Quantification of gene expression patterns to reveal the origins of abnormal morphogenesis.
The earliest developmental origins of dysmorphologies are poorly understood in many congenital diseases. They often remain elusive because the first signs of genetic misregulation may initiate as subtle changes in gene expression, which are hard to detect and can be obscured later in development by secondary effects. Here, we develop a method to trace back the origins of phenotypic abnormalities by accurately quantifying the 3D spatial distribution of gene expression domains in developing organs. By applying Geometric Morphometrics to 3D gene expression data obtained by Optical Projection Tomography, we determined that our approach is sensitive enough to find regulatory abnormalities that have never been detected previously. We identified subtle but significant differences in the gene expression of a downstream target of a Fgfr2 mutation associated with Apert syndrome, demonstrating that these mouse models can further our understanding of limb defects in the human condition. Our method can be applied to different organ systems and models to investigate the etiology of malformations.


Association between vitamin D supplementation and mortality: systematic review and meta-analysis.
To investigate whether vitamin D supplementation is associated with lower mortality in adults. Systematic review and meta-analysis of randomised controlled trials. Medline, Embase, and the Cochrane Central Register from their inception to 26 December 2018. Randomised controlled trials comparing vitamin D supplementation with a placebo or no treatment for mortality were included. Independent data extraction was conducted and study quality assessed. A meta-analysis was carried out by using fixed effects and random effects models to calculate risk ratio of death in the group receiving vitamin D supplementation and the control group. All cause mortality. 52 trials with a total of 75 454 participants were identified. Vitamin D supplementation was not associated with all cause mortality (risk ratio 0.98, 95% confidence interval 0.95 to 1.02, I2=0%), cardiovascular mortality (0.98, 0.88 to 1.08, 0%), or non-cancer, non-cardiovascular mortality (1.05, 0.93 to 1.18, 0%). Vitamin D supplementation statistically significantly reduced the risk of cancer death (0.84, 0.74 to 0.95, 0%). In subgroup analyses, all cause mortality was significantly lower in trials with vitamin D3 supplementation than in trials with vitamin D2 supplementation (P for interaction=0.04); neither vitamin D3 nor vitamin D2 was associated with a statistically significant reduction in all cause mortality. Vitamin D supplementation alone was not associated with all cause mortality in adults compared with placebo or no treatment. Vitamin D supplementation reduced the risk of cancer death by 16%. Additional large clinical studies are needed to determine whether vitamin D3 supplementation is associated with lower all cause mortality. PROSPERO registration number CRD42018117823.


Fructose and irritable bowel syndrome.
Irritable bowel syndrome (IBS) is a chronic disorder characterised by recurrent abdominal pain or discomfort and transit disturbances with heterogeneous pathophysiological mechanisms. The link between food and gastrointestinal (GI) symptoms is often reported by patients with IBS and the role of fructose has recently been highlighted. Fructose malabsorption can easily be assessed by hydrogen and/or methane breath test in response to 25 g fructose; and its prevalence is about 22 % in patients with IBS. The mechanism of fructose-related symptoms is incompletely understood. Osmotic load, fermentation and visceral hypersensitivity are likely to participate in GI symptoms in the IBS population and may be triggered or worsened by fructose. A low-fructose diet could be integrated in the overall treatment strategy, but its role and implication in the improvement of IBS symptoms should be evaluated. In the present review, we discuss fructose malabsorption in adult patients with IBS and the interest of a low-fructose diet in order to underline the important role of fructose in IBS.


Prioritization of Resilience Initiatives for Climate-Related Disasters in the Metropolitan City of Venice.
Increases in the magnitude and frequency of climate and other disruptive factors are placing environmental, economic, and social stresses on coastal systems. This is further exacerbated by land use transformations, urbanization, over-tourism, sociopolitical tensions, technological innovations, among others. A scenario-informed multicriteria decision analysis (MCDA) was applied in the Metropolitan City of Venice integrating qualitative (i.e., local stakeholder preferences) and quantitative information (i.e., climate-change projections) with the aim of enhancing system resilience to multiple climate-related threats. As part of this analysis, different groups of local stakeholders (e.g., local authorities, civil protection agencies, SMEs, NGOs) were asked to identify critical functions that needs to be sustained. Various policy initiatives were considered to support these critical functions. The MCDA was used to rank the initiatives across several scenarios describing main climate threats (e.g., storm surges, floods, heatwaves, drought). We found that many climate change scenarios were considered to be disruptive to stakeholders and influence alternative ranking. The management alternatives acting on physical domain generally enhance resilience across just a few scenarios while cognitive and informative initiatives provided resilience enhancement across most scenarios considered. With uncertainty of multiple stressors along with projected climate variability, a portfolio of cognitive and physical initiatives is recommended to enhance resilience.


Detection and occurrence of cyclopiazonic acid in cheeses.
Techniques for detection of cyclopiazonic acid in P. camemberti fermented cheeses are described. They include extraction with CHCl3-MeOH, purification, analysis and quantitation by thin-layer chromatography, and confirmation procedures. Recovery from spiked samples was 75-85%, and the lowest detectable level was 0.02 ppm. This toxic metabolite of P. camemberti was found in the crust of 11 of 20 cheeses of different brands, but not in the inner part. The highest levels were found in three samples: 0.4, 1, and 1.5 ppm. Cyclopiazonic acid doses eventually ingested by a consumer appear to be very low: 3 or 4 micrograms in a portion of the most contaminated sample.


Promoting Latinx health equity through community-engaged policy and practice reforms in North Carolina.
The Latinx Advocacy Team & Interdisciplinary Network for COVID-19 (LATIN-19) is a unique multi-sector coalition formed early in the COVID-19 pandemic to address the multi-level health inequities faced by Latinx communities in North Carolina. We utilized the National Institute on Minority Health and Health Disparities (NIMHD) Research Framework to conduct a directed content analysis of 58 LATIN-19 meeting minutes from April 2020 through October 2021. Application of the NIMHD Research Framework facilitated a comprehensive assessment of complex and multidimensional barriers and interventions contributing to Latinx health while centering on community voices and perspectives. Community interventions focused on reducing language barriers and increasing community-level access to social supports while policy interventions focused on increasing services to slow the spread of COVID-19. Our study adds to the literature by identifying community-based strategies to ensure the power of communities is accounted for in policy reforms that affect Latinx health outcomes across the U.S. Multisector coalitions, such as LATIN-19, can enable the improved understanding of underlying barriers and embed community priorities into policy solutions to address health inequities.


Genome assembly and analysis of Lactuca virosa: implications for lettuce breeding.
Lettuce (Lactuca sativa L.) is a leafy vegetable crop with ongoing breeding efforts related to quality, resilience, and innovative production systems. To breed resilient and resistant lettuce in the future, valuable genetic variation found in close relatives could be further exploited. Lactuca virosa (2x = 2n = 18), a wild relative assigned to the tertiary lettuce gene pool, has a much larger genome (3.7 Gbp) than Lactuca sativa (2.5 Gbp). It has been used in interspecific crosses and is a donor to modern crisphead lettuce cultivars. Here, we present a de novo reference assembly of L. virosa with high continuity and complete gene space. This assembly facilitated comparisons to the genome of L. sativa and to that of the wild species L. saligna, a representative of the secondary lettuce gene pool. To assess the diversity in gene content, we classified the genes of the 3 Lactuca species as core, accessory, and unique. In addition, we identified 3 interspecific chromosomal inversions compared to L. sativa, which each may cause recombination suppression and thus hamper future introgression breeding. Using 3-way comparisons in both reference-based and reference-free manners, we show that the proliferation of long-terminal repeat elements has driven the genome expansion of L. virosa. Further, we performed a genome-wide comparison of immune genes, nucleotide-binding leucine-rich repeat, and receptor-like kinases among Lactuca spp. and indicated the evolutionary patterns and mechanisms behind their expansions. These genome analyses greatly facilitate the understanding of genetic variation in L. virosa, which is beneficial for the breeding of improved lettuce varieties.


Combined Protein and Alkaloid Research of Chelidonium majus Latex Reveals CmMLP1 Accompanied by Alkaloids with Cytotoxic Potential to Human Cervical Carcinoma Cells.
Chelidonium majus L. is a latex-bearing plant used in traditional folk medicine to treat human papillomavirus (HPV)-caused warts, papillae, and condylomas. Its latex and extracts are rich in many low-molecular compounds and proteins, but there is little or no information on their potential interaction. We describe the isolation and identification of a novel major latex protein (CmMLP1) composed of 147 amino acids and present a model of its structure containing a conserved hydrophobic cavity with high affinity to berberine, 8-hydroxycheleritrine, and dihydroberberine. CmMLP1 and the accompanying three alkaloids were present in the eluted chromatographic fractions of latex. They decreased in vitro viability of human cervical cancer cells (HPV-negative and HPV-positive). We combined, for the first time, research on macromolecular and low-molecular-weight compounds of latex-bearing plants in contrast to other studies that investigated proteins and alkaloids separately. The observed interaction between latex protein and alkaloids may influence our knowledge on plant defense. The proposed toolbox may help in further understanding of plant disease resistance and in pharmacological research.


Frontal recruitment during response inhibition in older adults replicated with fMRI.
Recent research has explored age-related differences in multiple areas of cognitive functioning using fMRI, PET, and SPECT. However, because these studies used different tasks, subjects, and methods, little is known about whether the results of these studies are generalizable or repeatable. The present study replicated a previous study [Psychol. Aging 17 (2002) 56] using the same Go/No-go task with a subset of 11 of the original older adult subjects, and using the same fMRI scanner and imaging methods. A direct comparison was made between these participants at Time 1 and Time 2 for both behavioral and functional data. These participants were also compared to a new young adult group of 11 participants. Although the current young adult group did not perform as well as the original young adult group, the original finding of enhanced left prefrontal activation in older adults relative to younger adults was replicated. Furthermore, when comparing Time 1 to Time 2, older adults exhibited comparable areas of activation, but significantly greater magnitude of activation at Time 1 in a few clusters. The findings indicate that older adults exhibit more bilateral brain activity during this task than young adults, which appears compensatory and is repeatable over time. The magnitude of regional activation, however, may vary with extraneuronal factors such as signal-to-noise ratio or task experience. This study adds to existing research suggesting that bilateral frontal activation is a predominant finding in the aging literature, and not specific to certain tasks in age group comparisons.


