Conformational changes in the cyclic undecapeptide cyclosporin induced by interaction with metal ions. An FTIR study.
Infra-red spectra have been measured for the cyclic undecapeptide cyclosporin A (CsA) and three analogues CsC, CsD and CsH in acetonitrile and in the presence of 10:1 molar excess of Mg2+, Ca2+, Na+ or Li+ in the same solvent. Interaction with each of these ions is suggested by marked changes in band positions over the amide I region (1600-1700 cm-1). The formation of complexes of cyclosporin with calcium and magnesium ions is indicated by the presence of C = O stretching bands well outside the range normally expected for the amide I absorptions of free peptides. Although they share this characteristic, the spectra indicate that the mode and/or strength of Ca2+ binding is quite different from that of Mg2+ binding. In contrast, the two monovalent ions interact with CsA, CsC and CsD to yield spectra that are very similar to one another. The spectra are consistent with binding of the monovalent ions simultaneously to several carbonyl groups of the loop structure.


Immunochemical accessibility of ribosomal protein S4 in the 30 S ribosome. The interaction of S4 with S5 and S12.
The reactivity of protein S4-specific antibody preparations with 30 S ribosomal subunits and intermediates of in vitro subunit reconstitution has been characterized using a quantitative antibody binding assay. Anti-S4 antibody preparations did not react with native 30 S ribosomal subunits; however, they did react with various subunit assembly intermediates that lacked proteins S5 and S12. The inclusion of proteins S5 and S12 in reconstituted particles resulted in a large decrease in anti-S4 reactivity, and it was concluded that proteins S5 and S12 are primarily responsible for the masking of S4 antigenic determinants in the 30 S subunit. The effect of S5 and S12 on S4 accessibility is consistent with data from a variety of other approaches, suggesting that these proteins form a structural and functional domain in the small ribosomal subunit.


Induction of host preference in Drosophila melanogaster.
Individuals of Drosophila melanogaster were maintained as larvae and/or as adults on media made from one of the following natural breeding sties: apple, tomato, banana, or squash. The oviposition site preference of adults was not affected by the type of food they had developed on as larvae. However, prior exposure to either apple or tomato enhanced their preference for that food when subsequently given a choice between apple and tomato for oviposition. In a second experiment, adult flies were kept on media made from either apples, oranges, grapes, tomatoes, or onions; their oviposition site preferences were subsequently tested in a 5-choice situation. Prior exposure to a particular food did in some cases increase the acceptability of that food to flies. More remarkably, it sometimes modified the flies' responses to other foods, a phenomenon referred to here as cross-induction.


Progression in early erosive rheumatoid arthritis: 12 month results from a randomized controlled trial comparing methotrexate and gold sodium thiomalate.
To compare radiographic outcomes in patients with active early erosive rheumatoid arthritis (RA) who were treated with methotrexate (MTX) and gold sodium thiomalate (GSTM). A total of 174 patients from two centres were randomly assigned to receive weekly i.m. injections for 12 months of either 15 mg MTX or 50 mg GSTM in a double-blind fashion. Radiographic evaluations including standardized scoring of 38 joints of the hands, wrists and forefeet, and count of eroded joints, were carried out at baseline and after 6 and 12 months in all patients, including withdrawals. An intention-to-treat analysis revealed no statistically significant difference in the progression of radiographic scores between treatment groups after 6 months (3.4 with MTX vs 2.6 with GSTM, P = 0.66) and after 12 months (6.0 vs 4.8, P = 0.44). A similar pattern was observed for the number of joints with erosions. The slope of radiographic progression was significantly reduced in the second half-year compared to the first 6 months in both groups. Erythrocyte sedimentation rate and C-reactive protein at baseline, and the presence of rheumatoid factor (RF), were the main predictors of progression in bivariate analysis. RF remained as the only predictor for radiographic outcome in multivariable analysis. In parallel to clinical improvement, both GSTM and MTX reduce the slope of radiographic progression in patients with active erosive RA.


Primary signet-ring cell carcinoma of the lung: A report of seven cases.
Signet-ring cell carcinoma (SRCC) is an extremely rare subtype of adenocarcinoma with aggressive behavior that usually occurs in the gastrointestinal tract, prostate or breast. In this study, we described the clinicopathological and prognostic characteristics of, and the therapeutic strategies for seven patients with primary SRCC of the lung from Sichuan University West China Hospital to enhance our understanding of this kind of tumor. According to the information presented herein, it is believed that patients with primary pulmonary SRCC can live for a long time if the cancer is diagnosed early and treated actively. However, more investigations are still needed due to the limited reports about primary SRCC of the lung. KEY POINTS: SIGNIFICANT FINDINGS OF THE STUDY: Primary signet-ring cell carcinoma of the lung is an extremely rare subtype of lung adenocarcinoma and is relatively highly invasive. WHAT THIS STUDY ADDS: Early diagnosis and positive treatment lead to a good prognosis for patients with signet-ring cell carcinoma.


Adsorption of perfluoroalkyl substances on polyamide microplastics: Effect of sorbent and influence of environmental factors.
Microplastics (MPs) and perfluoroalkyl substances (PFASs) are two types of pollutants coexisting in the environment. Their co-exposure is a source of increasing concern. MPs present in the natural environment suppose an ideal surface for the sorption of hazardous contaminants. This study investigates the adsorption behaviour of six PFASs on polyamide (PA) MPs. Adsorption experiments under various internal (PA and PFASs dosage, PA particle size) and environmental (pH, ionic strength, dissolved organic matter) factors were carried out. Isotherm results (from 0.1 to 25 mg/L of PFASs) showed that the maximum adsorption capacity of the selected PFASs on the PA was as follows: perfluorooctanesulfonic acid (PFOS, 0.873 mg/g) > perfluorooctanoic acid (0.235 mg/g) > perfluoroheptanoic acid (0.231 mg/g) > perfluorohexanoic acid (0.201 mg/g) > perfluoropentanoic acid (0.192 mg/g) > perfluorobutanoic acid (0.188 mg/g) (pH 5.88, 0% salinity and 0% of dissolved organic matter). The PFOS has more tendency to be sorbed onto PA than perfluorocarboxilic acids. The MP characterization by scanning electron microscopy, X ray diffraction and Fourier transform infrared spectroscopy showed changes in the PA surface after adsorption assays. Pore filling, hydrophobic interactions and hydrogen bonds governed sorption process. The sorption capacity of PFASs was crucially affected by the PA size (from 19.6% to 99.9% for 3 mm and 50 μm particle size, respectively). The process was not significantly influenced by salinity while the dissolved organic matter exerted a negative effect (decrease from 100% to 26% for PFOS in presence of 25 mg/L of humic acid). Finally, adsorption rates of PFASs were quantified in real water matrices (influent and effluent wastewater, surface and tap water samples). The results revealed interactions between PA and PFASs and evidenced the role of PA as a vector to transport PFASs in the aquatic environment.


Revision reverse shoulder arthroplasty for the management of baseplate failure: an analysis of 676 revision reverse shoulder arthroplasty procedures.
Baseplate failure in reverse shoulder arthroplasty (RSA) is a rare but potentially catastrophic complication owing to poor patient outcomes and significant glenoid bone loss. The purpose of this study was to report on the prevalence, causes, and outcomes of revision RSA (rRSA) for baseplate failure or loosening. A retrospective review of our institutional database was performed to identify all patients treated for a failed RSA from 2006 to 2021 who required revision to another RSA (rRSA) performed by a single surgeon. A total of 676 failed RSA procedures were identified, and further analysis identified 46 patients (6.8%) who underwent rRSA for baseplate failure with a confirmed loose baseplate at the time of rRSA. The primary outcome was repeated failure of the reimplanted baseplate following rRSA. The mode of failure associated with baseplate failure was stratified into 1 of 3 groups: aseptic, septic, or traumatic. Twenty-four patients underwent primary revision, and 22 had undergone >1 previous arthroplasty prior to undergoing re-revision. Five patients underwent previous rRSA for baseplate failure performed by an outside surgeon. The criteria for secondary outcome analysis of final American Shoulder and Elbow Surgeons score, Simple Shoulder Test score, and range of motion were met by 32 patients and 23 patients at 1- and 2-year follow-up, respectively. Three patients (6.5%) had repeated baseplate failure requiring re-revision; 2 had baseplate failure at <1 year with associated periprosthetic infections and underwent conversion to hemiarthroplasty. The third patient experienced traumatic failure at 10 years and underwent successful rRSA. The mean American Shoulder and Elbow Surgeons scores at 1 and 2 years were 62.3 and 61.7, respectively. There was no significant difference in outcomes based on mode of baseplate failure (P = .232) or total arthroplasty burden (P = .305) at 1 year. There were 13 total complications in 11 patients, 5 of which required reoperation for reasons other than baseplate failure. In this study, rRSA for baseplate failure constituted 6.8% of all revisions performed over a period of 15 years. Re-revision for recurrent baseplate failure was required in 3 of 46 patients (6.5%). Complications and reoperation rates were higher than those for primary RSA but outcomes were comparable for revision of failed anatomic shoulder arthroplasty.


Toward Sub-Terahertz: Space-Time Coding Metasurface Transmitter for Wideband Wireless Communications.
A space-time coding metasurface (STCM) operating in the sub-terahertz band to construct new-architecture wireless communication systems is proposed. Specifically, a programmable STCM is designed with varactor-diode-tuned metasurface elements, enabling precise regulation of harmonic amplitudes and phases by adjusting the time delay and duty cycle of square-wave modulation signal loaded on the varactor diodes. Independent electromagnetic (EM) regulations in the space and time domains are achieved by STCM to realize flexible beam manipulations and information modulations. Based on these features, a sub-terahertz wireless communication link is constructed by employing STCM as a transmitter. Experimental results demonstrate that the STCM supports multiple modulation schemes including frequency-shift keying, phase-shift keying, and quadrature amplitude modulations in a wide frequency band. It is also shown that the STCM is capable of realizing wide-angle beam scanning in the range of ±45o , which offers an opportunity for user tracking during the communication. Thus, the STCM transmitter with high device density and low power consumption can provide low-complexity, low-cost, low-power, and low-heat solutions for building the next-generation wireless communication systems in the sub-terahertz frequency and even terahertz band.


