


Effect of exogenous nitric oxide in experimental trichinellosis.
Nitric oxide (NO) is a free radical that has been given much attention over the past few years. It has been nicknamed a "killer" and "mediator" due to its toxic and signaling properties. Apart from its regular physiological function, NO indirectly participates in infectious diseases. Our investigations showed that NO administered as a drug may involve higher histopathological changes in infected animals and can involve higher infection. This report seems to be the first presentation of the participation of NO reactive nitrogen intermediates in the morphological transformation of muscle cells in trichinellosis.


Crystals of a nucleosome core particle containing defined sequence DNA.
Nucleosome core particles were reconstituted from a DNA restriction fragment and histone octamers, crystallized, and the crystals examined by X-ray diffraction. A DNA fragment was engineered by site-directed mutagenesis to obtain a 146 base-pair sequence that takes up a symmetrical arrangement in the core particle. The resulting DNA sequence was cloned in multiple copies into pUC9 and excised as monomer via EcoRV to produce it in milligram quantities. Nucleosome core particles incorporating the DNA were reconstituted by salt gradient dialysis and purified by anion-exchange high-pressure liquid chromatography. DNase I digestion was used to demonstrate that the termini of the restriction fragment are located 73 base-pairs from the molecular dyad axis of the particle. The diffraction limits of crystals of defined sequence core particles extend along the principal direction to a approximately equal to 4 A, b approximately equal to 5 A and c approximately equal to 3 A, giving about a twofold increase in the number of measurable X-ray reflections over previous crystals containing mixed sequence DNA. The methods developed here should be useful in the study of other large protein-DNA complexes.


Mesenchymal cells hold the key to immune cell recruitment to and migration within melanoma.
Samaniego et al. (this issue) report on distinct tumor-associated mesenchymal cell (MC) populations in human melanomas. FAP(-)CD90(+) peritumoral MCs may be involved in immune cell recruitment from the bloodstream. FAP(+)CD90(-) intratumoral MCs were associated with extracellular matrix fiber deposition, and their numbers correlated with high immune cell infiltration. Thus, different MC subsets modulate the cellular composition of the intratumoral and peritumoral melanoma microenvironment.


Microscopic evidence for liquid-liquid separation in supersaturated CaCO3 solutions.
Recent experimental observations of the onset of calcium carbonate (CaCO3) mineralization suggest the emergence of a population of clusters that are stable rather than unstable as predicted by classical nucleation theory. This study uses molecular dynamics simulations to probe the structure, dynamics, and energetics of hydrated CaCO3 clusters and lattice gas simulations to explore the behavior of cluster populations before nucleation. Our results predict formation of a dense liquid phase through liquid-liquid separation within the concentration range in which clusters are observed. Coalescence and solidification of nanoscale droplets results in formation of a solid phase, the structure of which is consistent with amorphous CaCO3. The presence of a liquid-liquid binodal enables a diverse set of experimental observations to be reconciled within the context of established phase-separation mechanisms.


Human β defensins-1, an antimicrobial peptide, kills Candida glabrata by generating oxidative stress and arresting the cell cycle in G0/G1 phase.
Candida glabrata is the most frequently isolated non-albicans Candida species in clinical samples and is known to develop resistance to commonly used antifungal drugs. Human β defensins (hBDs) are antimicrobial peptides of immune systems and are active against a broad range of pathogens including Candida species. Herein, the antifungal effect of hBD-1 and its mechanism of action in C. glabrata was studied. The antifungal susceptibility of hBD-1 against C. glabrata was calculated by broth microdilution assay. To study the mechanism of antifungal action, the impact of hBD-1 on cell cycle, expression of oxidative stress enzymes, and membrane disintegration were assessed. The susceptibility results confirmed that hBD-1 possessed the minimum inhibitory concentration of 3.12 µg/mL and prevented the growth and caused yeast cell death to various extents. The peptide at subinhibitory and inhibitory concentrations blocked the cell cycle in C. glabrata in G0/G1 phase and disturbed the activity of primary and secondary antioxidant enzymes. Furthermore, at higher concentrations disruption of membrane integrity was observed. Altogether, hBD-1 showed candidicidal activity against C. glabrata and was able to induce oxidative stress and arrested cell cycle in C. auris and therefore has a potential to be developed as an antifungal drug against C. glabrata.


A CaV2.1 N-terminal fragment relieves the dominant-negative inhibition by an Episodic ataxia 2 mutant.
Episodic ataxia 2 (EA2) is an autosomal dominant disorder caused by mutations in the gene CACNA1A that encodes the pore-forming CaV2.1 calcium channel subunit. The majority of EA2 mutations reported so far are nonsense or deletion/insertion mutations predicted to form truncated proteins. Heterologous expression of wild-type CaV2.1, together with truncated constructs that mimic EA2 mutants, significantly suppressed wild-type calcium channel function, indicating that the truncated protein produces a dominant-negative effect (Jouvenceau et al., 2001; Page et al., 2004). A similar finding has been shown for CaV2.2 (Raghib et al., 2001). We show here that a highly conserved sequence in the cytoplasmic N-terminus is involved in this process, for both CaV2.1 and CaV2.2 channels. Additionally, we were able to interfere with the suppressive effect of an EA2 construct by mutating key N-terminal residues within it. We postulate that the N-terminus of the truncated channel plays an essential part in its interaction with the full-length CaV2.1, which prevents the correct folding of the wild-type channel. In agreement with this, we were able to disrupt the interaction between EA2 and the full length channel by co-expressing a free N-terminal peptide.


Massive haemolysis after intramuscular diclofenac in a patient who apparently tolerated oral medication.
Administration of diclofenac may lead to immune haemolytic anaemia (IHA) owing to the presence of drug-dependent antibodies and/or autoantibodies. A relationship with oral or intramuscular drug administration is unknown. Here, we describe a patient who apparently tolerated oral diclofenac but developed severe IHA following intramuscular injection of the drug. A 66-year-old-female was admitted to hospital because of jaundice and nausea, which were initially presumed to be manifestations of a postcholecystectomy syndrome. The patient soon developed haemolysis and renal failure. Although the symptoms and signs were suggestive of autoimmune haemolytic anaemia (AIHA), the patient had diclofenac-induced IHA. Serological testing, including detection of drug-dependent antibodies, was performed using standard techniques. The patient's serum was found to contain a highly reactive diclofenac-dependent red cell antibody of the immune complex type (titre 256 000). She recovered after 7 weeks of treatment with prednisolone, blood transfusions, haemodialysis and plasma exchange. Diclofenac-induced IHA should always be considered when a patient on diclofenac develops haemolysis.


Cytomegalovirus-associated gastric ulcer simulating malignancy.
A case is reported of cytomegalovirus (CMV) infection with radiological, gastroscopic and histological appearances which led to a mistaken diagnosis of carcinoma of the stomach.


A Recommended Package of Long-Term Care Services to Promote Healthy Ageing Based on a WHO Global Expert Consensus Study.
To reach consensus on a minimum list of long-term care (LTC) interventions to be included in a service package delivered through universal health coverage (UHC). A multistep expert consensus process. Multinational and multidisciplinary experts in LTC and ageing. The consensus process was composed of 3 stages: (1) a preconsultation round that built on an initial list of LTC interventions generated by a previous scoping review; (2) 2-round surveys to reach consensus on important, acceptable, and feasible interventions for LTC; (3) a panel meeting to finalize the consensus. The preconsultation round generated an initial list of 117 interventions. In round 1, 194 experts were contacted and 92 (47%) completed the survey. In round 2, the same experts contacted for round 1 were invited, and 115 (59%) completed the survey. Of the 115 respondents in round 2, 80 participated in round 1. Experts representing various disciplines (eg, geriatricians, family doctors, nurses, mental health, and rehabilitation professionals) participated in round 2, representing 42 countries. In round 1, 81 interventions achieved the predetermined threshold for importance, and in round 2, 41 interventions achieved the predetermined threshold for acceptability and feasibility. Nine conflicting interventions between rounds 1 and 2 were discussed in the panel meeting. The recommended list composed of 50 interventions were from 6 domains: unpaid and paid carers' support and training, person-centered assessment and care planning, prevention and management of intrinsic capacity decline, optimization of functional ability, interventions needing focused attention, and palliative care. An international discussion and consensus process generated a minimum list of LTC interventions to be included in a service package for UHC. This package will enable actions toward a more robust framework for integrated services for older people in need of LTC across the continuum of care.


