Assessments of vaccines for prenatal immunization.
The strategy of prenatal maternal immunization to protect the pregnant woman and her infant was first used with tetanus toxoid, when it was recognized that young infants had very high rates of tetanus disease, well before the age when infant immunizations are provided. Antenatal immunization has now been recommended and utilized for additional vaccines to prevent infections in pregnancy and the young infant. There are several issues to consider which are unique to the strategy of antenatal immunization. The first is that immunization of the pregnant woman will affect the woman who receives the vaccine, her developing fetus, and the young infant for several months after delivery. For this discussion, we will consider the availability of data for the maternal-fetal-infant triad in 4 aspects: This discussion will review available data from vaccines for prevention of tetanus, pneumococcal, influenza and pertussis infections used in antenatal maternal immunization programs.


Comparative studies of pulsatile and nonpulsatile flow during cardiopulmonary bypass. II. The effects on adrenal secretion of cortisol.
Previous studies have indicated that a significant reduction in plasma cortisol levels occurs during nonpulsatile cardiopulmonary bypass as a result of adrenocorticol hypofunction. The Stöckert pulsatile pump system described in Part I has been employed in a comparative study of plasma cortisol levels in 20 patients subjected to pulsatile or nonpulsatile perfusion during open-heart surgery. The plasma cortisol response pattern in the nonpulsatile group was identical to the pattern previously described, with no significant rise in cortisol levels during the period of perfusion. In the pulsatile group, however, plasma cortisol levels rose significantly during perfusion, reaching a mean level at the end of perfusion which was highly significantly greater than that in the nonpulsatile group (p less than 0.001). Correction of the plasma cortisol values for the effect of hemodilution was performed and, again, corrected cortisol values indicated a highly significant increase in end-bypass levels in the pulsatile groups (p less than 0.001). These results clearly indicate that the reduction in cortisol secretion during nonpulsatile bypass may be prevented by the use of pulsatile perfusion.


Does the temperature gradient correlate with the photodynamic diagnosis parameter numerical colour value (NCV)?
Photodynamic diagnosis (PDD) as well as thermovision belong to the category of non-invasive optical diagnosis techniques. Among many different skin cancer diseases, basal cell carcinoma (BCC) is the most frequently occurring one (almost 95% of all skin tumours). In contrast, seborrhoeic keratosis represents almost 70% of benign skin tumours. In this paper we present infrared thermography as an additional method, combined with PDD, to show the differentiation between these two skin mutations. The photodynamic diagnosis studies were performed by using the autofluorescence diagnosis system Xillix Onco. As an additional non-invasive diagnosis technique, thermovision studies were performed. Thermal imaging was done by using a Thermovision Camera A40M with a sensitivity of 0.07K. The thermograms of the chosen areas were performed in a special room with a temperature of 22.5±1°C. All patients were treated in the Chair and Clinic of Internal Diseases, Angiology and Physical Medicine in Bytom. Thirteen skin lesions were studied: 9 diagnosed as basal cell carcinoma and 4 as seborrhoeic keratosis. All skin lesions were confirmed in histopathological examinations. The results of the studies revealed significant differences in skin thermal mapping between patients suffering from basal cell carcinoma and seborrhoeic keratosis. It appears that benign skin lesions are characterised by a lower mean temperature than the surrounding healthy skin. To the contrary, cancerous skin mutations appeared on the thermal map at a higher mean temperature. Thermal images for the chosen skin lesions and temperature parameters derived from the thermograms are contiguous with the photodynamic diagnosis results and may give some additional diagnostic information.


Assessment of occupational and dietary exposures of feed handling workers to mycotoxins in rural areas from São Paulo, Brazil.
In the current study, the occupational and dietary exposures of feed handling workers (N = 28) to aflatoxins (AFs), fumonisins (FBs), ochratoxin A (OTA), deoxynivalenol (DON), zearalenone (ZEN), toxins T-2 and HT-2 were assessed for the first time in animal-producing farms and feed factories from São Paulo, Brazil. Mycotoxins in food (n = 244) and airborne dust (n = 27), as well as biomarkers in urine (n = 97) samples were determined by liquid chromatography coupled with tandem mass spectrometry. FBs were detected in all airborne dust samples, with concentrations ranging from 7.85 to 16,839 ng/m3. The mean probable daily intake (PDI) based on food data were 0.005, 0.769, 0.673 and 0.012 μg/kg of body weight (bw)/day for AFs, FBs, DON and ZEN, respectively. Mean PDI values obtained through urinary biomarkers were 0.29, 0.10, 0.50, 9.72 and 0.10 μg/kg body weight/day for AFB1, DON, OTA, FB1 and ZEN, respectively. The analyses based on urinary biomarkers revealed a potential health concern for OTA and FBs, although no potential health concern was observed with PDI calculated through food data. Results of this trial stress the need for preventive measures to avoid health risks of workers in Brazilian animal-producing farms and feed industries.


Evaluation of Tc-99m-labeled glycoprotein IIb/IIIa receptor antagonist DMP444 SPECT in patients with infective endocarditis.
Infective endocarditis (IE) is characterized by aggregation of activated platelets, fibrin, and bacteria. DMP444, a high-affinity glycoprotein IIb/IIIa receptor antagonist, binds to the fibrinogen-binding domain of activated platelets, depicting a key feature of IE. Tc-99m DMP444 scintigraphy was studied in a group of patients with possible IE. Tc-99m DMP444 (600 MBq; 16 mCi) planar and SPECT images of the heart were recorded in patients with possible IE for as long as 6 hours after injection. Results were compared to echocardiography and the Duke classification. Sixteen patients (age range, 37 to 78 years) participated. DMP444 imaging was positive on SPECT in five patients, and all had definite endocarditis (affecting both prosthetic and native valves). Eleven patients were DMP444 negative, seven with no proof of IE. The remaining four patients were classified as having IE, but three had been receiving adequate intravenous antibiotic regimens for > or = 2 weeks at the time of scintigraphy and one had Q-fever endocarditis. DMP444 SPECT allows in vivo visualization of IE if it is performed within 1 to 2 weeks after the start of antibiotic treatment. Given the high affinity of DMP444 for activated platelets, the results indicate the involvement of activated platelets in early IE.


Selective concentration of amines from aqueous solutions by a gas purging technique.
Amines are removed from heated, basic solutions saturated with salt by inert gas stripping and selectively trapped as coordination complexes on columns containing copper(II) salts coated on an inert support. An estimate of the amine concentrations at ppm levels can be made by measuring the length of the trapping column colored by the complexes. Concentrations of amines in ppb can be determined by eluting this column with potassium hydroxide and determining the amines in the effluent directly by gas chromatography. The procedure allows amines to be concentrated by a factor of 200 and removes potentially interfering substances from the sample.


Effects of contingent versus yoked temperature feedback on voluntary temperature control and cold stress tolerance.
Twenty-four male internals (locus of control) and 24 externals were instructed to increase finger temperature under one of three conditions: (1) contingent feedback (CF), (2) yoked sham feedback (YF), or (3) no feedback (NF). Five 13-min training sessions were given. Feedback was then removed and subjects tested for voluntary temperature control. Finally, the cold pressor test, a laboratory analogue of natural cold stress, was administered under no-feedback conditions. Results demonstrated voluntary control of peripheral temperature following contingent feedback training, but not after yoked feedback temperature training. Contrary to expectation, the acquisition of voluntary control did not attenuate the stress response to thermal pain. Differences between internals and externals throughout the study were generally insignificant.


Enhancement in functional stability of microbial endoglanases produced using paddy straw via treatment with manganese oxide based porous nanocomposite synthesized from mixed fruit waste.
Microbial cellulases are the enzymes used in numerous industrial biotechnological applications. Efficiency of celluloytic cocktails plays a key role in the conversion of biomass into biofuels, but limited production, high cost and low efficiency are the main obstacles to sustainable biorefining. The current work aims to establish a feasible approach for boosting the production of fungal endoglucanse (EG) and its functional stability utilizing nanocomposite materials based on manganese oxide. Herein, aqueous extract from mixed fruit waste was used to synthesize the nanocomposite sample, which was subsequently subjected to several characterization techniques for analysis. Following the solid-state fermentation of paddy straw, and by employing 75 mg nanocomposite, 192 IU/gds EG was produced under the optimal conditions, while 19 IU/gds FP and 98 IU/gds BGL production were recorded. The crude EG enzyme treated with nanocomposite also shows complete stability at pH 5.0 for 3.5 h while retaining thermal activity at 70 °C for 4 h.


Evidence of glutamatergic deficiency in schizophrenia.
Studies of amino acid release were carried out using frozen sections from brains of schizophrenics and controls. Synaptosomes were prepared via differential centrifugation in Ficoll allowing the veratridine-induced release of aspartate, glutamate, glycine, and GABA to be measured. The release of glutamate and gamma-aminobutyric acid (GABA) was reduced in the synaptosomes from schizophrenics. This decrease could be reversed partially by pre-incubation of the synaptosomes with haloperidol. Additionally, the activity of glutamate decarboxylase was decreased and partially restored by haloperidol pre-incubation. These data are consistent with the hypothesis of a glutamatergic/GABAergic deficit in schizophrenia.


Use of bioreactors in maxillofacial tissue engineering.
Engineering of various oral tissues is a challenging issue in contemporary maxillofacial reconstructive research. In contrast to the classic biomaterial approach, tissue engineering is based on the understanding of cell driven tissue formation, and aims to generate new functional tissues, rather than just to implant non-living space holders. Researchers hope to reach this goal by combining knowledge from biology, physics, materials science, engineering, and medicine in an integrated manner. Several major technical advances have been made in this field during the last decade, and clinical application is at the stage of first clinical trials. A recent limitation of extracorporally engineered cellular substitutes is the problem of growing enlarged tissues ex vivo. One of the main research topics is therefore to scale up artificial tissue constructs for use in extended defect situations. To overcome the monolayer inherent two-dimensional cell assembly, efforts have been made to grow cells in a three-dimensional space. Bioreactors have therefore been in focus for a considerable time to build up enlarged tissues. The shift from the ex vivo approach of cell multiplication to the generation of a real tissue growth is mirrored by the development of bioreactors, enabling scientists to grow more complex tissue constructs. This present review intends to provide an overview of the current state of art in maxillofacial tissue engineering by the use of bioreactors, its limitations and hopes, as well as the future research trends.