MELD remains the best predictor of mortality in outpatients with cirrhosis and severe ascites.
The Model for Endstage Liver Disease (MELD) score may put patients with severe ascites at a disadvantage because they often have a poor quality of life and high mortality despite a favourable MELD score. To develop a model that is better than the MELD score at predicting 1-year mortality among patients with cirrhosis, severe ascites and MELD ≤18. We used data from a randomised trial (SPARe-1) of patients with cirrhosis and severe ascites to develop a model to predict 1-year mortality. We used stepwise backward elimination and Cox regression to identify the strongest predictors. Performance was assessed with the C index and the Brier score. We examined performance in an external cohort of trial participants with cirrhosis and severe ascites (SPARe-2 participants). We included 308 patients with a 1-year mortality of 20.4%. The final prediction model (Severe Ascites Mortality score, "SAM score") included four variables: serum bilirubin, serum sodium, history of SBP (yes or no) and diabetes (yes or no). No indicators of quality of life were included. After correction for optimism bias, the SAM and MELD scores had nearly identical predictive ability. The external validation cohort included 149 patients whose 1-year mortality was 22.4%. The MELD score performed marginally better in this cohort, partly because the effects of SBP and diabetes on mortality were much smaller in this cohort. We did not succeed in developing a prediction model that was superior to the MELD score among patients with cirrhosis and severe ascites.


Improved detection of juxtacortical lesions using highly accelerated double inversion-recovery MRI in patients with multiple sclerosis.
The purpose of this study was to compare a highly-accelerated double inversion recovery (fast-DIR) sequence using a recent parallel imaging technique (CAIPIRINHA) with a conventional DIR (conv-DIR) sequence for image quality and the detection of juxtacortical and infratentorial multiple sclerosis (MS) lesions. A total of 38 patients with MS who underwent brain MRI at 3 T between 2020 and 2021 were included. There were 27 women and 12 men with a mean age of 40 ± 12.8 (standard deviation) years (range: 20-59 years). All patients underwent conv-DIR sequence and fast-DIR sequence. Fast-DIR was obtained with a T2-preparation module to improve contrast and an iterative denoising algorithm to compensate noise enhancement. Two blinded readers reported the number of juxtacortical and infratentorial MS lesions for fast-DIR and conv-DIR, confirmed by further consensus reading that was used as the standard of reference. Image quality and contrast were evaluated for fast-DIR and conv-DIR sequences. Comparisons between fast-DIR and conv-DIR sequences were performed using Wilcoxon test and Lin concordance correlation coefficient. Thirty-eight patients were analyzed. Fast-DIR imaging allowed detection of 289 juxtacortical lesions vs. 238 with conv-DIR, corresponding to a significant improved detection rate with fast-DIR (P < 0.001). Conversely, 117 infratentorial lesions were detected with conv-DIR sequence vs. 80 with fast-DIR sequence (P < 0.001). Inter-observer agreement for lesion detection with fast-DIR and conv-DIR was very high (Lin concordance correlation coefficient ranging between 0.86 and 0.96). Fast-DIR improves the detection of juxtacortical MS lesions, but is limited for the detection of infratentorial MS lesions.


A study on the willingness and influencing factors of novel coronavirus vaccination among medical personnel in North China.
To understand the awareness of the willingness to be vaccinated and influencing factors of the new coronavirus vaccine (neo-crown vaccine) among medical personnel in North China and to provide a theoretical basis and application guidelines for the feasibility of coronavirus vaccination by medical personnel to guide the public to actively be vaccinated by taking initiative and obtaining a coronavirus vaccination as soon as possible. From April 2021 to June 2021, medical staff in North China were selected to complete an online questionnaire survey using Questionnaire Star to analyze the willingness rate to be vaccinated with the new coronavirus vaccine, and the influencing factors were analyzed using binary logistic regression. Among 621 respondents, 85.7% were willing to be vaccinated after the launch of the new vaccine. In the questionnaire, respondents were asked to answer questions such as "Do you think it is better to receive as few vaccines as possible at the same time?," "If I get the new coronavirus vaccine, I may have serious side effects.," "The new coronavirus vaccine is safe.," "Specifically, for the new coronavirus vaccine, do you think it is safe?," and "Specifically, for the new coronavirus vaccine, do you think it is easy to administer?." These beliefs have an important influence on the vaccination of medical staff with the new coronavirus vaccine in Northern China (OR = 1.610,95% CI: 1.055 ~ 2.456; OR = 1.715,95% CI: 1.164 ~ 2.526; OR = 0.401, 95% CI: 0.212 ~ 0.760; OR = 0.352,95% CI: 0.147 ~ 0.843; OR = 3.688,95% CI: 1.281 ~ 10.502, respectively; All P values < .05). Medical staff have a high willingness to be vaccinated with the new coronavirus vaccine, which plays a positive role in the publicity of the vaccine.


Solar-driven methanogenesis with ultrahigh selectivity by turning down H2 production at biotic-abiotic interface.
Integration of methanogens with semiconductors is an effective approach to sustainable solar-driven methanogenesis. However, the H2 production rate by semiconductors largely exceeds that of methanogen metabolism, resulting in abundant H2 as side product. Here, we report that binary metallic active sites (namely, NiCu alloys) are incorporated into the interface between CdS semiconductors and Methanosarcina barkeri. The self-assembled Methanosarcina barkeri-NiCu@CdS exhibits nearly 100% CH4 selectivity with a quantum yield of 12.41 ± 0.16% under light illumination, which not only exceeds the reported biotic-abiotic hybrid systems but also is superior to most photocatalytic systems. Further investigation reveal that the Ni-Cu-Cu hollow sites in NiCu alloys can directly supply hydrogen atoms and electrons through photocatalysis to the Methanosarcina barkeri for methanogenesis via both extracellular and intracellular hydrogen cycles, effectively turning down the H2 production. This work provides important insights into the biotic-abiotic hybrid interface, and offers an avenue for engineering the methanogenesis process.


The effect of sodium ascorbate on the mechanical properties of hyaluronan-based vascular constructs.
Esterified hyaluronic acid (HYAFF) is routinely used for clinical tissue engineering applications such as skin and cartilage. In a previous study we developed a technique for in vitro generation of cylindrical constructs from cellularized HYAFF flat sheets. In the present investigation we studied the possibility to improve mechanical properties of this vascular construct by the addition of sodium ascorbate (SA). Non-woven HYAFF flat sheets were seeded with porcine aortic smooth muscle cells (SMCs) and cultured for 14 or 28 days with standard medium or medium added with SA. In selected experiments HYAFF sheets seeded with SMCs were wrapped to obtain cylindrical shape and then cultured in control medium or SA added medium for up to 28 days. We estimated cell viability for flat sheets, and performed histological examination, analysis of extracellular matrix (ECM) deposition and mechanical tests on tubular constructs. The number of viable cells and ECM deposition increased with time in constructs cultured in the presence of SA, as compared to control group. Moreover, SA improved mechanical properties of the vascular construct lowering material stiffness and increasing tensile strength as compared to untreated controls. The addition of SA to the medium improved cell proliferation and ECM synthesis on this biodegradable material, which leads to the formation of well organized, mechanical resistant tissue-engineered structure.


Dual role of NOX2 in respiratory syncytial virus- and sendai virus-induced activation of NF-kappaB in airway epithelial cells.
Human respiratory syncytial virus (RSV), a member of the Paramyxoviridae family, is the most important viral agent of pediatric respiratory tract disease worldwide. Human airway epithelial cells (AEC) are the primary targets of RSV. AEC are responsible for the secretion of a wide spectrum of cytokines and chemokines that are important mediators of the exacerbated airway inflammation triggered by the host in response to RSV infection. NF-kappaB is a key transcription factor responsible for the regulation of cytokine and chemokine gene expression and thus represents a potential therapeutic target. In the present study, we sought to delineate the role of RSV-induced reactive oxygen species in the regulation of the signaling pathways leading to NF-kappaB activation. First, we demonstrate that besides the well-characterized IkappaBalpha-dependent pathway, phosphorylation of p65 at Ser(536) is an essential event regulating NF-kappaB activation in response to RSV in A549. Using antioxidant and RNA-interference strategies, we show that a NADPH oxidase 2 (NOX2)-containing NADPH oxidase is an essential regulator of RSV-induced NF-kappaB activation. Molecular analyses revealed that NOX2 acts upstream of both the phosphorylation of IkappaBalpha at Ser(32) and of p65 at Ser(536) in A549 and normal human bronchial epithelial cells. Similar results were obtained in the context of infection by Sendai virus, thus demonstrating that the newly identified NOX2-dependent NF-kappaB activation pathway is not restricted to RSV among the Paramyxoviridae. These results illustrate a previously unrecognized dual role of NOX2 in the regulation of NF-kappaB in response to RSV and Sendai virus in human AEC.


Elucidation of innovative antibiofilm materials.
It is known for roughly a decade that bacterial communities (called biofilms) are responsible for significant enhanced antibiotherapy resistance. Biofilms are involved in tissue persistent infection, causing direct or collateral damage leading to chronic wounds development and impairing natural wound healing. In this study, we are interested in the development of supported protein materials which consist of asymmetric membranes as reservoir supports for the incorporation and controlled release of biomolecules capable of dissolving biofilms (or preventing their formation) and their use as wound dressing for chronic wound treatment. In a first step, polyhydroxyalkanoates (PHAs) asymmetric membranes were prepared using wet phase inversion technique. Scanning microscopy (SEM) analysis has showed the influence of different processing parameters. In a second step, the porous side of the membranes were functionalized with a surface treatment and then loaded with the antibiofilm agent (dispersin B). In a third step, the properties and antibiofilm performance of the loaded-membranes were evaluated. Exposure of Staphylococcus epidermidis biofilms to such systems weakly inhibited biofilm formation (weak preventive effect) but caused their detachment and disaggregation (strong curative effect). These initial results are promising since they open the way to a new generation of effective tools in the struggle against persistent bacterial infections exhibiting enhanced antibiotherapy resistance, and in particular in the case of infected chronic wounds.


Pituitary adenoma causing visual disturbances in a 6-year-old girl.
Pituitary adenomas rarely occur in young children, typically present with systemic symptoms, and rarely undergo malignant transformation. We report a 4-year-old girl who presented with visual disturbances initially diagnosed and treated as amblyopia. She subsequently developed headaches and a gait disturbance and was discovered to have a large, suprasellar, nonsecreting pituitary adenoma. The tumor was resected, but 22 months later she developed recurrence with malignant transformation.