An impact evaluation of the safe motherhood promotion project in Bangladesh: evidence from Japanese aid-funded technical cooperation.
This paper reports the findings from a quasi-experimental impact evaluation of the Safe Motherhood Promotion Project (SMPP) conducted in the Narsingdi district of Bangladesh. SMPP is a Japanese aid-funded technical cooperation project aimed at developing local capacities to tackle maternal and newborn health problems in rural areas. We assessed whether the project interventions, in particular, community-based activities under the Model Union approach, had a favorable impact on women's access to and knowledge of maternal health care during pregnancy and childbirth. The project comprises a package of interlinked interventions to facilitate safe motherhood practices at primary and secondary care levels. The primary-level activities focused on community mobilization through participatory approaches. The secondary-level activities aimed at strengthening organizational and personnel capacities for delivering emergency obstetric care (EmOC) at district and sub-district level hospitals. The project impact was estimated by difference-in-differences logistic regressions using two rounds of cross-sectional household survey data. The results showed that the project successfully increased the utilization of antenatal visits and postpartum EmOC services and also enhanced women's knowledge of danger signs during pregnancy and delivery. The project also reduced income inequalities in access to antenatal care. In contrast, we found no significant increase in the use of skilled birth attendants (SBA) in the project site. Nonetheless, community mobilization activities and the government's voucher scheme played a complementary role in promoting the use of SBA.


Risk Factors for Postoperative Complications Following Diverting Loop Ileostomy Takedown.
Diverting loop ileostomies are frequently created to divert the fecal stream in an effort to protect downstream anastomoses. These are later reversed to restore intestinal continuity. The goal of this study is to evaluate risk factors for postoperative complications following diverting loop ileostomy takedown. Patients who underwent diverting loop ileostomy takedown between January 1, 2010 and April 28, 2015 were identified in the Michigan Surgical Quality Collaborative registry. Candidate covariates were identified and a hierarchical logistic regression model was used to identify risk factors for postoperative complications. 1,737 patients met the inclusion criteria. Rates of postoperative complications were generally low. Mean length of stay (LOS) was 5.6 (± 4.5) days. Outcomes of interest were the following: overall morbidity, serious morbidity, extended LOS, SSI, UTI, pneumonia, readmission, reoperation, and mortality. Risk factors for these outcomes included the following: ASA class, bleeding disorder, prolonged operative time, race, tobacco use, gender, steroid use, peripheral vascular disease, weight loss, and functional status. Diverting loop ileostomy takedown has a complication rate of approximately 20%. Higher ASA class, longer operative times, history of bleeding disorder, and functional status were identified as risk factors for most complications.


Enzymatic responses reveal different physiological strategies employed by eurytolerant fish during extreme hot and cold cycling acclimation temperatures.
Heat waves and cold snaps are projected to rise in magnitude, duration, interval, and harshness in the coming years. The current literature examining thermal impacts on the physiology of organisms rarely uses chronic, variable thermal acclimations despite the fact that climate change predictions project a more variable environment. If we are to determine species' susceptibility to climate change, chronic and variable lab acclimations should be prioritized. Here, we acclimated the eurytolerant sheepshead minnow (Cyprinodon variegatus) to two extreme cycling thermal regimes: one warm [resting 27 °C with a spike to 33 °C for 8 h daily], one cold [resting 6.5 °C with a spike to 12 °C for 8 h daily], and three chronically stable conditions (10, 22, and 30 °C) for comparison. We measured enzymatic antioxidants (catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx)), total antioxidant capacity, lipid peroxidation (LPO) damage, and citrate synthase (CS) activity in white epaxial muscle. Of particular note, we found significant increases in log CAT activity and SOD concentration in the warm cycling temperatures, and significant increases in GPx activity in the cold cycling temperatures. We found no significant accumulation of LPO damage in any of our thermal acclimation treatments. Thus, sheepshead minnows demonstrate two particularly different mechanisms towards dealing with thermal variation in low and high temperatures. The enzymatic differences between low and high cycling temperatures may define pathways of eurytolerant organisms and how they may survive predicted variability in thermal regimes.


The differences in spiritual health between non-depressed and depressed nurses.
The aim of this study was to compare the differences in spiritual health between depressed and non-depressed nurses. Previous studies have revealed that spirituality can buffer emotional pressure and maintain health, even in cases of depression. Nurses may have a tendency to develop depression; however, the relationship between depression and spirituality in nurses has been investigated only rarely. A correlational study. The study was conducted using a convenience sample of 283 nurses who worked at a local hospital in northern Taiwan. We used a structured, self-administered questionnaire to obtain the data. This questionnaire included a spiritual health scale, the Beck Depression Inventory and personal data. The quantitative data were analysed using the t-test, one-way analysis of variance and logistic regression. All the participants were women, and 22·6% of the participants were ascertained to have depression. The non-depressed group had a higher average score for the different domains of the spiritual health scale than the depressed group. When personal and job-related variables were controlled, spirituality was a significant explanatory variable for depression. The spiritual health of the non-depressed nurses was better than that of the depressed nurses. The result was consistent with the previous studies on other populations. The spiritual health and depression of nurses should be paid attention by nursing administrators. Spiritual promoting programme in preventing depression should be examined in future researches.


Aggregation state of Mycobacterium tuberculosis impacts host immunity and augments pulmonary disease pathology.
In vitro phagocytosis of Mycobacterium tuberculosis (Mtb) aggregates (Mtb-AG), rather than similar numbers of single bacilli (Mtb-SC), induces host macrophage death and favors bacterial growth. Here, we examined whether aggregation contributes to enhanced Mtb pathogenicity in vivo in rabbit lungs. Rabbits were exposed to infectious aerosols containing mainly Mtb-AG or Mtb-SC. The lung bacterial load, systemic immune response, histology, and immune cell composition were investigated over time. Genome-wide transcriptome analysis, cellular and tissue-level assays, and immunofluorescent imaging were performed on lung tissue to define and compare immune activation and pathogenesis between Mtb-AG and Mtb-SC infection. Lung bacillary loads, disease scores, lesion size, and structure were significantly higher in Mtb-AG than Mtb-SC infected animals. Differences in immune cell distribution and activation were noted in the lungs of the two groups of infected animals. Consistently larger lung granulomas with large aggregates of Mtb, extensive necrotic foci, and elevated matrix metalloproteases expression were observed in Mtb-AG infected rabbits. Our findings suggest that bacillary aggregation increases Mtb fitness for improved growth and accelerates lung inflammation and infected host cell death, thereby exacerbating disease pathology in the lungs.


Patients with Psoriatic Arthritis Fulfilling the Minimal Disease Activity Criteria Do Not Have Swollen and Tender Joints, but Have Active Skin.
To evaluate components of the minimal disease activity (MDA) criteria in psoriatic arthritis (PsA). In patients achieving and not achieving MDA, fulfillment of each of the 7 criteria was evaluated. Among 41 patients with MDA, 7.4% did not fulfill the tender/swollen joint count whereas 49% did not fulfill the skin criteria. Of the 42 patients not fulfilling MDA, 100%, 76.5%, and 65% did not fulfill the patient pain score, the patient's global assessment, and the Psoriasis Area and Severity Index (PASI), respectively. A minority of patients with PsA fulfilling the MDA criteria presented active joints, but half had active skin. Visual analog scale scores and the PASI prevented patients from achieving MDA.


