Cellular and subcellular localization of nicotinamide adenine dinucleotide phosphate diaphorase activity.
To determine the cellular and subcellular distribution of nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) in the human placenta and thereby to shed light on the possible role of nitric oxide (NO) and NO synthase in this tissue. NADPH-d activity in 10 term placenta and in 10 first-trimester placentas was examined by enzyme histochemistry and by both light microscopy and electron microscopy. Light microscopy revealed that NADPH-d activity was marked in the syncytiotrophoblasts, moderate in the endothelium of cord vessels, and weak in the amniotic epithelia and chorionic trophoblasts. At the electron-microscopic level, NADPH-d activity was apparent as small patches distributed throughout the cytoplasm of the syncytiotrophoblasts. NO might be generated in the syncytiotrophoblast of the human placenta and might play a role in the regulation of placental hemodynamics or in the signaling between the syncytium and the villous mesenchyme.


Lymphoscintigraphy in high-risk melanoma of the trunk: predicting draining node groups, defining lymphatic channels and locating the sentinel node.
Lymphoscintigraphy was performed in 209 patients with high-risk melanoma of the trunk referred to the Sydney Melanoma Unit and considered for lymph node dissection. Lymphoscintigraphy accurately defined the draining lymph node groups and was 94% sensitive in detecting draining sites that contained metastases. When combined with the clinical finding of palpable lymph nodes, the sensitivity rose to 98%. Most patients showed lymph drainage to one or two node groups and only 22 patients showed drainage to 3 or more node groups. The major lymph channels could also be marked on the skin prior to incontinuity dissection. Most patients had multiple draining lymph channels and these often diverged significantly from each other in the path to the draining node group. The number and location of interval nodes could be determined and marked on the skin. These and the major lymph channels could thus be excised at the time of surgery. Unusual drainage patterns were sometimes seen; for example, three patients displayed a new lymph pathway with direct drainage from the back anteriorly to the para-aortic nodes. The location of the sentinel nodes in each draining lymph-node group could also be marked on the skin prior to surgery, enabling quick and accurate identification of this node, using the blue-dye technique if biopsy were to be performed. These findings lead us to recommend lymphoscintigraphy prior to wide local excision in patients with truncal melanoma who are candidates for surgery. Lymphoscintigraphy results will help plan surgery and lead to minimum surgical intervention, consistent with effective surgical management.


Highly Efficient Long-Wavelength Thermally Activated Delayed Fluorescence OLEDs Based on Dicyanopyrazino Phenanthrene Derivatives.
Highly efficient long-wavelength thermally activated delayed fluorescence (TADF) materials are developed using 2,3-dicyanopyrazino phenanthrene (DCPP) as the electron acceptor (A), and carbazole (Cz), diphenylamine (DPA), or 9,9-dimethyl-9,10-dihydroacridine (DMAC) as the electron donor (D). Because of the large, rigid π-conjugated structure and strong electron-withdrawing capability of DCPP, TADF molecules with emitting colors ranging from yellow to deep-red are realized with different electron-donating groups and π-conjugation length. The connecting modes between donor and acceptor, that is, with or without the phenyl ring as π-bridge, are also investigated to study the π-bridge effect on the thermal, photophysical, electrochemical, and electroluminescent properties. Yellow, orange, red, and deep-red organic light-emitting diodes (OLEDs) based on DCPP derivatives exhibit high efficiencies of 47.6 cd A-1 (14.8%), 34.5 cd A-1 (16.9%), 12.8 cd A-1 (10.1%), and 13.2 cd A-1 (15.1%), with Commission Internationale de L'Eclairage (CIE) coordinates of (0.44, 0.54), (0.53, 0.46), (0.60, 0.40), and (0.64, 0.36), respectively, which are among the best values for long-wavelength TADF OLEDs.


Assessment of Motor Control during Three-Dimensional Movements Tracking with Position-Varying Gravity Compensation.
Active movements are important in the rehabilitation training for patients with neurological motor disorders, while weight of upper limb impedes movements due to muscles weakness. The objective of this study is to develop a position-varying gravity compensation strategy for a cable-based rehabilitation robot. The control strategy can estimate real-time gravity torque according to position feedback. Then, the performance of this control strategy was compared with the other two kinds of gravity compensation strategies (i.e., without compensation and with fixed compensation) during movements tracking. Seven healthy subjects were invited to conduct tracking tasks along four different directions (i.e., upward, forward, leftward, and rightward). The performance of movements with different compensation strategies was compared in terms of root mean square error (RMSE) between target and actual moving trajectories, normalized jerk score (NJS), mean velocity ratio (MVR) of main motion direction, and the activation of six muscles. The results showed that there were significant effects in control strategies in all four directions with the RMSE and NJS values in the following order: without compensation > fixed compensation > position-varying compensation and MVR values in the following order: without compensation < fixed compensation < position-varying compensation (p < 0.05). Comparing with movements without compensation in all four directions, the activation of muscles during movements with position-varying compensation showed significant reductions, except the activations of triceps and in forward and leftward movements, the activations of upper trapezius and middle parts of deltoid in upward movements and the activations of posterior parts of deltoid in all four directions (p < 0.05). Therefore, with position-varying gravity compensation, the upper limb cable-based rehabilitation robotic system might assist subjects to perform movements with higher quality and improve the participation of robot-aided rehabilitation training. Further studies are needed to explore the effectiveness and clinic application across pathologies.


Regulatory volume decrease in HL-60 cells: importance of rapid changes in permeability of Cl- and organic solutes.
Results obtained through the use of inhibitors and isotope flux and equilibration techniques indicate that the regulatory volume decrease (RVD) response of human promyelocytic leukemic HL-60 cells occurs largely through the efflux of K+ and Cl- through separate conductive membrane pathways. These "channels" differ pharmacologically and in their modes of activation from those described in lymphocytes and Ehrlich ascites tumor cells. With use of measured 86Rb+ and 36Cl- fluxes, together with a diffusion kinetic model, the membrane potential (Em) and apparent K+ and Cl- permeabilities (PK and PCl) were estimated under various isotonic and hypotonic conditions. Under isotonic (300 mosM) conditions, Em is close to the Nernst potential for K+ and PCl is < 0.1 PK. Rapid and steeply graded increases in the measured Cl- efflux rate and calculated PCl occur with decreasing tonicity, with the largest increases at tonicities < 80% of isotonic. K+ efflux and the apparent PK increase only modestly with decreasing tonicity. At 50% tonicity, PCl rises to nearly 10 times PK, which should cause substantial membrane depolarization, with Em approaching the Nernst potential for Cl-. Gramicidin treatment markedly accelerates the rate of RVD and net 36Cl- efflux in hypotonic Na(+)-and Cl(-)-free media, providing further evidence that PK is rate limiting during RVD. K+ loss exceeds Cl- loss during RVD, and the total loss of K+ and Cl- is insufficient to account for the observed degree of volume recovery in 50% tonicity media, indicating that other (organic) osmolytes must take part in the HL-60 cell RVD response.


COSTS AND BENEFITS OF MOSQUITO REFRACTORINESS TO MALARIA PARASITES: IMPLICATIONS FOR GENETIC VARIABILITY OF MOSQUITOES AND GENETIC CONTROL OF MALARIA.
The problem of fitness costs associated with host resistance to parasitism is related to the evolution of parasite virulence, population genetic diversity and the dynamics of host-parasite relationships, and proposed strategies for disease control through the genetic manipulation of mosquito vectors. Two Aedes aegypti populations, refractory and susceptible to Plasmodium gallinaceum, were previously selected from the Moyo-In-Dry strain (MOYO) through inbreeding (F = 0.5). Reproductive success and survivorship of the two populations were compared, and the influence of the parasite on mosquito fitness also was evaluated. Fitness components studied include fecundity, adult survivorship and egg-to-adult developmental time, blood-meal size, and adult body size. The refractory population has a significantly shorter egg-to-adult developmental time and a smaller body size, takes a smaller blood meal, and subsequently lays fewer eggs than the susceptible population. The mean longevity of the refractory population is significantly shorter than the susceptible population. Exposure to the parasite exhibited little effect on the survivorship and fecundity of either population. Several factors may contribute to the lower fitness of the refractory population, including founder effect, inbreeding depression, the effect of other uncharacterized genes linked to genes conferring refractoriness, and pleiotropic effects associated with these genes. The results are discussed in relation to the genetic diversity of natural mosquito populations and their implications for the genetic control of malaria.


Systematic review and meta-analysis: is bowel preparation still necessary in small bowel capsule endoscopy?
Optimal bowel preparation for small bowel capsule endoscopy(SBCE) is controversial. This meta-analysis aimed to investigate the effects of laxatives in SBCE. A comprehensive literature search was conducted for studies investigating the use of laxatives in SBCE. The primary outcome was diagnostic yield(DY) for SB findings; secondary outcomes SB visualization quality(SBVQ) and completion rate(CR). Pooled odds ratios(ORs) with 95% confidence intervals(CIs) and number needed to treat(NNT) were calculated. Forty studies (4380 patients with laxatives, 2185 without) were included. Laxative use did not improve DY of SB findings overall (OR 1.11 (95%CI 0.85-1.44)) or for significant SB findings (OR 1.10 (95%CI 0.76-1.60)). However, SBVQ improved with the use of laxatives (OR 1.60 (95%CI 1.08-2.06)), NNT 14. The OR for completed SBCE was 1.30 (95%CI 0.95-1.78). Patients given polyethylene glycol(PEG) had lower DY than sodium phosphate(NaP). SBVQ improved more with NaP (NNT 7) than PEG (NNT 53). Laxatives do not significantly improve DY or CR in SBCE, but do improve SBQV. The use of laxatives may be beneficial in patients likely to have subtle findings. There are significant differences in methodology/definitions between studies, hence the need for standardized visualization scoring and recording of SBCE findings.


[Catalase activity of hydrocarbon-oxidizing bacteria].
The dynamics of catalase activity of the hydrocarbon-oxidizing bacteria Cordona terrae, Rhodococcus rubropertinctus, and Rhodococcus erythropolis during petroleum product destruction has been studied. A direct relationship between decreasing catalase activity of hydrocarbon-oxidizing microorganisms and the intensity of petroleum product destruction has been established experimentally. The revealed dependence allows one to consider the catalase activity of bacteria as an indicator of the initial stage of petroleum product oxidation and may be used for choosing destructor strains to construct biopreparations suitable for natural ecosystem remediation.


