Effects of flavonoid phytochemicals on cortisol production and on activities of steroidogenic enzymes in human adrenocortical H295R cells.
Inhibitory effects of flavonoid phytochemicals, flavones, flavonols and isoflavones on cortisol production were examined in human adrenal H295R cells stimulated with di-buthylyl cAMP. In addition, the inhibitory effects of these chemicals on the activity of P450scc, 3beta-HSD type II (3beta-HSD II), P450c17, P450c21 and P45011beta, steroidogenic enzymes involved in cortisol biosynthesis, were examined in the same cells. Exposure to 12.5 microM of the flavonoids 6-hydroxyflavone, 4'-hydroxyflavone, apigenin, daidzein, genistein and formononetin significantly decreased cortisol production (by 6.3, 69.6, 47.5, 26.6, 13.8 and 11.3%, respectively), and biochanin A significantly decreased cortisol production (by 47.3%) at a concentration of 25 microM without any significant cytotoxic effects or changes in cell number. Daidzin, the 7-glucoside of daidzein, did not alter cortisol production by H295R cells at concentrations over 10 microg/ml (24 microM). Daidzein-induced reduction of cortisol production by H295R cells was not inhibited by the estrogen receptor antagonist ICI 182,780. The flavonoids 6-hydroxyflavone, daidzein, genistein, biochanin A and formononetin strongly and significantly inhibited microsomal 3beta-HSD II activity at concentrations from 1 to 25 microM, and I(50) values were estimated to be 1.3, 2, 1, 0.5 and 2.7 microM, respectively. In addition, these flavonoids significantly inhibited microsomal P450c21 activity at 12.5 and/or 25 microM. In addition, 6-hydroxyflavone inhibited activity of microsomal P450c17 and mitochondrial P45011beta at 12.5 and/or 25 microM. Results of Lineweaver-Burk's plot analysis indicate that daidzein is a competitive inhibitor of the activity of 3beta-HSD II and P450c21. K(m) and V(max) values of 3beta-HSD II for DHEA were estimated to be 6.6 microM and 328pmol/minmg protein, respectively. K(m) and V(max) values of P450c21 for progesterone were estimated to be 2.8 microM and 16pmol/minmg protein, respectively. K(i) values of 3beta-HSD II and P450c21 for daidzein were estimated to be 2.9 and 33.3 microM, respectively.


The frequency and severity of cat allergy vs. dog allergy in atopic children.
Questions were put to parents accompanying 1238 children, 1 to 17 yr old, who had symptoms of respiratory tract allergy. Skin prick tests were then performed. Symptoms after exposure to cats and positive skin test results from cat hair extract were significantly more frequent than symptoms after exposure to dogs or reactions to dog hair extract. The prevalence of symptoms and positive skin test reactions to cat allergens increased with age, significantly more so than the reaction or symptoms after exposure to dog allergens. The greater frequency of sensitivity to cats was not caused by exposure to cats in more homes, since dogs significantly outnumbered cats as the household pet in both atopic and nonatopic families. However, greater intimacy of exposure to cats when they were present may have been a factor because cats, significantly more often than dogs, were inside the house and in the child's bedroom. Two subgroups were examined to determine whether those with cat sensitivity who owned cats had more severe symptoms than those with dog sensitivity who owned dogs. Numbers were small and differences not statistically significant, but those in the cat subgroup more frequently had persistent allergic nasal symptoms and abnormally low spirometric measurements than did those in the dog subgroup. Our findings indicate that children are more often allergic to cats than to dogs and suggest that the greater frequency of sensitization to cats may be due to increased intimacy of exposure to cats.


Noise reduction based on ICA decomposition and wavelet transform for the extraction of motor unit action potentials.
We have studied methods for noise reduction of myoelectric signals and for extraction of motor unit action potentials from these signals. Effective MUAP peak detection is the first important step in EMG decomposition. We first combined independent component analysis and wavelet filtering to remove power line interference, and then applied a wavelet filtering method and threshold estimation calculated using wavelet transform to suppress background noise and Gaussian white noise. The technique was applied to single-channel, short-period real myoelectric signals from normal subjects and to artificially generated EMG recordings. In contrast to existing methods based on amplitude single-threshold filtering of the original myoelectric signal or a conventional digitally filtered signal, our technique is fast and robust. Moreover, the proposed algorithm is substantially automatic. The performance has been evaluated with a set of synthetic and experimentally recorded myoelectric signals. The basic tool for testing was power spectrum density (PSD) estimation by the Welch method, which allowed us to analyze the PSD of nonstationary signals.


Late-onset episodic ataxia type 2 due to an in-frame insertion in CACNA1A.
Episodic ataxia type 2 (EA2) is caused by calcium channel (CACNA1A) mutations and typically begins before age 20 years. The molecular basis of late-onset EA2 is unclear. The authors describe a case of late-onset EA2 associated with the first multiple-base pair insertion in CACNA1A. Molecular expression revealed evidence of impaired calcium channel function, suggesting that genetically induced reduction in calcium channel function may associate with cases of late-onset EA2.


PTENα and PTENβ promote carcinogenesis through WDR5 and H3K4 trimethylation.
PTENα and PTENβ are two longer translational variants of phosphatase and tensin homolog (PTEN) messenger RNA. Their expressional regulations and functions in carcinogenesis remain largely unknown. Here, we demonstrate that, in contrast with the well-established tumour-suppressive role of canonical PTEN, PTENα and PTENβ promote tumourigenesis by directly interacting with the histone H3 lysine 4 (H3K4) presenter WDR5 to promote H3K4 trimethylation and maintain a tumour-promoting signature. We also show that USP9X and FBXW11 bind to the amino-terminal extensions of PTENα/β, and respectively deubiquitinate and ubiquitinate lysines 235 and 239 in PTENα to regulate PTENα/β stability. In accordance, USP9X promotes tumourigenesis and FBXW11 suppresses tumourigenesis through PTENα/β. Taken together, our results indicate that the Pten gene is a double-edged sword for carcinogenesis, and reinterpretation of the importance of the Pten gene in carcinogenesis is warranted.


Attitudes of Saudi mothers towards prolonged non-nutritive sucking habits in children.
The purpose of the present study was to evaluate Saudi mothers' attitude towards non-nutritive sucking habits by their children and report the methods they used to stop these habits. Across-sectional study involved 181 mothers of preschool children currently engaged in non-nutritive sucking habits (digit and pacifier) were studied. The information was obtained from a self-administered questionnaire completed by the mothers. The majority of mothers (69.1%) were from high socio-economic families, (77%) had university or higher education and more than half of them (58.6%) were employed. About 75% of the children were pacifier users, and 25% of them habitually sucked their digits. Nearly half of the mothers (43.5%) thought that the reason of acquiring the habit was because their children cried a lot at night. The majority of studied mothers (88.7%) considered sucking a harmful habit to their children' teeth, and 69.1% never accepted the sucking habit. High percentage (80.8%) of mothers tried to intervene with these habits and 61.0% of them tried their intervention when children were one year old or less. Most proposed reasons for mothers' intervention with sucking habits were their concerns that the habit might continue until the child become older (53.3%) followed by their concern that the habit might affect their children's permanent teeth (45.3%). The methods used by mothers were mostly non-invasive procedures which included restricting the use of pacifier to specific times in the day (63.0%), followed by reinforcement of positive behaviors and using rewards (26.0%). None of the mothers sought advice from pediatrician while only one mother (0.6%) consulted a dentist about sucking habits. This study shows that Saudi mothers are concerned about sucking habits and recognized the harmful effect on their children. These mothers, however, are in great need for education about ways of preventing the habits in the first place as well as professional advice and help in treatment cessation of already established habits.


Evaluation of the transforming growth factor beta1 codon 25 (Arg-->Pro) polymorphism in alcoholic liver disease.
Liver cirrhosis develops only in a minority of heavy drinkers. Genetic factors may account for some variation in the progression of fibrosis in alcoholic liver disease (ALD). Transforming growth factor beta 1 (TGFbeta1) is a key profibrogenic cytokine in fibrosis and its gene contains several polymorphic sites. A single nucleotide polymorphism at codon 25 has been suggested to affect fibrosis progression in patients with chronic hepatitis C virus infection, fatty liver disease, and hereditary hemochromatosis. Its contribution to the progression of ALD has not been investigated sufficiently so far. One-hundred-and-fifty-one heavy drinkers without apparent ALD, 149 individuals with alcoholic cirrhosis, and 220 alcoholic cirrhotics who underwent liver transplantation (LTX) were genotyped for TGFbeta1 codon 25 variants. Univariate analysis suggested that genotypes Arg/Pro or Pro/Pro are associated with decompensated liver cirrhosis requiring LTX. However, after adjusting for patients' age these genotypes did not confer a significant risk for cirrhosis requiring LTX. TGFbeta1 codon 25 genotypes Arg/Pro or Pro/Pro are not associated with alcoholic liver cirrhosis. Our study emphasizes the need for adequate statistical methods and accurate study design when evaluating the contribution of genetic variants to the course of chronic liver diseases.


Incorporating the service accomplishments into pre-registration curriculum to enhance reflective practice.
Much emphasis is being placed on the importance of reflective practice as a means to ensure that practitioners are competent in their practice. It is therefore important to ensure that student nurses acquire these reflective skills as part of their development throughout pre-registration curricula. Although reflective practice is seen as a major part of curricula activity, the style in which reflection is advocated takes many different formats. Strategies for developing reflection which focus on outcomes for students can become subjective and fail to place healthcare practice within the context of social structures and values. This paper offers a framework for reflection that promotes an outlook which is both objective and subjective, based on Mezirow's six levels of reflection (as adapted by Powell 1989) and O'Brien's (1987) five service accomplishments. Focus of reflection within the wider context of society and healthcare policy should enable development of a practitioner who is both competent in practice and can analyse and evaluate their practice.


Congenital infiltrative lipomas and retroperitoneal perirenal lipomas in a calf.
Congenital lipocytic tumours have rarely been reported in cattle. Lipomas are benign tumours, but infiltrative lipomas have significant health implications due to their aggressive infiltrative growth pattern. A calf was born with skeletal malformations and soft tissue proliferations, primarily on the external thoracic wall. The calf was euthanized for welfare reasons and submitted for post mortem examination. Necropsy, histopathology and post mortem computed tomography scanning revealed two types of lipocytic tumours. Widespread infiltrative lipomas were present in the muscles and connective tissues along the vertebral column and diffusely invaded the external soft tissues of the right thoracic wall. The neoplastic lipocytes had invaded intervertebral spaces thus causing congenital vertebral malformations, and further invaded the vertebral canal and the bone marrow of coccygeal vertebrae. Periosteal localization of the tumour was associated with costal hyperostosis. Two large retroperitoneal lipomas enclosed the kidneys and occupied much of the abdominal space. The development of congenital bone malformation in this calf illustrates the severe consequences of the infiltrative and aggressive growth of infiltrative lipomas during foetal development. The congenital retroperitoneal lipomas occupied a large part of abdominal cavity, but did not invade the adjacent tissues. Due to their large size, perirenal lipomas should be considered in calves with distended abdomen, even in cases without other signs of tumours.


