Ultrasound examination before amniocentesis and success of culture in genetic referrals. Six years' experience in Cape Town.
Our experience in Cape Town shows that ultrasound examination is of great benefit when amniocentesis is performed to obtain amniotic fluid cells for metaphase plates from patients at risk of carrying a fetus with a genetic disorder. Data taken over a period of 6 years show that the number of blood-contaminated fluid specimens decreases significantly when patients are scanned before amniocentesis is performed. The presence of blood in the fluid increases the possibility that cells will not grow in culture. There was no evidence to suggest that ultrasound examination inhibited amniotic fluid cell growth in culture.


Sexual behavior and wet dog shakes in the male rat: regulation by corticosterone.
The potential involvement of adrenal steroids in the regulation of 'wet dog shakes' (WDS) and sexual behavior was investigated in male rats treated or not with the serotonergic type 2A (5-HT2A) agonist DOI (5-HT2A receptor agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane). In Experiment 1, the frequency of both spontaneous and DOI-induced WDS were compared in adrenalectomized and sham-adrenalectomized rats. Adrenalectomy significantly reduced the frequency of DOI-induced WDS. In Experiment 2, adrenalectomized and sham-adrenalectomized rats received either corticosterone or oil chronically and were again scored for WDS behavior. Corticosterone effectively blocked the adrenalectomy-induced reduction of WDS in the DOI treatment condition. In Experiment 3, intact male rats were chronically administered either corticosterone or oil treatment. Animals were then compared on measures of both spontaneous and DOI-induced WDS and sexual behavior. Corticosterone significantly increased WDS and inhibited sexual behavior in both the spontaneous and DOI treatment conditions. These results suggest that the adrenal steroid corticosterone is important in the regulation of WDS and sexual behavior in the male rat and that this regulation may be mediated by activity at 5-HT2A receptors.


Connectionism and Behavioral Clusters: Differential Patterns in Predicting Expectations to Engage in Health Behaviors.
The traditional approach to health behavior research uses a single model to explain one behavior at a time. However, health behaviors are interrelated and different factors predict certain behaviors better than others. To conceptualize groups of health behaviors as memory events that elicit various beliefs. A connectionist approach was used to examine patterns of construct activation related to expectations to engage in health behavior clusters. A sample of lay people (N = 1,709) indicated their expectations to perform behaviors representing four clusters (Risk Avoidance, Nutrition & Exercise, Health Maintenance, and General Well-Being) and rated them on 14 constructs obtained from health behavior literature. Expectations to engage in all behavioral clusters were significantly and positively associated with "frequency of performance," "perceived behavioral control," and "anticipated regret," and negatively associated with "effort." However, each behavioral cluster was also predicted by activation of a unique pattern of predictors. A connectionist approach can be useful for understanding how different patterns of constructs relate to specific outcomes. The findings provide a rationale for lay people's cognitive schema of health behaviors, with each behavioral cluster possessing characteristics associated with distinct predictors of expectations to engage in it. These unique activation patterns point to factors that may be particularly significant for health interventions targeting different clusters of health behaviors.


[Study on the distribution of vitamin D receptor gene start codon polymorphism in the Achangs and Hans].
To detect the difference between the Chinese Achang and Han ethnic groups in Yunnan province in the distribution of vitamin D receptor (VDR) gene start codon polymorphism. Polymerase chain reaction-restriction fragment length polymorphism, gene sequencing and genetic analysis methods were used. A restriction fragment length polymorphism in the start codon of VDR (Fok I) gene was tested in the Achangs (n=68) and the Hans (n=92). The frequencies of FF, Ff and ff genotypes were found to be 18%, 35% and 47% in the Achangs, and 22%, 52% and 26% in the Hans, respectively. A significant difference was seen in the frequency distribution of VDR genotype between the Achangs and the Hans(Chi2=7.716, P=0.021). The Achang and Han ethnic groups differ in the frequency distribution of VDR gene start codon polymorphism.


Infrequent patterns of upper gastrointestinal tract malignancy.
The skin and the upper gastrointestinal tract are frequent sites of malignant tumors. However, cutaneous metastasis from primary gastrointestinal tract lesions remains a relative rarity. Similarly rare is spread of primary skin cancer (nonmelanomatous) to upper gastrointestinal tract. This paper presents an unusual example of primary esophageal carcinoma with synchronous skin and bone metastases and a case of squamous cell carcinoma of the stomach, possibly due to spread from a remote squamous cell carcinoma of the skin.


microRNA control of interferons and interferon induced anti-viral activity.
Interferons (IFNs) are cytokines that are spontaneously produced in response to virus infection. They act by binding to IFN-receptors (IFN-R), which trigger JAK/STAT cell signalling and the subsequent induction of hundreds of IFN-inducible genes, including both protein-coding and microRNA genes. IFN-induced genes then act synergistically to prevent virus replication and create an anti-viral state. miRNA are therefore integral to the innate response to virus infection and are important components of IFN-mediated biology. On the other hand viruses also encode miRNAs that in some cases interfere directly with the IFN response to infection. This review summarizes the important roles of miRNAs in virus infection acting both as IFN-stimulated anti-viral molecules and as critical regulators of IFNs and IFN-stimulated genes. It also highlights how recent knowledge in RNA editing influence miRNA control of virus infection.


Osteogenic differentiation of rat bone mesenchymal stem cells cultured on poly (hydroxybutyrate-co-hydroxyvalerate), poly (ε-caprolactone) scaffolds.
Bioresorbable biomaterials can fill bone defects and act as temporary scaffold to recruit MSCs to stimulate their differentiation. Among the different bioresorbable polymers studied, this work focuses on poly(hydroxybutyrate-co-hydroxyvalerate) (PHBV) and poly(ε-caprolactone) (PCL). Were prepared blends of PHBV and PCL to obtain PHBV based biomaterials with good tenacity, important for bone tissue repair, associated with biocompatible properties of PCL. This study assesses the viability of Vero cells on scaffolds of PHBV, PCL, and their blends and the osteogenic differentiation of mesenchymal stem cells (MSCs). Materials were characterized in surface morphology, DSC and Impact Strength (IS). Vero cells and MSCs were assessed by MTT assay, cytochemical and SEM analysis. MSC osteogenic differentiation was evaluated through alizarin red staining and ALP activity. We found some roughness onto surface materials. DSC showed that the blends presented two distinct melting peaks, characteristic of immiscible blends. IS test confirmed that PHBV-PCL blends is an alternative for increase the tenacity of PHBV. MTT assay showed cells with high metabolic activities on extract toxicity test, but with low activity in the direct contact test. SEM analysis showed spreading cells with irregular and flattened morphology on different substrates. Cytochemical study revealed that MSCs maintained their morphology, although in smaller number for MSCs. The development of nodules of mineralized organic matrix in MSC cultures was identified by alizarin red staining and osteogenic differentiation was confirmed by the quantification of ALP activity. Thus, our scaffolds did not interfere on viability of Vero cells or the osteogenic differentiation of MSCs.


Characterization of cellular senescence in doxorubicin-induced aging mice.
With a rise in the need to develop anti-aging drugs, a growing number of in vivo studies evaluating the efficacy of potential drug candidates have used doxorubicin-induced aging mice. However, changes in the biomarkers of senescent cells have not been reported in detail in these animals. To lay a foundation for the use of doxorubicin-induced aging mice, we examined the biomarkers of hepatic and renal senescent cells in these mice. We found that the 5 mg/kg doxorubicin dose is optimal to induce cellular senescence in mice. Subsequently, using this dose, we found that doxorubicin-induced an increase in senescence-associated β-galactosidase (SA-β-gal) positive cells in the kidney and lipofuscin accumulation in the liver. Some markers of senescent cells (p21WAF1/CIP1, p16INK4A, and γH2AX) were also significantly upregulated by doxorubicin and then counteracted by metformin treatment. These preliminary findings support the application of doxorubicin-induced aging mice as an animal model to evaluate the efficacy of anti-aging drug candidates.


[Metastatic screening before adjuvant chemotherapy in breast cancer].
Systematic metastasis staging in early breast cancer is no longer recommended. However, it is still performed before adjuvant chemotherapy. We assessed metastasis screening of asymptomatic women with a local breast cancer without lymph node involvement when adjuvant chemotherapy was indicated. The screening result was classified in 3 groups: "non-metastatic", "metastatic" and "suspect". For suspect screening, we analyzed the checking period and the consequences on cares. Out of 1545 patients with possible indication of chemotherapy, 690 indications of chemotherapy were validated by multidisciplinary meeting. Six hundred and thirty-nine metastasis screening were done. Five hundred and fifty-five screenings (86.9 %) were "non-metastatic", 3 screenings (0.5 %) were "metastatic" and 81 screenings (12.7 %) were "suspect". Out of this 81 suspect screening, only 47 screening have been checked, using 61 further investigations. No breast cancer metastasis was finally identified. Low rate of metastasis suggest reassessing metastasis screening before adjuvant chemotherapy for patients without lymph node involvement.


Exposomal research in the context of birth cohorts: What have they taught us?
To review birth cohorts with an exposomal approach and their key outcomes and challenges. Exposome encompasses all human environmental exposures from conception onward. The impact of environmental exposures is greatest in critical stages of life, including fetal and early childhood. Birth cohorts provide a good study setting to assess exposome in the sensitive periods of life. Here, we review birth cohorts with an exposomal approach and their key outcomes and challenges. MEDLINE was searched for birth cohorts that have used an exposomal approach. Relevant studies in English language were selected and reviewed. The outcomes of birth cohorts with an exposomal approach improve our understanding of the association between environmental exposures and childhood diseases. For example, results from The Canadian Healthy Infant Longitudinal Development Study suggest an association between first trimester exposure to traffic-related air pollution and increased risk of allergic sensitization at 12 months of age (P = .6). In a smaller Canadian birth cohort study, it was found that regular use of air fresheners (adjusted P = .04) and presence of mold in the residence (adjusted P < .001) were associated with early childhood wheezing and cough. The application of emerging molecular omics technologies and new analytical tools has facilitated the comprehensive assessment of exposome in birth cohorts. Birth cohort studies with an exposomal approach improve our understanding of the origin of childhood diseases by examining a complex network of environmental exposures during pregnancy and years beyond birth. International collaboration is required to develop large birth cohorts for better and more extensive assessment of exposome with standardized protocols and new statistical frameworks.