Antagonism of the serotonin (5-HT)-2 receptor and insulin sensitivity: implications for atypical antipsychotics.
Both conventional and second-generation antipsychotics have been associated with an increased risk for impaired glucose tolerance and diabetes mellitus. Though this has been largely attributed to weight gain, there may also be a direct, receptor-mediated effect of antipsychotics on glucose tolerance. We tested the hypothesis that antagonism of the serotonin (5-HT)-2 receptor impairs insulin sensitivity. Ten healthy male volunteers were included in a double-blind, placebo-controlled crossover study of a single dose of 40 mg of the 5-HT2 antagonist ketanserin versus placebo. Insulin sensitivity was measured by means of the euglycemic-hyperinsulinemic clamp technique. Subjects were treated with the alpha-1 adrenergic antagonist phenoxybenzamine in both parts of the study to control for ketanserin's effects at the level of this receptor. Compared with the placebo condition, subjects showed a significantly decreased insulin sensitivity after ketanserin (placebo: 9.4 +/- 3.6 mg/kg/min; ketanserin: 7.7 +/- 2.1 mg/kg/min; p = .047). The selective 5-HT2 antagonist ketanserin impaired insulin sensitivity. This effect was possibly mediated by suppression of 5-HT(2A) receptor mediated glucose uptake in skeletal muscle.


Rapid and quantitative detection of hepatitis A virus from green onion and strawberry rinses by use of real-time reverse transcription-PCR.
In this study, an immunomagnetic capture method and a real-time reverse transcription-PCR assay were used to quantify hepatitis A virus (HAV) in green onion and strawberry rinses. This combined protocol detected as low as 0.5 PFU HAV in produce rinses and concentrated HAV levels up to 20-fold.


Preparation of adsorptive polyethyleneimine/polyvinyl chloride electrospun nanofiber membrane: Characterization and application.
Landfilling and burning plastic waste, especially waste polyvinyl chloride (PVC), can produce highly toxic and carcinogenic by-products that threaten the ecosystem and human health. However, there is still a lack of proper methods for waste PVC recycling. Therefore, developing feasible ways for waste PVC recovery is urgently needed. The purpose of this study is to analyze the characteristics of PVC-based adsorptive nanofiber membranes and test their ability for the treatment of wastewater containing Cibacron Brilliant Yellow 3G-P, a widely used reactive dye. The polyethylenimine/polyvinyl chloride membrane (PEI/PVCM) was characterized by FTIR, FE-SEM, TGA, tensile analysis, water contact angle measurement, and zeta-potential analysis. The FTIR analysis confirmed that the PEI has successfully crosslinked with PVC. The FE-SEM images showed that the nanofibers constituting PEI/PVCM are compact with an average fiber diameter of 181 nm. The TGA results showed that the membrane was able to remain stable in wastewater below 150 °C. The average stress and strain of the PEI/PVCM were 7.64 ± 0.32 MPa and 934.14 ± 48.12%, respectively. The water contact angle and zeta potential analysis showed that after the introduction of PEI, the membrane converted from hydrophobic to hydrophilic, and the pHpzc was increased from 3.1 to 1.08. The pure water flux of the membrane was measured at 0.1 MPa and the result was 3013 ± 60 L/m2‧h. The wastewater purification capability of PEI/PVCM was measured at an initial dye concentration of 10 ppm and pH 4-9 at 0.1 MPa. The reusability of PEI/PVCM was verified through three adsorption-desorption cycles. The results demonstrated that the PEI/PVCM is a reusable membrane for efficient purification of wastewater containing reactive dyes over a wide pH range (pH 4-8).


Glycerol metabolism in patients with alcohol-induced liver cirrhosis.
The clearance rate of glycerol has been found to be impaired in alcoholic liver disease. However it remains unclear, if this can be ascribed to a defect of hepatic gluconeogenesis. Thus, the purpose of this work was to investigate glycerol clearance and hepatic glucose production in patients with liver cirrhosis. 13 patients with alcohol-induced Child B cirrhosis and 8 healthy volunteers were studied. Rates of appearance (R(a)) of glycerol, glucose and alanine were determined using stable isotope techniques. In addition indocyanine green clearance (ICGC) and plasma substrate concentrations were measured. Clearance rates were calculated as R(a) divided by the corresponding substrate concentration. R(a) of glycerol in patients was not different from controls, but glycerol clearance was significantly reduced (29 +/- 3 vs. 41 +/- 4 ml/kg/min). No differences in R(a) of glucose and alanine and corresponding plasma concentrations were observed. ICGC in patients was about 35% lower than reference values. Diminished glycerol clearance in patients with liver cirrhosis was not due to impaired hepatic gluconeogenesis. Since glycerol is almost completely extracted by the liver decreased glycerol clearance possibly simply reflected compromised liver perfusion as seen by reduced ICGC.


Concurrent occurrence of 3 beta,12 alpha-dihydroxy-5-cholenoic acid associated with 3 beta-hydroxy-5-cholenoic acid and their preferential urinary excretion in liver diseases.
3 beta-Hydroxy-(delta 5-3 beta-ol), 3 beta,12 alpha-dihydroxy-(delta 5-3 beta,12 alpha-ol), 3 beta,7 alpha-dihydroxy-(delta 5-3 beta,7 alpha-ol) and 3 beta,7 beta-dihydroxy-(delta 5-3 beta,7 beta-ol) 5-cholenoic acids were identified in patients with liver diseases by gas-liquid chromatography-mass spectrometry (GLC-MS). Of these unusual 3 beta-hydroxy-5-en-metabolites, delta 5-3 beta-ol and delta 5-3 beta,12 alpha-ol were found as major components in the urine of patients with liver diseases (cholestasis, liver cirrhosis, chronic hepatitis, acute hepatitis). Other 3 beta-dihydroxy-5-en-metabolites, delta 5-3 beta,7 alpha-ol and delta 5-3 beta,7 beta-ol, were found as minor components in the urine. The levels of delta 5-3 beta-ol and delta 5-3 beta,12 alpha-ol in urine were correlated with their levels in serum, with total bile acids in the urine, and with liver function, implying that the degree of their increment correlated well with the severity of liver diseases. The most abundant amounts of delta 5-3 beta-ol and delta 5-3 beta,12 alpha-ol were found in the urine as sulfate conjugates in comparison with bile, portal and hepatic venous sera, and liver tissue of the patients. The biliary excretion and hepatic extraction of these 3 beta-hydroxy-5-en-unsaturated bile acids were more impaired and inefficient than those of cholic and chenodeoxycholic acids.


Combining autologous bone marrow mononuclear cells seeded on collagen sponge with Nano Hydroxyapatite, and platelet-rich fibrin: Reporting a novel strategy for alveolar cleft bone regeneration.
The aim of this study was to examine and assess the use of autologous bone marrow mononuclear cells (BMMNCs) combined with platelet-rich fibrin (PRF) and nanohydroxyapatite for bone regeneration as an effective technique for alveolar cleft repair. This study included 20 patients with unilateral alveolar cleft defects and with an age range of 8-15 years. They were divided equally into two groups: Group A, received treatment via the regenerative approach which includes; autologous BMMNCs seeded on a collagen sponge in combination with nanohydroxyapatite and autologous PRF. Group B, received the standard alveolar bone grafting with iliac crest bone. The effectiveness of the new technique was evaluated and compared to the standard grafting technique through a 12-month follow-up via clinical and radiographic assessments. During the 12-month follow-up, Group A exhibited less donor site complications, faster and better soft tissue healing, and less postoperative pain, when compared to group B. 90% of the cases in group A, exhibited complete alveolar bone union verses 70% only in group B. Combination of BMMNCs, nanohydroxyapatite, and PRF greatly promote bone regeneration in alveolar cleft defects providing an alternative novel therapeutic strategy to the standard alveolar bone grafting.


CAR chasing: canine adenovirus vectors-all bite and no bark?
This review deals primarily with canine adenovirus serotype 2 (CAV-2) vectors and gives a simplified overview of how the various domains of virology, cellular and molecular biology, as well as immunology, come into play when trying to understand and ameliorate adenovirus (Ad)-mediated gene transfer. The generation of early region 1 (E1)-deleted (DeltaE1) CAV-2 vectors, the lack of pre-existing humoral immunity, trafficking, the use of the coxsackie B adenovirus receptor (CAR), the surprising neuronal tropism, and the ability to migrate via axons to afferent regions of the central and peripheral nervous system, are described. Due to these intrinsic properties, CAV-2 vectors may be powerful tools for the study of the pathophysiology and potential treatment of neurodegenerative diseases like lysosomal storage disorders, Parkinson's, Alzheimer's, Huntington's, amyotrophic lateral sclerosis, and others. Other potential uses include anti-tumoral and anti-viral vaccines, tracer of synaptic junctions, pain therapy, cancer therapy (e.g. K9 CRAds), and gene transfer to other somatic tissues.


Ball milling and hot-melt extrusion of indomethacin-l-arginine-vinylpyrrolidone-vinyl acetate copolymer: Solid-state properties and dissolution performance.
Commonly applied approaches to enhance the dissolution properties of low water-soluble crystalline active pharmaceutical ingredients (APIs) include their amorphization by incorporation into a polymeric matrix and the formation of amorphous solid dispersions, or blending APIs with low-molecular-weight excipients and the formation of a co-amorphous system. This study focused on the preparation and characterization of binary (consisting of indomethacin (IND) and polymer - copovidone (PVP VA 64), as a carrier, or amino acid - L-arginine (ARG), as a co-former) and ternary (comprising the same API, polymer, and amino acid) formulations. Formulations were produced by ball milling (BM) and/or hot-melt extrusion (HME), and extensive physicochemical characterization was performed. Specifically, the physicochemical and solid-state properties of a model IND-ARG system incorporated into a polymeric matrix of PVP VA 64 by HME and BM as well as by combined BM/HME method together with the impact of the preparation strategy on the dissolution profiles and long-term physical stability were investigated. Ball-milled binary and ternary formulations were found to be amorphous. The residual crystals corresponding to IND-ARG salt were identified in the ternary formulations produced via HME. Despite the presence of a crystalline phase, dissolution tests showed that ternary systems prepared by HME exhibited improved IND solubility when compared to pure crystalline IND and their corresponding physical mixture. None of the binary and ternary formulations that were initially fully amorphous did undergo recrystallization during the entire period of preservation (minimum of 12 months) in dry conditions at 25 °C.


Direct in situ determination of the polarization dependence of physisorption on ferroelectric surfaces.
The ability to manipulate dipole orientation in ferroelectric oxides holds promise as a method to tailor surface reactivity for specific applications. As ferroelectric domains can be patterned at the nanoscale, domain-specific surface chemistries may provide a method for fabrication of nanoscale devices. Although studies over the past 50 yr have suggested that ferroelectric domain orientation may affect the energetics of adsorption, definitive evidence is still lacking. Domain-dependent sticking coefficients are observed using temperature-programmed desorption and scanning surface potential microscopy, supported by first-principles calculations of the reaction coordinate. The first unambiguous observations of differences in the energetics of physisorption on ferroelectric domains are presented here for CH(3)OH and CO(2) on BaTiO(3) and Pb(Ti(0.52)Zr(0.48))O(3) surfaces.