Circulating extracellular vesicle-derived MARCKSL1 is a potential diagnostic non-invasive biomarker in metastatic colorectal cancer patients.
Extracellular vesicle-derived proteins are closely related to colorectal cancer metastasis, and early detection and diagnosis of colorectal cancer metastasis is very important to improve the prognosis. In this study, we evaluated the clinical significance of plasma EV-derived MARCKSL1 in differentiating patients with metastatic and nonmetastatic CRC. This study included 78 patients, including 40 patients with nonmetastatic colorectal cancer, 38 patients with metastatic colorectal cancer, and 15 healthy volunteers. The extracellular vesicles extracted from the participants' plasma were characterized through transmission electron microscopy, nanoparticle tracking analysis and western blotting. MARCKSL1 protein expression in the EVs was detected by ELISA, and the diagnostic efficacy of MARCKSL1 alone or in combination with CA125 and lymphocyte levels was evaluated by receiver operating characteristic curve (ROC) analysis. Pearson's correlation test was performed to detect the correlation between MARCKSL1, CA125, lymphocyte level and clinicopathological characteristics of tumors. The present study demonstrated that the level of circulating EV-derived MARCKSL1 in patients with metastatic colorectal cancer was significantly higher than that in patients with nonmetastatic colorectal cancer and healthy people. Combined with CA125 and lymphocyte levels, the best diagnostic effect was achieved, and the area under the ROC curve was 0.7480. Together, our findings indicated that circulating EV-derived MARCKSL1 could be used as a new potential diagnostic biomarker for metastatic CRC.


Effect of transection in the brainstem on short-term maintenance of deoxycorticosterone-salt hypertension.
Sections were made to determine supraspinal areas that participate in the maintenance of deoxycorticosterone (DOC)-salt hypertension. Blood pressure (BP) falls after cuts which severed: (a) the lateral connections between pons and midbrain, (b) the pathways between caudal hypothalamus and midbrain, and (c) parasagittal connections between medial and lateral hypothalamus. No changes in BP were found either after coronal cuts that severed a central area located at: (a) the pons-midbrain edge, (b) above the caudal hypothalamus, and (c) the level of the anterior hypothalamic area, or after parasagittal cuts at the level of the capsula interna or after a hypophysial stalk lesion. These results implicate the hypothalamus in the maintenance of DOC-salt hypertension. The hypothalamus-neural lobe system appears not to be involved in the lowering of BP found.


The myth of technology in health care.
Technology is believed to have liberated health care from dogmas, myths and speculations of earlier times. However, we are accused of using technology in an excessive, futile and even detrimental way, as if technology is compelling our actions. It appears to be like the monster threatening Dr. Frankenstein or like the sorcerer's broom in the hand of the apprentice. That is, the same technology that should liberate us from myths, appears to be mythical. The objective of this article is to investigate the background for the re-entrance of the myth: How we encounter it and how we can explain it. The main point is that a myth of technology is normative: it relates 'is' and 'ought' and directs our actions. This becomes particularly clear in health care. Hence, if there is a myth of technology, it is an ethical issue, and should be taken seriously.


The vascular morphology of melanoma is related to Breslow index: An in vivo study with dynamic optical coherence tomography.
Malignant melanoma is an aggressive skin cancer, which can lead to metastasis development. Vascularization enhancement is fundamental for tumor growth, worsening the prognosis. Dynamic optical coherence tomography (D-OCT) enables the in vivo evaluation of vascular patterns in skin lesions. In vivo evaluation of the melanoma vessel morphology by means of D-OCT and correlation with Breslow index. Retrospective analysis of histologically proven melanomas, evaluated by D-OCT at three different depths (150, 300 and 500 μm), was performed. Vessels were classified according to morphology (dots, blobs, coiled, line, curved, serpiginous), distribution (regular, irregular) and the presence/type of branches. The data were correlated with Breslow thickness. A total of 127 melanomas were evaluated. Dotted vessels were recorded at all depths, and their irregular distribution was associated with lesions thicker than 1.0 mm (from 75% to 91%), compared with thin ones (42%) at 150 μm (P = 0.031), and from 33% to 57% vs 18% at 300 μm (P = 0.021). Serpiginous and branching vessels with bulges were predominantly seen in melanomas thicker than 2 mm at 150 μm (from 14% to 27%, P < 0.001) and 300 μm of depth (from 36% to 54%, P < 0.001). Background noise hampered vessel detection at 500 μm. No correlation with dermoscopy/histology. Vascular pattern evaluation at 150 and 300 μm provided data on tumor microvascular asset and its pattern of progression in accordance with Breslow thickness. Since vascular progression is theoretically linked with tumor aggressiveness, the study of vascular pattern related with melanoma metastatization capability is warranted.


A new species of Clinostomum Leidy, 1856 in East Asia based on genomic and morphological data.
Metacercariae of Clinostomum Leidy, 1856 are frequently encountered in freshwater fish. In 2015, a provisional species of Clinostomum in People's Republic of China (PRC) was distinguished from C. complanatum (Rudolphi, 1819) in Europe based on divergent cytochrome c oxidase I (CO1). However, in subsequent studies in East Asia, the same divergent CO1 genotype was identified as C. complanatum. These matching sequences suggest that either the provisional East Asian species was incorrectly distinguished from C. complanatum in 2015 or that C. complanatum in East Asia was misidentified in later studies. We tested these alternatives by sequencing the mitochondrial genome of C. complanatum in Italy, which was 5.7% divergent from a previously published sequence from Clinostomum in PRC, including differences in 80 of 3390 (2.4%) translated amino acids. Partial CO1 sequences of specimens from PRC and those from Italy, Romania, and Turkey also each formed reciprocally monophyletic clades. Partial CO1 from the East Asian clade varied by mean 3.6% (range 2.4-4.8%) from C. complanatum from Italy, Romania, and Turkey; mean intra-clade CO1 variation was 0.3% (range 0-1.9%). Metacercariae from Europe and East Asia display significant morphometric variation, and data from the literature suggest morphological differences in the genital complex of adults. Although sequences of nuclear rDNA did not differ between isolates from the west and East Asia, taken together, these results lead us to describe a new species of Clinostomum.


Abnormal intrafusal muscle fibres in myotonic dystrophy: a study using serial sections.
Studies of the extent and complexity of intrafusal muscle fibre splitting in myotonic dystrophy have been carried out in three spindles obtained at muscle biopsy, and in nine spindles found in the lumbrical muscle of a case that came to necropsy. It is suggested that splitting, due to mechanical stresses, leads to a regenerative response in the separated fragments.


Rat gastric prepepsinogen: in vitro synthesis and partial amino-terminal signal sequence.
The major translation product of rat gastric mucosa RNA in a wheat germ cell-free system was identified as prepepsinogen by electrophoretic analysis of its immunoprecipitate on sodium dodecyl sulfate (SDS)-polyacrylamide gels and amino-terminal sequence determination. The translation product containing radioactive amino acids, purified by SDS-polyacrylamide gel electrophoresis, was shown to have an amino-terminal extension peptide comprising 16 amino acid residues. A partial amino acid sequence of this extension peptide is as follows: Met-X-X-Met-Val-Val-X-Leu-Leu-X-Leu-X-Leu-Leu-X-X-pepsinogen.


Influence of yeasts on bioactive compounds content of traditional sorghum beer (tchapalo) produced in Côte d'Ivoire.
Traditional sorghum beer is reputed for its therapeutic virtues in according the consumers. A number of biological active compounds like phenolic compounds (phenol, tannins, flavonoids, anthocyanins), diets fibers and compounds with clinically demonstrated antimalarial activity (quinine formate, quinine dihydrochloride, chloroquine) and antioxidant activity (2,2-diphenyl-1-picryl-hydrazyl and ferric reducing-antioxidant power methods) were evaluated in sorghum wort and beers fermented by wild yeasts and pure culture of Saccharomyces cerevisiae. The total phenol content in the samples ranged between 1254.69 ± 2.31 and 239.68 ± 11.92 μg/mL GAE. Antioxidant activity with 2,2-diphenyl-1-picryl-hydrazyl analysis method was high in sorghum wort with 73.33 ± 1.15% but with ferric reducing-antioxidant power analysis method, the antioxidant activity was high in beer from pure culture of Saccharomyces cerevisiae. No compounds with clinically demonstrated antimalarial activity were found in the samples. At bioactive compounds (phenolic compounds) content point view, statistical analysis showed similarity between the two beers.


Comparison of MRI, 64-slice MDCT and DSCT in assessing functional cardiac parameters of a moving heart phantom.
To compare magnetic resonance imaging (MRI), 64-slice multi-detector computed tomography (MDCT) and dual-source computed tomography (DSCT) in assessing global function parameters using a moving heart phantom. A moving heart phantom with known volumes (215-258 ml) moving at 50-100 beats per minute was examined by three different imaging modalities using clinically implemented scanning protocols. End-diastolic and end-systolic volumes were calculated by two experienced observers using dedicated post-processing tools. Ejection fraction (EF) and cardiac output (CO) were calculated and mutually compared using Bland-Altman plots. MRI underestimated the ejection EF by 16.1% with a Bland-Altman interval (B-A) of [-4.35 (-2.48) -0.60]. Sixty-four-slice MDCT overestimated the EF by 2.6% with a relatively wide B-A interval of [-3.40 (0.40) 4.20]. DSCT deviated the least from the known phantom volumes, underestimating the volumes by 0.8% with a B-A interval of [-1.17 (-0.13) 0.91]. CO analysis showed similar results. Furthermore, a good correlation was found between DSCT and MRI for EF and CO results. MRI systematically underestimates functional cardiac parameters, ejection fraction and cardiac output of a moving heart phantom. Sixty-four-slice MDCT underestimates or overestimates these functional parameters depending on the heart rate because of limited spatial resolution. DSCT deviates the least from these functional parameters compared to MRI, EBT and 64-slice MDCT.


Cardiovascular and respiratory effects of some anesthetics in the decerebrate rat.
The cardiovascular and respiratory effects of pentobarbital, ketamine, chloralose and urethane were studied in decerebrate rats. All the anesthetics reduced blood pressure and heart rate. Pentobarbital, chloralose and ketamine, but not urethane, reduced respiratory rate. None of these agents had a significant effect on tidal volume. All these anesthetics significantly attenuated the carotid occlusion, tilt and sodium cyanide chemo-receptor response. These results suggest that the decerebrate rat may be a more suitable preparation, compared to the anesthetized one, for studying cardiovascular and respiratory responses in this species.