Enteropathogenic Escherichia coli (EPEC): Does it have a role in colorectal tumourigenesis? A Prospective Cohort Study.
Despite the characterization of many aetiologic genetic changes. The specific causative factors in the development of sporadic colorectal cancer remain unclear. This study was performed to detect the possible role of Enteropathogenic Escherichia coli (EPEC) in developing colorectal carcinoma. Fresh biopsy specimens have been obtained from the colonic mucosa overlying the colorectal cancer as well as from the colon of the healthy controls. Culture, genotyping and virulence of EPEC were done using (nutrient broth culture, and PCR). Strains biochemically identified as Escherichia coli were selected from the surface of a MacConkey's plate and were serogrouped by slide agglutination tests. From January 2011 to June 2014, 213 colorectal cancer patients (Group 1) and 248 healthy controls (Group 2) were prospectively enrolled in this study. EPEC was positive in 108 (50.7%) in group 1 and 51 (20.6%) in group 2 (P = 0.0001). A significant difference between both groups was observed regarding serotyping, genotyping (eae gene) and virulence category (P = 0.0001). A significant difference between the 2 subgroups of colorectal cancer cases was observed regarding genotyping (eae, bfb genes) and virulence category. The incidence EPEC was higher significantly in patients with colorectal cancer. E. coli in patients with colorectal cancer significantly differed serotypically and genotypically from the E. coli in normal population. E. coli colonization of the colonic mucosa may be a cause colorectal cancer.


Standard median nerve ultrasound in carpal tunnel syndrome: A retrospective review of 1,021 cases.
Carpal tunnel syndrome (CTS) is diagnosed with electrodiagnostic (EDx) studies. Investigations have examined US cross sectional-area (CSA) and wrist to forearm ratio (WFR) cut-offs for screening EDx abnormalities in patients with suspected CTS. The objective of this study is to determine if these US parameters are effective in a real world population. This is a retrospective review of patients presenting to the Duke Electromyography (EMG) Laboratory during 2013-2014 with a final diagnosis of CTS. US diagnosis of CTS was based upon median nerve cross-sectional area of >9 mm2 and/or wrist-to-forearm ratio of >1.4. EDx studies were the gold standard for diagnosis. A total of 670 patients and 1,021 extremities were studied. US was positive in 97.6% of EDx confirmed CTS. Median nerve US is nearly as sensitive as the gold standard for EDx testing for the diagnosis of CTS. The data here suggest that US may have use as a screening tool prior to performing EDx testing for CTS.


Clinical Characteristics and Prognosis of Bloodstream Infection with Carbapenem-Resistant Pseudomonas aeruginosa in Patients with Hematologic Malignancies.
To analyze the clinical characteristics and prognostic risk factors of carbapenem-resistant Pseudomonas aeruginosa (CRPA) bloodstream infections in patients with hematologic malignancies. Medical records and drug susceptibility data of patients with hematologic malignancies complicated by CRPA bloodstream infections admitted to the Cancer Hospital of Zhengzhou University between January 1, 2018, and December 31, 2022, were retrospectively analyzed. A total of 64 patients were included in the study, with a mortality rate of 37.5% (24/64) at 28 days after the occurrence of CRPA bloodstream infection. In Cox regression analysis, an absolute neutrophil count <0.5×109/L at discharge (HR 0.039, 95% CI 0.006 ~ 0.258, p=0.001), admission to the intensive care unit (HR 7.546, 95% CI 1.345 ~ 42.338, p= 0.022), and a higher Pitt bacteremia score (HR 0.207, 95% CI 0.046 ~ 0.939, p = 0.041) were independent risk factors associated with 28-day mortality. Survival analysis showed that patients receiving ceftazidime-avibactam-based (HR 0.368, 95% CI 0.107~ 1.268, p = 0.023) or polymyxin B (HR 2.561, 95% CI 0.721 ~ 9.101, p = 0.015) therapy had a higher survival rate. Patients with hematologic neoplasms had high mortality from CRPA bloodstream infections, and admission to the intensive care unit, higher Pitt bacteremia score (PBS) scores, granulocyte deficiency, and granulocyte deficiency at discharge were independently associated with higher mortality. Early anti-infective treatment with ceftazidime-avibactam or polymyxin B may improve the clinical prognosis of patients.


Tackling the challenges of developing microneedle-based electrochemical sensors.
Microneedles provide unique advantages in biomedical areas, particularly biosensing, because of their opportunities for minimally invasive and convenient detection. This review introduces concepts of electrochemical microneedle-based sensors for minimally invasive analysis together with insights into skin compartments for designing successful microneedles. We discuss requirements for developing microneedle-based biosensors, including electrical and electrochemical behaviors of materials (such as metals, nanomaterials, and conducting polymers) which are the key factors for sensitive biosensors. We further emphasize immobilization strategies to attach biorecognition elements to electrode materials. Moreover, we detail advanced techniques that require state-of-the-art fabrications and materials to realize porous, biodegradable, and antifouling materials to enhance biosensing performances. We also emphasize studies of cytotoxicity and damage to the skin to elucidate biocompatible potentials. Furthermore, we highlight the latest advances in microneedles published from 2019 to 2022. This review also includes an overview of key remaining obstacles and opportunities where developments will push the advances continuously. The conclusion and outlook on the status of laboratory and commercial availability are added. We prospect that microneedle sensors will be integrated into a closed-loop system biodevice for diverse applications, e.g., detection and therapy. This review discusses concepts of electrochemical microneedle-based sensors for minimally invasive monitoring. We discuss requirements including geometry, mechanical, electrical, electrochemical properties, and immobilization strategy. We illustrate advanced techniques and materials to enrich biosensor features, e.g., porosity, dissolvable ability, and anti-fouling capability. Concern of toxicity is highlighted. We also illustrate recent applications and outlooks of recently published study that exploits microneedle-based biosensors.


Polyethyleneimine-protected silver cluster for label-free and highly selective detection of 2,4,6-trinitrotoluene.
Sensitive and selective detection of 2,4,6-trinitrotoluene (TNT) is critical for environmental protection and public health. In this work, a convenient synthesis strategy for preparation of fluorescent PEI-AgNCs was described and further a facile and label-free sensing strategy for detection of TNT was developed. The hyperbranched polyethyleneimine (PEI) were used as template to one-step synthesize functional PEI-AgNCs with bright fluorescence signal and rich amino groups on their surface. PEI can specifically bind to electron-deficient TNT through donor-receptor interaction to form Meissenheimer complex. Interestingly, the absorption spectra of the Meissenheimer complex overlap with the fluorescence emission peak of PEI-AgNCs, thus quenching fluorescence of PEI-Ag NCs through fluorescence resonance energy transfer (FRET). Furthermore, this bonding process also initiate aggregation of PEI-AgNCs and quench the fluorescence of PEI-AgNCs by the aggregation-induced quenching (AIQ) effect. The novel method demonstrates sensitivity with a detection limit for TNT have been obtained as 17 nM. In addition, the proposed sensing method also has good selectivity over other potential interference and displayed a good potential application value in real water samples with satisfactory recoveries, offering a promising platform for sensing TNT in public safety and security environment protection.


Short-term exposition to acute cadmium toxicity induces the loss of root gravitropic stimuli perception through PIN2-mediated auxin redistribution in Arabidopsis thaliana (L.) Heynh.
Cadmium (Cd), one of the most widespread and water-soluble polluting heavy metals, has been widely studied on plants, even if the mechanisms underlying its phytotoxicity remain elusive. Indeed, most experiments are performed using extensive exposure time to the toxicants, not observing the primary targets affected. The present work studied Cd effects on Arabidopsis thaliana (L.) Heynh's root apical meristem (RAM) exposed for short periods (24 h and 48 h) to acute phytotoxic concentrations (100 and 150 µM). The effects were studied through integrated morpho-histological, molecular, pharmacological and metabolomic analyses, highlighting that Cd inhibited primary root elongation by affecting the meristem zone via altering cell expansion. Moreover, Cd altered Auxin accumulation in RAM and affected PINs polar transporters, particularly PIN2. In addition, we observed that high Cd concentration induced accumulation of reactive oxygen species (ROS) in roots, which resulted in an altered organization of cortical microtubules and the starch and sucrose metabolism, altering the statolith formation and, consequently, the gravitropic root response. Our results demonstrated that short Cd exposition (24 h) affected cell expansion preferentially, altering auxin distribution and inducing ROS accumulation, which resulted in an alteration of gravitropic response and microtubules orientation pattern.


Reduced proactive inhibition in schizophrenia is related to corticostriatal dysfunction and poor working memory.
Inhibitory control is central to executive functioning and appears deficient in schizophrenia. However, it is unclear how inhibitory control is affected, what the underlying neural mechanisms are, whether these deficits are related to the illness itself or to increased risk for the illness, and whether there is a relation to impairments in other executive functions. We used functional magnetic resonance imaging to investigate two forms of inhibitory control: proactive inhibition (anticipation of stopping) and reactive inhibition (outright stopping). Twenty-four schizophrenia patients, 24 unaffected siblings, and 24 healthy control subjects performed a modified version of the stop-signal paradigm. To assess the relation between performance on inhibitory control and other executive functions, we correlated inhibitory control indices with working memory span. Compared with control subjects, proactive inhibition was reduced in patients and siblings. Reactive inhibition was unaffected. Reduced proactive inhibition was associated with a failure to activate the right striatum, the right inferior frontal cortex, and the left and right temporoparietal junction. Activation during reactive inhibition was unaffected. Those patients with the least proactive inhibition also showed the shortest working memory span. These results suggest that schizophrenia is associated with reduced proactive inhibition, probably resulting from corticostriatal dysfunction. This deficit is related to an increased risk for schizophrenia and likely reflects a general executive function deficit rather than a specific inhibitory control impairment.