Effects of transcutaneous auricular vagus nerve stimulation paired with tones on electrophysiological markers of auditory perception.
Transcutaneous auricular vagus nerve stimulation (taVNS) has been introduced as a non-invasive alternative to invasive vagus nerve stimulation (iVNS). While iVNS paired with tones has been highlighted as a potential effective therapy for the treatment of auditory disorders such as tinnitus, there is still scarce data available confirming the efficacy of non-invasive taVNS. Here, we assessed the effect of taVNS paired with acoustic stimuli on sensory-related electrophysiological responses. A total of 22 healthy participants were investigated with a taVNS tone-pairing paradigm using a within-subjects design. In a single session pure tones paired with either active taVNS or sham taVNS were repeatedly presented. Novel tones without electrical stimulation served as control condition. Auditory event related potentials and auditory cortex oscillations were compared before and after the tone pairing procedure between stimulation conditions. From pre to post pairing, we observed a decrease in the N1 amplitude and in theta power to tones paired with sham taVNS while these electrophysiological measures remained stable for tones paired with active taVNS a pattern mirroring auditory sensory processing of novel, unpaired control tones. Our results demonstrate the efficacy of a short-term application of non-invasive taVNS to modulate auditory processing in healthy individuals and, thereby, have potential implications for interventions in auditory processing deficits.


Incidence of Wra antigen and anti-Wra in a Spanish population.
This study reports the incidence of Wr(a) antigen and anti-Wr(a) in Valencia, Spain. The incidence of the Wr(a) antigen in 110,000 healthy blood donors was estimated. Likewise, the incidence of anti-Wr(a) was analyzed in a population consisting of 730 healthy blood donors, 356 pregnant women, and 581 patients who received transfusions from the area of Valencia, Spain. The incidence of Wr(a) antigen was 1 in 785. Overall, anti-Wr(a) was found in 59 samples: 20 healthy blood donors (1/37), 18 pregnant women (1/20), and 21 patients who received transfusions (1/28). The most frequent immunoglobulin class of anti-Wr(a) in healthy blood donors was immunoglobulin M, either alone (8 cases) or plus immunoglobulin G (IgG; 8 cases); the IgG1 and IgG3 were the IgG subclasses most frequently detected in pregnant women (12 cases) and in patients who received transfusions (12 cases). Only 51 percent of the anti-Wr(a) appeared to have the potential to be clinically significant. These data show that the incidence of Wr(a) antigen and anti-Wr(a) among the population from Valencia is similar to that reported in other European areas and suggest that the development of anti-Wr(a) is facilitated by the presence of a hyperactive immune system. The clinical relevance of anti-Wr(a) is limited, however.


Three diterpene dilactone glycosides from Podocarpus nagi.
Three water-soluble constituents, nagilactosides C-E, were isolated from Podocarpus nagi. Their structures were determined by chemical and spectroscopic methods, respectively. Nagilactoside C was identified as 1-deoxy-nagilactone A-2 alpha-O-beta-D-glucopyranosyl-(1-->3)-beta-D-glucopyranoside, nagilactoside D as 1-deoxy-nagilactone A-2 alpha-O-beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyranoside, and nagilactoside E as nagilactone A-1 beta-O-beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyransoide.


Assessing the usefulness of policy brief and policy dialogue as knowledge translation tools towards contextualizing the accountability framework for routine immunization at a subnational level in Nigeria.
Evidence suggests that implementing an accountability mechanism such as the accountability framework for routine immunization in Nigeria (AFRIN) will improve routine immunization (RI) performance. The fact that the AFRIN, which was developed in 2012, still had not been operationalized at the subnational level (Ebonyi State) by 2018 may in part account for the poor RI coverage (33%) in 2017. Knowledge translation (KT) is defined as the methods for closing the gaps from knowledge to practice. Policy briefs (useful in communicating research findings to policy-makers) and policy dialogues (that enable stakeholders to understand research evidence and create context-resonant implementation plans) are two KT tools. This study evaluated their usefulness in enabling policy-makers to contextualize AFRIN in Ebonyi State, Nigeria. The study design was cross-sectional descriptive with mixed-methods data collection. A policy brief developed from AFRIN guided deliberations in a 1-day multi-stakeholder policy dialogue by 30 policy actors. The usefulness of the KT tools in contextualizing policy recommendations in the AFRIN was assessed using validated questionnaires developed at McMaster University, Canada. At the end of the policy dialogue, the policy options in the policy brief were accepted but their implementation strategies were altered to suit the local context. The respondents' mean ratings (MNR) of the overall usefulness of the policy brief and the policy dialogue in contextualizing the implementation strategies were 6.39 and 6.67, respectively, on a seven-point Likert scale (very useful). The MNR of the different dimensions of the policy brief and policy dialogue ranged from 6.17 to 6.60 and from 6.10 to 6.83, respectively (i.e. moderately helpful to very helpful). The participants perceived the KT tools (policy brief and policy dialogue) as being very useful in contextualizing policy recommendations in a national policy document into state context-resonant implementable recommendations. We recommend the use of these KT tools in operationalizing AFRIN at the subnational level in Nigeria.


Formation of the Main Cores Present in Natural Products by Tandem Additions.
A rapid route to 5,5- and 5,6- bicyclic systems is provided by an 1,3-alkyl-shift process mediated by a hypervalent iodine reagent on aromatics. The structures obtained contain several unsaturations with different behaviors and reactivities. Such diversity allows further elaborations for the rapid formation of compact systems present in a variety of natural products. The potential for further transformations has been demonstrated by performing a double Michael addition. This cyclization process is regio- and stereoselective due to the presence of a former benzylic substituent. Furthermore, an extension of this approach has been accomplished on indole derivatives.


A comparison of the performance of nine commercially available anti-HTLV-I screening assays.
The performance of eight anti-HTLV-I enzyme immunoassays (EIAs) and one particle agglutination assay was compared with respect to sensitivity, specificity and delta values, by testing a panel containing 99 anti-HTLV-I positive and 126 anti-HTLV-I negative samples which had been characterised by western blot and some by radioimmunoprecipitation assay. The estimated sensitivities produced by these assays ranged between 99% and 100% and estimated specificities were between 95.2% and 100%. The performance of the EIAs was further differentiated by using the delta value which measures the ability of an assay to separate the positive and negative populations from the cutoff value. A delta value could not be calculated for the particle agglutination assay (Serodia) because the test readings were not quantitative. The EIAs most likely to correctly identify anti-HTLV-I positive and anti-HTLV-I negative samples included the Cambridge Biotech, Dupont, Genetic Systems and Olympus assays. Our findings suggest that there may be some difficulty in correctly identifying anti-HTLV-I negative samples using the Abbott, Cellular Products Incorporated (CPI), Coulter and Diagnostic Biotechnology assays. The Serodia assay produced comparable sensitivity and specificity to the eight EIAs.


Axonal transport studied in a single vertebrate neuron: the giant electromotor neuron of the electric catfish, Malapterurus electricus.
Axonal transport was studied using a single vertebrate neuron, the giant electromotor neuron of the electric catfish, Malapterurus electricus. The electric organs of this strongly electric fish are innervated by two neurons whose axons form one electric nerve each. After injection of [35S]methionine into the spinal cord at the level of the two perikarya radioactively labelled material is exported by fast flow as a small wave with a velocity of 5.8 mm/h and a somal release time of 91 min (29 degrees C). Slow flow investigated between 15 and 39 days had a velocity of 1.36 mm/d at 29 degrees C. Analysis of radiolabelled proteins by polyacrylamide gel electrophoresis revealed different patterns of labelling between slow and fast flow. The relative molecular mass of the two major proteins labelled on slow flow correspond to actin and tubulin. Labelled proteins of higher relative molecular mass may correspond to neurofilament proteins. Our results suggest that this vertebrate single-neuron and single-axon system can be used successfully for axonal transport studies.


Choice of urine sample predictive of microalbuminuria in patients with insulin-dependent diabetes mellitus.
Twenty-four-hour, four-hour (8 to 12 am), and overnight urine collections were examined for their ability to detect microalbuminuria in 292 patients with insulin-dependent diabetes mellitus (IDDM). Albumin excretion rate (AER) was measured and also estimated from the product of the urinary albumin/creatinine ratio (A/C) and the calculated 24-hour creatinine excretion. The fractional excretion of albumin (FEA) was also determined in aliquots from each urine sample. The correlation coefficients between measured 24-hour AER and estimated AER were 0.940 and 0.956 for four-hour and overnight collections, respectively (significance of each correlation, P less than 0.001). There was no advantage in using the FEA over the A/C ratio in predicting measured AER. Urinary A/C ratios (mg/mg) between 0.03 and 0.31 in the four-hour collections were highly predictive of microalbuminuria and of measured AER in the 24-hour collections: AER24-h (microgram/min/1.73 m2) = 2.74 + 0.870 x A/C4-h (all log10 values). In a subgroup of 175 patients having all three collections validated, 34 (20%) had microalbuminuria defined as AER 20 to 200 micrograms/min/1.73 m2 in at least two of the three samples and 44 (25%) had overt nephropathy (greater than 200 micrograms/min/1.73 m2). The ability of the AER in one urine collection to predict microalbuminuria in at least one of the other two collections was assessed in these 175 patients. Compared with the overnight urine collection, the four-hour collection had greater sensitivity while affording similar specificity and positive predictive value. Based on these data, the A/C ratio from a morning urine sample following initial AM voiding would seem adequate for the detection and monitoring of microalbuminuria in patients with IDDM.


Chimpanzee brain morphometry utilizing standardized MRI preprocessing and macroanatomical annotations.
Chimpanzees are among the closest living relatives to humans and, as such, provide a crucial comparative model for investigating primate brain evolution. In recent years, human brain mapping has strongly benefited from enhanced computational models and image processing pipelines that could also improve data analyses in animals by using species-specific templates. In this study, we use structural MRI data from the National Chimpanzee Brain Resource (NCBR) to develop the chimpanzee brain reference template Juna.Chimp for spatial registration and the macro-anatomical brain parcellation Davi130 for standardized whole-brain analysis. Additionally, we introduce a ready-to-use image processing pipeline built upon the CAT12 toolbox in SPM12, implementing a standard human image preprocessing framework in chimpanzees. Applying this approach to data from 194 subjects, we find strong evidence for human-like age-related gray matter atrophy in multiple regions of the chimpanzee brain, as well as, a general rightward asymmetry in brain regions.


