Myocarditis or inherited disease? - The multifaceted presentation of arrhythmogenic cardiomyopathy.
Arrhythmogenic right ventricular cardiomyopathy (ARVC) is now usually referred to as arrhythmogenic cardiomyopathy (ACM) because of the possible left and biventricular affection. In recent years, it has been shown that early-stage ACM, especially in women carrying a disease-causing variant in the DSP gene, may present with clinical signs of myocarditis. The female patient was diagnosed with myocarditis based on arrhythmia and findings on magnetic resonance imaging at the age of 24 years. An additional performed myocardial biopsy confirmed a lymphocytic inflammatory reaction. Subsequently, the patient experienced cardiac arrest because of ventricular fibrillation and was resuscitated. As a result, she received an implantable cardioverter defibrillator, and repeated ablations of recurrent ventricular tachycardia were performed. After four years, molecular genetic testing identified the heterozygous, likely pathogenic nonsense variant c.4789G > T, p.(Glu1597*) in DSP (NM_004415.4). Based on this finding, ACM could be diagnosed, and a heart transplantation was performed only a few months later because of rapid disease progression. Truncating variants in DSP have been associated with fulminant progression of arrhythmia. However, the currently used ARVC task force criteria are inadequate to detect DSP-associated ACM with left dominant presentation. Moreover, the initial diagnosis of myocarditis may distract from a more extensive search for other causes. Consequently, in cases of recurrent or unusually prolonged myocarditis, especially if present without detected pathogens, molecular genetic testing should be considered.


Fluorescent dye method for determination of the bilirubin-binding capacity of serum albumin.
A simple, rapid microfluorometric method utilizing a fluorescent dye, Direct Yellow 7, for quantitative measurement of serum albumin-binding capacity for bilirubin has been developed. The dye binds exclusively to serum albumin with enhancement of fluorescence. The dye shares bilirubin-binding sites on albumin with up to 2 mols of bilirubin per mol of albumin with differing affinities to the first and second sites. Lowered pH reduces albumin-binding capacity and exposure to light increases binding capacity of icteric sera. The binding capacity of adult human sera is greater than that of human cord sera or purified human serum albumin compared on albumin molar basis.


Artificial intelligence in retinal disease: clinical application, challenges, and future directions.
Retinal diseases are a leading cause of blindness in developed countries, accounting for the largest share of visually impaired children, working-age adults (inherited retinal disease), and elderly individuals (age-related macular degeneration). These conditions need specialised clinicians to interpret multimodal retinal imaging, with diagnosis and intervention potentially delayed. With an increasing and ageing population, this is becoming a global health priority. One solution is the development of artificial intelligence (AI) software to facilitate rapid data processing. Herein, we review research offering decision support for the diagnosis, classification, monitoring, and treatment of retinal disease using AI. We have prioritised diabetic retinopathy, age-related macular degeneration, inherited retinal disease, and retinopathy of prematurity. There is cautious optimism that these algorithms will be integrated into routine clinical practice to facilitate access to vision-saving treatments, improve efficiency of healthcare systems, and assist clinicians in processing the ever-increasing volume of multimodal data, thereby also liberating time for doctor-patient interaction and co-development of personalised management plans.


Selective immunodeficiency and malignant lymphoma of the central nervous system. Possible relationship to the Epstein-Barr virus.
This report presents the findings of a study of a 17-year-old male with a selective immunodeficiency to the Epstein-Barr virus, who died of a malignant lymphoma following clinical infectious mononucleosis. Autopsy findings and immunohistochemical techniques demonstrated a malignant lymphoma with B-lymphocyte characteristics which primarily involved the central nervous system (CNS). The relationship of the Epstein-Barr virus to lymphoproliferation is discussed.


Oral metronomic scheduling of anticancer therapy-based treatment compared to existing standard of care in locally advanced oral squamous cell cancers: A matched-pair analysis.
Head and neck cancers in developing countries present with advanced disease, compounded by poor access to tertiary care centers. We evaluated oral metronomic scheduling of anticancer therapy (MSAT) in advanced operable oral cancers, in conjunction with standard therapy. This was a retrospective matched-pair analysis carried out in a tertiary referral cancer center. Advanced operable oral cancer patients having a waiting period for surgery > 3 weeks were administered MSAT. Patients then underwent standard therapy (surgery +/- adjuvant radiation/chemoradiation) as warranted by the disease, followed by MSAT maintenance therapy. Outcomes of the MSAT group were compared with stage-matched controls with similar waiting periods. Survivals were found using the Kaplan-Meier method and compared between groups using the log rank test. Response was seen in 75% of 32 patients. Two-year disease-free survivals (DFS) in MSAT and control groups were 86.5 and 71.6%, respectively. Two-year DFS in MSAT group who received at least three months of MSAT was 94.6% (P = 0.03). Oral MSAT is an economical, effective, and safe adjuvant therapy for oral cancers. It has the potential for preventing progression of the disease and improving DFS.


Quality of Nursing Homes and Admission of Residents With Alzheimer's Disease and Related Dementias: The Potential Influence of Market Factors and State Policies.
This study aimed to examine the associations between nursing home (NH) quality and prevalence of newly admitted NH residents with Alzheimer's disease and related dementias (ADRD), and to assess the extent to which market-level wages for certified nursing assistants (CNAs) and state Medicaid behavioral and mental health add-on policy may influence such associations. Retrospective cohort study. The analytical sample included 2777 NHs with either high or low quality, located in urban areas of 41 states from 2011 to 2014. The outcome variable was the prevalence of ADRD among newly admitted NH residents. NH quality was defined as dichotomous, based on the Nursing Home Compare (NHC) star rating system. We considered an NH with 5-star rating as having high quality and with 1-star rating as having low quality. Information on county-level CNA wages and state Medicaid behavioral and mental health add-on policies was included. Linear regression models with NH random effects and robust standard errors were estimated. A set of sensitivity analyses were performed. After accounting for NH-level aggregated resident characteristics and market/state-level factors, the prevalence of ADRD among newly admitted residents was 3% lower in high-quality NHs compared with low-quality NHs (P < .01). A 1-dollar increase in CNA hourly wage was associated with a 0.9-percentage point decrease in the prevalence of ADRD among newly admitted residents (P < .01). State Medicaid behavioral and mental health add-on policy was associated with a 2.5-percentage point increase in the prevalence of ADRD in high-quality NHs (P < .05), but not in low-quality NHs. Our findings suggest that high-quality NHs are less likely to admit residents with ADRD. The effect size of this relationship is modest and may be influenced by state Medicaid behavioral and mental health add-on policies. Future studies are needed to better understand reasons leading to these associations so that effective interventions can be developed to incentivize high-quality NHs to more readily serve residents with ADRD.


COVID-19 pandemic lessons to facilitate future engagement in the global climate crisis.
The COVID-19 pandemic was declared a Public Health Emergency of International Concern (PHEIC) in January 2020. As of November 2020, over 54 million cases and over 1 million deaths have been reported globally. The sudden coronavirus global pandemic has also pointed to the importance of tackling the global climate crisis even more urgently. This article discusses six lessons drawn from the COVID-19 pandemic that can inform and facilitate greater future engagement in the global climate crisis. These lessons were identified through monitoring and analyzing media coverage of COVID-19 related events during the initial onset of COVID-19 in late January 2020 to June 30, 2020. The key lessons included the potentiality of reducing fossil fuel consumption and greenhouse emissions, the significance of responding late, a case for strong sustainability, the limits of rugged individualism, a (mis)trust in science, and the possibility of large-scale change. The insights put forward point to the fact that, like the COVID-19 pandemic, people need to continue to attach their health to expectations of government action in the context of the global climate crisis.


Anti-Virulence Properties of Plant Species: Correlation between In Vitro Activity and Efficacy in a Murine Model of Bacterial Infection.
Several plant extracts exhibit anti-virulence properties due to the interruption of bacterial quorum sensing (QS). However, studies on their effects at the preclinical level are scarce. Here, we used a murine model of abscess/necrosis induced by Pseudomonas aeruginosa to evaluate the anti-pathogenic efficacy of 24 plant extracts at a sub-inhibitory concentration. We analyzed their ability to inhibit QS-regulated virulence factors such as swarming, pyocyanin production, and secretion of the ExoU toxin via the type III secretion system (T3SS). Five of the seven extracts with the best anti-pathogenic activity reduced ExoU secretion, and the extracts of Diphysa americana and Hibiscus sabdariffa were identified as the most active. Therefore, the abscess/necrosis model allows identification of plant extracts that have the capacity to reduce pathogenicity of P. aeruginosa. Furthermore, we evaluated the activity of the plant extracts on Chromobacterium violaceum. T3SS (ΔescU) and QS (ΔcviI) mutant strains were assessed in both the abscess/necrosis and sepsis models. Only the ΔescU strain had lower pathogenicity in the animal models, although no activity of plant extracts was observed. These results demonstrate differences between the anti-virulence activity recorded in vitro and pathogenicity in vivo and between the roles of QS and T3S systems as virulence determinants.