Connectivity profiles of the insular network for speech control in healthy individuals and patients with spasmodic dysphonia.
The importance of insula in speech control is acknowledged but poorly understood, partly due to a variety of clinical symptoms resulting from insults to this structure. To clarify its structural organization within the speech network in healthy subjects, we used probabilistic diffusion tractography to examine insular connectivity with three cortical regions responsible for sound processing [Brodmann area (BA) 22], motor preparation (BA 44) and motor execution (laryngeal/orofacial primary motor cortex, BA 4). To assess insular reorganization in a speech disorder, we examined its structural connectivity in patients with spasmodic dysphonia (SD), a neurological condition that selectively affects speech production. We demonstrated structural segregation of insula into three non-overlapping regions, which receive distinct connections from BA 44 (anterior insula), BA 4 (mid-insula) and BA 22 (dorsal and posterior insula). There were no significant differences either in the number of streamlines connecting each insular subdivision to the cortical target or hemispheric lateralization of insular clusters and their projections between healthy subjects and SD patients. However, spatial distribution of the insular subdivisions connected to BA 4 and BA 44 was distinctly organized in healthy controls and SD patients, extending ventro-posteriorly in the former group and anterio-dorsally in the latter group. Our findings point to structural segregation of the insular sub-regions, which may be associated with the different aspects of sensorimotor and cognitive control of speech production. We suggest that distinct insular involvement may lead to different clinical manifestations when one or the other insular region and/or its connections undergo spatial reorganization.


A DNA methylation haplotype block landscape in human tissues and preimplantation embryos reveals regulatory elements defined by comethylation patterns.
DNA methylation and associated regulatory elements play a crucial role in gene expression regulation. Previous studies have focused primarily on the distribution of mean methylation levels. Advances in whole-genome bisulfite sequencing (WGBS) have enabled the characterization of DNA methylation haplotypes (MHAPs), representing CpG sites from the same read fragment on a single chromosome, and the subsequent identification of methylation haplotype blocks (MHBs), in which adjacent CpGs on the same fragment are comethylated. Using our expert-curated WGBS data sets, we report comprehensive landscapes of MHBs in 17 representative normal somatic human tissues and during early human embryonic development. Integrative analysis reveals MHBs as a distinctive type of regulatory element characterized by comethylation patterns rather than mean methylation levels. We show the enrichment of MHBs in open chromatin regions, tissue-specific histone marks, and enhancers, including super-enhancers. Moreover, we find that MHBs tend to localize near tissue-specific genes and show an association with differential gene expression that is independent of mean methylation. Similar findings are observed in the context of human embryonic development, highlighting the dynamic nature of MHBs during early development. Collectively, our comprehensive MHB landscapes provide valuable insights into the tissue specificity and developmental dynamics of DNA methylation.


Role of adult stem/progenitor cells in osseointegration and implant loosening.
The long-term stability of prosthetic implants is ultimately a function of the integrity of the biologic interaction between the resident tissues and cells and the biomaterial. Connective tissues of the skeleton undergo constant remodeling and turnover, and the interface with the implant biomaterial is therefore a dynamic structure that results from ongoing differentiation of progenitor cells into functional cellular phenotypes. An understanding of the regulation of the mechanisms by which progenitor cells initiate and maintain their interactions with the biomaterial surface while undergoing the necessary differentiation processes is thus essential to optimizing the long-term stability of prosthetic implants. This review presents evidence that the interactions between adult mesenchymal stem cells, as the principal progenitor cell type of skeletal connective tissues, and the biomaterial surfaces are influenced by surface chemistry and topography and regulated by the extracellular matrix and growth factors. Mesenchymal stem cells are also the targets of the wear debris particles that are a by-product of implant biomaterials, resulting in direct and microenvironmental effects, including apoptosis, suppression of proliferation and osteogenic differentiation, and the production of proinflammatory cytokines, that compromise the long-term stability of the bone-implant interface. These effects are initiated by endocytosis of the submicron particles by the mesenchymal stem cells. These observations strongly suggest that optimization of the stability of implant osseointegration must address factors that enhance and promote the biologic activities of the stem/progenitor cells of skeletal connective tissues.


Fine-Needle Aspiration is Superior to Needle Core Biopsy as a Sample Aquisition Method for Flow Cytometric Analysis in Suspected Hematologic Neoplasms.
Background: Common minimally invasive methods for acquiring samples for flow cytometric immunophenotyping (FCI) include fine needle aspiration (FNA) and needle core biopsy (NCB). FCI requires a sufficient quantity of viable cells for adequate evaluation. Methods: We collected patient data from our files of all FCI cases sampled via FNA or NCB from 1/1/03 and 6/1/12. Total Viable Cells (TVC) was calculated by multiplying the volume, viability and concentration and then converted to logarithmic scale as "Log TVC." Statistical analysis was performed using SPSS. Results: 571 FCI cases at our institution were reviewed covering the period from 2003 to 2012 and 456 total cases were analyzed. 116 cases were sampled by NCB and 340 were sampled by FNA. Comparing FNA to NCB subgroups demonstrated FNA to be superior in mean specimen viability, TVC, and cases with a final FCI interpretation. The cellularity of the sample (in Log TVC) correlates with the likelihood of achieving a FCI interpretation. The point where at least 50% of cases have a diagnostic FCI interpretation occurs between Log TVC of 5.0 - 5.25. However, FNA based cases had a higher proportion of samples with an indeterminate final diagnosis. Conclusions: FNA was found to be significantly superior to NCB in obtaining material for FCI. However, NCB resulted in fewer indeterminate final diagnoses due to benefit of histologic correlation. In our opinion, NCB for histology combined with dedicated FNA material for FCI may yield the best results for a minimally invasive approach to the diagnosis of hematologic neoplasms. © 2014 Clinical Cytometry Society.


Deciphering the mechanisms of tumorigenesis in human pancreatic ductal epithelial cells.
The most common genetic lesions in pancreatic ductal adenocarcinoma (PDAC) have been identified. However, significant gaps still exist in our understanding of how such genetic alterations act in concert to induce PDAC development. In this study, we investigated the mechanism of tumorigenic transformation in the immortalized human pancreatic ductal epithelial (HPDE) cell line by sequentially introducing PDAC signature alterations into this cell line. The phenotype for stable expression of mutant K-ras, Her2, p16/p14shRNA, and Smad4shRNA in HPDE cells was examined by assays for cell proliferation, migration, invasion, soft agar, and orthotopic tumorigenesis. The mechanisms of tumorigenic transformation were further explored by gene expression profiling and pathway analyses. The transformed cells exhibited enhanced proliferation, migration, and invasion, displayed anchorage-independent growth in soft agar, and grew orthotopic tumors with some histopathologic features of PDAC. We found that Smad4 played key roles in the tumorigenic transformation of HPDE cells. We further found that MDM2 and Bmi-1 were overexpressed in the tumorigenic HPDE cells and that Bmi-1 overexpression was regulated by Smad4. Ingenuity Pathway Analysis software analysis of microarray data revealed that dysregulation of integrin-linked kinase signaling and the cell cycle were the most significant changes involved in tumorigenic transformation. Altogether, this cell culture model closely recapitulated human pancreatic carcinogenesis from gene lesions, activation of specific signaling pathways, and some histopathologic features. The combination of activated K-ras and Her2 with inactivated p16/p14 and Smad4 was sufficient and essential to transform HPDE cells, thus revealing the potential tumorigenic mechanism.


Multi-Season Regional Analysis of Multi-Species Occupancy: Implications for Bird Conservation in Agricultural Lands in East-Central Argentina.
Rapid expansion and intensification of agriculture create challenges for the conservation of biodiversity and associated ecosystem services. In Argentina, the total row crop planted area has increased in recent decades with the expansion of soybean cultivation, homogenizing the landscape. In 2003 we started the first long-term, large-scale bird monitoring program in agroecosystems of central Argentina, in portions of the Pampas and Espinal ecoregions. Using data from this program, we evaluated the effect of land use and cover extent on birds between 2003-2012, accounting for imperfect detection probabilities using a Bayesian hierarchical, multi-species and multi-season occupancy model. We tested predictions that species diversity is positively related to habitat heterogeneity, which in intensified agroecosystems is thought to be mediated by food availability; thus the extent of land use and cover is predicted to affect foraging guilds differently. We also infer about ecosystem services provisioning and inform management recommendations for conservation of birds. Overall our results support the predictions. Although many species within each guild responded differently to land use and native forest cover, we identified generalities for most trophic guilds. For example, granivorous gleaners, ground insectivores and omnivores responded negatively to high proportions of soybean, while insectivore gleaners and aerial foragers seemed more tolerant. Habitat heterogeneity would likely benefit most species in an intensified agroecosystem, and can be achieved with a diversity of crops, pastures, and natural areas within the landscape. Although most studied species are insectivores, potentially beneficial for pest control, some guilds such as ground insectivores are poorly represented, suggesting that agricultural intensification reduces ecological functions, which may be recovered through management. Continuation of the bird monitoring program will allow us to continue to inform for conservation of birds in agroecosystems, identify research needed to reduce key uncertainties, and anticipate the effects of changes in agriculture in central Argentina.


Identification and validation of a glycolysis-related gene signature for depicting clinical characteristics and its relationship with tumor immunity in patients with colon cancer.
Colon cancer (CC) is one of the most common gastrointestinal malignant tumors with a high mortality rate. Glycolysis is an important pathway for tumors to obtain energy. However, its role in CC remains largely unknown. In present study, we analyzed glycolysis-related gene expression to depict clinical characteristics and its relationship with tumor immunity in CC to find potential target treatments. A prognostic model based on 13 glycolysis-related genes was established by univariate and multivariate Cox regression analyses. The efficacy of the gene model was tested via survival analysis, receiver operating characteristic analysis, and principal component analysis. Furthermore, our findings revealed and validated 13 glycolysis-related genes (NUP107, SEC13, ALDH7A1, ALG1, CHPF, FAM162A, FBP2, GALK1, IDH1, TGFA, VLDLR, XYLT2, and OGDHL), which constituted a prognostic prediction model. The model exhibited clinical implication potential, had a relatively high accuracy, and was closely associated with the patients' clinical features. In particular, the tumor stage could be clearly distinguished by glycolysis-related gene signatures. Finally, a significant difference between glycolysis-related gene colon cancer immunity and sensitive immune drugs was observed. Our glycolysis-related gene model could provide the basis for potential early individualized treatment. The 13 glycolysis-related gene signature was a reliable predictive tool for the prognosis of colon cancer. Our findings could help patients select targets for individualized treatment and immunotherapy strategies. The study findings advance our understanding of the potential mechanism of glycolysis in colon cancer.