Combination treatment of TRAIL, DFMO and radiation for malignant glioma cells.
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has shown potent and cancer-selective killing activity and drawn considerable attention as a promising therapy for cancer. Another promising cancer therapy is difluoromethylornithine (DFMO), an inhibitor of ornithine decarboxylase, which is oraly administered and well tolerated. Nevertheless, many types of cancer, including gliomas, have exhibited resistance to TRAIL-induced apoptosis and similarly the potency of DFMO should be enhanced to optimize therapeutic efficacy. In this study we sought to determine whether DFMO, in combination with TRAIL and radiation, could result in an enhanced anti-glioma effect in vitro. We investigated the effect of DFMO, TRAIL and radiation in various combinations on a panel of glioblastoma cell lines (A172, T98G, D54, U251MG). Viability and proliferation of the cells were examined with trypan blue exclusion assay, crystal violet and xCELLigence system. Apoptosis (Annexin-PI), cell cycle and activation of caspase-8 were tested with flow cytometry. BAD protein levels were determined by Western blot analysis. DFMO induced BAD overexpression. Combination treatment with DFMO, TRAIL and radiation significantly reduced cell viability in all cell lines tested. Increased induction of cell death and cell cycle arrest was confirmed with flow cytometry in A172 and D54 cell lines, while enhanced activation of annexin and caspase-8 was revealed in U251MG and T98G cells. The treatment of glioblastoma cell lines with combination of DFMO, TRAIL and radiation showed an enhanced effect. This combination treatment may represent a novel strategy for targeting glioblastoma.


The 3'-UTR (CA)n microsatellite on CD40LG gene as a possible genetic marker for rheumatoid arthritis in Mexican population: impact on CD40LG mRNA expression.
The objective of this study was to determine the association of the CD40LG 3'-UTR (CA)n microsatellite with rheumatoid arthritis (RA) and CD40LG mRNA levels in females from western Mexico. A case-control study with 219 RA patients and 175 control subjects (CS) was conducted. Genotyping was performed by polymerase chain reaction (PCR), X 2 test was used to compare genotype and allele frequencies, and odds ratios and 95% confidence intervals were calculated to evaluate the association between RA and the microsatellite. CD40LG mRNA expression was assessed by real-time quantitative PCR. For comparisons between groups, Kruskal-Wallis or Mann-Whitney U tests for non-parametric data and ANOVA test for parametric data were performed. Among the 13 different alleles identified, CA25 was the most represented (45.4% RA and 46.3% CS). Stratification according to CA repeats as <CA25, CA25, and >CA25 showed a tendency towards a higher frequency of >CA25 alleles in RA patients (29%) compared to CS (23.4%). There was no association between any genotype and the clinical parameters of RA patients. According to the 2-∆∆Cq method, CD40LG mRNA expression in RA patients was 4.5-fold higher compared to CS; this difference was significant when assessed by the 2-∆Cq method (p = 0.028). Compared to carriers of the CA25/CA25 genotype, CS carrying the <CA25/<CA25 genotypes showed greater CD40LG mRNA expression (9.97-fold), unlike RA patients, where expression was 2.55-fold higher for >CA25/>CA25 carriers. The 3'-UTR CD40LG (CA)n microsatellite is not a genetic marker for RA in western Mexican population; however, results suggest that it plays a role in the CD40LG mRNA expression.


Factors Associated with Reconstruction Failure and Major Complications After Postmastectomy Radiation to a Reconstructed Breast.
Postmastectomy radiation therapy is known to increase risk of complications in the reconstruction setting. We aim to identify the variables associated with reconstruction failure and other major complications. A prospectively collected institutional database was queried for patients with up to stage IIIC breast cancer treated from 2000 to 2017, undergoing mastectomy, immediate implant or autologous tissue reconstruction, and radiation to the reconstructed breast within 1 year of surgery. Reconstruction failure was defined as complication requiring surgical revision or implant removal. Additional major complications were defined as any infection, contracture, necrosis, or fibrosis. Covariates of interest included age, body mass index, smoking status, stage, hormone receptor and HER2 status, systemic therapy timing, radiation technique, nodal irradiation, and interval between surgery and start of postmastectomy radiation therapy. Differences in complication rates were assessed with χ² or Fisher exact tests. Competing risk regression was used to estimate hazard ratios; covariates were included one at a time to avoid over adjustment. A total of 206 reconstructed breasts in 202 patients resulted from our initial query, with 139 treated with intensity-modulated radiation therapy (IMRT) and 67 treated with conventional radiation therapy (CRT). Median follow-up was 45 months (range, 4-210 months); patient cohorts were generally similar. Eight patients were excluded from toxicity analysis for insufficient follow-up (<2 years). Overall, reconstruction failure and major complication rates were significantly lower in the IMRT group. Reconstruction failure rates were 3.0% for IMRT versus 16.4% for CRT (P = .002), and major complication rates were 6.8% for IMRT versus 24.6% for CRT (P < .001). On univariate analysis, CRT was significantly predictive of implant failure (hazard ratio, 5.54; P = .003) and increased complication rates (hazard ratio, 3.83; P = .001). Significance persisted on multivariable analysis. Survival outcomes were similar, with no difference in 2 year overall survival (P = .12) and local recurrence (P = .41). Using IMRT may improve reconstruction outcomes over CRT, with significantly lower reconstruction failure and complication rates without compromising local control or survival.


Mercury offloaded in Northern elephant seal hair affects coastal seawater surrounding rookery.
Methylmercury (MeHg) is a potent neurotoxin that is biomagnified approximately 1-10 million-fold in aquatic carnivores such as the Northern elephant seal (Mirounga angustirostris), whose excreta and molted pelage, in turn, constitute a source of environmental MeHg contamination at the base of marine food chains. The potential for this top-down contamination is greatest in coastal areas with productive marine ecosystems that provide ideal habitats for large marine mammal colonies that can number in the thousands. This recycling of MeHg was evidenced by comparing total mercury (HgT) and MeHg concentrations in seawater, and HgT in molted pelage of M. angustirostris, at the Año Nuevo State Reserve pinniped rookery with concentrations at neighboring coastal sites in Central California. Seawater MeHg concentrations around the rookery (average = 2.5 pM) were markedly higher than those at the comparison coastal sites (average = 0.30 pM), and were as high as 9.5 pM during the M. angustirostris molting season. As a consequence, excreta and molts from this marine mammal colony, and presumably other marine predator populations, constitute a major source of MeHg at the base of the local marine food chain.


Relations of pain threshold and pain tolerance in cold water with scores on Maudsley Personality Inventory and Manifest Anxiety Scale.
Testing 56 Japanese undergraduates, the relationships between pain threshold and pain tolerance in cold water and personality factors were investigated. Significant negative correlations of moderate magnitude between the pain threshold and scores on Maudsley Neuroticism and the Manifest Anxiety Scale were found. On the contrary, significant positive, moderate correlations between pain tolerance and the Maudsley Extraversion were obtained.


Dimethyl sulfoxide enhances effectiveness of skin antiseptics and reduces contamination rates of blood cultures.
Effective skin antisepsis is of central importance in the prevention of wound infections, colonization of medical devices, and nosocomial transmission of microorganisms. Current antiseptics have a suboptimal efficacy resulting in substantial infectious morbidity, mortality, and increased health care costs. Here, we introduce an in vitro method for antiseptic testing and a novel alcohol-based antiseptic containing 4 to 5% of the polar aprotic solvent dimethyl sulfoxide (DMSO). The DMSO-containing antiseptic resulted in a 1- to 2-log enhanced killing of Staphylococcus epidermidis and other microbes in vitro compared to the same antiseptic without DMSO. In a prospective clinical validation, blood culture contamination rates were reduced from 3.04% for 70% isopropanol-1% iodine (control antiseptic) to 1.04% for 70% isopropanol-1% iodine-5% DMSO (P < 0.01). Our results predict that improved skin antisepsis is possible using new formulations of antiseptics containing strongly polarized but nonionizing (polar aprotic) solvents.


Yeast community succession in cow dung composting process.
Yeast complexes in the composting process of cow dung prepared to fertilize the soil for growing vegetables and fruits were studied. The average abundance of yeasts changed during the four temperature stages of the composting process. The highest abundance of yeasts, 1.38 × 104 cfu/g, was observed in the second stage of heating from 20 to 40 °C; the lowest was studied in the stage with the highest temperature (65 °C), 1.68 × 103 cfu/g. A total of 19 yeast species were observed and identified: 11 ascomycetes and 8 basidiomycetes, belonging to five subphyla of Fungi: Saccharomycotina (10), Pezizomycotina (1), Agaricomycotina (5), Pucciniomycotina (2), and Ustilaginomycotina (1). The greatest diversity of yeasts was found in the initial (20 °C) and second (heating up to 40 °C) temperature stages of composting (Aureobasidium pullulans (yeast-like fungus), Candida parapsilosis, Candida saitoana, Candida santamariae, Candida tropicalis, Curvibasidium cygneicollum, Cutaneotrichosporon moniliforme, Debaryomyces fabryi, Debaryomyces hansenii, Filobasidium magnum, Kazachstania sp., Moesziomyces bullatus, Naganishia globosa, Papiliotrema flavescens, Rhodotorula mucilaginosa, Scheffersomyces insectosa, Torulaspora delbrueckii, Vanrija musci), and the lowest in the stage of maximum heating (65 °C) (C. parapsilosis, C. tropicalis, Cyberlindnera jadinii).The opportunistic yeasts C. parapsilosis and C. tropicalis were obtained not only in the initial, second and third temperature stages of the composting process, but also in mature compost in the final stage prepared for soil application. This study shows that the cow dung, used in the farm studied did not meet the microbiological safety criteria. The reduction of opportunistic yeast species was not achieved with the composting method used. The likelihood of these species entering agricultural products via compost and soil and developing as endophytes in the internal tissues of fruits is very high. Since some strains of opportunistic Candida species from cow dung exhibited virulent characteristics (they produced hydrolytic enzymes and were resistant to antifungal compounds), additional phenotypic and genetic studies of the compost strains and their comparison with clinical isolates should be pursued.


