[Comparison of effects of two kinds of soluble algae polysaccharide on blood lipid, liver lipid, platelet aggregation and growth in rats].
SD rats were fed with 1% cholesterol and 0.2% cholate for eight weeks. Sodium alginate and carrageenan, two kinds of soluble algae polysaccharide, were added to the fodder for the trial groups and none added for the control one. Results showed that 5% sodium alginate could lower lipid levels in the blood and liver and platelet aggregation (P < 0.05) in rats, but not affect their food intake and growth. Addition with 5% or 10% carrageenan had no obvious effects on lowering blood lipid and liver total cholesterol (P > 0.05), could not lower the ratio of liver weight to body weight, and had no stable (or sure) effect on lowering platelet aggregation. Ten percent of carrageenan could decrease their mean body weight by 12.17% in rats (P > 0.05), but a few rats suffered from slight diarrhea.


Academic affiliated training centers in humanitarian health, Part I: program characteristics and professionalization preferences of centers in North America.
The collaborative London based non-governmental organization network ELRHA (Enhancing Learning and Research for Humanitarian Assistance) supports partnerships between higher education institutions and humanitarian organizations worldwide with the objective to enhance the professionalization of the humanitarian sector. While coordination and control of the humanitarian sector has plagued the response to every major crisis, concerns highlighted by the 2010 Haitian earthquake response further catalyzed and accelerated the need to ensure competency-based professionalization of the humanitarian health care work force. The Harvard Humanitarian Initiative sponsored an independent survey of established academically affiliated training centers in North America that train humanitarian health care workers to determine their individual training center characteristics and preferences in the potential professionalization process. The survey revealed that a common thread of profession-specific skills and core humanitarian competencies were being offered in both residential and online programs with additional programs offering opportunities for field simulation experiences and more advanced degree programs. This study supports the potential for the development of like-minded academic affiliated and competency-based humanitarian health programs to organize themselves under ELRHA's regional "consultation hubs" worldwide that can assist and advocate for improved education and training opportunities in less served developing countries.


Surfactant behavior of ionic liquids involving a drug: from molecular interactions to self-assembly.
Aggregates formed in an aqueous medium by three ionic liquids CnMImIbu made up of 1-alkyl-3-methyl-imidazolium cation (n = 4, 6, 8) and ibuprofenate anion are investigated. Dynamic light scattering (DLS), cryogenic transmission electron microscopy (cryo-TEM), (1)H nuclear magnetic resonance measurements, and atom-scale molecular dynamics simulations are used to shed light on the main interactions governing the formation of the aggregates and their composition. At high concentration, mixed micelles are formed with a composition that depends on the imidazolium alkyl chain length. For the shortest alkyl chain, micelles are mainly composed of ibuprofenate anions with some imidazolium cations intercalated between the anions. Upon increasing the alkyl chain length, the composition of the aggregates gets enriched in imidazolium cations and aggregates of stoichiometric composition are obtained. Attractive interactions between these aggregates led to the formation of larger aggregates. As suggested by molecular simulations, these larger aggregates might constitute the early stage of phase separation. Transitions from micelles to vesicles or ribbons are observed due to dilution effects and changes in the chemical composition of the aggregates. We also show that aggregation can be probed using simple microscopic quantities such as radial distribution functions and average solvation numbers.


Gene length and detection bias in single cell RNA sequencing protocols.
Background: Single cell RNA sequencing (scRNA-seq) has rapidly gained popularity for profiling transcriptomes of hundreds to thousands of single cells. This technology has led to the discovery of novel cell types and revealed insights into the development of complex tissues. However, many technical challenges need to be overcome during data generation. Due to minute amounts of starting material, samples undergo extensive amplification, increasing technical variability. A solution for mitigating amplification biases is to include unique molecular identifiers (UMIs), which tag individual molecules. Transcript abundances are then estimated from the number of unique UMIs aligning to a specific gene, with PCR duplicates resulting in copies of the UMI not included in expression estimates. Methods: Here we investigate the effect of gene length bias in scRNA-Seq across a variety of datasets that differ in terms of capture technology, library preparation, cell types and species. Results: We find that scRNA-seq datasets that have been sequenced using a full-length transcript protocol exhibit gene length bias akin to bulk RNA-seq data. Specifically, shorter genes tend to have lower counts and a higher rate of dropout. In contrast, protocols that include UMIs do not exhibit gene length bias, with a mostly uniform rate of dropout across genes of varying length. Across four different scRNA-Seq datasets profiling mouse embryonic stem cells (mESCs), we found the subset of genes that are only detected in the UMI datasets tended to be shorter, while the subset of genes detected only in the full-length datasets tended to be longer. Conclusions: We find that the choice of scRNA-seq protocol influences the detection rate of genes, and that full-length datasets exhibit gene-length bias. In addition, despite clear differences between UMI and full-length transcript data, we illustrate that full-length and UMI data can be combined to reveal the underlying biology influencing expression of mESCs.


Genetics of Kawasaki disease: what we know and don't know.
Kawasaki disease (KD) is a leading cause of acquired heart disease in children in developed countries. Although it has been thought that symptoms of KD are related to hyperactivation of the immune system triggered by infection with some microorganisms, the etiological agent still remains unknown. In this situation, genetic factors underlying the disease pathogenesis, which have been suggested by epidemiological findings, are expected to be clues to the enigma. Recently, susceptibility genes for KD have been identified in succession by studies with a genome-wide approach. Recent advances in genetic studies for KD will be presented.


Risk stratification by the "EPA+DHA level" and the "EPA/AA ratio" focus on anti-inflammatory and antiarrhythmogenic effects of long-chain omega-3 fatty acids.
The identification of risks associated with sudden cardiac death requires further investigations. The question was addressed whether parameters can be established which not only describe an increased risk for an enhanced electrical instability of the heart but also of inflammatory events underlying plaque rupture. Emphasis is placed on dose-dependent effects of the long-chain omega-(omega-)3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Since free acids of EPA and DHA are required for most of their biological effects, it appears essential not only to build up stores in the body for release of these fatty acids, but also to provide a sustained uptake of EPA and DHA in the form of ethyl esters. In contrast to rapidly absorbed triacylglycerols from fish, ethyl esters are taken up more slowly within 24 h. For the administration of 1 g/day highly purified EPA+DHA ethyl esters (Omacor) to healthy volunteers, it is shown that EPA is increased from 0.6% to 1.4% within 10 days, while DHA is increased from 2.9% to 4.3%. After withdrawal, EPA and DHA approach baseline values within 10 days. A gas chromatographic procedure was established which requires only 10 microl of whole blood for the identification of more than 35 fatty acids. Evidence is summarized strengthening the concept that a low "EPA+DHA level" presents a risk for sudden cardiac death and that the administration of 840 mg/day of EPA+DHA ethyl esters raises the "EPA+DHA level" to approximately 6% that is associated with a marked protection from sudden cardiac death. For reducing pro-inflammatory eicosanoids and cytokines, a higher "EPA+DHA level" is required which can be achieved with an intake of 2-4 g/day of 84% EPA+DHA ethyl esters. For assessing influences from pro-inflammatory eicosanoids and cytokines, the EPA/arachidonic acid ratio ("EPA/AA ratio") was identified as diagnostic parameter. To assess the dietary EPA+DHA intake, fatty acids were determined in fish dishes of the cafeteria of the Philipps University Hospital Marburg, Germany. The EPA+DHA content of the popular Alaska Pollock was 125 +/- 70 mg/100 g. A once daily fish dish can thus not provide the 840 mg/day EPA+DHA administered in the GISSI Prevention Study in the form of ethyl ester which markedly reduced the risk of sudden cardiac death in postmyocardial infarction patients. Nonetheless, at least two preferably oily fish meals per week should be consumed as preventive measure by persons without coronary artery disease. With documented coronary heart disease, it was advised to consume approximately 1 g/day of EPA+DHA.


Mustela strandi (Mustelidae, Carnivora) from the Early Pleistocene of Crimea.
Abstract-The dentary of Mustela strandi Kormos, 1934 is described from the Lower Pleistocene deposits (Late Villafranchian, 1.8-1.5 Ma) of the Taurida cave in Crimea. It is the first finding of M. strandi in Russia. This extinct mustelid species is rarely found in the Lower and Middle Pleistocene of Central Europe.


Novel chemistry of invasive plants: exotic species have more unique metabolomic profiles than native congeners.
It is often assumed that exotic plants can become invasive when they possess novel secondary chemistry compared with native plants in the introduced range. Using untargeted metabolomic fingerprinting, we compared a broad range of metabolites of six successful exotic plant species and their native congeners of the family Asteraceae. Our results showed that plant chemistry is highly species-specific and diverse among both exotic and native species. Nonetheless, the exotic species had on average a higher total number of metabolites and more species-unique metabolites compared with their native congeners. Herbivory led to an overall increase in metabolites in all plant species. Generalist herbivore performance was lower on most of the exotic species compared with the native species. We conclude that high chemical diversity and large phytochemical uniqueness of the exotic species could be indicative of biological invasion potential.


Low serum adiponectin levels are predictive of advanced hepatic fibrosis in patients with NAFLD.
Adiponectin, an adipocytokine-mediating insulin action, has recently been found to be involved in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). The aim of this study was to assess possible associations between serum adiponectin levels and factors of the metabolic syndrome or histologic parameters in biopsy-proven NAFLD. Patients with persistently abnormal liver function tests satisfying inclusion criteria were subjected to liver biopsy. Fibrosis stage and the NAFLD activity score were recorded for each patient. Body mass index, waist-to-hip ratio, factors of the metabolic syndrome (central obesity, hyperglycemia, hypertriglyceridemia, low high-density lipoprotein, and hypertension), and biochemical tests were also recorded. Insulin resistance was calculated by the homeostasis model assessment method. Serum adiponectin concentration was measured by an enzyme-linked immunosorbent assay. Forty-two NAFLD patients, including 9 with compensated cirrhosis, were included in the study. The presence of each factor of the metabolic syndrome was associated with hypoadiponectinemia. Adiponectin negatively correlated with homeostasis model assessment (r=-0.551, P=0.001). Adiponectin concentration was negatively associated with higher stages of fibrosis (one-wayanalysis of variance, P=0.007), and was not associated with NAFLD activity score. Using multivariate logistic regression, adiponectin concentration, aspartate aminotransferase/alanine aminotransferase ratio, and the presence of waist-to-hip ratio >1 were independent predictors of advanced fibrosis. The receiver operating characteristic curve for detecting advanced fibrosis using a combination of the independent variables had an area under the curve of 0.902+/-0.054, P<0.0001. Low serum adiponectin levels in NAFLD patients are suggestive of advanced fibrosis. Therefore, assessment of serum adiponectin levels may be useful in clinical follow-up.