Dobutamine-induced mechanical alternans is a marker of poor prognosis in idiopathic dilated cardiomyopathy.
1. To date, few prognostic indicators for ambulatory patients with idiopathic dilated cardiomyopathy (IDCM) have been identified. The purpose of the present study was to investigate the relationship between the occurrence of dobutamine-induced mechanical alternans (MA) and prognosis in ambulatory patients with IDCM. 2. Left ventricular pressure was measured during right atrial pacing and after intravenous infusion of dobutamine at incremental doses in 90 ambulatory patients with IDCM in sinus rhythm. Endomyocardial biopsy specimens were also obtained for quantitative analysis of gene expression. The patients were followed up for a mean of 2.5 years. 3. Patients were classified into three groups: (i) 60 patients who exhibited neither pacing- nor dobutamine-induced MA (Group N); (ii) 20 patients who manifested only pacing-induced MA (Group P); and (iii) 10 patients who developed both pacing- and dobutamine-induced MA (Group D). The sarcoplasmic/endoplasmic reticulum calcium ATPase 2a:phospholamban mRNA ratio was significantly higher in Group D patients than in patients in Groups N or P. Multivariate analysis revealed that dobutamine-induced MA (odds ratio 4.05; 95% confidence interval 1.35-12.2) was a significant independent predictor of cardiac events. Cardiac event-free survival in Group D was significantly lower than in Groups N or P, as determined by Kaplan-Meier analysis (P=0.002). 4. The occurrence of dobutamine-induced MA is a potentially useful clinical predictor of poor prognosis in ambulatory patients with IDCM in sinus rhythm.


Accretionary processes in the early solar system: an experimental approach.
Micrometer-size silicate flakes do not accrete during impacts in the velocity range 1.5 to 9.5 kilometers per second. Conventional accretionary theories for silicate bodies are applicable only to particles whose orbits are similar. Metal-silicate fractionation in the solar system may have been affected by differences in the accretionary behavior of the metal and silicate particles.


Pericarditis After Breast Implant Rupture: A Case Report.
A ruptured breast implant is usually asymptomatic and accidentally discovered during an imaging test. However, implant ruptures can cause isolated silicone granulomas and cases of severe systemic disease. We report the first case of a 39-year-old female patient with augmentation breast implants and myopericarditis secondary to implant rupture. Many etiologies of myopericarditis were explored, but none were selected with the exception of the rupture of the implant in the left breast. Magnetic resonance imaging showed a prosthetic rupture with capsular intrusion and formation of a silicone granuloma with inflammation of the pericardium on contact. Clinical and radiological improvement was observed in the short term after surgical removal of the implant. A review of the literature was conducted supporting the hypothesis of an autoimmune and inflammatory syndrome induced by an adjuvant.


Effect of a 980-nm diode laser on post-operative pain after endodontic treatment in teeth with apical periodontitis: a randomized clinical trial.
This study aimed to assess the effect of a 980-nm diode laser following chemomechanical root canal preparation on the severity of post-operative pain (PP) after root canal treatment (RCT). This study included asymptomatic, single-rooted teeth with a periapical index (PAI) score of 3 or 4. All the patients received RCT, including dressing with calcium hydroxide (Ca(OH)2), during two visits. The patients were randomly divided into two groups (n:30): a control group, in which the final irrigation was performed using 5 ml of 2.5% sodium hypochlorite (NaOCI), followed by 5 ml of 17% and ethylenediaminetetraacetic acid (EDTA) and 5 ml of distilled water, and a laser group, in which the root canals were irradiated using a 980-nm diode laser after the final irrigation at both visits. The pain levels after both visits were evaluated using a visual analogue scale (VAS) after 8 h, 24 h, 48 h and 7 d. In addition, the time intervals to medication intake were recorded. The collected data were statistically analysed using the chi-square and Mann-Whitney U test (p < 0.05). The average pain level in the control group 24 h after the first visit was significantly higher than that in the laser group (p < 0.05). The average pain level 24 h and 48 h after the second visit was significantly higher in the control group (p < 0.05). The levels of PP 24 h after the first visit were higher than those after the second visit only in the control group (p < 0.05). After the first visit, analgesic use in the control group was significantly higher after 8 h (40%) and 24 h (23%) as compared with that in the laser group (p < 0.05). Root canal irradiation with a diode laser may reduce PP after RCT in single-rooted teeth with a PAI score of 3 or 4. Effect of the Diode Laser on Post-operative Pain After Endodontic Treatment in Teeth with Apical Periodontitis: NCT04486196. Registered 24 July 2020-Retrospectively registered, http://clinicaltrials.gov/ct2/show/NCT04486196.


Protection against fatal renal injury due to choline deficiency by renal decapsulation.
Decapsulation of the left kidney through a lumbar incision immediately prior to placing young rats on a choline-deficient diet afforded a significant degree of protection against animal mortality, compared with that which occurred as a result of the deficiency in the control groups. Decapsulation also was effective in reducing greatly the renal injury which developed in the decapsulated kidneys, as judged by a comparison of the decapsulated kidneys with the contralateral undecapsulated kidneys of the same animals. Decapsulation through an abdominal incision also was efficacious. Decapsulation after 4 or 5 days on the deficient diet, at which time relatively early renal lesions were present in most of the animals, afforded little if any protection. Experiments in which the usual adhesions between the decapsulated kidneys and surrounding tissues were prevented by covering the decapsulated kidneys with artificial capsules demonstrated that protection due to decapsulation could occur in the absence of adhesions. Renal denervation without removal of the renal capsule was not associated with a decrease in renal damage or animal mortality. Possible mechanisms of the protective effect of renal decapsulation in choline deficiency are discussed.


Laser surface estimation for microwave breast imaging systems.
Microwave breast imaging techniques involve collecting measurements from a breast that is positioned in a scanner. While the patient interface typically includes a hole through which the breast is placed when the patient lies in the prone position, the exact location and shape of breast are not known. In this paper, we explore the addition of a laser sensor and associated algorithms in order to provide a rapid and accurate estimate of the breast surface location. We demonstrate that the laser is capable of estimating surfaces with improved accuracy compared to microwave measurements. The impact of accurate surface estimation on images is shown, and results obtained from human scans are presented.


Modeling of Cutting Parameters and Tool Geometry for Multi-Criteria Optimization of Surface Roughness and Vibration via Response Surface Methodology in Turning of AISI 5140 Steel.
AISI 5140 is a steel alloy used for manufacturing parts of medium speed and medium load such as gears and shafts mainly used in automotive applications. Parts made from AISI 5140 steel require machining processes such as turning and milling to achieve the final part shape. Limited research has been reported on the machining vibration and surface roughness during turning of AISI 5140 in the open literature. Therefore, the main aim of this paper is to conduct a systematic study to determine the optimum cutting conditions, analysis of vibration and surface roughness under different cutting speeds, feed rates and cutting edge angles using response surface methodology (RSM). Prediction models were developed and optimum turning parameters were obtained for averaged surface roughness (Ra) and three components of vibration (axial, radial and tangential) using RSM. The results demonstrated that the feed rate was the most affecting parameter in increasing the surface roughness (69.4%) and axial vibration (65.8%) while cutting edge angle and cutting speed were dominant on radial vibration (75.5%) and tangential vibration (64.7%), respectively. In order to obtain minimum vibration for all components and surface roughness, the optimum parameters were determined as Vc = 190 m/min, f = 0.06 mm/rev, κ = 60° with high reliability (composite desirability = 90.5%). A good agreement between predicted and measured values was obtained with the developed model to predict surface roughness and vibration during turning of AISI 5140 within a 10% error range.


Odynophagia as the first symptom of monkeypox infection.
A 50-year-old patient with confirmed monkeypox infection presented with odynophagia and nocturnal dyspnea. Clinically, there was a lesion on the tongue without any skin lesions and fibrinous plaques on the right tonsil with asymmetry of the palatoglossal arch. Due to a suggested abscess in the CT scan, a tonsillectomy à chaud was performed. By pan-orthopox-specific polymerase chain reaction (PCR) the monkeypox infection was also confirmed in the tonsil tissue. Isolated oral findings may represent a monkeypox infection and should be considered as a currently important differential diagnosis, especially for patients at risks.


[Isolation and identification of some metabolites of phenyramidol (Cabral) from human urine (author's transl)].
The biological transformation of phenyramidol (I), some of which is also excreted unchanged, occurs by three main degradative pathways: 1. Hydroxylation of the pyridine ring in position 3 (metabolite V) and 5 (metabolite VI). 2. Cleavage of the ethanolamine chain with the formation of 2-aminopyridine (metabolite II) and presumably mandelic aldehyde. 3. Conjugation with glucuronic acid (metabolite III). Secondary reactions result in the production of: benzoyl carbinol (metabolite XV), benzoic acid (metabolite XI), mandelic acid (metabolite XII) and the glucuronides of V, VI, VII, XII and possibly II (metabolites VIII, IX, X, XIII and IV), all of which were also found as free, unconjugated compounds. A further, unusual reaction is the dimerisation of metabolite VI with the formation of a dipyridyl derivative (metabolite VII), which is excreted partly as the free compound, but mainly as the glucuronide (metabolite X). The occurrence of 2-(N-benzylamino)-pyridine (XIV) in the urine could not be explained. Four futher excretory products (metabolites XVI, XVII, XVIII and XIX) were not identified; XVI and XVII were extracted at an alkaline pH, whereas XVIII and XIX were extracted under neutral conditions. They could be detected both as free compounds, and after hydrolysis with HCl or alkali, but not after treatment with beta-glucuronidase.