Association between subjective well-being and all-cause mortality among older adults in China.
Although several studies in high-income countries have suggested a positive association between subjective well-being (SWB) and mortality, studies conducted in low- and middle-income countries, such as China, are scarce. The purpose of this study is to examine the association between SWB and all-cause mortality among the older Chinese population. Data were from the Chinese Longitudinal Healthy Longevity Survey (CLHLS), a population-based longitudinal cohort study in 22 of 31 provinces in mainland China. A total of 13,282 individuals aged 65 ≥ years who were recruited in 2002 and followed-up until 2018 were included. SWB was assessed with an eight-item tool covering life satisfaction, positive affect (including optimism, happiness, personal control and conscientiousness) and negative affect (including anxiety, loneliness and uselessness). Cox proportional hazards regression methods were carried out to estimate the association between SWB and total mortality, adjusting for a wide range of potential confounders. Subgroup analyses and interaction analyses were further conducted. During the 16.5 years of follow-up, 8459 deaths were identified. Greater SWB was independently associated with a reduced risk of all-cause mortality (adjusted hazard ratio [HR] = 0.85, 95% confidence interval [CI] = 0.81-0.89) after adjustment for age, sex, marital status, education level, place of residence, smoking status, drinking, exercise, diet, BMI, hypertension, diabetes, heart disease, cerebrovascular diseases and cancer. Of the eight individual SWB symptoms, only 2 items, feelings of uselessness (adjusted HR = 0.94, 95% CI = 0.89-0.99) and happiness (adjusted HR = 0.91, 95% CI = 0.86-0.95), were significantly associated with total mortality. Associations remained significant across all subgroups regardless of different characteristics. Higher SWB overall and 2 certain symptoms (feelings of uselessness and happiness) were independently associated with all-cause mortality risk among older Chinese adults. The association was consistent across different groups, suggesting that promoting a healthier SWB may be beneficial to all older individuals irrespective of their characteristics.


Nostalgia.
An attempt is made to differentiate between true and false nostalgia, with clinical illustrations from the analyses of a chronic psychotic patient, and a far less disturbed young woman, whose main symptom of vagueness clouded the analytic work, and her own perceptions and capacities. The significance of the differentiation for psychoanalytic work is stressed.


Intraocular pressure and central corneal thickness.
From the results of the Ocular Hypertension Treatment Study emerged the conclusion that ocular hypertensive subjects with thinner central corneal thickness (CCT) are at increased risk of developing glaucoma. Although possible underlying biases that could have led to this conclusion are still under investigation, there is an increasing interest in the scientific community to understand the potential mechanisms of this increased risk profile. It has been proposed that interindividual differences in CCT might be purely responsible for inaccuracies of the tonometric readings with potential underestimation of the true IOP in subjects with thinner CCT although it is becoming progressively clearer that the true IOP is unpredictable with linear correction formulas for CCT, and it is likely that other material properties of the cornea contribute, together with CCT, to the tonometric artifact. Recently, it has become possible to measure the biomechanical properties of the cornea in vivo and it has been suggested that differences in corneal biomechanics may be the expression of interindividual structural differences of the ocular tissues (including lamina cribrosa), with potential consequences on the interindividual susceptibility to the glaucomatous damage under the same IOP level. A possible underlying biological risk related to thinner CCTs, independent of the influence on tonometric reading, has been proposed and largely studied after the results of the OHTS were published. Besides the understanding of the mechanism underlying the role of CCT as a risk factor for the development of glaucoma, it is important to understand how the information about CCT should be integrated in the clinical management of both ocular hypertension (OHT) and glaucoma and whether other ocular properties should be measured to better understand the individual risk profile.


Solid-State Nonlinear Optical Properties of Mononuclear Copper(II) Complexes with Chiral Tridentate and Tetradentate Schiff Base Ligands.
Salen-type metal complexes have been actively studied for their nonlinear optical (NLO) properties, and push-pull compounds with charge asymmetry generated by electron releasing and withdrawing groups have shown promising results. As a continuation of our research in this field and aiming at solid-state features, herein we report on the synthesis of mononuclear copper(II) derivatives bearing either tridentate N2O Schiff bases L(a-c)- and pyridine as the forth ancillary ligand, [Cu(La-c)(py)](ClO4) (1a-c), or unsymmetrically-substituted push-pull tetradentate N2O2 Schiff base ligands, [Cu(5-A-5'-D-saldpen/chxn)] (2a-c), both derived from 5-substituted salicylaldehydes (sal) and the diamines (1R,2R)-1,2-diphenylethanediamine (dpen) and (1S,2S)-1,2-diaminocyclohexane (chxn). All compounds were characterized through elemental analysis, infrared and UV/visible spectroscopies, and mass spectrometry in order to guarantee their purity and assess their charge transfer properties. The structures of 1a-c were determined via single-crystal X-ray diffraction studies. The geometries of cations of 1a-c and of molecules 2a-c were optimized through DFT calculations. The solid-state NLO behavior was measured by the Kurtz-Perry powder technique @1.907 µm. All chiral derivatives possess non-zero quadratic electric susceptibility (χ(2)) and an efficiency of about 0.15-0.45 times that of standard urea.


Influence of breastfeeding and postnatal nutrition on cardiovascular remodeling induced by fetal growth restriction.
Our aim was to determine the influence of breastfeeding and postnatal nutrition on cardiovascular remodeling induced by fetal growth restriction (FGR). A cohort study including 81 children with birthweight <10th centile (FGR) and 121 with adequate fetal growth for gestational age (AGA) was conducted. Cardiovascular endpoints were left ventricular sphericity index (LVSI), carotid intima-media thickness (cIMT), and blood pressure (BP) at 4-5 y of age. The combined effect of FGR and postnatal variables-including breastfeeding, fat dietary intake, and BMI-on cardiovascular endpoints was assessed by linear and robust regressions. FGR was the strongest predictor of cardiovascular remodeling in childhood, leading to lower LVSI and increased cIMT and BP as compared with AGA. Breastfeeding >6 mo (coefficient: 0.0982) and healthy-fat dietary intake (coefficient: -0.0128) showed an independent beneficial effect on LVSI and cIMT, respectively. Overweight/obesity induced an additional increment of 1 SD on cIMT in FGR children (interaction coefficient: 0.0307) when compared with its effect in AGA. BMI increased systolic BP (coefficient: 0.7830) while weight catch-up increased diastolic BP (coefficient: 4.8929). Postnatal nutrition ameliorates cardiovascular remodeling induced by FGR. Breastfeeding and healthy-fat dietary intake improved while increased BMI worsened cardiovascular endpoints, which opens opportunities for targeted postnatal interventions from early life.


Increased stabilizing effects of amphiphilic excipients on freeze-drying of lactate dehydrogenase (LDH) by dispersion into sugar matrices.
The stabilizing effect of amphiphilic excipients and sugars against protein inactivation during freeze-drying was studied in relation to their physical states in freeze-dried cakes. Physical states of amphiphilic excipients were studied by powder X-ray diffractometry and differential scanning calorimetry (DSC). Stabilizing effects of excipients were studied using lactate dehydrogenase (LDH) as a model protein. Although poly(ethylene glycols) (PEGs) 1000 to 2000 crystallized when freeze-dried alone, the addition of sugars decreased their crystallinity by dispersing PEG into sugar-dominant matrices. Sugars species, molecular weight of PEGs, and buffer concentration also affected the crystallinity of PEGs. Sugars also dispersed some of other amphiphilic excipients, which tended to crystallize or become "microscopically liquid" when freeze-dried without sugar. Only the amphiphilic excipients that remained amorphous solid state protected the enzyme during freeze-drying in the absence of sugars. However, combinations of sucrose and all the amphiphilic excipients studied increased the stabilizing effects markedly. The remaining activities were greater than the sum of their individual ones. Various amphiphilic excipients are good stabilizers for freeze-drying of proteins when dispersed into sugar-dominant matrices.


Alginate Lyase Aly36B is a New Bacterial Member of the Polysaccharide Lyase Family 36 and Catalyzes by a Novel Mechanism With Lysine as Both the Catalytic Base and Catalytic Acid.
Alginate lyases, which are important in both basic and applied sciences, fall into ten polysaccharide lyase (PL) families. PL36 is a newly established family that includes 39 bacterial sequences and one eukaryotic sequence. Till now, the structures or catalytic mechanisms of PL36 alginate lyases have yet to be revealed. Here, we characterized a novel PL36 alginate lyase, Aly36B, from Chitinophaga sp. MD30. Aly36B is a polymannuronate specific endolytic alginate lyase. To probe the catalytic mechanism of Aly36B, the structures of wild-type Aly36B and its mutants (K143A/Y185A in complex with alginate tetrasaccharide and K143A/M171A with trisaccharide) were solved. The overall structure of Aly36B belongs to the β-jelly roll scaffold, adopting a typical β-sandwich fold. Aly36B contains a Ca2+, which is far away from the active center and plays an important role in stabilizing the structure of Aly36B. Based on structural and mutational analyses, the catalytic mechanism of Aly36B for alginate degradation was explained. During catalysis, Arg169, Tyr185, and Tyr187 are responsible for neutralizing the negative charge of the substrate, and Lys143 acts as both the catalytic base and the catalytic acid, which represents a new kind of catalytic mechanism of alginate lyases. Sequence alignment shows that these four residues involved in catalysis are highly conserved in all PL36 sequences, suggesting that PL36 alginate lyases may adopt a similar catalytic mechanism. Taken together, this study reveals the molecular structure and catalytic mechanism of a PL36 alginate lyase, broadening our knowledge on alginate lyases and facilitating future biotechnological applications of PL36 alginate lyases.