Genomic analysis of two rare human G3P[9] rotavirus strains in Ningxia, China.
G3P (Matthijnssens et al., 2008b [9]) is a rare combination of human rotavirus VP7/VP4 genotypes with a complex evolutionary pattern but limited related studies. Detailed genomic characterisation and genetic evolutionary analyses of G3P (Matthijnssens et al., 2008b [9]) rotaviruses have helped to enhance our understanding of rotavirus diversity. For the first time, we detected two human G3P (Matthijnssens et al., 2008b [9]) Rotavirus A (RVA) strains, RVA/Human-tc/CHN/2020999/2020/G3P (Matthijnssens et al., 2008b [9]) and RVA/Human-wt/CHN/23582009/2023/G3P (Matthijnssens et al., 2008b [9]), in diarrhoea patients from the Ningxia region of China, and carried out a whole-genome analysis of these strains. 2,020,999 and 23,582,009 have identical gene constellations: G3-P[9]-I2-R2-C2-M2-A3-N2-T3-E3-H3, and this genotypic constellation was reported first time in China. They are closely related in 11 genome segments. The genotypes of these two strains are different from the human RVA strains L621 and E2451, which are only G3P (Matthijnssens et al., 2008b [9]) strains reported so far in China, but are identical to those of the Thai feline strain Meesuk and the Korean human strain CAU12-2-51.Phylogenetic analysis showed that the VP6, VP1-VP3, and NSP2 genes of the two strains in this study clustered with human/bovine and feline/bovine rotavirus strains to form a sublineage distinct from the common DS-1-like G2 human rotavirus. In contrast, the VP7, VP4, NSP1, and NSP3-NSP5 gene segments were closely associated with human/feline rotavirus and feline rotavirus strains. These findings suggest that the evolutionary origin of the G3P (Matthijnssens et al., 2008b [9]) human rotavirus found in Ningxia, China, is consistent with the Meesuk and CAU12-2-51 strains, may have arisen through reassortment between uncommon human/bovine, feline/bovine rotavirus strains and human/feline, feline rotaviruses. However, VP1-VP2 gene segments did not have the same lineage as strains Meesuk and CAU12-2-51, suggesting that these genes might be derived from additional reassortment event.


Outcome of foot examinations in Tanzanian and Swedish diabetic patients, a comparative study.
The aim of the current study was to present the outcome of clinical nurse performed foot examinations in a group of Tanzanian diabetic patients and make comparisons with matched Swedish patients. Nurses working with diabetic patients in any country need to be familiar with foot problems in diabetic patients to educate patients about foot care. A comparative study examining diabetic patients in Tanzania and Sweden with a quantitative approach. One hundred and forty-five diabetic patients in each country were examined. They were matched in gender and age. All patients responded verbally to questions about individual foot-care and underwent clinical foot examination concerning existing foot lesions, sensitivity testing using Semmes-Weinstein monofilament (5.07) and, vibratory perception using a tuning fork (128 Hz). The Tanzanians had more reported foot problems than the Swedes. The latter reported problems due to poorly fitting footwear whilst the Tanzanians reported pain issues of the feet irrespective of footwear. In the Tanzanian group 37 patients presented with peripheral neuropathy (PN), 13 with peripheral vascular disease (PVD) and six had both PN and PVD. In the Swedish group of patients four had PN, three PVD, but none had both PN and PVD. Only 20 Tanzanians reported carrying out self-inspections of their feet, while 103 Swedes reported doing so. Nurse performed foot examinations showed that the Tanzanian diabetic patients in this study had poorer foot status than the Swedish study sample. Knowledge about foot problems in diabetic patients worldwide will hopefully improve education about self foot-care and therefore decrease incidence of foot lesions and other foot problems in this cohort.


Statin Use and Survival in Patients with Metastatic Castration-resistant Prostate Cancer Treated with Abiraterone Acetate.
Although statin use has been associated with favorable effects in various solid malignancies, no conclusive evidence is available at present. Statins are safe and inexpensive, and may synergize with novel antiandrogen agents abiraterone via pharmacokinetic interactions and decrease substrate availability for de novo androgen biosynthesis. To determine whether statin use affects survival in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with abiraterone. Medical records of patients with documented mCRPC between September 2011 and August 2016 were reviewed at multiple participating centers. This research was conducted in ten institutions, including both referral centers and local hospitals. A total of 187 patients receiving abiraterone for mCRPC between September 2011 and August 2016 were eligible for inclusion in this retrospective study. Patients were assessed for overall survival (OS), statin use at the time of treatment initiation, prostate-specific antigen (PSA) variations, and other variables of interest. Univariable and multivariable analysis was used to explore the association of variables of interest with OS and PSA declines. Statin use was a significant prognostic factor for longer OS in univariable (hazard ratio [HR] 0.51, 95% confidence interval [CI] 0.37-0.72; p<0.001) and multivariable analysis (HR 0.40, 95% CI 0.27-0.59; p<0.001) and was significantly associated with PSA declines (>50% decline at 12 wk: 72.1% in statin users vs 38.5% in non-users; p<0.001). Our study suggests a prognostic impact of statin use in patients receiving abiraterone for mCRPC. The mechanism of this interaction warrants elucidation, but may include enhancement of the antitumor activity of abiraterone as well as cardioprotective effects. We assessed the effects of statin use in patients with advanced prostate cancer receiving abiraterone. Patients treated with a statin plus abiraterone appeared to live longer than those treated with abiraterone only. Since no negative drug-drug interaction is known and statins are widely used and inexpensive, further studies assessing the use of abiraterone plus statins are warranted.


Application of the Subhuman Primate Pregnancy Test kit to pregnancy diagnosis in baboons.
The Subhuman Primate Pregnancy Test kit was used for diagnosis of pregnancy in 15 baboons. This hemagglutination inhibition test for urinary chorionic gonadotropin accurately indicated conception by positive responses in 106 of 109 specimens collected between 17 and 30 da after the estimated day of fertilization. Maximum hormone levels were reached during the middle of this 14-da interval. The rate of false positive and false negative results did not exceed 1%.


Isolated amnesia with slow onset and stable course, without ensuing dementia: MRI and PET data and a six-year neuropsychological follow-up.
Patient EDS presented with an amnesic disorder of insidious onset (4 years) that remained stable and restricted to memory functions over a 10-year course. Repeated neuropsychological evaluations over 6 years showed a moderate-to-severe, stable impairment of long-term memory and of memory for public events, and a milder, stable impairment of autobiographic memory and of short-term memory. Language, perception, praxis and 'frontal' functions were fully preserved. MRI showed atrophy of the right hippocampus, of the right mammillary body and of the sylvian fissure (bilaterally, but more marked on the left). On PET scan, metabolic activity in the mesial temporal structures was significantly reduced on the right and was at lower normal levels on the left. The disorder observed in EDS is similar to that recently reported in other patients. Possible etiologies of the selective amnesia observed in EDS are considered and their implications discussed.


Lymph flow in sheep with rapid cardiac ventricular pacing.
Increases in systemic venous pressure (Pv) associated with heart failure cause an increase in microvascular fluid filtration into the tissue spaces. By removing this excess filtrate from the tissues, lymphatic vessels help to prevent edema. However, the lymphatics drain into systemic veins and an increase in Pv may interfere with lymphatic flow. To test this, we cannulated caudal mediastinal node efferent lymphatics in sheep. We used rapid cardiac ventricular pacing (240-275 beats/min) to cause heart failure for 4-7 days. Each day we determined the lymph flow rate two ways. First, we adjusted the lymph cannula height so that the pressure at the outflow end of the lymphatic was zero. After we determined the lymph flow with zero outflow pressure, we raised the cannula so that outflow pressure was equal to the actual venous pressure. We quantitated the effect of venous pressure on lymph flow rate by comparing the flow rate with outflow pressure = Pv to the flow rate with zero out low pressure. At baseline, Pv = 5.0 +/- 2.5 (SD) cmH2O and we found no difference in the two lymph flow rates. Pacing caused Pv and both lymph flow rates to increase significantly. However for Pv < 15 cmH2O, we found little difference in the two lymph flow rates. Thus increases in Pv to 15 cmH2O at the outflow to the lymphatics had little effect on lymph flow. By comparison, Pv > 15 cmH2O slowed lymph flow by 55 +/- 29% relative to the lymph flow rate with zero outflow pressure. Thus Pv values > 15 cmH2O interfere with lymph flow from the sheep caudal mediastinal lymph node.


Water-Soluble Dual-Channel Fluorescent Probe for Sensitive Detection of Biothiols In Vitro and In Vivo.
Benefiting from high spatiotemporal resolution, deep tissue penetration, and excellent sensitivity, fluorescence imaging technology has been widely applied in cancer diagnosis and treatment. In recent years, a large number of fluorescent probes for monitoring the levels of endogenous biothiols have been reported, which have significant implications for cancer diagnosis and treatment. However, most probes still suffer from poor biological compatibility and easy attachment by the environment. This work presents the development of a water-soluble dual-channel fluorescent probe, named MAL-NBD, for sensitively detecting biothiols. Nonfluorescent MAL-NBD is transformed into fluorescent groups MAL and NBD-SR/NR through nucleophilic substitution by biologically active thiols, producing dual-channel fluorescence signals for precise detection of biologically active thiols. Taking advantage of the excellent biocompatibility and low biotoxicity, MAL-NBD is successfully used for imaging HeLa cancer cells and zebrafish larvae, promoting its potential application for the precise detection of biological thiols involved in physiological and pathological processes.


Small molecules targeting selected histone methyltransferases (HMTs) for cancer treatment: Current progress and novel strategies.
Histone methyltransferases (HMTs) play a critical role in gene post-translational regulation and diverse physiological processes, and are implicated in a plethora of human diseases, especially cancer. Increasing evidences demonstrate that HMTs may serve as a potential therapeutic target for cancer treatment. Thus, the development of HMTs inhibitor have been pursued with steadily increasing interest over the past decade. However, the disadvantages such as insufficient clinical efficacy, moderate selectivity, and propensity for acquired resistance have hindered the development of conventional HMT inhibitors. New technologies and methods are imperative to enhance the anticancer activity of HMT inhibitors. In this review, we first review the structure and biological functions of the several essential HMTs, such as EZH2, G9a, PRMT5, and DOT1L. The internal relationship between these HMTs and cancer is also expounded. Next, we mainly focus on the latest progress in the development of HMT modulators encompassing dual-target inhibitors, targeted protein degraders and covalent inhibitors from perspectives such as rational design, pharmacodynamics, pharmacokinetics, and clinical status. Lastly, we also discuss the challenges and future directions for HMT-based drug discovery for cancer therapy.