A new in vivo model to study invasion and metastasis of human bladder carcinoma.
An animal model to investigate the invasive and metastatic properties of human bladder transitional cell carcinoma (HTCC) was established. Two long-term HTCC cell lines (RT4 and EJ) and one HTCC cell line derived in our laboratory (LD-71) were tumorigenic when injected s.c. into nude mice but had little potential to invade locally or metastasize before the animals succumbed to tumor burden. Experimental lung metastases were, however, observed in approximately 60% of animals given injections of RT4 or EJ cell lines in the tail vein. The cells were also implanted transurethrally into the urinary bladders of athymic mice. RT4 cells, which were originally isolated from a superficial papillary tumor, produced histologically noninvasive tumors after transurethral inoculation with no evidence of metastasis. In contrast EJ cells, which were originally isolated from a more aggressive tumor, produced invasive tumors in nude mouse bladders and metastasized to the lungs spontaneously. The invasive cell line LD-71 was weakly tumorigenic and was successfully implanted into the bladder on only one of five attempts. The human origin of the implanted tumors was documented by Southern blot analysis using human repetitive DNA as a probe. The results indicate that the site of injection strongly influences the behavior of the resulting tumors and that intravesical implantation of these HTCC cell lines produces pathological expression of invasiveness and metastatic potential.


Smoking-dependent and haplotype-specific effects of endothelial nitric oxide synthase gene polymorphisms on angiographically assessed coronary artery disease in Caucasian- and African-Brazilians.
The nitric oxide produced by endothelial nitric oxide synthase (eNOS) plays a pivotal role in protecting the arterial wall from damages and atherosclerosis. The T-786C, the 27-bp repeat in intron 4, and the E298D eNOS gene polymorphisms were studied in 715 Brazilian patients (447 Caucasian- and 268 African-Brazilians) who underwent coronary angiography. The -786C frequency was increased in coronary artery disease (CAD) cases with significant lesions (> or =50% luminal obstruction) when compared with lesion-free controls; this difference was detected in smokers but not in nonsmokers, both in Caucasian- (p=0.011) and African-Brazilians (p=0.005). The interaction between -786C carriers and smoking was an independent CAD predictor (OR: 2.9, 95% CI: 1.4-5.9; p=0.003) in multiple logistic regression. The 298D mutation frequency was also higher among CAD cases (p=0.036) in African-Brazilian smokers, but this effect was not independent from other variables in the regression model. Though not associated with CAD, the 4-repeat allele combined with different T-786C alleles showed protective and susceptible effects in Caucasian-Brazilian smokers. The -786C/4-repeat/298E haplotype frequency was higher (p=0.020), whereas -786T/4-repeat/298E was lower (p=0.023) in these cases. These results showed a smoking-dependent effect of the T-786C eNOS polymorphism on CAD in both Caucasian- and African-Brazilians. Additionally, the haplotype analysis revealed different eNOS haplotypes associated with protection and susceptibility to the disease.


Luteinizing hormone determinations obtained with either a monoclonal and a polyclonal antibody radioimmunoassay and their correlations with clinical findings.
Detection of circulating levels of gonadotropin is fundamental in reproductive physiology and related disorders. The advent of monoclonal antibodies might supply the clinician with faster and more accurate estimates of these hormones. We have evaluated the hormonal determinations provided by a monoclonal assay and those generated from our previous assay, produced by the same manufacturer, based on polyclonal antibodies. Comparison was performed on blood samples collected from volunteers with regular menstruation (n = 51) or patients attending our Clinic. The correlation between data provided by the two assays fluctuated from the almost complete overlap of the physiological menstrual cycle to the striking dissociation of the patients (n = 13) receiving a Gonadotropin Hormone-Releasing Hormone analog for gonadotropin suppression. Intermediate coefficients of correlations were recorded in normal subjects undergoing a Gonadotropin Hormone-Releasing Hormone stimulation test (n = 12) and in patients with functional hypothalamic amenorrhea (n = 19) or polycystic ovarian disease (n = 37). Values obtained with the monoclonal assay tended to be lower than those recorded with the previous system. A closer correlation with the clinical findings was observed in the hormonal values originated with the monoclonal assay.


Normal endonuclease activities for damaged DNA during hepatocarcinogenesis.
Two endonuclease activities in rat liver for damaged DNA were assayed. Double-stranded, covalently closed DNA from phage PM2 was damaged by either ultraviolet irradiation or by heating at acid pH, and used as substrate for endonucleases specific for ultraviolet DNA damage and for DNA apurinic sites, respectively. The levels of both enzyme activities in livers of normal rats were compared to levels in livers of rats fed N-2-acetylaminofluorene. At critical stages of the carcinogenic regimen levels of both endonuclease activities were normal. This, together with other data, suggests that depression of excision-repair of DNA damage does not take place during experimental carcinogenesis.


Isolation of the major toxic protein from the skin venom of the crested newt, Triturus cristatus.
A new protein, of molecular weight 160,000, was isolated from the skin venom of the crested newt and partially characterized by bioassays and biochemical methods. This protein shows the same functional properties as the crude venom, which produces convulsions in mice and is cytotoxic.


The R2R3-MYB transcription factor OfMYB21 positively regulates linalool biosynthesis in Osmanthus fragrans flowers.
Osmanthus fragrans is a well-known landscape ornamental tree species for its pleasing floral fragrance and abundance of flowers. Linalool, the core floral volatiles of O. fragrans, has tremendous economic value in the pharmaceuticals, cleaning products and cosmetics industries. However, the transcriptional regulatory network for the biosynthesis of linalool in O. fragrans remains unclear. Here, OfMYB21, a potential transcription factor regulating the linalool synthetase OfTPS2, was identified using RNA-seq data and qRT-PCR analysis. Yeast one-hybrid, dual-luciferase and EMSA showed that OfMYB21 directly binds to the promoter of OfTPS2 and activates its expression. Overexpression of OfMYB21 in the petals of O. fragrans led to up-regulation of OfTPS2 and increased accumulation of linalool, while silencing of OfMYB21 led to down-regulation of OfTPS2 and decreased biosynthesis of linalool. Subsequently, yeast two-hybrid, pull-down and BiFC experiments showed that OfMYB21 interacts with JA signaling factors OfJAZ2/3 and OfMYC2. Interestingly, the interaction between OfMYC2 and OfMYB21 further enhanced the transcription of OfTPS2, whereas OfJAZ3 attenuated this effect. Overall, our studies provided novel finding on the regulatory mechanisms responsible for the biosynthesis of the volatile monoterpenoid linalool in O. fragrans.


Bilateral choroidal caverns in a child with pachychoroid and anxious personality.
To report a case of a 7-year-old male patient with bilateral choroidal caverns (CC) and pachychoroid. During the Italian COVID-19 lockdown, a 7-year old boy presented with bilateral vision decline that had started two weeks before. Structural optical coherence tomography revealed pachychoroid and CC bilaterally. Other ocular examinations were negative. The patient had an apprehensive personality and symptoms quickly resolved when he was provided with non-prescription glasses; his visual disturbances were thus considered to be functional and factitious. Our patient's symptoms remind us that the distress imposed upon psychologically frail subjects by the COVID-19 pandemic may have multifaceted manifestations. The discovery of CC in a pediatric patient with healthy eyes presents us with new questions about the processes of degeneration thought to be the cause for CC. Further studies are needed to estimate the prevalence of CC in the general adult and pediatric populations, as well as in patients with chorioretinal diseases.


4-Methyl-5-vinyl thiazole modified Ni-MOF/g-C3N4/CdS composites for efficient photocatalytic hydrogen evolution without precious metal cocatalysts.
The construction of heterojunction systems is an effective way to efficiently generate hydrogen by water photolysis. In this work, Ni-MOF (trimesic acid, (BTC)) and g-C3N4 (denoted as CN) were combined, and then Ni-MOF/CN was modified by 4-Methyl-5-vinyl thiazole (denoted as MVTh). Finally, CdS was loaded on the surface of Ni-MOF/CN/MVTh to prepare the photocatalyst Ni-MOF/g-C3N4/MVTh/CdS (denoted as Ni/CN/M/Cd) with a triangular closed-loop path heterojunction for the first time. As a photocatalyst without precious metal cocatalysts, Ni/CN/M/Cd displayed high H2 evolution (17.844 mmol·g-1·h-1) under an optimum CdS loading of 40 wt%. The H2 evolution rate was approximately 79 times that of Ni-MOF/CN and exceeded those of almost all catalysts based on MOF/CN in the literature. The triangular closed-loop heterojunction formed between Ni-MOF, g-C3N4, and CdS could realize the directional migration of photocarriers and significantly diminished the transfer resistance of carriers. The Ni2+ in Ni-MOF provided many cocatalytic sites for H2 evolution via g-C3N4 and CdS. Furthermore, charge carrier separation in Ni-MOF/CN/CdS improved after the innovative addition of MVTh. This study provides a reference for the construction of a closed-loop heterojunction system without precious metal cocatalysts.


Phytic acid functionalized magnetic adsorbents for facile enrichment of trace rare earth elements in environmental water, digested atmospheric particulates and the extracts followed by inductively coupled plasma mass spectrometry detection.
Phytic acid (PA) functionalized magnetic adsorbents was synthesized through simple process. The functionalized sorbents are featured with core-shell structure, good magnetism, chemical stability, selectivity, and fast adsorption/desorption dynamics for the preconcentration of trace rare earth elements (REEs). With the aid of inductively coupled plasma mass spectrometry detection, the prepared Fe3O4@SiO2@PA sorbents were employed for the separation and enrichment of 15 REEs from environmental water and atmospheric particulates with different sizes. Under the optimal conditions, the method presented an enrichment factor of 300-fold and low detection limits (0.002-1.1 ng/L) for 15 REEs, with the relative standard deviations of 1.4-4.4%. Environmental water samples were analyzed by the proposed method, and 15 REEs of 0.08-5.80 ng/L were found in local rainwater and river water. The REEs concentration in locally collected fine particulate matter was 0.01-0.93 ng/m3, 0.03-1.70 ng/m3 and 0.03-2.47 ng/m3 of REEs were found in inhalable particulate matter and total suspended particulate samples, respectively. The bioaccessibility of REEs in PM2.5 was evaluated by using Gamble's solution extraction, which was calculated to be 0.73-5.46%.


Mycotic encephalitis: predilection for grey matter.
In mycotic infections of the brain three patterns of abnormality may be observed: meningitis, granuloma, and encephalitis. The first two, consisting of diffuse meningeal enhancement and mass lesion respectively, can easily be visualised by CT or MRI, but are nonspecific. The third pattern has been described histopathologically; as the clinical picture is nonspecific and the diagnosis is often unsuspected, especially in immunocompetent patients, acquaintance with the characteristic CT and MRI patterns of mycotic encephalitis may help in establishing the correct diagnosis, with important therapeutic consequences.