Two hydroxypyruvate reductases encoded by OsHPR1 and OsHPR2 are involved in photorespiratory metabolism in rice.
Mutations in the photorespiration pathway display a lethal phenotype in atmospheric air, which can be fully recovered by elevated CO2 . An exception is that mutants of peroxisomal hydroxypyruvate reductase (HPR1) do not have this phenotype, indicating the presence of cytosolic bypass in the photorespiration pathway. In this study, we constructed overexpression of the OsHPR1 gene and RNA interference plants of OsHPR1 and OsHPR2 genes in rice (Oryza sativa L. cv. Zhonghua 11). Results from reverse transcription-polymerase chain reaction (RT-PCR), Western blot, and enzyme assays showed that HPR1 activity changed significantly in corresponding transgenic lines without any effect on HPR2 activity, which is the same for HPR2. However, metabolite analysis and the serine glyoxylate aminotransferase (SGAT) activity assay showed that the metabolite flux of photorespiration was disturbed in RNAi lines of both HPR genes. Furthermore, HPR1 and HPR2 proteins were located to the peroxisome and cytosol, respectively, by transient expression experiment. Double mutant hpr1 × hpr2 was generated by crossing individual mutant of hpr1 and hpr2. The phenotypes of all transgenic lines were determined in ambient air and CO2 -elevated air. The phenotype typical of photorespiration mutants was observed only where activity of both HPR1 and HPR2 were downregulated in the same line. These findings demonstrate that two hydroxypyruvate reductases encoded by OsHPR1 and OsHPR2 are involved in photorespiratory metabolism in rice.


Characterization of Escherichia coli isolated from cases of avian colibacillosis.
Forty-four western Canadian isolates of Escherichia coli associated with colibacillosis of turkeys and chickens were examined for serotype, antibiotic resistance, and production of aerobactin. The isolates belonged to fourteen O serogroups, with 39% of the strains being non-typeable. A high frequency of resistance to tetracycline, kanamycin, neomycin, cephalothin, streptomycin and erythromycin was observed. Most isolates produced aerobactin. Ten E. coli belonging to serogroups O1, O2 and O78 were also examined for pili production, hemagglutination, serum sensitivity, production of iron-regulated outer membrane proteins (IROMPS), and virulence. All isolates examined produced pili, exhibited mannose-sensitive hemagglutination of avian red blood cells and produced IROMPS under iron-restricted growth conditions. The five isolates of serogroup O1 and O2 were resistant to killing by turkey serum and were highly virulent. Only two of the five isolates of serogroup O78 were serum resistant. No correlation between serum resistance and virulence was observed in serogroup O78.


Exotic Carbonate Mineralization Recovered from a Deep Basalt Carbon Storage Demonstration.
Mitigating climate change requires transformational advances for carbon dioxide removal, including geologic carbon sequestration in reactive subsurface environments. The Wallula Basalt Carbon Storage Pilot Project demonstrated that CO2 injected into >800 m deep Columbia River Basalt Group flow top reservoirs mineralizes on month-year timescales. Herein, we present new optical petrography, micro-computed X-ray tomography, and electron microscopy results obtained from sidewall cores collected two years after CO2 injection. As no other anthropogenic carbonates from geologic carbon storage field studies have been recovered, this world-unique sample suite provides unparalleled insight for subsurface carbon mineralization products and paragenesis. Chemically zoned nodules with Ca/Mn-rich cores and Fe-dominant outer rims are prominent examples of the neoformed carbonate assemblages with ankerite-siderite compositions and exotic divalent cation correlations. Paragenetic insights for the timing of aragonite, silica, and fibrous zeolites are clarified based on mineral texture and spatial relationships, along with time-resolved downhole fluid sampling. Collectively, these results clarify the mineralogy, chemistry, and paragenesis of carbon mineralization, providing insight into the ultimate fate and transport of CO2 in reactive mafic-ultramafic reservoirs.


Quadrature phase interferometer for high resolution force spectroscopy.
In this article, we present a deflection measurement setup for Atomic Force Microscopy (AFM). It is based on a quadrature phase differential interferometer: we measure the optical path difference between a laser beam reflecting above the cantilever tip and a reference beam reflecting on the static base of the sensor. A design with very low environmental susceptibility and another allowing calibrated measurements on a wide spectral range are described. Both enable a very high resolution (down to 2.5×10(-15) m/√Hz), illustrated by thermal noise measurements on AFM cantilevers. They present an excellent long-term stability and a constant sensitivity independent of the optical phase of the interferometer. A quick review shows that our precision is equaling or out-performing the best results reported in the literature, but for a much larger deflection range, up to a few μm.


Risk Associated with the Use of Selected Ingredients in Food Supplements.
This review focuses on four new product categories of food supplements: pre-workout, fat burner/thermogenic, brain/cognitive booster, and hormone/testosterone booster. Many food supplements have been shown to be contaminated with unauthorized substances. In some cases, the ingredients in the new categories of dietary supplements were medicinal products or new synthetic compounds added without performing clinical trials. Some of the new ingredients in dietary supplements are plant materials that are registered in the pharmacopoeia as herbal medicines. In other cases, dietary supplements may contain plant materials that have no history of human use and are often used as materials to 'camouflage' stimulants. In the European Union, new ingredients of dietary supplements, according to European Food Safety Authority or unauthorized novel food. Furthermore, selected ingredients in dietary supplements may be prohibited in sports and are recognized as doping agents by World Anti-Doping Agency.


Scattering detection using a photonic-microfluidic integrated device with on-chip collection capabilities.
SU-8-based photonic-microfluidic integrated devices with on-chip beam shaping and collection capabilities were demonstrated in a scattering detection and counting application. Through the proper deployment of the tailored beam geometries via the on-chip excitation optics, excellent CV values were measured for 1, 2, and 5 μm blank beads, 16.4, 11.0, and 12.5%, respectively, coupled with a simple free-space optical detection scheme. The performance of these devices was found dependent on the combination of on-chip, lens-shaped beam geometry and bead size. While very low CVs were obtained when the combination was ideal, a nonideal combination could still result in acceptable CVs for flow cytometry; the reliability was confirmed via devices being able to resolve separate populations of 2.0 and 5.0 μm beads from their mixture with low CV values of 15.9 and 18.5%, respectively. On-chip collection using integrated on-chip optical waveguides was shown to be very reliable in comparison with a free-space collection scheme, yielding a coincident rate of 94.2%. A CV as low as 19.2% was obtained from the on-chip excitation and collection of 5 μm beads when the on-chip lens-shaped beam had a 6.0-μm beam waist.


Dopamine replacement therapy does not restore the full spectrum of normal pallidal activity in the 1-methyl-4-phenyl-1,2,3,6-tetra-hydropyridine primate model of Parkinsonism.
Current physiological studies emphasize the role of neuronal oscillations and synchronization in the pathophysiology of Parkinson's disease; however, little is known about their specific roles in the neuronal substrate of dopamine replacement therapy (DRT). We investigated oscillatory activity and correlations throughout the different states of levodopa-naive parkinsonism as well as "Off-On" and dyskinetic states of DRT in the external globus pallidum (GPe) of tremulous (vervet) and rigid-akinetic (macaque) monkeys and in the internal globus pallidum (GPi) of the vervet monkey. We found that, although oscillatory activity of cells and interneuronal correlation in both pallidal segments increases after induction of parkinsonism with 1-methyl-4-phenyl-1,2,3,6-tetra-hydropyridine (MPTP) and decreases in response to DRT, important differences exist between the two pallidal segments. In the GPi, the fraction of oscillatory cells and relative power of oscillations were significantly higher than in the GPe, and the dominant frequency was within the range of 7.5-13.5 Hz compared with a range of 4.5-7.5 Hz within the GPe. The interneuronal correlations were mostly oscillatory in the GPi, whereas at least half are non-oscillatory in the GPe. We demonstrate that the tremor characteristics after exposure to DRT do not resemble those of the normal or the levodopa-naive state. Moreover, although DRT reverses the MPTP-induced neuronal changes (rate, pattern, and pairwise correlations), the balance between GPe and GPi fails to restore. We therefore suggest that this imbalance reflects additional abnormal organization of the basal ganglia networks in response to dopamine replacement and may constitute the physiological substrate of the limitations and side effects of chronic DRT.


Argus: Interactive a priori Power Analysis.
A key challenge HCl researchers face when designing a controlled experiment is choosing the appropriate number of participants, or sample size. A priori power analysis examines the relationships among multiple parameters, including the complexity associated with human participants, e.g., order and fatigue effects, to calculate the statistical power of a given experiment design. We created Argus, a tool that supports interactive exploration of statistical power: Researchers specify experiment design scenarios with varying confounds and effect sizes. Argus then simulates data and visualizes statistical power across these scenarios, which lets researchers interactively weigh various trade-offs and make informed decisions about sample size. We describe the design and implementation of Argus, a usage scenario designing a visualization experiment, and a think-aloud study.


Glial U87 cells protect neuronal SH-SY5Y cells from indirect effect of radiation by reducing oxidative stress and apoptosis.
Recent studies have demonstrated the role of indirect effect of radiation in neurodegeneration. However, the role of glial cells in neuroprotection against indirect effect of radiation is still not clear, although they are known to protect neurons under stress conditions in central nervous system. Our study showed that indirect effect of radiation increased the oxidative stress that further enhances the expression of key apoptotic proteins and leads to neuronal cell death. We also investigated the indirect effect of radiation on neuronal cells in the presence of glial cells in a transwell co-culture system, while our analysis was focused on neuronal cells. Irradiated cell-conditioned medium (ICCM) was used as source of indirect radiation and neuroprotective effect was analyzed by various endpoints. It was observed that ICCM-induced reactive oxidative species level was significantly reduced in SH-SY5Y cells co-cultured with glial U87 cells, which might help to maintain the integrity of mitochondrial membrane potential. Increased levels of antioxidant enzyme superoxide dismutase and antioxidant glutathione were observed in SH-SY5Y cells co-cultured with glial U87 cells. Moreover, it was also observed that co-culture with glial cells inhibits the expression of ICCM-induced apoptotic proteins, i.e. Bax, cytochrome c, and caspase-3 in SH-SY5Y cells. Hence, it can be speculated that in co-culture system glial cells may protect the neuronal SH-SY5Y cells by reducing the ICCM-induced oxidative stress and apoptotic death.


The histiocytoses of childhood.
The histiocytoses of childhood include Langerhans' cell histiocytosis, haemophagocytic syndrome (familial and reactive), sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease), juvenile xanthogranuloma and malignant histiocytosis. These disorders show wide variation in their clinical presentation, prognosis and genetic implications. All are characterized by localized or generalized proliferation of histiocytes, but they differ in their morphology, histochemical and immunochemical staining patterns and electronmicroscopical features. On the basis of a comprehensive clinical history and critical interpretation of morphology and immunocytochemistry using an appropriately selected panel of antibodies, a diagnosis can be reached in the majority of cases.