Anticoccidial effects of Aloe secundiflora leaf extract against Eimeria tenella in broiler chicken.
Anticoccidial effects of Aloe secundiflora crude leaf extract was tested in broiler chickens following oral infection with Eimeria tenella. Sixty 22-day-old birds were divided into six groups of ten birds each. Three treatment groups A, B, and C were fed with the extract (100, 250, and 500 mg/day, respectively) mixed in feed for 10 days, and three control groups: group D (drug control) administered 300 mg/l of sulfachloropyrazine sodium soluble powder in drinking water for 5 days, group E (infected/non-medicated positive control), and group F (uninfected/non-medicated negative control). Except for group F, all groups were orally inoculated with 75,000 sporulated oocysts of E. tenella. The effects of the extract on E. tenella infection were evaluated by severity of bloody diarrhea, body weight (BW) gain, oocyst output, and lesion score. No bird in the treated groups died of coccidiosis, and severity of bloody diarrhea was milder than in the positive control group. BW gains in the treated groups were significantly higher than in group E (p < 0.05). The lesion scores of the treated groups were significantly lower than that of group E. Oocyst output in groups A, B, and C were 11.23, 8.24, and 6.82 × 106, respectively. As compared with the negative control group (12.84 × 106), the reductions in oocyst production were 12.54, 35.83, and 46.88%, respectively. Oocyst output significantly reduced with an increase in Aloe dosage. The findings of this study suggest that Aloe secundiflora extract presents an alternative anticoccidial agent for the control of avian coccidiosis.


The other functions of the sodium pump.
Na/K-ATPase (the sodium pump) was discovered in the 1950s as the plasma membrane enzyme that carries out the coupled active transports of Na+ and K+ across the membranes of nearly all eukaryotic cells. It was not until the 1990s when it was shown that besides pumping ions, Na/K-ATPase is also capable of stimulus-induced interactions with neighboring proteins that lead to activations of signal transduction pathways causing cell growth. This article is an attempt to review the progress of the research on these signaling functions of sodium pump during the past 2-3 decades. The covered topics include (a) the controversial digitalis-induced growth activations through the epidermal growth factor receptor and Src kinase in cardiac myocytes and several other cell types; (b) the extensive findings on digitalis-induced growth activations in cardiac myocytes and other cell types through phosphatidylinositol 3-kinases; and (c) a number of interesting but insufficiently studied signaling functions of the sodium pump.


Systematic variations associated with renal disease uncovered by parallel metabolomics of urine and serum.
Membranous nephropathy is an important glomerular disease characterized by podocyte injury and proteinuria, but no metabolomics research was reported as yet. Here, we performed a parallel metabolomics study, based on human urine and serum, to comprehensively profile systematic metabolic variations, identify differential metabolites, and understand the pathogenic mechanism of membranous nephropathy. There were obvious metabolic distinctions between the membranous nephropathy patients with urine protein lower than 3.5 g/24 h (LUPM) and those higher than 3.5 g/24 h (HUPM) by Partial Least Squares Discriminant Analysis (PLS-DA) model analysis. In total, 26 urine metabolites and 9 serum metabolites were identified to account for such differences, and the majority of metabolites were significantly increased in HUPM patients for both urines and serums. Combining the results of urine with serum, all differential metabolites were classified to 5 classes. This classification helps globally probe the systematic metabolic alterations before and after blood flowing through kidney. Citric acid and 4 amino acids were markedly increased only in the serum samples of HUPM patients, implying more impaired filtration function of kidneys of HUPM patients than LUPM patients. The dicarboxylic acids, phenolic acids, and cholesterol were significantly elevated only in urines of HUPM patients, suggesting more severe oxidative attacks than LUPM patients. Parallel metabolomics of urine and serum revealed the systematic metabolic variations associated with LUPM and HUPM patients, where HUPM patients suffered more severe injury of kidney function and oxidative stresses than LUPM patients. This research exhibited a promising application of parallel metabolomics in renal diseases.


Non-invasive Characterization of Glycosuria and Identification of Biomarkers in Diabetic Urine Using Fluorescence Spectroscopy and Machine Learning Algorithm.
The current study presents a steadfast, simple, and efficient approach for the non-invasive determination of glycosuria of diabetes mellitus using fluorescence spectroscopy. A Xenon arc lamp emitting light in the range of 200-950 nm was used as an excitation source for recording the fluorescent spectra from the urine samples. A consistent fluorescence emission peak of glucose at 450 nm was found in all samples for an excitation wavelength of 370 nm. For confirmation and comparison, the fluorescence spectra of non-diabetic (healthy controls) were also acquired in the same spectral range. It was found that fluorescence emission intensity at 450 nm increases with increasing glucose concentration in urine. In addition, optimized synchronous fluorescence emission at 357 nm was used for simultaneously determining a potential diabetes biomarker, Tryptophan (Trp) in urine. It was also found that the level of tryptophan decreases with the increase in urinary glucose concentration. The quantitative estimation of urinary glucose can be demonstrated based on the intensity of emission light carried by fluorescence light. Moreover, the dissimilarities were further emphasized using the hierarchical cluster analysis (HCA) algorithm. HCA gives an obvious separation in terms of dendrogram between the two data sets based on characteristic peaks acquired from their fluorescence emission signatures. These results recommend that urinary glucose and tryptophan fluorescence emission can be used as potential biomarkers for the non-invasive analysis of diabetes.


RNA-binding properties of Dendrolimus punctatus tetravirus p17 protein.
The RNA-binding properties of the p17 protein of Dendrolimus punctatus tetravirus were analysed. We have demonstrated that p17 protein, a nonstructural protein with a potentially important role in viral replication, is a RNA-binding protein, which has not been previously described for any member of the family Tetraviridae. P17 protein was expressed in Escherichia coli and was used in UV cross-linking analysis, using a digoxigenin-UTP-labeled RNA probe and chemical cross-linking analysis. The analyses demonstrated that p17 protein could bind to RNA. When analysed for capacity of p17 to form oligomers, the protein could form dimers and tetramers. Furthermore, the circular dichroism spectrums of viral RNA 3'-UTR proved that their secondary structures were consistent with yeast tRNA.


High-affinity potassium transporter from a mangrove tree Avicennia officinalis increases salinity tolerance of Arabidopsis thaliana.
Salinity reduces the growth and productivity of crop plants worldwide. Mangroves have evolved efficient ion homeostasis mechanisms to survive under their natural saline growth habitat. Information obtained from them may be utilized for increasing the salt tolerance of crop plants. We identified and characterized a high-affinity potassium transporter gene (AoHKT1) from Avicennia officinalis. The expression of AoHKT1 was induced by NaCl mainly in the leaves. Functional study by heterologous expression of AoHKT1 in Arabidopsis T-DNA insertional mutants athkt1-1 and athkt1-4 revealed that it could enhance the salt tolerance of the mutant plants. This was accompanied by an increase in K+ accumulation in the leaves. AoHKT1 was localized to the plasma membrane in Arabidopsis, and when expressed in yeast, it could complement the functions of both Na+ and K+ transporters. An attempt was made to identify the upstream regulator of AtHKT1, a close homolog of AoHKT1. Using chromatin immunoprecipitation, luciferase assay and yeast one-hybrid assays, WRKY9 was identified as the main transcription factor in the process. Furthermore, this was corroborated by the observation that AtHKT1 levels were significantly reduced in the atwrky9 seedlings. These findings revealed a part of the molecular regulatory mechanism of HKT1 induction in response to salt treatment in Arabidopsis. Our study suggests that AoHKT1 is a potential candidate for generating crop plants with increased salt tolerance.


Global Vaccine and Immunization Research Forum: Opportunities and challenges in vaccine discovery, development, and delivery.
The World Health Organization, the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health, and the Bill & Melinda Gates Foundation convened the first Global Vaccine and Immunization Research Forum (GVIRF) in March 2014. This first GVIRF aimed to track recent progress of the Global Vaccine Action Plan research and development agenda, identify opportunities and challenges, promote partnerships in vaccine research, and facilitate the inclusion of all stakeholders in vaccine research and development. Leading scientists, vaccine developers, and public health officials from around the world discussed scientific and technical challenges in vaccine development, research to improve the impact of immunization, and regulatory issues. This report summarizes the discussions and conclusions from the forum participants.


Integrative proteomic and gene expression analysis identify potential biomarkers for adjuvant trastuzumab resistance: analysis from the Fin-her phase III randomized trial.
Trastuzumab is a remarkably effective therapy for patients with human epidermal growth factor receptor 2 (HER2)--positive breast cancer (BC). However, not all women with high levels of HER2 benefit from trastuzumab. By integrating mRNA and protein expression data from Reverse-Phase Protein Array Analysis (RPPA) in HER2-positive BC, we developed gene expression metagenes that reflect pathway activation levels. Next we assessed the ability of these metagenes to predict resistance to adjuvant trastuzumab using gene expression data from two independent datasets.10 metagenes passed external validation (false discovery rate [fdr] < 0.05) and showed biological relevance with their pathway of origin. These metagenes were further screened for their association with trastuzumab resistance. An association with trastuzumab resistance was observed and validated only for the AnnexinA1 metagene (ANXA1). In the randomised phase III Fin-her study, tumours with low levels of the ANXA1 metagene showed a benefit from trastuzumab (multivariate: hazard ratio [HR] for distant recurrence = 0.16[95%CI 0.05-0.5]; p = 0.002; fdr = 0.03), while high expression levels of the ANXA1 metagene were associated with a lack of benefit to trastuzmab (HR = 1.29[95%CI 0.55-3.02]; p = 0.56). The association of ANXA1 with trastuzumab resistance was successfully validated in an independent series of subjects who had received trastuzumab with chemotherapy (Log Rank; p = 0.01).In conclusion, in HER2-positive BC, some proteins are associated with distinct gene expression profiles. Our findings identify the ANXA1metagene as a novel biomarker for trastuzumab resistance.


Increased local delivery of antagomir therapeutics to the rodent myocardium using ultrasound and microbubbles.
Recent developments in microRNA (miRNA) research have identified these as important mediators in the pathophysiological response upon myocardial infarction (MI). Specific miRNAs can inhibit the translation of entire groups of mRNAs, which are involved in specific processes in the pathophysiology after MI, e.g. the fibrotic, apoptotic or angiogenic response. By modulating miRNAs in the heart, these processes can be tuned to improve cardiac function. Antagomirs are effective miRNA-inhibitors, but have a low myocardial specificity and cardiac antagomir treatment therefore requires high doses, which causes side effects. In the present study, ultrasound-triggered microbubble destruction (UTMD) was studied to increase specific delivery of antagomir to the myocardium. Healthy control mice were treated with UTMD and sacrificed at 30min, 24h and 48h, after which antagomir delivery in the heart was analyzed, both qualitatively and quantitatively. Additionally, potential harmful effects of treatment were analyzed by monitoring ECG, analyzing neutrophil invasion and cell death in the heart, and measuring troponin I after treatment. Finally, UTMD was tested for delivery of antagomir in a model of ischemia-reperfusion (I/R) injury. We found that UTMD can significantly increase local antagomir delivery to the non-ischemic heart with modest side-effects like neutrophil invasion without causing apoptosis. Delivered antagomirs enter cardiomyocytes within 30min after treatment and remains there for at least 48h. Interestingly, after I/R injury antagomir already readily enters the infarcted zone and we observed no additional benefit of UTMD for antagomir delivery. This study is the first to explore cardiac antagomir delivery using UTMD. In addition, it is the first to study tissue distribution of short RNA based therapeutics (~22 base pairs) at both the cellular and organ levels after UTMD to the heart in general. In summary, UTMD provides a myocardial delivery strategy for non-vascular permeable cardiac conditions later in the I/R response or chronic conditions like cardiac hypertrophy.