Low power adder based auditory filter architecture.
Cochlea devices are powered up with the help of batteries and they should possess long working life to avoid replacing of devices at regular interval of years. Hence the devices with low power consumptions are required. In cochlea devices there are numerous filters, each responsible for frequency variant signals, which helps in identifying speech signals of different audible range. In this paper, multiplierless lookup table (LUT) based auditory filter is implemented. Power aware adder architectures are utilized to add the output samples of the LUT, available at every clock cycle. The design is developed and modeled using Verilog HDL, simulated using Mentor Graphics Model-Sim Simulator, and synthesized using Synopsys Design Compiler tool. The design was mapped to TSMC 65 nm technological node. The standard ASIC design methodology has been adapted to carry out the power analysis. The proposed FIR filter architecture has reduced the leakage power by 15% and increased its performance by 2.76%.


Case report: Neonatal diabetes mellitus caused by KCNJ11 mutation presenting with intracranial hemorrhage.
Neonatal diabetes mellitus (NDM) is a rare type of monogenic diabetes. At present, most published studies have focused on the types of gene mutations associated with NDM and the therapeutic effect of sulfonylureas (SUs) on the disease; few studies on NDM-associated intracranial hemorrhage (ICH) exist. In addition, p.V59M mutations generally lead to intermediate DEND (iDEND: intermediate developmental delay and neonatal diabetes) syndrome without epilepsy. Here, we present a case of a 1-month-old male infant who was diagnosed with NDM caused by a KCNJ11 missense mutation (p.V59M), presenting with cerebral injury. In the early stage of the disease, continuous insulin dose adjustment did not achieve an ideal level of blood glucose. Although blood glucose was subsequently controlled by oral SUs, which were administered after the genetic test result, the patient still displayed epilepsy and developmental delay. In this case report, we present our experience in the treatment of the infant, switching from insulin to oral SUs and we thought that SUs have limited effects on improving the prognosis of neurodevelopmental disturbances in NDM with foci of encephalomalacia. In addition, there may be a relationship between KCNJ11 missense mutations and cerebral injury, and further research must be carried out to confirm these points.


[Relation between uptake of 67Ga-citrate in salivary glands and irradiation doses].
A retrospective study is performed 67Ga-citrate uptake by scintigraphy to evaluate the relation between gallium uptake of salivary glands and radiotherapy with special reference to radiation dose and period after initial irradiation. Sixteen patients with radiotherapy to their head and neck regions were studied, undergone 67Ga scintigraphy for four times or more were investigated. The following results were obtained: 1. About half of the total number of salivary glands increased the uptake of 67Ga-citrate during radiotherapy. 2. The number of salivary glands which increased uptake in a group which received more than 30 Gy was greater than that in a group less than 30 Gy, and many of them remained with increased activity for one year after radiotherapy. 3. Uptake in glands that received dose less than 30 Gy showed rapid increasement initially, and showed decrease of uptake in six months after the irradiation. We concluded that there was different tendency of gallium uptake between a group of patient with irradiation of less than 30 Gy and that with irradiation of more than 30 Gy. It is suggested that we must always consider gallium uptake of salivary glands for long term after the radiotherapy, when we discuss the recurrence or metastases of neck lymph nodes of patients, who have performed radiotherapy to their head and neck regions, especially high dose irradiation.


Evaluation of a multiplex real-time PCR for detection of four bacterial agents commonly associated with bovine respiratory disease in bronchoalveolar lavage fluid.
Pasteurella multocida, Mannheimia haemolytica, Histophilus somni and Trueperella pyogenes are four bacterial agents commonly associated with bovine respiratory disease (BRD). In this study a bacterial multiplex real-time PCR (the RespoCheck PCR) was evaluated for the detection in bronchoalveolar lavage fluid (BALF) of these four bacterial agents. The analytical sensitivity of the multiplex real-time PCR assay determined on purified DNA and on bacterial cells of the four target pathogens was one to ten fg DNA/assay and 4 × 10-1 to 2 × 100 CFU/assay. The analytical specificity of the test was, as evaluated on a collection of 118 bacterial isolates, 98.3% for M. haemolytica and 100% for the other three target bacteria. A set of 160 BALF samples of calves originating from ten different herds with health problems related to BRD was examined with bacteriological methods and with the RespoCheck PCR. Using bacteriological examination as the gold standard, the diagnostic sensitivities and specificities of the four bacterial agents were respectively between 0.72 and 1.00 and between 0.70 and 0.99. Kappa values for agreement between results of bacteriological examination and PCRs were low for H. somni (0.17), moderate for P. multocida (0.52) and M. haemolytica (0.57), and good for T. pyogenes (0.79). The low and moderate kappa values seemed to be related to limitations of the bacteriological examination, this was especially the case for H. somni. It was concluded that the RespoCheck PCR assay is a valuable diagnostic tool for the simultaneous detection of the four bacterial agents in BALF of calves.


Promising Thermoelectric Bulk Materials with 2D Structures.
Given that more than two thirds of all energy is lost, mostly as waste heat, in utilization processes worldwide, thermoelectric materials, which can directly convert waste heat to electricity, provide an alternative option for optimizing energy utilization processes. After the prediction that superlattices may show high thermoelectric performance, various methods based on quantum effects and superlattice theory have been adopted to analyze bulk materials, leading to the rapid development of thermoelectric materials. Bulk materials with two-dimensional (2D) structures show outstanding properties, and their high performance originates from both their low thermal conductivity and high Seebeck coefficient due to their strong anisotropic features. Here, the advantages of superlattices for enhancing the thermoelectric performance, the transport mechanism in bulk materials with 2D structures, and optimization methods are discussed. The phenomenological transport mechanism in these materials indicates that thermal conductivities are reduced in 2D materials with intrinsically short mean free paths. Recent progress in the transport mechanisms of Bi2 Te3 -, SnSe-, and BiCuSeO-based systems is summarized. Finally, possible research directions to enhance the thermoelectric performance of bulk materials with 2D structures are briefly considered.


Sequence of a new DR12 allele with two silent mutations that affect PCR-SSP typing.
A new HLA-DR12 allele has been identified in a European Caucasoid bone marrow donor. The DRB1*12012 allele differs from DRB1*12011 by two silent substitutions at codons 72 and 78, two polymorphic positions used for DNA subtyping of the DR12 serotype. The co-occurence of the two nucleotide changes is unique to the DR12 group and results in a new PCR-SSP typing pattern. The complete HLA type of the donor is A24, A68; B55, B61; Cw*01, Cw*0304; DRB1*12012, DRB1*1402; DRB3*0101, DRB3*0202; DQB1*0301. HLA-DRB1*12012 is a rare allele as it occurs in < 0.2% of DR12 donors.


Preferences for birth center care in the Netherlands: an exploration of ethnic differences.
To examine the preferences for comprehensive services and facilities in a new proposed birth center which will be established in a large Dutch city, specifically among pregnant women from different ethnic backgrounds. The analyses of this study were based on a survey among 200 pregnant women living in The Hague, the Netherlands in 2011. Multiple linear regression was applied to analyze if preferences differ by ethnic background, controlling for various other predictors. Pregnant women had relatively strong preferences for comprehensive services and facilities to be offered by the new proposed birth center compared to both other dimensions of birth center care: extensive practical information and comfortable accommodation. With regard to ethnic differences, non-Dutch women had higher preferences for comprehensive care compared to Dutch women. This difference between Dutch and non-Dutch women increased with their level of education. Especially for non-Dutch women, birth centers that are able to provide comprehensive services and facilities can potentially be a good setting in which to give birth compared to hospitals or at home. In particular, higher educated non-Dutch women had a preference for the personalized care that could be offered by this new birth center.


Faecal microbiota transplantation (FMT) in the treatment of chronic refractory pouchitis: A systematic review and meta-analysis.
The aim of this systematic review and meta-analysis is to assess the efficacy and safety of faecal microbiota transplantation (FMT) in the treatment of chronic pouchitis. A PRISMA-compliant systematic review and meta-analysis was conducted using the following databases and clinical trial registers: Medline, Embase, Scopus, Cochrane Database of Systematic Reviews (CENTRAL), clinical trials.gov, ScienceDirect, and VHL (virtual health library). The primary outcome was clinical response/remission in patients treated with FMT. Secondary outcomes included safety profile, quality of life and changes in the gut microbiome. Seven observational cohort studies/case series and two randomised controlled trials with a total of 103 patients were included. The route, preparation, and quantity of FMT administered varied amongst the included studies. Clinical response rate of 42.6% with a remission rate of 29.8% was estimated in our cohort following FMT therapy. Minor, self-limiting adverse events were reported, and the treatment was well tolerated with a good short- and long-term safety profile.Successful FMT engraftment in recipients varied and on average microbial richness and diversity was lower in patients with pouchitis. In some instances, shifts with specific changes towards abundance of species suggestive of a 'healthier' pouch microbiota were observed following treatment with FMT. The evidence for FMT in the treatment of chronic pouchitis is sparse which limits any recommendations being made for its use in clinical practice. Current evidence from low-quality studies suggests a variable clinical response and remission rate but the treatment is well tolerated with a good safety profile. This review emphasises the need for rationally designed well powered randomised placebo-controlled trials to understand the efficacy of FMT for the treatment of pouchitis.


Single Enzyme Direct Biomineralization of CdSe and CdSe-CdS Core-Shell Quantum Dots.
Biomineralization is the process by which biological systems synthesize inorganic materials. Herein, we demonstrate an engineered cystathionine γ-lyase enzyme, smCSE that is active for the direct aqueous phase biomineralization of CdSe and CdSe-CdS core-shell nanocrystals. The nanocrystals are formed in an otherwise unreactive buffered solution of Cd acetate and selenocystine through enzymatic turnover of the selenocystine to form a reactive precursor, likely H2Se. The particle size of the CdSe core nanocrystals can be tuned by varying the incubation time to generated particle sizes between 2.74 ± 0.63 nm and 4.78 ± 1.16 nm formed after 20 min and 24 h of incubation, respectively. Subsequent purification and introduction of l-cysteine as a sulfur source facilitates the biomineralization of a CdS shell onto the CdSe cores. The quantum yield of the resulting CdSe-CdS core-shell particles is up to 12% in the aqueous phase; comparable to that reported for more traditional chemical synthesis routes for core-shell particles of similar size with similar shell coverage. This single-enzyme route to functional nanocrystals synthesis reveals the powerful potential of biomineralization processes.


Granulomatous inflammation in pineal germinoma. A cause of diagnostic failure at stereotaxic brain biopsy.
We report four patients with pineal germinoma in whom the initial procedure for obtaining a tissue diagnosis was a stereotaxic biopsy. In all four cases, the biopsy showed granulomatous inflammation with epithelioid cells and lymphocytes. In one case, the granulomatous inflammation was accompanied by classical germinoma. Another case exhibited malignant cells considered nondiagnostic for a specific neoplasm. Two cases had no evidence of a malignant tumor; they were composed entirely of granulomatous inflammation. In two of the three cases where the diagnosis was not established by the first biopsy, a second stereotaxic biopsy showed pineal germinoma. Tissue obtained at resection in the third patient revealed large areas of granulomatous inflammation accompanying the germinoma. Immunoperoxidase stains for ferritin and placental alkaline phosphatase did not increase diagnostic yield. We conclude that a finding of granulomatous inflammation in a stereotaxic biopsy specimen of a pineal mass should suggest a diagnosis of germinoma, followed by sampling from several different target points within the lesion.