Inhibition of the renin-angiotensin-system in Brattleboro rats with hereditary hypothalamic diabetes insipidus.
Brattleboro rats homozygous for hypothalamic hereditary diabetes insipidus (DI rats) were used to investigate the following questions: a) Do exogenous and endogenous angiotensin II (AII) have an antidiuretic effect in diabetes insipidus? b) Does AII mediate the antidiuresis induced by furosemide? The following results were obtained: 1. AII (5 mg/kg s.c. in oil) and furosemide (50 mg/kg i.p.) decreased urine flow and increased urinary sodium excretion. Furosemide led to a two-fold increase of AII plasma concentrations and a decrease of plasma sodium levels. 2. SQ 14 225 (2 x 2.5 mg/kg p.o.), an angiotensin I-converting enzyme inhibitor, led to an increase of urine flow and to a slightly elevated urinary sodium excretion. 3. When the formation of AII was blocked by SQ 14 225 (2 x 2.5 mg/kg p.o.), AII plasma concentrations were 2.5-fold decreased, but furosemide still reduced urine flow. We conclude that plasma AII might have an antidiuretic action in DI rats. However, AII does not mediate the antidiuresis induced by furosemide.


Cesarean Scar Pregnancy: Diagnosis and Pathogenesis.
Cesarean scar pregnancy is a potentially dangerous consequence of a previous cesarean delivery. If unrecognized and inadequately managed, it can lead to untoward complications throughout all three trimesters of the pregnancy. The rate of occurrence parallels the mounting rate of cesarean sections. The late consequences of cesarean delivery, such as placenta previa and placenta accrete, were known for a long time. However, it took more than a decade for the obstetric community to make the connection between the cesarean scar pregnancy and the placenta accreta spectrum. This article discusses the pathogenesis and diagnosis of cesarean scar pregnancy.


Trends and Rural-Urban Differences in Participation in Diabetes Self-management Education Among Adults in North Carolina: 2012-2017.
This study aimed to report recent trends in self-reported diabetes self-management education (DSME) participation rates among adults in North Carolina and to compare these rates between rural and urban residents. Data for this analysis were obtained from the NC Behavioral Risk Factor Surveillance System (BRFSS) for the years 2012, 2013, 2015, and 2017, when the survey included the diabetes module. Respondents were classified as having participated in DSME if they answered "Yes" to the question, "Have you ever taken a course or class in how to manage your diabetes yourself?" We used the Rural Urban Continuum Code to classify urban and rural residence. The study sample included 4368 adults 18 years or older with self-reported diabetes. We assessed the changes in DSME participation from 2012 to 2017. We used multiple logistic regression modeling to assess the association between rural residence and DSME participation. All analyses were conducted in Stata 14 and accounted for the survey design of the BRFSS. Statistical significance was set at P < .01. Overall, the DSME participation rates decreased slightly in the study period, from 55.8% in 2012 to 55.6% in 2013 to 56.5% in 2015 to 52.1% in 2017. By rural-urban residence, the rates were 52.3% versus 57.8% in 2012, 54.0% versus 56.5% in 2013, 48.8% versus 62.0% in 2015, and 46.7% versus 56.1% in 2017. The multiple logistic regression model results showed that rural residents were less likely to have participated in DSME (adjusted odds ratio = 0.78; 95% confidence interval, 0.64-0.94) than urban residents. Adults with higher income and education levels were also more likely to have participated in DSME (P < .01). The recent BRFSS data showed that the DSME participation rate declined slightly in North Carolina. There were persistent rural-urban disparities in DSME participation, with rural residents showing lower rates, and the gaps seemed to be widening. Continuous efforts are needed to bring more American Diabetes Association/American Association of Diabetes Educators programs to rural communities and assist persons with diabetes to participate in DSME training to reduce the burden of diabetes. Furthermore, those in rural areas may need additional support.


Mycotoxin production by different ochratoxigenic Aspergillus and Penicillium species on coffee- and wheat-based media.
Ochratoxin A (OTA) is one of the most widespread mycotoxins, and is produced by several Aspergillus or Penicillium species. Human exposure to OTA is mainly by intake of contaminated food, with cereal products, followed by coffee and red wine as the main sources of OTA. In this study, the OTA production of four ochratoxigenic fungi (two Aspergillus and two Penicillium species) was investigated in four different media, i.e. wheat and coffee model media as food-based media and two standard laboratory media (malt extract glucose agar, MEA and yeast extract sucrose agar, YES). Colony growth was documented and OTA concentrations in cultures were determined at day 2, 4 and 8 of incubation at 25°C by high-performance thin-layer chromatography (HPTLC) and high-performance liquid chromatography (HPLC). OTA production clearly depended upon time of incubation, fungal species, and medium composition. On coffee based medium, moderate OTA levels were produced by A. ochraceus BFE635 (9.8 μg/g) and by A. niger BFE632 (10.6 μg/g) on day 8 of incubation. In wheat-based medium, these strains produced much more OTA than in coffee. The highest OTA concentration (83.8 μg/g on day 8) was formed by A. ochraceus BFE635 followed by the other Aspergillus niger BFE632 (49 μg/g). Lower OTA levels were produced by P. verrucosum BFE550 and P. nordicum BFE487, in both wheat and in YES medium, whilst OTA was hardly detectable in coffee and in MEA in case of P. nordicum. Colony growth of the tested strains on different media was not indicative of OTA production. Guttation droplets developed on wheat-based medium with the Aspergillus strains within a week, and this phenomenon coincided with the high OTA amounts formed by these species. Results from this study add to our knowledge on the behaviour of ochratoxigenic fungal species when cultured on food based media.


Five-year trends of selected halogenated flame retardants in the atmosphere of Northeast China.
This study collected 227 pairs of gas phase and particle phase air samples in a typical urban city of Northeast China from 2008 to 2013. Four alternative halogenated flame retardants for polybrominated diphenyl ethers (PBDEs) were analyzed, namely 2-ethylhexyl 2,3,4,5-tetrabromobenzoate (EHTBB), bis (2-ethylhexyl) tetrabromophthalate (BEHTBP), syn-dechlorane plus (syn-DP) and anti-dechlorane plus (anti-DP). The average concentrations for EHTBB and BEHTBP were 5.2 ± 20 and 30 ± 200 pg/m3, respectively, while for syn-DP and anti-DPwere 1.9±5.1 and 5.8±18 pg/m3, respectively. Generally, they were frequently detected in the particle phase, and the gas/particle partitioning suggested they were the maximum partition chemicals. The fractional abundance of EHTBB (fEHTBB) and syn-DP (fsyn)were comparablewith those in other studies. Strong local sources were identified based on the air parcel backward trajectories and the potential source contribution function. The concentrations of these chemicals were significantly increased during this sampling campaign, possibly suggesting their increasing usages from 2008 to 2013 in China.


A biodegradable chipless sensor for wireless subsoil health monitoring.
Precision Agriculture (PA) is an integral component of the contemporary agricultural revolution that focuses on enhancing food productivity in proportion to the increasing global population while minimizing resource waste. While the recent advancements in PA, such as the integration of IoT (Internet of Things) sensors, have significantly improved the surveillance of field conditions to achieve high yields, the presence of batteries and electronic chips makes them expensive and non-biodegradable. To address these limitations, for the first time, we have developed a fully Degradable Intelligent Radio Transmitting Sensor (DIRTS) that allows remote sensing of subsoil volumetric water using drone-assisted wireless monitoring. The device consists of a simple miniaturized resonating antenna encapsulated in a biodegradable polymer material such that the resonant frequency of the device is dependent on the dielectric properties of the soil surrounding the encapsulated structure. The simple structure of DIRTS enables scalable additive manufacturing processes using cost-effective, biodegradable materials to fabricate them in a miniaturized size, thereby facilitating their automated distribution in the soil. As a proof-of-concept, we present the use of DIRTS in lab and field conditions where the sensors demonstrate the capability to detect volumetric water content within the range of 3.7-23.5% with a minimum sensitivity of 9.07 MHz/%. Remote sensing of DIRTS can be achieved from an elevation of 40 cm using drones to provide comparable performance to lab measurements. A systematic biodegradation study reveals that DIRTS can provide stable readings within the expected duration of 1 year with less than 4% change in sensitivity before signs of degradation. DIRTS provides a new steppingstone toward advancing precision agriculture while minimizing the environmental footprint.


Initial end-to-end testing of the ExacTrac dynamic deep inspiration breath hold workflow using a breath hold breast phantom.
ExacTrac Dynamic (ETD) provides a Deep Inspiration Breath Hold (DIBH) workflow for breast patients. Stereoscopic x-ray imaging combined with optical and thermal mapping allows localisation against simulation imaging, alongside surface guided breath hold monitoring. This work aimed to determine appropriate imaging parameters, the optimal Hounsfield Unit (HU) threshold for patient contour generation and workflow evaluation via end-to-end (E2E) positioning using a custom breast DIBH phantom. After localisation via existing Image Guidance (IG), stereoscopic imaging was performed with a range of parameters to determine best agreement. Similarly, residual errors in prepositioning were minimised using a range of HU threshold contours. E2E positioning was completed for clinical workflows allowing residual isocentre position error measurement and existing IG comparison. Parameters of 60 kV and 25mAs were determined appropriate for patient imaging and HU thresholds between -600 HU and -200 HU enabled adequate prepositioning. The average and standard deviation in residual isocentre position error was 1.0 ± 0.9 mm, 0.4 ± 1.0 mm and 0.1 ± 0.5 mm in the lateral, longitudinal and vertical directions, respectively. Errors measured using existing IG were -0.6 ± 1.1 mm, 0.5 ± 0.7 mm and 0.2 ± 0.4 mm in the lateral, longitudinal and vertical directions, and 0.0 ± 1.0o, 0.5 ± 1.7o and -0.8 ± 1.8o for pitch roll and yaw. The use of bone weighted matching increased residual error, while simulated reduction of DIBH volume maintained isocentre positioning accuracy despite anatomical changes. This initial testing indicated suitability for clinical implementation during DIBH breast treatments.