The implementation and efficacy of the Northwestern High Risk Spine Protocol.
The aims of this study were to determine the efficacy and feasibility of implementation of the intraoperative component of a high risk spine (HRS) protocol for improving perioperative patient safety in complex spine fusion surgery. In this paired availability study, the total number of red blood cell units transfused was used as a surrogate marker for our management protocol efficacy, and the number of protocol violations was used as a surrogate marker for protocol compliance. The 548 patients (284 traditional vs. 264 HRS protocol) were comparable in all demographics, coexisting diseases, preoperative medications, type of surgery, and number of posterior levels instrumented. However, the surgical duration was 70 minutes shorter in the new group (range, 32-108 minutes shorter; P < 0.0001) and the new protocol patients received a median of 1.1 units less of total red blood cell units (range, 0-2.4 units less; P = 0.006). There were only 7 (2.6%) protocol violations in the new protocol group. The intraoperative component of the HRS protocol, based on two Do-Confirm checklists that focused on 1) organized communication between intraoperative team members and 2) active maintenance of oxygen delivery and hemostasis appears to maintain a safe intraoperative environment and was readily implemented during a 3-year period.


E-cadherin, Snail, ZEB-1, DNMT1, DNMT3A and DNMT3B expression in normal and breast cancer tissues.
Breast cancer is known as one of very important cancers among females, given that a variety of external (i.e., environmental risk factors) and internal factors (i.e., genetics, and epigenetics) are related to the emergence and progression of breast cancer. Among genetic and epigenetic factors, DNA methyltransferase and EMT related genes have critical roles in breast cancer pathogenesis. In the study presented here, we investigated expression of DNA methyltransferases (e.g., DNMT1, DNMT3A and DNMT3B) and EMT related genes (e.g., E-cadherin, Snail, ZEB-1). Tissue samples were collected from 18 cancer and 24 normal breast tissues. We evaluated the expression levels of DNA methyltransferases and EMT related genes using Quantitative real-time PCR (qRT-PCR). Our results indicated that the expression levels of ZEB-1, Snail, and DNMT3B were increased in breast cancer subjects in comparison to the control group. On the other hand, there was a significant decrease in E-cadherin expression in breast cancer tissues in comparison to the normal tissues. Moreover, there were no significant changes for DNMT1 and DNMT3A expression in breast cancer tissues when compared to the normal tissues. Taken together, our finding show that up regulation of ZEB-1 and Snail could be associated with down regulation of E-cadherin and results in promotion of cancer cell invasion. Moreover, down regulation of E-cadherin may be related to deterioration of DNMT3B inpatients with breast cancer.


Augmentation method of triple phase boundary in thin film solid oxide fuel cell via physical vapor deposition.
Triple phase boundaries (TPBs) where electrode, electrolyte, and reactant meet altogether were augmented in thin film solid oxide fuel cell when Pt cathode was deposited on yttrium-doped barium zirconate electrolyte (BZY) via sputter. The augmented TPBs were observed to exist as three-dimensional structures, which is different from what are known to exist as two-dimensional planes or interfaces, by using energy dispersive spectroscopy (EDS). The permeating phenomenon of sputtered Pt into BZY was found to depend on dc sputtering power. Polarization curves showed increasing tendency of maximum powers in accordance with increasing thickness of Pt cathode and spectra of ac impedances showed decreasing tendency of faradaic resistances. If TPBs were located as an interfacial structure between electrode and electrolyte, oxygen could not diffuse well into TPBs, causing radius of semicircle in impedance spectra to decrease. The results are violating this expectation. As a result, as long as charge transfer resistance is a function of temperature, reactant concentration, activation barrier and TPB length, TPB must be only a factor to affect the results in this experiment.


Pichia hawaiiensis sp. nov., occurring in decaying bark of Charpentiera trees in the Hawaiian archipelago.
A description is given for Pichia hawaiiensis sp. nov., a nitrate-utilizing member of the genus Pichia E. C. Hansen emend. Kurtzman. Seven strains of the new species were isolated during the years 1972, 1973 and 1978 from rotting bark of the Hawaiian tree genera Charpentiera, Pisonia and Cheirodendron. P. hawaiiensis is heterothallic but appears to occur in nature mainly in the diploid state. Asci are deliquescent and produce up to four hat-shaped spores per ascus. Phylogenetic analysis of the 600 nucleotide D1/D2 domain of the 26S rDNA showed that P. hawaiiensis is most closely related to Pichia populi and Williopsis californica (syn. Hansenula californica). The type strain of P. hawaiiensis, isolated on the island of Hawaii from the rotting bark of Charpentiera sp. containing insect larvae, is strain UCD-FST 72-181T (= ATCC MYA-137T = CBS 8760T = NRRL Y-27270T).


Comparison of acute behavioral effects of sustained-release and immediate-release methylphenidate.
The rate of onset of a drug's effect is an important determinant of its abuse potential. This experiment examined the acute behavioral effects of orally administered sustained-release methylphenidate (SR; 20-40 mg), immediate-release methylphenidate (IR; 20-40 mg), and placebo in 10 healthy volunteers. Drug effects were assessed before drug administration and periodically afterwards for 6 hr using drug-effect questionnaires and performance measures that are sensitive to the acute effects of stimulants. The IR formulation produced stimulant-like drug effects (e.g., increased ratings of "good effects") that generally varied as a function of dose and time. The SR formulation produced only transient effects on these measures. These findings are consistent with previous research on the influence of rate of onset using other drugs and suggest that the abuse potential of IR methylphenidate may be greater than that of SR methylphenidate.


Critical inquiry and knowledge translation: exploring compatibilities and tensions.
Knowledge translation has been widely taken up as an innovative process to facilitate the uptake of research-derived knowledge into health care services. Drawing on a recent research project, we engage in a philosophic examination of how knowledge translation might serve as vehicle for the transfer of critically oriented knowledge regarding social justice, health inequities, and cultural safety into clinical practice. Through an explication of what might be considered disparate traditions (those of critical inquiry and knowledge translation), we identify compatibilities and discrepancies both within the critical tradition, and between critical inquiry and knowledge translation. The ontological and epistemological origins of the knowledge to be translated carry implications for the synthesis and translation phases of knowledge translation. In our case, the studies we synthesized were informed by various critical perspectives and hence we needed to reconcile differences that exist within the critical tradition. A review of the history of critical inquiry served to articulate the nature of these differences while identifying common purposes around which to strategically coalesce. Other challenges arise when knowledge translation and critical inquiry are brought together. Critique is one of the hallmark methods of critical inquiry and, yet, the engagement required for knowledge translation between researchers and health care administrators, practitioners, and other stakeholders makes an antagonistic stance of critique problematic. While knowledge translation offers expanded views of evidence and the complex processes of knowledge exchange, we have been alerted to the continual pull toward epistemologies and methods reminiscent of the positivist paradigm by their instrumental views of knowledge and assumptions of objectivity and political neutrality. These types of tensions have been productive for us as a research team in prompting a critical reconceptualization of knowledge translation.


A different perspective on macroscopic sampling of cholecystectomy specimens.
Because there may be interdepartmental differences in macroscopic sampling of cholecystectomy specimens, we aimed to investigate differences between the longitudinal sampling technique and our classical sampling technique in cholecystectomy specimens in which there was no obvious malignancy. Six hundred eight cholecystectomy specimens that were collected between 2011 and 2012 were included in this study. The first group included 273 specimens for which one sample was taken from each of the fundus, body, and neck regions (our classical technique). The second group included 335 specimens for which samples taken from the neck region and lengthwise from the fundus toward the neck were placed together in one cassette (longitudinal sampling). The Pearson chi-square, Fisher exact, and ANOVA tests were used and differences were considered significant at p<.05. In the statistical analysis, although gallbladders in the first group were bigger, the average length of the samples taken in the second group was greater. Inflammatory cells, pyloric metaplasia, intestinal metaplasia, low grade dysplasia, and invasive carcinoma were seen more often in the second group. In our study, the use of a longitudinal sampling technique enabled us to examine a longer mucosa and to detect more mucosal lesions than did our classical technique. Thus, longitudinal sampling can be an effective technique in detecting preinvasive lesions.


Designing an Educational Website to Improve Quality of Supportive Oncology Care for Women with Ovarian Cancer: An Expert Usability Review and Analysis.
A broad-based research team developed a Health Insurance Portability and Accountability Act (HIPAA)-compliant educational website for women with ovarian cancer to improve the quality of supportive oncology care. Prior to a randomized clinical trial of the website, initial usability testing was implemented to evaluate the website. The initial review found that 165/247 checklist items had sufficient information to allow for evaluation with the website achieving an overall score of 63%. By category, lowest scores were for the Home Page, Task Orientation, Page Layout & Visual Design, and Help, Feedback & Error Tolerance. Major issues thought to potentially impede actual usage were prioritized in redevelopment and the second usability review, conducted by the same expert, saw an improvement in scores. Incorporating usability concepts from the start of development, fulfilling the positive expectations of end-users and identifying technical and personal factors that optimize use may greatly enhance usage of health websites.


Outcome of pediatric heart transplantation in blood culture positive donors in the United States.
Active donor infection at the time of organ procurement poses a potential infection risk and may increase post-transplant morbidity and mortality in recipients. Our hypothesis was that pediatric heart transplant recipients from blood culture positive donors (BCPD) would have increased morbidity and mortality compared to non-blood culture positive donors (NBCPD). A retrospective analysis of pediatric heart transplant recipients using the organ procurement and transplant network (OPTN) between 1987 and 2015 was conducted. Recipient as well as donor data were analyzed. Propensity score matching with 1:2 ratios was performed for recipient variables. Post-transplant morbidity and mortality were compared for recipients of BCPD and NBCPD. Among 9618 heart transplant recipients, 450 (4.7%) were from culture positive donors. Recipients of BCPD had longer duration of listing as Status 1; diagnosis of congenital heart disease or restrictive cardiomyopathy and required support (IV inotropes, Inhaled NO and LVAD) prior to transplant. Post-transplant survival between the 2 groups was not different. Propensity-matched recipients had similar length of stay; stroke rate; need for dialysis; pacemaker implantation and treated rejection episodes in the first year post-transplant. Careful acceptance of BCPD may have the potential to increase availability of donor hearts in the pediatric population.