Applications of Resting State Functional MR Imaging to Traumatic Brain Injury.
Traumatic brain injury (TBI) is an important public health issue. TBI includes a broad spectrum of injury severities and abnormalities. Functional MR imaging (fMR imaging), both resting state (rs) and task, has been used often in research to study the effects of TBI. Although rs-fMR imaging is not currently applicable in clinical diagnosis of TBI, computer-aided tools are making this a possibility for the future. Specifically, graph theory is being used to study the change in networks after TBI. Machine learning methods allow researchers to build models capable of predicting injury severity and recovery trajectories.


Red And far-red regulation of filament movement correlates with the expression of phytochrome and FHY1 genes in Spirogyra varians (Zygnematales, Streptophyta)1.
Spirogyra filaments show unique photomovement that differs in response to blue, red, and far-red light. Phototropins involved in the blue-light movement have been characterized together with downstream signaling components, but the photoreceptors and mechanical effectors of red- and far-red light movement are not yet characterized. The filaments of Spirogyra varians slowly bent and aggregated to form a tangled mass in red light. In far-red light, the filaments unbent, stretched rapidly, and separated from each other. Mannitol and/or sorbitol treatment significantly inhibited this far-red light movement suggesting that turgor pressure is the driving force of this movement. The bending and aggregating movements of filaments in red light were not affected by osmotic change. Three phytochrome homologues isolated from S. varians showed unique phylogenetic characteristics. Two canonical phytochromes, named SvPHY1 and SvPHY2, and a noncanonical phytochrome named SvPHYX2. SvPHY1 is the first PHY1 family phytochrome reported in zygnematalean algae. The gene involved in the transport of phytochromes into the nucleus was characterized, and its expression in response to red and far-red light was measured using quantitative PCR. Our results suggest that the phytochromes and the genes involved in the transport system into the nucleus are well conserved in S. varians.


Focus on the impact of social factors and lifestyle on the disease burden of low back pain: findings from the global burden of disease study 2019.
Low back pain (LBP) is one of the leading causes of disability worldwide. Differences in social backgrounds and lifestyles in various regions and countries may contribute to the discrepancies in the disease burden of LBP. Based on the GBD 2019, we collected and analyzed numbers and age-standardized rates (ASR) of LBP disability-adjusted life years (DALYs). Temporal trends in ASR were also analyzed using estimated annual percentage change (EAPC). The Age-period-cohort (APC) model was used to estimate age, period and cohort trends in DALYs of LBP. An autoregressive integrated moving average (ARIMA) model was used to forecast DALYs of LBP trends from 2020 to 2035. The DALYs due to LBP increased from 1990 to 2019. The APC model showed that the risk of DALYs for global LBP increased with age and year and that the risk of DALYs was lower in the later-born cohort than in the earlier-born cohort. The main risk factors which GBD estimates were available for DALYs of LBP include smoking, occupational ergonomic factors and high BMI. It is expected that DALYs of LBP will continue to rise until 2035. From 1990 to 2019, the global disease burden of LBP remained high. It is necessary to pay attention to the influence of social factors and lifestyle on LBP. Focusing on the impact of social factors as well as lifestyle on the prognosis of LBP and targeting interventions may further reduce the disease burden of LBP.


The anticoagulant fraction from the leaves of Diospyros kaki L. has an antithrombotic activity.
The leaves of Persimmon (Diospyros kaki L.) has long been used for tea in Korea since it was thought to be effective against hypertension. An anticoagulant fraction was purified through gel filtration G-100, hydrophobic, gel filtration G-150, and FPLC, Phenyl superpose column chromatographies. The purified fraction was homogenous and its Mr was estimated 10,000 Da by gel filtration and SDS-PAGE. The purified fraction was sensitive to treatment of subtilisin B, but not to heat and its activity was not changed after periodate oxidation, indicating that the activity was not due to carbohydrates. It delayed thrombin time (TT), activated partial thromboplastin time (APTT), and prothrombin time (PT) using human plasma. TT was more sensitive than APTT and PT, suggesting that the anticoagulant activity may be caused by a degradation or a defect of fibrin or thrombin. It did not cause the hydrolysis of fibrin after incubation. However, it inhibited thrombin-catalyzed fibrin formation with a competitive inhibition pattern. These results indicate that it may be an antithrombotic agent and that it is bound to fibrinogen binding sites of thrombin.


Oxytocin acts as an antidepressant in two animal models of depression.
In the behavioral despair test in mice, oxytocin, i.p. injected 60 min before testing, significantly reduced the duration of immobility at doses of 0.250-1.0 mg/Kg; the effect being similar to that of imipramine (7.5-30 mg/Kg i.p.). A more powerful effect was obtained with a 10-day treatment schedule. In the learned helplessness test, oxytocin (0.500 mg/Kg/day i.p. for 8 days) significantly reduced the escape failures and the latency to escape, the effect being even more intense than that of imipramine (20 mg/Kg/day i.p. for 8 days). These results show a new behavioral effect of oxytocin, and further support its role of CNS regulatory peptide.


Incidence, timing and site of infections among pancreas transplant recipients.
The incidence, timing and site of infections among the different categories of pancreas transplant recipients were investigated. Patients were divided into three groups: pancreas transplant alone (PTA), pancreas after kidney transplant (PAK), or simultaneous pancreas and kidney (SPK) transplants. Length of follow-up, time to death, pancreas graft survival, incidence, timing and site of bacterial infections were noted. Our study showed that at least 75% of pancreas transplant recipients experienced at least one infection (range from 77.8% in the PTA group to 86.7% in the PAK group). The SPK group presented the highest rate of infections with 35.1 infections per 1000/patient-days. Symptomatic urinary tract infections were the most common cause of infection in all patients. The incidence of infections was higher during the first month after transplantation, except for the SPK transplant group, where infections occurred over a longer time period.


Pituitary apoplexy goes to the bar: litigation for delayed diagnosis, deficient vision, and death.
Over the past 15 years, I have reviewed the records of six patients whose physicians were alleged to have failed to diagnose a pituitary tumor before it bled ("apoplexy") or failed to recognize apoplexy after it had occurred. These cases were referred by attorneys involved in lawsuits alleging medical negligence. Their histories are summarized here from available clinical records, depositions, and other legal documents. None of these cases is still in litigation. The purpose of this commentary is to show how such legal case material is useful in alerting the medical community to pitfalls in diagnosis.


Percutaneous coronary intervention with or without on-site coronary artery bypass surgery: a systematic review and meta-analysis.
Current American Heart Association guidelines recommend against the performance of elective or primary percutaneous coronary intervention (PCI) without on-site surgical backup (i.e. a class III and IIb recommendation respectively). Despite this, numerous centers have already implemented PCI programs with no on-site surgery backup (NSOS). To evaluate the necessity for on-site surgical backup (SOS) when performing PCI we performed a systematic review and meta-analysis. English-language articles published from 1966 through December 2010 were retrieved using keyword searches of Medline and Scopus, supplemented by letters to authors and reviews of all bibliographies. Article inclusion and data extraction was performed by two independent reviewers. We identified 18 articles published between 1992 and 2009 which contained reported events on 1,150,200 patients. The combined odds ratio calculated using a random effects model for death with NSOS was 0.93 (95% CI, 0.80-1.09). In studies with data reported for primary PCI and elective PCI the OR for death was 0.91 (95% CI, 0.84-1.00) and 1.04 (95% CI, 0.67-1.63). A lack of effect of SOS was maintained when analysis was performed by study type or by either primary or elective PCI. No differences in rates of emergency coronary artery bypass grafting, post procedural myocardial infarction, target vessel revascularization, or cerebrovascular accidents were observed between SOS and NSOS centers. Both primary and elective PCI can safely be performed at NSOS centers without an increase in mortality or PCI related complications. AHA/ACC guidelines should reflect the lack of benefit conferred by on-site surgical backup. In establishing PCI programs, adequate operator/center volumes, patient selection, and geographic/population considerations should take precedence rather than the availability of on-site surgical backup during PCI.