Surgery or implantable hearing devices in children with congenital aural atresia: 25 years of our experience.
Congenital aural atresia and ear deformities have been the subject of serious discussions for centuries. These malformations are associated with significant aesthetic and functional problems. Outcome of the surgical solution is rarely optimal. Despite the gradual improvement of surgical techniques the surgery still remains associated with very limited short-term and mainly long-term functional outcome. Therefore, the priority treatment in modern otology becomes implantable devices--BAHA, Bonebridge and active middle ear implants. The functional and aesthetic outcomes of aural atresia reconstruction performed at Pediatric ENT Department of Children's University Hospital were retrospectively evaluated and compared with the results prospectively obtained from implantable hearing devices (BAHA, Vibrant Soundbridge, Bonebridge), which have been implanted in patients with aural atresia at Department of ORL HNS, University Hospital Bratislava. Aural atresia reconstruction has been performed in 34 patients during last 25 years. Results of the surgery could be viewed as excellent only in three patients (gain above 30 dB). Air conduction threshold has decreased after the surgery in seven patients, and in two cases total deafness occurred after the surgery. Patients gain on average 12 dB in auditory threshold after surgery. Hearing devices were implanted to the group of 11 children in order to improve their hearing. All of them were the patients with bilateral aural atresia. After implantation a significant improvement in hearing threshold occurred in all children (30-35 dB on average). Together with results of air conduction threshold in patient with aural atresia before and after surgery and implantation we also present a standard deviation. The functional outcome of implantable hearing devices in patients with bilateral aural atresia clearly dominates over the traditional reconstructive surgery. Aesthetic results in pinna deformity management remain a major concern for patients and parents. Implantable epithesis bring promising results. Since there is no universal solution to this disorder, the final selection of the treatment is upon the patient. Patients should opt for the most suitable solution through consultation with the surgeon, after clarifying the advantages and disadvantages of each option.


Synergistic effect of platelet-rich plasma injections and scalp lifting in androgenetic alopecia.
Androgenetic alopecia (AGA) is a common hair loss disorder, especially in men and the elderly. In this study, we analyzed the therapeutic effects of platelet-rich plasma (PRP) injections and embedded sutures in patients with AGA. In each participant, we administered different treatments in one area of hair loss that was divided into four sections. Each section received one of the following treatments: No treatment, PRP injection, suture embedding, and combined PRP injection/suture-embedded areas. The thickness of the scalp, and scalp perfusion were measured using an ultrasound imaging system and Moor FLPI full-field laser perfusion imaging system, respectively. The diameters of the hair were measured using optical microscopy. Our results show that PRP injection treatments increased the diameter of the hair (P = 0.034), and the combined PRP injection/suture-embedded treatments had a significant effect on the thickness of the scalp (P = 0.002), the blood flow (P = 0.014) through the scalp, and the diameter of the hair (P= 0.013). This study has demonstrated that there is a synergistic effect between PRP injections and suture embedding for increasing the thickness and blood flow of the scalp, and diameter of the hair. Combined PRP injection/suture-embedded PRP injections might have therapeutic benefit for patients with AGA.


The biomechanical effects of low-intensity ultrasound on healing tendons.
The effect of low-intensity ultrasound on the healing strength of tendons was studied in experimentally tenotomized, repaired and immobilized right tendo calcaneus (Achilles tendon) of 24 rabbits. Ten tendons were sonicated in continuous waves at a space-averaged intensity of 0.5 W cm-2 for 5 min every day. The remaining 14 tendons were mock-sonicated as controls. After nine consecutive treatments, the tendons were excised under anesthesia and compared for differences in tensile strength, tensile stress and energy absorption capacity. Sonication at 0.5 W cm-2 induced a significant increase in the tensile strength (p less than .02), tensile stress (p less than .005) and energy absorption capacity (p less than .001) of the tendons. These findings suggest that high-intensity sonication may not be necessary to augment the healing strength of tendons and that sonication at similarly low intensities may enhance the healing process of surgically repaired human tendo calcaneus.


Dataset of distribution transformers for predictive maintenance.
In electricity sector is possible to collect large quantities of data that contain information on relevant processes and events that occur in a given period. It gives a knowledge of the different operation conditions of the electrical network and its components. Through the treatment and analysis of these data is possible to propose market, cost reduction, reduction of failures and repairs in machines and inventory decrease strategies. Grid operator can implement strategies to improve indicators of reliability and quality of service. From a maintenance point of view, the equipment operating time is a relevant aspect to identify and solve failures without service suspensions. This paper aims to show distribution transformers failures characteristics data using historical data collected by the grid operator (Compañia Energética de Occidente) at Cauca Department (Colombia), under the cooperation of the Universidad del Cauca and Universidad del Valle. The dataset could be helpful to researchers and data scientists who use machine learning to develop applications that help engineers in predictive maintenance.


Pharmacokinetics of benzquinamide in man.
Using a newly developed sensitive gas chromatograph-mass spectrometer assay for benzquinamide, pharmacokinetics have been determined in man following the administration of intramuscular, oral, and rectal suppository doses. Drug is absorbed most rapidly from the intramuscular dose and least rapidly from suppositories. The mean apparent elimination half-life is 1.0-1.6 hr from all formulations. Benzquinamide is 33-39% bioavailable from the capsule and suppository formulations, relative to the intramuscular formulation. A high correlation between capsule and suppository bioavailabilities suggests that first-pass metabolism may account for at least part of the incomplete availability.


A Prospective Survey of the Incidence of Cranial and Cervical Nerve Injuries After Carotid Surgery.
To prospectively evaluate the involvement of the cranial nerves and cervical plexus branches during carotid surgery and to look for risk factors. All patients (n = 50) undergoing carotid endarterectomy between June 1st and October 31st, 2016 in our center were evaluated prospectively. A complete neurological examination was done before the intervention then daily until hospital discharge, and then at 2 months, 6 months and 1 year. A nasal endoscopy was systematically performed postoperatively before discharge by an ear, nose, and throat specialist. Twenty-six patients (52%) had at least one damaged nerve immediately after surgery. There were 15 cases involving the VII nerve (30%), 12 the C2-C3 branches (24%), 7 the XII nerve (14%), and 2 the X nerve (4%). At 2 months, 6 months, and 1 year, 22%, 16%, and 8% of lesions remained, respectively. We found no independent factor for nerve damage at 6 months or 1 year. In the case of dysphonia and/or dysphagia without recurrent nerve paralysis, 6 hematomas and 7 laryngeal edemas were identified under nasal endoscopy and all healed without sequelae. This prospective study showed cranial and cervical nerve injury to be much more frequent than expected in the short-term, when assessed by independent ear, nose, and throat and nasal endoscopy exam. Though mainly transient, these lesions can cause post-operative functional discomfort and must be disclosed preoperatively to the patient, in view of the judicialization of health care.


Resistance of hepatitis A virus in mussels subjected to different domestic cookings.
Hepatitis A is a worldwide infectious disease. Shellfish consumption has always been one of the major risk factors for hepatitis A infection, especially when these products are eaten raw or slightly cooked. Moreover, the cooking does not always guarantee the harmlessness of shellfish. The aim of the present study was to evaluate the hepatitis A virus (HAV) resistance in experimentally contaminated mussels, subjected to domestic cooking. Three different domestic preparations (mussel hors-d'oevre, mussel au gratin, mussels with tomato sauce) were performed according to the traditional Italian cookery using different time and temperature conditions. To detect HAV-RNA, RT-nested-PCR was used; the presence of the infectious virus in the positive samples was confirmed by an integrated cell culture-RT-PCR method. The infectious virus was completely inactivated only in "mussels in tomato sauce", while it was still present, even if not quantitatively determinable, in the other preparations. The study confirmed that some factors can influence the HAV sensitivity to thermal inactivation preventing a complete decontamination of the product.


Synthesis and characterization of oligodeoxyribonucleotides containing terminal phosphates. NMR, UV spectroscopic and thermodynamic analysis of duplex formation of [d(pGGAATTCC)]2, [d(GGAATTCCp)]2 and [d(pGGAATTCCp)]2.
Derivatives of the oligomer [d(GGAATTCC)]2 with 5' (5'-P), 3' (3'-P) and both 5' and 3' (5',3'-P2) terminal phosphate groups have been synthesized and studied by temperature dependent UV and NMR spectroscopic methods. Thermodynamic studies of the helix to strand transition indicate that addition of 3' phosphate groups has very little effect on the delta G degree for helix formation at 37 degrees C while addition of 5' phosphate groups adds approximately -0.5 kcal/mole to the delta G degree for duplex formation. The helix stabilization by 5' phosphate groups occurs at salt concentrations of 0.1 M and above, and is primarily enthalpic in origin. Tm studies as a function of ionic strength also indicate that the oligomers fall into two groups with the parent and 3'-P derivatives being similar but less stable than the 5'-P and 5',3'-P2 derivatives. Imino proton and 31P NMR studies also divide the oligomers into these same two groups based on spectral comparisons and temperature induced chemical shift and linewidth changes. 31P NMR analysis suggests that addition of 5' phosphate groups results in a small change in phosphodiester torsional angles in the g,t to g,g direction, indicating improved base stacking at the 5' end of the modified oligomer. No such changes are seen at the 3' end of the oligomer on adding 3' phosphate groups.


Surface Markers for the Identification of Cancer Stem Cells.
Cancer stem cells have genetic and functional characteristics that can turn them resistant to standard cancer therapeutic targets. Identification of these cells is challenging and is mostly done by detecting the expression of their antigens in a group of stem cells. Currently, there are a significant number of surface markers available which can detect the cancer stem cells by directly targeting their specific antigens present in cells. These markers possess differential expression patterns and sub-localizations in cancer stem cells when compared to non-neoplastic stem cells and somatic cells. In addition to molecular markers, multiple analytical methods and techniques including functional assays, cell sorting, filtration approaches, and xenotransplantation methods are used to identify cancer stem cells. This chapter will overview the functional significance of cancer stem cells, its biological correlations, specific markers, and detection methods.


Measurement of immunoglobulins G, A, and M levels in B-lymphocytes culture.
Nephelometric immunoassays were developed for human IgG, IgA, and IgM quantitation in B-lymphocytes culture media. They allowed measurement of immunoglobulin (Ig) levels over a broad range of concentrations with good accuracy and precision. The kinetics of Ig production in B-lymphocyte cultures was followed and the mean amount of each Ig was determined in six different samples after three days of culture. The nephelometric immunoassays reported here could be used to study, in vitro, the influence of various molecules (inhibitory or amplifying effect) on B-lymphocytes' functional capacities.