Anti-diabetic effect of vestibular stimulation is mediated via AMP-activated protein kinase.
There is abundant animal evidence that vestibular stimulation, particularly of the otolith organs, can trigger a shift in body mass composition towards a leaner physique. One way of non-invasively stimulating the otolith organs is via a small electrical current applied to the skin behind the ears. This technique is called vestibular nerve stimulation, or VeNS, and is believed to have a good safety profile. Thus, it has previously been argued that VeNS could be used in human health as a means of treating the complications of metabolic syndrome, such as obesity and type 2 diabetes mellitus. Weight loss itself is known to improve diabetic control, however, tantalizing evidence is now emerging that the improvements seen in the glycemic control of type 2 diabetics who undergo repeated vestibular stimulation are significantly better than would be expected on the basis of weight loss alone. As vestibular stimulation has been shown to increase levels of an anti-inflammatory protein, called sirtuin 1, we hypothesize here that VeNS will increase levels of an associated enzyme called AMP-activated protein kinase (AMPK). AMPK plays an important role in glucose and fat metabolism and is activated by exercise, as well as being a known target for certain anti-diabetic drugs. This hypothesis is readily amenable to clinical testing as specific assays for testing human AMPK are available. If substantiated, then this hypothesis could prove an important clinical insight and potentially offer a new treatment avenue for patients with type 2 diabetes; a condition which remains a major cause of morbidity and premature mortality worldwide.


Provisional full coverage for draining tooth. An endodontic/esthetic problem.
A procedure is presented that allows endodontic drainage to be established on a broken-down tooth while esthetics are maintained.


Day/night variations in turgor pressure in individual cells of Mesembryanthemum crystallinum L.
Using a pressure probe, turgor pressure was directly determined in leaf-mesophyll cells and the giant epidermal bladder cells of stems, petioles and leaves of the halophilic plant Mesembryanthemum crystallinum. Experimental plants were grown under non-saline conditions. They displayed the photosynthetic characteristics typical of C3-plants when 10 weeks old and performed weak CAM when 16 weeks old. In 10 week old plants, the turgor pressure (P) of bladder cells of stems was 0.30 MPa; of bladder cells of petioles 0.19 MPa, and of bladder cells of leaves 0.04 MPa. In bladder cells from leaves of 16 week old plants, marked changes in turgor pressure were observed during day/night cycles. Maximum turgor occurred at noon and was paralleled by a decrease in the osmotic pressure of the bladder cell sap. Similar changes in the cell water relations were observed in plants in which traspirational water loss was prevented by high ambient relative humidity. Turgor pressure of mesophyll cells also increased during day-time showing macimum values in the early morning. No such changes in turgor pressure and osmotic pressure were observed in bladder and mesophyll cells of the 10 week old plants not showing the diurnal acid fluctuation typical of CAM.


Circulating Cell-Free DNA Assessment in Biofluids from Children with Neuroblastoma Demonstrates Feasibility and Potential for Minimally Invasive Molecular Diagnostics.
Liquid biopsy strategies in pediatric patients are challenging due to low body weight. This study investigated cfDNA size distribution and concentration in blood, bone marrow, cerebrospinal fluid, and urine from 84 patients with neuroblastoma classified as low (n = 28), intermediate (n = 6), or high risk (n = 50) to provide key data for liquid biopsy biobanking strategies. The average volume of blood and bone marrow plasma provided ranged between 1 and 2 mL. Analysis of 637 DNA electropherograms obtained by Agilent TapeStation measurement revealed five different major profiles and characteristic DNA size distribution patterns for each of the biofluids. The proportion of samples containing primarily cfDNA was, at 85.5%, the highest for blood plasma. The median cfDNA concentration amounted to 6.28 ng/mL (blood plasma), 58.2 ng/mL (bone marrow plasma), 0.08 ng/mL (cerebrospinal fluid), and 0.49 ng/mL (urine) in samples. Meta-analysis of the dataset demonstrated that multiple cfDNA-based assays employing the same biofluid sample optimally require sampling volumes of 1 mL for blood and bone marrow plasma, 2 mL for cerebrospinal fluid, and as large as possible for urine samples. A favorable response to treatment was associated with a rapid decrease in blood-based cfDNA concentration in patients with high-risk neuroblastoma. Blood-based cfDNA concentration was not sufficient as a single parameter to indicate high-risk disease recurrence. We provide proof of concept that monitoring neuroblastoma-specific markers in very small blood volumes from infants is feasible.


Perinatal Outcomes After Statin Exposure During Pregnancy.
Statins are the drug class most commonly used to treat hyperlipidemia. Recently, they have been used during pregnancy for the prevention or treatment of preeclampsia. However, the safety of statin use during pregnancy has been questioned, and the sample sizes of most previous studies have been small. To examine the perinatal outcomes among offspring associated with maternal use of statins during pregnancy. This retrospective cohort study included 1 443 657 pregnant women 18 years of age or older with their first infant born during the period from January 1, 2004, to December 31, 2014. Data for this study were taken from the Taiwan National Health Insurance Research Database. Statistical analysis was performed from April 7, 2020, to July 31, 2021. Maternal statin use during pregnancy. Women who have received a diagnosis of hyperlipidemia before pregnancy and who were receiving prescription statins during pregnancy were the statin-exposed group. Data on congenital anomalies, birth weight, gestational age, preterm birth, low birth weight, very low birth weight, fetal distress, and Apgar score were compared between participants with and partcipants without statin exposure during pregnancy. Risk ratios (RRs) were calculated by multivariable analyses using Poisson regression models to adjust for potential confounders. Subgroup analysis was performed to compare offspring of women who used statins for more than 3 months prior to pregnancy and maintained or stopped statin use after pregnancy. A total of 469 women (mean [SD] age, 32.6 [5.4] years; mean [SD] gestational age, 38.4 [1.6] weeks) who used statins during pregnancy and 4690 age-matched controls (mean [SD] age, 32.0 [4.9] years; mean [SD] gestational age, 37.3 [2.4] weeks) with no statin exposure during pregnancy were enrolled. After controlling for maternal comorbidities and age, low birth weight was more common among offspring in the statin-exposed group (RR, 1.51 [95% CI, 1.05-2.16]), with a greater chance of preterm birth (RR, 1.99 [95% CI, 1.46-2.71]), and a lower 1-minute Apgar score (RR, 1.83 [95% CI, 1.04-3.20]). Congenital anomalies were not associated with statin exposure during pregnancy. In addition, multivariable analysis showed that there was no association between statin use for periconceptual hyperlipidemia and adverse perinatal outcomes among women who had used statins prior to pregnancy. This study suggests that statins may be safe when used during pregnancy because there was no association with congenital anomalies, but caution is needed because of an increased risk of low birth weight and preterm labor. The data also suggest that statins could be safely used during pregnancy for women with long-term use of statins before pregnancy.


The accuracy of using guided endodontics in access cavity preparation and the temperature changes of root surface: An in vitro study.
Guided endodontics is a successful technique that has been gradually applied to endodontic therapy in recent years without being affected by the operator's experience. However, the guided bur produces excessive heat during continuous rotation and friction with root canal walls, it is not clear whether the degree of temperature increase may lead to the periodontal ligament and alveolar bone damage. A total of 58 teeth were used, of which 40 teeth were not grouped, all used to evaluate the accuracy. 40 single-rooted premolars were scanned using CBCT and an intra-oral scanner, and 3D-printed guided plates were made with the pre-designed access. A custom-made guided bur was used to prepare the access cavities. The postoperative CBCT data and pre-designed pathways were matched to evaluate the deviation between the planned and virtual paths. The other 18 teeth were randomly divided into three groups (ET20 and ProTaper F3 as the control group, guided endodontics as the test group), with 6 teeth in each group. The temperature changes on the root surfaces were inspected with a thermocouple thermometer. The average deviation on the tip and the base of the bur was 0.30 mm and 0.28 mm (mesial/distal), and 0.28 mm and 0.25 mm (buccal/lingual). The average angle deviation was 3.62°. The mean root surface temperature rise of the guided endodontics group was the lowest (5.07 °C) (P < 0.05). The access cavity preparation performed with guided endodontics has feasible accuracy and low-temperature rise on the root surfaces. Due to the limitations of the study, whether it has high reliability and safety in clinical applications needs to be further studied in vivo.


Economic Evaluation of Rivaroxaban Versus Enoxaparin for Prevention of Venous Thromboembolism After Total Knee Replacement and Total Hip Replacement: A Systematic Review.
Deep vein thrombosis (DVT) and pulmonary embolism (PE) together are called venous thromboembolism (VTE) and impose a high economic burden on healthcare systems. Thousands of people are hospitalized annually due to benign and treatable diseases but die due to PE; with the adoption of appropriate prevention, these deaths can be prevented. To investigate the cost-effectiveness of using rivaroxaban versus enoxaparin in published economic analyses for prevention of VTE after total knee (TKR) or hip replacement (THR). In a systematic review electronic searches were performed on various online databases, including PubMed, Web of science, Embase, Scopus, Health Economic Evaluations Database (HEED), and ProQuest. The inclusion criteria were: studies that were conducted on the cost-effectiveness of rivaroxaban versus enoxaparin for the prevention of VTE after TKR and THR; cost-effectiveness studies conducted using decision analysis models based on the economic evaluation approach; studies with available full-text papers; and studies written in English and published between 2007 and 2019. The exclusion criteria were: studies with partial cost effectiveness (such as effectiveness assessment, cost assessment, quality-of-life assessment); studies written in languages other than English; and all protocols, conference abstracts, and letters to the editor. The Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklist was used to qualitatively evaluate the studies. Of a total of 537 initial studies, nine papers met the inclusion criteria. The time scope of studies ranged from 3 months to 5 years. Among the selected studies, some studies had included discount rates (n = 4) and the other studies did not utilize discount rates and were set to zero percent by default (n = 5). In all studies, direct medical costs, including costs related to the prevention, diagnosis, and treatment of VTE and PE, and management and monitoring of treatment costs were reviewed. The results of this systematic review showed that using rivaroxaban in patients undergoing total knee or hip replacement reduced costs and increased quality of life. However, since most of the studies had been conducted in developed countries, it is not possible to generalize the results to developing countries. Nonetheless, given that rivaroxaban is administered orally and does not require continuous monitoring, it will be less costly for patients and health systems and is more appropriate to administer it as a thromboprophylactic drug following total knee or hip replacement surgery.


A pilot study of the use of placental cord blood samples in monitoring for mutational events.
A pilot study exploring the examination of placental cord blood samples for mutant proteins with one-dimensional electrophoretic techniques is described. Although technical advances are such that the techniques employed in this study are now partially superceded, the practical problems encountered in this study would be typical of any monitoring program of this type. No mutations altering electrophoretic mobility among a battery of 51 different locus products were encountered in a total of 277,747 locus tests. When these data are combined with similar data from other studies, the mutation rate for electromorphs becomes 0.34 X 10(-5)/locus/generation.