Cingulate cortex in Parkinson's disease.
Once a diagnosis of Parkinson's disease (PD) has been made, even in its earliest prodromal form of subjective memory impairment, cognitive impairment has begun and involves anterior cingulate cortex (ACC). While the Braak staging scheme showed mid- to later-stage PD progression from cingulate allocortex adjacent to the corpus callosum and progressing into its neocortical moieties, the last decade has produced substantial information on the role of cingulate cortex in multiple symptoms, not just global measures of cognition. Voxel-based morphometry has been used in many studies of mild cognitive impairment (MCI) in PD to show reduced thickness in ACC and posterior cingulate cortex (PCC). Regional cerebral blood flow is altered in association with verbal IQ in all the PCC and anterior midcingulate cortex and executive impairments in ACC. Diffusion tensor imaging shows reduced fractional anisotropy throughout the entire cingulum bundle. Amnestic MCI is associated with reduced dopamine-2 receptor binding in ACC and, even in cognitively normal PD cases, dopaminergic pathways in ACC are impaired early in association with executive and language functions. The cholinergic system also has substantial changes in nicotinic and muscarinic receptor binding, and therapy with donepezil improves Mini-Mental State Exam scores and metabolism in pACC and dPCC. Cingulate cortex is also engaged in two critical symptoms: apathy and visual hallucinations. Finally, one can be optimistic that cingulate cortex will play an important role in developing new biomarkers of early PD. These methods have already been shown to be useful in cingulate cortex and include magnetic resonance spectroscopy, next-generation gene expression, and the new α-synuclein proximity ligation assay that specifically recognizes α-synuclein oligomers. Thus the future is bright for developing multivariate, multimodal biomarkers that include cingulate cortex.


Immunohistochemical expression of inhibin-alpha in human endometrium and the in vitro secretion of inhibin, estradiol and cortisol in cultured human endometrial glandular cells.
Inhibins are multipotent dimeric glycoproteins, composed of an alpha-subunit and one of two possible beta-subunits (betaA or betaB). Aims of this study were (a): the immunohistochemical characterisation of normal human endometrium for the inhibin-alpha subunit; (b) the assessment of the secretion and metabolism of inhibin, E2 and cortisol; (c) the evaluation of any relationship between these three substances in cell culture medium of isolated and cultivated normal human endometrial glandular cells. Samples of human endometrium were obtained from 34 premenopausal patients. Nineteen endometrial specimen (proliferative [PP] n=8; early secretory [ES] n=7; late secretory phase [LS] n=4) were brought into cell culture. Fifteen endometrial specimen (PP n=5; ES n=5; LS n=5) were paraffin-fixed and used for the immunohistochemical analysis for inhibin-alpha. Stromal and epithelial cells were separated by collagenase digestions, filtrations, sedimentations and Ficoll-gradient centrifugation. E2 and cortisol were measured with radioimmunoassay (RIA) and inhibin with enzyme-immunoassay (EIA). Statistical analysis was performed with the non-parametric Mann-Whitney rank-sum test and linear regression analysis. Inhibin-alpha showed a weak (positive) expression during proliferative phase, which increased significantly as the menstrual cycle continued. In secretory glands the mean inhibin concentration was higher than that from proliferative samples. A significant correlation was observed between inhibin and E2 (p<0.001) as well as cortisol and inhibin (p<0.0001) in glands from proliferative phase. Between inhibin and E2 (p<0.05) as well as inhibin and cortisol (p<0.002) a significant correlation in early secretory glands was also noted. In late secretory phase inhibin and E2 (r2=0.78650; p<0.0001), inhibin and cortisol (r2=0.58326; p<0.001) and E2 and cortisol (r2=0.52880; p<0.001) showed a significant correlation. In conclusion, we found a cyclical expression of inhibin-alpha subunit in the endometrium demonstrated by immunohistochemical means. A higher in vitro secretion of inhibin from secretory glands was also observed. In addition, a significant correlation between inhibin with E2 and cortisol in PP and ES glands and a significant correlation between inhibin, E2 and cortisol in LS glands could also be demonstrated. We conclude that inhibin can be associated with E2 and cortisol metabolism, playing an important role in paracrine/autocrine mechanisms in the endometrium and possibly exerting its function through cortisol and E2. The cortisol concentration also correlates with E2, suggesting a link between these steroids in the endometrial function. The correlation of inhibin, E2 and cortisol suggest complex autocrine/ paracrine mechanisms in human endometrial glands, modulated and controlled by all these three substances.


Evaporation-based method for preparing gelatin foams with aligned tubular pore structures.
Gelatin-based foams with aligned tubular pore structures were prepared via liquid-to-gas vaporization of tightly bound water in dehydrated gelatin hydrogels. This study elucidates the mechanism of the foaming process by investigating the secondary (i.e., helical) structure, molecular interactions, and water content of gelatin films before and after foaming using X-ray diffraction, Fourier transform infrared (FTIR) spectroscopy, differential scanning calorimetry and thermogravimetric analysis (TGA), respectively. Experimental data from gelatin samples prepared at various gelatin-to-water concentrations (5-30 wt.%) substantiate that resulting foam structures are similar in pore diameter (approximately 350 μm), shape, and density (0.05-0.22 g/cm(3)) to those fabricated using conventional methods (e.g., freeze-drying). Helical structures were identified in the films but were not evident in the foamed samples after vaporization (~150 °C), suggesting that the primary foaming mechanism is governed by the vaporization of water that is tightly bound in secondary structures (i.e., helices, β-turns, β-sheets) that are present in dehydrated gelatin films. FTIR and TGA data show that the foaming process leads to more disorder and reduced hydrogen bonding to hydroxyl groups in gelatin and that no thermal degradation of gelatin occurs before or after foaming.


Miniaturising the laboratory in emulsion droplets.
Biochemical and genetic assays can be both miniaturized and parallelized by compartmentalization in living cells. In vitro compartmentalization (IVC) offers an alternative strategy based on partitioning reactions in water droplets dispersed to form microscopic compartments in water-in-oil emulsions. The cell-like volumes of these compartments (as low as one femtolitre), the ability to freely determine and regulate their content and the large number of compartments (>10(10) per millilitre emulsion) have provided the basis for a range of new, ultra-high-throughput, cell-free technologies. This review describes the scope and potential of IVC in areas such as in vitro evolution of proteins and RNAs, cell-free cloning and sequencing, genetics, genomics, and proteomics.


Assessing the routine-practice gap for home blood pressure monitoring among Chinese adults with hypertension.
Home blood pressure monitoring (HBPM) is recommended for diagnosis, treatment adjustment and management of most hypertension cases in hypertension guidelines from multiple countries. This study aimed to evaluate HBPM behaviour and explore the routine-practice gap in HBPM among Chinese adults with hypertension. Data were collected from 20 communities across three cities and six townships in three provinces (Beijing, Shandong and Jiangsu) in China between October 2014 and November 2014. In total, 2272 patients with hypertension aged ≥35 years that were registered with a primary health station in their local communities were selected by simple random sampling. Among the 2272 participants, 45.3% owned a home blood pressure (BP) monitor. In addition, 27.5% (625/2272) engaged in HBPM weekly or more frequently. Healthcare providers' advice was the strongest factor contributing to home BP monitor ownership and weekly HBPM behaviour, with odds ratios of 13.50 and 8.97, respectively. Approximately 4.4% of participants had achieved optimal HBPM regimens (duplicate measurements in the morning and evening for 7 days). Patients with uncontrolled office-measured BP were more likely to conduct HBPM regularly in the morning and evening, measure their BP two or three times in each session and maintain 7 consecutive days of HBPM than patients with controlled office BP (8.8% vs. 5.8%, P = 0.042; 14.3% vs. 8.1%, P = 0.002; and 19.9% vs. 12.4%, P = 0.005, respectively). Only 16.0% (165/1030) of participants actively reported their HBPM readings to doctors. The HBPM strategies specified in hypertension guidelines are seldom achieved in actual practice in China. Only a small proportion of patients actively participate in using HBPM to enhance their hypertension care. HBPM may be improved by healthcare providers offering specific advice and training.