Acute stress affects the physiology and behavior of allergic mice.
Physical and psychological stressors have been implicated in acute asthma exacerbation. The objective of the current study was to determine the effects of forced swimming stress (FST) on allergic pulmonary inflammation in BALB/c mice. Eighty female mice were allocated to one of four treatments arranged in a 2 x 2 factorial consisting of two levels of allergy and two levels of stress. The effects of stress and allergy were assessed by examination of cytokines and leukocyte differentials in the bronchoalveolar lavage fluid, corticosterone and immunoglobulin (Ig) E in the plasma, leukocyte differentials in the peripheral blood, natural killer cytotoxicity, and histopathology of the lungs. Behavior was recorded during the FST. Stress and allergy increased plasma corticosterone in mice. Allergy increased IgE concentrations and pulmonary inflammation. Interleukin-4 was greater among allergic stressed and non-stressed mice and stressed, non-allergic mice compared with non-stressed, non-allergic mice. Interleukin-5 (IL-5) and 6 (IL-6) were greater among allergic stressed and non-stressed mice compared with non-allergic mice. Interleukin-5 and 6 were reduced among stressed-allergic mice compared with non-stressed, allergic mice. Stress and allergy shifted mice towards a T-helper 2 response as shown by increased interleukin-4. Stress reduced IL-5 and IL-6 in allergic mice but not non-allergic mice. Pulmonary inflammation was not reduced among allergic stressed mice in spite of elevated glucocorticoids. Mice induced to be allergic responded to FST differently than non-allergic mice. Our findings suggest that stress induces a differential response among allergic and non-allergic mice.


The effect of a flexed elbow on bowling speed in cricket.
The laws of bowling in cricket state 'a ball is fairly delivered in respect of the arm if, once the bowler's arm has reached the level of the shoulder in the delivery swing, the elbow joint is not straightened partially or completely from that point until the ball has left the hand'. Recently two prominent bowlers, under suspicion for transgressing this law, suggested that they are not 'throwing' but due to an elbow deformity are forced to bowl with a bent bowling arm. This study examined whether such bowlers can produce an additional contribution to wrist/ball release speed by internal rotation of the upper arm. The kinematics of a bowling arm were calculated using a simple two-link model (upper arm and forearm). Using reported internal rotation speeds of the upper arm from baseball and waterpolo, and bowling arm kinematics from cricket, the change in wrist speed was calculated as a function of effective arm length, and wrist distance from the internal rotation axis. A significant increase in wrist speed was noted. This suggests that bowlers who can maintain a fixed elbow flexion during delivery can produce distinctly greater wrist/ball speeds by using upper arm internal rotation.


Children's sleep: an interplay between culture and biology.
Pediatricians provide a major source of knowledge for parents about children's behavior and development, although their advice is largely based on their own cultural values and beliefs in interaction with their personal and clinical experience. This review presents cross-cultural aspects of children's sleep behavior in industrialized and complex modern societies and provides a basis for understanding dimensions and mechanisms of cultural differences. We submit that it is the interaction between culture and biology that establishes behavioral and developmental norms and expectations regarding normal and problematic children's sleep. Pediatricians need to recognize the cultural environment in which children live and be knowledgeable about how cultural beliefs and values of both families and physicians interact with the needs and biological characteristics of individual children.


Protein kinase C modulates the phase-delaying effects of light in the mammalian circadian clock.
The mammalian circadian pacemaker located in the suprachiasmatic nuclei (SCN) drives a vast array of biochemical and physiological processes with 24-h periodicity. The phasing of SCN pacemaker activity is tightly regulated by photic input from the retina. Recent work has implicated protein kinase C (PKC) as a regulator of photic input, although stimulus-induced PKC activity has not been examined. Here we used a combination of biochemical, immunohistochemical and behavioral techniques to examine both the regulation and role of PKC in light-induced clock entrainment in mice. We report that photic stimulation during the subjective night, but not during the subjective day, stimulates PKC activity within the SCN. To assess the role of PKC in clock entrainment, we employed an in-vivo infusion approach to deliver the PKC inhibitor bisindolylmaleimide I to the SCN. The disruption of PKC activity significantly enhanced the phase-shifting effects of light, indicating that PKC functions as a negative regulator of light entrainment. Importantly, bisindolylmaleimide I infusion in the absence of light treatment did not phase shift the clock, demonstrating that transient disruption of basal PKC activity does not affect inherent pacemaker activity. The capacity of light to stimulate immediate early gene expression in the SCN was not substantively altered by PKC inhibition, suggesting that PKC does not couple light to rapid transcriptional activation. Rather, a combination of in-vivo and cell culture assays indicates that PKC functions as an inhibitor of PERIOD1 degradation. Thus, PKC may influence clock entrainment via a post-translational mechanism that influences clock protein stability.


Influence of monocular deprivation during infancy on the later development of spatial and temporal vision.
Using the method of limits, we measured spatial and temporal vision in 15 patients, aged 4-28 years, who had been monocularly deprived of patterned visual input during infancy by a dense cataract. All patients showed losses in both spatial and temporal vision, with greater losses in spatial than in temporal vision. Losses were smaller when there had been more patching of the non-deprived eye. The results indicate that visual deprivation has smaller effects on the neural mechanisms mediating temporal vision than on those mediating spatial vision.


Benzodiazepine receptor-mediated experimental "anxiety" in primates.
The ethyl ester of beta-carboline-3-carboxylic acid has a high affinity for benzodiazepine receptors in the brain. In the rhesus monkey this substance produces an acute behavioral syndrome characterized by dramatic elevations in heart rate, blood pressure, plasma cortisol, and catecholamines. The effects are blocked by benzodiazepines and the specific benzodiazepine receptor antagonist Ro 15-1788. The benzodiazepine receptor may consist of several subsites or functional domains that independently recognize agonist, antagonists, or "active" antagonists such as beta-carboline-3-carboxylic acid ethyl ester. These results suggest that the benzodiazepine receptor is involved in both the affective and physiological manifestations of anxiety, and that the administration of beta-carboxylic acid ethyl ester to monkeys may provide a reliable and reproducible animal model of human anxiety.


Lipid chain mobility and packing in DOPC bilayers at cryogenic temperatures.
Low-temperature molecular mobility and packing in biological tissues are important for their survival upon cryopreservation. Electron paramagnetic resonance (EPR) in its pulsed version of electron spin echo (ESE) allows studying stochastic librations of spin-labeled molecules, the type of motion which dominates at low temperatures. These librations are characterized by the parameter <α2>τc where <α2> is the mean squared angular amplitude and τc is the correlation time for the motion. This parameter is known to be larger for higher temperature and for looser intermolecular structure. In this work, ESE data for the bilayers comprised of doubly-unsaturated DOPC (dioleoyl-glycero-phosphocholine) lipids and mono-unsaturated POPC (palmitoyl-oleoyl-glycero-phosphocholine) lipids with spin-labeled stearic acids added were obtained in the temperature range between 80 and 210 K; the results were compared also with the previously obtained data for fully-saturated DPPC (dipalmitoyl-glycero-phosphocholine) lipid bilayers [J. Phys. Chem. B2014, 118, 12,478-12,485; Appl. Magn. Reson. 2018, 49, 1369-1383]. It turned out that for DOPC bilayers the <α2>τc values are of intermediate magnitude between those for POPC and DPPC bilayers, which implies an intermediate density of lipid packing. A possible explanation of this result could be rearrangement at cryogenic temperatures of the DOPC lipid tails, with their terminal segments folding cooperatively. This interpretation is also in agreement with the known thermodynamic properties of gel-fluid transition for DOPC bilayer.


Efficient marker-based recurrent selection for multiple quantitative trait loci.
We studied the efficiency of recurrent selection based solely on marker genotypes (marker-based selection), in order to increase favourable allele frequency at 50 previously detected quantitative trait loci (QTLs). Two selection procedures were investigated, using computer simulations: (1) Truncation Selection (MTS), in which individuals are ranked based on marker score, and best individuals are selected for recombination; and (2) QTL Complementation Selection (QCS), in which individuals are selected such that their QTL composition complements those individuals already selected. Provided QTL locations are accurate, marker-based selection with a population size of 200 was very effective in rapidly increasing frequencies of favourable QTL alleles. QCS methods were more effective than MTS for improving the mean frequency and fixation of favourable QTL alleles. Marker-based selection was not very sensitive to a reduction in population size, and appears valuable to optimize the use of molecular markers in recurrent selection programmes.


In vitro and in vivo suppression of GJB2 expression by RNA interference.
Mutations in GJB2 (gap junction protein, beta-2) are the major cause of autosomal recessive non-syndromic hearing loss. A few allele variants of this gene also cause autosomal dominant non-syndromic hearing loss as a dominant-negative consequence of expression of the mutant protein. Allele-specific gene suppression by RNA interference (RNAi) is a potentially attractive strategy to prevent hearing loss caused by this mechanism. In this proof-of-principle study, we identified a potent GJB2-targeting short interfering RNA (siRNA) to post-transcriptionally silence the expression of the R75W allele variant of GJB2 in cultured mammalian cells. In a mouse model, this siRNA duplex selectively suppressed GJB2(R75W) expression by >70% of control levels, thereby preventing hearing loss. The level of endogenous murine Gjb2 expression was not affected. Our data show that RNAi can be used with specificity and efficiency in vivo to protect against hearing loss caused as a dominant-negative consequence of mutant gene expression.


Use of Nanomaterial-Based (Micro)Extraction Techniques for the Determination of Cosmetic-Related Compounds.
The high consumer demand for cosmetic products has caused the authorities and the industry to require rigorous analytical controls to assure their safety and efficacy. Thus, the determination of prohibited compounds that could be present at trace level due to unintended causes is increasingly important. Furthermore, some cosmetic ingredients can be percutaneously absorbed, further metabolized and eventually excreted or bioaccumulated. Either the parent compound and/or their metabolites can cause adverse health effects even at trace level. Moreover, due to the increasing use of cosmetics, some of their ingredients have reached the environment, where they are accumulated causing harmful effects in the flora and fauna at trace levels. To this regard, the development of sensitive analytical methods to determine these cosmetic-related compounds either for cosmetic control, for percutaneous absorption studies or for environmental surveillance monitoring is of high interest. In this sense, (micro)extraction techniques based on nanomaterials as extraction phase have attracted attention during the last years, since they allow to reach the desired selectivity. The aim of this review is to provide a compilation of those nanomaterial-based (micro)extraction techniques for the determination of cosmetic-related compounds in cosmetic, biological and/or environmental samples spanning from the first attempt in 2010 to the present.