Pyramidal resistance training: A brief review of acute responses and long-term adaptations.
One of the most popular training methods in weight rooms is the pyramidal. Despite this, its superiority over traditional training is still speculative. To review the effects of pyramid strength training on acute responses and long-term adaptations of this training method. The research was performed in PubMed, BIREME/BVS and Google Scholar databases using the search words in different combinations: 'strength training', 'resistance training', 'resistance exercise', 'strength exercise', 'pyramid', 'system pyramidal', 'crescent pyramid' and 'decrescent pyramid'. As inclusion criteria were considered: studies in English, which compared the effects of pyramidal training versus traditional training on acute responses and long-term adaptations. The TESTEX scale (0-15 points) was used to assess the methodological quality of the studies. This article included 15 studies (6 acute effect studies and 9 longitudinal studies), which evaluated hormonal, metabolic and performance responses, strength gains and muscle hypertrophy of strength training in pyramidal and traditional format. Studies were rated between good and excellent quality. The pyramid training protocol was not superior to the traditional protocol on acute physiological responses, strength gains and muscle hypertrophy. From a practical point of view, these findings allow us to say that the manipulation of this training method could be based on issues of periodization, motivation and/or even in personal preference. But, this is based on studies developed with repetition zones between 8 and 12 and/or intensities between 67% and 85% of 1RM.


Blindness and Autism: Parents' Perspectives on Diagnostic Challenges, Support Needs and Support Provision.
Autism spectrum disorder (ASD), with or without intellectual disability (ID), is common in children with congenital blindness. This complex combination of disabilities often involves many challenges for the family. This study explored parents' experiences of having a child with blindness and ASD (with or without ID), their support needs and experiences of the support provided. Interviews with eight parents, representing six families, were performed. The parents emphasized that assessment and diagnostic procedures must be performed by professionals with expertise in blind children's development, and ASD. The support was often perceived as fragmented and did not correspond to the families' needs. The results suggest that national guidelines should be produced, to ensure a more coordinated and tailored support to these families.


Highly sensitive and specific graphene/TiO2 impedimetric immunosensor based on plant-derived tetravalent envelope glycoprotein domain III (EDIII) probe antigen for dengue diagnosis.
This study reports on the development of a novel impedimetric immunosensor design using plant-derived antigenic glycoprotein for the detection of dengue virus (DENV) IgG antibodies. The electrochemical immunosensor platform was constructed using screen-printed carbon electrode (SPCE) modified with graphene/titanium dioxide (G/TiO2) nanocomposite to improve the electrode in terms electrochemical performance and specific surface area. A plant-derived dengue envelope domain III (EDIII) protein was used as the antigenic probe protein in this immunosensing strategy. Under optimised sensing conditions, the immunosensor demonstrated high sensitivity towards DENV IgG in a wide linear working range (62.5-2000 ng/mL), with a limit of detection of 2.81 ng/mL. The immunosensor showed high specificity for discriminating DENV IgG against antibodies of other infectious disease, including the closely related Zika virus (ZIKV). The reliability of the immunosensor in serological diagnosis was verified by challenging the immunosensor against serum samples, compared to conventional enzyme-linked immunosorbent assay (ELISA). As shown by its remarkable performance throughout the study, the devised immunosensor is proposed as a reliable and practical diagnostic tool for the serological detection of dengue in realistic applications.


Improving depression prediction using a novel feature selection algorithm coupled with context-aware analysis.
Developing machine learning based depression prediction method with information from long-term recordings is important and challenging to clinical diagnosis of depression. We developed a novel two-stage feature selection algorithm conducted on the high-dimensional (over thirty thousand) features constructed by a context-aware analysis on the data set of DAIC-WOZ, including audio, video, and semantic features. The prediction performance was compared with seven reference models. The preferred topics and feature categories related to the retained features were also analyzed respectively. Parsimonious subsets (tens of features) were selected by the proposed method in each case of prediction. We obtained the best performance in depression classification with F1-score as 0.96 (0.67), Precision as 1.00 (0.63), and Recall as 0.92 (0.71) on the development set (test set). We also achieved promising results in depression severity estimation with RMSE as 4.43 (5.11) and MAE as 3.22 (3.98), having a marginal difference with the best reference model (random forest with 'Selected-Text' features). Five most important topics related to depression were revealed. The audio features were predominant to the other feature categories in depression classification while the contributions of the three feature categories to severity estimation were almost equal. More depression samples in the database we used should be further included. The second stage of feature selection is relatively time-consuming. This pipeline of depression recognition as well as the preferred topics and feature categories are expected to be useful in supporting the diagnosis of psychological distress conditions.


Pulmonary ultrasound scoring system for intubated critically ill patients and its association with clinical metrics and mortality: A prospective cohort study.
Pulmonary ultrasound (PU) examination at the point-of-care can rapidly identify the etiology of acute respiratory failure (ARF) and assess treatment response. The often-subjective classification of PU abnormalities makes it difficult to document change over time and communicate findings across providers. The study goal was to develop a simple, PU scoring system that would allow for standardized documentation, have high interprovider agreement, and correlate with clinical metrics. In this prospective study of 250 adults intubated for ARF, a PU examination was performed at intubation, 48-hours later, and at extubation. A total lung score (TLS) was calculated. Clinical metrics and final diagnosis were extracted from the medical record. TLS correlated positively with mortality (P = .03), ventilator hours (P = .003), intensive care unit, and hospital length of stay (P = .003, P = .008), and decreasing PaO2 /FiO2 (P < .001). Agreement of PU findings was very good (kappa = 0.83). Baseline TLS and subscores differed significantly between ARF categories (nonpulmonary, obstructive, and parenchymal disease). A quick, scored, PU examination was associated with clinical metrics, including mortality among a diverse population of patients intubated for ARF. In addition to diagnostic and prognostic information at the bedside, a standardized and quantifiable approach to PU provides objectivity in serial assessment and may enhance communication of findings between providers.


Recombinant human leptin attenuates stress axis activity in common carp (Cyprinus carpio L.).
Proper functioning of the endocrine stress axis requires communication between the stress axis and other regulatory mechanisms. We here describe an intimate interplay between the stress axis and recombinant human leptin (rhLeptin) in a teleostean fish, the common carp Cyprinus carpio. Restraint stress (by netting up to 96h) increased plasma cortisol but did not affect hepatic leptin expression. Perifusion of pituitary glands or head kidneys with rhLeptin revealed direct effects of rhLeptin on both tissues. RhLeptin suppresses basal and CRF-induced ACTH-secretion in a rapid and concentration-dependent manner. The rhLeptin effect persisted for over an hour after administration had been terminated. RhLeptin decreases basal interrenal cortisol secretion in vitro, and by doing so attenuates ACTH-stimulated cortisol production; rhLeptin does not affect interrenal ACTH-sensitivity. Our findings show that the endocrine stress axis activity and leptin are inseparably linked in a teleostean fish, a notion relevant to further our insights in the evolution of leptin physiology in vertebrates.


Vascularization of hollow channel-modified porous silk scaffolds with endothelial cells for tissue regeneration.
Despite the promise for stem cell-based tissue engineering for regenerative therapy, slow and insufficient vascularization of large tissue constructs negatively impacts the survival and function of these transplanted cells. A combination of channeled porous silk scaffolds and prevascularization with endothelial cells was investigated to test the ability of this tissue engineering strategy to support rapid and extensive vascularization process. We report that hollow channels promote in vitro prevascularization by facilitating endothelial cell growth, VEGF secretion, and capillary-like tube formation. When implanted in vivo, the pre-established vascular networks in the hollow channel scaffolds anastomose with host vessels and exhibit accelerated vascular infiltration throughout the whole tissue construct, which provides timely and sufficient nutrients to ensure the survival of the transplanted stem cells. This tissue engineering strategy can promote the effective application of stem cell-based regeneration to improve future clinical applications.


SMT and TOFT: Why and How They are Opposite and Incompatible Paradigms.
The Somatic Mutation Theory (SMT) has been challenged on its fundamentals by the Tissue Organization Field Theory of Carcinogenesis (TOFT). However, a recent publication has questioned whether TOFT could be a valid alternative theory of carcinogenesis to that presented by SMT. Herein we critically review arguments supporting the irreducible opposition between the two theoretical approaches by highlighting differences regarding the philosophical, methodological and experimental approaches on which they respectively rely. We conclude that SMT has not explained carcinogenesis due to severe epistemological and empirical shortcomings, while TOFT is gaining momentum. The main issue is actually to submit SMT to rigorous testing. This concern includes the imperatives to seek evidence for disproving one's hypothesis, and to consider the whole, and not just selective evidence.


Positioning work related stress - GPs' reasoning about using the WSQ combined with feedback at consultation.
General practitioners (GPs) regularly handle cases related to stress and work capacity, but often find this work difficult. However, using an assessment tool in a structured way can increase GPs' awareness of the risk for sick leave and need of referrals to preventive measures. Today there is no established methodical practice for this in primary health care. The aim of this study was to explore GPs' reasoning about using the Work Stress Questionnaire combined with feedback at consultation as an early intervention to reduce sick leave. A focus group study was performed with 23 GPs at six primary health care centres. The discussions were analysed based on a method by Krueger. Three themes emerged. Positioning work-related stress describes the need to make fundamental standpoints on stress and how it should be handled, to make sense of their work concerning work-related stress. Making use of resources focuses on GPs performing to the best of their ability using assigned resources to treat patients with stress-related ill health, even if the resources were perceived as insufficient. Practising daily work focuses on the GPs' regular and preferred way of working set against the degree of intrusion and benefits. The two related themes making use of resources and practising daily work were mirrored through the third theme, positioning work-related stress, to form an understanding of how GPs should work with patients perceiving work-related stress. The GPs own competence and tools, those of other professionals and the time allocated were seen as important when treating patients perceiving ill health due to work-related stress. When resources were insufficient though, the GPs questioned their responsibility for these patients. The results also indicate that the GPs viewed their ordinary consultative way of working as sufficient to identify these patients. The intervention was therefore not seen as useful for early treatment of patients at risk of sick leave due to work-related stress. However, prevention is an important part of the PHC's responsibility, and strategies concerning stress-related ill health therefore need to be more thoroughly formulated and incorporated. ClinicalTrials.gov, NCT02480855 . Registered 20 May 2015.