Virus infection of Chlorella variabilis and enzymatic saccharification of algal biomass for bioethanol production.
Experiments were conducted to investigate the application of virus infection and amylolytic enzyme treatment on sugar release from Chlorella variabilis NC64A and bioethanol production from released sugars via Escherichia coli KO11 fermentation. Chlorella variabilis NC64A accumulated starch when it was cultured in a nitrogen-limited medium. The accumulated starch was not consumed during viral infection based on analysis of sugars released during infection. Both amylolytic enzyme addition and virus infection increased the hydrolysis of carbohydrates. Addition of amylolytic enzymes increased the release of glucose from algal biomass while virus addition increased the release of non-glucose neutral sugars. The combination of enzyme addition and virus infection also resulted in the highest ethanol production after fermentation. Acetic acid was generated as a co-product during fermentation in all sets of experiments. This study demonstrated that infection of microalgae with an algal virus resulted in disruption and hydrolysis of algal biomass to generate fermentable sugars.


TDP-43: an emerging new player in neurodegenerative diseases.
Until a couple of years ago, TAR-DNA-binding protein-43 (TDP-43) was a relatively unknown nuclear protein implicated in transcriptional repression and splicing. Since 2006, when the protein was reported to be present in inclusions in the neurons and/or glial cells of a range of neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), frontotemporal lobar degeneration with ubiquitin-positive, tau- and alpha-synuclein-negative inclusions (FTLD-U) and Alzheimer's disease (AD), many reports on the medical aspects of TDP-43 have been published. Here, we summarize the current literature on TDP-43, focusing on recent studies that provide clues to the function of TDP-43. Using this information and database analysis, we also suggest a molecular and cellular model for possible events in normal and diseased neurons in relation to the emerging importance of the function and dysfunction of this protein as a target for basic as well as translational research.


Aneurysmal bone cysts of the occipital bone.
Two cases of aneurysmal bone cysts are reported. Each patient presented with a palpable mass in the occipital region and signs of compression of structures in the posterior fossa. One of the cases is unique, in that the aneurysmal bone cyst was associated with an epidural hematoma in the posterior fossa. The pertinent literature is reviewed.


Retrotransposons. An RNA polymerase III subunit determines sites of retrotransposon integration.
Mobile genetic elements are ubiquitous. Their integration site influences genome stability and gene expression. The Ty1 retrotransposon of the yeast Saccharomyces cerevisiae integrates upstream of RNA polymerase III (Pol III)-transcribed genes, yet the primary determinant of target specificity has remained elusive. Here we describe an interaction between Ty1 integrase and the AC40 subunit of Pol III and demonstrate that AC40 is the predominant determinant targeting Ty1 integration upstream of Pol III-transcribed genes. Lack of an integrase-AC40 interaction dramatically alters target site choice, leading to a redistribution of Ty1 insertions in the genome, mainly to chromosome ends. The mechanism of target specificity allows Ty1 to proliferate and yet minimizes genetic damage to its host.


Simplified fixative medium for direct immunofluorescence in skin biopsies.
The main limitation for the use of direct immunofluorescence in skin biopsies was the necessity for frozen tissue. In 1973 Michel et al reported use of a liquid fixative, consisting of ammonium sulfate, N-ethyl-maleimide, magnesium sulfate, and potassium citrate, for handling skin biopsy specimens. The present study introduces a simplified liquid fixative medium consisting only of ammonium sulfate and saline. Comparisons of direct immunofluorescence findings in biopsy specimens transported in these two transport media and in fresh-frozen specimens revealed only minimal differences between the three different procedures.


Effectiveness of moisturiser for the prevention of skin tears in older adults residing in long-term care facilities: a clinical review.
In long-term care facilities the treatment of skin tears often takes a lot of nursing time, is costly and can negatively impact the residents' quality of life. The purpose of this clinical review was to investigate whether the application of moisturising lotion is beneficial in skin tear reduction in older adults residing in long-term care facilities. A literature review of original studies investigating the effect of moisturising lotion on skin tears in older adults (65+ years) was conducted. Results indicate that a minimum of twice daily application of moisturising lotion with neutral pH can reduce skin tears by 50% compared to usual care. Therefore, routine skin moisturising is recommended as one component of a skin tear prevention programme for this demogrpahic.


Back pain was less explained than leg pain: a cross-sectional study using magnetic resonance imaging in low back pain patients with and without radiculopathy.
Cross-sectional studies have shown associations between lumbar degenerative manifestations on magnetic resonance imaging (MRI) and low back pain (LBP). Disc herniations and other degenerative manifestations, however, frequently occur in asymptomatic individuals. The purpose of this cross-sectional study was to analyze for associations between pain intensity and degenerative manifestations and other pain variables in patients for whom prognostic factors have been published previously. Included were 141 consecutive patients with and without radiculopathy, all sick-listed 1-4 months due to low back pain and subsequently examined by MRI of the lumbar spine. Using different methods of grouping the degenerative manifestations, linear regression analyses were performed with the intensity of back + leg pain, back pain and leg pain as dependent variables covering actual pain and pain the preceding 2 weeks. The clinical classification into +/- radiculopathy was established before and independently of the standardised description of MRI findings. Radiculopathy was present in 43 % of the patients. Pain was best explained using rank-ordered degenerative manifestations on MRI. Back pain and leg pain were differently associated, and back pain was less explained than leg pain in the multivariate analyses (15 % vs. 31 % of the variation). Back pain intensity was higher in patients with type 1 Modic changes and in some patients with nerve root touch, but was not associated with disc herniations. Leg pain intensity was well explained by disc herniations causing MRI nerve root compromise and radiculopathy. In patients with radiculopathy, nerve root touch caused as much leg pain as nerve root displacement or compression. High intensity zones and osteophytes were not associated with back pain, but only associated with leg pain in patients with radiculopathy. Tender points explained some of the back pain, and widespread pain explained leg pain in some of the patients without radiculopathy. Back pain was associated with type 1 Modic changes, nerve root touch and tender points, whereas leg pain was associated with osteophytes, HIZ, disc herniation, all sorts of MRI nerve root compromise, radiculopathy and widespread pain.


The precursors of double dissociation between reading and spelling in a transparent orthography.
Research and clinical practitioners have mixed views whether reading and spelling difficulties should be combined or seen as separate. This study examined the following: (a) if double dissociation between reading and spelling can be identified in a transparent orthography (Finnish) and (b) the cognitive and noncognitive precursors of this phenomenon. Finnish-speaking children (n = 1963) were assessed on reading fluency and spelling in grades 1, 2, 3, and 4. Dissociation groups in reading and spelling were formed based on stable difficulties in grades 1-4. The groups were compared in kindergarten phonological awareness, rapid automatized naming, letter knowledge, home literacy environment, and task-avoidant behavior. The results indicated that the double dissociation groups could be identified even in the context of a highly transparent orthography: 41 children were unexpected poor spellers (SD), 36 were unexpected poor readers (RD), and 59 were poor in both reading and spelling (RSD). The RSD group performed poorest on all cognitive skills and showed the most task-avoidant behavior, the RD group performed poorly particularly on rapid automatized naming and letter knowledge, and the SD group had difficulties on phonological awareness and letter knowledge. Fathers' shared book reading was less frequent in the RD and RSD groups than in the other groups. The findings suggest that there are discernible double dissociation groups with distinct cognitive profiles. This further suggests that the identification of difficulties in Finnish and the planning of teaching and remediation practices should include both reading and spelling assessments.


Graphene and graphene oxide as new nanocarriers for drug delivery applications.
The biomedical applications of graphene-based materials, including drug delivery, have grown rapidly in the past few years. Graphene and graphene oxide have been extensively explored as some of the most promising biomaterials for biomedical applications due to their unique properties: two-dimensional planar structure, large surface area, chemical and mechanical stability, superb conductivity and good biocompatibility. These properties result in promising applications for the design of advanced drug delivery systems and delivery of a broad range of therapeutics. In this review we present an overview of recent advances in this field of research. We briefly describe current methods for the surface modification of graphene-based nanocarriers, their biocompatibility and toxicity, followed by a summary of the most appealing examples demonstrated for the delivery of anti-cancer drugs and genes. Additionally, new drug delivery concepts based on controlling mechanisms, including targeting and stimulation with pH, chemical interactions, thermal, photo- and magnetic induction, are discussed. Finally the review is summarized, with a brief conclusion of future prospects and challenges in this field.


Seeding variability of different alpha synuclein strains in synucleinopathies.
Currently, the exact reasons why different α-synucleinopathies exhibit variable pathologies and phenotypes are still unknown. A potential explanation may be the existence of distinctive α-synuclein conformers or strains. Here, we intend to analyze the seeding activity of dementia with Lewy bodies (DLB) and Parkinson's disease (PD) brain-derived α-synuclein seeds by real-time quaking-induced conversion (RT-QuIC) and to investigate the structure and morphology of the α-synuclein aggregates generated by RT-QuIC. A misfolded α-synuclein-enriched brain fraction from frontal cortex and substantia nigra pars compacta tissue, isolated by several filtration and centrifugation steps, was subjected to α-synuclein/RT-QuIC analysis. Our study included neuropathologically well-characterized cases with DLB, PD, and controls (Ctrl). Biochemical and morphological analyses of RT-QuIC products were conducted by western blot, dot blot analysis, Raman spectroscopy, atomic force microscopy, and transmission electron microscopy. Independently from the brain region, we observed different seeding kinetics of α-synuclein in the RT-QuIC in patients with DLB compared to PD and Ctrl. Biochemical characterization of the RT-QuIC product indicated the generation of a proteinase K-resistant and fibrillary α-synuclein species in DLB-seeded reactions, whereas PD and control seeds failed in the conversion of wild-type α-synuclein substrate. Structural variances of α-synuclein seeding kinetics and products in DLB and PD indicated, for the first time, the existence of different α-synuclein strains in these groups. Therefore, our study contributes to a better understanding of the clinical heterogeneity among α-synucleinopathies, offers an opportunity for a specific diagnosis, and opens new avenues for the future development of strain-specific therapies. Ann Neurol 2019;85:691-703.