The altered metabolic pathways of diffuse large B-cell lymphoma not otherwise specified.
Altered metabolic fingerprints of Diffuse large B-cell lymphoma, not otherwise specified (DLBCL NOS) may offer novel opportunities to identify new biomarkers and improve the understanding of its pathogenesis. This study aimed to investigate the modified metabolic pathways in extranodal, germinal center B-cell (GCB) and non-GCB DLBCL NOS from the head and neck. Formalin-fixed paraffin-embedded (FFPE) tissues from eleven DLBCL NOS classified according to Hans' algorithm using immunohistochemistry, and five normal lymphoid tissues (LT) were analyzed by high-performance liquid chromatography-mass spectrometry-based untargeted metabolomics. Partial Least Squares Discriminant Analysis showed that GCB and non-GCB DLBCL NOS have a distinct metabolomics profile, being the former more similar to normal lymphoid tissues. Metabolite pathway enrichment analysis indicated the following altered pathways: arachidonic acid, tyrosine, xenobiotics, vitamin E metabolism, and vitamin A. Our findings support that GCB and non-GCB DLBCL NOS has a distinct metabolomic profile, in which GCB possibly shares more metabolic similarities with LT than non-GCB DLBCL NOS.


Recruitment of dendritic cells in human liver with metastases.
Dendritic cells (DCs) play a key role in the generation of antitumor immune responses as the most potent professional antigen-presenting cells. In this study we examined the distribution of DCs subsets in selected areas of liver metastases and adjacent liver tissue of 74 patients with gastrointestinal cancers (14 gastric, 47 colon, and 13 rectal) using immunohistochemistry for the DCs markers S-100 protein, HLA-DR, CD1a, and CD83. S-100 protein-positive DCs were localized mainly in clusters in metastases and at the tumor border with the surrounding liver tissue, while HLA-DR-positive DCs were significantly more in number (P<0.0001) and were diffusely distributed in metastasis stroma and at the tumor border. S-100 protein-positive DCs with mature phenotype were presented around metastases and in the sinusoidal lumena, whereas S-100 protein-positive DCs with less mature phenotype based on their ultrastructure were scattered in the tumor stroma. CD1a- and CD83-positive DCs were observed predominantly in small groups or as single cells in the tumor stroma and in the invasive margin. The numbers of CD1a-positive DCs (immature) and CD83-positive DCs (mature) were comparable, but significantly lower than that of S-100 protein-positive (P<0.0001) and HLA-DR-positive cells (P<0.0001).We observed more S-100 protein-positive DCs and HLA-DR-expressing cells in the sinusoids and portal tracts of the liver tissue, surrounding metastases, than in control liver tissue. In conclusion, this study provides additional information on the functional subtypes and distribution of DCs infiltrating metastatic tissue and local liver environment in patients with liver metastases from gastrointestinal cancers.


Four substituted benzohydrazides: hydrogen-bonded structures in one, two and three dimensions.
The molecules of 2,6-dichlorobenzohydrazide, C7H6Cl2N2O, are linked into simple chains by a single N-H...O hydrogen bond, while in the isomeric compound 2,4-dichlorobenzohydrazide, the molecules are linked by N-H...N and N-H...O hydrogen bonds into complex sheets comprising an inner polar layer sandwiched between two non-polar layers. In 4-amino-2-chlorobenzohydrazide monohydrate, C7H8ClN3O.H2O, the components are linked into a three-dimensional framework by a combination of O-H...O, O-H...N, N-H...N and N-H...O hydrogen bonds, and in 2-nitrobenzohydrazide, C7H7N3O3, a three-dimensional framework is formed by a combination of N-H...N and N-H...O hydrogen bonds.


Biodegradable Gelatin Methacrylate Gel as a Potential Scaffold for Bone Tissue Engineering of Canine Adipose-Derived Stem Cells.
Therapeutic potential of adipose derived stem cells (ADSCs) has widely been explored for treatment of orthopedic ailments. Transplantation of cells encapsulated in a scaffold facilitates 3 dimensional modelling of the tissue for the cases where well-defined spatial distribution of cells is desired for implantation. Present study aims to encapsulate canine ADSCs (cADSCs) in biodegradable methacrylated gelatin gel (GelMA) scaffold followed by their osteogenic differentiation for fabrication of a three dimensional bone tissue construct. Different percentages (5, 10 and 20%) and different methacrylation levels of gel (GelMAhigh and GelMAlow) were tested for degradation. Porosity of 10% GelMA was compared by SEM imaging. Gels with the fastest degradation rate (5% GelMAhigh and GelMAlow) were chosen for cell encapsulation since degradation of scaffold is of prime importance when the gel is intended to be used for implantation. Finally, cADSCs encapsulated in 5% GelMAlow demonstrated best morphology and were differentiated osteogenically. We developed a modified protocol for isolation of RNA from cells encapsulated in GelMA. Osteogenic differentiation was affirmed by the presence of osteo-specific gene expression by reverse transcriptase PCR in addition to von Kossa staining of the construct. GelMA is an excellent biodegradable scaffold for encapsulation of cADSCs without altering their osteogenic potential. This osteo-induced cellular scaffold implant opens a new therapeutic horizon in the area of tissue engineering in orthopedics.


Burnout in U.S. Military Orthopaedic Residents and Staff Physicians.
The purpose of this study was to measure the prevalence of burnout among military orthopaedic residents and staff surgeons at the U.S. Army Medical Center. 37 residents and 21 staff surgeons of a military orthopaedic residency program were asked to voluntarily complete an anonymous electronic survey. The survey consisted of two parts: first, a demographic section including questions about relationship status, work hours, deployment history, medical education debt, mentorship, and job satisfaction and second, the Maslach Burnout Inventory. 27 residents and 11 staff completed the survey for a 67% response rate. The rate of burnout among military orthopaedic surgeons in our study was 7.7% (3.7% of residents and 16.7% of staff surgeons). In addition, 25.6% of surgeons (33% of residents and 8.3% of staff) were found to be at risk of burnout. Future studies should focus on causal relationships among specific aspects of the work environment and possible preventive or protective measures. Expanding future studies to include multiple study sites would improve the quality and generalizability of the results.


Acute exacerbation of hepatitis C in hepatocellular carcinoma patients receiving chemotherapy.
Acute hepatitis C exacerbations can occur in cancer patients carrying hepatitis C virus (HCV) when receiving systemic chemotherapy. However, clinical studies evaluating these complications remain rare due to the lack of clinically proven effective and tolerable anti-HCV treatments at late cancer stages. Furthermore, no data were available regarding hepatitis C exacerbation in advanced hepatocellular carcinoma (HCC) patients receiving chemotherapy. To address this issue, 48 patients with HCV-related advanced HCC, who underwent systemic chemotherapy using 5- fluorouracil, cisplatin, and mitoxantrone from 2008 to 2014 were analyzed. Nine patients developed acute hepatitis exacerbations defined by HCV-RNA elevation ≥10-fold and alanine transaminase (ALT) elevation ≥5-fold of the upper normal limit. Six were genotype 1b and 3 were genotype 2. Three patterns of clinical courses were observed including single episode of exacerbation (n = 5), fluctuated flares (n = 3), and delayed exacerbation (n = 1). Hepatic failure developed in five patients. Patients with acute exacerbations were less likely to have pretreatment ascites (11.1% vs. 53.8%; P = 0.028) and displayed a lower baseline ALT (44.1 ± 28.5 U/L vs. 72.6 ± 19.2 U/L; P = 0.007). Paradoxically, despite a high risk of hepatic failure, occurrence of hepatitis C exacerbation was associated with a favorable overall survival (P = 0.027; 22.8 vs. 5.4 months). In conclusion, hepatitis C exacerbation can occur in HCC patients receiving chemotherapy, leading to liver failure. However, the flare was associated with a better overall survival, possibly due to its association with a better baseline liver function. J. Med. Virol. 89:153-160, 2017. © 2016 Wiley Periodicals, Inc.


Evidence for interaction with the water subphase as the origin and stabilization of nano-domain in semi-fluorinated alkanes monolayer at the air/water interface.
Multilayer films of semifluorinated alkanes (SFAs) at the air/water interface were studied in situ by grazing incidence small-angle X-ray scattering (GISAXS). The results provide evidence that the first layer in contact with the water subphase, buried below the overlayers, exhibits the same supramolecular hexagonal structure that is observed in the monolayer before the collapse, at non-zero surface pressure. We believe this result clearly demonstrates the major role of the interactions between the first layer of SFAs and the water subphase to the formation of the structure.


Photomodulation of bacterial growth and biofilm formation using carbohydrate-based surfactants.
Naturally occurring and synthetic carbohydrate amphiphiles have emerged as a promising class of antimicrobial and antiadhesive agents that act through a number of dynamic and often poorly understood mechanisms. In this paper, we provide the first report on the application of azobenzene trans-cis photoisomerization for effecting spatial and temporal control over bacterial growth and biofilm formation using carbohydrate-based surfactants. Photocontrollable surface tension studies and small angle neutron scattering (SANS) revealed the diverse geometries and dimensions of self-assemblies (micelles) made possible through variation of the head group and UV-visible light irradiation. Using these light-addressable amphiphiles, we demonstrate optical control over the antibacterial activity and formation of biofilms against multi-drug resistant (MDR) Pseudomonas aeruginosa, methicillin-resistant Staphylococcus aureus (MRSA) and Gram-negative Escherichia coli. To probe the mechanism of bioactivity further, we evaluated the impact of trans-cis photoisomerization in these surfactants on bacterial motility and revealed photomodulated enhancement in swarming motility in P. aeruginosa. These light-responsive amphiphiles should attract significant interest as a new class of antibacterial agents and as investigational tools for probing the complex mechanisms underpinning bacterial adhesion and biofilm formation.