Beyond the COVID Pandemic, Telemedicine, and Health Care.
This article reviews the current experience and the flaws encountered in the rush to deploy telemedicine as a substitute for in-person care in response to the raging coronavirus (COVID-19) pandemic; the preceding fault lines in the U.S. health care system that exacerbated the problem; and the importance of emerging from this calamity with a clear vision for necessary health care reforms. It starts with the premise that the precursors of catastrophes of this magnitude provide a valid basis for planning corrective measures, improved preparedness, and ultimately serious health reform. Such reform should include standardized protocols for proper deployment of telemedicine to triage patients to the appropriate level and source of care at the point of need, proper use of relevant technological innovations to deliver precision medicine, and the development of regional networks to coordinate and improve access to care while streamlining the care process. The other essential element is a universal payment system that puts the United States at par with the rest of the industrialized countries, regardless of variation among them. The ultimate goal is creating an efficient, effective, accessible, and equitable system of care. Although timing is uncertain, the pandemic will be brought under control. The path to a better future after the pandemic offers some consolation for the massive loss of life and treasure during this pandemic.


The sixth rhino: a taxonomic re-assessment of the critically endangered northern white rhinoceros.
The two forms of white rhinoceros; northern and southern, have had contrasting conservation histories. The Northern form, once fairly numerous is now critically endangered, while the southern form has recovered from a few individuals to a population of a few thousand. Since their last taxonomic assessment over three decades ago, new material and analytical techniques have become available, necessitating a review of available information and re-assessment of the taxonomy. Dental morphology and cranial anatomy clearly diagnosed the southern and northern forms. The differentiation was well supported by dental metrics, cranial growth and craniometry, and corresponded with differences in post-cranial skeleton, external measurements and external features. No distinctive differences were found in the limited descriptions of their behavior and ecology. Fossil history indicated the antiquity of the genus, dating back at least to early Pliocene and evolution into a number of diagnosable forms. The fossil skulls examined fell outside the two extant forms in the craniometric analysis. Genetic divergence between the two forms was consistent across both nuclear and mitochondrial genomes, and indicated a separation of over a million years. On re-assessing the taxonomy of the two forms we find them to be morphologically and genetically distinct, warranting the recognition of the taxa formerly designated as subspecies; Ceratotherium simum simum the southern form and Ceratotherium simum cottoni the northern form, as two distinct species Ceratotherium simum and Ceratotherium cottoni respectively. The recognition of the northern form as a distinct species has profound implications for its conservation.


Hereditary pancreatic cancer.
Pancreatic cancer is one of the deadliest malignancies. Therefore, there is an urgent need to detect pancreatic cancer in an earlier stage to improve outcomes. A variety of hereditary cancer syndromes have been associated with an increased risk of developing pancreatic cancer, and these individuals may benefit from surveillance programs. Surveillance programs have shown potential to improve outcomes, but have important risks such as overtreatment. In this review we will discuss the definitions and epidemiology of hereditary pancreatic cancer, recommendations for genetic testing and participation in surveillance. Important aspects are differences in surveillance strategies, target lesions, and potential benefits and harms of surveillance. Lastly we will highlight future directions for research and improvement of care for individuals at high-risk of pancreatic cancer.


Teleretinal screening for diabetic retinopathy in six Los Angeles urban safety-net clinics: initial findings.
Diabetic retinopathy is a leading cause of blindness in US adults. This paper presents initial results of a teleretinal screening project for diabetic retinopathy involving six Los Angeles safety net clinics. A total of 1,943 patients have been screened for diabetic retinopathy by three ophthalmologist readers, with 416 receiving a recommendation for referral to specialty care. Of the cases recommended for referral, 24 had proliferative diabetic retinopathy, 62 had severe non-proliferative diabetic retinopathy (NPDR), 60 had moderate NPDR, 19 had mild NPDR, 138 had a non-diabetic condition, such as glaucoma, 63 had clinically significant macular edema without retinopathy and 50 had non-gradable images. Between 3% and 12.2% of retinal images taken at the clinics were assessed by readers as inadequate for any interpretation. The study shows the feasibility and challenges of teleretinal screening for diabetic retinopathy in urban areas facing specialist shortages and an overburdened, under-resourced safety net care-delivery system.


Expression of five selected human mismatch repair genes simultaneously detected in normal and cancer cell lines by a nonradioactive multiplex reverse transcription-polymerase chain reaction.
Abnormalities in at least 1 of 5 mismatch repair (MMR) genes (hMSH2, hMLH1, hPMS1, hPMS2 and GTBP/hMSH6) are found in hereditary nonpolyposis colon cancer and sporadic colon cancers. We used a single-reaction multiplex reverse transcription (RT)-polymerase chain reaction (PCR), with the beta-actin gene as an internal control, to simultaneously evaluate expression of these 5 known human MMR genes in normal and tumor cell lines with known or uncharacterized mutations in MMR genes. The relative quantitation of the transcripts is demonstrated by controlling the number of PCR cycles and titrating cDNA with a dose-curve. The 13 normal cell lines tested were derived from normal lymphocytes, skin, thymus, breast, lung, colon, liver and kidney. The 26 cancer cell lines were derived from melanoma and cancers of the brain, breast, lung, colon, pancreas and prostate. All 5 MMR genes were ubiquitously expressed in all normal cell lines tested, suggesting their housekeeping roles. Aberrant MMR gene expression was only observed in the colon cancer cell lines. Two previously uncharacterized colon cancer cell lines did not express hMLH1. These data suggest that this nonradioactive multiplex RT-PCR assay for MMR gene expression may be useful for fast screening for genetic alterations that may affect gene expression and so may aid molecular analysis of MMR-related colon cancer.


Salinity tolerance of Populus.
The genus Populus has a wide distribution in different climatic zones. Besides its economic and ecological relevance, Populus also serves as a model for elucidating physiological and molecular mechanisms of stress tolerance in tree species. In this review, adaptation strategies of poplars to excess soil salinity are addressed at different scales, from the cellular to the whole-plant level. Striking differences in salt tolerance exist among different poplar species and ecotypes, with Populus euphratica being outstanding in this respect. Key mechanisms identified in this species to mediate salt tolerance are compartmentalisation of Cl(-) in the vacuoles of the root cortex cells, diminished xylem loading of NaCl, activation of Na(+) extrusion into the soil solution under stress, together with simultaneously avoiding excessive K(+) loss by regulation of depolarisation-activated cation channels. This leads to improved maintenance of the K(+)/Na(+) balance, a crucial precondition for survival under salt stress. Leaf cells of this species are able to compartmentalise Na(+) preferentially in the apoplast, whereas in susceptible poplar species, as well as in crop plants, vacuolar Na(+) deposition precedes apoplastic transport. ABA, Ca(2+)and ROS are involved in stress sensing, with higher or faster activation of defences in tolerant than in susceptible poplar species. P. euphratica develops leaf succulence after prolonged salt exposure as a plastic morphological adaptation that leads to salt dilution. Transgenic approaches to improve salt tolerance by transformation of candidate genes have had limited success, since salt tolerance is a multigenic trait. In future attempts towards increased salt resistance, barriers between different poplar sections must be overcome and application of novel biotechnological tools, such as gene stacking, are recommended.


Specific methods for theophylline assay in biological samples.
The objective of monitoring theophylline plasma levels in therapeutic work is well established, and the consequences of using unspecific analytical methods are obvious. For the determination of pharmacokinetic parameters, concentrations far below the therapeutic range must often be measured. Interferences acceptable in therapeutic monitoring of theophylline could cause severe inaccuracy at these drug levels. The term specificity and its meaning are discussed in general and in relation to the different steps of the analytical procedure (e.g., sampling and sample work-up). Different analytical methods for theophylline are discussed in terms of specificity. Plasma concentrations of paraxanthine (1,7-dimethylxanthine)--a metabolite of caffeine--as high as 3 microgram/ml have been observed, and the compound can interfere in various theophylline assay methods. An example is given of the pharmacokinetic consequences.


Arresting calcium-regulated sperm metabolic dynamics enables prolonged fertility in poultry liquid semen storage.
The preservation of liquid semen is pivotal for both industrial livestock production and genetic management/conservation of species with sperm that are not highly cryo-tolerant. Nevertheless, with regard to poultry semen, even brief in vitro storage periods can lead to a notable decline in fertility, despite the in vivo capacity to maintain fertility for several weeks when within the hen's sperm storage tubules. For fertility in sperm, intracellular calcium ions ([Ca2+]i) play a key role in signaling towards modifying energy metabolism. While reducing [Ca2+]i has been found to enhance the preservation of sperm fertility in some mammals, the connection between semen fertility and calcium availability in avian sperm has received limited attention. In this study, we demonstrate that the use of extracellular and intracellular calcium chelators in liquid semen extenders, specifically EGTA and EGTA-AM, has distinct effects on prolonging the fertility of chicken sperm. These results were validated through in vivo fertility tests. Mechanistically, the effects observed were linked to coordination of mitochondrial metabolism and ATP catabolism. Despite both calcium chelators inducing hypoxia, they differentially regulated mitochondrial respiration and ATP accumulation. This regulation was closely linked to a bimodal control of dynein ATPase activity; a direct initial activation with reduction in [Ca2+]i, and subsequent suppression by cytoplasmic acidification caused by lactic acid. These findings not only contribute to advancing poultry liquid semen preservation techniques, but also elucidates biologically relevant mechanisms that may underlie storage within the female reproductive tract in birds.


A major role of the MEKK1-MKK1/2-MPK4 pathway in ROS signalling.
Over the last few years, it has become evident that reactive oxygen species (ROS) signalling plays an important role in various physiological responses, including pathogen defense and stomatal opening/closure. On the other hand, ROS overproduction is detrimental for proper plant growth and development, indicating that the regulation of an appropriate redox balance is essential for plants. ROS homeostasis in plants involves the mitogen-activated protein kinase (MAPK) pathway consisting of the MAPK kinase kinase MEKK1 and the MAPK MPK4. Phenotypic and molecular analysis revealed that the MAPK kinases MKK1 and MKK2 are part of a cascade, regulating ROS and salicylic acid (SA) accumulation. Gene expression analysis shows that of 32 transcription factors reported to be highly responsive to multiple ROS-inducing conditions, 20 are regulated by the MEKK1, predominantly via the MEKK1-MKK1/2-MPK4 pathway. However, MEKK1 also functions on other as yet unknown pathways and part of the MEKK1-dependent MPK4 responses are regulated independently of MKK1 and MKK2. Overall, this analysis emphasizes the central role of this MAPK cascade in oxidative stress signalling, but also indicates the high level of complexity revealed by this signalling network.