The Question of Global Society in Post-Corona Time: Towards a Paradigm Shift.
Whether the COVID-19 has natural or laboratory roots, it has so far posed serious challenges for many of the current human paradigms and the longer it takes, the greater impacts it will have on today's world order. This paradigm shift and a new sight at the post-Corona era led us to the question of which factors caused the epidemic to spread more or less indifferent countries of the world and what was the global responses to prevent this epidemic? Following that, what is important, is the consequences of this epidemic, which can be considered in the question of a paradigm shift in the post-Corona time.


Hypered laparoscopic and endoscopic management of lower gastrointestinal bleeding from metastatic Jejunal and ileal choriocarcinoma of unknown primary.
Choriocarcinoma is form of malignant neoplasm that arise from trophoblastic cells that occurs mostly in ovaries and testes and it can metastasis to lungs, liver or to gastrointestinal tract. This is 37 years old female presented as a case of lower gi bleeding and was diagnosed to have metastatic jejunal and ilium choriocarcinoma of unknown primary and underwent ileocecal resection first then followed up with small bowel resection around 60 cm from duodenojejunal junction with primary anastomosis. The patient was found to have liver and brain metastasis and received chemotherapy with full response. Choriocarcinoma is the most aggressive form of gestational trophoblastic disease that metastasizes through the lymphatic and hematogenous routes, and when its metastasis to the small bowel it's considered the worst prognosis with high mortality rate. Treatment consists of surgery and combined chemotherapy which is what our patient responded with. Metastatic choriocarcinoma with unknown primary can be treated surgically with chemotherapy.


cMYC expression in thyroid follicular cell-derived carcinomas: a role in thyroid tumorigenesis.
cMYC regulates approximately 15% of human genes and is involved in up to 20% of all human cancers. Reports discussing cMYC protein expression in thyroid carcinomas are limited, with controversies pertaining to cMYC expression patterns noted in the literature. The aims of the current study were to clarify patterns and intensities of cMYC expression in follicular cell-derived thyroid carcinomas across a spectrum of cancer morphologies and disease aggressivities, to correlate cMYC with BRAFV600E expression, and to evaluate the potential role of cMYC in progression of well-differentiated thyroid carcinomas into less well-differentiated carcinomas. Immunohistochemical studies using specific monoclonal antibodies for cMYC and BRAFV600E were performed on tissue microarrays built from follicular cell-derived thyroid carcinomas (25 papillary, 24 follicular, 24 oncocytic variant of follicular, and 21 undifferentiated). In addition, cMYC IHC testing was also performed on whole tissue tumor sections from a subset of patients. Nodular hyperplasia cases were used as non-neoplastic controls. Appropriate positive and negative controls were included. cMYC was expressed almost exclusively in a nuclear fashion in both thyroid carcinomas and nodular hyperplasias. cMYC expression was weakly positive in both nodular hyperplasias and well-differentiated carcinomas. The majority of undifferentiated carcinomas (UDCs) showed strong nuclear cMYC positivity. PTC cases that were positive for cMYC (6/25) harbored the BRAF V600E mutation. A correlation was confirmed between cMYC intensity and tumor size in UDCs. UDC cases that developed out of well-differentiated thyroid carcinomas showed frank overexpression of cMYC in the undifferentiated tumor components. Our study suggests that nuclear overexpression of cMYC correlates with tumorigenesis / dedifferentiation in follicular cell derived thyroid carcinomas, a concept that has not been shown before on whole tissue sections.


The case of spontaneous stoma closure in patient with loop ileostomy.
An ileostomy is a mean to empty the contents of the bowel via ileum rather than usual anal route to prevent distal anastomotic leak. It is considered a controlled entero-cutaneous (EC) fistula which prevents contamination of peritoneal cavity, protecting the peri-stomal skin from effluent and excoriation. Spontaneous closure of ileostomy is a very rare phenomenon. Thus, we hereby report a case of spontaneous closure of ileostomy. An 18-years male presented with complaints of pain abdomen, vomiting for 6 days. Chest X-ray showed free air under the right dome of diaphragm suggestive of pneumo-peritoneum. So explorative laparotomy with primary repair of ileal perforation with diversion loop ileostomy (2 ft proximal to ileocecal junction) was performed. Over the months stoma retracted and eventually spontaneous closure of stoma took place after 4 months of surgery. Retraction of stoma depends on multiple factors. Firstly, on patient's general condition, if he/she is malnourished/obese/immunocompromised then retraction occurs due to poor healing of wound. Secondly, it results from inadequate mobilization of bowel. Separation of stoma with muco-cutaneous fascial planes leads to gradual retraction of stoma which is primary mechanism of spontaneous closure of stoma. To summarize, gradual retraction of stoma (complication of an ileostomy) and healing of EC fistula has to be correlated to know the complex mechanism of spontaneous closure of an ileostomy.


Cerebral Amyloid Angiopathy-Related Inflammation (CAA-ri): Presentation at an Unusual Age.
Cerebral amyloid angiopathy-related inflammation (CAA-ri) is a less common but aggressive manifestation of CAA caused by an autoimmune reaction to the amyloid-beta (Ab) deposits in affected vessels. Here, we report the case of a 96-year-old patient, with a history of Alzheimer's disease, who presented to our hospital due to a sudden onset of high-intensity holocranial headache followed by dysarthria, left hemiplegia, and gaze deviation to the right. MRI of the brain was performed, which revealed a heterogeneous hypointense signal on the right frontal T2 and fluid-attenuated inversion recovery (FLAIR) sequences, with an asymmetric hyperintensity surrounding the lesion compatible with perilesional vasogenic edema. Given the clinical radiographic findings, a diagnosis of CAA-ri was established and immediate treatment with intravenous corticosteroids was started, with a rapid clinical response and remarkable improvement in follow-up neuroimaging.


[Updated S3-Guideline Colitis ulcerosa. German Society for Digestive and Metabolic Diseases (DGVS) - AWMF Registry 021/009].
This guideline provides evidence-based key recommendations for diagnosis and treatment of ulcerative colitis and upgrades the 2011 version. The guideline was developed by an interdisciplinary team of gastroenterologists, surgeons, pathologists, nutrition experts, and patient support groups under the auspice of the German Society for Gastroenterology and Metabolic Diseases. The guideline used structural S3 consensus-based methodology and includes statements on clinical practice, prevention, infectiological problems, surgery and nutrition.


Effect of papulacandin B and calcofluor white on the incorporation of mannoproteins in the wall of Candida albicans blastospores.
Incorporation of mannoproteins into the walls of Candida albicans blastospores (yeast phase) was followed by continuous labelling and pulse-chase experiments. The effect in the process of compounds that interfere with synthesis (papulacandin B) or assembly (calcofluor white) of structural polymers was also assessed. Mannoproteins which are kept in place by non-covalent bonds (mainly hydrogen bonds) were incorporated rapidly after their release into the periplasmic space, this process being blocked by calcofluor white. The stain had no effect on the incorporation of covalently linked mannoproteins. Papulacandin B inhibited formation of beta-glucans and incorporation of covalently linked mannoprotein molecules, whereas incorporation of hydrogen-bonded species took place normally. The results suggest that the formation of the non-covalent bonds between the mannoproteins occurs once they are secreted into the periplasmic space, whereas the formation of covalent connections between mannoproteins and wall glucan takes place at the level of the plasma membrane.