Gerontological nurse specialists.
This article focuses on the development of a new role highlighted in The NHS Plan (DoH 2000a), nurse specialist for older people or gerontological nurse specialist.


The interactions of ZDHHC5/GOLGA7 with SARS-CoV-2 spike (S) protein and their effects on S protein's subcellular localization, palmitoylation and pseudovirus entry.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein determines virus entry and the palmitoylation of S protein affects virus infection. An acyltransferase complex ZDHHC5/GOGAL7 that interacts with S protein was detected by affinity purification mass spectrometry (AP-MS). However, the palmitoylated cysteine residues of S protein, the effects of ZDHHC5 or GOLGA7 knockout on S protein's subcellular localization, palmitoylation, pseudovirus entry and the enzyme for depalmitoylation of S protein are not clear. The palmitoylated cysteine residues of S protein were identified by acyl-biotin exchange (ABE) assays. The interactions between S protein and host proteins were analyzed by co-immunoprecipitation (co-IP) assays. Subcellular localizations of S protein and host proteins were analyzed by fluorescence microscopy. ZDHHC5 or GOGAL7 gene was edited by CRISPR-Cas9. The entry efficiencies of SARS-CoV-2 pseudovirus into A549 and Hela cells were analyzed by measuring the activity of Renilla luciferase. In this investigation, all ten cysteine residues in the endodomain of S protein were palmitoylated. The interaction of S protein with ZDHHC5 or GOLGA7 was confirmed. The interaction and colocalization of S protein with ZDHHC5 or GOLGA7 were independent of the ten cysteine residues in the endodomain of S protein. The interaction between S protein and ZDHHC5 was independent of the enzymatic activity and the PDZ-binding domain of ZDHHC5. Three cell lines HEK293T, A549 and Hela lacking ZDHHC5 or GOLGA7 were constructed. Furthermore, S proteins still interacted with one host protein in HEK293T cells lacking the other. ZDHHC5 or GOLGA7 knockout had no significant effect on S protein's subcellular localization or palmitoylation, but significantly decreased the entry efficiencies of SARS-CoV-2 pseudovirus into A549 and Hela cells, while varying degrees of entry efficiencies may be linked to the cell types. Additionally, the S protein interacted with the depalmitoylase APT2. ZDHHC5 and GOLGA7 played important roles in SARS-CoV-2 pseudovirus entry, but the reason why the two host proteins affected pseudovirus entry remains to be further explored. This study extends the knowledge about the interactions between SARS-CoV-2 S protein and host proteins and probably provides a reference for the corresponding antiviral methods.


Transcriptional analysis distinguishes breast implant-associated anaplastic large cell lymphoma from other peripheral T-cell lymphomas.
Breast implant-associated anaplastic large cell lymphoma is a new provisional entity in the revised World Health Organization classification of lymphoid malignancies, the pathogenesis and cell of origin of which are still unknown. We performed gene expression profiling of microdissected breast implant-associated anaplastic large cell lymphoma samples and compared their transcriptional profiles with those previously obtained from normal T-cells and other peripheral T-cell lymphomas and validated expression of selected markers by immunohistochemistry. Our results indicate that most breast implant-associated anaplastic large cell lymphomas exhibit an activated CD4+ memory T-cell phenotype, which is associated with CD25 and FoxP3 expression. Gene ontology analyses revealed upregulation of genes involved in cell motility programs (e.g., CCR6, MET, HGF, CXCL14) in breast implant-associated anaplastic large cell lymphomas compared to normal CD4+ T-cells and upregulation of genes involved in myeloid cell differentiation (e.g., PPARg, JAK2, SPI-1, GAB2) and viral gene transcription (e.g., RPS10, RPL17, RPS29, RPL18A) compared to other types of peripheral T-cell lymphomas. Gene set enrichment analyses also revealed shared features between the molecular profiles of breast implant-associated anaplastic large cell lymphomas and other types of anaplastic large cell lymphomas, including downregulation of T-cell receptor signaling and STAT3 activation. Our findings provide novel insights into the biology of this rare disease and further evidence that breast implant-associated anaplastic large cell lymphoma represents a distinct peripheral T-cell lymphoma entity.


Role of gender in the behavioral effects of peripheral sympathetic ingrowth.
Following cholinergic denervation of the hippocampal formation, peripheral sympathetic nerves originating from the superior cervical ganglia grow into the hippocampus. As gender is known to alter the anatomy of hippocampal sympathetic ingrowth, we assessed the effect of this variable on the behavioral recovery following ingrowth. Adult male or female rats were trained on a standard version of a radial-8-arm maze task until they reached a specific learning criterion. Animals from each sex then underwent one of three surgical procedures: sham surgery, medial septal lesions plus superior cervical ganglionectomy, or medial septal lesion plus sham ganglionectomy. Reacquisition of the maze was then assessed. Prior to surgery, male animals acquired the task significantly faster than female animals. Following surgery male and female rats recovered overall performance at similar rates. However, marked group differences were observed. In males, the control group recovered faster than the group with medial septal lesion plus ganglionectomy, which recovered faster than the medial septal lesion group. In females, the control group recovered faster than the medial septal lesion group, which in turn recovered faster than the medial septal ganglionectomy group. The results of this study clearly demonstrate that gender can influence the behavioral effects of hippocampal sympathetic ingrowth. We believe that this is the first report in which gender has been shown to alter the behavioral effect of a neuronal reorganization.


Interaction of monogalactosyldiacylglycerol with cytochrome b₆f complex in surface films.
The interaction of monogalactosyldiacylglycerol (MGDG) with cytochrome b(6)f complex (cyt b(6)f), a major component of the photosynthetic apparatus, was studied in Langmuir monolayers during compression/expansion cycling and at constant surface pressure mode. The surface pressure/area isotherms of the mixed films were analyzed in terms of surface compressional modulus and two-dimensional virial equation of state. The morphology and the surface potential of the monolayers were monitored by Brewster angle microscopy and vibrating plate sensor respectively. Our results suggested that there is a specific interaction between MGDG and cyt b(6)f which resulted in depletion of lipid molecules from the interface. The current work sheds light on the still unclear question how b(6)f complex gets in touch with the major compound of the thylakoid membranes, the non-charged lipid MGDG. The interaction occured even at very low sub-nanomolar concentration of the complex. This effect most probably could be attributed to hydrogen bonding between the galactose headgroup of the lipid and the protein moiety of cyt b(6)f.


Tocilizumab: a new therapy for large vessel vasculitis.
Large vessel vasculitis represents mainly two main diseases: giant cell arteritis and Takayasu arteritis. Recent advancements in the treatment for different rheumatic diseases refractory to disease-modifying antirheumatic agents with biologic agents have resulted in remarkable efficacy and tolerability. However, treatments for large vessel vasculitis (LVV) with tumor necrosis factor-α inhibitors have yielded conflicting results. Recently, very promising results have been reported in patients treated with tocilizumab. The purpose of this review is to summarize the current treatment strategies of LVV and the recent evidence on the use of tocilizumab in LVV.


Brucella melitensis Biovar 1 and Brucella abortus S19 Vaccine Strain Infections in Milkers Working at Cattle Farms in the Khartoum Area, Sudan.
Human brucellosis is a preventable zoonoses that may become persistent, causing, if left untreated, severe localized disease. Occupational exposure to infected animals or animal products and consumption of fresh contaminated dairy are main risk factors. One hundred farmworkers employed at two cattle farms one in Khartoum North and one in Omdurman were screened for the presence of specific antibodies and seropositive workers were invited to donate a blood sample for blood culture. Molecular typing was used to characterize Brucella isolates. Ten percent of farmworkers tested seropositive and while Brucella melitensis biovar 1 was isolated from the blood of three individuals, an isolate identical to the B. abortus S19 vaccine strain was isolated from a fourth person. All four bacteremic individuals were employed as milkers and did not have obvious disease. The isolation of the highly infectious pathogen B. melitensis from seropositive workers is consistent with the notion that the pathogen may persist in the blood without causing overt disease. While vaccination with strain S19 is essential for the control of bovine brucellosis the vaccine strain may be transmitted to the human population and protective measures remain important to prevent exposure also in view of the presence of B. melitensis. To create awareness for this potentially severe disease more information on the prevalence of the pathogen in different risk groups and in livestock in the Sudan is needed.


The effect of propylthiouracil (PTU) on heat production in chickens maintained on different levels of nutrition.
Using the method of forced feeding on higher and lower levels, two groups of chickens differring in growth rate were obtained. In the chickens of the two groups 72 measurements of heat production were made. Chickens of these groups were compared considering either the same age or similar body weight. It has been found that propythiouracil treatment (120 mg/kg duging 10 consecutive days) decreases heat production in the chickens of both groups. However, this effect was much more pronounced in the birds maintained on the higher level of nutrition and growing more rapidly than in those maintained on the lower level of nutrition and growing slowly.