Reference-based benefit design changes consumers' choices and employers' payments for ambulatory surgery.
Some employers are using reference-based benefit (RBB) designs, also known as "reference-based pricing," to encourage patients to select lower-price ambulatory surgery centers instead of expensive hospital outpatient departments. This article analyzes the impact of such benefit designs for cataract removal surgery from the period 2009-13, using data on 2,347 surgical patients covered by the California Public Employees Retirement System (CalPERS), in comparison to 14,867 patients enrolled in non-CalPERS Anthem Blue Cross plans, which are not covered by RBB. After adjusting for changes in patient case-mix and other factors, the shift to RBB was associated with an increase in ambulatory surgery center use by 8.6 percentage points compared to trends among Anthem enrollees. Total employer and employee payments per procedure, after adjusting for changes in case-mix severity and market factors, declined by 19.7 percent compared with Anthem enrollees not subject to RBB. Consumer cost-sharing requirements increased for CalPERS patients who continued to use hospital outpatient departments but who were not exempted from RBB because of geographic or clinical factors. Reference-based benefits for cataract surgery saved CalPERS $1.3 million in the two years after implementation.


Active exploration of faces in police lineups increases discrimination accuracy.
Eyewitness identifications play a key role in the justice system, but eyewitnesses can make errors, often with profound consequences. We used findings from basic science and innovative technologies to develop and test whether a novel interactive lineup procedure, wherein witnesses can rotate and dynamically view the lineup faces from different angles, improves witness discrimination accuracy compared with a widely used procedure in laboratories and police forces around the world-the static frontal-pose photo lineup. No novel procedure has previously been shown to improve witness discrimination accuracy. In Experiment 1, participants (N = 220) identified culprits from sequentially presented interactive lineups or static frontal-pose photo lineups. In Experiment 2, participants (N = 8,507) identified culprits from interactive lineups that were either presented sequentially, simultaneously wherein the faces could be moved independently, or simultaneously wherein the faces moved jointly into the same angle. Sequential interactive lineups enhanced witness discrimination accuracy compared with static photo lineups, and simultaneous interactive lineups enhanced witness discrimination accuracy compared with sequential interactive lineups. These finding were true both when participants viewed suspects who were of the same or different ethnicity/race as themselves. Our findings exemplify how basic science can be used to address the important applied policy issue on how best to conduct a police lineup and reduce eyewitness errors. (PsycInfo Database Record (c) 2022 APA, all rights reserved).


The use of m-sequences in the analysis of visual neurons: linear receptive field properties.
We have used Sutter's (1987) spatiotemporal m-sequence method to map the receptive fields of neurons in the visual system of the cat. The stimulus consisted of a grid of 16 x 16 square regions, each of which was modulated in time by a pseudorandom binary signal, known as an m-sequence. Several strategies for displaying the m-sequence stimulus are presented. The results of the method are illustrated with two examples. For both geniculate neurons and cortical simple cells, the measurement of first-order response properties with the m-sequence method provided a detailed characterization of classical receptive-field structures. First, we measured a spatiotemporal map of both the center and surround of a Y-cell in the lateral geniculate nucleus (LGN). The time courses of the center responses was biphasic: OFF at short latencies, ON at longer latencies. The surround was also biphasic--ON then OFF--but somewhat slower. Second, we mapped the response properties of an area 17 directional simple cell. The response dynamics of the ON and OFF subregions varied considerably; the time to peak ranged over more than a factor of two. This spatiotemporal inseparability is related to the cell's directional selectivity (Reid et al., 1987, 1991; McLean & Palmer, 1989; McLean et al., 1994). The detail with which the time course of response can be measured at many different positions is one of the strengths of the m-sequence method.


Supporting children of parents who are dying.
Nurses, parents and other family members tend to feel ill equipped when talking to children about a parent's impending death. Adults often feel the need to protect children from the reality of a parent's imminent death. However, research indicates that children experience increased levels of anxiety when information regarding a parent's terminal prognosis is withheld from them. As a result, not telling children that their parent is dying does not avert a fearful situation for the child but, rather, it denies the child access to accurate information and appropriate emotional support. Oncology nurses are uniquely placed to provide guidance to parents on this topic. This paper will include a nursing narrative and practical strategies for communicating with children whose parents are dying.


Pathogenesis and epidemiology of border disease.
The pathogenesis of BD virus infection of sheep is reviewed briefly. The most serious consequences occur when susceptible pregnant sheep are infected. The virus crosses the placenta readily and can cause foetal death with resorption, mummification or stillbirths. Other lambs survive, however, and are born with varying degrees of tremor and/or hairy fleeces. Many such "hairy-shaker" lambs die shortly after birth but survivors gradually recover. These survivors plus other apparently normal lambs can be persistently infected with virus and excrete it constantly often for the rest of their lives. It is these persistently infected sheep that are the key to the epidemiology of the virus and may be responsible for its introduction into a susceptible flock. In addition, cattle grazed with sheep are potentially an important source of pestiviruses capable of causing BD since in some herds the prevalence of cattle persistently infected with pestivirus is one to three per cent. Results are presented of studies on antigenic relation ships among Scottish isolates of cattle pestiviruses (BVD) and BD viruses, and the conclusion drawn that while a single strain of BVDV may be suitable for use as a cattle vaccine this would not be very efficacious in preventing BD since two antigenically distinguishable strains of BD virus have been identified. An effective vaccine against BD would have to protect sheep against both these strains and ideally a cattle vaccine should also contain both strains.


Leptin Modulates the Metastasis of Canine Inflammatory Mammary Adenocarcinoma Cells Through Downregulation of Lysosomal Protective Protein Cathepsin A (CTSA).
Canine malignant mammary gland tumors present with a poor prognosis due to metastasis to other organs, such as lung and lymph node metastases. Unlike in human studies where obesity has been shown to increase the risk of breast cancer, this has not been well studied in veterinary science. In our preliminary study, we discovered that leptin downregulated cathepsin A, which is responsible for lysosomal-associated membrane protein 2a (LAMP2a) degradation. LAMP2a is a rate-limiting factor in chaperone-mediated autophagy and is highly active in malignant cancers. Therefore, in this study, alterations in metastatic capacity through cathepsin A by leptin, which are secreted at high levels in the blood of obese patients, were investigated. We used a canine inflammatory mammary gland adenocarcinoma (CHMp) cell line cultured with RPMI-1640 and 10% fetal bovine serum. The samples were then subjected to real-time polymerase chain reaction, Western blot, immunocytochemistry, and lysosome isolation to investigate and visualize the metastasis and chaperone-mediated autophagy-related proteins. Results showed that leptin downregulated cathepsin A expression at both transcript and protein levels, whereas LAMP2a, the rate-limiting factor of chaperone-mediated autophagy, was upregulated by inhibition of LAMP2a degradation. Furthermore, leptin promoted LAMP2a multimerization through the lysosomal mTORC2 (mTOR complex 2)/PH domain and leucine rich repeat protein phosphatase 1 (PHLPP1)/AKT1 (Serine/threonine-protein kinase 1) pathway. These findings suggest that targeting leptin receptors can alleviate mammary gland cancer cell metastasis in dogs.


Cortical cell populations from rabbit kidney isolated by free-flow electrophoresis: characterization by measurement of hormone-sensitive adenylate cyclase.
Free-flow electrophoresis allows the separation of different cell populations from a cell suspension isolated from rabbit kidney cortex after perfusion of the kidneys with a calcium-binder, followed by gentle mechanical treatment. After electrophoretic separation, analysis of the adenylate cyclase activities after stimulation by various hormones allows the precise determination of the origin of the cell populations with different electrophoretic mobilities. Adenylate cyclase from the slow-moving main cell population was only sensitive to parathyroid hormone. These cells had also high alkaline phosphatase content, further demonstrating their proximal origin. The various fast-moving cell populations had adenylate cyclase sensitive to isoproterenol and arginine vasopressin but were less sensitive to parathyroid hormone than the slow-moving cells. Their alkaline phosphatase content was also much lower. This indicates that these fast-moving cell populations originate from both the granulous segment of the distal tubule and from the collecting ducts. The adenylate cyclase activity and the cyclic AMP contents of isolated proximal cells maintained in culture medium were also investigated.


Sustained increases in plasma epinephrine concentration do not modulate renin release.
We examined the relationship between plasma renin activity (PRA) and renal arterial pressure (RAP) during 1) control conditions, 2) acute, and 3) chronic intravenous epinephrine (EPI) infusion (125 ng.kg-1.min-1). In eight conscious uninephrectomized dogs maintained on a normal sodium intake, the renin stimulus-response curve (RSRC) was determined by a stepwise reduction in RAP with an inflatable occluder around the renal artery controlled by a servo unit. The RSRC could be approximated by two lines intersecting at a threshold pressure (approximately 20 mmHg below control RAP). In the high-pressure range, PRA was relatively insensitive to changes in RAP, whereas, below threshold pressure, changes in RAP had large effects on PRA. During acute EPI infusion there was approximately a 40% increase in heart rate (control = 57 +/- 3 beats/min) and hematocrit (control = 30 +/- 1%) in association with a rise in plasma EPI concentration from 73 +/- 16 to 1,413 +/- 100 pg/ml; mean arterial pressure (MAP) was unchanged (94 +/- 3 mmHg). Moreover, EPI acutely increased basal PRA from 0.3 +/- 0.1 to 0.8 +/- 0.3 ng angiotensin I.ml-1.h-1 and shifted the RSRC to the right (increasing threshold pressure 7 mmHg) without altering the slope of the RSRC curve either above or below threshold pressure. In contrast, although plasma EPI concentration and hematocrit remained elevated during chronic EPI infusion, heart rate and basal PRA returned to preinfusion values. In addition, there were no significant long-term changes in MAP or in any of the parameters of the RSRC.(ABSTRACT TRUNCATED AT 250 WORDS)


Transfer of nitrate reductase genes of the cyanobacterium Nostoc muscorum into Rhizobium japonicum.
Transformation of Rhizobium japonicum CB1809 was studied using DNA from the cyanobacterium Nostoc muscorum ATCC 27893. A spontaneous nitrate reductase deficient (Nar-) mutant (NR-6) of R. japonicum CB1809 was isolated with a frequency of 8.4 X 10(-7). Streptomycin (Sm) and Neomycin (Neo) resistance markers were introduced into strain NR-6, and the resulting strain was designated NR-6 SmR NeoR. Experiments with cyanobacterial DNA and live cells of strain NR-6 SmR NeoR indicated transformation of nitrate reductase (nar) genes of N. muscorum into this strain. This conclusion was supported by the reversion frequency of strain NR-6 SmR NeoR to Nar+ and the transformation frequency when recipient cells were exposed to N. muscorum DNA (with heat-treated DNA as control). Comparisons of growth, nitrate uptake, assimilatory nitrate reductase activity and nodulation of parent CB1809, NR-6 SmR NeoR and five transformant clones (Nar+) suggest that there may be considerable homology between the nar genes of R. japonicum CB1809 and N. muscorum.


