Aldolase A isoenzyme levels in serum and tissues of patients with liver diseases.
A radioimmunoassay specific for human aldolase A was used to measure human aldolase A levels in human tissue and serum of patients with various liver diseases. The method was a double-antibody technique using radio-iodinated purified aldolase A, chicken antibody to aldolase A, and rabbit antibody to chicken immunoglobulin G. Normal liver tissue contains only a small amount of aldolase A. In contrast, aldolase A predominates in liver cell carcinoma tissue. Aldolase A levels in the sera of normal subjects were 171 +/- 39 ng/ml (mean +/- 2 SD). In almost all of the nonmalignant liver diseases, the aldolase A levels remained less than 210 ng/ml. The serum aldolase A levels increased remarkable only in fulminant hepatitis. in contrast, 32 of 34 patients with liver cell carcinoma and all of 29 patients with metastatic liver carcinoma showed clearly increased serum aldolase A levels. More patients with primary liver cell carcinoma had increased serum aldolase A levels than elevations of serum alpha-fetoprotein. These results suggest that the determination of aldolase A by radioimmunoassay may be useful to differentiate malignant form nonmalignant liver diseases.


A novel early mobility bundle improves length of stay and rates of readmission among hospitalized general medicine patients.
Inpatient early mobility initiatives are effective therapeutic interventions for improving patient outcomes and decreasing use of hospital resources among adult ICU and general medicine patients. To establish and demonstrate guidelines for early patient ambulation, we developed and implemented a novel multidisciplinary mobility bundle utilizing the JH-HLM (Johns Hopkins Highest Level of Mobility) scale for mobility classification, on a single adult general medicine unit of a community hospital. Our results show that patients admitted to the unit after implementation of the mobility bundle had improved mobility scores, reduced rates of 30-day hospital readmission, and a shortened length of hospital stay. This study emphasizes the importance of measuring mobility using a systematic method, easing workflow among unit practitioners, and allowing mobility initiatives to be jointly driven by nursing, physical therapy, and physicians.


Enhancement of the water solubility and antioxidant capacities of mangiferin by transglucosylation using a cyclodextrin glycosyltransferase.
This study aimed to enhance the water solubility and antioxidant properties of mangiferin by transglucosylation using cyclodextrin glycosyltransferase (CGTase) from Thermoanaerobacter sp. The highest mangiferin to mangiferin glucoside conversion yield achieved was 88.9% using 60 mU/mL CGTase, 25 mM mangiferin, and 10% starch (w/v), with incubation at 60 °C for 10 h. The product of transglucosylation was purified and its chemical structure was determined to be glucosyl-α-(1→4)-mangiferin (MGF-g1) using matrix-assisted laser desorption ionization time-of-flight mass spectrometry and nuclear magnetic resonance spectroscopy. The water solubility of MGF-g1 was 5,093 times higher than that of mangiferin. MGF-g1 exhibited 1.6-fold higher 2,2-diphenyl-1-picrylhydrazyl radical scavenging activity, 1.24-fold higher oxygen radical antioxidant capacity, and 1.19-fold higher ferric reducing ability power, compared to mangiferin. Moreover, the cyclooxygenase-2 inhibitory activity (IC50) of mangiferin and MGF-g1 were 76.44 ± 11.7 μM and 59.74 ± 2.8 μM, respectively. Our results suggest that the novel MGF-g1 has potential applications as a functional material in the food and pharmaceutical industries.


DNA methylation in newborns conceived by assisted reproductive technology.
Assisted reproductive technology (ART) may affect fetal development through epigenetic mechanisms as the timing of ART procedures coincides with the extensive epigenetic remodeling occurring between fertilization and embryo implantation. However, it is unknown to what extent ART procedures alter the fetal epigenome. Underlying parental characteristics and subfertility may also play a role. Here we identify differences in cord blood DNA methylation, measured using the Illumina EPIC platform, between 962 ART conceived and 983 naturally conceived singleton newborns. We show that ART conceived newborns display widespread differences in DNA methylation, and overall less methylation across the genome. There were 607 genome-wide differentially methylated CpGs. We find differences in 176 known genes, including genes related to growth, neurodevelopment, and other health outcomes that have been associated with ART. Both fresh and frozen embryo transfer show DNA methylation differences. Associations persist after controlling for parents' DNA methylation, and are not explained by parental subfertility.


Trastuzumab deruxtecan in recurrent uterine serous carcinoma resistant to trastuzmab based-chemotherapy.
Treatment of uterine serous carcinoma (USC) is challenging; effective treatment options for metastatic and recurrent disease are needed. A 68-year-old woman with recurrent, metastatic, USC overexpressing HER2/neu experienced durable response to the antibody drug conjugate (ADC) trastuzumab-deruxtecan (T-DXd), after failing multiple standard and experimental treatments targeting HER2/neu. She experienced a significant reduction in disease burden, disappearance of metastatic back bone pain as well as normalization of CA-125 quickly after starting treatment. Her disease continued to show response to treatment over 5 months and 7 cycles of T-DXd therapy. She did not experience any dose-limiting side effects and tolerated treatment with 5.4 mg/kg T-DXd without issue. T-DXd may present a new treatment option for chemotherapy-resistant uterine serous carcinoma.


Effectiveness of varicocelectomy in varicoceles diagnosed by physical examination versus Doppler studies.
The purpose of this study is to compare the effectiveness of varicocelectomy for improving the spermogram in treating varicoceles diagnosed by physical examination and those diagnosed by Doppler but with a negative physical examination. The charts of 112 patients were retrospectively analyzed and the patients divided in two groups: group A, where the varicocele was detected by physical examination, and group B, where physical examination was negative but Doppler studies revealed the presence of stasis or backflow in the pampiniform plexus of the spermatic veins. In subjects complaining of infertility, the two groups were similar with regard to age distribution and duration of infertility. After varicocelectomy, 85% of patients in group A had improved spermogram, compared with only 27% in group B. This difference was statistically significant (P less than 0.0001).


Determination of Disk Diffusion and MIC Quality Control Guidelines for Solithromycin, a Novel Fluoroketolide Antibacterial, against Neisseria gonorrhoeae.
This solithromycin quality control study was performed to establish quality control (QC) ranges for the N. gonorrhoeae ATCC 49226 control strain for MIC agar dilution testing (AD) and zones by disk diffusion testing (DD). The following ranges were established: AD, 0.03 to 0.25 μg/ml, and DD, 33 to 43 mm. In January 2015, the CLSI Subcommittee on Antimicrobial Susceptibility Testing approved these ranges, which will be important when evaluating solithromycin against clinical isolates of N. gonorrhoeae.


Serum SIRT1 Is Associated with Frailty and Adipokines in Older Adults.
Because frailty is a major health concern among older patients, identifying frailty-related biomarkers will help in the early detection and prevention of frailty. Thus, we aimed to determine the association between circulating levels of silent mating-type information regulation 2 homolog 1 (SIRT1) and frailty. We assessed circulating SIRT1 levels in 16 robust, 74 prefrail, and 40 frail older adults. Frailty was diagnosed based on the Fried phenotype. Circulating cytokine and adipokine (e.g., vaspin, adiponectin, and leptin) levels were assessed. Differences in SIRT1 levels among the three subject groups were compared; correlations of SIRT1 levels with physical function and adipokine and cytokine levels were analyzed. Serum SIRT1 levels were significantly higher among frail older adults than among robust ones. Older adults with slowness or weight loss had high SIRT1 levels. Serum SIRT1 levels negatively correlated with gait speed, even after adjustment for age and sex; age; and insulin, vaspin, and leptin levels; they correlated negatively with phospholipase A2 levels. High SIRT1 levels were observed in frail elderly patients and were correlated with decreased physical function. Insulin and adipokine levels might be the link between SIRT1 and frailty, whereas inflammation may not be involved in this process.


The Lion King of ovulation induction.
Melvin Taymor's daughter, Julie Taymor, directed the musical version of The Lion King, which won six Tony Awards. Known for her revolutionary staging, she became the first woman to be awarded a Tony for Best Direction of a Musical.


Spatial distribution of predicted transcription factor binding sites in Drosophila ChIP peaks.
In the development of the Drosophila embryo, gene expression is directed by the sequence-specific interactions of a large network of protein transcription factors (TFs) and DNA cis-regulatory binding sites. Once the identity of the typically 8-10bp binding sites for any given TF has been determined by one of several experimental procedures, the sequences can be represented in a position weight matrix (PWM) and used to predict the location of additional TF binding sites elsewhere in the genome. Often, alignments of large (>200bp) genomic fragments that have been experimentally determined to bind the TF of interest in Chromatin Immunoprecipitation (ChIP) studies are trimmed under the assumption that the majority of the binding sites are located near the center of all the aligned fragments. In this study, ChIP/chip datasets are analyzed using the corresponding PWMs for the well-studied TFs; CAUDAL, HUNCHBACK, KNIRPS and KRUPPEL, to determine the distribution of predicted binding sites. All four TFs are critical regulators of gene expression along the anterio-posterior axis in early Drosophila development. For all four TFs, the ChIP peaks contain multiple binding sites that are broadly distributed across the genomic region represented by the peak, regardless of the prediction stringency criteria used. This result suggests that ChIP peak trimming may exclude functional binding sites from subsequent analyses.


Synthesis and in vitro antiproliferative activity against human cancer cell lines of novel 5-(4-methyl-benzylidene)-thiazolidine-2,4-diones.
A series of novel 5-(4-methyl-benzylidene)-thiazolidine-2,4-dione derivatives 6 (a-d) and 7 (a-g) were synthesized with different substituted aromatic sulfonyl chlorides (R-SO(2)-Cl) and alkyl halides (R-X) and were characterized by (1)H NMR, LC/MS, FTIR and elemental analyses. All the compounds synthesised were evaluated for their cell antiproliferation activity by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. The antiproliferative effects of the synthesised compounds were tested against viable human skin fibroblast cell line and carcinoma cell lines namely HeLa cells, HT-29 cells, MCF-7 cells, HepG-2 cells by adopting positive and negative control. The importance of the nitro group on thiazolidinone moiety was confirmed and it was concluded that the fourth position of the substituted aryl ring plays a dominant role and was responsible for the antiproliferative activity. Among the synthesized compounds only 6a, 7e and 7g have potent antiproliferative activity on all the carcinoma cell lines tested.