Myocardial function in alcoholic cardiac beriberi.
A case of alcoholic beriberi is described. Left ventricular systolic function as measured by the radionuclide ejection fraction showed an abnormal fall with exercise. Subsequent return to normal with the administration of thiamine suggests myocardial involvement in the condition.


Conversion therapy for massive hepatocellular carcinoma: A case report and literature review.
For potentially resectable HCC, a more aggressive conversion therapy strategy (high-intensity combined with multiple treatment modalities) can be used. Hepatocellular carcinoma (HCC) is the sixth most common malignancy worldwide. The best treatment for HCC is radical surgical resection, but 70%-80% of patients are ineligible for surgery. Although conversion therapy is an established treatment strategy for various solid tumors, there is no uniform protocol for treating HCC. In this case, we present a 69-year-old male patient diagnosed with massive HCC with Barcelona clinical liver cancer (BCLC) stage B. Because of the insufficient volume of the future liver remnant, we believed radical surgical resection was temporarily impossible. Therefore, the patient received conversion therapy, including four cycles of transcatheter arterial embolization (TAE) and hepatic arterial infusion chemotherapy (HAIC-Folfox), lenvatinib (8 mg orally once a day), and tislelizumab (an anti-PD-1 antibody, 200 mg intravenously once every 3 weeks). Fortunately, the patient achieved a good treatment response (smaller lesions and improved liver function) and underwent radical surgery finally. There was no clinical evidence of recurrence at 6 months of follow-up. For potentially resectable HCC, this case reveals that a more aggressive conversion therapy strategy (high-intensity combined with multiple treatment modalities) can be used.


Hemodynamic nature of black-blood enhancement in long-term coiled cerebral aneurysms.
Vessel wall imaging (VWI) with black-blood (BB) technique can demonstrate aneurysmal enhancement preluding to growth/rupture in treatment-naive cerebral aneurysms. Interestingly, recent works showed that BB enhancement may also occur in endovascularly treated aneurysms, though its meaning is controversial. Hypothesizing a flow-related mechanism of BB enhancement, we explored its relationship with incomplete occlusion status and coil packing density at DSA. We analyzed the subjects undergoing 3T MRI between January 2017 and October 2020 for a previous aneurysmal coiling. All the MRI studies included pre- and post-contrast 3D BB sequences. The presence of intra-aneurysmal pre-contrast BB signal was assessed. BB enhancement (when present) was classified as follows: (1) enhancement at the neck, (2) intrasaccular/intra-coil enhancement, and (3) peripheral enhancement. Coil packing density and aneurysmal occlusion status (according to the modified Raymond-Roy classification, MRRC) were determined on post-treatment DSA and compared with BB findings using generalized linear mixed-effect model and ANOVA. Significant p values were <0.05. Forty-eight aneurysms from 44 patients were eligible for analysis. Pre-contrast BB signal was observed in 50% of the aneurysms and showed a relationship with baseline aneurysmal size. BB enhancement was detectable in 31 aneurysms (65%), being significantly associated with incomplete aneurysmal occlusion and reduced coil packing density at DSA. BB enhancement of coiled aneurysms is related with increasing degrees of post-coiling aneurysmal remnants and with loose coil packing density at DSA. This supports a hemodynamic interpretation of BB enhancement in long-term coiled aneurysms.


Human Embryonic Stem Cells-Derived Mesenchymal Stem Cells Reduce the Symptom of Psoriasis in Imiquimod-Induced Skin Model.
Mesenchymal stem cells (MSCs) can be used for a wide range of therapeutic applications because of not only their differentiation potential but also their ability to secrete bioactive factors. Recently, several studies have suggested the use of human embryonic stem cell-derived MSCs (hE-MSCs) as an alternative for regenerative cellular therapy due to mass production of MSCs from a single donor. We generated hE-MSCs from embryonic stem cell lines, SNUhES3, and analyzed immune properties of these cells. Also, we evaluated the in-vivo therapeutic potential of hE-MSCs in immune-mediated inflammatory skin disease. The cell showed the suppression of immunity associated with allogenic peripheral blood mononuclear cells in mixed lymphocyte response assay. We also detected that cytokines and growth factor related to the immune response were secreted from these cells. To assessed the in-vivo therapeutic potential of hE-MSCs in immune-mediated inflammatory skin disease, we used imiquimod (IMQ)-induced skin psoriasis mouse model. The score of clinical skin was significantly reduced in the hE-MSCs treated group compared with control IMQ group. In histological analysis, the IMQ-induced epidermal thickness was significantly decreased by hE-MSCs treatment. It was correlated with splenomegaly induced by IMQ which was also improved in the hE-MSCs. Moreover, IMQ-induced inflammatory cytokines; Th1 cytokines (TNF-α, IFN-α, IFN-γ,and IL-27) and Th17 cytokines (IL-17A and IL-23), in the serum and skin showed marked inhibition by hE-MSCs. These results suggested that hE-MSCs have a potency of immune modulation in psoriasis, which might be the key factor for the improved psoriasis.


One-step extraction of oat protein by choline chloride-alcohol deep eutectic solvents: Role of chain length of dihydric alcohol.
The aim of this study is to investigate the effect of dihydric alcohol chain length (1,2-ethanediol, 1,3-propanediol, and 1,4-butanediol) on the structure of deep eutectic solvents (DESs) and the properties of the extracted oat proteins. Herein, five anhydrous and nine hydrated DESs were successfully prepared by mixing choline chloride, dihydric alcohol, and/or water in a heating method. The structures of DESs were confirmed by FTIR and 1H NMR. Among them, only four anhydrous and six hydrated DESs were able to extract oat proteins from flours by one-step extraction. SDS-PAGE and FTIR analyses indicated that the structural properties of the oat proteins were highly reliant on the composition of the DESs; while physicochemical properties were primarily ruled by the environmental pH. Overall, the hydrated DES composing of all food-grade compounds, including choline chloride, 1,3-propanediol, and water at a molar ratio of 1:3:1, demonstrated its great potential for one-step biorefinery of oat proteins.


Measles, Mumps, Rubella, and Varicella Zoster Virus Serology and Infections in Solid Organ Transplant Recipients During the First Year Posttransplantation.
Mumps, measles, rubella, and varicella zoster (MMRV) viruses may cause severe infections in seronegative adult solid organ transplant (SOT) recipients, but can be prevented by vaccination. We aimed to determine MMRV serostatus in adult SOT recipients before and 1 year after transplantation as well as evidence of MMRV infections in a large, prospective cohort of SOT recipients. This was a prospective study of 1182 adult SOT recipients included in the Management of Posttransplant Infections in Collaborating Hospitals (MATCH) cohort from 2011 to 2017 with a 1-year follow-up. Systematic monitoring of MMRV serology was performed prior to transplantation and 1 year posttransplantation. Polymerase chain reaction (PCR) was used to confirm viral replication in SOT recipients presenting with clinical evidence of infection. Among 1182 adult SOT recipients, 28 (2.4%), 77 (6.5%), 65 (5.5%), and 22 (1.9%) were seronegative for measles, mumps, rubella, and varicella zoster virus (VZV), respectively, and 165 (14%) were seronegative for at least 1 of the MMRV viruses. One year posttransplantation, 29 of 823 (3.5%) of seropositive SOT recipients had seroreverted, and 63 of 111 (57%) of seronegative SOT recipients seroconverted for at least 1 MMRV virus. No evidence of measles, mumps, or rubella infection was found, but 8 (0.7%) SOT recipients developed symptoms and had a positive VZV PCR. A large proportion of SOT recipients were seronegative for at least 1 of the MMRV viruses. MMRV infections in SOT recipients may disseminate and become fatal, and although only a few cases of VZV infection were detected, results from this study suggest increase attention toward vaccination of patients waiting for SOT.


Permanent control of massive tumor bleeding with intraluminal balloon catheters.
Proximal ligation usually controls bleeding from a tumor-eroded carotid artery. When this maneuver failed, two intraluminal balloon catheters were passed distally into the vessel, after which they were inflated and left in place for six weeks. The patient had no neurologic sequelae or further bleeding before succumbing to tumor progression 10 months later.


Polyplex-mediated inhibition of chemokine receptor CXCR4 and chromatin-remodeling enzyme NCOA3 impedes pancreatic cancer progression and metastasis.
Pancreatic cancer (PC) is one of the most aggressive malignancies due to intense desmoplasia, extreme hypoxia and inherent chemoresistance. Studies have implicated the expression of chemokine receptor CXCR4 and nuclear receptor co-activator-3 (NCOA3) in the development of desmoplasia and metastatic spread of PC. Using a series of polymeric CXCR4 antagonists (PCX), we optimized formulation of PCX/siNCOA3 polyplexes to simultaneously target CXCR4 and NCOA3 in PC. Cholesterol-modified PCX showed maximum CXCR4 antagonism, NCOA3 silencing and inhibition of PC cell migration in vitro. The optimized PCX/siNCOA3 polyplexes were used in evaluating antitumor and antimetastatic activity in orthotopic mouse model of metastatic PC. The polyplexes displayed significant inhibition of primary tumor growth, which was accompanied by a decrease in tumor necrosis and increased tumor perfusion. The polyplexes also showed significant antimetastatic effect and effective suppression of metastasis to distant organs. Overall, dual-function PCX/siNCOA3 polyplexes can effectively regulate tumor microenvironment to decrease progression and dissemination of PC.