Effects of apomorphine on sexual behavior in young and middle-aged rats.
Apomorphine (APO), the prototypical dopamine agonist, produced different effects on the copulatory patterns of sexually vigorous male rats depending on the dose, the time between treatment and behavioral observation and the age of the animals. Prior to any drug treatment, middle-aged males (13 months of age) exhibited prolonged latencies to ejaculation and intervals between intromissions when compared to young male rats (3 months of age). In mating tests to young male rats initiated six minutes after treatment, administration of low doses of APO was followed by reductions in the ejaculatory threshold (0.05-0.8 mg/kg). The greatest reduction in the ejaculatory threshold was observed after administration of 0.4 mg/kg APO. No such facilitation of ejaculatory behavior was evident in the middle-aged males. Age-related differences in APO-induced changes in ejaculation latency (0.05-0.8 mg/kg), intromission frequency (0.05-0.4 mg/kg), copulatory efficacy (0.2 and 0.8 mg/kg) and intercopulatory interval (0.8 mg/kg) were evident. Doses of APO above 0.4 mg/kg in young males and above 0.2 mg/kg in middle-aged males elicited dose-related decreases in the number of rats engaging in copulatory activity, with 3 mg/kg effecting a virtual elimination in both age groups. In mating tests initiated 60 minutes after treatment, no decrease in the number of rats engaging in copulatory activity was seen in the young animals, and 3 mg/kg caused only a minor reduction in the number of middle-aged males achieving ejaculation.(ABSTRACT TRUNCATED AT 250 WORDS)


A dominant negative form of inositol 1,4,5-trisphosphate receptor induces metacyclogenesis and increases mitochondrial density in Trypanosoma cruzi.
Inositol 1,4,5-trisphosphate receptor (IP3R) is a key regulator of intracellular Ca(2+) concentration that release Ca(2+) from Ca(2+) stores in response to various external stimuli. IP3R also works as a signal hub which form a platform for interacting with various proteins involved in diverse cell signaling. Previously, we have identified an IP3R homolog in the parasitic protist, Trypanosoma cruzi (TcIP3R). Parasites expressing reduced or increased levels of TcIP3R displayed defects in growth, transformation, and infectivity. In the present study, we established parasitic strains expressing a dominant negative form of TcIP3R, named DN-TcIP3R, to further investigate the physiological role(s) of TcIP3R. We found that the growth of epimastigotes expressing DN-TcIP3R was significantly slower than that of parasites with TcIP3R expression levels that were approximately 65% of wild-type levels. The expression of DN-TcIP3R in epimastigotes induced metacyclogenesis even in the normal growth medium. Furthermore, these epimastigotes showed the presence of dense mitochondria under a transmission electron microscope. Our findings confirm that TcIP3R is crucial for epimastigote growth, as previously reported. They also suggest that a strong inhibition of the IP3R-mediated signaling induces metacyclogenesis and that mitochondrial integrity is closely associated with this signaling.


Publisher Correction: Mechanics of a multilayer epithelium instruct tumour architecture and function.
An amendment to this paper has been published and can be accessed via a link at the top of the paper.


Relationship between apical periodontitis and atherosclerosis in rats: lipid profile and histological study.
To investigate the relationship between apical periodontitis and atherosclerosis in rats by lipid profile and carotid artery intima tunic measurement, and histological and histometric evaluation of periapical lesions. Forty male Wistar rats were allocated into four groups: control (C), with apical periodontitis (AP), with atherosclerosis (AT) and with AP and AT (AP + AT). Atherosclerosis was induced using a high-lipid diet associated with a surgical ligature in the carotid artery and a super dosage of vitamin D3 . AP was induced via pulp exposure to the oral environment. At 45 and 75 days, serum levels of total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) were measured. The maxillary and mandibular jaws and carotid artery were collected and processed for histological analysis. The Kruskal-Wallis or Mann-Whitney test was performed for nonparametric data, and the Tukey's or Student's t-test was performed for parametric data (P < 0.05). In nonatherosclerotic animals, the induction of apical periodontitis increased TG levels significantly, from 63.1 ± 11.4 mg dL-1 in group C to 88.2 ± 7.9 mg dL-1 in the AP group (P < 0.05). The induction of AP was associated with a trend for higher TC and LDL-C levels in atherosclerotic animals (P > 0.05); however, it only significantly increased TG levels, from 93.2 ± 18.0 mg dL-1 in AT group to 121.9 ± 14.5 mg dL-1 in the AP + AT group (P < 0.05). Animals in the AP + AT group had a 36.5% increase in the thickness of the carotid intima tunic when compared with the AT group (P < 0.05). The intensity of the inflammatory infiltrate was significantly larger in the AP + AT group when compared with AP group (P < 0.05). The AP + AT group exhibited significantly greater alveolar bone loss, with a periapical lesion size of 206.4 ± 56.3 × 104 μm2 , compared with 151.4 ± 49.1 × 104 μm2 in the AP group (P < 0.05). Apical periodontitis influenced triglyceride levels, increasing them even in the absence of atherosclerosis, and influenced the increase in the thickness of the carotid artery intima tunic in the presence of atherosclerosis. Atherosclerosis intensified the inflammatory reaction and increased bone resorption in periapical lesions.


The glycosylation state of the precursors of the cathepsin B-like proteinase from human malignant ascitic fluid: possible implication in the secretory pathway of these proenzymes.
We have investigated the structure of the carbohydrate moiety of the precursors of the cathepsin B-like proteinase (PCBt). The largest precursor has an apparent molecular size (Mr) of 45-47 Kd and it contains 3 N-linked oligosaccharide chains which were Endo beta N acetylglucosaminidase H (Endo H)-resistant forms. On the other hand, these chains were sequentially removed by Endo beta N acetylglucosaminidase F (Endo F). Both results indicate a complex type structure for these oligosaccharides. As usual in these cases, sialic acids were also found. In the deglycosylated state, PCBt has a Mr value of 36 Kd closely related to the 35.9 Kd Mr for human Pro CB, deduced from the cDNa sequence. These findings may explain the extracellular location of PCBt in malignancy: complex oligosaccharides are in most cases associated with secretory or membrane bound glycoproteins. On the contrary, mannose-rich types are involved in the lysosomal routage.


HLA antigens and thyroid autoantibodies in patients with Graves' disease and their first degree relatives.
Patients with Graves' disease (n = 105) had an increased frequency of HLA-B8 (40%) and a reduced frequency of HLA-B12 (24.8%) when compared with random controls (n = 117; 24.8% and 40.2% respectively). Comparison of patients with their first degree relatives (n = 118) shows the frequency deviations in these antigens to be characteristic of the families from which patients with Graves' disease are drawn, rather than of the disease itself. The haplotypes, identified in eight-six patients and 113 relatives, indicate that the excess of HLA-B8 in patients and their relatives is primarily due to the halpotype 1-8. The relative risk for an HLA-B8 individual of developing Graves' disease is 2.02, whilst the relative risk for an individual of haplotype 1-8 is 4.23. No significant associations were found between the incidence of any HLA antigen or combination thereof and the presence or absence of thyroglobulin and thyroid microsomal antibodies, or antibodies which interact with the TSH receptor.


A Comparative Study on the Biodiversity and Species Richness of Phlebotomine Sand Flies (Diptera: Psychodidae) in Kermanshah and Khuzestan Provinces of Iran.
Leishmaniasis is one of the most important vector-borne and neglected tropical diseases in many parts of the world. The main objective of this study was to determine the biodiversity of phlebotomine sand flies (Diptera: Psychodidae, Phlebotominae) in Khuzestan and Kermanshah Provinces of Iran. Sampling was conducted in Khuzestan and Kermanshah Provinces using sticky paper traps and CDC light traps. The samples were then stored in 96% alcohol-containing vials, mounted, and identified. Afterward, the alpha diversity (using Simpson's, Shannon-Weiner's diversity, evenness, Maghalef's, Menhinick's, Hill N 1 and N 2 indices) and beta diversity indices (using Sorensen's and Jaccard's coefficients) were calculated. A total of 4302 sand flies were caught and identified which comprised mostly of Phlebotomus papatasi, Ph. alexandri and Ph. sergenti. It was found that among the four counties of Ahvaz, Shush, Shushtar and Dezful in Khuzestan Province, Shush had the lowest, and Shushtar, the highest amount of species diversity and evenness. In the four studied counties of Kermanshah Province, species diversity in Kermanshah County had the lowest amount and Sarpol-e-Zahab, the highest. The species richness in Kermanshah County was the lowest, while Qasr-e-Shirin County had the highest amount. An overview of the biodiversity of phlebotomine sand flies in Kermanshah County in Kermanshah Province, and Shush County in Khuzestan Province, showed less stability in community structure of these vectors, which can be counted as an alarm for emerging dominant vectors among the studied counties and have the potential to increase the prevalence of leishmaniasis.


Beyond the borders of keloid formation: A case report.
The keloid scar is a cutaneous mass characterized by nodular fibroblastic proliferation of dermis and a predilection for distinctive anatomical locations. However, keloid extension to neighbouring tissue as a nonsyndromic entity has not been described. In the present report, a case involving a 48-year-old woman with extensive bilateral keloids of the ear lobules and neck following ear piercing is presented.


Electron Leak From the Mitochondrial Electron Transport Chain Complex I at Site IQ Is Crucial for Oxygen Sensing in Rabbit and Human Ductus Arteriosus.
Background As partial pressure of oxygen (pO2) rises with the first breath, the ductus arteriosus (DA) constricts, diverting blood flow to the pulmonary circulation. The DA's O2 sensor resides within smooth muscle cells. The DA smooth muscle cells' mitochondrial electron transport chain (ETC) produces reactive oxygen species (ROS) in proportion to oxygen tension, causing vasoconstriction by regulating redox-sensitive ion channels and enzymes. To identify which ETC complex contributes most to DA O2 sensing and determine whether ROS mediate O2 sensing independent of metabolism, we used electron leak suppressors, S1QEL (suppressor of site IQ electron leak) and S3QEL (suppressor of site IIIQo electron leak), which decrease ROS production by inhibiting electron leak from quinone sites IQ and IIIQo, respectively. Methods and Results The effects of S1QEL, S3QEL, and ETC inhibitors (rotenone and antimycin A) on DA tone, mitochondrial metabolism, O2-induced changes in intracellular calcium, and ROS were studied in rabbit DA rings, and human and rabbit DA smooth muscle cells. S1QEL's effects on DA patency were assessed in rabbit kits, using micro computed tomography. In DA rings, S1QEL, but not S3QEL, reversed O2-induced constriction (P=0.0034) without reducing phenylephrine-induced constriction. S1QEL did not inhibit mitochondrial metabolism or ETC-I activity. In human DA smooth muscle cells, S1QEL and rotenone inhibited O2-induced increases in intracellular calcium (P=0.02 and 0.001, respectively), a surrogate for DA constriction. S1QEL inhibited O2-induced ROS generation (P=0.02). In vivo, S1QEL prevented O2-induced DA closure (P<0.0001). Conclusions S1QEL, but not S3QEL, inhibited O2-induced rises in ROS and DA constriction ex vivo and in vivo. DA O2 sensing relies on pO2-dependent changes in electron leak at site IQ in ETC-I, independent of metabolism. S1QEL offers a therapeutic means to maintain DA patency.