A Phase I, randomized, placebo-controlled, 3-day, ascending-dose study of GS-9451, an NS3/4A protease inhibitor, in genotype 1 hepatitis C patients.
GS-9451 is a novel inhibitor of the HCV NS3/4A protease and demonstrates potent in vitro suppression of HCV genotype 1 replicons. The safety, pharmacokinetics and antiviral efficacy of GS-9451 were evaluated in a Phase I study in treatment-naive, HCV genotype-1-infected patients. Patients were randomized to 3 days of once-daily dosing with placebo (n=8) or GS-9451 60 mg (n=8 genotype 1a), 200 mg (n=8 genotype 1a; n=8 genotype 1b) or 400 mg (n=9 genotype 1a). Plasma samples were collected up to and on day 14 for pharmacokinetic evaluation, serum HCV RNA quantitation and NS3 sequencing. No patients interrupted or discontinued dosing because of an adverse event. The median (range) maximal HCV RNA reductions from baseline were -0.88 (-1.24- -0.64), -3.19 (-3.31- -2.94) and -3.64 (-4.08- -3.54) log10 IU/ml in genotype 1a patients receiving 60, 200 and 400 mg/day GS-9451, respectively, and -3.48 (-3.54- -3.03) log10 IU/ml in genotype 1b patients receiving GS-9451 200 mg/day. Median half-life ranged from 14 to 17 h. Day 3 mean concentration at the end of dosing interval was 5.5- and 17-fold above protein-binding adjusted mean 50% effective inhibitory concentration in 200 mg and 400 mg cohorts, respectively. No resistance mutations were detected with GS-9451 60 mg/day. In the 200 mg/day or 400 mg/day groups, predominant mutations were NS3 R155 (R155K) in genotype 1a patients and D168 (D168E, D168V and D168G) in genotype 1b patients. GS-9451 was well-tolerated. During 3 days of monotherapy, GS-9451 200 mg/day or 400 mg/day demonstrated potent antiviral activity in both HCV genotype 1a- and 1b-infected patients. GS-9451 is currently being evaluated in combination regimens with and without pegylated interferon-α.


Patterns of symptoms following surgery for esophageal cancer.
To explore patterns of symptoms before and after surgery for cancer of the esophagus. Longitudinal, descriptive study. An urban comprehensive cancer center in the northeastern United States. 218 patients with cancer of the esophagus undergoing esophagectomy. Symptoms were assessed by self-report before surgery, at the first postoperative visit, and at 6 and 12 months postsurgery. Symptoms and demographic and clinical variables, including stage, treatment, gender, and comorbidities. Patients with esophageal cancer reported numerous symptoms before and after esophagectomy. Several patterns of symptoms were identified. General cancer symptoms (e.g., pain, cough, shortness of breath, weight loss) were reported as worse after surgery but recovered to baseline by one year. A second pattern of esophageal-specific symptoms (feeling full too quickly, feeling bloated, nausea, and diarrhea) worsened after surgery and did not recover to baseline by one year. Reflux was the only symptom that did not worsen after surgery but did worsen significantly during the first year of recovery. Patients with esophageal cancer experienced multiple prolonged symptoms following surgical treatment for their disease. General cancer symptoms resolved by one year post-treatment, whereas esophageal-specific symptoms worsened after surgery and did not recover to baseline. Identification of symptom patterns preoperatively and during recovery can assist nurses in developing intervention protocols to minimize long-term complications for patients with esophageal cancer. Patients with esophageal cancer are at risk for multiple prolonged symptoms following surgery. Symptom assessment should occur often after surgery and include a broad range of symptoms.


Prescription Patterns of Novel Antihyperglycemic Medications.
Glucagon-like peptide-1 agonists (GLP-1a) and sodium-glucose cotransporter-2 inhibitors (SGLT-2i) are recommended in carefully selected patients with type 2 diabetes. This study will assess prescription of these medications and investigate predictors of prescription. This retrospective cross-sectional study included 31,354 patients. Data including sociodemographic descriptors, clinical histories, medications, and health insurance providers were extracted from a health system's administrative databases. Variables to be associated with prescription of a GLP-1a or SGLT-2i were assessed using a multivariable logistic regression model. Mean age was 62.58 years and 40.8% identified as African American. Only 3.4% were prescribed a GLP-1a and 2.1% received a SGLT-2i. Logistic regression demonstrated lower odds of receiving either medication in the highest age-group (70 to 79 years) (GLP-1a: odds ratio [OR] 0.44, P < .01, SGLT-2i: OR 0.39, P < .01) and in African Americans (GLP-1a: OR 0.64, P < .01, SGLT-2i: OR 0.28, P < .01). Atherosclerotic cardiovascular disease was not associated with GLP-1a prescription (P = .54) and conferred lower odds of being prescribed SGLT-2i (OR 0.68, P < .01). History of chronic kidney disease conferred lower odds of receiving GLP-1a and was not associated with the odds of receiving SGLT-2i. Prescription of GLP-1a and SGLT-2i medications was low as compared with existing literature. Advanced age and African American race were negatively associated with prescription of these medications. Contrary to guideline recommendations; atherosclerotic cardiovascular disease and chronic kidney disease were not positively associated with prescription.


Preoperative cardiac risk assessment for noncardiac surgery.
Patients presenting for noncardiac surgery should receive careful preoperative cardiac risk stratification. This has implications not only for the perioperative period, but also for long-term survival. After an initial clinical evaluation, certain patients will be referred for noninvasive testing. Those without significant inducible ischemia at a high workload have a low risk for perioperative cardiac complications. Patients who are unable to exercise adequately may require alternative forms of testing, of which dipyridamole thallium scintigraphy is the most thoroughly studied and validated option. Patients with either high-risk clinical profiles or significant thallium redistribution merit consideration for preoperative coronary angiography. Treatment options for high-risk patients include: (1) Proceeding with surgery as planned along with aggressive perioperative monitoring and anti-ischemic therapy, (2) coronary angiography with subsequent myocardial revascularization as appropriate before elective surgery, (3) selecting an alternative, lower risk surgical approach, and (4) cancellation of surgery in lieu of a trial of conservative therapy.


β-Cyclodextrin network crosslinked by novel phosphonium-based tetrakiscarboxylic acid derived from PH3 tail gas: Synthesis and application for rapid removal of organic dyes from wastewater.
Organic dyes, such as methyl orange (MO), Congo red (CR), crystal violet (CV) and methylene blue (MB), are common organic pollutants existing in wastewater. Therefore, the exploration of bio-based adsorbents for the efficient removal of organic dyes from wastewater has gained many attentions. Here, we report a PCl3-free synthetic method for the synthesis of phosphonium-containing polymers, in which the prepared tetrakis(2-carboxyethyl) phosphonium chloride-crosslinked β-cyclodextrin (TCPC-β-CD) polymers were applied to the removal of dyes from water. The effects of contact time, pH (1-11), and dye concentration were investigated. The selected dye molecules could be captured by the host-gest inclusion of β-CD cavities, and the phosphonium and carboxyl groups in the polymer structure would respectively facilitate the removal of cationic dyes (MB and CV) and anionic dyes (MO and CR) via electrostatic interactions. In a mono-component system, over 99 % of MB could be removed from water within the first 10 min. Based on the Langmuir model, the calculated maximum adsorption capacities of MO, CR, MB, and CV were 180.43, 426.34, 306.57, and 470.11 mg/g (or 0.55, 0.61, 0.96 and 1.15 mmol/g), respectively. Additionally, TCPC-β-CD was easily regenerated using 1 % HCl in ethanol, and the regenerative adsorbent still showed high removal capacities for MO, CR, and MB even after seven treatment cycles.


Early Career Challenges in Setting Up an Endoscopic Spine Surgery Practice.
After the completion of an endoscopic spinal surgery fellowship, the next challenge for the newly minted consultant is to set up a viable and sustainable endoscopic practice. A successful practice of endoscopic spine surgery is dependent on several factors, such as anesthetic support; surgical expertise; support for provision and maintenance of endoscopic equipment; cost of equipment; administrative and nursing support; postoperative care services to optimize patients' outcome and satisfaction; patients' ideas, concerns, and expectations, as well as continuing medical education. In this article, a perspective is given on the early career challenges that a fellowship-trained endoscopic surgeon may encounter in the period leading to first successful endoscopic spinal surgery.