Distinctive sodium and calcium regulation associated with sex differences in atrial electrophysiology of rabbits.
Sex and sodium/calcium regulation play critical roles in cardiac electrophysiology and atrial arrhythmogenesis. We investigated whether sodium and calcium contributed to sex differences in atrial electrophysiology. Whole-cell patch clamp techniques and the indo-1 fluorometric ratio technique were used to investigate the ionic current and intracellular calcium in single isolated male and female rabbit myocytes from the left atrium posterior wall (LAPW) and right atrium (RA). Female LAPW (n=95) and RA (n=49) myocytes had larger cell widths (15.1±0.4 vs. 13.8±0.4 μm, p<0.05; 14.9±0.6 vs. 13.5±0.4 μm, p<0.05) than male LAPW (n=142) and RA (n=57) myocytes. Male LAPW myocytes (n=26) had a higher incidence (57 vs. 16%, p<0.05) of delayed afterdepolarizations (DADs) than female LAPW myocytes (n=24) but there were similar incidences (20 vs. 20%, p>0.05) of DADs in male and female RA myocytes. The late sodium current, calcium transients, and sarcoplasmic reticulum calcium contents were larger in male than female LAPW myocytes but were similar in male and female RA myocytes. However, the ICa-L and nickel-sensitive sodium/calcium exchanger currents were similar between two groups. Different from those in female myocytes, ouabain (10 μM) only induced repeated atrial beats (0 to 45%, p<0.05) in male myocytes (n=11). Moreover, ranolazine (3 μM) perfusion (4.5±0.6 vs. 1 min, p<0.05) was required to decrease the amplitude of DADs in male but not female LAPW myocytes. Increased late sodium currents and calcium contents may contribute to higher arrhythmogenesis in male LAPW myocytes.


The M1 subunit of ribonucleotide reductase refines mapping of genetic rearrangements at chromosome 11p15.
We report the first use of the ribonucleotide reductase M1 subunit (RRM1) locus as a marker to assist in defining genetic rearrangements at 11p15. Our sample consisted of 21 Wilms' tumors from 18 patients, and one adrenal adenoma from a patient with Beckwith-Wiedemann syndrome, preexisting chromosome 11 maps being refined by the use of the RRM1 locus in all cases. Significantly, one Wilms' tumor showed loss of heterozygosity at the RRM1 locus only, whereas the adrenal adenoma showed a maintenance of heterozygosity at the RRM1 locus, loss having been previously demonstrated at the c-Ha-ras locus. The relevance of this finding to the location of one or more disease-associated loci at 11p15 is discussed.


Inhibition of rabbit reticulocyte lysate protein synthesis by heavy metal ions involves the phosphorylation of the alpha-subunit of the eukaryotic initiation factor 2.
The effect of heavy metal ions (in particular Cd2+, Hg2+, and Pb2+) on protein synthesis in hemin-supplemented reticulocyte lysates was investigated. Heavy metal ions were found to inhibit protein synthesis in hemin-supplemented lysates with biphasic kinetics. The shut off of protein synthesis occurred in conjunction with the phosphorylation of the alpha-subunit of the eukaryotic initiation factor (eIF) 2, the loss of reversing factor (RF) activity, and the disaggregation of polyribosomes. Addition of eIF-2 or RF to heavy metal ion-inhibited lysates restored protein synthesis to levels observed in hemin-supplemented controls. The stimulation of protein synthesis observed upon the addition of cAMP to heavy metal ion-inhibited lysates correlated with the inhibition of eIF-2 alpha phosphorylation and the restoration of RF activity. The partial restoration of protein synthesis observed upon the addition of MgGTP to heavy metal ion-inhibited lysates correlated with a partial inhibition of eIF-2 alpha phosphorylation. Addition of glucose 6-phosphate was found to have no effect on protein synthesis of eIF-2 alpha phosphorylation under these conditions. Antiserum raised to the reticulocyte heme-regulated eIF-2 alpha kinase inhibited the phosphorylation of eIF-2 alpha catalyzed by Hg2+-inhibited lysate. The inhibition of protein synthesis observed in the presence of heavy metal ions correlated with the relative biological toxicity of the ions. Highly toxic ions (AsO-2, Cd2+, Hg2+, Pb2+) inhibited protein synthesis by 50% at concentrations of 2.5-10 microM. Cu2+, Fe3+, and Zn2+, which are moderately to slightly toxic ions, inhibited protein synthesis by 50% at concentrations of 40, 250, and 300 microM, respectively. The data presented here indicate that heavy metal ions inhibit protein chain initiation in hemin-supplemented lysates by stimulating the phosphorylation of eIF-2 alpha apparently through the activation of the heme-regulated eIF-2 alpha kinase rather than through inhibition of the rate of eIF-2 alpha dephosphorylation.


HLA-A, B, Cw and DRB1, DRB3/4/5, DQB1, DPB1 frequencies in German immunoglobulin A-deficient individuals.
HLA class I and II frequencies and haplotype frequencies were determined in 80 German immunoglobulin (Ig)A-deficient individuals and 157 healthy controls with normal IgA levels using serological and DNA typing methods. For several alleles, significant associations were found, which could be explained mainly in the context of a positive association with three different extended haplotypes (HLA-B*08:DRB1*0301: DQB1*0201, HLA-B*14:DRB1*0102:DQB1*0501 and HLA-B*44:DRB1*0701:DQB1*0202) and a negative association with a fourth haplotype (HLA-B*07:DRB1*1501:DQB1*0602). Furthermore, for the first time this study reports a positive association of IgA deficiency with DPB1 alleles. Homozygosity rate for the gene loci DRB1 and DQB1 was increased in IgA deficiency. Further analysis suggested a different pattern of HLA associations depending on the degree of IgA deficiency and the gender of the IgA-deficient individuals.


Spontaneous closure of an extensive postdebridement perineal wound in a newly diagnosed diabetic patient presenting with necrotizing fasciitis.
Diabetes mellitus may present for the first time with necrotizing fasciitis. Early treatment of septic shock and immediate surgical debridement reduces mortality. A diverting loop colostomy prevents soiling of extensive postdebridement wound. Local wound care together with good glycemic and infection control leads to spontaneous wound closure.


Effects of physical exercise on plasma levels of brain-derived neurotrophic factor and depressive symptoms in elderly women--a randomized clinical trial.
To investigate the effect of 2 standardized exercise programs, muscle strength exercises (SE) and aerobic exercises (AE), on the plasma levels of brain-derived neurotrophic factor (BDNF) and depressive symptoms in 451 elderly women. A randomized controlled trial. Belo Horizonte/MG-Brazil. Community-dwelling older women (N=451; age, 65-89y). The participants were divided into 2 groups: SE and AE. Both protocols lasted 10 weeks, and 30 sessions (1-h sessions) in total were performed 3 times a week under the direct supervision of physical therapists. Plasma levels of BDNF (enzyme-linked immunosorbent assay) and depressive symptoms (Geriatric Depression Scale). There was a significant difference for BDNF plasma levels between the SE and AE groups (P=.009). Post hoc analysis revealed a pre-post intervention difference in BDNF levels only for the SE group (P=.008). A statistically significant difference was found for the pre- and postintervention Geriatric Depression Scale scores in both groups (P=.001), showing that the effects of both exercise protocols were comparable regarding depressive symptoms (P=.185). The present findings have demonstrated the positive effect of muscle strengthening and aerobic intervention on depressive symptoms in community-dwelling elderly women. Interestingly, only SE significantly increased the plasma levels of BDNF in our sample. The positive effects of physical exercise on depressive symptoms in the elderly were not mediated by BDNF.


Label-free supersandwich electrochemiluminescence assay for detection of sub-nanomolar Hg2+.
A label-free supersandwich electrochemiluminescence assay based on T-Hg(2+)-T coordination and the intercalation of Ru(phen)(3)(2+) for Hg(2+) analysis was developed with excellent sensitivity and selectivity.


Synergistic activity of aminoglycoside-beta-lactam combinations against Pseudomonas aeruginosa with an unusual aminoglycoside antibiogram.
The bactericidal activity of aminoglycosides alone and in combination with various beta-lactams was studied by the time-kill technique against ten Pseudomonas aeruginosa isolates with an unusual antibiogram (amikacin-resistant, gentamicin-resistant, tobramycin-susceptible [ArGrTs]). Previous studies have indicated that ArGrTs isolates are moderately resistant to all aminoglycosides and many are multiply resistant to beta-lactams. Aminoglycoside-beta-lactam combinations showed infrequent synergistic (16%) or enhanced killing (12%) against the ArGrTs isolates. Synergistic activity, when present, was more likely to occur with tobramycin and amikacin than with gentamicin, even though these differences were not statistically significant. Antibiotic resistance patterns were not predictive of synergy or enhanced killing. Systemic infections produced by ArGrTs isolates that are multiply resistant to the beta-lactams may not respond to combination therapy with an aminoglycoside and beta-lactam. Alternative treatment with polymyxin B or a quinolone may be required for these infections.


The role of gadoxetic acid-enhanced MRI features for predicting microvascular invasion in patients with hepatocellular carcinoma.
To evaluate the predictive value of gadoxetic acid-enhanced MRI features (focused on Liver Imaging Reporting and Data System (LI-RADS) v2018 features and non-LI-RADS imaging features) for microvascular invasion (MVI) of hepatocellular carcinoma (HCC). From October 2018 to December 2020, 134 patients who underwent gadoxetic acid-enhanced MRI with a pathological diagnosis of HCC after hepatectomy were enrolled in this retrospective study. Two radiologists assessed the pre-hepatectomy LI-RADS v2018 imaging features and non-LI-RADS features to identify independent predictors of MVI of HCC with a logistic regression model. Four MRI features were found to be independent predictors of MVI: corona enhancement [odds ratio (OR) 5.787; 95% confidence interval (CI) 1.180, 28.369; p = 0.030], mosaic architecture (OR 7.097; 95% CI 1.299, 38.783; p = 0.024), nonsmooth tumor margin (OR 13.131; 95% CI 3.950, 43.649; p < 0.001), and peritumoral hypointensity on hepatobiliary phase (HBP) (OR 33.123; 95% CI 2.897, 378.688; p = 0.005). When one of four imaging features was present, the sensitivity was 93.2% (41/44), and the specificity was 71.1% (64/90). The four imaging features including corona enhancement, mosaic architecture, nonsmooth tumor margin, and peritumoral hypointensity on HBP can be used as preoperative imaging biomarkers for predicting MVI in patients at high risk for HCC. When one of the four imaging features is present, MVI can be predicted with a sensitivity > 90%.