Isolation and sequence analysis of a chalcone synthase cDNA of Matthiola incana R. Br. (Brassicaceae).
A cDNA clone (pcM12) of the chalcone synthase (CHS) of Matthiola incana R. Br. (Brassicaceae) was isolated from a cDNA library, sequenced and analysed. It comprises the complete coding sequence for the CHS and 5' and 3' untranslated regions. The deduced amino acid sequence shows that the Matthiola incana CHS consists of 394 amino acid residues. Comparison with CHS amino acid sequences of other plants indicates more than 82% homology.


Relationship between composite matrix molecular structure and properties.
The synthesis of three novel dimethacrylate esters for use as the monomer phase in dental composites was studied. The monomers were prepared by the reaction of glycidyl methacrylate with phthalic, isophthalic and terephthalic acids, respectively, and the reaction products were found to be mixtures of isomers. The monomers obtained from the reaction of phthalic and isophthalic acids were low-viscosity liquids and the relationship between viscosity and molecular structure was studied. The low viscosity of these di-hydroxyl containing monomers was shown to be due to intramolecular hydrogen bonding. This reduced monomer viscosity compared with BisGMA allowed a reduction in the quantity of diluent monomer triethyleneglycoldimethacrylate (TEGDMA) required to give standard viscosities of 1 and 2 Pas resulting in a modest decrease (ca. 10%) in polymerization shrinkage compared with that exhibited by BisGMA/TEGDMA solutions of equivalent viscosities. A number of properties relevant to the use of these as potential core monomers in dental composites were determined for both monomer and polymer systems.


The rate of recovery of intestinal morphology following anthelmintic treatment of parasitised sheep.
Sixteen sheep which had previously been infected with Ostertagia circumcincta were dosed with 4000 Trichostrongylus colubriformis larvae/day for four weeks, then given anthelmintic and killed at intervals thereafter. Histological examination of the small intestine showed that two to three weeks were required for restoration of a normal mucosal architecture.


Experimental infection of inbred mice with herpes simplex virus. VI. Effect of interferon on in vitro virus replication in macrophages.
Peritoneal exudate cells (PEC) of DBA/2 mice, after 7 days of in vitro preculture and consisting of virtually 100 per cent macrophages, were able to support the replication of Herpes Simplex Virus type 1 strain WAL (HSV). Using a standard medium based on Dulbecco's Modified Eagle Medium (D-MEM), no virus replication was observed in freshly isolated PEC. However a medium based on RPMI 1640 consistently yielded higher virus titres in precultured PEC than the D-MEM medium, and also allowed virus replication in freshly isolated PEC. Macrophages derived from the spleens or the bone marrow, and precultured in the same way as PEC represented a highly pure population and were permissive for infection with HSV. Titres of about 10(6) PFU HSV were observed in PEC 48 hours after infection with 10(3) or 10(6) PFU. However, whereas a complete destruction of the cell monolayer was observed 24 hours after infection with 10(6) PFU, complete cytopathogenicity in PEC infected with 10(3) PFU required at least twice this time. In the latter situation, plaque formation was observed 24 hours after infection. PEC of different strains of mice were compared. Of these, PEC of all mice that are susceptible to HSV infection in vivo replicated HSV to the same degree as PEC of DBA/2 mice, whereas PEC of resistant C57BL/6 and C3H/HeJ mice produced 1000 fold lower titres of viral progeny. Whereas the number of infectious centres were equal in PEC of DBA/2 and C57BL/6 mice, the plaques observed after infection of confluent PEC with a low MOI were considerable smaller in cells from C57BL/6 mice. Furthermore, significantly higher titres of interferon were measured in the supernatants of HSV-infected C57BL/6 macrophages than in those of DBA/2 macrophages, and the former were made fully susceptible by the in vitro addition of an anti-interferon serum.


Non-enzymatic browning induced by chlorogenic acid quinone mediated catechin oxidation.
Non-enzymatic oxidation has become a significant issue in the juice industry, inducing browning, flavor deterioration, and nutrient degradation, where catechin oxidation plays a vital role. Here, a novel chlorogenic acid quinone-mediated catechin oxidation was compared with the autoxidation pathway, where the former reaction was significantly faster (0.1326 L·mol-1·min-1) than the autoxidation rate of 4.25E-5 L·mol-1·min-1. The significance of the chlorogenic acid quinone-mediated catechin oxidation was further confirmed in the apple juice showing that chlorogenic acid quinone decreased faster in catechin enriched juice than in chlorogenic acid enriched juice. In addition, chlorogenic acid and catechin quinone hardly changed, but catechin and chlorogenic acid quinone kept decreasing during the browning process. These suggested that chlorogenic acid quinone mediated oxidation dominated the non-enzymatic browning in juice and might act as a self-perpetuating oxidizer, catalyzing the formation of catechin quinone constantly.


Efflux of monoclonal antibodies from rat brain by neonatal Fc receptor, FcRn.
Monoclonal antibody (mAb) engineering that optimizes binding to receptors present on brain vascular endothelial cells has enabled them to cross through the blood-brain barrier (BBB) and access the brain parenchyma to treat neurological diseases. However, once in the brain the extent to which receptor-mediated reverse transcytosis clears mAb from the brain is unknown. The aim of this study was to determine the contribution of the neonatal Fc-receptor (FcRn) in rat brain efflux employing two different in vivo drug delivery models. Two mAb variants with substantially different affinities to FcRn, and no known neuronal targets, (IgG1 N434A and H435A) were administered to rats via intranasal-to-central nervous system (CNS) and intra-cranial dosing techniques. Levels of full-length IgG were quantified in serum and brain hemispheres by a sensitive enzyme-linked immunosorbent assay (ELISA). Following intra-nasal delivery, low cerebral hemisphere levels of variants were obtained at 20min, with a trend towards faster clearance of the high FcRn binder (N434A); however, the relatively higher serum levels confounded analysis of brain FcRn contribution to efflux. Using stereotaxic coordinates, we optimized the timing and dosing regimen for injection of mAb into the cortex. Levels of N434A, but not H435A, decreased in the cerebral hemispheres following bilateral injection into the rat cortex and higher levels of N434A were detected in serum compared to H435A after 24h. Immunohistochemical staining of human IgG1 in sections of cortex was consistent with these results, illustrating relatively less intense immunostaining in N434A than H435A dosed animals. Using two in vivo methods with direct cranial administration, we conclude that FcRn plays an important role in efflux of IgG from the rat brain.


The French Gaucher's disease registry: clinical characteristics, complications and treatment of 562 patients.
Clinical features, complications and treatments of Gaucher's disease (GD), a rare autosomal-recessive disorder due to a confirmed lysosomal enzyme (glucocerebrosidase) deficiency, are described. All patients with known GD, living in France, with ≥ 1 consultations (1980-2010), were included in the French GD registry, yielding the following 4 groups: the entire cohort, with clinical description; and its subgroups: patients with ≥ 1 follow-up visits, to investigate complications; recently followed (2009-2010) patients; and patients treated during 2009-2010, to examine complications before and during treatment. Data are expressed as medians (range) for continuous variables and numbers (%) for categorical variables. Among the 562 registry patients, 265 (49.6%) were females; 454 (85.0%) had type 1, 22 (4.1%) type 2, 37 (6.9%) perinatal-lethal type and 21 (3.9%) type 3. Median ages at first GD symptoms and diagnosis, respectively, were 15 (0-77) and 22 (0-84) years for all types. The first symptom diagnosing GD was splenomegaly and/or thrombocytopenia (37.6% and 26.3%, respectively). Bone-marrow aspiration and/or biopsy yielded the diagnosis for 54.7% of the patients, with enzyme deficiency confirming GD for all patients. Birth incidence rate was estimated at 1/50,000 and prevalence at 1/136,000. For the 378 followed patients, median follow-up was 16.2 (0.1-67.6) years. Major clinical complications were bone events (BE; avascular necrosis, bone infarct or pathological fracture) for 109 patients, splenectomy for 104, and Parkinson's disease for 14; 38 patients died (neurological complications for 15 type-2 and 3 type-3 patients, GD complications for 11 type-1 and another disease for 9 type-1 patients). Forty-six had monoclonal gammopathy. Among 283 recently followed patients, 36 were untreated and 247 had been treated during 2009-2010; 216 patients received treatment in December 2010 (126 with imiglucerase, 45 velaglucerase, 24 taliglucerase, 21 miglustat). BE occurred before (130 in 67 patients) and under treatment (60 in 41 patients) with respective estimated frequencies (95% CI) of first BE at 10 years of 20.3% (14.1%-26.5%) and 19.8% (13.5%-26.1%). This registry enabled the epidemiological description of GD in France and showed that BE occur even during treatment.


Complications of Endovascular and Open Aneurysm Surgery in the Era of Flow Diversion.
The techniques used for treatment of intracranial aneurysms have progressed dramatically over the decades. The introduction of modern endovascular techniques and the continued refinement of progressively less invasive neurosurgical approaches have contributed to steadily improving clinical outcomes. Moreover, innovations such as flow-diverting stents have achieved dramatic success and have gained rapid widespread adoption. Particularly in lesions for which the application of conventional treatment techniques is difficult, flow diversion technology has revolutionized aneurysm management. This review provides a discussion on the morbidity and mortality encountered in the treatment of intracranial aneurysms in the modern era. Common adverse events faced in the management of these lesions with open surgery and various endovascular techniques are highlighted.


Positive regulation by nitrite of the nitrate assimilation operon in the cyanobacteria Synechococcus sp. strain PCC 7942 and Plectonema boryanum.
In the absence of fixation of ammonium to glutamine, nitrate and nitrite activated transcription of the nitrate assimilation (nirA-nrtABCD-narB) operon of Synechococcus sp. strain PCC 7942. In a nitrate reductase-deficient mutant, only nitrite activated transcription, indicating that nitrite is the actual activator of the operon. Nitrate and nitrite were also found to activate the transcription of a nitrate assimilation operon in the filamentous nonheterocystous nitrogen-fixing cyanobacterium Plectonema boryanum.


Is an occupational examination superior to an occupational health history alone for preplacement screening in health care settings?
To determine whether preplacement recommendations following an occupationally focused medical history is different from those following an occupational consultation. This was a retrospective cohort study of 172 applicants to our institution. Following provider review of occupational history survey alone, none of the applicants had restrictions recommended. In comparison, only 163 applicants (94.7%) were recommended to be hired without restrictions following provider review of the same patient's occupational history and examination (P = 0.0078). A well-designed questionnaire is useful for screening applicants for preplacement examinations and assures sufficient detail to allow for a large proportion of individuals to proceed to employment without an occupational examination. However, in this study, a small but statistically significant portion (5%) of applicants required occupational examinations for appropriate work recommendations.