Practical issues in data-driven model-free adaptive control for an omnidirectional mobile manipulator.
This article focuses on addressing three practical issues encountered when applying a data-driven model-free adaptive control (MFAC) approach to mobile robots. The first practical issue lies in a common assumption in MFAC schemes that the sign of all elements in pseudo-partial derivative (PPD) should be constant, while it cannot be satisfied if omnidirectional mobile manipulators (OMMs) move with platform rotation. To solve this problem, a new coordinate frame is introduced, which is crucial for applying MFAC to any mobile robots with rotation. The second one is that the initial value setting method for estimation of PPD is unclear. Improper settings may easily lead to control system instability. An initial value setting method for estimation of PPD is proposed with explicit physical interpretation. Lastly, applying the typical MFAC scheme directly to OMM fails to converge well to the desired trajectory. To tackle this, a new data-driven MFAC controller is proposed by incorporating a sliding mode control. Finally, experimental tests on an OMM are carried out to verify the effectiveness of the proposed control scheme. To the best of our knowledge, this is the first MFAC scheme that has been experimentally verified on a prototype mobile robot with rotation.


Preoperative diagnosis and prognosis in 40 Parathyroid Carcinoma Patients.
Parathyroid carcinoma (PC) is a rare disease which is difficult to diagnose preoperatively and predict prognosis. The goal of this study was to analyse the preoperative predictive factors and prognostic factors in PC patients and to evaluate the possibility of diagnosing PC preoperatively. This is a retrospective study from Jan 2000 to Aug 2015 conducted in Shanghai Ruijin Hospital. Comparisons were made between 40 parathyroid carcinoma patients and 282 patients with benign parathyroid lesions during the same period. All patients underwent parathyroid surgery, and the results were certified by paraffin pathology. Prognostic factors were analysed in the 40 PC patients. Patients with higher levels of intact parathyroid hormone (P < 0·001, OR = 1·001, CI: 1·000-1·002), calcium (P = 0·008, OR = 3·395, CI: 1·382-8·341) and a larger parathyroid volume (P = 0·001, OR = 2·023, CI: 1·333-3·071) were more likely to have PC. Local excision (P = 0·008, OR = 4·992, CI: 1·533-16·252), stage III in the Schulte staging system (P = 0·039, OR = 9·600, CI: 1·12-82·322), high risk in the Schulte Risk Classification (P = 0·012, OR = 5·466, CI: 1·448-20·628) and first surgery by other medical teams (P = 0·008, OR = 4·992, CI: 1·496-15·037) were associated with PC recurrence. Calcium (P = 0·01, OR = 7·270, CI: 1·611-32·812), intact parathyroid hormone (P = 0·037, OR = 1·001, CI: 1·000-1·001), local excision (P = 0·009, OR = 6·875, CI: 1·633-28·936) and recurrence (P = 0·014, OR = 7·762, CI: 1·504-40·055) were associated with death. A preoperative diagnostic system may provide a new method to distinguish PC from benign parathyroid lesions before surgery. For PC patients who did not undergo en-bloc resection at first operation, timely further surgery may offer a second chance of cure. Early diagnosis and surgery are pivotal to reduce mortality in PC patients.


Blood exosome marker miRNA-30d-5p: Role and regulation mechanism in cell stemness and gemcitabine resistance of hepatocellular carcinoma.
Cancer stem cells (CSCs) are different from regular cancer cells because of their self-renewal feature and differentiation potential, which establishes the backbone of the vital role of CSCs in the progress and drug resistance of hepatocellular carcinoma (HCC). The objective of this study was to evaluate the effects of blood exosome-derived miRNA-30d-5p on the stemness and gemcitabine resistance of HCC cells and the underlying mechanisms. The expression data of HCC-related miRNAs and mRNAs were downloaded from TCGA database and analyzed for differences. Employing the databases of starBase, TargetScan, miRDB, and mirDIP, we conducted target gene prediction upstream of mRNA. The expression of miRNA-30d-5p and SOCS3 mRNA was assayed by qRT-PCR, and the binding between them was validated by dual luciferase assay. CCK-8 was employed to evaluate cell viability and the IC50 value of gemcitabine. Cells were subjected to a sphere-forming assay to assess their ability to form spheres. Western blot was applied to evaluate the levels of cell surface marker proteins (Nanog, CD133, and Oct4) and exosome markers (CD9, CD81, and FLOT1). Bioinformatics analysis found that SOCS3 expression was down-regulated in HCC. qRT-PCR showed that SOCS3 expression was notably lower in HCC cell lines than in normal liver cell WRL68. At the cellular functional level, SOCS3 overexpression inhibited the viability, sphere-forming ability, stemness, and gemcitabine resistance of HCC cells. Bioinformatics analysis demonstrated that miRNA-30d-5p was the upstream regulator of SOCS3 and highly expressed in HCC tissues and cells. Dual luciferase assay demonstrated that miRNA-30d-5p could bind SOCS3. Rescue experiments showed that upregulating SOCS3 could reverse the effects of miRNA-30d-5p overexpression on the viability, sphere-forming ability, and gemcitabine sensitivity of HCC cells. Blood exosome-derived miRNA-30d-5p promoted the stemness and gemcitabine resistance of HCC cells by repressing SOCS3 expression. Hence, the miRNA-30d-5p/SOCS3 axis might be a therapeutic target for chemotherapy resistance and a feasible marker for the prognosis of HCC patients.


The prognostic value of pretreatment inflammatory biomarkers in primary angiosarcoma.
Recent studies have suggested a significant relationship between inflammatory indexes such as the neutrophil-to-lymphocyte ratio (NLR) and survival outcomes in various cancers. The aim of the present study was to evaluate the prognostic value of 6 pretreatment inflammatory markers in patients with primary angiosarcoma (AS) which is a rare and highly malignant type of soft tissue sarcoma. Fifty-six patients diagnosed with primary AS at West China Hospital between August 2009 and July 2016 were retrospectively enrolled. The value of each biomarker was calculated for its correlation with patients' overall survival. The low tumor grade, tumor size <5 cm, metastatic status, surgical treatment and low level of monocyte-to-lymphocyte ratio, NLR and lactate dehydrogenase (LDH) were correlated with better survival outcome in univariate analyses. In multivariate analyses, high levels of NLR (HR 2.673, 95% CI 1.253-5.703, p=0.011) and LDH (HR 2.964, 95% CI 1.464-5.998, p=0.003) were selected as independent prognostic factors. This study identifies the elevated pretreatment levels of NLR and LDH as prognostic markers in patients with primary AS.


Digital versus conventional impressions for fixed prosthodontics: A systematic review and meta-analysis.
Limited evidence is available for the marginal and internal fit of fixed dental restorations fabricated with digital impressions compared with those fabricated with conventional impressions. The purpose of this systematic review was to compare marginal and internal fit of fixed dental restorations fabricated with digital techniques to those fabricated using conventional impression techniques and to determine the effect of different variables on the accuracy of fit. Medline, Cochrane, and EMBASE databases were electronically searched and enriched by hand searches. Studies evaluating the fit of fixed dental restorations fabricated with digital and conventional impression techniques were identified. Pooled data were statistically analyzed, and factors affecting the accuracy of fit were identified, and their impact on accuracy of fit outcomes were assessed. Dental restorations fabricated with digital impression techniques exhibited similar marginal misfit to those fabricated with conventional impression techniques (P>.05). Both marginal and internal discrepancies were greater for stone die casts, whereas digital dies produced restorations with the smallest discrepancies (P<.05). When a digital impression was used to generate stereolithographic (SLA)/polyurethane dies, misfit values were intermediate. The fabrication technique, the type of restoration, and the impression material had no effect on misfit values (P>.05), whereas die and restoration materials were statistically associated (P<.05). Although conclusions were based mainly on in vitro studies, the digital impression technique provided better marginal and internal fit of fixed restorations than conventional techniques did.


First Acute-Course Electroconvulsive Therapy for Moderate-to-Severe Depression Benefits Patients With or Without Accompanying Baseline Cognitive Impairment.
Researchers are increasingly investigating therapeutic response associated with new patient subgroups as a way to improve electroconvulsive therapy (ECT) treatment outcomes and reduce adverse events. This study is the first to examine baseline cognitive impairment status as a predictor of clinical outcome in first acute-course ECT patients. Baseline cognitive function at various thresholds and serial depressive symptom severity data from first-time ECT patients were examined using generalized linear mixed-effects models. Of 1345 patients who met the inclusion criteria, 617 had available data at their third assessment visit (~15th treatment visit). There was a robust improvement in depression symptoms over time (P < 0.0001), and cognitive function was not associated with baseline levels of depressive symptoms or serially measured change in self-reported symptom severity during acute-phase ECT. These results indicate that an acute course of ECT for the treatment of moderate-to-severe depression benefits patients with or without accompanying baseline cognitive impairment. These findings may be useful in informing shared decision-making discussions about ECT risks and expected benefits.