RTMS parameters in tinnitus trials: a systematic review.
Over the past few years extensive body of research was produced investigating the effects of repetitive transcranial magnetic stimulation (rTMS) for the treatment of chronic tinnitus with heterogeneous results. This heterogeneity is exemplified by two recently published large-scale clinical trials reporting different outcomes. Technical aspects of rTMS were suspected as a potential source for this incongruency. The aim of this systematic review is to examine the overall efficacy as well as to identify possible technical factors relevant for the effectiveness of rTMS tinnitus trials. Via a literature search appropriate original research papers were identified and rTMS parameters were extracted from each study arm for subsequent statistical analysis with respect to observed effects (significant vs. not significant pre-post rTMS effects). Our findings indicate that verum rTMS is superior to sham rTMS as demonstrated by the proportion of significant pre-post contrasts. Some relevant rTMS parameters (e.g., pulse waveform) are not reported. Lower rTMS stimulation intensity was associated with significant effects in verum rTMS arms. An additional stimulation of the DLPFC to the temporal cortex was not found to promote efficacy. Future research should consider differential effects of rTMS induced by technical parameters and strive for an exhaustive reporting of relevant rTMS parameters.


Outcomes of a NYC Public Hospital System Low-Threshold Tele-Buprenorphine Bridge Clinic at 1 Year.
Background: This study evaluated clinical outcomes of a low barrier tele-buprenorphine bridge program for NYC residents with opioid use disorder (OUD) at 1 year during the coronavirus disease 2019 (COVID-19) pandemic. Methods and materials: This retrospective analysis of the NYC Health + Hospitals (NYC H + H) Virtual Buprenorphine Clinic registry assessed baseline demographic and clinical characteristics, rates of referrals to community treatment, and induction-related adverse events among city residents with OUD, from March 2020 to the end of March 2021. Results: The program enrolled 199 patients, of whom 62.3% were provided same-day visits (n = 124). Patients were enrolled in the program for a median of 14 days (range 0-130 days). Referrals sources included hospital and clinic staff (n = 83, 47.7%), word of mouth (n = 30, 17.2%), and correctional health or reentry services (n = 30, 17.2%). Induction-related adverse events were mostly limited to precipitated withdrawal symptoms (n = 21, 5%). Roughly half of patients were referred to community treatment (n = 109, 54.8%) and of those 51.4% (n = 56/109) completed at least one visit in community treatment. Discussion: Our experience indicates that a low threshold tele-buprenorphine bridge program in place of a safe and feasible approach to facilitating entry in community treatment for underserved people who use opioids in a large metropolitan area.


Single-cell RNA-seq and computational analysis using temporal mixture modelling resolves Th1/Tfh fate bifurcation in malaria.
Differentiation of naïve CD4+ T cells into functionally distinct T helper subsets is crucial for the orchestration of immune responses. Due to extensive heterogeneity and multiple overlapping transcriptional programs in differentiating T cell populations, this process has remained a challenge for systematic dissection in vivo. By using single-cell transcriptomics and computational analysis using a temporal mixtures of Gaussian processes model, termed GPfates, we reconstructed the developmental trajectories of Th1 and Tfh cells during blood-stage Plasmodium infection in mice. By tracking clonality using endogenous TCR sequences, we first demonstrated that Th1/Tfh bifurcation had occurred at both population and single-clone levels. Next, we identified genes whose expression was associated with Th1 or Tfh fates, and demonstrated a T-cell intrinsic role for Galectin-1 in supporting a Th1 differentiation. We also revealed the close molecular relationship between Th1 and IL-10-producing Tr1 cells in this infection. Th1 and Tfh fates emerged from a highly proliferative precursor that upregulated aerobic glycolysis and accelerated cell cycling as cytokine expression began. Dynamic gene expression of chemokine receptors around bifurcation predicted roles for cell-cell in driving Th1/Tfh fates. In particular, we found that precursor Th cells were coached towards a Th1 but not a Tfh fate by inflammatory monocytes. Thus, by integrating genomic and computational approaches, our study has provided two unique resources, a database www.PlasmoTH.org, which facilitates discovery of novel factors controlling Th1/Tfh fate commitment, and more generally, GPfates, a modelling framework for characterizing cell differentiation towards multiple fates.


Neotropical primary bat cell lines show restricted dengue virus replication.
Dengue is the most widespread arboviral disease affecting humans. Bats are recognized carriers of emerging viral zoonoses and have been proposed as dengue reservoirs, since RNA/NS1 and/or antiviral antibodies have been detected. Yet, experimental inoculation of Artibeus bats failed to show virus replication. This conflicting results prevent drawing further conclusions of whether bats sustain dengue infection. To test bat cellular permissivity to dengue infection, we established primary bat embryonic cells from diverse organs and tissues of Artibeus jamaicensis, Molossus sinaloae, and Desmodus rotundus. We observed a limited serotype-, organ-, and bat species- specific dengue susceptibility. Only some Molossus-derived primary cells sustained poorly initial Dengue serotype-1 replication, though it was latter absent. To elucidate if Molossus bats may play a role in dengue replication, ecological or in vivo experiments must be performed. Taken together our results show that Dengue did not replicate efficiently in cell lines derived from Neotropical bat species.


[Orphan drugs].
The paper discusses the problems of orphan drugs from the standpoint of the attitude of state authorities in the USA, Japan, and particularly Europe (the European Union) to their definition and the formation of appropriate legislation--financial provision for the development, production, provision of exclusive sale rights--which warranties the availability of the drug to every patient suffering from a rare disease.


The impact of the 2006 Massachusetts health care reform law on spine surgery patient payer-mix status and age.
OBJECTIVE Several similarities exist between the Massachusetts health care reform law of 2006 and the Affordable Care Act (ACA). The authors' prior neurosurgical research showed a decrease in uninsured surgeries without a significant change in surgical volume after the Massachusetts reform. An analysis of the payer-mix status and the age of spine surgery patients, before and after the policy, should provide insight into the future impact of the ACA on spine surgery in the US. METHODS Using the Massachusetts State Inpatient Database and spine ICD-9-CM procedure codes, the authors obtained demographic information on patients undergoing spine surgery between 2001 and 2012. Payer-mix status was assigned as Medicare, Medicaid, private insurance, uninsured, or other, which included government-funded programs and workers' compensation. A comparison of the payer-mix status and patient age, both before and after the policy, was performed. The New York State data were used as a control. RESULTS The authors analyzed 81,821 spine surgeries performed in Massachusetts and 248,757 in New York. After 2008, there was a decrease in uninsured and private insurance spine surgeries, with a subsequent increase in the Medicare and "other" categories for Massachusetts. Medicaid case numbers did not change. This correlated to an increase in surgeries performed in the age group of patients 65-84 years old, with a decrease in surgeries for those 18-44 years old. New York showed an increase in all insurance categories and all adult age groups. CONCLUSIONS After the Massachusetts reform, spine surgery decreased in private insurance and uninsured categories, with the majority of these surgeries transitioning to Medicare. Moreover, individuals who were younger than 65 years did not show an increase in spine surgeries, despite having greater access to health insurance. In a health care system that requires insurance, the decrease in private insurance is primarily due to an increasing elderly population. The Massachusetts model continues to show that this type of policy is not causing extreme shifts in the payer mix, and suggests that spine surgery will continue to thrive in the current US health care system.


Yanhusuo extract inhibits metastasis of breast cancer cells by modulating mitogen-activated protein kinase signaling pathways.
Yanhusuo (Corydalis yanhusuo W.T. Wang) is a well-known traditional Chinese medicine (TCM). In this study, we attempted to characterize in detail the signaling cascades that produce its anti-metastatic effect on the human breast cancer cell line, MDA-MB-231. We found that the yanhusuo extract inhibited the migration and invasion of MDA-MB-231 cells in vitro. In addition, the yanhusuo extract inhibited the mRNA expression and activity of metalloproteinase-9 (MMP-9). The anti-cancer metastasis effect of yanhusuo involved the activation of p38 and inhibition of ERK1/2 and SAPK/JNK mitogen-activated protein kinase (MAPK) signaling. Our experiments identified the biological activity of yanhusuo against cancer metastasis in vitro and provide a rationale for its further investigation.


Invited commentary: comparing physical activity across countries--current strengths and weaknesses.
Physical activity is thought to be important for various health outcomes, but population levels are suspected to be low. There is a lack of large-scale comparable data with which to assess temporal trends and make between-population comparisons. Continued increases in the use of objective monitoring, especially in longitudinal studies, would be very valuable in public health research, and both self-reported and objective data may help to start developing explanations regarding any observed population differences. There is much scope for more international surveillance of physical activity levels using historically comparable measurement tools, as well as making current data available for reanalysis. The continued use of objective measurement tools with transparent research protocols and data reduction strategies would also be beneficial for future research. Prospective objective physical activity data across different countries would allow us to learn from areas successful in maintaining or even increasing population physical activity levels. Physical activity surveillance using objective measures is needed worldwide, not only in Western countries but also in developing countries, as obesity and related metabolic disorders are a global problem, and it is therefore appropriate that the solution is similarly large scale in nature.


Evaluation of a nurse-care management system to improve outcomes in patients with complicated diabetes.
This study evaluated the efficacy of a nurse-care management system designed to improve outcomes in patients with complicated diabetes. In this randomized controlled trial that took place at Kaiser Permanente Medical Center in Santa Clara, CA, 169 patients with longstanding diabetes, one or more major medical comorbid conditions, and HbA(lc) >10% received a special intervention (n = 84) or usual medical care (n = 85) for 1 year. Patients met with a nurse-care manager to establish individual outcome goals, attended group sessions once a week for up to 4 weeks, and received telephone calls to manage medications and self-care activities. HbA(lc), LDL, HDL, and total cholesterol, triglycerides, fasting glucose, systolic and diastolic blood pressure, BMI, and psychosocial factors were measured at baseline and 1 year later. Annualized physician visits were determined for the year before and during the study. At 1 year, the mean reductions in HbA(lc), total cholesterol, and LDL cholesterol were significantly greater for the intervention group compared with the usual care group. Significantly more patients in the intervention group met the goals for HbA(1c) (<7.5%) than patients in usual care (42.6 vs. 24.6%, P < 0.03, chi(2)). There were no significant differences in any of the psychosocial variables or in physician visits. A nurse-care management program can significantly improve some medical outcomes in patients with complicated diabetes without increasing physician visits.