Beta-blockers are associated with better long-term survival in patients with Takotsubo syndrome.
The advantage of beta-blockers has been postulated in patients with Takotsubo syndrome (TTS) given the pathophysiological role of catecholamines. We hypothesised that beta-blocker treatment after discharge may improve the long-term clinical outcome in this patient population. This was an observational, multicentre study including consecutive patients with TTS diagnosis prospectively enrolled in the Takotsubo Italian Network (TIN) register from January 2007 to December 2018. TTS was diagnosed according to the TIN, Heart Failure Association and InterTAK Diagnostic Criteria. The primary study outcome was the occurrence of all-cause death at the longest available follow-up; secondary outcomes were TTS recurrence, cardiac and non-cardiac death. The study population included 825 patients (median age: 72.0 (63.0-78.0) years; 91.9 % female): 488 (59.2%) were discharged on beta-blockers and 337 (40.8%) without beta-blockers. The median follow-up was 24.0 months. The adjusted Cox regression analysis showed a significantly lower risk for all-cause death (adjusted HR: 0.563; 95% CI: 0.356 to 0.889) and non-cardiac death (adjusted HR: 0.525; 95% CI: 0.309 to 0.893) in patients receiving versus those not receiving beta-blockers, but no significant differences in terms of TTS recurrence (adjusted HR: 0.607; 95% CI: 0.311 to 1.187) and cardiac death (adjusted HR: 0.699; 95% CI: 0.284 to 1.722). The positive survival effect of beta-blockers was higher in patients with hypertension than in those without (pinteraction=0.014), and in patients who developed cardiogenic shock during the acute phase than in those who did not (pinteraction=0.047). In this real-world register population, beta-blockers were associated with a significantly higher long-term survival, particularly in patients with hypertension and in those who developed cardiogenic shock during the acute phase.


Acute resistance exercise with blood flow restriction in elderly hypertensive women: haemodynamic, rating of perceived exertion and blood lactate.
This study aimed to compare haemodynamic, rating of perceived exertion and blood lactate responses during resistance exercise with blood flow restriction (BFR) compared with traditional high-intensity resistance exercise in hypertensive older women. Eighteen hypertensive women (age = 67·0 ± 1·7 years.) undertook three random sessions: (i) three sets; 10 repetitions; 20% of one repetition maximum (1RM) with BFR; (ii) three sets; 10 repetitions; 65% of 1RM; without BFR; and (iii) no-exercise with BFR. The exercise sessions were performed on knee extension equipment. Systolic (SBP) and diastolic blood pressure (DBP), heart rate (HR), stroke volume (SV) and cardiac output (CO) were significantly higher (P<0·05) in all sets of exercise sessions than the control. No statistically significant differences were detected between exercise sessions. However, SBP, DBP and systemic vascular resistance were higher (P<0·05) and SV and CO were lower (P<0·05) during the rest intervals in the session with BFR. The perceived exertion was significantly higher (P<0·01) in the 1st (4·8 ± 0·4 versus 3·1 ± 0·3), 2nd (7·3 ± 0·4 versus 5·7 ± 0·4) and 3rd sets (8·6 ± 0·5 versus 7·5 ± 0·4) of the traditional high-intensity resistance exercise compared with the exercise with BFR. Blood lactate was higher (P<0·05) in the traditional high-intensity resistance exercise (6·2 ± 0·7 mmol) than in the exercise with BFR (4·5 ± 0·4 mmol). In comparison with high-intensity resistance exercise, low-intensity resistance exercise with BFR can elicit: (i) same haemodynamic values during exercise; (ii) lower rating of perceived exertion; (iii) lower blood lactate; (iv) higher haemodynamic demand during the rest intervals.


Status epilepticus secondary to hypertensive encephalopathy as the presenting manifestation of Guillain-Barré syndrome.
Malignant hypertension due to autonomic dysfunction is a known complication of Guillain-Barré syndrome. We describe a child who presented with status epilepticus secondary to hypertensive encephalopathy who, in recovery, was found to be areflexic. Nerve conduction studies confirmed the clinical diagnosis of Guillain-Barré syndrome. She was treated with antihypertensive and antiseizure medications and intravenous immune globulin with complete resolution of her autonomic symptoms and improvement in her weakness. Guillain-Barré syndrome may result in hypertensive encephalopathy that can manifest as status epilepticus before the onset of motor symptoms.


Molecular evolution in court: analysis of a large hepatitis C virus outbreak from an evolving source.
Molecular phylogenetic analyses are used increasingly in the epidemiological investigation of outbreaks and transmission cases involving rapidly evolving RNA viruses. Here, we present the results of such an analysis that contributed to the conviction of an anesthetist as being responsible for the infection of 275 of his patients with hepatitis C virus. We obtained sequences of the NS5B and E1-E2 regions in the viral genome for 322 patients suspected to have been infected by the doctor, and for 44 local, unrelated controls. The analysis of 4,184 cloned sequences of the E1-E2 region allowed us to exclude 47 patients from the outbreak. A subset of patients had known dates of infection. We used these data to calibrate a relaxed molecular clock and to determine a rough estimate of the time of infection for each patient. A similar analysis led to an estimate for the time of infection of the source. The date turned out to be 10 years before the detection of the outbreak. The number of patients infected was small at first, but it increased substantially in the months before the detection of the outbreak. We have developed a procedure to integrate molecular phylogenetic reconstructions of rapidly evolving viral populations into a forensic setting adequate for molecular epidemiological analysis of outbreaks and transmission events. We applied this procedure to a large outbreak of hepatitis C virus caused by a single source and the results obtained played a key role in the trial that led to the conviction of the suspected source.


A Web Tool for Generating High Quality Machine-readable Biological Pathways.
PathWhiz is a web server built to facilitate the creation of colorful, interactive, visually pleasing pathway diagrams that are rich in biological information. The pathways generated by this online application are machine-readable and fully compatible with essentially all web-browsers and computer operating systems. It uses a specially developed, web-enabled pathway drawing interface that permits the selection and placement of different combinations of pre-drawn biological or biochemical entities to depict reactions, interactions, transport processes and binding events. This palette of entities consists of chemical compounds, proteins, nucleic acids, cellular membranes, subcellular structures, tissues, and organs. All of the visual elements in it can be interactively adjusted and customized. Furthermore, because this tool is a web server, all pathways and pathway elements are publicly accessible. This kind of pathway "crowd sourcing" means that PathWhiz already contains a large and rapidly growing collection of previously drawn pathways and pathway elements. Here we describe a protocol for the quick and easy creation of new pathways and the alteration of existing pathways. To further facilitate pathway editing and creation, the tool contains replication and propagation functions. The replication function allows existing pathways to be used as templates to create or edit new pathways. The propagation function allows one to take an existing pathway and automatically propagate it across different species. Pathways created with this tool can be "re-styled" into different formats (KEGG-like or text-book like), colored with different backgrounds, exported to BioPAX, SBGN-ML, SBML, or PWML data exchange formats, and downloaded as PNG or SVG images. The pathways can easily be incorporated into online databases, integrated into presentations, posters or publications, or used exclusively for online visualization and exploration. This protocol has been successfully applied to generate over 2,000 pathway diagrams, which are now found in many online databases including HMDB, DrugBank, SMPDB, and ECMDB.


Novel planar-structure electrochemical devices for highly flexible semitransparent power generation/storage sources.
Flexible and transparent power sources are highly desirable in realizing next-generation all-in-one bendable, implantable, and wearable electronic systems. The developed power sources are either flexible but opaque or semitransparent but lack of flexibility. Therefore, there is increasing recognition of the need for a new concept of electrochemical device structure design that allows both high flexibility and transparency. In this paper, we present a new concept for electrochemical device design--a two-dimensional planar comb-teeth architecture on PET substrate--to achieve both high mechanical flexibility and light transparency. Two types of prototypes--dye-sensitized solar cells and supercapacitors--have been fabricated as planar devices and demonstrated excellent device performance, such as good light transparency, excellent flexibility, outstanding multiple large bending tolerance, light weight, effective prevention of short circuits during bending, and high device integration with up-date microelectronics, compared to conventional sandwich structure devices. Our planar design provides an attractive strategy toward the development of flexible, semitransparent electrochemical devices for fully all-in-one elegant and wearable energy management.


Mutation in Saccharomyces cerevisiae conferring streptomycin and cold sensitivity by affecting ribosome formation and function.
A cold-sensitive, streptomycin-sensitive mutant of Saccharomyces cerevisiae accumulates a 28S ribonucleoprotein particle when grown at low temperature. This particle contains 17S ribosomal ribonculeic acid which is degraded when exposed to ribonuclease. The particle does not serve as a precursor to 60 and 40S ribosomal subunits nor is it turned over when growth is allowed to resume at the permissive temperature; rather it is only diluted by growth. That streptomycin sensitivity (allelic with cold sensitivity) is ribosomal is evidenced by the inhibition of protein synthesis in vitro by streptomycin and the binding of labeled streptomycin to the mutant but not the parental 40S ribosomal subunit.


No Association of filaggrin copy number variation and atopic dermatitis risk in White and Black Americans.
Atopic dermatitis (AD) is a chronic, inflammatory skin condition with a multifactorial pathophysiology. The filaggrin gene (FLG) has particularly been implicated given loss of function (LoF) mutations in this gene lead to skin barrier dysfunction and such mutations can increase a patient's likelihood of developing AD. FLG has intragenic copy number variation (CNV), which impacts the total amount of filaggrin produced. Previous research reported a dose-dependent effect such that as amount of FLG increases, risk of AD decreases. To gain a better understanding, we evaluated FLG CNV in a large case-control study of Whites and Blacks with and without AD. The goal of our study was to determine whether FLG CNV has a dose-dependent effect on the risk of developing AD and to determine whether FLG CNV varies by race. The frequencies and odds ratios comparing a given CNV by race or race within those with AD did not significantly vary. It had been thought that FLG CNV might vary by race and represent an important association with AD in Black AD subjects. However, our work suggests that while there are racial differences with respect to CNV, these differences do not appear to explain AD risk.


Application of quantitative immunofluorescence assays to analyze the expression of cell contact proteins during Zika virus infections.
Zika Virus (ZIKV) is an RNA virus that belongs to the Flavivirus (FV) genus. In the last years, several unique characteristics of ZIKV among FV have been revealed, as the multiple routes of transmission and its ability to reach different human tissues, including the central nervous system. Thus, one of the most intriguing features of ZIKV biology is its ability to cross diverse complex biological barriers. The main aim of this study is to contribute to the understanding of the still unclear mechanisms behind this viral activity. We investigated an African strain and two South American ZIKV isolates belonging to the Asian lineage, in order to characterize possible differences regarding their ability to disturb intercellular junctions. The Asian isolates correspond to an imported (Venezuelan) and an autochthonous (Argentinian) ZIKV strain for which there is still no data available. We focused on occludin and DLG1 expression as markers of tight and adherent junctions, respectively. For this, we applied a quantitative immunofluorescence assay that can ascertain alterations in the cell junction proteins expression in the infected cells. Our findings indicated that the different ZIKV strains were able to reduce the levels of both polarity proteins without altering their overall cell distribution. Moreover, the grade of this effect was strain-dependent, being the DLG1 reduction higher for the African and Asian Venezuelan isolates and, on the contrary, occludin down-regulation was more noticeable for the Argentinian strain. Interestingly, among both junction proteins the viral infection caused a relative larger reduction in DLG1 expression for all viruses, suggesting DLG1 may be of particular relevance for ZIKV infections. Taken together, this study contributes to the knowledge of the biological mechanisms involved in ZIKV cytopathogenesis, with a special focus on regional isolates.