[Typical emergencies in otorhinolaryngology-a monocentric analysis of the seasonal course].
The incidence of acute ear, nose, and throat (ENT) diagnoses is influenced by multiple parameters, for example meteorological and seasonal influences. By better understanding the triggering factors, prophylactic approaches can be developed. A retrospective analysis was performed over 6 years of all patients who presented to the university hospital because of typical and minor ENT emergencies. The diagnoses impacted cerumen, acute otitis media, acute otitis externa, nasal bone fracture, epistaxis, acute tonsillitis, acute rhinosinusitis, and peritonsillar abscess were analyzed. A total of 32,968 cases were analyzed. Epistaxis was the most common of the investigated emergency diagnoses, accounting for 24.5% (8082 cases). Epistaxis, acute otitis media, and acute rhinosinusitis occurred significantly more frequently in the colder half of the year. There was no significant correlation of the incidence of nasal bone fracture with public holidays. Acute otitis externa correlated significantly with the local summer vacations. In calendar week 38, the fewest total emergency presentations occurred, whereas in calendar week 52, the most emergency presentations occurred. Seasonal and meteorological factors play a significant role in the pathogenesis of many emergency ENT diagnoses.


Associations between bone mineral density, body composition and amenorrhoea in females with eating disorders: a systematic review and meta-analysis.
Lower bone mineral density (BMD) increases the risk of osteoporosis in individuals with eating disorders (EDs), particularly women with anorexia nervosa (AN), making them susceptible to pain and fractures throughout adulthood. In AN, low weight, hypothalamic amenorrhoea, and longer illness duration are established risk factors for low BMD, and in people with other EDs a history of AN seems to be an important risk factor for low BMD. To conduct a systematic review and meta-analysis of BMD in individuals with EDs, including AN, bulimia nervosa (BN), binge-eating disorder (BED) and other specified feeding or eating disorders (OSFED) compared to healthy controls (HC). Following PRISMA guidelines, electronic databases were reviewed and supplemented with a literature search until 2/2022 of publications measuring BMD (dual-energy X-ray absorptiometry or dual photon absorptiometry) in females with any current ED diagnosis and a HC group. Primary outcomes were spine, hip, femur and total body BMD. Explanatory variables were fat mass, lean mass and ED clinical characteristics (age, illness duration, body mass index (BMI), amenorrhoea occurrence and duration, and oral contraceptives use). Forty-three studies were identified (N = 4163 women, mean age 23.4 years, min: 14.0, max: 37.4). No study with individuals with BED met the inclusion criteria. BMD in individuals with AN (total body, spine, hip, and femur), with BN (total body and spine) and with OSFED (spine) was lower than in HC. Meta-regression analyses of women with any ED (AN, BN or OSFED) (N = 2058) showed low BMI, low fat mass, low lean mass and being amenorrhoeic significantly associated with lower total body and spine BMD. In AN, only low fat mass was significantly associated with low total body BMD. Predictors of low BMD were low BMI, low fat mass, low lean mass and amenorrhoea, but not age or illness duration. In people with EDs, body composition measurement and menstrual status, in addition to BMI, are likely to provide a more accurate assessment of individual risk to low BMD and osteoporosis.


TikTok: a far-reaching opportunity for health professionals to address weight loss.
Recent behavioral research indicates that social media may be successfully integrated into weight loss interventions to mitigate the obesity epidemic that has been linked with type two diabetes, cardiovascular diseases, cancers, as well as poor psychological health. This study aimed to examine the content and characteristics of 100 most trending TikTok videos related to weight loss. This was a cross-sectional, descriptive study. Videos were analyzed for source, predominant theme, and inclusion of specific content. Independent two-tailed t-tests assessed the effect of content on number of comments, likes, and forwards garnered by the videos. More than 90% of the videos were consumer generated, indicating a missed opportunity by health professionals to use social media to provide accurate information regarding weight loss. Less than one-fifth of the videos were informational but significantly influenced the number of comments (P < .001) and likes (P = .002). Videos mentioning benefits ((P < .001) and speed of weight loss (P = .003) significantly influenced the number of forwards, whereas those that mentioned recipes (P = .005) and how to lose weight (P = .003) significantly affected the number of comments. The results underscore the need for further research to elucidate the effectiveness of social media in impacting weight loss, as well as how they may supplement traditional health promotion and behavior interventions for weight loss.


A case of left leg necrotizing fasciitis caused by streptococcus pyogenes in a healthy Japanese man.
•We experienced a case of necrotizing fasciitis (NF) due to Group A streptococcus in a healthy Japanese man.•Cutaneous manifestations with NF can be initially minimal.•It is important to recognize that one of the characteristic symptoms of NF is severe pain out of proportion.•When NF is suspect, emergent surgical exploration and debridement are required.


Inhibition of cystathionine gamma-lyase and the biosynthesis of endogenous hydrogen sulphide ameliorates gentamicin-induced nephrotoxicity.
Clinical use of gentamicin over prolonged periods is limited because of dose- and time-dependent nephrotoxicity. Primarily, lysosomal phospholipidosis, intracellular oxidative stress and heightened inflammation have been implicated. Hydrogen sulphide is an endogenously produced signal transduction molecule with strong anti-inflammatory, anti-apoptotic and cytoprotective properties. In several models of inflammatory disease however, tissue damage has been associated with increased activity of cystathionine gamma-lyase, biosynthesis of hydrogen sulphide and activation of leukocytes. The aim of this study was to determine effects of inhibiting hydrogen sulphide biosynthesis by DL-propargyl glycine (an irreversible inhibitor of cystathionine gamma-lyase) on inflammation, necrosis and renal function, following treatment with gentamicin in rats. Adult female Sprague-Dawley rats were divided into six groups and treated with; physiological saline, sodium hydrosulphide, DL-propargyl glycine, gentamicin, a combination of gentamicin and sodium hydrosulphide, or gentamicin and DL-propargyl glycine respectively. Gentamicin-induced histopathological changes including inflammatory cell infiltration and tubular necrosis were attenuated by co-administering gentamicin with DL-propargyl glycine (P<0.05 compared to saline controls and P<0.05 compared to gentamicin only). Similarly, DL-propargyl glycine caused a significant reduction (P<0.05) in lipid peroxidation, production of superoxide and the activation of tumour necrosis factor-alpha in gentamicin-treated animals. These data show that protective effects of DL-propargyl glycine might be related at least in part, to the reduced inflammatory responses observed in animals treated with both gentamicin and DL-propargyl glycine. Thus, enzyme systems involved in hydrogen sulphide biosynthesis may offer a viable therapeutic target in alleviating the nephrotoxic effects of gentamicin.


Unprecedented reactivity of an aluminium hydride complex with ArNH2BH3: nucleophilic substitution versus deprotonation.
Reaction of DIPPnacnacAlH(2) with DIPPNH(2)BH(3) did not give the anticipated deprotonation but nucleophilic substitution at B was observed instead. The product DIPPnacnacAl(BH(4))(2) was isolated and structurally characterized. Nucleophilic displacement at B might play a role in mechanistic pathways related to metal amidoborane complexes.


Corneal morphology and visual outcomes in LASIK patients after orthokeratology: A pilot study.
For the first time, this study shows that corneas that previous undergone orthokeratology treatment do not respond differently to LASIK compared with previous soft contact lens wear experience. To evaluate and compare the corneal morphology and visual outcomes of long-term soft and orthokeratology (OK) contact lens fitting in wearers undergoing corneal refractive surgery (LASIK) for myopia correction. Sixteen (16) myopic patients wearing hydrophilic soft contact lens (SCL, n = 8 subjects, control group) and OK (n = 8 subjects, OK group) lenses who undergone LASIK were retrospectively evaluated. Preoperative fitting of contact lenses and one year postoperative were studied using Pentacam (Oculus, Inc. GmbH, Wetzlar, Germany). Corneal pachymetry and volume, corneal topography, anterior and posterior surface elevation data and the anterior surface aberrometry of the cornea were recorded and used for fitting. Age, refractive error and topographic parameters before LASIK did not showed statistically significant differences between the two study groups. LASIK post-treatment results showed identical changes in both control and OK groups and did not show significant differences in all the parameters evaluated. The changes on corneal parameters and HOA due to refractive surgery intervention were not different between Control and OK group (p > 0.050). Corneal changes due to OK treatment are reversible after its discontinuation. The present study gives an overview of how OK does not impair future LASIK surgery for the correction of myopia and does not influence the success/results of such intervention. These findings suggest that OK CL wear does not change corneal biomechanics and does not compromise a possible LASIK refractive surgery. Although this is a pilot study and there is a need of evaluate this results/changes in future studies.


Association of long noncoding RNA MALAT1 with the radiosensitivity of lung adenocarcinoma cells via the miR-140/PD-L1 axis.
To investigate the effect of MALAT1 on the modulating the radiosensitivity of lung adenocarcinoma, through regulation of the expression of the miR-140/PD-L1 axis. The online databases UALCAN and dbDEMC were searched for the MALAT1 and miR-140 expressions in patients with lung adenocarcinoma (LUAD), respectively. Then analyze their relationship with overall survival rates separately in the UALCAN and ONCOMIR databases. A functional analysis was performed for A549 cells by transfecting small-interfering RNAs or corresponding plasmids after radiotherapy. Xenograft models of LUAD exposed to radiation were established to further observe the effects of MALAT1 on the radiosensitivity of LUAD. The luciferase assay and reverse transcription-polymerase chain reaction were performed to assess the interaction between miR-140 and MALAT1 or PD-L1. MALAT1 were overexpressed in human LUAD tumor tissues and cell lines, while miR-140 were inhibited. MALAT1 knockdown or miR-140 increase suppressed cell proliferation and promoted cell apoptosis in LUAD after irradiation. LUAD xenograft tumor growth was also inhibited by MALAT1 knockdown combined with irradiation. miR-140 could directly bind with MALAT1 or PD-L1. Furthermore, MALAT1 knockdown inhibited PD-L1 mRNA and protein expressions by upregulating miR-140 in LUAD cells. MALAT1 may function as a sponge for miR-140a-3p to enhance the PD-L1 expression and decrease the radiosensitivity of LUAD. Our results suggest that MALAT1 might be a promising therapeutic target for the radiotherapy sensitization of LUAD.


Modification of human pancreatic amylase isozymes by peptidoglutaminase I and II.
The effects of peptidoglutaminase (PGln-ase) I and II on human pancreatic juice amylase purified as an isozyme were investigated. Several amylase isozymes were formed which corresponded to minor components of pancreatic amylase isozymes, indicating that appearance of amylase isozymes are due to enzymic deamidation. A similar result was observed when the purified amylase isozyme was incubated with the supernatant of human pancreatic juice whose amylase was previously removed by adsorption onto raw corn starch. These findings are discussed in connection with amylase isozymes in the sera of the patients suffering from pancreatic inflammation.