Early recognition of bovine respiratory disease in calves using automated continuous monitoring of cough sounds.
Bovine respiratory disease (BRD) complex in calves impairs health and welfare and causes severe economic losses for the Stockperson. Early recognition of BRD should lead to earlier veterinary (antibiotic/anti-inflammatory) treatment interventions thereby reducing the severity of the disease and associated costs. Coughing is one of the clinical manifestations of BRD. It is believed that by automatically and continuously monitoring the sounds within calf houses, and analysing the coughing frequency, early recognition of BRD in calves is possible. Therefore, the objective of the present study was to develop an automated calf cough monitor and examine its potential as an early warning system for BRD in artificially reared dairy calves. The coughing sounds of 62 calves were continuously recorded by a microphone over a three-month period. A sound analysis algorithm was developed to distinguish calf coughs from other sounds (e.g. mechanical sounds). During the sound recording period the health of the calves was assessed and scored periodically per week by a trained human observer. Calves presenting with BRD received antibiotic and/or anti-inflammatory treatment and the dates of treatment were recorded. This treatment date reference served as a comparison for the investigation of whether an increase in coughing frequency could be related to calves developing BRD. The calf cough detection algorithm achieved 50.3% sensitivity, 99.2% specificity and 87.5% precision. Four out of five periods, where coughing frequency was observed to be increased, coincided with the development of BRD in more than one calf. This period of increased coughing frequency was always observed before the calves were treated. Therefore, the calf cough monitor has the potential to identify early onset of BRD in calves.


A New Projection From the Deep Cerebellar Nuclei to the Hippocampus via the Ventrolateral and Laterodorsal Thalamus in Mice.
The cerebellar involvement in cognitive functions such as attention, language, working memory, emotion, goal-directed behavior and spatial navigation is constantly growing. However, an exact connectivity map between the hippocampus and cerebellum in mice is still unknown. Here, we conducted a tracing study to identify the sequence of transsynaptic, cerebellar-hippocampal connections in the mouse brain using combinations of Recombinant adeno-associated virus (rAAV) and pseudotyped deletion-mutant rabies (RABV) viruses. Stereotaxic injection of a primarily anterograde rAAV-WGA (wheat germ agglutinin)-Cre tracer virus in the deep cerebellar nuclei (DCN) of a Cre-dependent tdTomato reporter mouse resulted in strong tdTomato labeling in hippocampal CA1 neurons, retrosplenial cortex (RSC), rhinal cortex (RC) as well as thalamic and cerebellar areas. Whereas hippocampal injections with the retrograde tracer virus rAAV-TTC (tetanus toxin C fragment)-eGFP, displayed eGFP positive cells in the rhinal cortex and subiculum. To determine the sequence of mono-transsynaptic connections between the cerebellum and hippocampus, we used the retrograde tracer RABVΔG-eGFP(EnvA). The tracing revealed a direct connection from the dentate gyrus (DG) in the hippocampus to the RSC, RC and subiculum (S), which are monosynaptically connected to thalamic laterodorsal and ventrolateral areas. These thalamic nuclei are directly connected to cerebellar fastigial (FN), interposed (IntP) and lateral (Lat) nuclei, discovering a new projection route from the fastigial to the laterodorsal thalamic nucleus in the mouse brain. Collectively, our findings suggest a new cerebellar-hippocampal connection via the laterodorsal and ventrolateral thalamus to RSC, RC and S. These results strengthen the notion of the cerebellum's involvement in cognitive functions such as spatial navigation via a polysynaptic circuitry.


Hydroxysafflor Yellow A Attenuates the Apoptosis of Peripheral Blood CD4+ T Lymphocytes in a Murine Model of Sepsis.
Sepsis is generally considered as a severe condition of inflammation that leads to lymphocyte apoptosis and multiple organ dysfunction. Hydroxysafflor yellow A (HSYA) exerts anti-inflammatory and anti-apoptotic effects in infectious diseases. However, the therapeutic effect of HSYA on polymicrobial sepsis remains unknown. This study was undertaken to investigate the therapeutic effects and the mechanisms of action of HSYA on immunosuppression in a murine model of sepsis induced by cecal ligation and puncture (CLP). NIH mice were randomly divided into four groups: control group, sham group, CLP group, and CLP+HSYA group. HSYA (120 mg/kg) was intravenously injected into experimental mice at 12 h before CLP, concurrent with CLP and 12 h after CLP. The levels of circulating inflammatory cytokines, the apoptosis of CD4+ and CD8+ T lymphocytes, and protein expression of cytochrome C (Cytc), Bax, Bcl-2, cleaved caspase-9, and cleaved caspase-3 were examined. Plasma levels of IL-6, IL-10 and TNF-alpha as well as the apoptosis of CD4+ T lymphocytes were increased compared with sham group. These changes were accompanied by increases of pro-apoptotic proteins including Cytc, Bax, cleaved caspase-9, and cleaved caspase-3 and decreases of anti-apoptotic protein Bcl-2 in CD4+ T lymphocytes from mice undergoing CLP. In contrast, we fail to observe significant effect of HSYA on the apoptosis of CD8+ T lymphocytes in CLP-treated group. Of note, HSYA treatment reversed all above changes observed in CD4+ T lymphocytes, and significantly increased the ratio of CD4+:CD8+ T lymphocytes in CLP-treated mice. In conclusion, HSYA was an effective therapeutic agent in ameliorating sepsis-induced apoptosis of CD4+ T lymphocytes probably through its anti-inflammatory and anti-apoptotic effects.


Diffusion of HEMA from resin cements through different dentin thicknesses in vitro.
To evaluate the in vitro diffusion of 2-hydroxyethyl methacrylate (HEMA) from the resin cements through different thicknesses of dentin using high-performance liquid chromatography (HPLC) at two time intervals. 60 freshly extracted caries- and restoration-free human third molar teeth were used in this study. Standardized box-shaped Class I inlay cavities (6 mm long, 3 mm wide and 2 mm deep) were prepared in all teeth with a high-speed handpiece mounted on a standard cavity machine. The remaining dentin thickness (RDT) between the pulpal wall of the cavity and the roof of the pulp chamber was measured at multiple points for each tooth so that two main groups of 30 teeth each were prepared with an RDT range 0.5-1.9 and 2.0-3.5 mm, respectively. Each of these main groups was divided into three subgroups (n = 10), according to the resin cements tested (RelyX ARC, Panavia F 2.0, Multilink Automix). Lithium disilicate-based ceramic inlays (IPS Empress 2) were manufactured to restore the prepared cavities. A polypropylene chamber containing 1 ml distilled water was attached to the cemento-enamel junction of each tooth. Then, ceramic inlays were cemented with resin cements according to the manufacturers' instructions. Water elutes were analyzed by HPLC at 4.32 minutes and 24 hours. HEMA diffusion amounts were analyzed using three-way ANOVA and Tukey's HSD tests (P < 0.05). HEMA was detected in the pulp chamber elutes of all the teeth. The amounts of released HEMA did not significantly differ between time periods. The diffused HEMA amounts were significantly different between the RDT of 0.5-1.9 and 2.0-3.5 mm (P < 0.05) and between resin cements tested (P < 0.05). Decreasing RDT substantially increased the amount of HEMA that diffused through the dentin to the pulp space.


The Dutch Hip and Groin Outcome Score: Cross-cultural Adaptation and Validation According to the COSMIN Checklist.
Study Design Clinical measurement. Background The Copenhagen Hip and Groin Outcome Score (HAGOS) was developed as a patient-reported outcome measure for young, active individuals with hip and groin pain. Objectives To cross-culturally adapt and validate a Dutch version of the HAGOS. Methods Adaptation and validation were performed according to existing guidelines and the COnsensus-based Standards for the selection of health Measurement INstruments checklist. Physically active (Tegner activity score of greater than 2) adults between 18 and 50 years of age with hip and groin pain (numeric pain score of 1 or greater) were included in the study. Reliability (test-retest, internal consistency) was assessed in clinically stable patients. Construct validity was determined by calculating Spearman correlations between the scores on the HAGOS and scores on the Hip disability and Osteoarthritis Outcome Score and European Quality of Life-5 Dimensions subscales. Fifteen hypotheses were defined a priori. Interpretability was considered good when floor and ceiling effects were present in less than 15% of individuals. Results A Dutch version of the HAGOS was created. Its reliability was tested in 129 individuals and its validity in 194 participants. Test-retest reliability was good (intraclass correlation coefficient = 0.83-0.87). Internal consistency was good (Cronbach α = .81-.92). Construct validity was considered good: 13 of 15 (87%) hypotheses were confirmed. Floor effects (21%) were present for the physical activity subscale. Conclusion The Dutch HAGOS is a reliable and valid patient-reported outcome measure and performs similarly to the original version in its target population. It can be used in clinical as well as research settings. Presence of floor effects should be considered for the physical activity subscale. J Orthop Sports Phys Ther 2018;48(4):299-306. doi:10.2519/jospt.2018.7883.


The role of the mammalian DNA end-processing enzyme polynucleotide kinase 3'-phosphatase in spinocerebellar ataxia type 3 pathogenesis.
DNA strand-breaks (SBs) with non-ligatable ends are generated by ionizing radiation, oxidative stress, various chemotherapeutic agents, and also as base excision repair (BER) intermediates. Several neurological diseases have already been identified as being due to a deficiency in DNA end-processing activities. Two common dirty ends, 3'-P and 5'-OH, are processed by mammalian polynucleotide kinase 3'-phosphatase (PNKP), a bifunctional enzyme with 3'-phosphatase and 5'-kinase activities. We have made the unexpected observation that PNKP stably associates with Ataxin-3 (ATXN3), a polyglutamine repeat-containing protein mutated in spinocerebellar ataxia type 3 (SCA3), also known as Machado-Joseph Disease (MJD). This disease is one of the most common dominantly inherited ataxias worldwide; the defect in SCA3 is due to CAG repeat expansion (from the normal 14-41 to 55-82 repeats) in the ATXN3 coding region. However, how the expanded form gains its toxic function is still not clearly understood. Here we report that purified wild-type (WT) ATXN3 stimulates, and by contrast the mutant form specifically inhibits, PNKP's 3' phosphatase activity in vitro. ATXN3-deficient cells also show decreased PNKP activity. Furthermore, transgenic mice conditionally expressing the pathological form of human ATXN3 also showed decreased 3'-phosphatase activity of PNKP, mostly in the deep cerebellar nuclei, one of the most affected regions in MJD patients' brain. Finally, long amplicon quantitative PCR analysis of human MJD patients' brain samples showed a significant accumulation of DNA strand breaks. Our results thus indicate that the accumulation of DNA strand breaks due to functional deficiency of PNKP is etiologically linked to the pathogenesis of SCA3/MJD.