Characterizing the Molecular Architecture of Hydrogels and Crosslinked Polymer Networks beyond Flory-Rehner. II: Experiments.
We previously [Borges, F. T. P. Biomacromolecules 2020, 21(12), 5104-5118] introduced a novel methodology for the characterization of the dimensions and architecture of hydrogel networks that provides more detailed information than the classical Flory-Rehner theory [Canal, T.; Peppas, N. A. J. Biomed. Mater. Res. 1989, 23, 1183-1193]. In this article, we illustrate our methodology by applying it to the phototerpolymerization of N-vinyl-2-pyrrolidone (NVP), ethylene glycol methyl ether acrylate (EGA), and poly(ethylene glycol) diacrylate (PEGDA). The experimental design includes 120 formulations using different fractions of the three monomers. Experimental measurements determined the mass swelling ratio and were coupled with theory to compute the internal dimensions of the network. Results demonstrate how the use of a macromeric crosslinker leads to unique network architectures not predicted by classical F-R theory, e.g., the figure shows that the mass between crosslinks predicted by F-R is actually distributed between branches and the backbone. The methodology presented offers a path toward optimizing/customizing hydrogel properties to suit the size and shape of the specific therapeutic targeted for drug delivery.


Towards next generation antisense oligonucleotides: mesylphosphoramidate modification improves therapeutic index and duration of effect of gapmer antisense oligonucleotides.
The PS modification enhances the nuclease stability and protein binding properties of gapmer antisense oligonucleotides (ASOs) and is one of very few modifications that support RNaseH1 activity. We evaluated the effect of introducing stereorandom and chiral mesyl-phosphoramidate (MsPA) linkages in the DNA gap and flanks of gapmer PS ASOs and characterized the effect of these linkages on RNA-binding, nuclease stability, protein binding, pro-inflammatory profile, antisense activity and toxicity in cells and in mice. We show that all PS linkages in a gapmer ASO can be replaced with MsPA without compromising chemical stability and RNA binding affinity but these designs reduced activity. However, replacing up to 5 PS in the gap with MsPA was well tolerated and replacing specific PS linkages at appropriate locations was able to greatly reduce both immune stimulation and cytotoxicity. The improved nuclease stability of MsPA over PS translated to significant improvement in the duration of ASO action in mice which was comparable to that of enhanced stabilized siRNA designs. Our work highlights the combination of PS and MsPA linkages as a next generation chemical platform for identifying ASO drugs with improved potency and therapeutic index, reduced pro-inflammatory effects and extended duration of effect.


[Gender differences in workplace bullying].
Despite the attention that international Agencies give to the gender issue in situations of workplace bullying, few investigations have been performed on this topic. The aim of the study is describe the gender differences in victims of workplace bullying observed in an Italian survey. A total of 243 subjects (124 males and 119 females) were examined at the Centre for Occupational Stress and Harassment of the "Clinica del Lavoro Luigi Devoto" (University of Milan and IRCCS Foundation); they were selected among patients who met the criteria for being considered victims of negative actions at work leading to workplace bullying. Data regarding the person, workplace and the workplace bullying situation were collected by means of an ad hoc questionnaire. Analysis of the data, compared with those of IS-TAT 2002, showed a higher prevalence of females subjected to negative actions at work. In women, the risk of being subjected to negative actions leading to workplace bullying was shown to increase in the 34-44 age range and to decrease in higher age ranges; in men the risk remained elevated also after 55 years of age. In general, women were victims of negative actions regarding personal values related to emotional-relational factors, while men were attacked on their work performance. Sexual harassment, may mark the onset of other types of psychological harassment or can be one of its components.


Primary and secondary stroke prevention in nonrheumatic atrial fibrillation by oral anticoagulation.
The risk of stroke or embolism in atrial fibrillation (AF) patients can be reduced by 68% by oral anticoagulation (OAC). This review is aimed to (1) summarize indications for OAC in patients with AF, (2) give an overview of the current knowledge of risk factors for bleeding complications of OAC and (3) give practical recommendations for an optimal OAC therapy in the neurological setting. Indications for OAC are increased age (>75 years), arterial hypertension, diabetes mellitus, previous thromboembolism, heart failure and, probably, coronary heart disease. Risk factors for bleeding complications are overanticoagulation with international normalized ratios (INRs) >3.0, increased age, arterial hypertension, diabetes mellitus, previous thromboembolism, polypharmacy, the early phase of OAC therapy and a lack of patients' education. Before initiation of OAC, the patient should be screened for potential bleeding sites. Careful monitoring of OAC comprises fixed appointments for the INR value determination, tracking for the patient, if he does not attend, advices about pain therapy, information about the influence of diet on the INR value and drug interaction, unscheduled INR determination in case of acute disorders and regular assessment if OAC is still indicated. Monitoring of OAC needs an effort, which has to be adequately estimated by the health care system.


A novel function for galectin-1 at the crossroad of innate and adaptive immunity: galectin-1 regulates monocyte/macrophage physiology through a nonapoptotic ERK-dependent pathway.
Several environmental factors can differentially regulate monocyte and macrophage response patterns, resulting in the display of distinct functional phenotypes. Galectin-1, an endogenous lectin found at peripheral lymphoid organs and inflammatory sites, has shown immunoregulatory activity in vivo in experimental models of autoimmunity and cancer. Whereas compelling evidence has been accumulated regarding the effects of galectin-1 on T cell fate, limited information is available on how galectin-1 may impact other immune cell types. In the present study, we report a novel role for galectin-1 in the regulation of monocyte and macrophage physiology. Treatment with galectin-1 in vitro differentially regulates constitutive and inducible FcgammaRI expression on human monocytes and FcgammaRI-dependent phagocytosis. In addition, galectin-1 inhibits IFN-gamma-induced MHC class II (MHC-II) expression and MHC-II-dependent Ag presentation in a dose-dependent manner. These regulatory effects were also evident in mouse macrophages recruited in response to inflammatory stimuli following treatment with recombinant galectin-1 and further confirmed in galectin-1-deficient mice. Investigation of the mechanisms involved in these functions showed that galectin-1 does not affect survival of human monocytes, but rather influences FcgammaRI- and MHC-II-dependent functions through active mechanisms involving modulation of an ERK1/2-dependent pathway. Our results provide evidence of a novel unrecognized role for galectin-1 in the control of monocyte/macrophage physiology with potential implications at the crossroad of innate and adaptive immunity.


Real-time 3D transoesophageal echocardiography for guiding Amplatzer septal occluder device deployment in an adult patient with atrial septal defect.
A 32-year-old male with secundum atrial septal defect underwent percutaneous transcatheter occlusion. The procedure was performed under general anaesthesia and guided by real-time 3D transoesophageal echocardiography (TEE) (i.e. 33, matrix probe 2-7 MHz). The device delivery system was advanced through a femoral vein catheter and placed in the left upper pulmonary vein. A 3D left atrial view was instantaneously obtained. The size of the septal occluder was chosen according to the balloon catheter method. A 12 mm Amplatzer device was deployed under real-time 3D TEE without fluoroscopy. The 3D views depicted the progression of the left-side disc from the left atrial cavity towards the septum. Left and right atrial views demonstrated the perfect application of the device to the atrial septum. Keeping a steady traction on the delivery rod, the right-side disc of the device was then deployed on the right atrial side of the defect. A pushing and pulling of the delivery cable ensured that the device was in a secure and stable position. Absence of peri prosthetic residual shunt was assessed by 2D colour Doppler TEE before release. Transthoracic echocardiography performed the day after ensured the right position of the device. Real-time 3D TEE is a very recent technology allowing on-line guidance of atrial septal occluder device deployment; such imaging should increase delivery safety and decrease fluoroscopy time.


Maternal and Neonatal Markers of the Homocysteine Pathway and Fetal Growth: The Generation R Study.
Suboptimal dietary intake during pregnancy may have long-term health implications in children. These effects may be mediated by fetal growth. We investigated the associations of early pregnancy and umbilical cord total homocysteine (tHcy), folate, and total and active vitamin B12 concentrations with fetal growth parameters repeatedly measured in pregnancy and at birth. This study was performed in 5890 pregnant women, participating in a population-based prospective cohort study. Blood samples were obtained from women in early pregnancy and from the umbilical vein at delivery. Fetal size parameters were repeatedly measured by ultrasound. Information about birth anthropometrics was retrieved from medical records. High early pregnancy maternal tHcy (≥8.31 μmol/L), as compared with low maternal homocysteine (≤5.80 μmol/L), and low early pregnancy maternal folate (≤9.10 nmol/L), as compared with high maternal folate (≥25.81 nmol/L) concentrations, were associated with reduced weight growth patterns throughout pregnancy, resulting in birthweight differences of -102.3 g (95% CI -139.6, -65.0) and -113.0 g (95% CI -159.6, -66.3), respectively. Low umbilical cord folate concentrations (≤15.20 nmol/L) as compared with high umbilical cord folate concentrations (≥28.41 nmol/L) were also associated with a lower birthweight and birth length (P < 0.001). Interestingly, compared with higher umbilical cord vitamin B12 , lower vitamin B12 concentrations were associated with a higher weight, length, and head circumference at birth (P < 0.01). Early pregnancy maternal and umbilical cord markers of the homocysteine pathway are significantly associated with fetal growth patterns. These differences arise from mid-pregnancy onwards.


Incidence and risk factors for early-onset hypertension after allogeneic hematopoietic stem cell transplantation in children.
Survivors of pediatric hematopoietic stem cell transplantation (HSCT) are at risk for developing hypertension. The objectives of this study are to evaluate the prevalence and risk factors of early onset hypertension during the engraftment period after HSCT. This is a retrospective study of 157 consecutive patients (mean age at HSCT: 9.1±5.1 years) who underwent HSCT for acute myeloid leukemia (n=47), acute lymphoblastic leukemia (n=43), severe aplastic anemia (n=41), and other reasons (n=26). Blood pressure data were collected at five time points: 0, 7, 14, 21, and 28 days after HSCT. Hypertension was defined as having systolic and/or diastolic blood pressure ≥95th percentile according to age, gender, and height. To analyze the risk factors related to hypertension, data, including patients' demographic and transplant characteristics, were reviewed. Hypertension developed in 59 patients (38%), among whom 12 (7.6%) required long term therapy. Thirty-two (54%) patients had systolic and diastolic, 8 (14%) had only systolic, and 19 (32%) had only diastolic hypertension. Younger age, acute graft-versus-host disease, sinusoidal obstruction syndrome, treatment with antifungal agent, and greater increase in serum creatinine (Cr) levels were associated with hypertension. Multivariate analysis showed that younger age at HSCT and greater increase in serum Cr level were independent risk factors for hypertension. Prevalence of hypertension during immediate post-HSCT period is high, especially in younger children. A greater increase in Cr after HSCT was significantly associated with hypertension. Further study is needed to elucidate long-term cardiovascular complications in pediatric HSCT survivors.