[Survey on blood pressure and serum lipids in Hei Yi Zhuang Chinese living in Guangxi].
To investigate the levels of blood pressure and serum lipids, and examine the relationship between hypertension and hyperlipidemia in Hei Yi Zhuang Chinese living in Guangxi. A total of 1056 people of Hei Yi Zhuang ethnicity were studied. Blood pressure, body height, body weight, and serum levels of lipids and apolipoprotein were measured. The data were compared with those in 925 people of Han ethnicity, who live in the same region. Systolic blood pressure and pulse pressure were significantly higher in Hei Yi Zhuang than Han Chinese (P < 0.001). The prevalence of isolated systolic hypertension and hypertension was also significantly higher in Hei Yi Zhuang than Han Chinese (P < 0.001). Serum concentrations of total cholesterol, triglycerides, low-density lipoprotein cholesterol, and apolipoprotein (Apo) B, and the prevalence of hypercholesterolemia and hyperlipidemia were significantly lower in Hei Yi Zhuang than Han Chinese (P < 0.05). Serum concentrations of high-density lipoprotein cholesterol and the Apo A1 to Apo B ratio were significantly higher in Hei Yi Zhuang than Han Chinese (P < 0.001). The prevalence of hypertension in Hei Yi Zhuang Chinese was positively associated with triglycerides (r = 0.425, P < 0.05), whereas the prevalence of hypertension in Han Chinese was positively correlated with total cholesterol (r = 0.623, P < 0.001). The present study revealed a significant difference in blood pressure and serum lipids between Hei Yi Zhuang and Han ethnic groups, and an association between hypertension and hyperlipidemia.


Dermatoscopic evaluation and histopathological correlation of acquired dermal macular hyperpigmentation.
Acquired dermal macular hyperpigmentation (ADMH) is a hypernym encompassing Riehl's melanosis, lichen planus pigmentosus, and ashy dermatoses that show significant clinicopathological overlap. We sought to describe the dermatoscopic features of ADMH and correlate them with histopathological findings. This was a prospective observational study performed in two phases. A detailed clinical and dermatoscopic examination was performed, and skin biopsies were obtained in 51 patients. Two dermatologists and a blinded dermatopathologist studied archived dermatoscopic images and histopathology specimens, respectively. Dermatoscopic features noted were (i) pigment structures; dots (82.4%), globules (66.7%) and blotches (56.9%) that spared the eccrine and hair follicle openings; (ii) telangiectasia (82.4%); (iii) accentuation of the normal pseudoreticular pigmentary network (33.3%); (iv) owl's eye structures (15.7%). Four dermatoscopic grades of disease severity were identified: grade 1 - dotted; grade 2 - Chinese letter; grade 3 - reticulate; and grade 4 - diffuse. Density of melanin incontinence on histopathology correlated positively with size of pigment structures (r = 0.7, P < 0.000) and grades of disease severity (r = 0.75, P < 0.000) on dermatoscopy. Increasing grades of disease severity can be detected dermatoscopically, which correlate well with histopathological features. A carefully performed dermatoscopy aids in better patient counseling regarding disease severity.


Biochar-based asymmetric membrane for selective removal and oxidation of hydrophobic organic pollutants.
Hydrophobic organic pollutants (HOCs) in the complex groundwater and soil pose serious technical challenges for sustainable remediation. Herein, an asymmetric membrane (PCAM), inspired by the plant cuticle, was comprised of a top polydimethylsiloxane layer being selectively penetrable to HOCs from complex solution with humic acid, followed by transfer and catalyst layers with biochar pyrolyzed by 300 °C (BC300) and 700 °C (BC700). The PCAM triggered the advanced oxidation of the coming pollutant. The graphitized biochar layer of the PCAM acted as catalysts that induced HOC removal through a non-radical oxidation pathway. Compared to one type biochar membrane, the sequential multi-biochar composite membrane had a faster removal efficiency. The greater uptake and transport performance of multi-biochar composite membrane could be due to the larger pore size and distribution properties of PCAM physicochemical properties and oxidative degradation of peroxymonosulfate. The developed PCAM technology benefits from selective adsorption and catalytic oxidation and has the potential to be applied in complex environmental restoration.


Radiocesium distribution and fluxes in the typical Cryptomeria japonica forest at the late stage after the accident at Fukushima Dai-Ichi Nuclear Power Plant.
The Fukushima-derived radiocesium distribution in the typical Japanese cedar (Cryptomeria japonica D. Don) forest ecosystem was determined. In four years after the Fukushima accident, about 74% of the total radiocesium inventory was localized in soil, 20% was in the litter, and only 6% was associated with the aboveground biomass. Most of the radiocesium that was initially intercepted by the tree canopies has been already transported to the ground surface. The importance of the processes for removal of radiocesium from the tree canopies decreased in the order litterfall > throughfall >> stemflow. Within the tree compartments, the largest radiocesium activity fraction, about 46%, was observed in old foliage, which indicates that the process of removal of the initial deposit from the tree crowns has not yet completed. The aggregate soil-to-wood transfer factor was 1.1⋅10-3 m2 kg-1 d.w., which is close to the geometric means of transfer factors recommended by IAEA for other coniferous tree species. Further studies in Fukushima forest are necessary to assess the variation of this parameter under various soil-landscape conditions. Presence of the residues of the initial deposits does not allow to obtain the accurate values of the annual radiocesium fluxes in the ecosystem. Based on the conservative assumptions, the ranges of the fluxes were estimated. Analysis of the flux structures shows that up to percents of the total radiocesium activity in the ecosystem may be involved into biogenic cycling.


Efficacy of Internal Limiting Membrane Flap Techniques with Vitrectomy for Macular Detachment Associated with an Optic Disc Pit.
To compare the anatomical and functional outcome of adjuvant pars plana vitrectomy (PPV) procedures using the techniques of translocation of an internal limiting membrane (ILM) flap and transplantation of an inverted ILM flap for the treatment of chronic and/or refractory optic disc pit (ODP) maculopathy. In this prospective interventional case series study, 9 patients (9 eyes) with chronic and/or refractory ODP maculopathy underwent PPV with either translocation of an ILM flap or transplantation of an inverted ILM flap as adjuvant techniques along with gas tamponade. The anatomical success, rates of macular reattachment, and visual improvement were assessed. The mean preoperative central retinal thickness (CRT) was 723.4 µm (range: 366-1,151). The mean postoperative CRT was 398.1 ± 212.2 µm (range: 210-758). An increased preoperative CRT was associated with a lower chance of postoperative reattachment of the macula (p = 0.047). The overall reattachment rate at the end of the follow-up period was 56% (n = 5). The mean preoperative visual acuity (logMAR unit [Snellen acuity]) was 0.48 (20/60) (range: 1.30 [20/400] to 0.10 [20/25]). The mean change in best corrected visual acuity (BCVA) was 0.48 ± 0.233 logMAR units (approx. 3 lines of visual improvement). ILM flap techniques are logical and straightforward approaches as adjuvants to PPV treatment of ODP maculopathy. They could be viable adjuvant treatments for improvement in BCVA and CRT in patients with ODP maculopathy.


Socioeconomic status, lifestyle factors and oral premalignant lesions.
Several studies have suggested that low socioeconomic status (SES) is associated with a higher risk of oral cancer, but the association with oral premalignant lesions has not yet been explored. The aim of this study was to examine the association of education, occupation, income and SES index with oral premalignant lesions. A case-control study was conducted with data from the baseline screening of a randomized oral cancer screening trial in Kerala, India. There were a total of 927 oral leukoplakia, 170 oral submucous fibrosis, 100 erythroplakia and 115 multiple oral premalignant lesion cases and 47,773 controls. Subjects with high SES index had protective ORs for oral premalignant lesions, ranging from 0.6 to 0.7, after adjustment for age, sex, BMI, tobacco chewing, smoking, drinking and fruit/vegetable intake. Higher education levels were also associated with decreased risk of all four oral premalignant lesions. Protective ORs for income were observed for oral leukoplakia and possibly oral submucous fibrosis and erythroplakia. SES may be associated with oral premalignant lesions because of access to medical care, health related behaviors, living environment or psychosocial factors. Though the mechanism for the association is not clear, higher SES index, education and income were associated with decreased risk of oral premalignant lesions in our study.


Intraluminal calcium as a primary regulator of endoplasmic reticulum function.
The concentration of Ca2+ inside the lumen of endoplasmic reticulum (ER) regulates a vast array of spatiotemporally distinct cellular processes, from intracellular Ca2+ signals to intra-ER protein processing and cell death. This review summarises recent data on the mechanisms of luminal Ca2+-dependent regulation of Ca2+ release and uptake as well as ER regulation of cellular adaptive processes. In addition we discuss general biophysical properties of the ER membrane, as trans-endomembrane Ca2+ fluxes are subject to basic electrical forces, determined by factors such as the membrane potential of the ER and the ease with which Ca2+ fluxes are able to change this potential (i.e. the resistance of the ER membrane). Although these electrical forces undoubtedly play a fundamental role in shaping [Ca2+](ER) dynamics, at present there is very little direct experimental information about the biophysical properties of the ER membrane. Further studies of how intraluminal [Ca2+] is regulated, best carried out with direct measurements, are vital for understanding how Ca2+ orchestrates cell function. Direct monitoring of [Ca2+](ER) under conditions where the cytosolic [Ca2+] is known may also help to capture elusive biophysical information about the ER, such as the potential difference across the ER membrane.


[Dependence of the chromatin condensation process on the temperature and ionic strength of the media: investigation using gel electrophoresis in low density agarose].
Conformational mobility of 30 nm nucleosomal fiber under temperature variations at different ionic strength of the medium has been analyzed. A new property of chromatin organization has been characterized, namely, nucleosomal solenoid condensation in response to increase of temperature. This property is analogous to salt-induced condensation and becomes particularly prominent at low ionic strength. In this context previously obtained data on changes in the DNA linking number of topological domains are discussed. It is concluded that these changes probably arise from modification of supernucleosomal level of chromatin organization.


Common genetic polymorphisms in pre-microRNAs and risk of bladder cancer.
At present, inconsistent association between single nucleotide polymorphism (SNP) in pre-miRNAs (hsa-mir-196a2 rs11614913 C/T, hsa-mir-499 rs3746444 A/G, and hsa-mir-146a rs2910164 C/G) and bladder cancer were obtained in limited studies. We performed a case-control study to test whether these three common polymorphisms are associated with bladder cancer. One hundred fifty-nine patients affected by bladder cancer and 298 unrelated healthy subjects were enrolled in the study. Using polymerase chain reaction-restriction fragment length polymorphism assay (PCR-RFLP), genotypes of these three SNPs were determined, and their associations with bladder cancer, as well as with clinic pathological factors, and tumor progression were analyzed. No association between bladder cancer risk and variant allele of hsa-mir-196a2 rs11614913 C/T, hsa-mir-499 rs3746444 A/G, or hsa-mir-146a rs2910164 C/G was observed. Heterozygous genotype (CT genotype) of rs11614913 was associated with a significantly decreased bladder cancer risk (P = 0.004, OR = 0.56, 95 % CI = 0.38-0.83). Further stratified analyses showed that rs2910164 is associated with the tumor stage in a recessive model and with metastasis in a dominant model (P = 0.012, OR = 0.20, 95 % CI = 0.05-0.72 and P = 0.04, OR = 2.63, 95 % CI = 1.03-6.67, respectively). No association between hsa-mir-499 rs3746444 A/G and bladder cancer was observed. Our results suggested hsa-mir-196a2 rs11614913 C/T is associated with a significantly decreased risk of bladder cancer and hsa-mir-146a rs2910164 GG genotype is associated with clinical stage and metastasis in bladder cancer.