[Control of smoking to reduce the incidence of bronchial cancer: application of Evin's law in France].
In France, 30% of adults smoke, and males smoke a little bit more than females. Young people smoke more and more, and 50% of 18-24 years-old males and females smoke. Tobacco causes 60,000 deaths each year in France. Publicity is now forbidden (Evins's law). Price of cigarette has been multiplied by two. Interdiction of smoking in public and closed places is however insufficiently respected. Budget devoted to information, education, and prevention, is also dramatically insufficient. By contrast, due to vigilance of the Comité National Contre le Tabagisme, tobacco sales decreased from 1991 to 1997 of 11.1%, and cigarette sales of 14.5%. French situation must be replaced in European and international context. European regulation on smoking interdiction increases the impact of the French legislation.


Effect of pravastatin sodium, a new inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, on very-low-density lipoprotein composition and kinetics in hyperlipidemia associated with experimental nephrosis.
The effect of Pravastatin sodium (CS-514), a new inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA R) on very-low-density lipoprotein (VLDL) composition and kinetics was studied in normal and experimental nephrotic rats under fasting conditions. Nephrotic rats, induced by a single intraperitoneal injection of puromycin aminonucleoside (100 mg/kg body weight), had significantly higher plasma lipids and apoprotein (apo) B concentrations than controls. The hypertriglyceridemia associated with nephrosis was mainly due to a markedly elevated VLDL-triglyceride (TG) concentration. Pravastatin sodium was administrated as a 0.04% solution in drinking water for 7 days to normal control and nephrotic rats. Plasma TG concentration in both control and nephrotic rats was significantly reduced by the treatment with Pravastatin, but plasma cholesterol levels were not reduced by the treatment in either group of rats. TG, cholesterol, phospholipid, and apo B concentrations in nephrotic VLDL were significantly reduced by Pravastatin treatment, whereas only TG was decreased in control VLDL. Pravastatin reduced the apo B 100 + 95/48 ratio in nephrotic VLDL. Pravastatin did not alter the lipid concentration of low-density lipoprotein (LDL) and high-density lipoprotein (HDL) in control and nephrotic rats. VLDL-TG turnover studies showed that TG secretion rate was significantly suppressed by Pravastatin administration without affecting its removal in both groups of rats. These suggested that Pravastatin, an inhibitor of cholesterol biosynthesis, can reduce VLDL concentration by rectifying the overproduction of VLDL exhibited in nephrotic rats.


The prevalence of risk factors for cardiovascular diseases among Polish surgical patients over 65 years.
Cardiovascular diseases (CVDs) are the leading cause of mortality among adults in Poland. A number of risk factors have significant influence on CVD incidence. Early identification of risk factors related to our lifestyle facilitates taking proper actions aiming at the reduction of their negative impact on health. The aim of the study was to compare the prevalence of CVD risk factors between patients aged over 65 years and patients of other age groups in surgical wards. The study was conducted for assessment and finding the distribution of major risk factors of CVD among 420 patients aged 18-84 years who were hospitalized in surgical wards. Interview, anthropometric measurements, blood pressure, and fasting blood tests for biochemical analysis were conducted in all subjects. Statistical analysis of the material was performed using Student's t-test, chi-square test, Fisher's exact test, Mann-Whitney U-test, and analysis of variance. While abdominal obesity (83.3%), overweight and obesity (68%), hypertension (65.1%), hypercholesterolemia (33.3%), and low level of physical activity (29.1%) were the most common CVD risk factors among patients over 65 years old, abdominal obesity (36.2%), overweight and obesity (36.1%), and current smoking were the most common CVD risk factors among patients up to the age of 35. In the age group over 65, the least prevalent risk factors for CVD were diabetes mellitus (14.8%), depressive episodes (13.6%), abuse of alcohol (11.4%), and smoking (7.8%). In the group under 35 years, we have not reported any cases of hypercholesterolemia and a lesser number of patients suffered from diabetes and HTN. Distribution of the major risk factors for CVD is quite high in the adult population, especially in the age group over 65, which can result in serious problems of health and increased rates of chronic diseases, especially CVDs.


An elastin-based vasculogenic scaffold promotes marginal islet mass engraftment and function at an extrahepatic site.
In islet transplantation, one of the major obstacles to optimal engraftment is the loss of islet natural vascularization and islet-specific extracellular matrix (ECM) during the islet isolation process. Thus, transplanted islets must re-establish nutritional and physical support through formation of new blood vessels and new ECM. To promote this critical process, we developed an elastin-based vasculogenic and ECM-promoting scaffold engineered for extrahepatic islet transplantation. The scaffold by design consisted of type I collagen (Coll) blended with 20wt% of elastin (E) shown to promote angiogenesis as well as de novo ECM deposition. The resulting "CollE" scaffolds h ad interconnected pores with a size distribution tailored to accommodate seeding of islets as well as growth of new blood vessels. In vitro, CollE scaffolds enabled prolonged culture of murine islets for up to one week while preserving their integrity, viability and function. In vivo, after only four weeks post-transplant of a marginal islet mass, CollE scaffolds demonstrated enhanced vascularization of the transplanted islets in the epididymal fat pad and promoted a prompt reversal of hyperglycemia in previously diabetic recipients. This outcome was comparable to that of kidney capsular (KC) islet transplantation, and superior to that of islets transplanted on the control collagen-only scaffolds (Coll). Crucial genes associated with angiogenesis (VEGFA, PDGFB, FGF1, and COL3A1) as well as de novo islet-specific matrix deposition (COL6A1, COL4A1, LAMA2 and FN1) were all significantly upregulated in islets on CollE scaffolds in comparison to those on Coll scaffolds. Finally, CollE scaffolds were also able to support human islet culture in vitro. In conclusion, CollE scaffolds have the potential to improve the clinical outcome of marginal islet transplantation at extrahepatic sites by promoting angiogenesis and islet-specific ECM deposition.


Brown Adipocyte ADRB3 Mediates Cardioprotection via Suppressing Exosomal iNOS.
The ADRB3 (β3-adrenergic receptors), which is predominantly expressed in brown adipose tissue (BAT), can activate BAT and improve metabolic health. Previous studies indicate that the endocrine function of BAT is associated with cardiac homeostasis and diseases. Here, we investigate the role of ADRB3 activation-mediated BAT function in cardiac remodeling. BKO (brown adipocyte-specific ADRB3 knockout) and littermate control mice were subjected to Ang II (angiotensin II) for 28 days. Exosomes from ADRB3 antagonist SR59230A (SR-exo) or agonist mirabegron (MR-exo) treated brown adipocytes were intravenously injected to Ang II-infused mice. BKO markedly accelerated cardiac hypertrophy and fibrosis compared with control mice after Ang II infusion. In vitro, ADRB3 KO rather than control brown adipocytes aggravated expression of fibrotic genes in cardiac fibroblasts, and this difference was not detected after exosome inhibitor treatment. Consistently, BKO brown adipocyte-derived exosomes accelerated Ang II-induced cardiac fibroblast dysfunction compared with control exosomes. Furthermore, SR-exo significantly aggravated Ang II-induced cardiac remodeling, whereas MR-exo attenuated cardiac dysfunction. Mechanistically, ADRB3 KO or SR59230A treatment in brown adipocytes resulted an increase of iNOS (inducible nitric oxide synthase) in exosomes. Knockdown of iNOS in brown adipocytes reversed SR-exo-aggravated cardiac remodeling. Our data illustrated a new endocrine pattern of BAT in regulating cardiac remodeling, suggesting that activation of ADRB3 in brown adipocytes offers cardiac protection through suppressing exosomal iNOS.


Contribution of Duffy antigen to chemokine function.
In addition to classical G protein-coupled receptors (GPCRs), a group of alternative, "silent" chemokine receptors has recently been identified. These serpentine molecules are not coupled to G proteins and subsequent signaling cascades, but can efficiently internalize their cognate chemokine ligands, thus act as "interceptors" (internalizing receptors). Here we discuss a mechanism by which a member of this family, Duffy antigen (DARC), contributes to chemokine-induced leukocyte emigration. Cumulative experimental evidence suggests that DARC on venular endothelium mediates chemokine internalization at the abluminal surface followed by transcytosis and transfer of the chemokine cargo onto the luminal surface. DARC is also expressed on the erythrocyte surface of DARC positive individuals. Erythrocyte DARC binds plasma chemokines which results, on one hand, in impediment of the chemokines loss from the circulation and, on the other hand, in neutralization of chemokines in the blood. This leads to leukocyte protection from inadvertent "desensitization" and enhancement of leukocyte recruitment.