Molecular cloning and in silico analysis of chalcone isomerase from Polygonum minus.
Chalcone isomerase (CHI; EC 184.108.40.206) is one of the key enzymes in the flavonoid biosynthetic pathway that is responsible for the intramolecular cyclization of chalcones into specific 2S-flavanones. In this study, the open reading frame (ORF) of CHI was successfully isolated from the cDNA of Polygonum minus at 711-bp long, encoding for 236 amino acid residues, with a predicted molecular weight of 25.4 kDa. Multiple sequence alignment and phylogenetic analysis revealed that the conserved residues (Thr50, Tyr108, Asn115, and Ser192) in the cleft of CHI enzyme group active site are present in PmCHI protein sequence and classified as type I. PmCHI comprises more hydrophobic residues without a signal peptide and transmembrane helices. The three-dimensional (3D) structure of PmCHI predicted through homology modeling was validated by Ramachandran plot and Verify3D, with values within the acceptable range of a good model. PmCHI was cloned into pET-28b(+) plasmid, expressed in Escherichia coli BL21(DE3) at 16 °C and partially purified. These findings contribute to a deeper understanding of the PmCHI protein and its potential for further characterization of its functional properties in the flavonoid biosynthetic pathway.


Expression of antimicrobial peptides in the amniotic fluid of women with cervical insufficiency.
Cervical insufficiency (CI) is associated with intra-amniotic infection or inflammation. Antimicrobial peptides (AMPs) in amniotic fluid may protect the fetus against microbial invasion, giving their broad-spectrum microbiocidal properties. We evaluated changes in amniotic fluid AMP expression in women with CI and assessed whether these changes are related to their pregnancy outcomes. We evaluated amniotic fluid human neutrophil peptide 3 (HNP-3), human β-defensin-2 (hBD-2), and LL-37 levels in 66 women with CI and 25 normal controls at 16-24 weeks of gestation. The CI group was divided into short cervix and cervical dilation groups, and the cervical dilation group was further divided into preterm and full-term delivery groups according to the pregnancy outcomes, and AMP expression was analyzed in each group. HNP-3 and hBD-2 levels were higher in women with CI than in normal controls and in the cervical dilation as compared to the short cervix group. Among women with cervical dilation, 22 delivered at full-term, and 23 had spontaneous preterm births. The hBD-2 level in amniotic fluid mid-pregnancy was higher in the full-term delivery than in the preterm delivery groups. However, LL-37 levels in amniotic fluid were low in women with CI and normal controls. Amniotic fluid HNP-3 and hBD-2 levels increased in women with CI compared with normal controls. Moreover, increased amniotic fluid hBD-2 levels mid-pregnancy were associated with favorable pregnancy outcomes in women with CI. AMPs in the amniotic fluid may participate in host defense against ascending infection in women with CI.


Suicide risk and violence risk in alcoholics. Predictors of aggressive risk.
The purposes of the study were: a) to examine whether risk for suicide and risk for violence were positively or negatively correlated; and b) to investigate potential predictors/mediators of suicide risk alone, violence risk alone, and risk for both suicide and violence. Suicide risk and violence risk were considered outcome variables. The predictor/mediator variables were eight ego defense mechanisms and 13 dysfunctional personality styles (both have been linked to aggressive risk). Seventy-four male alcoholics were administered questionnaire measures of suicide risk and violence risk, defenses, and disordered personality functioning. Results indicated that suicide and violence risk were significantly positively correlated. Three sets of predictor/mediator variables were identified: those predicting violence risk alone, those predicting suicide risk alone, and those predicting combined aggressive risk (risk for both suicide and violence). Connections obtained between predictor/mediator variables and outcome variables were explained in the context of existent clinical theory.


Manufacturing next-generation regulatory T-cell therapies.
Regulatory T-cell (Treg) therapy has shown promise in treating autoimmune diseases, transplant rejection, or graft-versus-host disease in early clinical trials. These trials have demonstrated that cell therapy using polyclonal Tregs is feasible and safe, however, the field has been limited by the lack of polyclonal cell specificity and consequent large cell numbers required, and the difficulty in generating autologous products for some patients. Thus, the field is moving toward 'next generation' Treg cell therapies that include genetic modification strategies to engineer specificity and/or modify function, as well as methods to generate Tregs in vitro. In this review, we describe how genetic modification of Tregs using viral transduction or gene editing may be incorporated into Treg manufacturing protocols. We also describe how Tregs may be generated via FOXP3 gene editing or overexpression, or by differentiation from pluripotent stem cells. The application of these various types of engineered Tregs is discussed.


A review and numerical assessment of the random walk particle tracking method.
We review the basic mathematical concepts of random walk particle tracking (RWPT) and its advantages and limitations. Three different numerical approaches to overcome the local mass conservation problem of the random walk methodology are examined: (i) the interpolation method, (ii) the reflection principle, and (iii) the generalized stochastic differential equations (GSDE). Analytical solutions of the spatial moments for a two-layer system are compared to model predictions using the different techniques and results demonstrate that the interpolation method reproduces correctly average velocity, but fails to reproduce macrodispersion at higher hydraulic conductivity contrasts between the two layers. On the contrary, the reflection principle and the GSDE approach underestimate average velocity, but reproduce macrodispersion better for high contrasts. The different behavior is based on an artificial shift of mass for increasing heterogeneities for the GSDE approach and the reflection principle, whereas the interpolation method suffers from the smoothing of the dispersion tensor. The behavior of these approaches was furthermore analyzed in two-dimensional heterogeneous hydraulic conductivity fields, which are characterized by different random function models. Solute transport was simulated correctly by all three approaches for the reference fields having Gaussian structures or non-Gaussian structures with an isotropic spatial correlation, even for a variance of the natural log of hydraulic conductivity of sigma(lnK)(2)=4. However, for the non-Gaussian model with a strong anisotropic spatial correlation and a variance of sigma(lnK)(2)=2 and higher, the interpolation method was the only technique modelling solute transport correctly. Furthermore, we discuss the general applicability of random walk particle tracking in comparison to the standard transport models and conclude that in advection-dominated problems using a high spatial discretization or requiring the performance of many model runs, RWPT represents a good alternative for modelling contaminant transport.


Self-assembled Möbius strips with controlled helicity.
Different from molecular level topology, the development of supramolecular topology has been limited due to a lack of reliable synthetic methods. Here we describe a supramolecular strategy of accessing Möbius strip, a fascinating topological object featured with only a single edge and single side. Through bending and cyclization of twisted nanofibers self-assembled from chiral glutamate amphiphiles, supramolecular nano-toroids with various twist numbers were obtained. Electron microscopic techniques could clearly identify the formation of Möbius strips when twist numbers on the toroidal fibers are odd ones. Spectroscopic and morphological analysis indicates that the helicity of the Möbius strips and nano-toroids stems from the molecular chirality of glutamate molecules. Therefore, M- and P-helical Möbius strips could be formed from L- and D-amphiphiles, respectively. Our experimental results and theoretical simulations may advance the prospect of creating chiral topologically complex structures via supramolecular approach.


Differences in inflammatory cytokine and Toll-like receptor genes and bacterial vaginosis in pregnancy.
This study was undertaken to estimate the frequency of inflammatory cytokine and Toll-like receptor gene polymorphisms in women with and without bacterial vaginosis (BV) in pregnancy. A secondary analysis was performed of pregnant women at less than 30 weeks' gestation enrolled as part of 2 multicenter studies. Eight hundred eighty-five women were assessed for BV (defined as Nugent's vaginal Gram stain score 7-10 and a pH > 4.5). Comparisons were made between women with or without BV. Extracted maternal DNA was analyzed for 7 cytokine (interleukin [IL] 1beta-511, IL1beta Exon 5 +3954, IL6-174, IL8-845, IL10-1082, tumor necrosis factor alpha-238 [TNFalpha-238], TNFalpha-308) and 2 Toll-like receptor (TLR-4 299, TLR-4 399) gene polymorphisms. BV was diagnosed in 497 women and 388 did not have BV. Genotype and allele frequency analyses revealed associations with BV and polymorphisms at the IL1beta Exon 5 +3954, IL6-174, IL10-1082, and TLR-4 399 loci. Women with BV were less likely to be homozygous (C/C) for IL1beta Exon 5 +3954 (P = .04). Women with BV were also less likely to have polymorphisms at the IL10-1082 (P = .03) and TLR-4 399 (P = .04) loci in the univariate analysis. Women with BV were more likely to be heterozygous (G/C) for the IL6-174 genotype (P < .0001). Multivariate analysis, controlling for maternal race, confirmed the following associations with BV: IL1beta Exon 5 +3954 (odds Ratio [OR] 0.5, 95% CI 0.3-0.9) and IL6-174 (OR 2.2, 95% CI 1.6-3.1). In addition, polymorphism at the IL8-845 locus was associated with a decreased risk for BV (OR 0.6, 95% CI 0.4-1.0). After controlling for race, polymorphisms at the IL1beta Exon 5 +3954, IL6-174, and IL8-845 loci were associated with an altered rate of BV in pregnancy.


The effect of calcium and vitamin D supplements on blood pressure in postmenopausal women: myth or reality?
Hypertension is a highly prevalent disease with serious cardiovascular and renal complications. Many studies have demonstrated a weak correlation between the consumption of calcium (or calcium plus vitamin D) and blood pressure, suggesting that calcium supplements might reduce blood pressure. However, the results to date remain controversial. In this study, we assessed the effect of calcium and vitamin D supplementation on the blood pressure of postmenopausal women with hypertension as a population group in which the use of calcium supplements is prevalent. This triple-blind randomized clinical trial enrolled 98 women of postmenopausal age with hypertension in 2019. The study period was 8 weeks with close follow-up. We used 24-h ambulatory blood pressure monitoring to record the initial and final blood pressure in all participants. The changes in both the mean systolic (p = 0.047) and diastolic blood pressure (p = 0.015) were suggestive of an increase in blood pressure after consuming calcium and vitamin D supplements. Among patients who had been using calcium channel blockers, calcium and vitamin D supplementation caused a notable increase compared to baseline systolic (p = 0.019) and diastolic blood pressures (p = 0.001). The present results differ from those of previous studies. This suggests that calcium supplementation for postmenopausal women with hypertension requires the close observation of blood pressure to prevent any further increase, especially in women who are being treated with calcium channel blockers (clinicaltrial.gov registration: NCT04618952).