Fate of 5-fluorouracil, doxorubicin, epirubicin, and daunorubicin in hospital wastewater and their elimination by activated sludge and treatment in a membrane-bio-reactor system.
Antineoplastic agents are applied in cancer therapy and end up in hospital wastewater by human excretions. In this study, the raw wastewater of the sewer of the oncologic in-patient treatment ward of the Vienna University Hospital was monitored for 98 d over 2 years for the cytostatics 5-fluorouracil (5-FU), doxorubicin (DOX), epirubicin, and daunorubicin. In a next step, the elimination of the drugs by a membrane-bio-reactor system was investigated. In addition, their fate in wastewater and elimination by activated sludge was investigated with radio-labelled substances. During the monitoring periods, concentration levels ranging from <8.6 to 124 microgl(-1) for 5-FU and from <0.26 to 1.35 microgl(-1) for DOX were determined. The concentrations analysed fitted the lower ranges calculated by an input-output model. Treatment of oncologic wastewater in the membrane bio-reactor as well as the analysis of the effluents of the Vienna University Hospital resulted in concentrations below the limit of detection. Investigations with radio-labelled compounds showed that 5-FU is eliminated from the liquid phase below the limit of detection. But, up to 25% of radio-labelled equivalents of the drug's amount were found in the gaseous phase and only a marginal part in the solid phase, this indicates that at least one part of the drug is biodegraded. For the anthracyclines more than 90% was eliminated from the liquid phase. In this case, adsorption to suspended solids seems to be the major elimination pathway, as up to 30% of the radio-labelled equivalents of the drug's amount was detected in the solid phase. Our results indicate that the investigated anticancer drugs are eliminated by sewage treatment plants, either by biodegradation or adsorption.


Distribution, sources and risk assessment of polycyclic aromatic hydrocarbons in surface sediments from the Yellow Sea coast, China.
To study the distribution, sources, ecological/health risks, and the impact of regional economic variations on polycyclic aromatic hydrocarbons (PAHs) contaminations along the coast of the Yellow Sea in China, sediments from a broad coastal coverage were collected and analyzed. The total contents of 16 priority PAHs varied between 1.4 and 1675.9 ng/g except in the site of H18 (3191.4 ng/g) adjacent to Qingdao City, with an average value of 295.7 ng/g. PAH pollution along the coast presented a distinctive geographical feature, which was closely linked to local human activities, such as Rongcheng with industrial zones and aquacultural areas, and Yancheng Wetland with developed aquaculture. The source analysis results indicated that PAHs were mainly from pyrolytic sources, with smaller contributions from petroleum spills and combustion. Risk assessment suggested that PAH pollution along the Yellow Sea coast showed negligible biological risks and health risks in most areas.


Risk factors for prehypertension and their interactive effect: a cross- sectional survey in China.
Individuals with prehypertension are at higher risk of developing hypertension and cardiovascular diseases, while the interaction between factors may aggravate prehypertension risk. Therefore, this study aimed to evaluate the risk factors for prehypertension in Chinese middle-aged and elderly adults, and explore the potentially interactive effect of evaluated factors. All the participants that came from a community based cross-sectional survey were investigated in Bengbu, China, by being interviewed with a questionnaire. Body mass index (BMI), Waist circumference (WC) and lipid accumulation product (LAP) that reflect participants' obesity were also calculated. In addition, logistic regression model was applied to explore the risk factors of prehypertension, followed by the assessment of the interactive effects between risk factors on prehypertension by the relative excess risk due to interaction (RERI), attributable proportion due to interaction (AP) and synergy index (SI). A total of 1777 participants were enrolled in this study, among which the prevalence of normtension, prehypertension and hypertension were 41.70%, 33.93% and 24.37% respectively. According to the multivariate logistic regression analysis, age (OR: 1.01, 95%CI: 1.00-1.02), smoking (OR: 1.67, 95%CI: 1.22-2.29), family history of cardiovascular diseases (OR: 1.52, 95%CI: 1.14-2.02), general obesity (OR: 1.51, 95%CI: 1.15-1.97) and LAP (OR: 2.58, 95%CI: 1.76-3.80) were all defined as the major factors that significantly related with the risk of prehypertension. When identifying prehypertension risk, the receiver-operating characteristics (ROC) curves (AUC) analysis indicated that LAP performed better than BMI in males (Z = 2.05, P = 0.03) and females (Z = 2.12, P = 0.03), but was superior to WC only in females (Z = 2.43, P = 0.01). What is more, there were significant interactive effects of LAP with family history of cardiovascular diseases (RERI: 1.88, 95%CI: 0.25-3.51; AP: 0.44, 95%CI: 0.20-0.69; SI: 2.37, 95%CI: 1.22-4.60) and smoking (RERI: 1.99, 95%CI: 0.04-3.93; AP: 0.42, 95%CI: 0.17-0.67; SI: 2.16, 95%CI: 1.68-4.00) on prehypertension risk. The value of AP (0.40, 95%CI: 0.03-0.77) also indicated a significant interaction between family history of cardiovascular diseases and smoking on prehypertension. Prehypertension is currently prevalent in Chinese adults. This study indicated that age, family history of cardiovascular diseases, smoking, general obesity and LAP were significantly related with prehypertension risk. Furthermore, interactive effects on risk of prehypertension had been demonstrated in this study as well, which would help researchers to build strategy against prehypertension more comprehensively and scientifically.


Evaluation of the hypoglycaemic effect of Memecylon umbellatum in normal and alloxan diabetic mice.
Oral administration of an alcoholic extract of the leaves of Memecylon umbellatum led to a significant lowering of serum glucose levels in normal and alloxan-induced diabetic mice. Although the mechanism of action is unknown, the magnitude of glucose reduction in both the animal models is encouraging. The results indicate that M. umbellatum has interesting possibilities as a source of oral hypoglycaemic agents.


Reliability of Respiratory System Compliance Calculation During Assisted Mechanical Ventilation: A Retrospective Study.
To compare respiratory system compliance (C rs ) calculation during controlled mechanical ventilation (MV) and, subsequently, during assisted MV. This is a single-center, retrospective, observational study. This study was conducted on patients admitted to Neuro-ICU of Niguarda Hospital (tertiary referral hospital). We analyzed every patient greater than or equal to 18 years old having a C rs measurement in controlled and in assisted MV within 60 minutes. Plateau pressure (P plat ) was considered reliable if it was deemed visually stable for at least 2 seconds. Inspiratory pause was incorporated to detect P plat in controlled and assisted MV. Calculation of C rs and driving pressure were achieved. A total of 101 patients were studied. An acceptable agreement was found (Bland-Altman plot bias -3.9, level of agreement upper 21.6, lower -29.6). C rs in assisted MV was 64.1 (52.6-79.3) and in controlled MV it was 61.2 (50-71.2) mL/cm H 2o ( p = 0.006). No statistical difference was found in C rs (assisted vs controlled MV) when peak pressure was lower than P plat nor when peak pressure was higher than P plat . A P plat visually stable for at least 2 seconds leads to reliable C rs calculation during assisted MV.


A human neoplastic hematopoietic cell line producing a fibroblast type of interferon.
1301 is a subline of the EBV-genome negative T leukemia line CCRF-CEM. IF was induced by Sendai virus. By use of neutralizing antisera and by studies of some physical properties it could be shown that IF was of the fibroblast type. This was confirmed by its antiviral effect on heterologous cell lines.


A pilot study of ondansetron plus metopimazine vs. ondansetron monotherapy in children receiving highly emetogenic chemotherapy: a Bayesian randomized serial N-of-1 trials design.
Chemotherapy-induced nausea and vomiting is problematic in paediatric brain tumour treatment protocols which often discourage the use of corticosteroids as anti-emetics. The dopamine receptor antagonist, metopimazine, is an effective anti-emetic in combination with ondansetron in adults. The present study was designed to assess its efficacy in children with cancer, a group in which it has not been studied previously. We conducted a series of randomized, multiple-crossover, double-blind, placebo-controlled N-of-1 trials comparing ondansetron/metopimazine with ondansetron monotherapy in children with brain tumours receiving highly emetogenic therapy and combined the individual results using Bayesian statistical modeling. Ten of twelve enrolled patients completed at least one chemotherapy cycle on study (median=2.5 cycles, range 1-11). Two patients were unable to complete any cycles, and a further three patients withdrew from the study prior to completing all cycles because of an inability to tolerate the taste of the study drug. Combination therapy increased the proportion of days during which patients had no emesis (overall odds ratio=1.52, 95% credible region=0.32-6.40, probability of odds ratio>1=72%), decreased the number of emetic episodes per day (overall rate ratio=0.67, 95% credible region=0.15-3.14, probability of rate ratio<1=75%) and decreased parents' ratings of their child's distress. The drug was more effective during the delayed chemotherapy phase than the acute phase. No adverse events were attributed to metopimazine. Based on this pilot study, we believe that the high likelihood that metopimazine is an effective adjunct to ondansetron monotherapy suggests that this combination therapy is worthy of further study in children receiving emetogenic chemotherapy.


Effect of Primary Prophylactic Antiseizure Medication for Seizure Prevention Following Intracerebral Hemorrhage in the ERICH Study.
Intracerebral hemorrhage (ICH) has the highest morbidity and mortality rate of any stroke subtype and clinicians often administer prophylactic antiseizure medications (ASMs) as a means of preventing post-stroke seizures, particularly following lobar ICH. However, evidence for ASM efficacy in preventing seizures and reducing disability is lacking given limited randomized trials. Herein, we report analysis from a large prospective observational study that evaluates the effect of primary prophylactic ASM administration on seizure occurrence and disability following ICH. Primary analysis was performed on 1630 patients with ICH enrolled in the ERICH study. A propensity score for administration of prophylactic ASM was developed and patients were matched by the closest propensity score (difference < 0.1). McNemar's test was used to compare occurrence of in-hospital seizure and disability, defined by modified Rankin Score (mRS) ≥ 3 at 3 months post ICH. Of the 815 matched pairs of patients treated with primary prophylactic ASM, there was no significant difference in seizure occurrence (p = 0.4631) or disability (p = 0.4653). Subset analysis of 280 matched pairs of patients with primary lobar ICH similarly revealed no significant difference in seizure occurrence (p = 0.1011) or disability (p = 1.00) between prophylactically treated and untreated patients. Although current guidelines do not recommend primary prophylactic ASM following ICH, clinical use remains widespread. Data from the ERICH study did not find an association between administering primary prophylactic ASM and preventing seizures or reducing disability following ICH, thus providing evidence to influence clinical practice and patient care.