Intrahippocampal Effects of Nickel Injection on the Affective and Cognitive Response in Wistar Rat: Potential Role of Oxidative Stress.
The present study focused on affective and cognitive behaviors in male Wistar rats, following direct and unique exposure to nickel chloride (NiCl2), as well as the possible involvement of oxidative stress. The rats were exposed to NiCl2 (300 μM), by intracerebral administration of 2 μL of this metal at the right hippocampus, using the stereotaxic approach. Five days after the surgery, a battery of behavioral tests was performed, including the open-field test (OFT) and elevated plus maze test (EPM) to assess the state of anxiety-like behavior and forced swimming test (FST) for depressive-like behavior. Y-maze and Morris Water Maze (MWM) were used to evaluate working memory and spatial learning. Thereafter, oxidative stress markers of the hippocampus were evaluated. The results confirm that NiCl2 exerts anxiogenic effects in both anxiety tests and depressogenic effects in the FST. In addition, MWM and Y-maze data show that NiCl2 causes memory and spatial learning disorders. The biochemical assay results showed that intrahippocampal injection of NiCl2 increased the levels of nitric oxide and lipid peroxidation (p < 0.001), while the activities of catalase and superoxide dismutase were significantly decreased in the hippocampus (p < 0.01). Overall, these results suggest that NiCl2 causes affective and cognitive disorders and oxidative stress in rats.


Association between chronic conditions and urinary incontinence in females: a cross-sectional study using national survey data.
Urinary incontinence affects up to half of women, yet few speak to their health care provider about or receive treatment for the condition. To aid with identifying subpopulations at risk for urinary incontinence, we examined the associations between 10 chronic health conditions and urinary incontinence among Canadian adult females. We conducted a cross-sectional analysis of survey data from the Canadian Community Health Survey (2013-2014) involving female respondents aged 25 years or older living in a private dwelling. Presence of chronic conditions and urinary incontinence were measured by self-report. We used logistic regression modelling with sampling weights, controlling for age, income, ethnicity, body mass index and smoking. Multiple imputation and probabilistic bias analysis were used to address missing covariate data and unmeasured confounding from parity. Our analysis included 60 186 respondents representing more than 12 million Canadian females, of whom 45.8% (95% confidence interval [CI] 45.0%-46.6%) reported at least 1 chronic condition. Chronic conditions were associated with more than twice the odds of urinary incontinence (adjusted odds ratio [OR] 2.42, 95% CI 2.02-2.89). Associations were largest for bowel disorders (adjusted OR 2.92, 95% CI 2.44-3.49); modest for chronic obstructive pulmonary disease (adjusted OR 2.00, 95% CI 1.63-2.45), asthma (adjusted OR 1.82, 95% CI 1.52-2.19), arthritis (adjusted OR 1.98, 95% CI 1.74-2.24) and heart disease (adjusted OR 1.73, 95% CI 1.48-2.02); and smallest for diabetes (adjusted OR 1.20, 95% CI 1.02-1.41) and high blood pressure (adjusted OR 1.27, 95% CI 1.12-1.44). Results slightly attenuated but did not substantively change after imputation and bias analysis. We found that chronic conditions are associated with significantly higher odds of comorbid urinary incontinence among Canadian adult females, which is consistent with previous research. Our findings support routine inquiry regarding urinary incontinence symptoms among women accessing health care for chronic conditions.


Reduced inhibition of endothelial-derived relaxing factor causes the hyperdynamic circulation in chronic severe anemia.
Patients with chronic severe anemia have a vasodilated state and hyperdynamic circulation. The cause of vasodilation in these patients is not known. We postulate that the low levels of hemoglobin in these patients results in reduced inhibition of basal EDRF activity leading to generalized vasodilation.


Trajectory for 66 patients treated with periacetabular osteotomy (PAO) and subsequent total hip arthroplasty: a follow-up study including 1378 hips from the Aarhus PAO database.
Outcomes for patients treated with PAO and subsequent total hip arthroplasty (THA) remain unclear. We evaluated patient-reported outcomes among patients treated with PAO and subsequent THA and investigated differences in the number of additional surgical procedures after PAO among patients treated with PAO and subsequent THA and patients treated with PAO only. 1378 hips underwent PAO and subsequently 66 hips were treated with THA. We evaluated the Hip disability and Osteoarthritis Outcome Score (HOOS) and physical activity questions for the 66 hips. Additional surgery after PAO was identified through inquiry to the Danish National Patient Registry. 13% undergoing PAO and subsequent THA reported a HOOS pain score ≤ 50 indicating a clinical failure. The risk difference for hip arthroscopy after PAO within 2 and 4 years was 14% (CI 5-23%) and 26% (CI 15-38%) in favor of hips treated with PAO only. Similarly, the risk difference for screw removal within 2 and 4 years was 19% (CI 8-29%) and 23% (CI 12-34%). 87% of patients undergoing PAO and subsequent THA had little or no hip pain. However, these patients received a high number of additional surgeries after PAO. Surgeons and patients may consider if additional surgery after PAO may be the first choice in a series of actions leading to conversion to THA.


Trichostatin A activates the osteopontin gene promoter through AP1 site.
In this study, we investigated osteoblastic differentiation by trichostatin A (TSA), a histone deacetylase inhibitor in mouse undifferentiated mesenchymal cell line. TSA increased the osteopontin (OPN) mRNA level and OPN protein. Deletion analysis of the promoter region revealed TSA-induced luciferase response was regulated by -75 to -65 of the OPN promoter. There was an AP1-binding sequence at the site of the OPN promoter. In an electrophoretic mobility shift assay, bands of the complexes were supershifted by addition of antibody to c-fos and phosphorylated c-jun. These data suggested that AP1 plays a crucial role in the TSA-induced OPN expression.


Modulation of gut microbiota by Ilex kudingcha improves dextran sulfate sodium-induced colitis.
Increasing evidence shows that the gut microbiota contributes to the occurrence and development of colitis. Kudingcha (KDC), made from the leaves of Ilex kudingcha, could mitigate inflammation, however, little is known about the relationship between modulatory effect on gut microbiota by KDC and improvement of colitis. In this study, the attenuating effects of KDC extract (KDCE) on dextran sulfate sodium (DSS)-induced colitis and gut microbiota in C57BL/6 mice were investigated. It was found that the supplementation of KDCE could alleviate typical symptoms of IBD including weight loss, colon shortening, intestinal barrier damage, and decreases in the colitis disease activity index and pro-inflammatory cytokines. Moreover, KDCE supplementation could reverse the alteration of gut microbiota in the colitic mice by increasing the abundances of potential beneficial bacteria, e.g. Odoribacter, Prevotella and Helicobacter, and decreasing the abundances of potential harmful bacteria, e.g. Parabacteroides, Bacteroides, Turicibacter, Parasutterella and Lachnospiraceae. The levels of short-chain fatty acids in feces, cecum contents and serum were also regulated by KDCE. Furthermore, the correlation analysis suggested that KDCE could attenuate DSS-induced colitis which might be related to the alteration of gut microbiota. Therefore, the modulation of gut microbiota by KDCE might be a potential strategy for improving inflammation-driven diseases.


Hypothermic regional perfusion for protection of the spinal cord during periods of ischemia.
Ischemic spinal cord injury with resulting postoperative paraplegia is an inherent risk for operations on the thoracic aorta. The mechanism of injury is not clearly understood, and numerous adjuncts to avoid this complication have been suggested, with conflicting clinical results. A new technique of hypothermic regional perfusion of the spinal cord is described. Fifteen female pigs weighing 21 to 39 kg were used for the experiment. The control group consisted of 5 animals in which the thoracic aorta was clamped at the distal arch for 30 minutes. All of these animals sustained postoperative neurological damage. Eighty percent sustained postoperative paraplegia, and 20% had severe spasticity of the hind legs that precluded normal ambulation. The experimental group consisted of 10 animals in which hypothermic regional perfusion was performed for 30 minutes after cross-clamping of the distal arch. Perfusion cooling was followed by 30 minutes of ischemia in 5 animals and 45 minutes of ischemia in the remaining 5. All animals that underwent hypothermic regional perfusion were able to walk postoperatively, and no evidence of ischemic injury was found at postmortem examination of the spinal cords. This technique proved to be simple and effective in protecting the spinal cord for up to 45 minutes of ischemia in the experimental group. The clinical implications of this concept are promising for patients undergoing operations on the thoracic aorta.


Morphospecies and molecular diversity of 'lace corals': the genus Reteporella (Bryozoa: Cheilostomatida) in the central North Atlantic Azores Archipelago.
As in most bryozoans, taxonomy and systematics of species in the genus Reteporella Busk, 1884 (family Phidoloporidae) has hitherto almost exclusively been based on morphological characters. From the central North Atlantic Azores Archipelago, nine Reteporella species have historically been reported, none of which have as yet been revised. Aiming to characterise the diversity and biogeographic distribution of Azorean Reteporella species, phylogenetic reconstructions were conducted on a dataset of 103 Azorean Reteporella specimens, based on the markers cytochrome C oxidase subunit 1, small and large ribosomal RNA subunits. Morphological identification was based on scanning electron microscopy and complemented the molecular inferences. Our results reveal two genetically distinct Azorean Reteporella clades, paraphyletic to eastern Atlantic and Mediterranean taxa. Moreover, an overall concordance between morphological and molecular species can be shown, and the actual bryozoan diversity in the Azores is greater than previously acknowledged as the dataset comprises three historically reported species and four putative new taxa, all of which are likely to be endemic. The inclusion of Mediterranean Reteporella specimens also revealed new species in the Adriatic and Ligurian Sea, whilst the inclusion of additional phidoloporid taxa hints at the non-monophyly of the genus Reteporella. Being the first detailed genetic study on the genus Reteporella, the high divergence levels inferred within the genus Reteporella and family Phidoloporidae calls for the need of further revision. Nevertheless, the overall concordance between morphospecies and COI data suggest the potential adequacy of a 3% cut-off to distinguish Reteporella species. The discovery of new species in the remote Azores Archipelago as well as in the well-studied Mediterranean Sea indicates a general underestimation of bryozoan diversity. This study constitutes yet another example of the importance of integrative taxonomical approaches on understudied taxa, contributing to cataloguing genetic and morphological diversity.