[Trigeminal involvement as the presentation of syringomyella and of an abnormality of the occipito-vertebral junction (author's transl)].
Trigeminal involvement in syringomyelia or in a malformation of the occipito-vertebral junction may rarely be the presenting feature of the disorder. Two cases are reported: in the first, recurrent pruritus of the side of the nose due to sensory involvement of CN V was the presenting feature of syringomyelia; in the second, a malformation of the occipito-vertebral junction presented with refractory and painful trismus by irritation of the motor part of the trigeminal nerve.


An uncommon cause of myalgia: A case report on systemic lupus erythematous myopathy.
Myositis in systemic lupus erythematous may present in a wide range of clinical spectrum. It can be part of an overlap syndrome, or mixed connective tissue disease or a musculoskeletal manifestation of systemic lupus erythematous itself. Here, we present a young girl with an underlying systemic lupus erythematous presented with the typical manifestation of severe proximal myopathy in the background of normal creatine kinase values. The diagnosis of systemic lupus erythematous myopathy was made after excluding other more common causes of myopathies which in itself is a very rare occurrence. A normal creatine kinase values does not exclude systemic lupus erythematous myositis, but make the diagnosis more challenging. However, there are other parameters or diagnostic tools which can be used to exclude a myositis. This case elucidates the importance of history and physical examination in the face of some conflicting laboratory data.


Physiological and proteomic changes of Castanopsis fissa in response to drought stress.
Castanopsis fissa is a native, broadleaf tree species in Guangdong with characteristics of barrenness and fast growth and is often used as a pioneer species for vegetation restoration with excellent ecological benefits. To explore the response of C.fissa to drought, this study investigated the drought tolerance mechanism of C.fissa using physiological and proteomic assessments. Using a potted continuous drought experimental method with normal water supply as a control, we measured photosynthetic parameters, antioxidant enzyme activities, and osmoregulatory substances of C. fissa in response to drought stress for 1 to 4 weeks, respectively. In addition, we used TMT quantitative proteomics to identify differentially expressed proteins (DEPs) between the drought-stress-treated C. fissa leaves and the control leaves. With the extension of drought stress time, the photosynthetic indexes and peroxidase (POD) activity of C. fissa leaves showed a decreasing trend. The malondialdehyde (MDA) content; superoxide Dismutase (SOD) and catalase (CAT) activities; and proline (Pro), soluble sugar (SS) and soluble protein (SP) contents showed an overall increasing trend, all of which reached significant differences at 4 w of stress. We identified 177 and 529 DEPs in the 2 and 4 weeks drought-stress leaves, respectively, in reference to the control leaves. These DEPs were closely related to physiological metabolic processes such as photosynthesis, energy and carbohydrate metabolism, stress response and defense, transcriptional regulation, and signal ion transduction. Drought stress mainly affects photosynthesis, carbohydrate metabolism, and protein synthesis and degradation in C. fissa leaves. At 2 weeks of stress, the expression of carbon metabolism, pyruvate metabolism and ribosome-related proteins was significantly changed, however, and at 4 weeks of stress, protein processing in the endoplasmic reticulum and spliceosome-related proteins were significantly increased in plant leaves. To alleviate the effect of water unavailability, the drought-stressed C.fissa leaves increased its oxidative protective enzyme system to eliminate excess reactive oxygen species (ROS) and also increased its Pro and SP contents to maintain the intracellular osmotic potential balance.


Comma-Shaped Columellar Strut for Nasal Tip Plasty in East Asian Rhinoplasty.
For East Asians, rhinoplasty procedures are predominantly focused on reconstructing a well-defined nasal tip. In this study, the authors present a new graft design for the columellar strut that is similar to the shape of a comma mark. As one integrated piece, the graft undertakes the roles of providing solid support for the tip, modifying different angles, as well as relationships between the tip and columella. One hundred and sixty-five female patients, ranging in age from 18 to 42 years (average 27.1 years), received augmentation rhinoplasty surgery over the past 4 years with an average postoperative follow-up of 12 months. Among these patients, 78 of them were primary cases and others were secondary or more. The cartilaginous framework was reconstructed based on comma strut with other grafts including spreaders and dorsal onlay grafts. Patients' own evaluations on the overall improvements of the nose rendered high satisfaction rate. During the long-term follow-up, 8 cases presented asymmetrical nostrils with slightly deviated columella; minor revision surgeries were performed. Another 3 cases presented dorsal graft warping and were also corrected. No other major complications were encountered. The comma strut provides a reliable support for the nasal tip; its dual curved structure plays the instrumental role in defining the lobular-columellar angle as well as modifying the supratip break. This graft design offers good control of tip and columella; as a result, consistent, reproducible results can be achieved. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .


Human cytomegalovirus glycoprotein UL141 targets the TRAIL death receptors to thwart host innate antiviral defenses.
Death receptors (DRs) of the TNFR superfamily contribute to antiviral immunity by promoting apoptosis and regulating immune homeostasis during infection, and viral inhibition of DR signaling can alter immune defenses. Here we identify the human cytomegalovirus (HCMV) UL141 glycoprotein as necessary and sufficient to restrict TRAIL DR function. Despite showing no primary sequence homology to TNF family cytokines, UL141 binds the ectodomains of both human TRAIL DRs with affinities comparable to the natural ligand TRAIL. UL141 binding promotes intracellular retention of the DRs, thus protecting virus infected cells from TRAIL and TRAIL-dependent NK cell-mediated killing. The identification of UL141 as a herpesvirus modulator of the TRAIL DRs strongly implicates this pathway as a regulator of host defense to HCMV and highlights UL141 as a pleiotropic inhibitor of NK cell effector function.


Computational structural analysis of proteins of Mycobacterium tuberculosis and a resource for identifying off-targets.
Advancement in technology has helped to solve structures of several proteins including M. tuberculosis (MTB) proteins. Identifying similarity between protein structures could not only yield valuable clues to their function, but can also be employed for motif finding, protein docking and off-target identification. The current study has undertaken analysis of structures of all MTB gene products with available structures was analyzed. Majority of the MTB proteins belonged to the α/β class. 23 different protein folds are used in the MTB protein structures. Of these, the TIM barrel fold was found to be highly conserved even at very low sequence identity. We identified 21 paralogs and 27 analogs of MTB based on domains and EC classification. Our analysis revealed that many of the current drug targets share structural similarity with other proteins within the MTB genome, which could probably be off-targets. Results of this analysis have been made available in the Mycobacterium tuberculosis Structural Database (http://bmi.icmr.org.in/mtbsd/MtbSD.php/search.php) which is a useful resource for current and novel drug targets of MTB.


Endocrine Complications of Cystic Fibrosis.
Endocrine comorbidities have become increasingly important medical considerations as improving cystic fibrosis (CF) care increases life expectancy. Although the underlying pathophysiology of CF-related diabetes remains elusive, the use of novel technologies and therapeutics seeks to improve both CF-related outcomes and quality of life. Improvements in the overall health of those with CF have tempered concerns about pubertal delay and short stature; however, other comorbidities such as hypogonadism and bone disease are increasingly recognized. Following the introduction of highly effective modulator therapies there are many lessons to be learned about their long-term impact on endocrine comorbidities.


Preparation and preclinical evaluation of 177Lu-nimotuzumab targeting epidermal growth factor receptor overexpressing tumors.
Nimotuzumab (h-R3) is a humanized monoclonal antibody (mAb) which recognizes the external domain of the epidermal growth factor receptor (EGFR) with high specificity. It was demonstrated that h-R3 has a unique clinical profile for immunotherapy of adult gliomas and pediatric pontine gliomas. The aim of this work was to evaluate the conjugate (177)Lu-h-R3 as a potential radioimmunoconjugate for radioimmunotherapy (RIT) of tumors overexpressing EGFR. h-R3 was modified with the macrocylcic ligand S-2-(4-isothiocyanatobenzyl)-1,4,7,10-tetraazacyclododecane tetraacetic acid (p-SCN-Bn-DOTA) and the acyclic ligand S-2-(4-Isothiocyanatobenzyl)-diethylenetriamine pentaacetic acid (p-SCN-Bn-DTPA); the immunoconjugates were labeled with no-carried added (177)Lu. Specificity and affinity were tested using radioimmunoassays in a cell line overexpressing EGFR. Biodistribution in mice, healthy or bearing A431 epithelial carcinoma xenografts, was performed for 11 days. Tumor uptake, the influence of the nature of the chelate and the way of administration were studied. Absorbed dose in tumor and selected organs was calculated using the OLINDA/EXM software; the data from the animals was extrapolated to humans. (177)Lu-h-R3 conjugates were obtained with specific activity up to 915 MBq/mg without significant loss of immunoreactivity. The binding of (177)Lu-h-R3 conjugates to A431 cells showed to be EGFR specific, and the affinity was similar to native h-R3. Tumor uptake reached a maximum value of 22.4±3.1 %ID/g at 72 h and remained ~20% ID/g over 1 week. Locoregional application showed better tumor/nontumor ratios than intravenous application. (177)Lu-h-R3 should be considered for further evaluations as a potential radiopharmaceutical for RIT of tumors overexpressing EGFR.


Spatial interrelationships between proteoglycans and extracellular matrix proteins in cell cultures.
Immunolabelling of cultured cells for chondroitin-sulfate proteoglycan (CSPG), in conjunction with antibodies to fibronectin, collagen and laminin, revealed the spatial interrelationships between the different matrix components. CSPG was organized in two major forms. Fibronectin-independent dotted patterns of CSPG were detected on the substrate and cell surfaces at early stages after plating. At later stages, however, significant overlapping was found between the two extracellular matrix components. Immunoelectron microscopic examination indicated that the CSPG was organized as granules of varying sizes which were associated with the cell surface, the substrate, or with the periphery of the fibronectin network.


Sialo-cutaneous fistula with ectopic submandibular gland sialolith, revealing a hidden ipsilateral enlarged and elongated styloid process: a consideration based on CT findings.
Sialolithiasis is a common salivary pathology, and an uncommon complication of sialadenitis and sialolithiasis is the formation of fistulous tracts to other compartments. Submandibular gland sialo-oral fistulae are not particularly remarkable, given the location of the gland and Wharton's duct, but submandibular sialolith-associated fistulae to other cervico-facial compartments (transcervical sialo-cutaneous and sialo-pharyngeal fistulae) are much less common. We report herein an unusual case of a 49-year-old obese man with sialo-cutaneous fistula containing a large, ectopic sialolith in subcutaneous tissue that was expected to undergo spontaneous elimination, but revealed hidden Eagle syndrome featuring an ipsilateral enlarged, elongated styloid process. Furthermore, we offer a thorough review of the literature regarding sialo-fistulae and highlight the relationship between an abnormal styloid process and submandibular sialadenitis with sialolithiasis and new tract formation based on computed tomography.