The Effect of Intruder Density on Territoriality and Dominance in Male Swimming Crab (Portunus trituberculatus).
Territorial behavior of animals is affected by numerous factors, one being the number of intruders. The swimming crab (Portunus trituberculatus), an important commercial and ecological species on the continental shelf of Asia, usually needs to defend its territory from intrusion by other crabs, especially in habitats with high densities of conspecifics. To clarify the underlying patterns of how P. trituberculatus protects its territory, we assessed the territorial behavior of occupant crabs (territory holders) when presented with different numbers of intruders using an indoor observation system. We calculated the territory size of the occupants and quantified their behavioral responses to intruders. With an increased number of intruders, the territory size the occupants owned significantly decreased, and their behavior adjusted accordingly. Besides, the territorial behavior score, reflecting the territoriality of crab, decreased significantly. Furthermore, in a high density group that had seven intruders, the occupants showed a higher dominance hierarchy than the intruders, indicating the ascendancy of occupants in territorial competition with intruders. These results revealed that as the number of intruders increased, the territory size of P. trituberculatus shrunk because the fight for territory became more intense.


The Heidelberg foot measurement method: development, description and assessment.
The aim of this study was to develop and evaluate a kinematic measurement method for the foot that could be applied clinically to measure foot function including all typical foot deformities. The ankle was modelled as two anatomically based hinge joints rotating around anatomical axes estimated by the use of projection angles. For the mid- and forefoot a descriptive approach was chosen by defining angles between anatomical landmarks or reference points derived from these landmarks. The motion of 17 markers on the lower leg and foot was measured during walking gait on 10 adult participants with no known abnormalities to determine the pattern of normal foot motion, assess reliability and provide a reference against which pathological foot behaviour could be compared. Functional angles for mid- and forefoot motions were developed to improve clinical applications of the data. The combination of anatomically and technically oriented marker placement on the foot is a reliable basis for reproducible kinematic measurements and the method was shown to be viable for clinical practice.


[Biological implants in abdominal wall hernia surgery].
Permanent synthetic materials are currently of choice for abdominal wall hernia repair. However, they are not ideal as short- and long-term complications with these have been reported. Extracellular matrix-derived biological implants (EMDBI) have emerged as a result of research and development into new materials. Several types of EMDBI have appeared in the last few years, each with its own manufacture characteristics and different from the rest. The current panorama of the xenogeneic EMDBI available in Spain is analysed, their complications, the unknown factors arising in the long-term, and the clinical experience available on incisional and inguinal hernias.


A Woman in Her 30s With a Past History of HIV Disease Presented With Recurrent Fever, Night Sweats, and Small Bilateral Pulmonary Nodules.
A woman in her 30s presented with recurrent low-grade fever and cough (onset, 1 week). She reported occasional night sweats and weight loss of approximately 20 pounds over the past 4 months. She denied nausea, vomiting, diarrhea, or any urinary complaints. Her past medical history was significant for chronic hepatitis C and HIV infection, the latter diagnosed in 2001. She was noncompliant with highly active antiretroviral therapy for more than 4 years and had pneumocystis pneumonia 2 years prior to this presentation. She had a 10-pack per year smoking history and reported active use of cocaine and heroin. The patient denied any occupational exposures.


Dynamic contrast-enhanced MRI to characterize angiogenesis in primary epithelial ovarian cancer: An exploratory study.
Angiogenesis is essential for tumor growth. Currently, there are no established imaging biomarkers to show angiogenesis in tumor tissue. The aim of this prospective study was to evaluate whether semiquantitative and pharmacokinetic DCE-MRI perfusion parameters could be used to assess angiogenesis in epithelial ovarian cancer (EOC). We enrolled 38 patients with primary EOC treated in 2011-2014. DCE-MRI was performed with a 3.0 T imaging system before the surgical treatment. Two different sizes of ROI were used to evaluate semiquantitative and pharmacokinetic DCE perfusion parameters: a large ROI (L-ROI) covering the whole primary lesion on one plane and a small ROI (S-ROI) covering a small solid, highly enhancing focus. Tissue samples from tumors were collected during the surgery. Immunohistochemistry was used to measure the expression of vascular endothelial growth factor (VEGF), its receptors (VEGFRs) and to analyse microvascular density (MVD) and the number of microvessels. VEGF expression correlated inversely with Ktrans (L-ROI, r = -0.395 (p = 0.009), S-ROI, r = -0.390, (p = 0.010)), Ve (L-ROI, r = -0.395 (p = 0.009), S-ROI, r = -0.412 (p = 0.006)) and Vp (L-ROI, r = -0.388 (p = 0.011), S-ROI, r = -0.339 (p = 0.028)) values in EOC. Higher VEGFR-2 correlated with lower DCE parameters Ktrans (L-ROI, r = -0.311 (p = 0.040), S-ROI, r = -0.337 (p = 0.025)) and Ve (L-ROI, r = -0.305 (p = 0.044), S-ROI, r = -0.355 (p = 0.018)). We also found that MVD and the number of microvessels correlated positively with AUC, Peak and WashIn values. We observed that several DCE-MRI parameters correlated with VEGF and VEGFR-2 expression and MVD. Thus, both semiquantitative and pharmacokinetic perfusion parameters of DCE-MRI represent promising tools for the assessment of angiogenesis in EOC.


Adipocytokines and disease progression in endometrial cancer: a systematic review.
The objective of the study was to document the effect of adipocytokines on endometrial cancer progression. A search of the databases CINAHL, Medline, PubMed, Cochrane, Web of Science, Embase and Google Scholar was performed for English language articles from January 2000 to December 2020 using the keywords: (Endometrial cancer) AND (progression OR metastasis) AND (adipocytokine OR adiponectin OR leptin OR visfatin OR IL-6 OR TNF-α OR adipokine OR cytokine). Forty-nine studies on adipocytokines have been included in this review. Adiponectin has been linked with anti-proliferative and anti-metastatic effects on endometrial cancer cells and is associated with a better prognosis. Leptin, visfatin and resistin are linked to the stimulation of endometrial cancer growth, proliferation, invasion and metastasis and are associated with worse prognosis or with a higher grade/stage of endometrial cancer. IL-6, Il-11, IL-31, IL-33, TNF-α, TGF-β1, SDF-1 and CXCR are involved in endometrial cancer cell growth and metastasis or involved in epithelial mesenchymal transformation (EMT) or associated with advanced disease. Adipocytokines have been found to directly impact endometrial cancer cell proliferation, invasion and migration. These molecules and their signalling pathways may be used to determine prognosis and course of the disease and may also be exploited as potential targets for cancer treatment and prevention of progression.


[Hip arthroplasty : Operation preliminary to the prosthetic surgery].
At a time when prosthetic hip surgery becomes more widespread with the use of cementless prostheses, of hydroxyapatite or of metal-metal or alumina-alumina bearings, it is important to recall that prosthetic hip surgery makes it possible to obtain a high percentage of good results whose longevity depends on good indications.The Pauwels inter-trochanteric osteotomy allows one to increase the weight bearing surface. Shelf operations and pelvic osteotomies, allow one to reconstruct a receptive acetabular cavity.One should bear in mind that this surgery cannot be definitive. It will lead in the long term to the hip replacement. It must therefore endeavour to reconstruct the anatomy and avoid creating problematic deformities for the subsequent arthroplasty.


Correction to "Homobimetallic Au(I)-Au(I) and Heterotrimetallic Au(I)-Fe(II)-Au(I) Complexes with Dialkyldithiophosphates and Phosphine Ligands: Structural Characterization, DFT Analysis, and Tyrosinase Inhibitory and Biological Effects".
[This corrects the article DOI: 10.1021/acsomega.3c00645.].


Otoacoustic emissions in a song bird.
Synchronously evoked otoacoustic emissions (SEOAEs) were found in about two thirds (61%) of 56 ears of the starling Sturnus vulgaris. They appeared with rather broad synchronization widths (about 200 Hz) and predominantly at frequencies in the upper half of the hearing range of this bird. SEOAEs varied in level from below -30 dB to 2 dB SPL and showed typically nonlinear intensity functions. The emissions were present even following extirpation of the middle-ear muscle and could be suppressed by anaesthetics. Using Halothane, it was possible to determine the time course of this suppressive effect. Using second tones, typical iso-suppression tuning curves were obtained. The similarities and differences between the characteristics of these SEOAEs and emissions in other nonmammals and in mammals are discussed with regard to anatomical differences in inner-ear structure.


An ultrastructural study of the musculature of the pond snail Lymnaea stagnalis (l.).
The ultrastructure of the musculature of Lymnaea stagnalis was studied. Each of the six muscle systems of the body wall, previously distinguished in an anatomical study, has its own type of smooth muscle, characterised by the size and number of the myofilaments, number of mitochondria and distribution of smooth endoplasmic reticulum. The visceral musculature comprises both smooth and striated muscle. Cross-striated muscle is found in the heart and proximal aorta, obliquely striated muscle in the buccal mass, gizzard and vas deferens. Myofibroblasts and myoendothelial cells were also distinguished. On the basis of the observations it is concluded that striated muscles in L. stagnalis contract and relax more rapidly and have a higher endurance than smooth muscles, but that the latter can contract over a wider range. Among smooth muscles the head retractor muscle contracts most rapidly, the shell muscle is most powerful and the diagonal muscle is slow to contract but has a relatively high endurance. The latter muscle, together with the horizontal foot muscle, plays a major role in maintenance of the hydrostatic skeleton. A model for the organisation of the smooth muscles is deduced from the ultrastructural observations. It implies that the myosin-paramyosin filaments change their actin filament partners during contraction. This agrees with a model deduced for other smooth muscles on the basis of physiological experiments and X-ray diffraction analysis.


The ex-situ and in-situ ultrasonic assisted oxidation of corn starch: A comparative study.
The objective of this study was to evaluate the differences in ex-situ (starch treated by ultrasonication and oxidation sequentially, U-OS) and in-situ (starch treated by ultrasonication and oxidation simultaneously, UOS) ultrasonic assisted oxidation process of corn starch, which were studied in contrast to the traditional oxidized starches (OS). Fourier-transform infrared spectra confirmed the successful oxidation of all modified starches samples. In comparison to the OS, the carboxyl contents of U-OS and UOS increased by 56% and 112%, respectively. The same increase trend was also found for the carbonyl contents. The significance raise was attributed to the great increase of pores and specific surface areas in the starch granule after ultrasonic irradiation which promoted the penetration of the sodium hypochlorite into the starch granules with higher chances for chemical reactions. SEM and pore size distribution characterizations further verified this result. However, the method of in-situ ultrasonic assisted oxidation can simultaneously accelerate the increase of pores and the penetration process. Consequently, the starches with higher oxidation degree can be more efficiently prepared by the strategy of in-situ ultrasonic assisted oxidation.