The Effect of SARS-CoV-2 Spike Protein RBD-Epitope on Immunometabolic State and Functional Performance of Cultured Primary Cardiomyocytes Subjected to Hypoxia and Reoxygenation.
Cardio complications such as arrhythmias and myocardial damage are common in COVID-19 patients. SARS-CoV-2 interacts with the cardiovascular system primarily via the ACE2 receptor. Cardiomyocyte damage in SARS-CoV-2 infection may stem from inflammation, hypoxia-reoxygenation injury, and direct toxicity; however, the precise mechanisms are unclear. In this study, we simulated hypoxia-reoxygenation conditions commonly seen in SARS-CoV-2-infected patients and studied the impact of the SARS-CoV-2 spike protein RBD-epitope on primary rat cardiomyocytes to gain insight into the potential mechanisms underlying COVID-19-related cardiac complications. Cell metabolic activity was evaluated with PrestoBlueTM. Gene expression of proinflammatory markers was measured by qRT-PCR and their secretion was quantified by Luminex assay. Cardiomyocyte contractility was analysed using the Myocyter plugin of ImageJ. Mitochondrial respiration was determined through Seahorse Mito Stress Test. In hypoxia-reoxygenation conditions, treatment of the SARS-CoV-2 spike RBD-epitope reduced the metabolic activity of primary cardiomyocytes, upregulated Il1β and Cxcl1 expression, and elevated GM-CSF and CCL2 cytokines secretion. Contraction time increased, while amplitude and beating frequency decreased. Acute treatment with a virus RBD-epitope inhibited mitochondrial respiration and lowered ATP production. Under ischaemia-reperfusion, the SARS-CoV-2 RBD-epitope induces cardiomyocyte injury linked to impaired mitochondrial activity.


[Renal handling of 3,5,3'-triiodothyronine (T3) in the dog studied by stopflow analysis].
In order to investigate the renal handling of 3,5,3'-triiodothyronine (T3), we studied the clearance of T3 (CT3) in dogs and the site of tubular secretion and reabsorption of T3 in dog kidney using the stopflow technique (Malvin et al.). Four female dogs, weighing between 12.2 and 17.8 kg, were used for CT3 measurement. Fourteen anesthetized dogs, weighing between 7.8 and 17.5 kg, were used for the stopflow study. After the catheter was inserted into the left ureter, 15% mannitol solution and isotonic saline containing both 0.2% PSP and 0.5% creatinine or 0.1% inulin, were infused and then 10-30 micrograms/kg of T3 or 100 micrograms/kg of T4 was injected as a bolus. When the urine flow reached a stable state of at least 5 ml/min about one-hr after T3 or T4 injection, the ureteral catheter was clamped shut for 10 min. After the release of the clamp, 20 fractions of urine, 1 ml each, were collected sequentially. The changes in pH and PSP concentrations were used as indices of urine from the distal and proximal tubules, respectively. Urinary T3 was determined by RIA. CT3 was obtained by calculating the ratio of the 24-hr urinary T3 excretion to the serum free T3 concentration. CT3, 51.9 +/- 12.3 ml/min, was greater than the clearance of creatinine (Ccr), 23.8 +/- 4.7 ml/min, suggesting that T3 is secreted at the tubules in dogs. Almost immediately after the release of the clamped ureter, the concentration of urinary T3, corrected with excreted urinary creatinine or inulin, was increased, reaching the maximum value at No. 2 or 3 fraction. This maximum urinary T3 value was followed by decreased concentrations of urinary T3, reaching the minimum around No. 13--15 fraction. The fraction with the highest urinary T3 concentration was close to the one with the lowest pH, and the fraction with the lowest urinary T3 concentration was close to the one with the highest PSP concentration. These data suggest that T3 might be reabsorbed or metabolized at the level of the proximal tubules and secreted into the urine at the level of the distal tubules.


Poor parenting and antisocial behavior among homeless young adults: links to dating violence perpetration and victimization.
Though research has examined risk factors associated with street victimization among homeless young people, little is known about dating violence experiences among this group. Given homeless youths' elevated rates of child maltreatment, it is likely that they are at high risk for dating violence. As such, the current study examined the association between child maltreatment and parental warmth with dating violence perpetration and victimization through substance use and delinquency among a sample of 172 homeless males and females. Results from path analysis revealed that physical abuse, sexual abuse, and neglect were all significant correlates of both substance use and delinquency, whereas lack of parental warmth was only associated with substance use. Neglect and substance use had direct effects on dating violence and substance use and was found to mediate the relationship between physical abuse and dating violence. Finally, females, older youth, and non-Whites had significantly higher levels of dating violence compared with their counterparts.


Introducing high-cost health care to patients: dentists' accounts of offering dental implant treatment.
The decision-making process within health care has been widely researched, with shared decision-making, where both patients and clinicians share technical and personal information, often being cited as the ideal model. To date, much of this research has focused on systems where patients receive their care and treatment free at the point of contact (either in government-funded schemes or in insurance-based schemes). Oral health care often involves patients making direct payments for their care and treatment, and less is known about how this payment affects the decision-making process. It is clear that patient characteristics influence decision-making, but previous evidence suggests that clinicians may assume characteristics rather than eliciting them directly. The aim was to explore the influences on how dentists' engaged in the decision-making process surrounding a high-cost item of health care, dental implant treatments (DITs). A qualitative study using semi-structured interviews was undertaken using a purposive sample of primary care dentists (n = 25). Thematic analysis was undertaken to reveal emerging key themes. There were differences in how dentists discussed and offered implants. Dentists made decisions about whether to offer implants based on business factors, professional and legal obligations and whether they perceived the patient to be motivated to have treatment and their ability to pay. There was evidence that assessment of these characteristics was often based on assumptions derived from elements such as the appearance of the patient, the state of the patient's mouth and demographic details. The data suggest that there is a conflict between three elements of acting as a healthcare professional: minimizing provision of unneeded treatment, trying to fully involve patients in shared decisions and acting as a business person with the potential for financial gain. It might be expected that in the context of a high-cost healthcare intervention for which patients pay the bill themselves, that decision-making would be closer to an informed than a paternalistic model. Our research suggests that paternalistic decision-making is still practised and is influenced by assumptions about patient characteristics. Better tools and training may be required to support clinicians in this area of practice.


Abusive head trauma in children: a comparison of male and female perpetrators.
To evaluate the effect of perpetrator gender on victim presentation and outcomes, and perpetrator legal outcomes for abusive head trauma (AHT). We performed a retrospective chart review of AHT cases from 1998 to 2008. Patient clinical data and information regarding perpetrator legal outcome was obtained. Relationship of brain injury and retinal hemorrhages (RHs) and differences in categorical variables of perpetrator gender were compared by using Fisher's exact test. Differences in continuous variables between perpetrator gender were compared by using the Mann-Whitney Test. There were 34 cases of AHT with identified perpetrators, 17 of each gender. Mean age of the victims was 9.4 months (SD: 7.8). Thirty-two (94%) had intracranial hemorrhages, 14 (41%) had both primary and secondary brain injury, 28 (82%) had RHs, and 6 (18%) died. The severity of RH was related to the severity of brain injuries (P = .01). The median age for female perpetrators (34 years) was higher than that for males (27 years; P = .001). Six categorical variables were associated with male perpetrator gender: acute presenting symptoms of cardiopulmonary or respiratory arrest (P = .025), worse clinical outcome (P = .012), neurosurgical intervention (P = .037), death (P = .018), perpetrator confession (P = .0001), and conviction (P = .005). There were significant perpetrator gender differences of AHT in children. Male perpetrators were younger and more likely to confess and be convicted. Victims of male perpetrators had more serious acute presentations and neurosurgical intervention and suffered worse clinical outcomes.


Transient HIF2A inhibition promotes satellite cell proliferation and muscle regeneration.
The remarkable regeneration capability of skeletal muscle depends on the coordinated proliferation and differentiation of satellite cells (SCs). The self-renewal of SCs is critical for long-term maintenance of muscle regeneration potential. Hypoxia profoundly affects the proliferation, differentiation, and self-renewal of cultured myoblasts. However, the physiological relevance of hypoxia and hypoxia signaling in SCs in vivo remains largely unknown. Here, we demonstrate that SCs are in an intrinsic hypoxic state in vivo and express hypoxia-inducible factor 2A (HIF2A). HIF2A promotes the stemness and long-term homeostatic maintenance of SCs by maintaining their quiescence, increasing their self-renewal, and blocking their myogenic differentiation. HIF2A stabilization in SCs cultured under normoxia augments their engraftment potential in regenerative muscle. Conversely, HIF2A ablation leads to the depletion of SCs and their consequent regenerative failure in the long-term. In contrast, transient pharmacological inhibition of HIF2A accelerates muscle regeneration by increasing SC proliferation and differentiation. Mechanistically, HIF2A induces the quiescence and self-renewal of SCs by binding the promoter of the Spry1 gene and activating Spry1 expression. These findings suggest that HIF2A is a pivotal mediator of hypoxia signaling in SCs and may be therapeutically targeted to improve muscle regeneration.


Bacterial Concentration Detection using a PCB-based Contactless Conductivity Sensor.
Capacitively coupled contactless conductivity detection (C⁴D) is an improved approach to avoid the problems of labor-intensive, time-consuming and insufficient accuracy of plate count as well as the high-cost apparatus of flow cytometry (FCM) in bacterial counting. This article describes a novel electrode-integrated printed-circuit-board (PCB)-based C⁴D device, which supports the simple and safe exchange of capillaries and improves the sensitivity and repeatability of the contactless detection. Furthermore, no syringe pump is needed in the detection, it reduces the system size, and, more importantly, avoids the effect on the bacteria due to high pressure. The recovered bacteria after C⁴D detection at excitation of 25 Vpp and 60⁻120 kHz were analyzed by flow cytometry, and a survival rate higher than 96% was given. It was verified that C⁴D detection did not influence the bacterial viability. Moreover, bacteria concentrations from 10⁶ cells/mL to 10⁸ cells/mL were measured in a linear range, and relative standard deviation (RSD) is below 0.2%. In addition, the effects on bacteria and C⁴D from background solutions were discussed. In contrast to common methods used in most laboratories, this method may provide a simple solution to in situ detection of bacterial cultures.