Successful treatment of acute head and neck dog bite wounds without antibiotics.
Dog bites continue to be the most common bite injury in the United States. We previously reported a series of 61 patients with 215 dog bite wounds. Of these, 55 patients had 188 dog bite wounds of the head and neck area which were treated with copious saline pressure irrigation, meticulous wound and wound edge debridement, repeated copious saline pressure irrigation, adequate antibiotic coverage, wound closure, and close postoperative monitoring. A wound infection rate of .53% and a patient infection rate of 1.8% were obtained using this protocol. Our present study uses the same protocol with the exclusion of antibiotic coverage. Our series of 49 patients with 145 head and neck wounds reveals a wound infection rate of 1.4% and a patient infection rate of 4%. This is not statistically significantly different from the outcome of the previous study.


Malignant melanoma and levodopa.
A patient with Parkinson's disease developed a malignant melanoma within a congenital nevus after starting levodopa therapy. Levodopa has a central role in the metabolism of the melanocyte but data do not permit the conclusion that it promotes the development of malignant melanoma. However, patients receiving levodopa should be monitored for skin changes suggestive of melanoma.


In silico characterization of ligand-receptor interactions for U-47700, N,N-didesmethyl-U-47700, U-50488 at mu- and kappa-opioid receptors.
The increasing misuse of novel synthetic opioids (NSOs) represents a serious public health concern. In this regard, U-47700 (trans-3,4-dichloro-N-[2-(dimethylamino)cyclohexyl]-N-methylbenzamide) and related "U-compounds" emerged on recreational drug markets as synthetic substitutes for illicit heroin and constituents of counterfeit pain medications. While the pharmacology of U-compounds has been investigated using in vitro and in vivo methods, there is still a lack of understanding about the details of ligand-receptor interactions at the molecular level. To this end, we have developed a molecular modeling protocol based on docking and molecular dynamics simulations to assess the nature of ligand-receptor interactions for U-47700, N,N-didesmethyl U-47700, and U-50488 at the mu-opioid receptor (MOR) and kappa-opioid receptor (KOR). The evaluation of ligand-receptor and ligand-receptor-membrane interaction energies enabled the identification of subtle conformational shifts in the receptors induced by ligand binding. Interestingly, the removal of two key methyl groups from U-47700, to form N,N-didesmethyl U-47700, caused a loss of hydrogen bond contact with tryptophan (Trp)229, which may underlie the lower interaction energy and reduced MOR affinity for the compound. Taken together, our results are consistent with the reported biological findings for U-compounds and provide a molecular basis for the MOR selectivity of U-47700 and KOR selectivity of U-50488.


Can We Accurately Measure Axial Segment Coordination during Turning Using Inertial Measurement Units (IMUs)?
Camera-based 3D motion analysis systems are considered to be the gold standard for movement analysis. However, using such equipment in a clinical setting is prohibitive due to the expense and time-consuming nature of data collection and analysis. Therefore, Inertial Measurement Units (IMUs) have been suggested as an alternative to measure movement in clinical settings. One area which is both important and challenging is the assessment of turning kinematics in individuals with movement disorders. This study aimed to validate the use of IMUs in the measurement of turning kinematics in healthy adults compared to a camera-based 3D motion analysis system. Data were collected from twelve participants using a Vicon motion analysis system which were compared with data from four IMUs placed on the forehead, middle thorax, and feet in order to determine accuracy and reliability. The results demonstrated that the IMU sensors produced reliable kinematic measures and showed excellent reliability (ICCs 0.80-0.98) and no significant differences were seen in paired t-tests in all parameters when comparing the two systems. This suggests that the IMU sensors provide a viable alternative to camera-based motion capture that could be used in isolation to gather data from individuals with movement disorders in clinical settings and real-life situations.


Impact of Tinnitus Masking on Auditory Brainstem Response Results.
Tinnitus- the perception of sound without external stimulation can also lead to disruption in the quality of life and has been over the years been benefitted by tinnitus masking. Hence this study to understand the effectiveness of tinnitus masking using the Auditory Brainstem Response (ABR) Test. The intention of this experimental research design is to determine whether tinnitus masking as treatment for tinnitus makes a significant difference in auditory evoked brainstem responses before and after masking for understanding the effectiveness of the treatment objectively and possible quantification of benefit measurement through ABR. 30 subjects with normal hearing and unilateral tinnitus were assessed using ABR before and after tinnitus masking. Data was collected and compared to evaluate pre-masking and post-masking values of Latency-Intensity function and Interpeak Latency differences. Data was analyzed using descriptive statistics, test of homogeneity of variances and Two-way ANOVA. Both latency-intensity functions and interpeak latency differences showed significant differences before and after tinnitus masking with significance values of Two-way ANOVA as .001, (Calculated at p < .05). Despite the patient's subjective feedback, objective proof of the patient's benefit is a necessity. Therefore, this study shows that ABR shows significant differences in patients treated with tinnitus masking. Further suggesting benefit quantification of tinnitus masking as a treatment to tinnitus suffering individuals and for further understanding the intricacies of changes in the central auditory pathway due to masking.


New insulin-like proteins with atypical disulfide bond pattern characterized in Caenorhabditis elegans by comparative sequence analysis and homology modeling.
We have identified three new families of insulin homologs in Caenorhabditis elegans. In two of these families, concerted mutations suggest that an additional disulfide bond links B and A domains, and that the A-domain internal disulfide bond is substituted by a hydrophobic interaction. Homology modeling remarkably confirms these predictions and shows that despite this atypical disulfide bond pattern and the absence of C-like peptide, all these proteins may adopt the same fold as the insulin. Interestingly, whereas we identified 10 insulin-like peptides, only one insulin-like-receptor (daf-2) has been found. We propose that these insulin-related peptides may correspond to different activators or inhibitors of the daf-2 insulin-regulating pathway.


Atorvastatin improves survival in septic rats: effect on tissue inflammatory pathway and on insulin signaling.
The aim of the present study was to investigate whether the survival-improving effect of atorvastatin in sepsis is accompanied by a reduction in tissue activation of inflammatory pathways and, in parallel, an improvement in tissue insulin signaling in rats. Diffuse sepsis was induced by cecal ligation and puncture surgery (CLP) in male Wistar rats. Serum glucose and inflammatory cytokines levels were assessed 24 h after CLP. The effect of atorvastatin on survival of septic animals was investigated in parallel with insulin signaling and its modulators in liver, muscle and adipose tissue. Atorvastatin improves survival in septic rats and this improvement is accompanied by a marked improvement in insulin sensitivity, characterized by an increase in glucose disappearance rate during the insulin tolerance test. Sepsis induced an increase in the expression/activation of TLR4 and its downstream signaling JNK and IKK/NF-κB activation, and blunted insulin-induced insulin signaling in liver, muscle and adipose tissue; atorvastatin reversed all these alterations in parallel with a decrease in circulating levels of TNF-α and IL-6. In summary, this study demonstrates that atorvastatin treatment increased survival, with a significant effect upon insulin sensitivity, improving insulin signaling in peripheral tissues of rats during peritoneal-induced sepsis. The effect of atorvastatin on the suppression of the TLR-dependent inflammatory pathway may play a central role in regulation of insulin signaling and survival in sepsis insult.


Branchial sinus of the piriform fossa: reappraisal of third and fourth branchial anomalies.
The objective of this study was to review clinical and embryologic aspects of third and fourth branchial anomalies. Retrospective study. We reviewed the institutional and departmental databases at our institution to identify all cases of third and fourth branchial anomalies encountered from 1992 to 2006. All patient records were examined with respect to demographics, clinical history, and radiologic and pathologic reports. We identified 17 cases of third and fourth branchial anomalies, the largest series of its kind reported to date. The lesions were predominantly left sided, all presenting with neck infection. Fistula formation was iatrogenic, secondary to incision and drainage. Preoperative direct laryngoscopy always revealed a pit within the apex of the piriform fossa. Surgical excision involved ipsilateral thyroidectomy as the lesion passed through the thyroid gland. No lesions following the classical course of a either a third or fourth branchial anomaly were identified. The clinical presentation of branchial sinuses arising from the piriform fossa is more in keeping with derivation from the thymopharyngeal duct (of the third pouch) than the hypothetical course of third and fourth branchial fistulae.


Changes in the expression and cytological localization of betacellulin and its receptors (ErbB-1 and ErbB-4) in the trophoblasts in human placenta over the course of pregnancy.
Betacellulin (BTC), purified and cloned from mouse beta cell tumor (BTC-JC10), is regarded as a new member of the epidermal growth factor family. The present study was conducted to clarify the expression of BTC and its receptors, ErbB-1 and ErbB-4, in the trophoblasts in the human placenta over the course of pregnancy. Human placental tissues were obtained from 4 pregnant women at the 4th to 5th week of pregnancy (very early placentas), 10 women at the 6th to 12th week (early placentas), 5 women at the 18th to 21st week (mid placentas) and 8 women at the 38th and 40th week (term placentas). The mRNA expressions of BTC, erbB-1 and erbB-4 were evaluated by quantitative RT-PCR with Southern blotting and the expression of the soluble form of BTC was determined by western immunoblot with a specific antibody to BTC protein. Immunohistochemical staining of BTC, ErbB-1 and ErbB-4 was also performed. The levels of BTC mRNA expression in early and mid placentas were significantly higher than those in term placentas. The soluble form of BTC protein with an estimated molecular mass of 9.5 kDa was expressed in early and mid placentas, whereas the soluble form was not detected in term placentas. BTC from very early placentas until mid placentas was immunolocalized in syncytiotrophoblasts (S-cells), and was most abundant in early placentas. In contrast, BTC was immunolocalized in extravillous trophoblasts (EVTs), but not in villous trophoblasts in term placentas. The levels of erbB-1 mRNA in the early and mid placentas were significantly higher than those in term placentas, whereas the levels of erbB-4 mRNA in early placentas were significantly lower than those in mid and term placentas. ErbB-1 was immunolocalized in cytotrophoblasts in very early placentas, whereas it was immunolocalized in S-cells from early until term placentas. ErbB-4 from very early placentas until mid placentas was immunolocalized in S-cells, whereas ErbB-4 in the term placentas was detected in EVTs, but not in villous trophoblasts. These findings provide evidence for changes in expression and cytological localization of BTC and its receptors in the trophoblasts in human placenta over the course of pregnancy. BTC may play a pivotal role as a local growth factor in promoting the differentiated villous trophoblastic function via ErbB-1 in early placentas and in contributing to placental growth through the maintenance of EVT cell function via ErbB-4 in term placentas.