Oxidative inactivation of the molybdenum-iron-protein component of nitrogenase from clostridium pasteurianum.
The sensitivity of the molybdenum-iron(MoFe)-protein of Clostridium pasteurianum nitrogenase toward oxidation has been studied by determining the enzymatic activity of this component after incubating it anaerobically in ferricyanide solutions of various oxidizing strengths (as measured by their oxidation potentials). It was found that the MoFe-protein remains active at potentials up to +350 mV (vs. standard hydrogen electrode) but becomes readily inactivated at more oxidizing potentials, after a lag period, depending on the potential level and temperature. Oxidative inactivation by ferricyanide results in the release of most of the Mo, Fe and S atoms from the protein which causes the loss of the absorption bands in the visible region. The metals and sulfur could be re-incorporated by incubation in a mixture containing thiol, sulfide, molybdate, and ferric iron. The EPR spectrum of the oxidatively inactivated MoFe-protein showed that both the high- and low-field signals are readily affected. Re-incorporation of the metals and sulfur into the "bleached" protein produced an EPR spectrum similar to that of the air-inactivated protein. Incubation of the Mo-Fe-protein with mersalyl abolished its enzymic activity. The difference spectrum before and after mersalyl treatment resembles that of the soluble spinach ferredoxin.


Synthesis of boronic acid analogs of L-arginine as alternate substrates or inhibitors of nitric oxide synthase.
The asymmetric synthesis of an unprotected alpha-amino boronic acid analog of L-arginine 1a (boroarg-OH. 2 HCl) and its N alpha-acetyl derivative 1b (Ac-boroarg-OH. HCl) is described. These compounds were evaluated as substrates and inhibitors of recombinant nitric oxide synthases (NOS). Boroarg-OH 1a selectively inhibited inducible NOS (IC50 = 50 microM) compared to the neuronal isoform (IC50 = 300 microM).


Prior beetroot juice ingestion offsets endothelial dysfunction following prolonged sitting.
Nutritional strategies to prevent endothelial dysfunction following prolonged sitting remain largely unknown. Given that beetroot juice (BRJ) ingestion enhances nitric oxide (NO) bioavailability, we aimed to evaluate whether prior BRJ ingestion would prevent sitting-induced endothelial dysfunction in the leg. Eleven healthy young males (n = 7) and females (n = 4) underwent two experimental trials of prolonged sitting with prior: 1) placebo (PL) ingestion (PL trial) and 2) BRJ ingestion (BRJ trial). All subjects ingested 140 mL of PL or BRJ (∼0.0055 or ∼12.8 mmol of nitrate, respectively) immediately before 3 h of sitting. Pre- and post-sitting measurements of popliteal artery flow-mediated dilation (FMD) and blood pressure, and blood collection were undertaken. During the sitting period, an hourly assessment of popliteal artery diameter and blood velocity, blood pressure, and blood collection were performed. Popliteal artery blood flow and shear rate were significantly and similarly reduced during the sitting period in both trials (P < 0.001). Plasma nitrate and NOx (total nitrite and nitrate) concentrations were significantly increased relative to baseline in the only BRJ trial, and the overall concentrations were significantly higher in the BRJ trial (P < 0.001). Popliteal artery FMD was significantly reduced after the sitting period in the PL trial (P < 0.05), whereas no reduction was observed in the BRJ trial. Therefore, prior BRJ ingestion would prevent sitting-induced leg endothelial dysfunction via enhancing NO bioavailability.NEW & NOTEWORTHY The present study elucidates that beetroot juice ingestion before prolonged sitting offsets sitting-induced leg endothelial dysfunction. Data from the present study provides novel physiological information that enhancing NO bioavailability by dietary nitrate supplementation is an effective tool for prevention of the detrimental vascular effects of prolonged sitting.


Challenges of an outcome-based perspective for marriage and family therapy education.
Marriage and family therapy (MFT) and marriage and family therapy education (MFTE) have undergone many changes during the short history of MFT. This article describes the current trends and controversies in MFTE, including shifts toward outcome-based education (OBE). We present recommendations for MFTE, including the move toward OBE, the development of core competencies of MFT, attention to interdisciplinary issues, and recognition of the need for both foundational education and encouragement of trainees' unique styles and approaches.


A paclitaxel-conjugated adenovirus vector for targeted drug delivery for tumor therapy.
Tumor-targeted drug delivery is an attractive strategy in cancer treatment. Our previous study demonstrated that modified adenovirus has strong tumor targeting ability and less toxicity to surrounding normal tissue. In this study, Paclitaxel (PTX), a widely used clinical anticancer drug, was conjugated to folate-modified adenovirus (Ad) nanoparticles by using succinic anhydride and Fmoc-Glu(OtBu)-OH linkers to form two prodrugs, FA-Ad-Suc-PTX and FA-Ad-ICG02-Glu-PTX. Near-infrared (NIR) fluorescent dye ICG-Der-02 was attached to -NH(2)-Glu(OtBu)-PTX for in vivo optical imaging. In vitro and acute toxicity study demonstrates the low toxicity of the prodrug FA-Ad-Suc-PTX and FA-Ad-ICG02-Glu-PTX compared to the free drug. The dynamic behaviors and targeting ability of FA-Ad-ICG02-Glu-PTX on MDA-MB-231 tumor-bearing mice were investigated by NIR fluorescence imaging. The result show that PTX-conjugated Ad vector could enhance the targeting and residence time in tumor site. In vitro and in vivo studies demonstrate that Coxsackie adenovirus receptor (CAR) or foliate receptor (FR)-mediated uptake of FA-Ad-loaded PTX induced highly anti-tumor activity. The results support the potential of using chemically modified Ad vector as drug-loaded tumor-targeting delivery system.


HBsAg loss in a New Zealand community study with 28-year follow-up: rates, predictors and long-term outcomes.
HBsAg seroclearance is the most desired endpoint in chronic hepatitis B (CHB) but occurs uncommonly. Recent studies have shown baseline HBsAg levels to be predictive of HBsAg loss up to 10 years. We report the 28-year rates of HBsAg loss and outcomes in the Kawerau study cohort from New Zealand, and assess the predictive value of baseline HBsAg levels to predict long-term HBsAg loss. The 1984 Kawerau community study identified 572 CHB patients, followed up for 28 years (41 % HBeAg-positive, median age 17 years, range 1-71 years). In 2012, surviving individuals attended a local clinic for an interview, blood tests and transient elastography. 384/218 (74 %) surviving individuals attended the clinic in 2012. Spontaneous HBsAg loss occurred in 145 (33 %) after 12,702 person-years of follow-up (1.14 per 100 person-years). Liver stiffness measurements were significantly lower if HBsAg loss occurred <50 years (mean 6.1 kPa) versus >50 years (mean 11.6 kPa), p = 0.0002. No HCC occurred following HBsAg loss (median follow-up 72 months). Predictors of HBsAg loss were older age and lower baseline HBsAg level (HR for HBsAg loss at 28 years 2.7 (95 % CI 1.7-4.2), 6.7 (95 % CI 3.9-11.4) and 9.4 (95 % CI 5.2-16.9), respectively, for HBsAg 1000-9999, 100-999 and <100 IU/mL compared to HBsAg >10,000 IU/mL at baseline, (p < 0.0001). Baseline HBsAg was a superior predictor of HBsAg loss compared to HBV DNA at all time-points: AUROC at 15 years: 0.87 (95 % CI 0.82-0.93) versus 0.73 (95 % CI 0.66-0.80) (p < 0.0001) and AUROC at 28 years: 0.74 (95 % CI 0.69-0.79) versus 0.67 (95 % CI 0.62-0.72) (p = 0.0007). The optimal cut-off HBsAg level to predict HBsAg seroclearance at 28 years is HBsAg <10,000 IU/mL (sensitivity 72 %, specificity 64 %, NPV 88 %). Rates of HBsAg loss in our community cohort were high, and occurred earlier than previously reported. Earlier HBsAg loss was associated with less severe liver fibrosis. Baseline HBsAg level was a good predictor of long-term HBsAg loss up to 28 years and superior to HBV DNA.


Management of septate uterus by flexible hysteroscopy and Nd:YAG laser.
To evaluate the efficiency of flexible Nd-YAG laser hysteroscopic metroplasty. We present a retrospective study of 17 patients treated for septate uteri between 1990 and 1995. The indication of hysteroscopy was recurrent abortion in nine cases and eight with primary infertility with indication of IVF in another five cases. We did not prescribe any pretreatment. A flexible hysteroscope with a 100-W Nd:YAG laser was used with glycine-controlled flow. The septum was divided by the laser after exploration of the cavity. We proposed a control office hysteroscopy 2 months after surgery to prevent uterine adhesions. There was no complication. Twelve patients conceived with 10 live births at term and two spontaneous abortions. Four are still infertile, two were lost from the study and two no longer desired pregnancy. Resectoscopic studies showed the same results. The advantages of this method are the excellent ergonomic properties of the fibroscope and the safety of the laser. We suggest that metroplasty does not improve the pregnancy rate but only the pregnancy outcome of these patients. However, for those with the indication of IVF the procedure seems useful in avoiding abortion.


Dorsal medullary inspiratory neurons: effects of superior laryngeal afferent stimulation.
In decerebrate paralyzed cats ventilated with a cycle-triggered pump, we examined the responses of inspiratory (I) neurons in the region of the ventrolateral nucleus tractus solitarius (NTS) to single electrical stimuli delivered to the ipsilateral superior laryngeal nerve (SLN). Sixty-five I neurons were classified as: I(-), I(0), I(+, early), I(+, late) or I(other) on the basis of responses to lung inflation, and as I(bulbophrenic) or I(non-bulbophrenic) on the basis of evidence of an excitatory projection to the contralateral phrenic motoneuron pool. The peristimulus histograms of contralateral phrenic activity showed an early peak of excitation with average latency of 4.9 +/- 0.1 ms (mean +/- S.E.M.), followed by depression at 7.3 +/- 0.2 ms, start of recovery from depression at 22.7 +/- 1.0 ms, and recovery to control levels at 28.4 +/- 1.1 ms. The peristimulus histograms of ipsilateral I unit activity showed an initial excitation (latency 2.9 +/- 0.3 ms), followed by spiking silence (latency 6.0 +/- 0.6 ms) and recovery to control discharge frequency at 38.8 +/- 3.6 ms. This time of inhibition was significantly longer than the time of phrenic depression, suggesting that other bulbophrenic excitatory projections are able to rapidly compensate for decreased NTS output. Subgroups of I neurons, as classified by lung inflation tests, did not differ significantly with respect to these timing variables. In contrast, latencies of excitation for I(bulbophrenic) neurons were significantly less than for I(non-bulbophrenic) neurons.