Bringing the brain into personality assessment: Is there a place for event-related potentials?
Advances in technology have provided opportunities to assess physiological correlates and further our understanding of a number of constructs, including personality traits. Event-related potentials (ERPs), scalp-recorded measures of brain activity with millisecond temporal resolution, show properties that make them potential candidates for integrating neurophysiological methods into personality research. Several commonly used ERPs have trait-like properties including test-retest stability approaching .8 over two weeks. Additionally, ERP methods are relatively inexpensive and tolerable compared to other neurophysiological methods (e.g., functional magnetic resonance imaging [fMRI]) making them easier to obtain sample sizes required for individual differences research. Finally, the tasks that elicit ERPs are flexible enough to allow researchers to customize the tasks to the psychological constructs of interest. These factors suggest that ERPs could potentially be useful in the study of personality and individual differences. A baseline approach to this line of inquiry is to examine the properties of ERPs as neurophysiological individual differences markers and probe their links to personality traits as assessed by self-report questionnaires. This article does this for three well-studied ERPs. Techniques commonly used in personality assessment research-but rarely in ERP research-were applied to these candidate ERPs to examine their psychometric properties and personality correlates. Overall, although ERPs show promising properties as neurophysiological indicators of individual differences, they were only marginally related with existing personality traits. Further research clarifying the ERPs measurement properties and potential links with known personality processes is needed. Finally, we list some strategies to further integrate these two areas of research. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


Roseomonas wenyumeiae sp. nov., isolated from faeces of Tibetan antelopes (Pantholops hodgsonii) on the Qinghai-Tibet Plateau.
Two Gram-stain-negative, catalase- and oxidase-positive, non-spore-forming, aerobic, motile, flagellated, and coccus-shaped strains (Z23T and Z24) were isolated from faeces of Tibetan antelopes (Pantholops hodgsonii) on the Qinghai-Tibet Plateau, PR China. Results of the morphological, biochemical, and phylogenetic studies indicated that they were similar to each other, but distinct from existing species of the genus Roseomonas. The proposed type strain, Z23T, had 97.8, 97.1 and 96.8 % 16S rRNA similarity to Roseomonas ludipueritiae DSM 14915T, Roseomonas aerofrigidensis JCM 31878T and Roseomonas aerophila KACC 16529T. Results from further phylogenetic analyses based on the 16S rRNA gene and 857 core genes indicated that the two strains were members of Roseomonas, but clearly separated from the currently recognized species. Strains Z23T had 43.8 %, 25.0 % DNA-DNA relatedness and 91.2, 81.3 % ANI values with R. ludipueritiae DSM 14915T and R. aerophila KACC 16529T. The genomic DNA G+C content of strain Z23T was 68.6 mol%. The major cellular fatty acids of strain Z23T were C18 : 1ω7c and/or C18 : 1ω6c and C19 : 0cyclo ω8c. The cell-wall sugars included glucose, rhamnose and ribose. Q-10 was the sole respiratory quinone, and spermidine was the major polyamine component. Polar lipids present in strain Z23T were phosphatidylcholine, diphosphatidylglycerol, phosphatidylethanolamine, aminophospholipid, phosphatidylglycerol, three aminolipids, two phospholipids and two unidentified lipids. Based on the distinct differences from other Roseomonas species judged from the genotypic and phenotypic data, a novel species represented by Z23T and Z24, Roseomonas wenyumeiae sp. nov., is proposed. The type strain is Z23T (=CGMCC 1.16540T=DSM 106207T).


Epidural morphine infusion. Continuous pain relief.
Epidural morphine infusion is an effective and relatively safe route for postoperative analgesia. Lanz , Theiss , Reiss , and Sommer performed research supporting the use of epidural morphine. Following lumbar epidural anesthesia for orthopedic operations, 174 patients underwent the following study. At the end of surgery under double-blind conditions, 57 patients in group 1 received 0.1 mg/kg of morphine in 15 ml of normal saline epidurally and normal saline 0.01 ml/kg intramuscularly. Patients in group 2 (57 patients) received intramuscular morphine 0.1 mg/kg and normal saline 15 ml epidurally. Patients in group 3 (60 patients) received normal saline 15 ml epidurally and normal saline 0.01 ml/kg intramuscularly. Postoperative pain was less frequent, of shorter duration, and less severe following epidural morphine (group 1). Sympathetic block was only partial; patients still noticed pressure due to a dressing or cast. There was no motor blockade and active mobilization occurred earlier. Following epidural morphine, alertness was heightened, patients were more cooperative, and respiratory depression and postoperative pneumonia were less than after systemic administration of narcotics.(ABSTRACT TRUNCATED AT 250 WORDS)


Validation of the European system for cardiac operative risk evaluation II in a large Taiwan cardiac surgical centre.
The European System for Cardiac Operative Risk Evaluation (EuroSCORE II) is a well-established scoring system for predicting mortality in cardiac surgery. This system was derived predominantly from a European patient cohort; however, no validation of this system has been conducted in Taiwan. We sought to assess the performance of EuroSCORE II at a tertiary centre. The 2161 adult patients receiving cardiac surgery between 2017 and 2020 in our institution were included. Overall, the in-hospital mortality rate was 7.89%. The performance of EuroSCORE II was assessed using the area under the receiver operator curve (AUC) for discrimination and the Hosmer-Lemeshow (H-L) test for calibration. Data were analysed for type of surgery, risk stratification, and status of the operation. EuroSCORE II had good discriminative power (AUC=0.854, 95% Confidence Interval (CI): 0.822-0.885) and good calibration (χ2=5.19, p=0.82) for all types of surgery except ventricular assist devices (AUC=0.618, 95% CI: 0.497-0.738). EuroSCORE II also showed good calibration for most types of surgery except coronary artery bypass surgery (CABG) combined procedure (P=0.033), heart transplantation (HT) (P=0.017), and urgent operation (P=0.041). EuroSCORE II significantly underestimated the risk for CABG combined procedure and urgent operations, and overestimated the risk for HT. EuroSCORE II had satisfactory discrimination and calibration power to predict surgical mortality in Taiwan. However, the model is poorly calibrated for CABG combined procedure, HT, urgent operation, and, likely, lower- and higher-risk patients.


Identification of signaling pathways, matrix-digestion enzymes, and motility components controlling Vibrio cholerae biofilm dispersal.
Bacteria alternate between being free-swimming and existing as members of sessile multicellular communities called biofilms. The biofilm lifecycle occurs in three stages: cell attachment, biofilm maturation, and biofilm dispersal. Vibrio cholerae biofilms are hyperinfectious, and biofilm formation and dispersal are considered central to disease transmission. While biofilm formation is well studied, almost nothing is known about biofilm dispersal. Here, we conducted an imaging screen for V. cholerae mutants that fail to disperse, revealing three classes of dispersal components: signal transduction proteins, matrix-degradation enzymes, and motility factors. Signaling proteins dominated the screen and among them, we focused on an uncharacterized two-component sensory system that we term DbfS/DbfR for dispersal of biofilm sensor/regulator. Phospho-DbfR represses biofilm dispersal. DbfS dephosphorylates and thereby inactivates DbfR, which permits dispersal. Matrix degradation requires two enzymes: LapG, which cleaves adhesins, and RbmB, which digests matrix polysaccharides. Reorientation in swimming direction, mediated by CheY3, is necessary for cells to escape from the porous biofilm matrix. We suggest that these components act sequentially: signaling launches dispersal by terminating matrix production and triggering matrix digestion, and subsequent cell motility permits escape from biofilms. This study lays the groundwork for interventions aimed at modulating V. cholerae biofilm dispersal to ameliorate disease.


What Is the Lobular Branch of the Great Auricular Nerve? Anatomical Description and Significance in Rhytidectomy.
Current literature suggests that preserving the lobular branch of the great auricular nerve has greater impact on sensory function of the auricle than preservation of the posterior branch during rhytidectomy. However, no methodology exists to efficiently and accurately determine the topographic location of the lobular branch. This study describes the branching characteristics of the lobular branch and algorithmic surface markings to assist surgeons in preservation of the great auricular nerve during rhytidectomy flap elevation. The lobular branch was dissected in 50 cadaveric necks. Measurements were taken from the lobular branch to conchal cartilage, tragus, and antitragus. The anterior branch was measured to its superficial musculoaponeurotic system insertion, and the posterior branch was measured to the mastoid process. The McKinney point was marked and the great auricular nerve diameter was recorded. Branching pattern and location of branches within the Ozturk 30-degree angle were documented. Basic statistics were performed. The lobular branch was present in all specimens and distributed to three regions. In 85 percent of specimens, the lobular branch resided directly inferior to the antitragus; in the remaining specimens, it was located directly inferior to the tragus. Preoperative markings consisting of two vertical lines from the tragus and antitragus to the McKinney point can be used to outline the predicted location of the lobular branch. This study delineates the location of the lobular branch of the great auricular nerve. The authors translate these findings into a quick and simple intraoperative marking, which can assist surgeons in avoiding lobular branch injury during rhytidectomy dissection.


Current perception threshold: an adjunctive test for detection of acquired demyelinating polyneuropathies.
Current Perception Threshold (CPT) evaluation quantifies the sensory threshold to transcutaneous electrical stimulation of three sensory fiber subtypes: A-beta (2,000 Hz), A-delta (250 Hz) and C fibers (5 Hz). Demyelinating polyneuropathies tend to affect larger myelinated fibers before smaller unmyelinated fibers, and they usually begin at the proximal nerve roots or terminal axons, due to relative weakness of the blood-nerve barrier in these locations. Axonal polyneuropathies tend to affect smaller fibers before larger fibers, in a distal to proximal gradient. Ten patients with demyelinating polyneuropathy and ten patients with axonal polyneuropathy underwent CPT testing. CPT comparisons were made with regard to side-to-side asymmetries, fiber type involvement, and the ratio of fiber types involved. The C2, lateral antebrachial cutaneous, and sural distributions were examined bilaterally. Demyelinating polyneuropathies were detected with 50% sensitivity and 100% specificity. This diagnostic sensitivity is similar to that of published criteria based upon motor nerve conduction. CPT testing can distinguish demyelinating from axonal polyneuropathies. It may be particularly helpful in patients with predominantly sensory symptoms in whom EMG/NCS data may be equivocal, or in patients who decline EMG/NCS studies.