Association between HLA class II genes and autoantibodies to cyclic citrullinated peptides (CCPs) influences the severity of rheumatoid arthritis.
The functional role of HLA class II molecules in the pathogenesis of rheumatoid arthritis (RA) is unclear. HLA class II molecules are involved in the interaction between T and B lymphocytes required for long-lived B cell responses and generation of high-affinity IgG antibodies. We undertook this study to investigate the relationship between HLA class II gene polymorphisms and RA-specific IgG antibodies against cyclic citrullinated peptides (anti-CCP antibodies). High-resolution HLA-DR and DQ typing and anti-CCP-2 antibody testing were performed on 268 RA patients from the Early Arthritis Clinic cohort at the Department of Rheumatology of the Leiden University Medical Center. The presence of anti-CCP antibodies was analyzed in carriers of the different DR and DQ alleles. Disease progression was measured over a period of 4 years by scoring radiographs of the hands and feet using the Sharp/van der Heijde method. Carriership of the individual alleles HLA-DRB1*0401, DRB1*1001, DQB1*0302, and DQB1*0501 was associated with the presence of anti-CCP antibodies. Carriers of DQ-DR genotypes containing proposed RA susceptibility alleles were significantly more often anti-CCP antibody positive. Carriership of one or two HLA-DRB1 shared epitope (SE) alleles was significantly associated with production of anti-CCP antibodies (odds ratio [OR] 3.3, 95% confidence interval [95% CI] 1.8-6.0 and OR 13.3, 95% CI 4.6-40.4, respectively). An increased rate of joint destruction was observed in SE+, anti-CCP+ patients (mean Sharp score 7.6 points per year) compared with that in SE-, anti-CCP+ patients (2.4 points per year) (P = 0.04), SE+, anti-CCP- patients (1.6 points per year) (P < 0.001), and SE-, anti-CCP- patients (1.6 points per year) (P < 0.001). HLA class II RA susceptibility alleles are associated with production of anti-CCP antibodies. Moreover, more severe disease progression is found in RA patients with both anti-CCP antibodies and SE alleles.


Immunological studies in tropical splenomegaly syndrome in Uganda.
An immunological evaluation carried out in eight patients with the tropical splenomegaly syndrome showed no evidence of impairment in cellular or humoral immunity, though raised levels of macroglobulins were noted in four patients. Hence gross immunological deficiency cannot be associated with the intense lymphoreticular proliferation observed in this disorder.


[Evaluate the value of (18)F-FDG PET-CT imaging in predicting the mutationsin epidermal growth factor receptor in lung adenocarcinoma].
Objective: To investigate the value of maximum Standardized Uptake Value(SUVmax), Metabolic Tumor Volume (MTV) and Total Lesion Glycolysis (TLG) calculated from (18)F-FDG PET-CT in predicting the presence of epidermal growth factor receptor (EGFR) mutations in lung adenocarcinoma. Methods: We retrospectively reviewed 137 lung adenocarcinoma patients with EGFR mutations testing and pretreatment (18)F-FDG PET-CT. Receiver Operating Characteristic (ROC) curve analysis was performed to quantify the predictive value of SUVmax、MTV、TLG. A multivariate logistic regression analysis was used to evaluate the predictive value of EGFR mutation. Results: Among 137 lung adenocarcinoma patients, 86(62.8%, 86/137) were identified with EGFR mutations. The SUVmax, MTV and TLG were 7.4, 5.28 cm(3,) 20.20, respectively. The optimal cut-off values of SUVmax, MTV and TLG were 7.99(AUC=0.658, 95% CI=0.566~0.752, P=0.002), 6.09 cm(3)(AUC=0.644, 95% CI=0.550~0.737, P=0.005), 35.08(AUC=0.650, 95% CI= 0.557~0.744, P=0.003), respectively. Multivariate analysis showed that TLG and smoking status were the most significant predictors of EGFR mutation(all P<0.05). Conclusion: TLG in (18)F-FDG PET/CT is an independent factor for predicting EGFR mutation in patients with lung adenocarcinoma, and has certain reference value for predicting EGFR mutation.


Functional connectivity between mesial temporal and default mode structures may help lateralize surgical temporal lobe epilepsy.
The most common surgically treatable epilepsy syndrome is mesial temporal lobe epilepsy (mTLE). Preoperative noninvasive lateralization of mTLE is challenging in part due to rapid contralateral seizure spread. Abnormal connections in both the mesial temporal lobe and resting-state networks have been described in mTLE, but it is unclear if connectivity between these networks may aid in lateralization. In 52 patients with left mTLE (LmTLE) or right mTLE (RmTLE) and 52 matched control subjects, the authors acquired 20 minutes of resting-state functional MRI (fMRI) and evaluated functional connectivity of bilateral hippocampi and amygdalae with selected resting-state networks. They used Pearson correlation, network-based statistic, and dynamic causal modeling. Also, to evaluate the clinical utility of a resting-state connectivity model in lateralizing unilateral presurgical mTLE patients, they used receiver operating characteristic curve analysis. RmTLE patients demonstrated decreased nondirected connectivity between the right hippocampus and default mode network compared with LmTLE patients and control subjects. Network-based statistic analysis revealed that the network with most decreased connectivity that distinguished LmTLE from RmTLE patients included the right hippocampus and amygdala, right lateral orbitofrontal cortices, and bilateral inferior parietal lobules, precuneus, and medial orbitofrontal cortices. Dynamic causal modeling analysis revealed that cross-hemispheric connectivity between hippocampi and amygdalae was predominantly inward toward the epileptogenic side. A regression model incorporating these connectivity patterns was used to accurately lateralize mTLE patients with an area under the receiver operating characteristic curve of 0.87. Evaluating fMRI connectivity between mesial temporal structures and default mode network may aid in mTLE lateralization, reduce need for intracranial monitoring, and guide surgical planning.


A review of the biological and pharmacological activities of mesalazine or 5-aminosalicylic acid (5-ASA): an anti-ulcer and anti-oxidant drug.
Mesalazine, also known as 5-aminosalicylic acid (5-ASA), is a synthetic drug from the family of nonsteroidal anti-inflammatory drugs (NSAIDs) used for inflammatory diseases of the gastrointestinal tract. However, 5-ASA has also been used for various other diseases due to its pharmacological effects, but they are usually scattered across various publications, which may limit further research and clinical use of this drug. This review is a summary of published information on the biological and pharmacological effects of 5-ASA with the aim of identifying its anti-oxidant role and medicinal use. 5-ASA data have been collected from 1987 to February 2021 using major databases such as Web of Science, PubMed, Elsevier, Wiley Online Library, Springer, Google Scholar, etc. According to research, the pharmacological and biological effects of 5-ASA include treatment of inflammatory bowel disease, and anti-oxidant, anti-inflammatory, antibacterial, antifungal, anticancer, anti-amyloid, gastric protection (gastroprotective), and antidiverticulosis properties. Numerous pharmacological studies have shown that 5-ASA is an anti-oxidant and anti-ulcer compound with high therapeutic potential that, if the appropriate dose is discovered, its chemical structure changes and its effectiveness is optimized, 5-ASA has been used experimentally for other diseases.


Is There any Concordance between of IHC with FISH in HER2-Positive Breast Cancer Patients?
Background: In developed or developing countries, the most common cancer in women is breast cancer with a pick in 40-50 years in Asia. Herein, we compared the association between IHC with FISH in HER2-positive breast cancer patients and affection of trastuzumab on disease free survival and overall survival (OS). Subjects and Methods: Immunohistochemical (IHC) analysis of hormone receptors and HER2 was performed in 133 patients with breast cancer between 2003 and 2014. Patients were selected for Herceptin adjuvant treatment, according to IHC 3+ or FISH+. The specimens for pathology reports were fixed at 10% neutral-buffered formalin (pH=7.4) for 24 hours, then sliced into 4 μm sections. Results: The mean age of patients at diagnosis was 46.39 years (range, 24-78 years), 100% female. Concordance rates between IHC and FISH were 31.1% for IHC 2+ and 84.1% for IHC 3+ (p<0.001). The 87 patients had age ≤50 years and 46 patients had >50 years. Of the 133 patients, 30 patients (22.6%) had metastasis and 72 (54.1%) had right involvement. Ninety three (69.9%) patients had lymph node invasion. 48 patients (36.1%) were treated with trastuzumab and 85 (63.9%) were treated without trsastuzumab. The 10-year survival rate was 70% and the mean survival was 49 months. Conclusion: We recommend clinicians that FISH analysis is as a predictor in breast cancer patients with IHC score 2+. In contrast, FISH analysis of IHC 3+ samples was no useful. Trastuzumab therapy is effective and tolerated for breast cancer with IHC 3+ and probably IHC 2+/FISH+.


Genes, environment and immunity in the development of rheumatoid arthritis.
The combined role of genes, environment and immunity in the development of rheumatoid arthritis (RA) has been the subject of recent investigations. New data support a gene-environment interaction between smoking and the MHC class II HLA-DRB1 shared epitope (SE) genes in anti-citrulline antibody (anti-CP(+)) RA but not in anti-CP(-) disease. These data from genetic epidemiology, together with information on citrullination in the lungs of smokers, have prompted the formulation of a new etiological hypothesis for anti-CP(+) RA, suggesting that smoking in the context of HLA-DR SE might trigger immunity to citrulline-modified proteins and that this immunity, after several years, might cause arthritis.


Continuous subcutaneous insulin infusion vs multiple daily injections in pregnant women with type 1 diabetes mellitus: a systematic review and meta-analysis of randomised controlled trials and observational studies.
Randomised controlled trials (RCTs) have shown an advantage of continuous subcutaneous insulin infusion (CSII) over multiple daily injections (MDI) in the general type 1 diabetes mellitus (T1DM) population. RCT data on T1DM management in pregnancy remain limited. We performed a systematic review of both RCTs and non-RCTs evaluating CSII vs MDI in T1DM-complicated pregnancy. Electronic databases were searched for studies comparing CSII with MDI in T1DM-complicated pregnancy. A meta-analysis provided point estimates with 95% confidence intervals (CI). Continuous outcomes were reported as weighted mean differences (WMD) or standardised mean differences (SMD), and dichotomous data as relative risk (RR). The search identified 47 studies, including 43 non-RCTs, reporting on 7824 pregnancies. The meta-analysis showed a lower HbA1c level with CSII vs MDI in the first trimester (WMD: -0.45%; 95%CI: -0.62, -0.27). This difference decreased in subsequent trimesters. Compared to MDI, therapy with CSII resulted in higher gestational weight gain (GWG) (WMD: 1.02 kg; 95%CI: 0.41, 1.62), and lower daily insulin dose requirements in the first (SMD: -0.46; 95%CI: -0.68, -0.24) and subsequent trimesters. Moreover, infants from the CSII group were more likely to be large for gestational age (LGA) (RR: 1.16; 95%CI: 1.07, 1.24) and less likely to be small for gestational age (SGA) (RR: 0.66; 95%CI: 0.45; 0.97). In T1DM-complicated pregnancy, CSII compared to MDI therapy resulted in better first trimester glycaemic control; this difference decreased in subsequent trimesters. CSII therapy was associated with lower insulin requirements, higher GWG and altered risk for infants being LGA and SGA.