Coupled-enzyme and direct assays for uroporphyrinogen III synthase activity in human erythrocytes and cultured lymphoblasts. Enzymatic diagnosis of heterozygotes and homozygotes with congenital erythropoietic porphyria.
Rapid and reproducible assays for uroporphyrinogen III synthase (URO-S; EC 22.214.171.124) have been developed and used to determine the enzymatic activity in human erythrocytes and cultured lymphoid cells. In the coupled-enzyme assay, porphobilinogen was first converted to hydroxymethylbilane, the natural substrate for URO-S, by hydroxymethylbilane synthase which was conveniently obtained from heat-treated erythrocyte lysates. In the direct assay, synthetic hydroxymethylbilane was used as substrate. In both assays, the uroporphyrinogen reaction products were oxidized to their respective uroporphyrin isomers, which were then resolved and quantitated by reversed-phase high-pressure liquid chromatography. Both assays were optimized for pH, substrate concentration, and linearity with time and protein concentration. The mean URO-S activities in normal human erythrocyte lysates determined by the coupled-enzyme and direct assays were 7.41 +/- 1.35 and 7.64 +/- 1.73 units/mg protein, respectively. In normal human cultured lymphoid cells, the mean activities were 13.7 +/- 1.39 and 17.6 +/- 1.15 units/mg protein for the coupled-enzyme and direct assays, respectively. In four families with congenital erythropoietic porphyria, both assays reliably identified the markedly decreased URO-S activities in erythrocytes and cultured lymphoid cells from affected homozygotes and the half-normal activities in these sources from obligate heterozygotes. The coupled-enzyme assay was easier to perform and was suited for clinical diagnostic assays and for monitoring enzyme purification procedures, while the direct assay, which required substrate preparation and technical dexterity, was best for kinetic studies of URO-S.


Cross-modal transfer after auditory task-switching training.
Task-switching training was shown to improve performance not only for the trained tasks (i.e., reduced performance costs resulting from the task switches), but also for structurally similar (near transfer) or even dissimilar tasks (far transfer). However, it is still unclear whether the improvement is specific to the trained input modality or whether cognitive control occurs at an amodal processing level enabling transfer of set-shifting abilities to different input modalities. In this study, training and transfer was assessed for an auditory task-switching paradigm in which spoken words from different semantic categories were presented dichotically requiring participants to switch between two auditory categorization tasks. Cross-modal transfer of task-switching training was assessed in terms of the performance costs in a visual task-switching situation using tasks that were structurally similar to the trained tasks. The 4-day training significantly reduced the costs resulting from mixing the two auditory tasks, as compared to both an active (auditory single-task training) and a passive control group (no training). More importantly, the auditory task-switching training was also found to reduce the mixing costs for untrained visual tasks, indicating cross-modal transfer. This finding suggests that the improvement resulting from task-switching training is not specific to the trained stimulus modality, but it seems to be driven by a cognitive control mechanism operating at an amodal processing level. The training did not reveal any far-transfer effects to working memory, inhibition, or fluid intelligence, suggesting that the modality-independent enhancement of set-shifting does not generalize to other cognitive control functions.


Evidence-based evaluation of abdominal drainage in pancreatic surgery.
Pancreatic fistula is the most common and dreaded complication after pancreatic resection, responsible for high morbidity and mortality (2 to 30%). Prophylactic drainage of the operative site is usually put in place to decrease and/or detect postoperative pancreatic fistula (POPF) early. However, this policy is currently debated and the data from the literature are unclear. The goal of this update is to analyze the most recent evidence-based data with regard to prophylactic abdominal drainage after pancreatic resection (pancreatoduodenectomy [PD] or distal pancreatectomy [PD]). This systematic review of the literature between 1990 and 2020 sought to answer the following questions: should drainage of the operative site after pancreatectomy be routine or adapted to the risk of POPF? If a drainage is used, how long should it remain in the abdomen, what criteria should be used to decide to remove it, and what type of drainage should be preferred? Has the introduction of laparoscopy changed our practice? The literature seems to indicate that it is not possible to recommend the omission of routine drainage after pancreatic resection. By contrast, an approach based on the risk of POPF using the fistula risk score seems beneficial. When a drain is placed, early removal (within 5 days) seems feasible based on clinical, laboratory (C-reactive protein, leukocyte count, neutrophile/lymphocyte ratio, dosage and dynamic of amylase in the drains on D1, D3±D5) and radiological findings. This is in line with the development of enhanced recovery programs after pancreatic surgery. Finally, this literature review did not find any specific data relative to mini-invasive pancreatic surgery.


Noise analysis of a combined optical coherence tomograph and a confocal scanning ophthalmoscope.
A fiberized optical coherence tomographic (OCT) system is modified to produce a confocal image similar to that produced by a scanning laser ophthalmoscope. Two possible configurations are presented, one that can deliver either an OCT or a confocal image and another that is capable of producing both the OCT and the confocal images simultaneously. Using the later configuration, we demonstrate such images from the retina in the living eye. The penalty in terms of performance reduction introduced into the optical coherence tomograph when integrated with a confocal receiver and the signal-to-noise ratio analysis for the different confocal receiver configurations are presented.


Molecular phylogeny of litostome ciliates (Ciliophora, Litostomatea) with emphasis on free-living haptorian genera.
The monophyly of the litostomes was tested using nine newly sequenced and four previously unpublished small subunit ribosomal RNA (SSrRNA) gene sequences from free-living Haptoria as well as from endosymbiotic Trichostomatia: the vestibuliferids Balantidium coli and Isotricha prostoma, the cyclotrichiid Mesodinium pulex, and the haptorids Loxophyllum rostratum, Dileptus sp., Enchelyodon sp., Enchelys polynucleata, Epispathidium papilliferum (isolates A and B), Spathidium stammeri, Arcuospathidium muscorum, Arcuospathidium cultriforme, and the unusual Teuthophrys trisulca. Phylogenetic analyses depicted the litostomes as a monophyletic group consisting of the trichostomes (subclass Trichostomatia) and the free-living haptorians (subclass Haptoria). The cyclotrichiids Mesodinium and Myrionecta (order Cyclotrichiida) branched either basally within or outside the Litostomatea. In most analyses, the haptorians did not receive support as a monophyletic group. Instead, Dileptus branched basally to all litostome taxa, and Epispathidium papilliferum grouped with the Subclass Trichostomatia. Some subgroupings, however, of haptorian genera corresponded to suggested superfamilial taxa (e.g., orders Spathidiida and Pleurostomatida). Within the monophyletic trichostomes, we can distinguish three clades: (1) an Australian clade; (2) the order Entodiniomorphida; and (3) the order Vestibuliferida. However, Balantidium, currently classified in the Vestibuliferida, did not group with the other vestibuliferids, suggesting that this order may be paraphyletic.


Correction: Phylogenetic analysis of hepatitis C virus among HIV/ HCV co-infected patients in Nigeria.
[This corrects the article DOI: 10.1371/journal.pone.0210724.].


Why is school leadership key to transforming education? Structural and cultural assumptions for quality education in diverse contexts.
Failing to recognize the role of leaders in quality and equitable schooling is unfortunate and must be redressed. Leadership is fundamentally about organized agency and collective vision, not managerialism, since it is an organizational quality, not merely a positionality attribute. Most important, if change is to be systemic and transformative, it cannot occur uniquely at the individual teachers' level. School organization is fundamental to circulating and consolidating new innovative actions, cognitive schemes, and behaviors in coherent collective practices. This article engages with the relevance of governance patterns, school organization, and wider cultural and pedagogical factors that shape various leadership configurations. It formulates several assumptions that clarify the importance of leadership in any organized change. The way teachers act and represent their reality is strongly influenced by the architecture of their organization, while their ability to act with agency is directly linked to the existence of flat or prominent hierarchies, both potentially problematic for deep and systemic change. A hierarchical imposition from above as well as a lack of leadership vision in fragmented school cultures cannot determine any transformation.


Human pituitary development and application of iPSCs for pituitary disease.
The pituitary plays a pivotal role in maintaining systemic homeostasis by secreting several hormones. During fetal development, the pituitary develops from the oral ectoderm in contact with the adjacent hypothalamus. This process is regulated by the fine-tuned expression of transcription and growth factors. Impairments of this process result in congenital pituitary hypoplasia leading to dysfunction of the pituitary. Although animal models such as knockout mice have helped to clarify these underlying mechanisms, the developmental processes of the human pituitary gland and the mechanisms of human pituitary disorders have not been fully understood. This is because, at least in part, of the lack of a human pituitary developmental model. Recently, methods for in vitro induction of the pituitary gland from human pluripotent stem cells were developed. These models can be utilized not only for regenerative medicine but also for human pituitary studies on developmental biology and for modeling of pituitary disorders, such as hypopituitarism and pituitary tumors. In this review, we provide an overview of recent progress in the applications of pluripotent stem cells for pituitary research and discuss further perspectives for pituitary studies.


Rapid pre-screening of cervical smears as a method of internal quality control in a cervical screening programme.
To evaluate the performance of rapid pre-screening (RPS) as a method of internal quality control in the cytopathological examination of cervical smears for cervical cancer screening. The sample consisted of 6135 cervical smears submitted to RPS and routine screening (RS) methods. The smears classified as negative in RPS and RS were considered final diagnoses, and were not, therefore, submitted to any additional review. The smears identified as suspect or unsatisfactory according to RPS were analysed separately by two different cytologists irrespective of the diagnosis reached in RS. Smears considered abnormal or unsatisfactory at RS were also reviewed. When both cytologists issued concordant diagnoses, this was considered the final diagnosis. Discordant results were analysed by a third cytologist and a consensus meeting was held to define the final diagnosis. Taking abnormalities detected by RS as the denominator, RPS had a sensitivity of 63.0% for the detection of all abnormal smears and 96.7% for high grade squamous intraepithelial lesion (HSIL). When compared with the final diagnosis, sensitivity of RPS for all abnormal smears was 74.9% and for HSIL 95.0%. Of the 529 abnormal smears confirmed in the final diagnosis, 2.15% were detected only by the RPS. RPS is an effective alternative method of internal quality control with high sensitivity for the detection of more severe lesions. It also permits monitoring of the laboratory rate of false-negative results, and allows constant evaluation of the performance both of the pre-screening and RS cytologists.


Goblet cell carcinoid tumor of the appendix. Report of five cases and review of the literature.
Five cases of goblet cell carcinoid tumor of the appendix showed characteristic histologic features that justified classification of these lesions as mucinous variants of carcinoid tumor. The tumor has low-grade malignancy, and metastases are uncommon. Resemblance to mucinous adenocarcinoma of the appendix is striking, and the features that help to differentiate the two lesions are delineated.