Characterization of glutathione-dependent inhibition of lipid peroxidation of isolated rat liver nuclei.
Glutathione (GSH) is known to play an important role in protecting cells against oxidative stress. The present study was undertaken to assess the ability of GSH to protect isolated rat liver nuclei against NADPH-induced peroxidation. Nuclei were isolated from rat liver homogenates by discontinuous sucrose gradient centrifugation, and lipid peroxidation was induced by 1.7 mM ADP, 0.11 mM EDTA, 0.1 mM FeCl3, and either 1 mM NADPH or 0.5 mM ascorbate. The amount of lipid peroxidation was determined by measuring the formation of thiobarbituric acid-reactive products and the disappearance of lipid unsaturated fatty acid moieties. The addition of GSH (0.1 to 1.0 mM) produced a concentration-dependent lag period prior to the onset of lipid peroxidation. This GSH-induced lag period was abolished by pretreatment of nuclei with trypsin, thiol modifying reagents, disulfides, or heating nuclei at 60 degrees C for 15 min. Nuclei which were incubated with GSH also catalyzed the conversion of cumene hydroperoxide to cumyl alcohol. Similarly, this activity was also inhibited by thiol modifying reagents, disulfides, and heating nuclei at 60 degrees C for 15 min. The data suggest that a GSH-dependent peroxidase activity is associated with rat liver nuclear membranes which are capable of inhibiting lipid peroxidation.


Total Hip Arthroplasty After Prior Acetabular Fracture: Infection Is a Real Concern.
Acetabular fractures often require surgical intervention for fracture fixation and can result in premature osteoarthritis of the hip joint. This study hypothesized that total hip arthroplasty (THA) in patients with a prior acetabular fracture who had undergone open reduction and internal fixation (ORIF) is associated with a higher rate of subsequent periprosthetic joint infection (PJI). About 72 patients with a history of acetabular fracture that required ORIF, undergoing conversion THA between 2000 and 2017 at our institution, were matched based on age, gender, body mass index, Charlson comorbidity index, and date of surgery in a 1:3 ratio with 215 patients receiving primary THA. The mean follow-up for the conversion THA cohort was 2.9 years (range, 1-12.15) and 3.06 years (range, 1-12.96) for the primary THA. Patients with a previous acetabular fracture, compared with the primary THA patients, had longer operative times, greater operative blood loss, and an increased need for allogeneic blood transfusion (26.4% vs 4.7%). Most notably, PJI rate was significantly higher in acetabular fracture group at 6.9% compared with 0.5% in the control group. Complications, such as aseptic revision, venous thromboembolism, and mortality, were similar between both groups. The present study demonstrates that conversion THA in patients with prior ORIF of acetabular fractures is associated with higher complication rate, in particular PJI, and less optimal outcome compared with patients undergoing primary THA. The latter findings compel us to seek and implement specific strategies that aim to reduce the risk of subsequent PJI in these patients.


Application of Resting State Functional MR Imaging to Presurgical Mapping: Language Mapping.
Resting state functional MR imaging (rs-fMR imaging) has become an indispensable tool for examining brain function. The greatest opportunity to translate rs-fMR imaging from the research domain into clinical use is as a tool for examining intrinsic brain networks for preoperative planning. Many studies have demonstrated concordance of intrinsic motor networks from rs-fMR imaging data with task-fMR imaging and direct cortical stimulation. Earlier reports show concordance of language networks as well, although more recent studies with larger numbers of subjects demonstrate subject-level variability that needs to be further investigated and addressed before widespread implementation of rs-fMR imaging for preoperative planning.


A History of the Lobes of the Brain.
The division of the cerebrum into 5 lobes is widely accepted in the scientific community. Despite this, a history of the lobes of the brain has not been discussed in the literature. Therefore, this article recounts this history with emphasis on the contributions of Thomas Willis (1664), Felix Vicq d'Azyr (1796), Johann-Christian Reil (1796), François Chaussier (1807), and Louis Pierre Gratiolet and François Leuret (1857) into one of the most widely accepted concepts in neuroanatomy.


The intertwined metabolism during symbiotic nitrogen fixation elucidated by metabolic modelling.
Genome-scale metabolic network models can be used for various analyses including the prediction of metabolic responses to changes in the environment. Legumes are well known for their rhizobial symbiosis that introduces nitrogen into the global nutrient cycle. Here, we describe a fully compartmentalised, mass and charge-balanced, genome-scale model of the clover Medicago truncatula, which has been adopted as a model organism for legumes. We employed flux balance analysis to demonstrate that the network is capable of producing biomass components in experimentally observed proportions, during day and night. By connecting the plant model to a model of its rhizobial symbiont, Sinorhizobium meliloti, we were able to investigate the effects of the symbiosis on metabolic fluxes and plant growth and could demonstrate how oxygen availability influences metabolic exchanges between plant and symbiont, thus elucidating potential benefits of inter organism amino acid cycling. We thus provide a modelling framework, in which the interlinked metabolism of plants and nodules can be studied from a theoretical perspective.


Predictors of voluntary home-smoking restrictions and associations with an objective measure of in-home smoking among subsidized housing tenants.
Examine predictors of voluntary home-smoking restrictions (HSRs) and associations with an objective measure of in-home smoking. Cross-sectional. Publicly subsidized multiunit housing units managed by private company in Columbus, Ohio, without a smoke-free housing policy. Probability sample of primary leaseholders (N = 301, 64% response rate). Self-reported knowledge, attitudes, and behaviors collected during face-to-face survey in fall 2011, including individual (e.g., knowledge of health effects), social (e.g., number of friends who smoke), and environmental (e.g., safety) factors hypothesized to be related to having HSRs. Surface nicotine concentration (μg/m(2)) based on samples collected from wood surface in respondents' living rooms (n = 279). Multiple linear and logistic regression were used to identify factors associated with having HSRs and with indoor surface nicotine concentrations. Fewer than one-third (29.2%) of tenants had complete HSRs, while more than half (55.8%) had partial restrictions. Several individual and social factors, but no environmental/community factors, were associated with having HSRs. Type of HSRs (p < .001) and smoking status (p < .001) were independently associated with mean surface nicotine concentrations. Few subsidized housing tenants voluntarily limit in-home smoking. Partial restrictions could be considered as a harm reduction strategy but may be less effective among smokers. Strategies to change social norms are also needed to modify in-home smoking behavior among subsidized housing tenants.


Bordetella bronchicanis (bronchiseptica) infection in man: review and a case report.
Bordetella bronchicanis is a common respiratory tract commensal of mammals. Rarely it causes whooping cough in children. Compromised adults in hospitals may be colonised, and one terminal pneumonia is on record. The fatal pneumonia of a malnourished alcoholic described here was contracted at home.


Problem-Solving Therapy in the Elderly.
We systematically reviewed randomized clinical trials of problem-solving therapy (PST) in older adults. Our results indicate that PST led to greater reduction in depressive symptoms of late-life major depression than supportive therapy (ST) and reminiscence therapy. PST resulted in reductions in depression comparable with those of paroxetine and placebo in patients with minor depression and dysthymia, although paroxetine led to greater reductions than placebo. In home health care, PST was more effective than usual care in reducing symptoms of depression in undiagnosed patients. PST reduced disability more than ST in patients with major depression and executive dysfunction. Preliminary data suggest that a home-delivered adaptation of PST that includes environmental adaptations and caregiver involvement is efficacious in reducing disability in depressed patients with advanced cognitive impairment or early dementia. In patients with macular degeneration, PST led to improvement in vision-related disability comparable to that of ST, but PST led to greater improvement in measures of vision-related quality of life. Among stroke patients, PST participants were less likely to develop a major or minor depressive episode than those receiving placebo treatment, although the results were not sustained in a more conservative statistical analysis. Among patients with macular degeneration, PST participants had significantly lower 2-month incidence rates of major depression than usual care participants and were less likely to suffer persistent depression at 6 months. Finally, among stroke patients, PST participants were less likely to develop apathy than those receiving placebo treatment. PST also has been delivered via phone, Internet, and videophone, and there is evidence of feasibility and acceptability. Further, preliminary data indicate that PST delivered through the Internet resulted in a reduction in depression comparable with that of in-person PST in home-care patients. PST delivered via videophone results in an improvement in hospice caregivers' quality of life and a reduction in anxiety comparable to those of in-person PST. PST-treated patients with cognitive impairment may require additional compensatory strategies, such as written notes, memory devices, environmental adaptations, and caregiver involvement.


Live agent preference and social action monitoring in the macaque mid-superior temporal sulcus region.
Mentalizing, the ability to infer the mental states of others, is a cornerstone of adaptive social intelligence. While functional brain mapping of human mentalizing has progressed considerably, its evolutionary signature in nonhuman primates remains debated. The discovery that the middle part of the macaque superior temporal sulcus (mid-STS) region has a connectional fingerprint most similar to the human temporoparietal junction (TPJ)-a crucial node in the mentalizing network-raises the possibility that these cortical areas may also share basic functional properties associated with mentalizing. Here, we show that this is the case in aspects of a preference for live social interactions and in a theoretical framework of predictive coding. Macaque monkeys were trained to perform a turn-taking choice task with another real monkey partner sitting directly face-to-face or a filmed partner appearing in prerecorded videos. We found that about three-fourths of task-related mid-STS neurons exhibited agent-dependent activity, most responding selectively or preferentially to the partner's action. At the population level, activities of these partner-type neurons were significantly greater under live-partner compared to video-recorded-partner task conditions. Furthermore, a subset of the partner-type neurons responded proactively when predictions about the partner's action were violated. This prediction error coding was specific to the action domain; almost none of the neurons signaled error in the prediction of reward. The present findings highlight unique roles of the macaque mid-STS at the single-neuron level and further delineate its functional parallels with the human TPJ in social cognitive processes associated with mentalizing.