Unexpected effects of absorbed normal rabbit serum and bovine serum albumin on survival of Haemophilus influenzae type b in the infant rat.
In the course of using the infant rat model to determine the ability of various rabbit antisera to protect against challenge by Haemophilus influenzae type b we made two unexpected observations. In these experiments 4-day-old rats were inoculated s.c. on the dorsum with either rabbit serum or physiological buffers (sham serum) and then were challenged the next day with H. influenzae type b injected i.p. Bacteremia, as a marker for disease, was measured 24 h later on day 6. We observed the following. (i) Pre-immune, i.e., normal rabbit serum, containing minimal levels of antibodies to outer membrane proteins and depleted of antibodies to capsule and lipopolysaccharide, nevertheless significantly (P less than 0.01) protected the rats from challenge with H. influenzae type b when compared to a sham inoculation of buffer; (ii) In the absence of a serum inoculation on day 4 (a buffer was used as a sham serum inoculation), the levels of bacteremia obtained after inoculation with bacteria on day 5 depended upon the composition of the buffer in which the H. influenzae inoculum was suspended. Use of phosphate buffered saline (PBS) resulted in higher levels of bacteremia than PBS containing 0.5% bovine serum albumin (PBS-BSA) (P less than 0.001), i.e. the BSA apparently acted to protect the rats from H. influenzae infection. In fact the use of PBS-BSA as an inoculum buffer masked the protective effect noted above of the absorbed normal rabbit serum.


Utilizing Learning Analytics in Radiology: A Pilot Study of an e-Learning Platform in Medical Student Education.
Learning analytics is a rapidly advancing scientific field that enables data-driven insights and personalized learning experiences. However, traditional methods for teaching and assessing radiology skills do not provide the data needed to leverage this technology in radiology education. In this paper, we implemented rapmed.net, an interactive radiology e-learning platform designed to utilize learning analytics tools in radiology education. Second-year medical students' pattern recognition skills were evaluated using time to solve a case, dice score, and consensus score, while their interpretation abilities were assessed through multiple-choice questions (MCQs). Assessments were conducted before and after a pulmonary radiology block to examine the learning progress. Our results show that a comprehensive assessment of students' radiological skills using consensus maps, dice scores, time metrics, and MCQs revealed shortcomings traditional MCQs would not have detected. Learning analytics tools allow for a better understanding of students' radiology skills and pave the way for a data-driven educational approach in radiology. As one of the most important skills for physicians across all disciplines, improving radiology education will contribute to better healthcare outcomes.


Study on association between genetic polymorphisms of haem oxygenase-1, tumour necrosis factor, cadmium exposure and malaria pathogenicity and severity.
Malaria is the most important public health problems in tropical and sub-tropical countries. Haem oxygenase (HO) enzyme and the pro-inflammatory cytokine tumour necrosis factor (TNF) have been proposed as one of the factors that may play significant role in pathogenicity/severity of malaria infection. HO is the enzyme of the microsomal haem degradation pathway that yields biliverdin, carbon monoxide, and iron. In this study, the association between malaria disease pathogenicity/severity and (GT)n repeat polymorphism in the promoter region of the inducible HO-1 including the effect of cadmium exposure (potent inducer of HO-1 transcription) as well as polymorphism of TNF were investigated. Blood samples were collected from 329 cases non-severe malaria with acute uncomplicated Plasmodium falciparum malaria (UM) and 80 cases with Plasmodium vivax malaria (VM), and 77 cases with severe or cerebral malaria (SM) for analysis of genetic polymorphisms of HO-1 and TNF and cadmium levels. These patients consisted of 123 (25.3%) Thai, 243 (50.0%) Burmese and 120 (24.7%) Karen who were present at Mae Sot General Hospital, Mae Sot, Tak Province, Thailand. The number of (GT)n repeats of the HO-1 gene in all patients varied between 16 and 39 and categorized to short (S), medium (M) and long (L) GTn repeats. The genotype of (GT)n repeat of HO-1 was found to be significantly different among the three ethnic groups of patients. Significantly higher frequency of S/L genotype was found in Burmese compared with Thai patients, while significantly lower frequencies of S/S and M/L but higher frequency of M/M genotype was observed in Burmese compared with Karen patients. No significant association between HO-1 and TNF polymorphisms including the inducing effect of cadmium and malaria pathogenicity/severity was observed. Difference in the expression of HO-1 genotype in different ethnic groups may contribute to different severity of malaria disease. With this limited sample size, the finding of the lack of association between malaria disease pathogenicity/severity genetic polymorphisms of HO-1 (GT)n repeat as well as TNF observed in this study may not entirely exclude their possible link with malaria disease pathogenicity/severity. Further study in larger sample size is required.


Effects of inorganic nutrient levels on the biodegradation of benzene, toluene, and xylene (BTX) by Pseudomonas spp. in a laboratory porous media sand aquifer model.
The effect of inorganic nutrients (sulfate, phosphate, and ammonium chloride) on the aerobic biodegradation of benzene, toluene, and xylene (BTX) by Pseudomonas spp. was studied in the laboratory using a glass sand tank. The increase of nutrient levels resulted in enhanced bacterial growth and BTX degradation. Sulfate and phosphate serve as key electron acceptors in the microbiological processes degrading BTX. The observed bacterial morphological changes during BTX degradation reveal that the filamentous bacteria were the dominant species at low temperatures about 20 degrees C. The spherical and rod-shaped cells became dominant at higher temperatures ranging from 25 degrees C to 28 degrees C. When the BTX mixture was allowed to be biodegraded for longer incubation periods of 21-42 h at high phosphate concentrations, large amounts of rod-shaped cells were clustered. The morphological adaptation appears to be controlled by the temperature and nutrient levels in the sandy medium where Pseudomonas spp. thrives.


Is Pseudomonas infection associated with worse outcomes in pediatric perforated appendicitis?
There is little information on the effects of Pseudomonas infection on outcomes in perforated appendicitis. As Pseudomonas is not covered by many empiric appendicitis antibiotic regiments, we hypothesized that children with Pseudomonas would have worse outcomes. Patients <18 years old undergoing appendectomy for perforated appendicitis at a tertiary children's hospital 2015-2019 were included and were stratified by presence of Pseudomonas on intraoperative culture. The primary outcome was post-operative organ-space infection (SSI). Intraoperative cultures were collected in 58.4% of patients (n = 149/255) with 22.2% (n = 33) positive for Pseudomonas. SSIs occurred in 21.2% of children with Pseudomonas compared to 20.7% of children without Pseudomonas (p = 0.9). Children with Pseudomonas had longer antibiotic duration (9.1 vs. 6.7 days, p = 0.03) and LOS (6.7 vs. 5.9 days, p = 0.03) than those without, but a similar rate of post-operative interventions (12.2% vs. 19.0%, p = 0.4), hospital costs ($28,860 vs. $23,945, p = 0.3), ED visits (9.1% vs. 19.9%, p = 0.3), and readmissions (9.1% vs. 9.5%, p = 1). Pseudomonas was identified in 22% children with perforated appendicitis and was associated with longer antibiotic durations and LOS, but similar rates of SSI, post-operative interventions, and readmissions compared to children without Pseudomonas. Empiric coverage of Pseudomonas may not be necessary.


On the promine/retine theory of cell division: now and then.
Although the glyoxalase system was discovered in 1913, its function in the biological network is still a subject of debate. An attractive theory on its role was described by Albert Szent-Györgyi in the 1960s. From a bird's eye view, the promine/retine concept of Szent-Györgyi seems to give a plausible role for this ubiquitous enzyme system, but on going into detail, it obviously suffers from several uncertainties which have not been discussed until now. Here, a critical overview of the theory is presented by taking the pros and cons into account. It looks as though more data object to the theory than give support to it; and the search for anticancer medicines stimulated by the theory has not resulted in a new way of treatment of tumors, either. Hence, it is feared that the theory suggested for the biological role of glyoxalase pathway cannot be accepted, as it is.