Direct Growth of Bismuth Film as Anode for Aqueous Rechargeable Batteries in LiOH, NaOH and KOH Electrolytes.
As promising candidates for next-generation energy storage devices, aqueous rechargeable batteries are safer and cheaper than organic Li ion batteries. But due to the narrow voltage window of aqueous electrolytes, proper anode materials with low redox potential and high capacity are quite rare. In this work, bismuth electrode film was directly grown by a facile hydrothermal route and tested in LiOH, NaOH and KOH electrolytes. With low redox potential (reduction/oxidation potentials at ca. -0.85/-0.52 V vs. SCE, respectively) and high specific capacity (170 mAh·g-1 at current density of 0.5 A·g-1 in KOH electrolyte), Bi was demonstrated as a suitable anode material for aqueous batteries. Furthermore, by electrochemical impedance spectroscopy (EIS) analysis, we found that with smaller Rs and faster ion diffusion coefficient, Bi electrode film in KOH electrolyte exhibited better electrochemical performance than in LiOH and NaOH electrolytes.


Gitelman syndrome: genetic and expression analysis of the thiazide-sensitive sodium-chloride transporter in blood cells.
Gitelman syndrome is caused by mutations of the SLC12A3 gene, which encodes the thiazide-sensitive NaCl transporter NCCT. Although several mutations causing Gitelman syndrome have been described, their molecular consequences have been rarely studied. We report a patient with Gitelman syndrome due to a mutation in the GT donor splicing site of intron 9. The analysis of RNA from peripheral blood cells showed a complete deletion of exon 9. This case report confirms the feasibility of using readily accessible blood cells to study the expression of the SLC12A3 gene, a procedure that may facilitate further studies of the functional genomics of Gitelman syndrome.


Sensitive and Direct Optical Monitoring of Release and Cellular Uptake of Aqueous CO from CO-Releasing Molecules.
Dynamics of release and cellular uptake of aqueous CO from CO-releasing molecules (CORMs) significantly affect signaling and cell viability. So far, it has been mainly observed by IR, UV-visible, and fluorescence techniques, which suffer from poor sensitivity and slow response time. Here, we show how to directly probe the mass transfer of aqueous CO from CORMs to cells using a fluidic chamber integrated with live cells and Raman reporters of large-area Au@Pd core-shell nanoparticle assembly to emulate a physiologically relevant microenvironment. We sensitively and directly detect CO release from trace CORMs of as low as 100 nM by measuring the Raman transitions of CO via rapid chemisorption onto the surface of the Au@Pd nanoparticles. By using our method, we successfully observe the dynamics of CO release from CORM-2 despite its very short half-life. We also reveal that the initial rate of CO release from CORM-3 is dramatically decreased by tens to hundreds of times when exposed to physiologically relevant pH variations from 7.4 to 2.5, which can be attributed to the acid hydrolysis of the CO ligand. CORM-2 tends to quickly release CO regardless of pH, probably because of its rapid cleavage into two monomeric Ru complexes by the co-solvent. The decrease in the initial rate at lower temperatures is more significant for CORM-3 than for CORM-2. Finally, we observe that the cellular uptake of aqueous CO from CORM-3 by lung cancer cells is approximately 2 times higher than that of normal lung cells.


The calcineurin-NFAT pathway negatively regulates megakaryopoiesis.
The calcium regulated calcineurin-nuclear factor of activated T cells (NFAT) pathway modulates the physiology of numerous cell types, including hematopoietic. Upon activation, calcineurin dephosphorylates NFAT family transcription factors, triggering their nuclear entry and activation or repression of target genes. NFATc1 and c2 isoforms are expressed in megakaryocytes. Moreover, human chromosome 21 (Hsa21) encodes several negative regulators of calcineurin-NFAT, candidates in the pathogenesis of Down syndrome (trisomy 21)-associated transient myeloproliferative disorder and acute megakaryoblastic leukemia. To investigate the role of calcineurin-NFAT in megakaryopoiesis, we examined wild-type mice treated with the calcineurin inhibitor cyclosporin A and transgenic mice expressing a targeted single extra copy of Dscr1, an Hsa21-encoded calcineurin inhibitor. Both murine models exhibited thrombocytosis with increased megakaryocytes and megakaryocyte progenitors. Pharmacological or genetic inhibition of calcineurin in mice caused accumulation of megakaryocytes exhibiting enhanced 5-bromo-2'-deoxyuridine uptake and increased expression of messenger RNAs encoding CDK4 and G1 cyclins, which promote cell division. Additionally, human megakaryocytes with trisomy 21 show increased proliferation and decreased NFAT activation compared with euploid controls. Our data indicate that inhibition of calcineurin-NFAT drives proliferation of megakaryocyte precursors by de-repressing genes that drive cell division, providing insights into mechanisms of normal megakaryopoiesis and megakaryocytic abnormalities that accompany Down syndrome.


Limitations of cadence-based walking for assessing bouts of moderate-to vigorous-intensity physical activity under free-living conditions.
The purpose of the present investigation was to examine the relationship between the accumulation of 1000 steps in 10 minutes (1K) and 3000 steps in 30 minutes (3K) with the amount and intensity of daily physical activity. Thirty-three adults (16 males and 17 females, 53 ± 19 years) wore an accelerometer (Lifecorder) for seven consecutive days in order to determine the number of steps and the time spent in physical activity at light intensity (LPA), moderate intensity (MPA), vigorous intensity (VPA) and moderate to vigorous intensity (MVPA). Furthermore, based on the minute-by-minute stepping rate, the number, intensity and duration of walking bouts (1K and 3K) were evaluated. The daily number of steps, LPA, MPA and VPA were significantly higher on the days with 1K or 3K compared with that observed on the days without 1K or 3K (P <0.05). The duration of 1K was not found to be correlated with an MVPA >10 minutes. An MVPA >10 minutes was less than 2 min · day(-1) on the days with 1K or 3K. Therefore, it is doubtful that the concept of cadence is an alternative indicator for the commonly used definition of MVPA. It remains unclear whether participation in 1K and 3K guarantees that an individual will meet the current MVPA guidelines.


The role of brain shift, patient age, and Parkinson's disease duration in the difference between anatomical and electrophysiological targets for subthalamic stimulation.
Although microrecording is common in subthalamic stimulation, microelectrode monitoring prolongs surgical time and may increase the risk of haemorrhagic complications. The main reason for electrophysiological mapping is the discrepancy between the calculated anatomical and final electrophysiological targets. The aim of this paper is to describe the relationship between anatomical and electrophysiological targets defined as the best electrophysiological recordings from multiple parallel electrode tracts, explaining the target discrepancy with attention paid to the role of brain shift and patient- and disease-related factors. Subthalamic electrodes were stereotactically implanted in 58 patients using microrecording by means of parallel electrodes at defined distances. The relationship between the final electrode placement to its anatomical trajectory and the relationship between the definitive electrodes implanted on the right and left sides were analysed, as was the influence of patient age, Parkinson's disease duration, and late motor complications duration. Final electrode placement matched the anatomical trajectory in 53.4% of patients on the right side and 43.1% of patients on the left side. Electrode positions were symmetrical in 38.3% of patients. The analysis of left and right electrode positions does not prove a statistically significant prevalence of lateral and posterior final electrode trajectories as could be expected from lateral and posterior movements of the brain caused by brain shift, although there was some tendency for a larger percentage of lateral electrodes on the left side. Age, Parkinson's disease duration, and L-DOPA effect duration were not confirmed as responsible factors. The difference between anatomical trajectory and final electrode placement supports the use of functional microelectrode monitoring in subthalamic deep brain stimulation. Brain shift is not the only causative factor of the difference. The possible roles of age, Parkinson's disease duration, and late motor complications duration were also not confirmed by study results.


Association between Mediterranean diet adherence and colorectal cancer: a dose-response meta-analysis.
Mounting epidemiologic studies have investigated the potential inverse association between Mediterranean diet (MD) adherence and colorectal cancer (CRC) incidence and mortality. This meta-analysis aimed to investigate the association between MD adherence and CRC incidence and mortality. PubMed, Embase, and Web of Science were searched to identify eligible studies through September 2019. A random-effects model was used to estimate summary RRs and 95% CIs. This meta-analysis included 13 prospective cohort studies, of which 9 reported CRC incidence and 5 reported CRC mortality. The summary RR of CRC incidence was 0.90 (95% CI: 0.84, 0.96) for highest compared with lowest MD adherence and 0.96 (95% CI: 0.94, 0.99) per 2-score increase in MD adherence. The summary RRs for highest compared with lowest MD adherence were 0.82 for rectal cancer (95% CI: 0.71, 0.95), 0.94 for proximal colon cancer (95% CI: 0.87, 1.02), and 0.91 for distal colon cancer (95% CI: 0.79, 1.04). Neither the summary HR of overall mortality for highest compared with lowest pre- and postdiagnosis MD adherence, nor the summary HR of CRC-specific mortality for highest compared with lowest prediagnosis MD adherence achieved a value with statistical significance. Our meta-analysis supports the inverse association of MD adherence with CRC incidence, but not with overall mortality or CRC-specific mortality among those diagnosed with CRC.


Embryonic development of the ventral body wall and its congenital malformations.
Congenital abdominal wall defects, frequently associated with other anomalies, are found in many forms. Consequently, there is still controversy in the literature concerning nomenclature, classification, and pathogenesis. Recently, we proposed a new nomenclature and classification of abdominal wall defects based on the early development of the umbilical cord and of the ventral body wall. According to this classification the complete spectrum of abdominal wall defects, including cloacal exstrophy, bladder exstrophy, and epispadias, can be subdivided into four types: primary (thoraco-)abdominoschisis, omphalocele, body wall dysplasia, and secondary (thoraco-)abdominoschisis. Each type is characterized by its specific configuration of the placenta, the membranes, the umbilical cord, and the fetus. Anomalies such as urachal remnants and omphalomesenteric duct malformations can be explained by disturbances during later stages of umbilical cord development.