Past, present, and future perspectives of heparins in clinical settings and the role of impaired renal function.
Heparin, whose discovery goes back one hundred years, was first detected as a thromboplastin from liver tissue, and its anticoagulant action was only identified later. The procoagulant action of heparin, which was later characterized as an immunologic reaction by binding to platelet-factor IV, presenting as heparin-induced thrombocytopenia, remains as a side effect. For more than 60 years heparin has been the immediate anticoagulant of choice in many clinical indications. Further development of heparins resulted in the production of low-molecular weight heparins and Fondaparinux, which substituted heparin for many indications and has received many more new indications, including administration for non-anticoagulant purposes. This development is still ongoing and has resulted in more than 300 registered clinical trials at the end of 2015. All types of heparins are still investigated in patients with impairment of renal function to improve the safety of treatment. New therapeutic strategies for the prevention and treatment of thromboembolism, as well as of the non-anticoagulant actions of natural and modified types of heparins, are studied intensively. The clinical study designs include treatment with vitamin-K and non-vitamin K oral anticoagulants. Consequently, heparins, low-molecular weight heparins and Fondaparinux play an important role in the human health care system.


Extended Signal-Space Separation Method for Improved Interference Suppression in MEG.
Magnetoencephalography (MEG) signals typically reflect a mixture of neuromagnetic fields, subject-related artifacts, external interference and sensor noise. Even inside a magnetically shielded room, external interference can be significantly stronger than brain signals. Methods such as signal-space projection (SSP) and signal-space separation (SSS) have been developed to suppress this residual interference, but their performance might not be sufficient in cases of strong interference or when the sources of interference change over time. Here we suggest a new method, extended signal-space separation (eSSS), which combines a physical model of the magnetic fields (as in SSS) with a statistical description of the interference (as in SSP). We demonstrate the performance of this method via simulations and experimental MEG data. The eSSS method clearly outperforms SSS and SSP in interference suppression regardless of the extent of a priori information available on the interference sources. We also show that the method does not cause location or amplitude bias in dipole modeling. Our eSSS method provides better data quality than SSP or SSS and can be readily combined with other SSS-based methods, such as spatiotemporal SSS or head movement compensation. Thus, eSSS extends and complements the interference suppression techniques currently available for MEG. Due to its ability to suppress external interference to the level of sensor noise, eSSS can facilitate single-trial data analysis, exemplified in automated analysis of epileptic data. Such an enhanced suppression is especially important in environments with large interference fields.


Breast cancer diagnosis and prognosis using a high b-value non-Gaussian continuous-time random-walk model.
To compare the diagnostic performance of mono-exponential model-derived apparent diffusion coefficient (ADC), continuous-time random-walk (CTRW) model-derived Dm, α, β and their combinations in discriminating malignancy of breast lesions, and investigate the association between model-derived parameters and prognosis-related immunohistochemical indices. A total of 85 patients with breast lesions (51 malignant, 34 benign) were analysed in this retrospective study. Clinical characteristics include oestrogen receptor (ER), progesterone receptor (PR), human epidermal receptor 2 (HER2), and Ki-67. The ADC was fitted using a mono-exponential model (b-values = 0, 800 s/mm2), while Dm, α, and β were fitted using a CTRW model. Independent Student's t-test and the Mann-Whitney U-test were used for the comparison of parameters. Discrimination performance was accomplished by receiver operating characteristic (ROC) analysis, and Spearman's correlation analysis was used to explore the association between immunohistochemical indices and diffusion parameters, the statistical significance level was p<0.05. Dm and ADC demonstrated similar performance in differentiating malignant and benign lesions (AUC = 0.928 versus 0.930), while the combination of Dm, α, and β could improve the AUC to 0.969. The combined parameter generated by ADC, Dm, α, and β was effective in identifying the ER+/ER- and PR+/PR- patients. Temporal heterogeneity parameter α correlated significantly with the expression of PR. Diffusion parameters derived from the CTRW model could effectively discriminate the malignancy of breast lesions. Meanwhile, the hormone receptor expression could be distinguished by combined diffusion parameters, and have the potential to reflect the prognosis.


Early steps in androgen biosynthesis: from cholesterol to DHEA.
Sex steroids, both androgens and oestrogens, are made from dehydroepiandrosterone (DHEA). The biosynthesis of DHEA from cholesterol entails four steps. First, cholesterol enters the mitochondria with the assistance of a recently described factor called the steroidogenic acute regulatory protein (StAR). Mutations in the StAR gene cause congenital lipoid adrenal hyperplasia. Next, cholesterol is converted to pregnenolone by the cholesterol side chain cleavage enzyme, P450scc. Mutations in the gene for P450scc and for its electron transfer partners, ferredoxin reductase and ferredoxin, have not been described and are probably incompatible with term gestation. Third, pregnenolone undergoes 17 alpha-hydroxylation by microsomal P450c17. Finally, 17-OH pregnenolone is converted to DHEA by the 17,20 lyase activity of P450c17. Isolated 17,20 lyase deficiency is rare, but the identification of its genetic basis and the study of P450c17 enzymology have recently clarified the mechanisms by which DHEA synthesis may be regulated in adrenarche, and have suggested that the lesion underlying polycystic ovary syndrome might involve a serine kinase.


Plankton time - space dynamics in German Bight - a systems approach.
Long term continuous plankton measurements at Helgoland (North Sea) have provided a set of data which could be used for ecological functional analysis with respect to prey predator theory. Local dynamics display trophic feedback between selected populations. Phytoplankton, small copepods, Noctiluca miliaris, Pleurobrachia pileus and Beroe gracilis conform with theoretical assumptions. The functional relationships are less significant in averaged population dynamics compared with single ear processes. The local prey-predator cycles are to be understood as population waves travelling through German Bight. Such population waves over an area of 18 000 km2 have been investigated and are displayed for the above given zooplankton populations as computer graphics and analysed in their progression for the population of P. pileus.


Making β cells from adult tissues.
β-Cell replacement represents an attractive prospect for diabetes therapy. Although much hope has been placed on derivation of insulin-producing cells from human pluripotent stem cells, this approach continues to face considerable challenges. Cells from adult human tissues, with both stem/progenitor and mature phenotypes, offer a possible alternative. This review summarizes recent progress in two major strategies based on this cell source, ex vivo expansion of human islet β cells and conversion of non-β cells into insulin-producing cells by nuclear reprogramming, and examines the obstacles that remain to be overcome for bringing these strategies closer to clinical application in diabetes therapy.


Predicting Patients Found to Have Malignancy at Nipple Duct Surgery.
The unexpected diagnosis of breast cancer following total duct excision is distressing for patients. Despite advances in radiology and the description of suspicious nipple discharge, pre-operative diagnosis of malignancy still evades us. The aim of this study was to review the pathological findings of total duct excision and microdochectomy with reference to pre-operative symptoms, ultrasound, or mammographic findings and identify features associated with increased likelihood of malignant disease. Data were collected retrospectively of all patients who underwent total duct excision surgery in a single centre (2011-2017). Pre-operative demographics, symptoms, and imaging findings were recorded and correlated with subsequent pathology. 214 patients underwent total duct excision; data were available for 211. Median age was 53 years. 175/211 (82.9%) patients had benign pathology (duct ectasia, papilloma without atypia, fibrocystic change) on final histological examination, 21/211 (10%) had "risk" lesions (papilloma with atypia, atypical ductal hyperplasia), and 15/211 (7.1%) had malignancy (ductal carcinoma in situ). Of the 15 patients with malignant lesions, 6/15 (40%) had normal imaging (M1, U1). 71/211 (33.6%) had normal imaging (M1, U1): 60/71 (84.5%) had benign disease, 5/71 (7%) had "risk" lesions, and 6/71 (8.5%) had malignant lesions. 83/211 (39.3%) patients presented with bloody discharge: 64/83 (77.1%) had benign pathology, 9/83 (10.8%) risk, and 10/83 (12%) malignancy. 38/211 (18%) patients presented with non-bloody discharge: 32/38 (84.2%) had benign disease, 4/38 (10.5%) risk, and 2/38 (5.3%) malignant lesions. Neither imaging nor presenting symptoms correlate with the likelihood of malignant disease being present at final pathology. Even with advances in pre-operative diagnosis, total duct excision remains an essential diagnostic and therapeutic procedure.


An alternative approach to the apex of the left ventricle.
Because of the risk of performing a left ventriculotomy in a patient with a left ventricular mass as well as decreased myocardial function, secondary to a myocardiopathy, my colleagues and I sought an alternate method for removal of the mass. Our decision to follow the procedure to be described in this report provided ideal access to the tumor, and the excellent results obtained in this and a subsequent case established the validity of this alternative to a left ventriculotomy. Although we realize not all masses of this nature need be removed, we present this technique as a useful addition to our armamentarium.


The Amborella genome: an evolutionary reference for plant biology.
The nuclear genome sequence of Amborella trichopoda, the sister species to all other extant angiosperms, will be an exceptional resource for plant genomics.


Is breastfeeding in MS harmful or not? An answer from real-world Czech data.
The influence of breastfeeding and it´s duration on the course of multiple sclerosis (MS) is unclear. Here we analyzed a real-world data for breastfeeding women with MS and their disease course collected from a Czech national registry ReMuS. To identify risk factors associated with not initiating breastfeeding after delivery, to analyze the impact of breastfeeding on the MS disease course, evaluate the assumption, that breastfeeding is not harmful in MS patients, and compare the disease course by breastfeeding status. Using propensity score matching we compared Expanded Disability Status Scale (EDSS), confirmed disease worsening (CDW) and annual relapse rate (ARR) in breastfeeding and non-breastfeeding MS patients according to disease duration, disease modifying treatment (DMT) before pregnancy, last EDSS score before conception, age, and ARR during pregnancy. We also compared these parameters between breastfeeding patients not using a DMT and non-breastfeeding patients who resumed DMT within 3 months after delivery. EDSS, ARR, and CDW were collected at 12, 24, and 36 months after delivery. A total of 1681 pregnancies that ended in delivery were analyzed from 2013 through 2020. Change in ARR and EDSS values and 6-months CDW did not significantly differ between the analyzed groups. Compared with non-breastfeeding women who resumed DMT early after delivery, breastfeeding women with MS did not experience worse clinical outcomes even without initiating a DMT. Breastfeeding in Czech women with MS did not negatively affect the disease course and can be supported. Patients with MS can be treated with certain DMTs alongside breastfeeding and there is no need to stop breastfeeding, if the patient is clinically stable.