Functionalized human umbilical cord mesenchymal stem cells and injectable HA/Gel hydrogel synergy in endometrial repair and fertility recovery.
Intrauterine adhesions (IUA) caused by endometrial injury are one of the main causes of female infertility. The current treatments for endometrial injury offer limited clinical benefits and cannot improve endometrial receptivity and pregnancy outcomes. Tissue engineering and regenerative medicine are considered potential solutions to address this concern and may offer effective treatment methods for the regeneration of injured human endometrium. Herein, we prepared an injectable hydrogel based on oxidized hyaluronic acid (HA-CHO) and hydrazide-grafted gelatin (Gel-ADH). The injectable hydrogel showed satisfactory biocompatibility when mixed with human umbilical cord mesenchymal stem cells (hUCMSCs). In an endometrial injury rat model, the treatment with hUCMSCs-loaded injectable hydrogel significantly enhanced the thickness of the endometrium and increased the abundance of blood vessels and glands in the injured endometrium compared to the control group. The hUCMSCs-loaded injectable hydrogel treatment significantly reduced endometrial fibrosis, decreased the expression of the pro-inflammatory factors (IL-1β and IL-6) and increased the expression of the anti-inflammatory factor (IL-10). This treatment induced endometrial VEGF expression by activating the MEK/ERK1/2 signaling pathway. Moreover, this treatment improved endometrial receptivity to the embryo and restored the embryo implantation rate similar to the sham group (48% in the sham group vs 46% in the treatment group), and this treatment achieved pregnancy and live birth in rats with endometrial injury. In addition, we also preliminarily validated the safety of this treatment in the maternal rats and fetuses. Collectively, our study showed that the hUCMSCs-loaded injectable hydrogel hold potential as an effective treatment strategy promoting rapid recovery of endometrial injury, and this hydrogel is a promising biomaterial for regenerative medicine applications. STATEMENT OF SIGNIFICANCE: 1. Oxidized hyaluronic acid (HA-CHO)/hydrazide-grafted gelatin (Gel-ADH) hydrogel combined with human umbilical cord mesenchymal stem cells (hUCMSCs) are effective in improving the regeneration of endometrium in the endometrial injury rat model. 2. The hUCMSCs-loaded hydrogel treatment promotes the expression of endometrial VEGF through MEK/ERK1/2 signaling pathway and regulates the balance of inflammatory factors. 3. The embryo implantation and live birth rates restore to normal level in the endometrial injury rat model, and the hydrogel has no adverse effects on maternal rats, fetuses, and offspring development after the treatments.


[Epidemiology and monitoring of closed abdominal injuries].
The authors review the epidemiological and aetiopathogenetic characteristics of abdominal blunt injuries (118 cases) monitored in a homogeneous manner. The relatively young age of the patients, the diagnostic difficulties encountered and the frequent presence of associated lesions call for the rigorous application of a predetermined clinico-diagnostic protocol.


Mature Twin Neonates Exhibit Oxidative Stress via Nitric Oxide Synthase Dysfunctionality: A Prognostic Stress Marker in the Red Blood Cells and Umbilical Cord Vessels.
Intrauterine hypoxic condition increases the generation of reactive oxygen species and fetal oxidative stress. Multiple pregnancy always bears an additional oxidative stress condition with severe complications, such as prematurity, structural abnormalities, delayed development and low birthweight. The umbilical cord (UC) vessels, along with circulating fetal red blood cells (RBCs), highly determine the oxygenation status of fetus and regulate the feto-placental circulation. As UC lacks innervation, the activation of the endothelial nitric oxide synthase (NOS3) is fundamental for proper NO production. Therefore, we aimed to study the NOS3 activation pathways along with damages to macromolecules in the endothelium of UC vessels and RBCs of mature non-discordant twins, in connection to major differences in their birth weight. We provide evidence that, under severe hypoxic conditions such as twin pregnancy, the NOS3-related NO production pathways are altered both in UC vessels and RBCs; moreover, the extent of changes is highly birthweight-specific. Furthermore, macromolecular damages are prominent in the RBCs and arteries compared to the vein, with a similar increase in the Arginase1 level, which is believed to play a role in NOS3 functionality, resulting in endothelial dysfunctionality, which might have relevance to the major etiologies of cardiovascular diseases in later life.


Extracorporeal shock wave lithotripsy for ureteral stones: a retrospective analysis of 417 cases.
We treated 417 patients with upper ureteral stones with extracorporeal shock wave lithotripsy. All patients with obstructing stones underwent retrograde manipulation, which was successful in 57 per cent. Management of obstructing stones in situ (215 patients) with and without decompression of the collecting system required additional treatments in 13 per cent and ancillary procedures in 25 per cent. Nonocclusive ureteral stones were not manipulated. Treatment of these stones in situ slightly increased the need for postoperative ancillary procedures, compared to successful repositioning into the kidney (5.9 versus 3 per cent). Secondary treatments, however, were necessary as often as with occlusive stones. The main reason for failure of extracorporeal shock wave lithotripsy was the lack of fluid around an impacted stone. An energy absorptive effect of muscle tissue for stones projecting on the psoas muscle could not be demonstrated. The best and most consistent results were obtained when the stone was manipulated successfully into the renal collecting system.


Hemorheological parameters in patients with gynecologic malignancies.
Thromboembolic events account for a significant number of complications during surgical and chemotherapeutic treatment for gynecologic malignancies. Besides changes in the hemostatic system, changes in hemorheological parameters facilitate initiation and promotion of thrombotic disease. We used a rheoaggregometer to determine erythrocyte aggregation and a capillary viscosimeter to evaluate plasma viscosity in patients with gynecologic malignancies at the time of primary diagnosis and during follow-up and compared the results to those for a normal control group. We found a significant elevation in plasma viscosity and erythrocyte aggregation as well as in fibrinogen and globulin concentrations in cancer patients. The extent of this rise was related to the tumor volume. Treatment with cisplatin, doxorubicin, and cyclophosphamide resulted in a further rise in erythrocyte aggregation which is attributed to a direct effect on the erythrocyte membrane. Thus, additional factors contributing to the risk of thrombosis in these patients were defined. Additional administration of rheologically active agents might improve the results of thrombosis prophylaxis.


Carotid artery occlusion and computed tomography. A clinicoradiological study.
Computed tomography (CT scanning) was carried out on 35 patients with proven occlusion of the carotid artery. There was a clear correlation of the clinical picture with the CT demonstration of cerebral infarct; 14 patients had no identifiable infarct. The findings were also correlated with angiographic data. The degree of cross or collateral filling of the middle cerebral artery on the affected side correlated better with the clinical features than with the CT data. Radioisotope studies were positive in only 50% of cases in which CT had shown infarction; this was related to the time interval between the onset of symptoms and scanning. The significance of these findings and their relationship to previous clinical necropsy data are discussed.


Major Advances and Discoveries in Diabetes - 2019 in Review.
This review is based on a recent invited lecture at the American Diabetes Association's 79th annual Scientific Sessions entitled "Major Advances and Discoveries in Diabetes - The Year in Review." Here I provide a written account of my presentation entitled "Major Discoveries in Diabetes over the Past Year." I highlight several recent advances in basic science that are relevant for the diabetes field, with insight into how the key takeaways impact basic science. I also speculate on how these breakthroughs challenge the field to move the basic science "discovery" into the clinic, as well as offering a perspective on unanswered questions in relation to these advances. The review should in no way be taken as an endorsement of the highlighted work or a denunciation of any work not selected. Rather, it is a personal reflection that provides a glimpse into what is on the horizon in this rapidly evolving and exciting field!


Quantitative immunochromatographic analysis: theory and application to theophylline immunoassay.
The development of an immunochromatographic technique suitable for rapid analysis of biological fluids is described. Quasi-one-dimensional antibody lattices specific for theophylline were constructed by packing Sepharose beads conjugated with specific antibody into specially designed narrow capillary tubes. The design of these capillary columns was such that they would subtract a preset threshold quantity of antigen (label and analyte) from the total amount presented. Labeled antigen, which appeared in the flowthrough, could then be used to precisely quantitate the analyte present. The ideal format would permit very precise subtraction of 100% of the available antigen up to the threshold amount and none of the remainder. The microcolumn described here comes close to this ideal behavior through the attainment of very high ratios of bound/free antigen. The elevated bound/free ratio could be explained by theoretical analysis of the effect on equilibria of the high antibody concentration in this quasi-one-dimensional system. Lattices containing anti-theophylline antibodies were used to develop a competitive enzyme immunoassay for theophylline which demonstrated a dose-response that was closely similar to that predicted by theoretical treatment. The entire assay procedure was performed in less than 30 min and demonstrated a sensitivity limit of approximately 20 ng/ml. Preliminary studies on clinical serum samples suggest that this assay has potential for the routine analysis of biological fluids.


What Actually Happened.
The medical team found the patient to lack medical decisionmaking capacity. However, the team felt that the patient was still able to respond appropriately to some situations. KS had displayed a consistent refusal of all medical treatments that made her uncomfortable or caused pain. During her sister's visits, the patient would be much more receptive to eating. A meeting was planned with the patient's sister in which the ethicist explained that the patient was not able to make her own decisions. The patient's sister agreed that she would honor the patient's wishes but would let the team make any decisions outside of what she knew about the patient's preferences. The patient's sister agreed and was willing to be at the patient's bedside as much as she could to encourage her eating. If the patient's condition worsened, it was discussed that the team honor the patient's wishes and not force a feeding tube on her. The patient's code status was also addressed, and KS's sister felt comfortable in communicating to the team that the patient would not want to be resuscitated if medical treatments would not be able to improve her current quality of life. A natural passing away would be most amenable to the patient. The patient was discharged to her nursing home with a physician order for life-sustaining treatment (POLST) form signed by the sister documenting a do-not-resuscitate code status with comfort-focused treatments.


Caveolae-Associated Molecules, Tumor Stroma, and Cancer Drug Resistance: Current Findings and Future Perspectives.
The discovery of small, "cave-like" invaginations at the plasma membrane, called caveola, has opened up a new and exciting research area in health and diseases revolving around this cellular ultrastructure. Caveolae are rich in cholesterol and orchestrate cellular signaling events. Within caveola, the caveola-associated proteins, caveolins and cavins, are critical components for the formation of these lipid rafts, their dynamics, and cellular pathophysiology. Their alterations underlie human diseases such as lipodystrophy, muscular dystrophy, cardiovascular disease, and diabetes. The expression of caveolins and cavins is modulated in tumors and in tumor stroma, and their alterations are connected with cancer progression and treatment resistance. To date, although substantial breakthroughs in cancer drug development have been made, drug resistance remains a problem leading to treatment failures and challenging translation and bench-to-bedside research. Here, we summarize the current progress in understanding cancer drug resistance in the context of caveola-associated molecules and tumor stroma and discuss how we can potentially design therapeutic avenues to target these molecules in order to overcome treatment resistance.