Attempts to obtain anti(D2 dopamine receptor) antibodies via the anti-idiotypic route.
Five stable hybridomas have been obtained that secrete monoclonal antibodies against the D2-dopamine receptor-selective drug spiperone. Each monoclonal antibody has been characterized in terms of its ability to bind a range of dopamine-receptor-selective ligands. One monoclonal antibody has been purified by Protein A affinity chromatography and used to immunize mice. Anti-idiotypic antisera and one hybridoma secreting an anti-idiotypic monoclonal antibody were obtained and shown to inhibit [3H]spiperone binding to the anti-spiperone antibody used for immunization. Neither the antisera nor the anti-idiotypic monoclonal antibody, however, inhibited binding of [3H]spiperone to D2-dopamine receptors.


Preference assessments as a tool to evaluate environmental enrichment.
Environmental enrichment is an important tool utilized to improve animal welfare in zoological institutions through opportunity for mental and physical stimulation. Many past studies have focused on the impact enrichment has on animal behavior; however, none have conducted preference assessments on enrichment items to examine the relationship between animals' preferences and interaction with enrichment over a 24-hr period. Ten-minute free operant, paired-choice preference assessments were implemented in Study 1 to determine the enrichment preferences of African lions (N = 3). Following Study 1, Study 2 was conducted, which examined the behavior of African lions with enrichment items over the course of 30, 24-hr trials to evaluate the relationship between preferences established in Study 1 and long-term interaction with the enrichment. Generalized estimating equations revealed a statistically significant relationship between the percentage of time the enrichment was approached first and the average duration of interaction in Study 1 to the total duration of interaction and the percent of hours interacted with the item in Study 2. Additionally, the first 2 min of the preference data resulted in comparable statistically significant findings, demonstrating shorter preference assessments can produce similar results. The results support our prediction that preference assessments can be used to estimate the amount of interaction with enrichment over the course of time, with preferred items being interacted with more frequently and in longer duration. Information gained from this study suggests preference assessments can be a time and cost-effective tool to evaluate enrichment preference and predicted efficacy.


Perturbations in nitrogen metabolism of brain and liver of rat following repeated benthiocarb administration.
Effects of repeated administration of benthiocarb on the nitrogen metabolism of hepatic and neuronal systems have been studied. Repeated benthiocarb treatment was associated with significant decrease in proteins with a concomitant increase in free amino acids (FAA) and specific activity levels of proteases suggesting impaired protein synthesis or elevated proteolysis. The glycogenic aminotransferases showed a significant elevation in both the tissues indicating high feeding of ketoacids into oxidative pathway for efficient operation of TCA cycle to combat energy crisis during induced benthiocarb stress. However, the activity levels of branched-chain aminotransferases decreased suggesting their reduced contribution of intermediates to TCA cycle. A comparative evaluation of the activity levels of ammonogenic enzymes, AMP deaminase, adenosine deaminase and glutamate dehydrogenase (GDH) indicated that ammonia was mostly contributed by nucleotide deamination rather than by oxidative deamination. GDH exhibited reduced activity due to low availability of glutamate. In accordance with increased levels of urea, the activity levels of arginase, a terminal enzyme of urea cycle was increased suggesting increased urea cycle operation in order to combat the increased ammonia content. As the presence of urea cycle in the brain is rather doubtful, the conversion of ammonia to glutamine for the synthesis of GABA is envisaged in brain whereas in liver, excess ammonia was converted to urea through ornithine-arginine reacting system. The increased glutaminase activity observed during benthiocarb intoxication is accounted for counteracting acidosis or maintenance of metabolic homeostasis. Arginase, a terminal enzyme of ornithine cycle showed increased activity denoting the efficient potentiality of tissues to avert ammonia toxicity. The changes observed in tissues of rat administered with benthiocarb reflects a shift in nitrogen metabolism for efficient mobilization of end products of protein catabolism.


Disaster risk from a macroeconomic perspective: a metric for fiscal vulnerability evaluation.
The Disaster Deficit Index (DDI) measures macroeconomic and financial risk in a country according to possible catastrophic scenario events. Extreme disasters can generate financial deficit due to sudden and elevated need of resources to restore affected inventories. The DDI captures the relationship between the economic loss that a country could experience when a catastrophic event occurs and the availability of funds to address the situation. The proposed model utilises the procedures of the insurance industry in establishing probable losses, based on critical impacts during a given period of exposure; for economic resilience, the model allows one to calculate the country's financial ability to cope with a critical impact. There are limitations and costs associated with access to resources that one must consider as feasible values according to the country's macroeconomic and financial conditions. This paper presents the DDI model and the results of its application to 19 countries of the Americas and aims to guide governmental decision-making in disaster risk reduction.


Correlation of SATB1 overexpression with the progression of human rectal cancer.
To date, the association between special AT-rich sequence-binding protein 1 (SATB1) and colorectal cancer (CRC) has not been reported. This study was aimed at investigating the expression and potential role of SATB1 in human rectal cancers. Ninety-three paired samples of rectal cancer and distant normal rectal tissue were analyzed by quantitative real-time PCR (qRT-PCR) and immunohistochemistry (IHC), and the correlations between SATB1 expression and clinicopathological parameters were evaluated. The expression profiles of SATB1 were also investigated in a panel of five human colon carcinoma cell lines. The general level of SATB1 mRNA in rectal cancer tissues was statistically significantly higher than that in normal mucosa (P = 0.043). The rate of positive SATB1 protein expression in rectal cancers (44.1%) was significantly higher than that in normal tissues (25.8%) by IHC analysis (P = 0.009). Overexpression of SATB1 mRNA was more predominant in patients with earlier onset of rectal cancer (P = 0.033). SATB1 expression correlated with invasive depth and tumor node metastasis (TNM) stage at both protein and mRNA levels (P < 0.05). Furthermore, SATB1 expression in the poorly metastatic KM12C cells was significantly lower than the highly metastatic KM12SM and KM12L4A cells and higher than the HCT116 and SW480 cells (P = 0.001). These results were further confirmed by Western blotting. Our results indicate that SATB1 may play an important role in the progression of human rectal cancer, which represents a possible new mechanism underlying CRC.


Relationship between the characteristic traits of polycystic ovary syndrome and susceptibility genes.
Polycystic ovary syndrome (PCOS) is a highly complex disorder influenced by genetic and environmental factors. Previous genome-wide association studies (GWAS) on Han Chinese, Korean, and European populations identified multiple PCOS-susceptible loci; however, only a few studies reported the association of susceptibility genes with disease phenotypic traits. This cross-sectional study aimed to investigate the association between PCOS susceptibility genes from GWAS and disease-related clinical features. A total of 1,810 reproductive-aged women were recruited, including 927 control women and 883 women with PCOS, diagnosed based on the European Society for Human Reproduction and Embryology criteria. Genomic DNA was extracted and genotyped, and a Bonferroni test was performed to determine the association between 12 independent SNPs and the clinical features of PCOS. In women with PCOS, rs11031006, nearest to FSHB, was significantly associated with free testosterone (P = 1.94 × 10-3) and luteinizing hormone (P = 1.96 × 10-3) levels. The menstruation number per year, ovarian follicular number, ovarian volume, and insulin sensitivity index were not associated with any SNP. In the control group, no SNPs were associated with any PCOS traits. Collectively, our results suggest that FSHB may play an important role in the development and progression of PCOS.


The use of magnetically-controlled growing rods to treat children with early-onset scoliosis: early radiological results in 19 children.
We undertook a prospective non-randomised radiological study to evaluate the preliminary results of using magnetically-controlled growing rods (MAGEC System, Ellipse technology) to treat children with early-onset scoliosis. Between January 2011 and January 2015, 19 children were treated with magnetically-controlled growing rods (MCGRs) and underwent distraction at three-monthly intervals. The mean age of our cohort was 9.1 years (4 to 14) and the mean follow-up 22.4 months (5.1 to 35.2). Of the 19 children, eight underwent conversion from traditional growing rods. Whole spine radiographs were carried out pre- and post-operatively: image intensification was used during each lengthening in the outpatient department. The measurements evaluated were Cobb angle, thoracic kyphosis, proximal junctional kyphosis and spinal growth from T1 to S1. The mean pre-, post-operative and latest follow-up Cobb angles were 62° (37.4 to 95.8), 45.1° (16.6 to 96.2) and 43.2° (11.9 to 90.5), respectively (p < 0.05). The mean pre-, post-operative and latest follow-up T1-S1 lengths were 288.1 mm (223.2 to 351.7), 298.8 mm (251 to 355.7) and 331.1 mm (275 to 391.9), respectively (p < 0.05). In all, three patients developed proximal pull-out of their fixation and required revision surgery: there were no subsequent complications. There were no complications of outpatient distraction. Our study shows that MCGRs provide stable correction of the deformity in early-onset scoliosis in both primary and revision procedures. They have the potential to reduce the need for multiple operations and thereby minimise the potential complications associated with traditional growing rod systems. Cite this article: Bone Joint J 2016;98-B:1240-47.


Classification of Streptomyces spore surfaces into five groups.
Streptomyces spores surfaces have been classified into five groups, smooth, warty, spiny, hairy, and rugose, by examination of carbon replicas of spores with the transmission electron microscope and by direct examination of spores with the scanning electron microscope.


Dehydration enhances cellular and humoral immunity in a mesic snake community.
The immunocompetence of a community of free-living animals can be affected by seasonality, sex, and parasite burden. However, each of these factors is often examined independently. Recent studies have also found that dehydration can enhance aspects of immunocompetence in drought-adapted species. To explore how all of these factors interact, and their effect on the immune system in mesic-adapted species, we collected blood samples from a community of free-ranging snakes in coastal South Carolina, United States, across 2 years. We specifically examined (a) how sex and seasonality influence humoral and cellular immunocompetence and parasite burden, (b) the dynamics among hydration state, parasite burden, and immunocompetence, and (c) whether mesic-adapted species also show enhanced innate immunity with dehydration. Consistent with previous work on drought-adapted species, we found that dehydration enhances multiple aspects of humoral immunity in mesic species, and we are the first to report that dehydration also enhances aspects of cellular immunocompetence. Contrary to previous results in other squamates, sex and season did not impact immunocompetence or parasite prevalence. Our results also reveal complex interactions among parasite prevalence, immunocompetence, and hydration state demonstrating that hydration state and parasitism are two ubiquitous factors that should continue to be considered in future studies examining ecoimmunological variation.