N-1, C-3 substituted indoles as 5-LOX inhibitors--in vitro enzyme immunoaasay, mass spectral and molecular docking investigations.
Based upon the structures of some known 5-LOX inhibitors, a set of five compounds carrying appropriate substituents at N-1 and C-3 of indole were synthesized and investigated for 5-LOX inhibitory activities. Fifty percent inhibitory concn (IC(50)) of these compounds ranges from 0.6 to 5 μM and found to be comparable to that of clinically used 5-LOX inhibitor, zileuton. The compounds under present investigations exhibited appreciable interactions with 5-LOX as apparent from their association constants calculated from the mass spectral data. Compound 5a with a tosyl group at N-1 and pyrolidinyl-1,2-dione substituent at C-3 of indole, exhibiting IC(50) 0.6 μM and stoichiometry of 1:7 in the enzyme-compound complex was identified as highly potent 5-LOX inhibitor and seems to be suitable for further investigations.


Achieving optimal gingival esthetics around restored natural teeth and implants. Rationale, concepts, and techniques.
The role of prosthetic restorations in the final appearance of the surrounding soft tissues has long been recognized. Innovative prosthodontic concepts as described should be used to enhance the biologic as well as the esthetic data of the supporting tissues, in natural teeth and implants alike. Combined dental treatment modalities of different kinds (i.e., orthodontics, periodontal treatment) are often required for optimal results. Meticulous care and attention to the delicate soft tissues should be given throughout all phases of the treatment, with a view to achieving a functional, healthy, and esthetic oral environment.


Optical recording of synaptic potentials from processes of single neurons using intracellular potentiometric dyes.
To record post synaptic potentials or electrical activity from processes of single cells in a central nervous system (CNS) preparation in situ, voltage sensitive dyes can be injected intracellularly, thereby staining only the cell under investigation. We report the structure, evaluation, and synthesis of 11 fluorescent styryl dyes developed for iontophoretic injection. The optical signals that represent small synaptic potentials from single processes of iontophoretically injected cells are expected to be very small and, therefore, such measurements are not easy. We report the methodology that permitted the optical recording of action potentials from a 3-micron axon and the recording of small synaptic potentials from the processes of single cells in the segmental ganglia of the leech. The same dyes also proved useful for optical recording of action potentials of anterogradely labeled axons, following local extracellular injection at a remote site in a mammalian CNS preparation.


Caerulin-induced pro-inflammatory response in macrophages requires TRAF3-p38 signaling activation.
Acute pancreatitis is a common threat to human health. Caerulin provokes severe inflammations, causing injuries to surrounding pancreatic cells. TNF receptor-associated factor 3 (TRAF3) is a highly versatile regulator of immune response. The current study aims to understand the potential effect of TRAF3 on caerulin-induced pro-inflammatory responses. In the primary-cultured mouse bone marrow-derived macrophages (BMDMs), caerulin induced TRAF3 protein stabilization, which formed a complex with mitogen-activated protein kinase kinase 3 (MKK3) to mediate downstream p38 activation. Lentiviral shRNA-mediated TRAF3 stable knockdown significantly attenuated caerulin-induced MKK3-p38 activation and production of several key pro-inflammatory cytokines, including interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α) and IL-17. Remarkably, TRAF3 knockdown in caerulin-stimulated BMDMs also alleviated cytotoxicity to Panc02 and primary mouse pancreatic cells. Thus, TRAF3 is required for caerulin-induced p38 activation and macrophage-mediated pro-inflammatory responses. TRAF3 expression in macrophages could be a novel therapeutic target protein for the treatment of acute pancreatitis.


A synergic approach to enhance long-term culture and manipulation of MiaPaCa-2 pancreatic cancer spheroids.
Tumour spheroids have the potential to be used as preclinical chemo-sensitivity assays. However, the production of three-dimensional (3D) tumour spheroids remains challenging as not all tumour cell lines form spheroids with regular morphologies and spheroid transfer often induces disaggregation. In the field of pancreatic cancer, the MiaPaCa-2 cell line is an interesting model for research but it is known for its difficulty to form stable spheroids; also, when formed, spheroids from this cell line are weak and arduous to manage and to harvest for further analyses such as multiple staining and imaging. In this work, we compared different methods (i.e. hanging drop, round-bottom wells and Matrigel embedding, each of them with or without methylcellulose in the media) to evaluate which one allowed to better overpass these limitations. Morphometric analysis indicated that hanging drop in presence of methylcellulose leaded to well-organized spheroids; interestingly, quantitative PCR (qPCR) analysis reflected the morphometric characterization, indicating that same spheroids expressed the highest values of CD44, VIMENTIN, TGF-β1 and Ki-67. In addition, we investigated the generation of MiaPaCa-2 spheroids when cultured on substrates of different hydrophobicity, in order to minimize the area in contact with the culture media and to further improve spheroid formation.


Giant Controllable Magnetization Changes Induced by Structural Phase Transitions in a Metamagnetic Artificial Multiferroic.
The realization of a controllable metamagnetic transition from AFM to FM ordering would open the door to a plethora of new spintronics based devices that, rather than reorienting spins in a ferromagnet, harness direct control of a materials intrinsic magnetic ordering. In this study FeRh films with drastically reduced transition temperatures and a large magneto-thermal hysteresis were produced for magnetocaloric and spintronics applications. Remarkably, giant controllable magnetization changes (measured to be as high has ~25%) are realized by manipulating the strain transfer from the external lattice when subjected to two structural phase transitions of BaTiO3 (001) single crystal substrate. These magnetization changes are the largest seen to date to be controllably induced in the FeRh system. Using polarized neutron reflectometry we reveal how just a slight in plane surface strain change at ~290C results in a massive magnetic transformation in the bottom half of the film clearly demonstrating a strong lattice-spin coupling in FeRh. By means of these substrate induced strain changes we show a way to reproducibly explore the effects of temperature and strain on the relative stabilities of the FM and AFM phases in multi-domain metamagnetic systems. This study also demonstrates for the first time the depth dependent nature of a controllable magnetic order using strain in an artificial multiferroic heterostructure.


Multiple-Ascending-Dose Phase 1 Clinical Study of the Safety, Tolerability, and Pharmacokinetics of CRS3123, a Narrow-Spectrum Agent with Minimal Disruption of Normal Gut Microbiota.
CRS3123 is a novel small molecule that potently inhibits methionyl-tRNA synthetase of Clostridioides difficile, inhibiting C. difficile toxin production and spore formation. CRS3123 has been evaluated in a multiple-ascending-dose placebo-controlled phase 1 trial. Thirty healthy subjects, ages 18 to 45 years, were randomized into three cohorts of 10 subjects each, receiving either 200, 400, or 600 mg of CRS3123 (8 subjects per cohort) or placebo (2 subjects per cohort) by oral administration twice daily for 10 days. CRS3123 was generally safe and well tolerated, with no serious adverse events (SAEs) or severe treatment-emergent adverse events (TEAEs) reported. All subjects completed their assigned treatment and follow-up visits, and there were no trends in systemic, vital sign, or laboratory TEAEs. There were no QTcF interval changes or any clinically significant changes in other electrocardiogram (ECG) intervals or morphology. CRS3123 showed limited but detectable systemic uptake; although absorption increased with increasing dose, the increase was less than dose proportional. Importantly, the bulk of the oral dose was not absorbed, and fecal concentrations were substantially above the MIC90 value of 1 μg/ml at all dosages tested. Subjects receiving either of the two lower doses of CRS3123 exhibited minimal disruption of normal gut microbiota after 10 days of twice-daily dosing. CRS3123 was inactive against important commensal anaerobes, including Bacteroides, bifidobacteria, and commensal clostridia. Microbiome data showed favorable differentiation compared to other CDI therapeutics. These results support further development of CRS3123 as an oral agent for the treatment of CDI. (This study has been registered at Clinicaltrials.gov under identifier NCT02106338.).


Development and validation of a parametric human mandible model to determine internal stresses for the future design optimization of maxillofacial implants.
Large segmental mandible bone defects still represent a challenge for endogenous regeneration. Despite the bone's capacity to heal in many clinical situations, bone defects over a critical size do not heal spontaneously. An emerging treatment of critically sized mandibular defects is the implantation of individually manufactured scaffolds consisting of biodegradable magnesium alloys. Biomedical engineers faced the challenge of developing a scaffold structure that not only provides sufficient stability, but also stimulates and promotes bone growth while considering the degradation of the magnesium alloy. The porosity of the scaffold must also support bone ingrowth and neovascularization. For an optimal design and subsequent structural optimization knowledge of external load cases is essential. However, currently the muscle and joint forces of the mandible cannot be measured directly. The aim of our study was therefore the development of a parametric human mandible model to determine the relevant boundary conditions for the subsequent structural optimization of individual jawbone implants. Using a model-based approach, determining the essential external load of the mandible as a function of the age and sex of a patient individually and the realistic simulation of the mechanical stress for patient-specific loads and anatomies has been realized. The developed model is successfully validated by evaluating the deformations and stresses of the lower jaw of a possible patient and comparing them with the results of dental research. Based on the results of the modelling, in a subsequent optimization process section forces at the interface between the bone tissue and jawbone implant can be determined and used to optimize the design of the jawbone implant.