High prevalence of hepatitis B and poor knowledge on hepatitis B and C viral infections among barbers: a cross-sectional study of the Obuasi municipality, Ghana.
Barbers, while shaving, may be accidentally exposed to the blood and bodily fluids of their customers increasing their risk of contraction of HBV and HCV infections. Hence, this study aimed at examining the prevalence and knowledge of barbers on HBV and HCV infections in the Obuasi municipality of Ghana. A work place based cross-sectional study was conducted from January to April 2015 at the Obuasi municipality in the Ashanti Region of Ghana. Two hundred (200) barbers were conveniently recruited and blood sample of each participant collected for the detection of HBsAg and HCV antibodies. Data on socio demographic characteristics, and knowledge on HBV and HCV infections were collected using a structured and pre-tested questionnaire. Analysis was performed using SPSS version 16.0, and P < 0.05 was considered statistically significant. The prevalence of HBV and HCV among the barbers were 14.5 % and 0.5 % respectively. HBV was highest among barbers within 20-29 years (58.6 %). Majority (90.5 %) of the participants had heard of HBV infection before. The mode of transmission of HBV was unknown by 64.5 % of the participants and 64.0 % did not perceive themselves to be at risk for HBV. Most of the participants had never heard of HCV infection (61.3 %), and unaware of any mode of transmission of HCV (97.0 %). The radio was the major source of information on HBV (57.5 %) and HCV (25.0 %) infections. High prevalence of HBV and low knowledge on HBV and HCV infections was found among barbers. Barbers need to be educated on viral hepatitis to reduce the acquisition of HBV and HCV infections.


Plasma oestriol in pregnancies complicated by diabetes mellitus.
We studied the plasma oestriol concentration during increasing gestation in 192 normal pregnancies and 96 pregnancies complicated by diabetes mellitus. Among the 96 patients there were 16 established, 32 gestational, 29 'persistent' gestational and 19 either gestational or 'persistent' gestational diabetic pregnancies. Serial blood samples were collected and their concentrations of oestriol (total oestriol) determined by radioimmunoassay. The distribution of birthweights and placental weights around each gestational period was skewed to the right. Therefore, the 5th and 95th percentiles were obtained after computing a logarithmic transformation of the data. The incidence of big and small babies in all diabetic groups, except that in the gestational diabetic group, was significantly higher than that in the group of normal pregnant women. The distribution of oestriol concentrations was also skewed to the right and had to be normalized by logarithmic transformation. The oestriol profile in normal pregnancies had a wide scatter, especially after the 37th week. Serial measurements with reference to the normal oestriol profile showed a detection rate of approximately 85% for both normal and abnormal foetal outcome. There were 15% of false negative and 16% of false positive results. Results in this study indicate that serial blood oestriol measurement may be a useful additional index for foetal monitoring in pregnancies in diabetic women. Furthermore, if large scale screenings using a single estimation are performed, it is best carried out between the 33rd and 34th week of gestation.


Use of Patient-Reported Outcomes to Understand & Measure the Patient Experience of Novel Cell and Gene Therapies.
Patient reported outcomes (PROs) are the gold standard for assessing patients' experience of treatment in oncology, defined in the 21st Century Cures Act as information about patients' experiences with a disease or condition, including the impact of a disease or condition, or a related therapy or clinical investigation on patients' lives; and patient preferences with respect to treatment of their disease or condition [1]. PROs provide a comprehensive assessment of the benefits and risks of new medical products, as well as essential data to inform real-world use. Although RCTs are the ultimate source for information for evaluating products in development, they are not always feasible for rare diseases with few or no effective treatment options available. Thus, it is important to consider other measures that can help to improve the strength of evidence for cell and gene therapies targeting rare indications. While collection of PROs and other patient experience endpoints does not resolve the difficulty of conducting trials in small populations, doing so contributes empirical evidence that informs both product development and patient access. Additionally, including routine collection of PROs in registries may provide supplemental data to further characterize the benefit:risk profile of cell and gene therapies at follow-up times that would be infeasible to operationalize in a clinical trial setting.


Rating dental arch relationships and palatal morphology with the EUROCRAN index on three different formats of dental casts in children with unilateral cleft lip and palate.
The EUROCRAN index has been used in inter-center studies to assess dental arch relationship (DAR) and palatal morphology (PM) in children with unilateral cleft lip and palate (UCLP). For this type of inter-center research, a scoring method that could be performed over the internet would be the most effective. Therefore, the aim of this study was to investigate the reliability of application of the EUROCRAN index on 3D digital models or photographs of plaster models instead of using plaster models. The EUROCRAN reference models were presented in three formats: plaster models, 2D photographs of plaster models, and 3D digital models. Plaster models of children with UCLP (n = 45) were rated. Of each case, all three formats were rated by six calibrated observers in random order. The strength of agreement of the ratings was assessed with kappa statistics. Concordance among observers was evaluated with the intra-class correlation coefficient (ICC). The ICC showed a good inter-observer agreement for the DAR and poor inter-observer agreement for the PM. Intra-observer agreement for the DAR was moderate to very good, yet for the PM poor to moderate. Comparison between the three formats per observer for the DAR was good or very good and for the PM moderate to poor. The overall results show that the EUROCRAN index is an acceptable and reliable scoring method for the DAR on plaster models, 2D photographs of plaster models, and 3D digital models. However, due to the small range of deviations in palatal morphology between the cases in our study, the PM component of the index was difficult to assess. In clinical audits and inter-center studies, plaster models can be substituted by 2D photographs of plaster casts or 3D digital models when grading treatment outcome with the EUROCRAN index.


An E-health system for monitoring elderly health based on Internet of Things and Fog computing.
With the significant increase in the number of elderly in the world and the resulting health problems of these increasing, finding technical solutions to address this problem has become a pressing necessity, particularly in the field of health care. This paper proposes an e-health system for monitoring elderly health based on the Internet of Things (IoT) and Fog computing. The system was developed using Mysignals HW V2 platform and an Android app that plays the role of Fog server, which enables the collection of physiological parameters and general health parameters from elderly periodically. This Android app enables also the elderly and their families to follow their health, and they can also communicate with health care providers (administrators and doctors) and receive recommendations, notifications and alerts. By evaluating this system, we find the most users they consider useful, easy to use and learn, suggesting that our proposal can improve the quality of health care for elderly.


Comparative study of Co3O4(111), CoFe2O4(111), and Fe3O4(111) thin film electrocatalysts for the oxygen evolution reaction.
Water electrolysis to produce 'green H2' with renewable energy is a promising option for the upcoming green economy. However, the slow and complex oxygen evolution reaction at the anode limits the efficiency. Co3O4 with added iron is a capable catalyst for this reaction, but the role of iron is presently unclear. To investigate this topic, we compare epitaxial Co3O4(111), CoFe2O4(111), and Fe3O4(111) thin film model electrocatalysts, combining quasi in-situ preparation and characterization in ultra-high vacuum with electrochemistry experiments. The well-defined composition and structure of the thin epitaxial films permits the obtention of quantitatively comparable results. CoFe2O4(111) is found to be up to about four times more active than Co3O4(111) and about nine times more than Fe3O4(111), with the activity depending acutely on the Co/Fe concentration ratio. Under reaction conditions, all three oxides are covered by oxyhydroxide. For CoFe2O4(111), the oxyhydroxide's Fe/Co concentration ratio is stabilized by partial iron dissolution.


Dermatopathology for the surgical pathologist: a pattern-based approach to the diagnosis of inflammatory skin disorders (part II).
The accurate diagnosis of inflammatory conditions in dermatopathology requires integrating the histopathologic findings with the clinical features. This second part of a 2-part review of inflammatory cutaneous conditions presents a pattern-based approach to the diagnosis of dermatologic disorders and reviews the salient clinical and histologic features.


What Does a Modern Anatomist Look like? Current Trends in the Training of Anatomy Educators.
Anatomical sciences are foundational to the health professions, yet little is known about the qualifications of anatomy educators at the graduate and professional level in the United States. Moreover, there is concern that the number of qualified anatomy educators being trained may be insufficient to meet the growing demand posed by new and expanded programs in medicine and allied health specialties. The authors surveyed anatomists from across the country to (i) characterize the educational credentials of current anatomy educators and (ii) assess the perceived need for education-focused postdoctoral positions or formal mentorships to prepare anatomists for teaching-intensive faculty positions. To probe the survey responses more deeply, one-on-one interviews were conducted with eight individuals selected to represent a diverse sample of respondents in terms of institution, gender, and academic rank. Results indicate that 30-40% of educators at the graduate level and approximately 60% of those at the undergraduate level lack graduate coursework in histology, embryology, and neuroanatomy. Forty-five percent of respondents had completed a postdoctoral fellowship. Eighty-six percent replied "yes/maybe" to the question of whether an anatomy education postdoctoral fellowship would benefit doctoral graduates. The top 3 reasons for this recommendation were to (i) establish independent educational research, (ii) improve a publication record, and (iii) gain additional teaching experience. Notable weaknesses of education-focused postdoctoral training were related to finances, fear of exploitation, and undervaluing of teaching. Moving forward, postdoctoral fellowships and other forms of postgraduate training may represent a key strategy for training anatomists in the current educational climate. Anat Sci Educ 00: 000-000. © 2018 American Association of Anatomists.


In vitro cell aggregation and cell adhesion molecules in Crohn's disease.
Lack of a suitable model has hindered efforts to understand inflammation and granuloma formation in Crohn's disease. Granulomalike aggregates of circulating mononuclear cells are produced in vitro by cultures of cells with polyacrylamide beads. To identify features of in vitro aggregates, which are similar to tissue granulomas of Crohn's disease, the gross morphology and immunohistological appearance of the aggregates produced with peripheral blood mononuclear cells from patients with Crohn's disease were analyzed, and the size of in vitro aggregates was correlated with clinical activity of the disease. Blocking antibodies were used to evaluate the role of cell-adhesion molecules in the formation of in vitro aggregates. The size of in vitro aggregates correlates very significantly with clinical activity (P < 0.001). In active Crohn's disease, in vitro aggregates show immunohistological features of hypersensitivity type granulomas. Blocking antibodies against leukocyte function associated antigen LFA-2 (CD2), LFA-3 (CD58), and Mac-1 (CD11b/CD18) inhibit in vitro aggregate formation. In vitro aggregates model in vivo granulomas in size and organization. Cell adhesion molecules like CD2, CD58, and CD11b/CD18 may be involved in granuloma-formation of Crohn's disease.