Transudative chylothorax: report of two cases and review of the literature.
Transudative chylothorax is a rare entity that has been associated with a limited range of clinical settings. To date, transudative chylothoraces have been described in only 13 patients, most commonly as a result of hepatic cirrhosis. Recognition of the transudative nature of these effusions is important to avoid unnecessary diagnostic testing and inappropriate management strategies. This report describes the presentation, diagnosis and management of two patients with transudative chylothoraces, and provides a brief review of the relevant literature.


Difficulties of children with symptoms of attention-deficit/hyperactivity disorder in processing temporal information concerning everyday life events.
It has been hypothesized that children with attention-deficit/hyperactivity disorder (ADHD) present difficulties in processing time durations. However, so far evidence on this difficulty and its related mechanisms has been unclear and collected only with rating scales or laboratory experimental tasks. The current study examined whether this difficulty can be seen in children carrying out everyday actions (e.g., telephone calls, cooking activities) and to what extent it is influenced by working memory (WM) abilities. In total, 182 children aged 7 to 10 years were included in the study: 91 children with ADHD symptoms and 91 typically developing (TD) children matched for gender and other characteristics. We administered sequence reordering, time reproduction, and duration comparison tasks, and as stimuli we used six movies lasting 10 to 60 s showing three women completing six different actions. We also collected measures of verbal and visuospatial WM tests (digit span and Corsi task). Children with ADHD symptoms tended to underestimate the long durations and were less accurate than TD children in remembering the exact order of events and in comparing the duration of two different events. These difficulties appeared to be related to WM abilities.


Ossification of human thyroid cartilage. Scanning electron microscopic study.
The architecture of the cartilage already developed within ossified areas have shown apparent differences not only depending on their location within cartilage territory but also due to their chemical composition. The cartilage areas exhibiting a markedly advanced ossification process have shown rather high concentration level of Ca, P and Si.


Functional properties of ryanodine receptors from rat dorsal root ganglia.
The properties of ryanodine receptors (RyRs) from rat dorsal root ganglia (DRGs) have been studied. The density of RyRs (Bmax) determined by [3H]ryanodine binding was 63 fmol/mg protein with a dissociation constant (Kd) of 1.5 nM. [3H]Ryanodine binding increased with caffeine, decreased with ruthenium red and tetracaine, and was insensitive to millimolar concentrations of Mg2+ or Ca2+. DRG RyRs reconstituted in planar lipid bilayers were Ca2+-dependent and displayed the classical long-lived subconductance state in response to ryanodine; however, unlike cardiac and skeletal RyRs, they lacked Ca2+-dependent inactivation. Antibodies against RyR3, but not against RyR1 or RyR2, detected DRG RyRs. Thus, DRG RyRs are immunologically related to RyR3, but their lack of divalent cation inhibition is unique among RyR subtypes.


Non-additive genetic components contribute significantly to population-wide gene expression variation.
Gene expression variation, an essential step between genomic variation and phenotypic landscape, is collectively controlled by local (cis) and distant (trans) regulatory changes. Nevertheless, how these regulatory elements differentially influence the heritability of expression traits remains unclear. Here, we bridge this gap by analyzing the transcriptomes of a large diallel panel consisting of 323 unique hybrids originated from genetically divergent yeast isolates. We estimated the broad- and narrow-sense heritability across 5,087 transcript abundance traits and showed that non-additive components account for 36% of the phenotypic variance on average. By comparing allelic expression ratios in the hybrid and the corresponding parental pair, we identified regulatory changes in 25% of all cases, with a majority acting in trans. We further showed that trans-regulation could underlie coordinated expression variation across highly connected genes, resulting in significantly higher non-additive variance and most likely in some of the missing heritability of gene expression traits.


Risk factors for reporting adverse events and for study withdrawal in a population-based trial of vitamin D supplementation.
With increasing numbers of randomized controlled trials (RCTs) investigating potential health events of vitamin D supplementation, a better understanding is required of the risk factors for adverse events and for study withdrawals. This analysis aimed to identify baseline risk factors of reporting an adverse event in a multi-year randomized double-blinded placebo-controlled trial of vitamin D supplementation. The secondary aim was to investigate if adverse events were associated with study withdrawals. We analyzed data from the Vitamin D Assessment (ViDA) study: 5110 adults, aged 50-84 years, living in Auckland, New Zealand. Monthly doses of 100,000 IU vitamin D3 or placebo were mailed to participants homes, with a questionnaire to collect data on adverse events and adherence to the study capsule (initially monthly, then 4-monthly). Median follow-up was 3.3 years. Data were analysed using multivariable log-binomial regression and Cox-regression. During the follow-up period, 818 people reported adverse events and 412 withdrew or stopped returning questionnaires. Vitamin D was not associated with reporting of adverse events. Of sociodemographic factors, ethnicity was associated with reporting adverse events: compared to European participants, Maori and Pacific Islander people were more likely to report an adverse event. Non-smokers were more likely to report an adverse event, compared to smokers (adjusted hazard ratio (HR) = 1.80; 95%CI = 1.24, 2.62); as were those who had reported a history of depression (adjusted HR = 1.27; 95%CI = 1.01, 1.60) or a recent cough or cold (adjusted HR = 1.22; 95%CI = 1.03, 1.44) at baseline. Reporting of adverse events was not associated with withdrawals (adjusted HR = 1.12; 95%CI = 0.86, 1.46). These data did not identify any clear pattern in the factors associated with self-reported adverse events, which themselves did not increase risk of withdrawals.


Genetic association of APOA5 and APOE with metabolic syndrome and their interaction with health-related behavior in Korean men.
Genome-wide association studies have been used extensively to identify genetic variants linked to metabolic syndrome (MetS), but most of them have been conducted in non-Asian populations. This study aimed to evaluate the association between MetS and previously studied single nucleotide polymorphisms (SNPs), and their interaction with health-related behavior in Korean men. Seventeen SNPs were genotyped and their association with MetS and its components was tested in 1193 men who enrolled in the study at Seoul National University Hospital. We found that rs662799 near APOA5 and rs769450 in APOE had significant association with MetS and its components. The SNP rs662799 was associated with increased risk of MetS, elevated triglyceride (TG) and low levels of high-density lipoprotein, while rs769450 was associated with a decreased risk of TG. The SNPs showed interactions between alcohol drinking and physical activity, and TG levels in Korean men. We have identified the genetic association and environmental interaction for MetS in Korean men. These results suggest that a strategy of prevention and treatment should be tailored to personal genotype and the population.


The impact of thigmotaxis deprivation on the development of the German cockroach (Blattella germanica).
Thigmotaxis is required in small animals. In this study, we examined how the shelter angle affects the development of German cockroaches, Blattella germanica. Groups and individual cockroaches showed a strong preference for shelters with an angle of ≤40° after 15 min or 24 h in shelter-selection trials. For cockroaches that developed in 90/180-degree shelters, survival and fecundity were low, and the nymphal stage lasted longer. Post-molting transcriptomes of second- and sixth-instar nymphs were analyzed at 12 h and 2 days post-molting. Upregulation was observed in genes related to ATP metabolism and cellular amide metabolism. Chitin-based cuticle development and postembryonic development-related genes were downregulated. The stress responses of cockroaches that developed in shelters with angles of 90° were similar to those of gregarious cockroaches experiencing social isolation. For German cockroaches, environmental tactile stimuli are crucial to development and homeostasis.


Controlled synthesis of Pt nanoparticles via seeding growth and their shape-dependent catalytic activity.
Through a seed-mediated growth route, Pt nanoparticles (NPs) with tunable shape and size were prepared, such as octahedral, cuboctahedral, branched and rice-like. Three nanometer Pt NPs were prepared and dispersed in oleyl amine to form seed solution and then Pt precursor (platinum acetylacetonate (Pt(acac)(2))) was added. Under high temperature, oleyl amine as both reducing and protective agents can reduce Pt precursor to Pt atoms which selectively deposit on seeds surface to form variously structured Pt NPs. By adjusting the reactive conditions (the molar ratio of Pt metals from Pt(acac)(2) and seed (PPS), the seed diameter, the addition route of Pt(acac)(2)), the NPs growth could be controlled to fall into kinetic or thermodynamic regime, producing variously shaped NPs. On the basis of observed results, a reaction mechanism in which the resulting NP shape had strong dependence on c/s (c=precursor concentration, s=available deposition surface area) was figured out. The obtained NPs were supported on black carbon to act as Pt/C catalysts for oxidization of methanol and results show that the catalysts from branched NPs had higher catalytic activity and stability than ones from polyhedral NPs.


Design principles of proton-pumping haem-copper oxidases.
Transmembrane electrochemical proton gradients are used to store free energy in biological systems, and to drive the synthesis of biomolecules and transmembrane transport. These gradients are maintained by membrane-bound proton transporters that employ free energy provided by, for example, electron transfer or light. In recent years, the structures of several membrane proteins involved in proton translocation have been determined, and indicate that both protein-bound water molecules and protonatable amino acid residues play central roles in transmembrane proton conduction. From these structures, in combination with functional studies, have emerged general principles of proton transfer across membranes and control mechanisms for such reactions, in particular with regard to the electron-transfer-driven proton pump cytochrome c oxidase.


Avoidance behaviour of aquatic macroinvertebrates for real-time detection of micropollutant surge in wastewater effluents.
Micropollutants are regularly detected at the outlets of wastewater treatment plants (WWTPs). Across urban and industrial WWTPs, monitoring directives only require assessment for a handful of chemicals via sampling methods that fail to capture the temporal variability in micropollutant discharge. In this study, we develop a biotest for real-time on-line monitoring of micropollutant discharge dynamics in WWTPs effluents. The selected biomonitoring device ToxMate uses videotracking of invertebrate movement, which was used to deduce avoidance behaviour of the amphipod Gammarus fossarum. Organism conditioning was set up to induce a state of minimal locomotor activity in basal conditions to maximise avoidance signal sensitivity to micropollutant spikes. We showed that with a standardised protocol, it was possible to minimise both overall movement and sensitivity to physio-chemical variations typical to WWTP effluents, as well as capture the spikes of two micropollutants upon exposure (copper and methomyl). Spikes in avoidance behaviour were consistently seen for the two chemicals, as well as a strong correlation between avoidance intensity and spiked concentration. A two-year effluent monitoring case study also illustrates how this biomonitoring method is suitable for real-time on-site monitoring, and shows a promising non-targeted approach for characterising complex micropollutant discharge variability at WWTP effluents, which today remains poorly understood.