Long-term monitoring reveals widespread and severe declines of understory birds in a protected Neotropical forest.
Long-term studies on the population dynamics of tropical resident birds are few, and it remains poorly understood how their populations have fared in recent decades. Here, we analyzed a 44-y population study of a Neotropical understory bird assemblage from a protected forest reserve in central Panama to determine if and how populations have changed from 1977 to 2020. Using the number of birds captured in mist nets as an index of local abundance, we estimated trends over time for a diverse suite of 57 resident species that comprised a broad range of ecological and behavioral traits. Estimated abundances of 40 (∼70%) species declined over the sampling period, whereas only 2 increased. Furthermore, declines were severe: 35 of the 40 declining species exhibited large proportional losses in estimated abundance, amounting to ≥50% of their initial estimated abundances. Declines were largely independent of ecology (i.e., body mass, foraging guild, or initial abundance) or phylogenetic affiliation. These widespread, severe declines are particularly alarming, given that they occurred in a relatively large (∼22,000-ha) forested area in the absence of local fragmentation or recent land-use change. Our findings provide robust evidence of tropical bird declines in intact forests and bolster a large body of literature from temperate regions suggesting that bird populations may be declining at a global scale. Identifying the ecological mechanisms underlying these declines should be an urgent conservation priority.


Validation of dbEST-SSRs and transferability of some other solanaceous species SSR in ashwagandha [Withania Somnifera (L.) Dunal].
Cross-species transferability and expressed sequence tags (ESTs) in public databases are cost-effective means for developing simple sequence repeats (SSRs) for less-studied species like medicinal plants. In this study, 11 EST-SSR markers developed from 742 available ESTs of Withania Somnifera EST sequences and 95 SSR primer pairs derived from other solanaceous crops (tomato, eggplant, chili, and tobacco) were utilized for their amplification and validation. Out of 11, 10 EST-SSRs showed good amplification quality and produced 13 loci with a product size ranging between 167 and 291 bp. Similarly, of the 95 cross-genera SSR loci assayed, 20 (21 %) markers showed the transferability of 5, 27, 32, and 14.2 % from eggplant, chili, tomato, and tobacco, respectively, to ashwagandha. In toto, these 30 SSR markers reported here will be valuable resources and may be applicable for the analysis of intra- and inter-specific genetic diversity in ashwagandha for which till date no information about SSR is available.


Effects of dimethyl sulfoxide, allopurinol, 21-aminosteroid U-74389G, and manganese chloride on low-flow ischemia and reperfusion of the large colon in horses.
Thirty horses were randomly assigned to 1 of 5 groups. All horses were anesthetized and subjected to ventral midline celiotomy, then the large colon was exteriorized and instrumented. Colonic arterial blood flow was reduced to 20% of baseline (BL) and was maintained for 3 hours. Colonic blood flow was then restored, and the colon was reperfused for an additional 3 hours. One of 5 drug solutions was administered via the jugular vein 30 minutes prior to colonic reperfusion: group 1, 0.9% NaCl; group 2, dimethyl sulfoxide: 1 g/kg of body weight; group 3, allopurinol: 25 mg/kg; group 4, 21-aminosteroid U-74389G: 10 mg/kg; and group 5, manganese chloride (MnCl2): 10 mg/kg. Hemodynamic variables were monitored and recorded at 30-minutes intervals. Systemic arterial, systemic venous (SV), and colonic venous (CV) blood samples were collected for measurement of blood gas tensions, oximetry, lactate concentration, PCV, and plasma total protein concentration. The eicosanoids, 6-keto prostaglandin F1 alpha, prostaglandin E2, and thromboxane B2, were measured in CV blood, and endotoxin was measured in CV and SV blood. Full-thickness biopsy specimens were harvested from the left ventral colon for histologic evaluation and determination of wet weight-to-dry weight ratios (WW:DW). Data were analyzed, using two-way ANOVA for repeated measures, and statistical significance was set at P < 0.05. Heart rate, mean arterial pressure, and cardiac output increased with MnCl2 infusion; heart rate and cardiac output remained increased throughout the study, but mean arterial pressure returned to BL values within 30 minutes after completion of MnCl2 infusion. Other drug-induced changes were not significant. There were significant increases in mean pulmonary artery and mean right atrial pressures at 2 and 2.5 hours in horses of all groups, but other changes across time or differences among groups were not observed. Mean pulmonary artery pressure remained increased through 6 hours in all groups, but mean right atrial pressure had returned to BL values at 3 hours. Mean colonic arterial pressure was significantly decreased at 30 minutes of ischemia and remained decreased through 6 hours; however, by 3.25 hours it was significantly higher than the value at 3 hours of ischemia. Colonic arterial resistance decreased during ischemia and remained decreased throughout reperfusion in all groups; there were no differences among groups for colonic arterial resistance.(ABSTRACT TRUNCATED AT 400 WORDS)


Further investigation of the pathogenicity, immunogenicity and stability of precocious Eimeria acervulina.
Attenuated lines of Eimeria acervulina were isolated between 62 and 72 h post-infection from the Houghton (H) strain. The inoculation of small numbers of oocysts of precocious (HP) lines gave substantial protection to Light Sussex chicks kept on litter against challenge with the virulent H strain. The precocious trait of the 72 h HP line was shown to be stable because the kinetics of oocyst production remained unaltered after 9 consecutive passages through birds in which only late developing oocysts were used for passage. The precocious 62 h HP line was subjected to further selection for 5 consecutive passages. The resultant (62 A HP) line was shown to be more attenuated than the 72 h HP line but remained capable of immunizing chicks against challenge with the H strain.


Development of Medication-Related Osteonecrosis of the Jaw After Extraction of Teeth With Experimental Periapical Disease.
Medication-related osteonecrosis of the jaw (MRONJ) is a rare but severe side effect of antiresorptive medications. Most animal models use tooth extraction as an instigating local factor to induce MRONJ, with varied results. However, these teeth are healthy and absent of dental disease, a rare finding that does not reflect clinical practices. The authors hypothesized that extraction of teeth with periapical inflammation would lead to MRONJ in rats treated with high-dose bisphosphonates. Rats were pretreated with zoledronic acid (ZA) for 1 week. Pulp exposure (PE) was established by exposing the pulpal chamber of the first and second molars. Experimental periapical disease (EPD) was induced by PE and bacterial inoculation into pulp chambers of the first and second mandibular molars. The mandibular molars were extracted 4 weeks after PE or EPD, and animals were euthanized 4 weeks after tooth extraction. Extraction sockets were assessed clinically, radiographically, and histologically. Clinically, radiographically, and histologically, socket healing was observed in all vehicle-treated animals and in ZA-treated animals after extraction of healthy teeth or teeth with PE. In contrast, bone exposure, lack of socket healing, and osteonecrosis were present in most ZA-treated animals after extraction of teeth with EPD. Bacterial presence was noted in areas of osteonecrotic alveolar bone. These data support a synergistic contribution of severe dental disease and tooth extraction to MRONJ pathogenesis. Importantly, this model is amenable to manipulation of methodologic conditions for the dissection of parameters involved in MRONJ pathogenesis.


Long-term effect of trauma splenectomy on blood glucose.
Increasing evidence suggests that the spleen harbors stem cells that act as precursors to insulin-producing pancreas cells. Additionally, small studies with short-term follow-up associate splenectomy with increased rates of diabetes mellitus. The purpose of this study was to analyze the long-term effect of trauma splenectomy on blood glucose. Patients were included if a blood glucose level was measured more than 5 y after trauma splenectomy or laparotomy with bowel repair. Mean blood glucose level was then compared between the two groups. During the 10-y study period 61 patients underwent trauma splenectomy and 50 survived until discharge. In comparison, 229 patients underwent trauma laparotomy and bowel repair and 207 survived until discharge. Nine splenectomy patients compared with 12 control patients had, blood glucose measured at least 5 y after initial trauma. Mean follow-up period was not significantly different between groups (splenectomy 82.8 ± 17.6 mo versus control 96.0 ± 44.3 mo, P = 0.41). In the splenectomy cohort mean glucose level was significantly higher compared with the control (114 ± 34 mg/dL versus 90 ± 13 mg/dL, P = 0.04), as was the number of patients with recorded blood glucose level greater than 130 mg/dL (4 patient versus 0 patients P = 0.02). One new diagnosis of diabetes mellitus was noted only in the trauma splenectomy cohort. This small study suggests that trauma splenectomy may be associated with hyperglycemia at long-term follow-up.


From kissing to coitus? Sex-of-partner differences in the sexual milestone achievement of young men.
Scientific information regarding normative patterns of young men's sexual behavior is insufficient, especially regarding the impact of sex of partner. We explored the age at which 255 young adult men achieved several milestones (e.g., first kiss, manual-genital contact, intercourse) as well as the sequence of milestone achievement and stability in sex-of-partner preferences as a function of sex-of-partner experiences. Mean ages of milestone achievement were consistent with the extant empirical literature. Men with only female partners were younger at first kiss and first relationship, and older at first intercourse than men with only male partners; they also reported an almost universal sequence of milestone achievement and little change in sex-of-partner preferences. Most men with male partners reported increased preference for male partners over time. Men with partners of both sexes tended to demonstrate patterns consistent with the relevant sex-of-partner group. Findings suggested a common male sexual trajectory and sex-of-partner dependent trajectories.


[The tick stings! Observations on a misnomer]].
Dermatology enjoys a unique distinction of visualizing its subject matter and should attain complete unity between a dermatologic term and the clinical concept therewith expressed. Clear and definite terminology seems indispensable. Unfortunately wrong designations sanctioned by daily use are incorporated in official nomenclature. How parasitology tells us that a tick stings and that a "tick bite" is a misnomer is detailed in this article.


Nipple-sparing mastectomy: where are we now?
Surgical treatment of breast cancer has evolved from radical mastectomy with routine removal of the nipple-areolar complex (NAC) to breast conservative therapy with preservation of the breast and NAC. When breast conservation is not appropriate or the patient desires mastectomy for risk reduction, conventional therapy still consists of mastectomy with removal of the NAC, followed by reconstruction. Rising interest in improved cosmesis has led to the introduction of the skin-sparing and nipple-sparing mastectomy (NSM) as potential alternatives to mastectomy. There has been much controversy regarding the oncologic safety of these procedures, and the NSM has also introduced a set of complications, such as nipple and areolar necrosis, that are not a concern with total mastectomy. From our review of the literature, we feel that NSM may be a viable option in the appropriate setting, and that its risks and complications are acceptable when compared to the traditional surgical treatment of breast cancer.


[Digital arteritis preceding the diagnosis of a malignant B cell lymphoma].
We report the case of a young smoker woman who developed a severe acrosyndrome of rapid onset, involving both hands except the thumbs. The angiography showed digital arteritis. Antinuclear antibodies were present at high level. Three months later, a large B cell lymphoma was diagnosed. Complete remission was achieved, but the acrosyndrome persisted with only partial improvement. The antinuclear antibodies disappeared. The paraneoplastic nature of the acrosyndrome is discussed.