Higher order neurocognition in pediatric brain tumor survivors: What can we learn from white matter microstructure?
Pediatric brain tumor survivors (PBTS) experience neurocognitive late effects, including problems with working memory, processing speed, and other higher order skills. These skill domains are subserved by various white matter (WM) pathways, but not much is known about these brain-behavior links in PBTS. This study examined the anterior corona radiata (ACR), inferior fronto-occipital fasciculi (IFOF), and superior longitudinal fasciculi (SLF) by analyzing associations among diffusion metrics and neurocognition. Thirteen PBTS and 10 healthy controls (HC), aged 9-14 years, completed performance-based measures of processing speed and executive function, and parents rated their child's day-to-day executive skills. Children underwent magnetic resonance imaging (MRI) with diffusion weighted imaging that yielded fractional anisotropy (FA) and mean diffusivity (MD) values. Independent samples t-tests assessed group differences on neurocognitive and imaging measures, and pooled within-group correlations examined relationships among measures across groups. PBTS performed more poorly than HC on measures of processing speed, divided attention, and shifting (d = -1.08 to -1.44). WM microstructure differences were significant in MD values for the bilateral SLF and ACR, with PBTS showing higher diffusivity (d = 0.75 to 1.21). Better processing speed, divided attention, and shifting were associated with lower diffusivity in the IFOF, SLF, and ACR, but were not strongly correlated with FA. PBTS demonstrate poorer neurocognitive functioning that is linked to differences in WM microstructure, as evidenced by higher diffusivity in the ACR, SLF, and IFOF. These findings support the use of MD in understanding alterations in WM microstructure in PTBS and shed light on potential functions of these pathways.


A systematic evaluation on the relationship between hypo-osmoregulation and hyper-osmoregulation in decapods of different habitats.
Decapods occupy all aquatic, and terrestrial and semi-terrestrial environments. According to their osmoregulatory capacity, they can be osmoconformers or osmoregulators (hypo or hyperegulators). The goal of this study is to gather data available in the literature for aquatic decapods and verify if the rare hyporegulatory capacity of decapods is associated with hyper-regulatory capacity. The metric used to quantify osmoregulation was the osmotic capacity (OC), the gradient between external and internal (hemolymph) osmolalities. We employ phylogenetic comparative methods using 83 species of decapods to test the correlation between hyper OC and hypo OC, beyond the ancestral state for osmolality habitat, which was used to reconstruct the colonization route. Our analysis showed a phylogenetic signal for habitat osmolality, hyper OC and hypo OC, suggesting that hyper-hyporegulators decapods occupy similar habitats and show similar hyper and hyporegulatory capacities. Our findings reveal that all hyper-hyporegulators decapods (mainly shrimps and crabs) originated in estuarine waters. Hyper OC and hypo OC are correlated in decapods, suggesting correlated evolution. The analysis showed that species which inhabit environments with intense salinity variation such as estuaries, supratidal and mangrove habitats, all undergo selective pressure to acquire efficient hyper-hyporegulatory mechanisms, aided by low permeabilities. Therefore, hyporegulation can be observed in any colonization route that passes through environments with extreme variations in salinity, such as estuaries or brackish water.


The economics, financing and implementation of HIV treatment as prevention: what will it take to get there?
The 2013 Lancet Commission Report, Global Health 2035, rightly pointed out that we are at a unique place in history where a "grand convergence" of health initiatives to reduce both infectious diseases, and child and maternal mortality--diseases that still plague low income countries--would yield good returns in terms of development and health outcomes. This would also be a good economic investment. Such investments would support achieving health goals of reducing under-five (U5) mortality to 16 per 1000 live births, reducing deaths due to HIV/AIDS to 8 per 100,000 population, and reducing annual TB deaths to 4 per 100,000 population. Treatment as prevention (TasP) holds enormous potential in reducing HIV transmission, and morbidity and mortality associated with HIV/AIDS--and therefore contributing to Global Health 2035 goals. However, TasP requires large financial investments and poses significant implementation challenges. In this review, we discuss the potential effectiveness, financing and implementation of TasP. Overall, we conclude that TasP shows great promise as a cost-effective intervention to address the dual aims of reducing new HIV infections and reducing the global burden of HIV-related disease. Successful implementation will be no easy feat, though. The dramatic increases in the numbers of persons who need antiretroviral therapy (ART) under a TasP approach will pose enormous challenges at all stages of the HIV treatment cascade: HIV diagnosis, antiretroviral (ARV) initiation, ARV adherence and retention, and increased drug resistance with long-term enrolment on ART. Overcoming these implementation challenges will require targeted implementation, not focusing exclusively on TasP, most-at-risk population (MARP)-friendly services for key populations, integrating services, task shifting, more efficient programme management, balancing supply and demand, integration into universal health coverage efforts, demand creation, improved ART retention and adherence strategies, the use of incentives to improve HIV treatment outcomes and reduce unit costs, continued operational research and tapping into technological innovations.


CMV reactivation drives posttransplant T-cell reconstitution and results in defects in the underlying TCRβ repertoire.
Although cytomegalovirus (CMV) reactivation has long been implicated in posttransplant immune dysfunction, the molecular mechanisms that drive this phenomenon remain undetermined. To address this, we combined multiparameter flow cytometric analysis and T-cell subpopulation sorting with high-throughput sequencing of the T-cell repertoire, to produce a thorough evaluation of the impact of CMV reactivation on T-cell reconstitution after unrelated-donor hematopoietic stem cell transplant. We observed that CMV reactivation drove a >50-fold specific expansion of Granzyme B(high)/CD28(low)/CD57(high)/CD8(+) effector memory T cells (Tem) and resulted in a linked contraction of all naive T cells, including CD31(+)/CD4(+) putative thymic emigrants. T-cell receptor β (TCRβ) deep sequencing revealed a striking contraction of CD8(+) Tem diversity due to CMV-specific clonal expansions in reactivating patients. In addition to querying the topography of the expanding CMV-specific T-cell clones, deep sequencing allowed us, for the first time, to exhaustively evaluate the underlying TCR repertoire. Our results reveal new evidence for significant defects in the underlying CD8 Tem TCR repertoire in patients who reactivate CMV, providing the first molecular evidence that, in addition to driving expansion of virus-specific cells, CMV reactivation has a detrimental impact on the integrity and heterogeneity of the rest of the T-cell repertoire. This trial was registered at www.clinicaltrials.gov as #NCT01012492.


Colonic diverticular bleeding: urgent colonoscopy without purging and endoscopic treatment with epinephrine and hemoclips.
Diverticular disease is the most frequent cause of lower gastrointestinal bleeding. Most of the times, bleeding stops without any intervention but in 10-20% of the cases it is necessary to treat the hemorrhage. Several modalities of endoscopic treatment have been described after purging the colon. We present five cases of severe diverticular bleeding treated with injection of epinephrine and hemoclips. All the colonoscopies were performed without purging of the colon in an emergency setting, with correct visualization of the point of bleeding. Patients recovered well avoiding other aggressive procedures such as angiography or surgery.


Effects of microbial elicitor on production of hypocrellin by Shiraia bambusicola.
Some endophyte isolates were isolated in a bamboo pole sample parasitized the fungus Shiraia bambusicola from Zhejiang Province. After screening through hypocrellin bacteriostatic effect and fermentation test, we got the isolate TX4 of bacterial elicitor and GZUIFR-TT1 of fungal elicitor which had certain effect to promote S. bambusicola to produce hypocrellin. The Plackett-Burman design was introduced to evaluate the effects of nine factors based on single-factor test. Yeast extract, glucose, and isolate GZUIFR-TT1 elicitor were found to be the critical activity factors for increasing the total hypocrellin production. So we identified the isolate GZUIFR-TT1 as Trametes sp. Through response surface methodology, we obtained the optimum production conditions as follows: yeast extract, 2.99 g/L; glucose, 32.45 g/L; and Trametes sp. elicitor, 81.40 μg/mL. Under the above conditions, the experimental value of hypocrellin production was 102.60 mg/L, compared with the control it increased about 7.90 times.


Interventional and surgical management of internal jugular venous stenosis: a narrative review.
A small subset of patients with presumed idiopathic intracranial hypertension are found to have isolated internal jugular vein stenosis (IJVS). To review the current interventions used in patients who present with intracranial hypertension secondary to IJVS. In December 2020, we performed a literature search on Pubmed/Medline and Scopus databases for original articles studying surgical and endovascular interventions used for intracranial hypertension in the setting of internal jugular vein stenosis. No date, patient population, or study type was excluded. All studies that included at least one case in which a surgical or endovascular intervention was used to treat IJVS were included. Selection criteria for patients varied, most commonly defined by identification of compression of the internal jugular vein. The 17 studies included in this review ranged from case reports to large single-center cohort studies. The most used surgical intervention was styloidectomy. Styloidectomy had an overall better outcome success rate (79%) than angioplasty/stenting (66%). No complications were recorded in any of the surgical cases analyzed. Outcome measures varied, but all studies recorded clinical symptoms of the patients. Few current large cohort studies analyze surgical and endovascular interventions for patients with IJVS. Notably, the most common intervention is styloidectomy, followed by internal jugular vein stenting. By understanding the trends and experience of interventionalists and surgeons, more focused and larger studies can be performed to determine effective strategies with the best clinical outcomes.