Bariatric surgery in severe obesity and end-stage heart failure with mechanical circulatory support as a bridge to successful heart transplantation: a case report.
We present the first report of the concurrent use of mechanical circulatory support and bariatric surgery in a morbidly obese patient as a bridge to successful heart transplantation. The concurrent use of mechanical circulatory support and bariatric surgery allowed the patient to lose weight and subsequently to qualify for placement on the heart transplant waiting list. This strategy supports consideration of patients previously deemed unsuitable for heart transplantation owing to morbid obesity. Careful patient selection and strict monitoring of the immunosuppressive regimens are important considerations for a favorable outcome.


CA-125 ovarian cancer associated antigen in cancer and pregnancy: interpretation of enzyme immunoassay and immunoradiometric assay.
Serum CA-125 concentrations were determined using both immunoradiometric assay (IRMA) and enzyme immunoassay (EIA) in 67 patients with various diseases including cancer and in 100 pregnant women with respect to the stage of pregnancy. Correlation of values obtained by the two methods was good except for the first and second trimester of pregnancy. However, IRMA concentrations were 80-200% higher than those obtained by EIA, the larger differences being observed in the critical range of 35-100 U/mL. Therefore, the alternate use of the two methods should be avoided and the cutoff levels should be redefined for each procedure.


Heterogeneous Predisposing Factors and Etiology of Edema of the Uvula in a Spanish Population.
Edema of the uvula (EU) may appear in isolation or in association with clinical manifestations such as urticaria, angioedema, and anaphylaxis. EU may lead to upper airway obstruction, provoking obstructive respiratory distress and asphyxia. Objective: We sought to investigate the etiology of and predisposing factors for EU in a large population of patients referred to an outpatient clinic. In this 3-year follow-up cohort study, 171 patients presenting with EU were identified and classified as having isolated EU or nonisolated EU. The etiology of each patient's condition was studied, and possible predisposing factors were recorded. An allergology work-up and a statistical study (bivariate/multivariate analyses) were performed. The predisposing factors for both groups of EU patients were found to be different. The etiology of the problem was identified for most patients; allergy to Anisakis simplex was the most common cause in both groups. Nonsteroidal anti-inflammatory drugs and antibiotics were also found to be triggers in both groups. Isolated EU was associated with snoring, an elongated uvula, and having experienced previous episodes of EU. We found no associations between groups of EU patients and gender, obesity, smoking, alcohol consumption, personal and family history of atopy, and obstructive sleep apnea. Allergy to A simplex was the most commonly recorded cause.


Parametric evaluation of electrical discharge coatings on nickel-titanium shape memory alloy in deionized water.
Nickel-titanium shape memory alloy (NiTi) has a unique capacity to restore its initial shape after deformation, which is highly applicable to orthopaedic implantations, especially for the minimization of invasive surgeries. The high nickel content of this alloy can lead to unfavourable effects on the human body upon dissolution; thus, a reliable barrier of coatings on the NiTi surface is required to alleviate the nickel migration and increase its biocompatibility. In this paper, analyses of a titanium oxide layer development on NiTi surface using electrical discharge coating (EDC) process is presented. The recast layer thickness, crater sizes, and surface roughness were characterized based on five parameters; polarity, discharge duration, pulse interval, peak current, and gap voltage. The results show that the discharge duration is the most significant parameter to influence all responses, followed by peak current. The surface characteristics of the EDC substrate is depending on the crater formations and is highly correlated with the discharge energy intensity. As a result, appropriate parametric conditions of the electrical discharge coating process can enhance the NiTi surface for future medical applications, without compromising the shape memory effect.


Transradial stenting of a carotid pseudoaneurysm.
Carotid pseudoaneurysms are rare and, if treated endovascularly, are usually approached via the femoral artery. We report the case of transradial stenting of an anastomotic carotid pseudoaneurysm secondary to vertebral transposition through an existing carotid-subclavian bypass.


Generic values for soil-to-plant transfer factors of radiocesium.
There is a need for soil-to-plant transfer factors of radionuclides that take into account all possible crops on all soil varieties to support dose assessment studies. Because only limited experimental data exist for worldwide soil systems, such values should necessarily have a generic character. This paper describes a generic system for 137Cs, mainly based on a reference soil-to-plant transfer factor which depends solely on soil properties such as nutrient status, exchangeable K-content, pH and moisture content. Crops are divided into crop groups, cereals serving as reference group. The transfer of other crop groups can be calculated by multiplying data for cereals by a conversion factor. Existing data present in the IUR (International Union of Radioecologists) databank and in large part the work of a FAO (Food and Agriculture Organisation)/IAEA(International Atomic Energy Agency)/IUR project on tropical systems provided the basis for the derivation of the conversion factors and reference values.


Developing Kaspar: A Humanoid Robot for Children with Autism.
In the late 1990s using robotic technology to assist children with Autistic Spectrum Condition (ASD) emerged as a potentially useful area of research. Since then the field of assistive robotics for children with ASD has grown considerably with many academics trialling different robots and approaches. One such robot is the humanoid robot Kaspar that was originally developed in 2005 and has continually been built upon since, taking advantage of technological developments along the way. A key principle in the development of Kaspar since its creation has been to ensure that all of the advances to the platform are driven by the requirements of the users. In this paper we discuss the development of Kaspar's design and explain the rationale behind each change to the platform. Designing and building a humanoid robot to interact with and help children with ASD is a multidisciplinary challenge that requires knowledge of the mechanical engineering, electrical engineering, Human-Computer Interaction (HCI), Child-Robot Interaction (CRI) and knowledge of ASD. The Kaspar robot has benefited from the wealth of knowledge accrued over years of experience in robot-assisted therapy for children with ASD. By showing the journey of how the Kaspar robot has developed we aim to assist others in the field develop such technologies further.


Self-warming blankets versus active warming by forced-air devices for preventing hypothermia: A systematic review and meta-analysis.
Unintended perioperative hypothermia is a significant complication for patients undergoing anesthesia. Different measures are routinely undertaken to prevent hypothermia and its consequences. The evidence comparing the impact of self-warming blankets and forced-air warming is scarce. Therefore, this meta-analysis aimed to evaluate the efficacy of self-warming blankets compared to forced-air devices regarding the incidence of perioperative hypothermia. We searched the Web of Science, Cochrane Central Register of Controlled Trials, PubMed, and Scopus for relevant studies from inception until December 2022. We included comparative studies with patients allocated to undergo warming using a self-warming blanket or forced air warming. All concerned outcomes were pooled as odds ratios or mean differences (MDs) in the meta-analysis models using Review Manager (RevMan version 5.4). Our results from 8 studies (597 patients) favored self-warming blankets over forced-air devices in terms of core temperature at 120 and 180 minutes after induction of general anesthesia (MD = 0.33, 95% confidence interval [CI] [0.14-0.51], P = .0006), (MD = 0.62, 95% CI [0.09-1.14], P = .02), respectively. However, the overall effect did not favor either of the 2 groups for the incidence of hypothermia (odds ratio = 0.69, 95% CI [0.18-2.62]). Ultimately, self-warming blankets have a more significant effect than forced-air warming systems in terms of maintaining normothermia of core temperature after induction anesthesia. However, the present evidence is not enough to verify the efficacy of the 2 warming techniques in the incidence of hypothermia. Further studies with large sample sizes are recommended.


Endoscopic treatment of Zenker's diverticulum.
The most important aspect of the surgical management of Zenker's diverticulum is probably the cricopharyngeal myotomy. Endoscopic diverticulotomy can be performed with a needle-knife papillotome, which allows simultaneous myotomy of the upper esophageal sphincter. Since 1978, 47 patients (28 men and 19 women 51 to 81 years of age) underwent endoscopic diverticulotomy. Most patients underwent more than one treatment session (mean value 2.2). The procedure was performed with sedation. Tubes were not used, and oral intake of food was begun the first day after the operation. Forty-five (95.74%) patients had no dysphagia or only occasional, mild dysphagia during the postoperative course. No fistula, no recurrent laryngeal paralysis, and no deaths occurred. Endoscopic diverticulotomy seems to be a good choice of therapy at least for patients with associated diseases that increase surgical risk.


Non-enzymatic transcription of an oligodeoxynucleotide 14 residues long.
The 14-mer oligodeoxynucleotide d(C3GC3GC3GC2) acts as a template to facilitate the cooligomerization of guanosine 5'-phospho-2-methylimidazolide and cytidine 5'-phospho-2-methylimidazolide. The predominant products are a series of 3'-5'-linked oligonucleotides, complementary to the template, ranging in length from GGC to GGCGGGCGGGCGGG. Thus simple, non-enzymatic template-directed reactions can result in the accurate transfer of substantial amounts of information from template to products. The 15-mer oligodeoxynucleotide d(C3GC3GC3GC3) is also an efficient template, but directs the synthesis of the same family of products that are formed on the 14-mer template. This unexpected finding is explained by the preferential conversion of the dimer GG to GGC rather than to GGG. These results are interesting in the context of molecular evolution. They suggest that the detailed kinetics of template-directed synthesis could form the basis for the selection of one replicating oligonucleotide from a family of closely related oligonucleotides.


Bilateral C shape configuration in maxillary first molars.
The C-shaped canal is unusual. It is most frequently reported in mandibular molars. A case of bilateral C-shaped canals in maxillary molars is reported here.


Patients' first-year adherence to different anti-osteoporotic therapy after hip fractures.
Osteoporosis medication treatment is recommended after geriatric fractures. However, the percentage of patients receiving anti-osteoporotic treatment after a hip fracture is extremely low. The aim of this study was to evaluate the adherence to different anti-osteoporotic medications in elderly patients following hip fracture. This retrospective study included 520 patients treated with osteoporotic hip fracture between March 2014 and June 2019. The patients were asked to choose the medication for osteoporosis treatment at discharge. Adherence was monitored by follow-up visits to the outpatient clinic at 1 year following surgery. Of 520 patients with baseline data, osteoporosis medications were prescribed to 250 (48.1%) patients. Of these patients, 110 (44.0%) took subcutaneous denosumab, 69 (27.6%) took oral selective estrogen receptor modulator, 55 (21.0%) took intravenous bisphosphonate. At 12 months, we followed up 178 (71.2%) patients. Of those prescribed a bone protection medication, only 85 patients (34.0%) reported still taking their medication 1 year later. The rate of adherence to 6-month subcutaneous denosumab injection was significantly higher than that for quarterly intravenous bisphosphonates (p = 0.024) or daily oral tablets (p = 0.028). This study revealed patients' adherence for osteoporosis treatments after hip fracture. 6-month subcutaneous denosumab injection was preferred over 3-month intravenous injection or daily oral tablets in this elderly population and exhibited significant lower discontinuation rates. However, because of the limited power of the study, further research is required to identify the reasons behind non-adherence and to improve adherence to anti-osteoporosis medications.