Cleaner production of Chinese cabbage by intercropping from Cd contaminated soil: Effects of hyperaccumulator variety and planting strip width.
The utilization of Cd-contaminated soil in vegetable crop production can lighten the food crisis and improve the soil environmental resilience. Intercropping is a reliable technology in safety production from contaminated soil. A field-scale experiment was carried out to unravel how plant species and pattern affect the growth and Cd uptake of Chinese cabbage from Cd contaminated land. Among all the intercropping systems designed in this study, one row of Chinese cabbage intercropping with one row of Solanum nigrum L. is the best planting mode (high yields (2.78 kg/m2) and low Cd accumulation (0.02 mg/kg) of Chinese cabbage). Combined with the in-depth joint analysis of diverse soil physicochemical features (soil nutrient characteristics and microbial community structure), biomass yield and quality, and soil microbiological properties, we elaborated that two measures (screening hyperaccumulation types and controlling planting strip width) were the major factors in determining the growth of the aboveground and underground parts of Chinese cabbage respectively, thus directly regulating the application effectiveness of intercropping technology. The intertwined mechanisms (interspecific and intraspecific relationship) of different intercropping systems are summarized, which include better utilization of space, light and other resources in the aboveground part, bioavailability of nutrient, drive of soil bacteria and alleviated soil Cd stress in the underground part, etc. Our research outputs indicate the effectiveness and feasibility of intercropping can be improved by optimizing the streamline configuration and plant mode, which provide theory of reference and practical evidence for warranting the food safety and agricultural soil remediation simultaneously.


PI3K/AKT/p53 pathway inhibits infectious spleen and kidney necrosis virus infection by regulating autophagy and immune responses.
The PI3K/AKT/p53 signaling pathway is activated by various types of cellular stimuli or pathogenic infection, and then regulates fundamental cellular functions to combat these stimulations. Here, we studied the meaningful roles of PI3K/AKT/p53 in regulating cellular machine such as autophagy, immune responses, as well as antiviral activity in Chinese perch brain (CPB) cells infected by infectious spleen and kidney necrosis virus (ISKNV), which is an agent caused devastating losses in mandarin fish (Siniperca chuatsi) industry. We found that ISKNV infection induced up-regulation of host PI3K/AKT/p53 axis, but inhibited autophagy in CPB cells. Interestingly, activation of PI3K/AKT/p53 axis factors trough agonists or overexpression dramatically decreased host autophagy level, inhibited ISKNV replication, and elevated the expression of immune-related genes in CPB cells. In contrast, suppression of PI3K/AKT/p53 pathway by inhibitors or small interfering RNA (siRNA)-mediated gene silence increased the autophagy and ISKNV replication, but down-regulated immune responses in CPB cells. All these results indicate that PI3K/AKT/p53 pathway plays an important role in anti-ISKNV infection and can be used as a new target for controlling ISKNV disease.


Erratum: Meta-QTL and haplo-pheno analysis reveal superior haplotype combinations associated with low grain chalkiness under high temperature in rice.
[This corrects the article DOI: 10.3389/fpls.2023.1133115.].


Neck length and mean arterial pressure in the sauropod dinosaurs.
How blood was able to reach the heads of the long-necked sauropod dinosaurs has long been a matter of debate and several hypotheses have been presented. For example, it has been proposed that sauropods had exceptionally large hearts, multiple 'normal' sized hearts spaced at regular intervals up the neck or held their necks horizontal, or that the siphon effect was in operation. By means of an experimental model, we demonstrate that the siphon principle is able to explain how blood was able to adequately perfuse the sauropod brain. The return venous circulation may have been protected from complete collapse by a structure akin to the vertebral venous plexus. We derive an equation relating neck height and mean arterial pressure, which indicates that with a mean arterial pressure similar to that of the giraffe, the maximum safe vertical distance between heart and head would have been about 12 m. A hypothesis is presented that the maximum neck length in the fossil record is due to the siphon height limit. The equation indicates that to migrate over high ground, sauropods would have had to either significantly increase their mean arterial pressure or keep their necks below a certain height dependent on altitude.


Auxin-mediated root branching is determined by the form of available nitrogen.
To improve water and nutrient acquisition from the soil, plants can modulate their root system architecture. Despite the importance of changes in root architecture to exploit local nutrient patches occurring in heterogenous soils or after placed fertilization, mechanisms integrating external nutrient signals into the root developmental programme remain poorly understood. Here, we show that local ammonium supply stimulates the accumulation of shoot-derived auxin in the root vasculature and promotes lateral root emergence to build a highly branched root system. Activities of pH and auxin reporters indicate that ammonium uptake mediated by ammonium transporters acidifies the root apoplast, which increases pH-dependent import of protonated auxin into cortical and epidermal cells overlaying lateral root primordia, and subsequently promotes their emergence from the parental root. Thereby, ammonium-induced and H+-ATPase-mediated acidification of the apoplast allows auxin to bypass the auxin importers AUX1 and LAX3. In nitrogen-deficient plants, auxin also accumulates in the root vasculature but a more alkaline apoplast leads to retention of auxin in these tissues and prevents lateral root formation. Our study highlights the impact of externally available nitrogen forms on pH-dependent radial auxin mobility and its regulatory function in organ development.


Clinical pattern of checkpoint inhibitor-induced liver injury in a multicentre cohort.
Immune checkpoint inhibitors (ICIs) have changed the landscape of cancer therapy. Liver toxicity occurs in up to 25% of patients treated with ICIs. The aim of our study was to describe the different clinical patterns of ICI-induced hepatitis and to assess their outcome. We conducted a retrospective observational study of patients with checkpoint inhibitor-induced liver injury (CHILI) discussed in multidisciplinary meetings between December 2018 and March 2022 in three French centres specialised in ICI toxicity management (Montpellier, Toulouse, Lyon). The hepatitis clinical pattern was analysed by the ratio of serum alanine aminotransferase (ALT) and alkaline phosphatase (ALP) (R value = (ALT/ULN)/(ALP/ULN)) for characterisation as cholestatic (R ≤2), hepatocellular (R ≥5), or mixed (2 <R <5). We included 117 patients with CHILI. The clinical pattern was hepatocellular in 38.5%, cholestatic in 36.8%, and mixed in 24.8% of patients. High-grade hepatitis severity (grade ≥3 according to the Common Terminology Criteria for Adverse Events system) was significantly associated with the hepatocellular hepatitis (p <0.05). No cases of severe acute hepatitis were reported. Liver biopsy was performed in 41.9% of patients: granulomatous lesions, endothelitis, or lymphocytic cholangitis were described. Biliary stenosis occurred in eight patients (6.8%) and was significantly more frequent in the cholestatic clinical pattern (p < 0.001). Steroids alone were mainly administered to patients with a hepatocellular clinical pattern (26.5%), and ursodeoxycholic acid was more frequently used in the cholestatic pattern (19.7%) than in the hepatocellular or mixed clinical pattern (p <0.001). Seventeen patients improved without any treatment. Among the 51 patients (43.6%) rechallenged with ICIs, 12 (23.5%) developed CHILI recurrence. This large cohort indicates the different clinical patterns of ICI-induced liver injury and highlights that the cholestatic and hepatocellular patterns are the most frequent with different outcomes. ICIs can induce hepatitis. In this retrospective series, we report 117 cases of ICI-induced hepatitis, mostly grades 3 and 4. We find a similar distribution of the different patterns of hepatitis. ICI could be resumed without systematic recurrence of hepatitis.


[Significance of the statistical characteristics of the sinus rhythm of the heart].
Statistical analysis of prolonged continuous recordings of the ECG RR intervals was carried out in 64 patients with purulent surgical infection. The following indices were considered: the mean value of the RR intervals, the mean quadratic deviation (delta), the variation amplitude, the 1st and the 3rd correlation coefficients, the excess, asymmetry, the RR/delta ratio. Besides, the size and the shape of the autoregression could was analyzed. Statistically significant differences of the RR/delta ratio, of the mean quadratic deviation, and of the variation amplitude were revealed in 3 groups of patients differing by the severity of condition. These differences were reflected in the size and shape of the autoregression cloud. The results obtained suggest that statistical characteristics of prolonged recordings of the cardiac rhythm could be used for objective assessment of the severity of the patient's condition and of the therapeutic effect in the patients with a purulent surgical infection.


French Validation of the Camouflaging Autistic Traits Questionnaire (CAT-Q).
Autistic camouflaging is a collection of strategies used to hide autistic characteristics. It can have serious consequences on autistic people's mental health and needs to be addressed and measured in clinical practice. The purpose of this study is to evaluate the psychometric properties of the French adaptation of the Camouflaging Autistic Traits Questionnaire. 1227 participants (744 autistic, 483 non-autistic) answered the French version of the CAT-Q in an online survey or on paper. Confirmatory factor analysis, measurement invariance testing, internal consistency analysis (McDonald's ω), and convergent validity with the DASS-21 depression subscale were conducted. Test-rest reliability was assessed on a sample of 22 autistic volunteers using intraclass correlation coefficient. A good fit was found for the original three-factor structure as well as a good internal consistency, excellent test-retest reliability and highly significant convergent validity. Measurement invariance testing indicates however that the meaning behind items is different for autistic vs. non-autistic people. The French version of the CAT-Q can be used in clinical settings to assess camouflaging behaviors and intent to camouflage. Further research is needed to clarify the camouflage construct and whether reported measurement noninvariance are due to cultural differences or a true difference in what camouflaging might mean for non-autistic people.


Integral electrical characteristics and local plasma parameters of a RF ion thruster.
Comprehensive diagnostics has been carried out for a RF ion thruster based on inductively coupled plasma (ICP) source with an external flat antenna coil enhanced by ferrite core. The ICP was confined within a cylindrical chamber with low aspect ratio to minimize plasma loss to the chamber wall. Integral diagnostics of the ICP electrical parameters (RF power balance and coil current) allowed for evaluation of the antenna coils, matching networks, and eddy current loss and the true RF power deposited to plasma. Spatially resolved electron energy distribution functions, plasma density, electron temperatures, and plasma potentials were measured with movable Langmuir probes.