Apolipoprotein E LDL receptor-binding domain-containing high-density lipoprotein: a nanovehicle to transport curcumin, an antioxidant and anti-amyloid bioflavonoid.
Curcumin is an antioxidant and anti-inflammatory bioflavonoid that has been recently identified as an anti-amyloid agent as well. To make it more available in its potent form as a potential amyloid disaggregation agent, we employed high-density lipoproteins (HDL), which are lipid-protein complexes that transport plasma cholesterol, to transport curcumin. The objective of this study was to employ reconstituted HDL containing human apoE3 N-terminal (NT) domain, as a vehicle to transport curcumin. The NT domain serves as a ligand to mediate binding and uptake of lipoprotein complexes via the low-density lipoprotein receptor (LDLr) family of proteins located at the cell surface. Reconstituted HDL was prepared with phospholipids and recombinant apoE3-NT domain in the absence or presence of curcumin. Non-denaturing polyacrylamide gel electrophoresis indicated that the molecular mass and Stokes' diameter of HDL bearing curcumin were ~670kDa and ~17nm, respectively, while electron microscopy revealed the presence of discoidal particles. Fluorescence emission spectra of HDL bearing (the intrinsically fluorescent) curcumin indicated that the wavelength of maximal fluorescence emission (λ(max)) of curcumin was ~495nm, which is highly blue-shifted compared to λ(max) of curcumin in solvents of varying polarity (λ(max) ranging from 515-575nm) or in aqueous buffers. In addition, an enormous enhancement in fluorescence emission intensity was noted in curcumin-containing HDL compared to curcumin in aqueous buffers. Curcumin fluorescence emission was quenched to a significant extent by lipid-based quenchers but not by aqueous quenchers. These observations indicate that curcumin has partitioned efficiently into the hydrophobic milieu of the phospholipid bilayer of HDL. Functional assays indicated that the LDLr-binding ability of curcumin-containing HDL with apoE3-NT is similar to that of HDL without curcumin. Taken together, we report that apoE-containing HDL has a tremendous potential as a 'nanovehicle' with a homing device to transport curcumin to target sites.


Improved immunodiagnosis of human cysticercosis with scolex protein antigens.
Crude antigenic extract (CAE) and a scolex protein antigen (SPA) of Taenia solium cysticerci were used in indirect haemagglutination (IH) and enzyme-linked immunosorbent assay (ELISA) to detect serum antibodies in cysticercosis patients. Complement fixation (CF) was used for comparison with antigens obtained as an alcoholic extract of CAE (ACAE) and SPA (ASPA). For each test, a dilution was chosen which showed no cross-reactivity with sera from patients with other parasitic diseases such as taeniasis, schistosomiasis, ancylostomiasis, ascaridiasis, strongyloidiasis, Chagas' disease and syphilis. For the CF, 1:4 was the discriminative dilution determined; for IH, 1:16 and for ELISA, 1:256. The CF could detect serum antibodies to cysticerci in 45% of patients when ACAE antigen was used and 73% using ASPA. In the IH, serum antibody was detected in 73% of patients when CAE was used and 86% using SPA. In ELISA 63% of patients were positive when CAE was used and 91% using SPA. The use of SPA improved the serological distinction between infected and uninfected patients in all tests and the ELISA showed a significantly higher capacity to detect infected patients.


Iterative RF pulse design for multidimensional, small-tip-angle selective excitation.
The excitation k-space perspective on small-tip-angle selective excitation has facilitated RF pulse designs in a range of MR applications. In this paper, k-space-based design of multidimensional RF pulses is formulated as a quadratic optimization problem, and solved efficiently by the iterative conjugate-gradient (CG) algorithm. Compared to conventional design approaches, such as the conjugate-phase (CP) method, the new design approach is beneficial in several regards. It generally produces more accurate excitation patterns. The improvement is particularly significant when k-space is undersampled, and it can potentially shorten pulse lengths. A prominent improvement in accuracy is also observed when large off-resonance gradients are present. A further boost in excitation accuracy can be accomplished in regions of interest (ROIs) if they are specified together with "don't-care" regions. The density compensation function (DCF) is no longer required. In addition, regularization techniques allow control over integrated and peak pulse power.


Early treatment with ursodeoxycholic acid for cholestasis in children on parenteral nutrition because of primary intestinal failure.
There is conflicting evidence as to whether ursodeoxycholic acid (UDCA) reduces the incidence of parenteral nutrition-associated cholestasis. To investigate the efficacy of UDCA on parenteral nutrition-associated cholestasis in children with intestinal failure due to short bowel syndrome or to other causes. Children with cholestasis received 30 mg/kg/day UDCA. Improvement or normalization of parenteral nutrition-associated cholestasis was evaluated at 6 months of therapy and at the last follow-up. In a subgroup of children, serum UDCA levels were measured while receiving UDCA and after 4 weeks withdrawal. Twelve children were treated with UDCA. Full remission or partial improvement of parenteral nutrition-associated cholestasis occurred in 11 of 12 children. In three of four children, withdrawal of UDCA was associated with a rebound rise of cholestasis. Only one of 12 treated children showed no improvement and in this patient, in contrast to four other patients, plasma levels of UDCA did not increase during treatment. Ursodeoxycholic acid was effective in controlling parenteral nutrition-associated cholestasis. The efficacy of UDCA also in children with short bowel is related to intestinal absorption.


Preventing and reducing the impacts of intimate partner violence: Opportunities for Australian ambulance services.
Violence against women is pervasive worldwide, and a high proportion of the most damaging violence is perpetrated by male intimate partners. The Australian government is committed to action to prevent such violence; however, strategies require input and collaboration from all agencies engaging patients, including ambulance services. To date no Australian ambulance service has published comprehensive guidelines or strategies to improve health outcomes for intimate partner violence patients in line with national strategies. To propose key actions for Australian ambulance services to undertake to reduce the impacts of intimate partner violence in line with national strategies. We reviewed the Australian government's National Plan to reduce violence towards women and its supporting literature, and created key actions for Australian ambulance services. Our review has yielded four key actions that Australian ambulance services could undertake immediately for the benefit of intimate partner violence patients. Actions include collaboration with external agencies, education, data collection and championing values promoting zero tolerance of violence towards women. Australian ambulance services are currently underserving intimate partner violence patients and must undertake immediate action. Successful strategies to address knowledge and policy gaps will require significant input and guidance from key organisations, including advocacy groups, police and EDs. It is likely that EDs will need to take the lead in creating comprehensive policies and guidelines from which ambulance services can derive their own policies. Failure to address this practice gap might result in paramedics becoming a barrier for intimate partner patients to receive appropriate care and support.


Nicotine potentiation of haloperidol-induced catalepsy: striatal mechanisms.
Nicotine potentiated the catalepsy produced by haloperidol. The excitotoxin quinolinic acid (QA) selectively destroys striatal neurons when injected directly into the striatum. Bilateral QA lesions of the rat striatum (150 nmol) significantly reduced the catalepsy produced by haloperidol as well as the ability of nicotine to potentiate haloperidol-induced catalepsy. A second experiment examined whether the ability of nicotine to potentiate haloperidol-induced catalepsy was associated with a potentiation of dopamine turnover following haloperidol. Nicotine alone produced a mild increase in dopamine turnover relative to saline treated controls while haloperidol produced a marked increase in dopamine turnover relative to saline- and nicotine-treated controls. However, the combined administration of haloperidol and nicotine did not further elevate dopamine turnover over that observed following haloperidol alone. The results indicated that: 1) nicotine could not potentiate haloperidol-induced catalepsy without an intact striatum and 2) the behavioral effect of nicotine and haloperidol cotreatment was not due to any change in dopamine turnover.


Measuring receptor recycling in polarized MDCK cells.
Recycling of proteins such as channels, pumps, and receptors is critical for epithelial cell function. In this chapter we present a method to measure receptor recycling in polarized Madin-Darby canine kidney cells using an iodinated ligand. We describe a technique to iodinate transferrin (Tf), we discuss how (125)I-Tf can be used to label a cohort of endocytosed Tf receptor, and then we provide methods to measure the rate of recycling of the (125)I-Tf-receptor complex. We also show how this approach, which is easily adaptable to other proteins, can be used to simultaneously measure the normally small amount of (125)I-Tf transcytosis and degradation.


[Teratospermia consisting of the absence of the head of the spermatozoa because of a fault in the joint between the head and the neck of the sperm in man (author's transl)].
An ultrastructural sperm study was conducted in a sterile man whose sperm count showed 100 percent headless spermatozoa. Testicular biopsy showed abnormal spermatogenesis : within the spermatid, the sperm head developed separately from the flagellum, which alone was ejected during spermiation.


Transcriptomic analysis of micropapillary high grade T1 urothelial bladder cancer.
No consensus currently exist on the optimal treatment of patients with high-risk nonmuscle invasive (HGT1) micropapillary variant of bladder cancer (MPBC). Transcripsome analysis may allow stratification of MPBC-HGT1 enabling prediction of recurrence and guide therapeutic management for individual patients. Whole transcriptome RNA-Sequencing of tumors from 23 patients with MPBC-HGT1 and 64 conventional urothelial carcinomas (cUC) (reference set) was performed. Differentially expressed genes between MPBC-HGT1 and cUC-HGT1 were explored. Cox proportional hazard models and Kapplan-Meier methods were used to assess the relation between time to progression (TTP) and individual gene expression adjusting for clinical covariates. Over 3000 genes were differentially expressed in MPBC-HGT1 as compared with cUC-HGT1 and a 26-gene signature is characteristic of MPBC within HGT1. A set of three genes; CD36, FAPB3 and RAETE1; were significantly associated with TTP. High expression of FABP3 and CD36 were associated with shorter TTP (p = 0.045 and p = 0.08) as was low expression of RAET1E (p = 0.01). Our study suggest that a 26-gene signature can define MPBC-HGT1 within conventional urothelial carcinomas. A prognostic risk index of three genes (FABP3, CD36 and RAET1E) was found to be associated with shorter TTP and may help classify a group of patients with MPBC-HGT1 with high-risk of early progression. These observations might have implications in terms of radical cystectomy recommendation in MPBC patients.


Amino acid sulfur as a source of sulfate for sulfated proteoglycans produced by Swiss mouse 3T3 cells.
The uptake of sulfate by Swiss mouse 3T3 cells is blocked in the presence of 1 mM 4-isothiocyano-4'-acetamido-stilbene-2,2-disulfonic acid (SITS). In the absence of an exogenous source of sulfate, glycosaminoglycans produced by cells in the presence of the inhibitor are sulfated to the same extent as those produced by cells grown in its absence. The sulfate utilized in the absence of medium sulfate has been identified as that produced by the oxidation of the sulfur present in the amino acids cysteine and methionine. This finding indicates that, under conditions of restricted exogenous sulfate, caution is needed in the interpretation of data obtained with the use of [35S]methionine and/or [35S]cysteine as a general protein label, since both tyrosine and a variety of types of protein-linked carbohydrate chains may be modified by sulfation.