Dietary changes in temporal relation to multiple sclerosis in the Faroe Islands: an evaluation of literary sources.
In order to generate additional hypotheses on a possible role of dietary factors in the etiology of multiple sclerosis, the ethnographic literature and other relevant sources from the Faroe Islands were reviewed. A transitory occurrence in the first half of the 20th century was evident for the extended consumption of oat products, of fulmars possibly infected with ornithosis virus, and of foodstuffs treated with wood smoke or smoke condensates. The hypothetical basis of these considerations must be emphasized.


Electrochemical impedimetric DNA sensing based on multi-walled carbon nanotubes-SnO2-chitosan nanocomposite.
A sensitive electrochemical impedimetric DNA biosensor based on the integration of tin oxide (SnO2) nanoparticles, chitosan (CHIT) and multi-walled carbon nanotubes (MWNTs) is presented in this paper. The MWNTs-SnO2-CHIT composite modified gold electrode was characterized by cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). Compared with individual MWNTs-CHIT, SnO2-CHIT and bare gold electrode, this composite showed the most obvious electrochemical signal of the redox probe [Fe(CN)6](3-/4-). According to the change of the electron transfer resistance (R(et)) induced by the hybridization, target DNA was successfully detected via EIS. This DNA electrochemical biosensor was applied to detect phosphinothricin acetyltransferase (PAT) gene in transgenic corn. The synergistic effect of the MWNTs-SnO2-CHIT remarkably enhanced DNA immobilization and hybridization detection. The dynamic detection range was from 1.0×10(-11) mol/L to 1.0×10(-6) mol/L with a detection limit of 2.5×10(-12) mol/L. This sensing platform showed inner advantage, such as simplicity, good stability, and high sensitivity.


Preferential usage of tRNA isoaccepting species in collagen synthesis.
A new double label technique is described for determining the usage of individual isoaccepting tRNA species by in vitro protein-synthesizing systems. Employing this method we show that of four major species of glycyl-tRNA one which is cognate to GGU and GGC is used predominantly in collagen synthesis by polysomes isolated from embryonic chick calvaria. A similar preferential usage was found for one of two alanyl-tRNA species. No preference for any particular isoaccepting tRNA species was observed in the synthesis of noncollagenous proteins by either calvaria or liver polysomes except for the disproportionate usage of one lysyl-tRNA species. Whether such preferential usage permits translational control of collagen synthesis in vivo remains to be determined.


A numerical investigation of mathematical modelling in 3D hexagonal porous prism on oil recovery using nanoflooding.
The use of nanomaterials as a means of recovering heavy and light oil from petroleum reservoirs has increased over the preceding twenty years. Most researchers have found that injecting a nanoparticle dispersion (nanofluids) has led to good results and increased the amount of oil that can be recovered. In this research, we aim to imitate the three-dimensional hexagonal prism in the existence of SiO2 and Al2O3 nanoparticles for better oil recovery. Porosity (0.1≤φ≤0.4), mass flow rate (0.05mL/min≤Q≤0.05ml/min), nanoparticle concentration (0.01≤ψ≤0.04), and the effect of relative permeability (kr) on oil and water saturation in the presence of gravity under different time durations are all investigated. The result obtained for the model is verified with existing experimental data. The results indicated that the infulence of nanoparticle volume fraction (VF) is significant in enhancing the oil recovery rate. It is also observed that at low porosity values the oil recovery is maximum. The maximum oil recovery is attained at low values of mass flow rate in the 3D hexagonal prism in the presence of silicon and aluminium nanoparticles It is also observed that the use of SiO2 gives a better oil recovery rate than Al2O3. It is also observed that maximum oil recovery is obtained at 99% at a flow rate of 0.05 mL/min in the presence of silicon injection.


Multidimensional protein identification technology for direct-tissue proteomics of heart.
Multidimensional protein identification technology (MudPIT) is an invaluable approach to identify proteins at large-scale level. Here, we describe a procedure of investigation to functional characterize the proteomic profile of complex samples such as those from cardiac tissues. In particular, we focus on the main steps concerning sample preparation, MudPIT analysis, tandem mass spectra processing, and biomarker discovery using label-free approaches. Finally, we report a data-derived systems biology approach to identify groups of proteins of over-, under-, and normal expression.


Rhodium(III)-Catalyzed Oxidative C-H/C-H Cross-Coupling of Heteroarenes and Masked Benzylamines.
The first example of oxidative C-H/C-H cross-coupling of oxalyl amide-protected benzylamines and various heteroarenes in the presence of a rhodium(III) catalyst has been developed. The route provides a means of synthesizing ortho-heteroarylated benzylamines. The methodology presents broad substrate scope, great functional group tolerance, and good to excellent yields in the synthesis of substituted benzylamines. The study also reveals that the thienoisoquinoline derivatives can be accessed through the intramolecular amination of thiophenyl-substituted benzylamines with palladium(II).


Cu/Zn Superoxide Dismutase (Sod1) regulates the canonical Wnt signaling pathway.
Cu/Zn Superoxide Dismutase (Sod1) catalyzes the disproportionation of cytotoxic superoxide radicals (O2•-) into oxygen (O2) and hydrogen peroxide (H2O2), a key signaling molecule. In Saccharomyces cerevisiae, we previously discovered that Sod1 participates in an H2O2-mediated redox signaling circuit that links nutrient availability to the control of energy metabolism. In response to glucose and O2, Sod1-derived H2O2 stabilizes a pair of conserved plasma membrane kinases - yeast casein kinase 1 and 2 (Yck1/2) - that signal glycolytic growth and the repression of respiration. The Yck1/2 homolog in humans, casein kinase 1-γ (CK1γ), is an integral component of the Wingless and Int-1 (Wnt) signaling pathway, which is essential for regulating cell fate and proliferation in early development and adult tissue and is dysregulated in many cancers. Herein, we establish the conservation of the SOD1/YCK1 redox signaling axis in humans by finding that SOD1 regulates CK1γ expression in human embryonic kidney 293 (HEK293) cells and is required for canonical Wnt signaling and Wnt-dependent cell proliferation.


Differential response of adherent and unanchored melanoma cells to bromodeoxyuridine evidenced by specific lectin-binding protein changes.
The possible differential response of adherent and nonadherent cells of the same tumor type to pyrimidine analogues has been investigated. We show that bromodeoxyuridine (BUdR) increases interactions of attached cells with their substrate without markedly affecting the cell adhesion properties of the same cells when these are not anchored. However, evidence for an adhesion-independent response of both cell types to BUdR has been obtained with lectin binding assays using 125I-labelled Lens culinaris agglutinin (LCA). This revealed a greatly increased binding of LCA to a large glycoconjugate in all cultures exposed to the halogenated pyrimidine. Attachment-dependent effects of BUdR were manifested in flattened cells by a greater LCA-binding to a 240-kDa protein and by increased interaction of 125I-labelled wheat-germ agglutinin (WGA) with a 200-kDa protein and a large glycoconjugate sharply defined in electrophoresis. Although both tumor cell aggregates and anchored cells exhibit detectable responses to pyrimidine analogues such as BUdR, the corresponding effects are thus manifested unequally in cells with different adhesion properties.


Studies on the mechanism of insulin resistance after injury in the mouse.
Acute insulin resistance developed after scald injury in the mouse. After 2h plasma glucose and insulin concentrations were each raised about two-fold. Glucose metabolism was studied in vitro in soleus muscles isolated at this time. Glycolysis and glycogen synthesis, and their stimulation by insulin, were unchanged in muscles from scalded mice, and insulin-stimulated transport of 2-deoxyglucose slightly increased, showing that the insulin resistance seen in vivo is not maintained in isolated tissues. Binding of insulin to liver cell membranes prepared from scalded mice was unaltered, whilst that of glucagon was slightly but significantly reduced, showing that changes in polypeptide-hormone receptors can occur within this short time. It was concluded that the acute loss of sensitivity to insulin after injury does not result from a change in insulin receptor sites and presumably reflects an impairment of glucose metabolism in vivo mediated by circulating hormones.