Cellular content of ribosomal RNA in relation to the progression and competence signals governing proliferation of 3T3 and SV40-3T3 cells.
The method for differential fluorescence staining of cellular RNA and DNA by acridine orange (AO) was optimized for 3T3 and SV40-3T3 cells. Cellular contents of DNA and of ribosomal RNA (rRNA) were determined by dual-channel flow cytometry during cell-density-dependent proliferation and after stimulation of quiescent cells. With increasing density of 3T3 cells, cellular content of rRNA decreases by about 60%, whereas SV40-3T3 cells do not exhibit a significant dependence of rRNA content on cell density. 3T3 cells stimulated early after becoming quiescent resume reaccumulation of rRNA after a delay of only 4 h, whereas cells maintained at quiescence for several days exhibit a delay of about 12 h before a significant rise of rRNA is observed. The extent of rise of cellular rRNA content after different regimens of stimulation of quiescent 3T3 cells does not correlate well with the fraction of cells entering the cell cycle. These and other reported instances of discordance between rRNA content and stimulation into the cell cycle are resolved by showing that of the two signals governing entry into the cell cycle only the progression signal, but not the competence signal is associated with reaccumulation of cellular rRNA. The present results are consistent with the progression function being in essence the achievement of a threshold number of ribosomes per cell, which in conjunction with the competence signal is sufficient for initiation of the cell cycle.


Utilization of digital differential display to identify novel targets of Oct3/4.
Embryonic stem (ES) cells proliferate infinitely while maintaining pluripotency. The POU family transcription factor Oct3/4 is specifically expressed in ES cells and early embryos and plays a critical role in self-renewal of ES cells. However, only a few examples of Oct3/4 target genes have been identified. In this chapter, we describe our strategy to isolate novel Oct3/4 target genes. We first identify genes that are specifically expressed in ES cells by means of digital differential display of expressed sequence tag databases. Reporter gene and gel mobility shift assays are used to confirm the role of Oct3/4. Identification of novel Oct3/4 targets will facilitate our understanding of pluripotency.


The effect of tocopherol on the structure and permeability of phosphatidylcholine liposomes.
There are numerous phospholipid formulations that incorporate α-tocopherol as a stabilizing agent but there are few studies of the effect of α-tocopherol on phospholipid structure and bilayer permeability. This study uses synchrotron X-ray powder diffraction methods to investigate how α-tocopherol changes the structure of distearoylphosphatidylcholines bilayers. Increasing proportions of α-tocopherol up to 20 mol% induces ripple structures in the bilayers. Two types of ripple structure are produced which are seen in electron micrographs of freeze-fracture replicas with periodicities of 16 and 12 nm, respectively. The stoichiometry of phospholipid: α-tocopherol in the ripple structures at 37 °C is 8:1. The presence of α-tocopherol tends to reduce the angle of tilt of the hydrocarbon chains of the phospholipid in the gel phase from about 34° to the bilayer normal at 20 °C into a more vertical orientation. Increasing proportions of α-tocopherol progressively decrease the temperature of the gel to liquid-crystal phase transition of the phospholipid. The presence of up to 20 mol% α-tocopherol in 1-palmitoyl-2-oleoyl-phosphocholine inhibits leakage of phenol red dye from liposomes. The effect of 7 mol% α-tocopherol on leakage was compared with phospholipid liposomes containing 50 mol% cholesterol. The cholesterol-containing liposomes inhibited leakage to a greater extent than the vesicles incorporating α-tocopherol but the effect of α-tocopherol at equivalent molar proportions was comparable to cholesterol.


Nasotracheal intubation in traumatic craniofacial dislocation: use of the lighted stylet.
The coexistence of facial trauma and suspected cervical spine injury represents a difficult problem in airway management. The successful use of guided nasotracheal intubation using a flexible lighted stylet is described, and its application to the critically injured patient is emphasized.


Methodological aspects and characteristics of participants in the study on the prevalence of obesity in children and adolescents in Florianópolis, Southern Brazil, 2018-2019: EPOCA study.
To describe the methodological aspects and characteristics of the participants of the EPOCA survey. The study was conducted with schoolchildren aged between seven to 14 years old from 30 schools in Florianópolis, Southern Brazil. Body mass, height, girths, and skinfold thicknesses were measured. Food consumption and physical activity from the previous day were self-reported using the validated Web-CAAFE questionnaire. Adolescents completed a specific questionnaire about physical activity, meal consumption, and weight control behaviors. Parents/guardians responded to a sociodemographic and habits questionnaire. A total of 1671 schoolchildren participated in the study (response rate: 27.2%). About 63% of schoolchildren were enrolled in public schools. Most studied in the morning shift (54.2%), were female (53.1%) and aged between seven and 10 years (58.1%). The prevalence of overweight was 33.7% and obesity was 11.3%. The data obtained will allow us to assess the trend in the prevalence of overweight and obesity and associated factors when compared to other surveys performed. Descriptions of the logistics and protocols can help in the development and improvement of similar studies. It is hoped that the results of EPOCA 2018/2019 may help in the design of obesity prevention policies and programs for this population.


Bilateral exudative retinal detachment in undiagnosed ocular syphilis after treatment with corticosteroids.
A case of a young Caucasian male who presented bilateral papilledema is described. He was misdiagnosed with bilateral anterior optic neuritis, developing panuveitis and exudative bilateral retinal detachment after being treated with megadoses of corticosteroids. He was finally diagnosed with ocular syphilis and treated with intravenous aqueous crystalline penicillin for 14 days, with complete resolution of his symptoms.


Efficacy and safety of omalizumab in Japanese and Korean patients with refractory chronic spontaneous urticaria.
Many patients with chronic spontaneous/idiopathic urticaria (CSU/CIU) do not respond adequately to treatment with non-sedating H1 antihistamines (H1AH). There are limited studies on use of omalizumab as add-on therapy for treatment of CSU in an Asian population. The POLARIS study (NCT02329223), representing the first randomized, double-blind, placebo-controlled phase III trial of omalizumab for CSU in an Eastern Asian population, evaluated efficacy and safety of omalizumab as add-on therapy for treatment of CSU. This 26-week multicenter (41 Japanese/Korean sites) study enrolled patients (12-75 years) who were symptomatic despite H1AH treatment. Eligible participants (N=218) were randomized 1:1:1 to receive three subcutaneous injections of omalizumab 300mg, 150mg, or placebo every 4 weeks, followed by 12 weeks of follow-up. Primary outcome was change from baseline to Week 12 (Wk12) in weekly itch severity score (ISS7). Safety was assessed through the summary of adverse events (AEs). Baseline demographics and disease characteristics were generally well balanced across treatment groups. At Wk12, statistically significant decreases from baseline were observed in ISS7 with omalizumab vs placebo (mean changes -10.22, -8.80, and -6.51 for omalizumab 300mg, 150mg and placebo; p<0.001 and p=0.006 vs placebo, respectively). Overall AE incidence was similar across treatment groups (54.8%, 57.7%, and 55.4% in omalizumab 300mg, 150mg, and placebo groups, respectively); nasopharyngitis was the most frequently reported AE in all treatment arms. The POLARIS study demonstrates that omalizumab is an efficacious and well-tolerated add-on therapy in Japanese and Korean H1AH-refractory patients with CSU.


A decision support tool to place drinking water sources in rural communities.
Installing more drinking water sources is a promising way to achieve the 6th sustainable development goal "Clean water and sanitation" in rural communities. A key parameter for the installation of new water pumps is geographical position, because the number of people who could gain access to drinking water depends on the location of the pump. To improve the choice of the most appropriate location, we propose a decision support tool to place a new drinking water source in a rural community. This tool relies on four complementary maps, which are obtained from GPS data, survey data, and a water source choice model. The first map shows the spatial distribution of the households and of the existing water sources in the village. The three remaining maps present the following quantities as a function of the position of a new drinking water source in the village: the number of users of the new drinking water source, the improvement of drinking water access, and the daily water demand per capita at the new drinking water source. The decision support tool is applied to a village in Burkina Faso. Results indicate that using the proposed method could allow eight times more people to gain access to drinking water in comparison to a random positioning of the new drinking water source. The original contribution of this work is, first, the consideration of existing water sources in the village, as well as seasonality. Second, we base our analysis on a water source choice model, which accounts for water quality in addition to the distance to the water source. Third, we consider the variability of the water volume collected by the households throughout the village. The developed tool is generic, transferable to other villages and useful for various decision-making entities (e.g. local authorities and non-governmental organizations).


Microbial monitoring of the influence of the stabilization degree of sludge when applied to soil.
The aim of this study was to establish the degree of stabilization of sludge and its influence on the evolution of total aerobic micro-organisms and those of faecal origin when the sludge is applied to soil. Two different sludges were used, from a food industry (D) and from an urban treatment plant, (E). Both sludges were stabilized aerobically in laboratory conditions. The stabilization process was monitored by following the evolution of pathogenic micro-organisms and the content of total solids and volatile matter in suspension, while on the other hand the microbial evolution of the samples of soil plus sludge and control soil (S) were monitored over an incubation period of 80 days. After 20 or 40 days of incubation, in both sludge treatments the populations of pathogenic micro-organisms of faecal origin were below detectable limits, regardless of the degree of stabilization of the sludge. Soil without sludge treatment did not show pathogenic micro-organisms.


Characterization of an Unusual DS-1-Like G8P[8] Rotavirus Strain from Japan in 2017: Evolution of Emerging DS-1-Like G8P[8] Strains through Reassortment.
The emergence of unusual DS-1-like intergenogroup reassortant rotaviruses with a bovine-like G8 genotype (DS-1-like G8P[8] strains) has been reported in several Asian countries. During the rotavirus surveillance program in Japan in 2017, a DS-1-like G8P[8] strain (RVA/Human-wt/JPN/SO1162/2017/G8P[8]) was identified in 43 rotavirus-positive stool samples. Strain SO1162 was shown to have a unique genotype constellation, including genes from both genogroup 1 and 2: G8-P[8]-I2-R2-C2-M2-A2-N2-T2-E2-H2. Phylogenetic analysis revealed that the VP1 gene of strain SO1162 appeared to have originated from DS-1-like G1P[8] strains from Thailand and Vietnam, while the remaining 10 genes were closely related to those of previously reported DS-1-like G8P[8] strains. Thus, SO1162 was suggested to be a reassortant strain that acquired the VP1 gene from Southeast Asian DS-1-like G1P[8] strains on the genetic background of co-circulating DS-1-like G8P[8] strains. Our findings provide important insights into the evolutionary dynamics of emerging DS-1-like G8P[8] strains.