Androgen deprivation-mediated cytoreduction before interstitial brachytherapy for prostate cancer does not abrogate the elevated risk of urinary morbidity associated with larger initial prostate volume.
We examined whether prostate volume reduction after a short course of androgen deprivation (AD) lowered the risks of acute and chronic urinary morbidity related to radioactive seed implantation for low-risk prostate cancer. Eighty-one patients received AD for cytoreduction before interstitial brachytherapy alone. Urinary morbidity was carefully assessed for all patients during a median followup of 53 (range, 23-78) months after treatment. Outcomes were then compared with those of a control group of 81 patients who were matched 1:1 based on identical prostate volume measured at the time of radioactive seed implant, but who had not received AD. Despite effective cytoreduction (median, 30% prostate volume reduction) with AD, prolonged catheterization was required significantly more often for patients who had received AD when compared with the control group of patients who were implanted at identical prostate volumes but who had not received AD (27% vs. 9%, p = 0.02). This finding remained statistically significant on multivariate analysis (p = 0.04). Surgical intervention (9% vs. 4%, p = 0.09) and subsequent urinary incontinence (4% vs. 1%, p = 0.16) were also more frequent among patients who had received AD when compared with implant volume-matched controls. Patients who achieved smaller prostate volumes through the use of AD maintained a significantly elevated risk (threefold) for urinary complications, commensurate with their initially large prostate volume, when compared with a control group of patients who were implanted at identical prostate volumes but who had not received AD. Therefore, patients presenting with larger prostate glands that would warrant a short course of AD before implant should be counseled accordingly when discussing options for local therapy.


The long-term effects of uranyl nitrate on the structure and function of the rat kidney.
Studies were undertaken to determine the long-term effects of the nephrotoxin, uranyl nitrate, on the function and structure of the rat kidney. Animals were injected with 10 mg/kg B.Wt. of uranyl nitrate and renal function studies were performed one, two, four and eight weeks after drug administration. Light microscopy and scanning and transmission electron microscopy were used to characterize the morphologic changes at each time interval. Glomerular filtration rate was significantly reduced (P less than 0.01) one week (0.18 +/- 0.06 ml/min/100 gm B.Wt.) and two weeks (0.54 +/- 0.09 ml/min/100 gm B.Wt.) after drug treatment compared to controls (1.01 +/- 0.4 ml/min/100 gm B.Wt.) and returned to normal values by four weeks. The fractional excretion of sodium was significantly increased (P less than 0.01) one week after uranyl nitrate treatment (2.45% +/- 0.82) compared to controls (0.29% +/- 0.11). No further differences in this parameter were noted after one week. At all time intervals studied the pars recta of the proximal tubule (S2 and S3 segments) was the most consistently damaged region of the nephron. Acute tubular necrosis and tubular regeneration of these segments were evident one and two weeks after drug administration. Many of the tubules were widely dilated and lined by low-lying squamous epithelial cells. By four weeks some of these pars recta segments could be classified as microcysts and this type of lesion persisted as long as eight weeks after treatment. Regeneration of most injured proximal tubules was complete by eight weeks. Atrophic proximal tubules, marked interstitial fibrosis and a mononuclear cell infiltration, consistent with a chronic type of injury, were noted at the later time intervals. These results suggest that uranyl nitrate induces a persistent injury to the kidneys of rats causing lesions as long as eight weeks after injection.


[Stewart and Bergstrom Syndrome. Contribution of a new observation (author's transl)].
Authors report a new observation to the Stewart and Bergstrom syndrome, which to their knowledge, can be the second case in the medical literature.


Hepatobiliary scintigraphy in arteriohepatic dysplasia (Alagille's syndrome). A report of two cases.
Hepatobiliary scintigraphy has proven to be of great utility in distinguishing biliary atresia from other causes of neonatal cholestasis. Arteriohepatic dysplasia (Alagille's syndrome) is an uncommon entity characterized by typical facial features, pulmonary artery stenosis, and a liver disorder which presents during the neonatal period as progressive jaundice. Two neonates, who were later shown to have Alagille's syndrome, underwent hepatobiliary scintigraphy to rule out biliary atresia. Findings on the hepatobiliary scans from the two patients were similar to those usually associated with biliary atresia and both finally required surgical exploration to rule out biliary atresia. The findings on hepatobiliary scans in these patients with Alagille's syndrome are discussed and compared with those associated with other forms of neonatal cholestasis.


Genome-wide association study identifies susceptibility loci for acute myeloid leukemia.
Acute myeloid leukemia (AML) is a hematological malignancy with an undefined heritable risk. Here we perform a meta-analysis of three genome-wide association studies, with replication in a fourth study, incorporating a total of 4018 AML cases and 10488 controls. We identify a genome-wide significant risk locus for AML at 11q13.2 (rs4930561; P = 2.15 × 10-8; KMT5B). We also identify a genome-wide significant risk locus for the cytogenetically normal AML sub-group (N = 1287) at 6p21.32 (rs3916765; P = 1.51 × 10-10; HLA). Our results inform on AML etiology and identify putative functional genes operating in histone methylation (KMT5B) and immune function (HLA).


Jaw mobility changes in patients with upper aerodigestive tract cancer undergoing radiation therapy.
Radiation therapy is a therapeutic modality widely used for treatment of upper aerodigestive tract (UADT) neoplasms. However, its action is not restricted to tumor cells, and it may cause a variety of adverse reactions, including reduced jaw mobility. A prospective cohort study was conducted to assess changes in jaw mobility in patients with UADT cancer undergoing radiation therapy. Fifty-six patients completed the study. The results showed a significant reduction in mouth opening (p<0.001), right lateral excursion (p=0.038) and left lateral excursion (p=0.035) of the jaw, a significant increase in the presence (p<0.001) and severity of oral mucositis (p<0.001), and a significant decrease in performance status (p<0.001) after radiation therapy. Thirty-six patients (64.3%) exhibited reduction in mouth opening after treatment. The variables significantly associated with mouth opening reduction on bivariate analysis were: modification of diet (p=0.037), radiation field (p=0.024), presence of mucositis (p=0.003), and reduction in performance status (p=0.007). After adjustment by the multivariate model, the only variables that remained significantly associated with reduction in mouth opening were presence of mucositis (p=0.018) and reduction in performance status (p=0.47). These findings indicate that patients with upper aerodigestive tract cancer experience reduced jaw mobility after radiation therapy, which is strongly correlated with mucositis and reduced functional ability.


The effect of a fever-like response on the secondary antibody response of the rat.
Since fever appears to modulate the primary humoral immune response, a fever-like response was induced in 18 rats by cooling their preoptic areas during the first five days after re-immunization with sheep erythrocytes. The titre of antibodies in these rats was the same as that in 17 control animals, indicating that the febrile response does not influence the magnitude of the secondary antibody response. It is suggested that only those fevers evolving in the early phase of a primary, natural infection may modulate the magnitude of the humoral immune response to the pathogen.


Suppression of human cytotoxic lymphocytes by methylprednisolone. An immunosuppressive mechanism of action of steroids.
In order to gain insight into the immunosuppresive mechanism of action of corticosteroids, an in vitro model of the cellular immune response was used to study the effect of methylprednisolone on human lymphocyte-mediated cytotoxicity. Concentrations from 0.25 to 10 microgram/ml were equally effective in producing 74% suppression lymphocyte-mediated cytotoxicity when the steroid was present during the entire period of in vitro sensitization. A 12.5-fold increase in effector to target cell ratio was required to achieve 30% 51Cr release when cytotoxic lymphocytes were generated in the prescence of methylprednisolone. Lymphocyte-mediated cytotoxicity was suppressed 48% when methylprednisolone was present only during the initial 24 hr of the 7-day in vitro sensitization period. Methylprednisolone also effectively inhibited cytotoxicity when it was incubated with sensitized lymphocytes for 3hr before incubating these cells with target cells. Our observations suggest that two of the major immunosuppressive mechanisms of action methylprednisolone are suppression of the generation of cytotoxic lymphocytes and suppression of specifically sensitized cytotoxic lymphocytes.


Mania and sexual risk: associations with behavioral self-regulation.
Risky sexual behavior among young adults is a central public health concern. Hallmark cognitive effects of mania involve grandiose extrinsic goal-setting, which may be part of a tendency to approach rewarding cues while underestimating potential negative consequences. Poor impulse control also reflects a tendency to seek reward and rely on emotional decision-making. In contrast, effortful control is associated with adaptive decision making. Participants (n=595) completed measures of impulsivity, risk for mania, and risky sexual behavior. Relationships between risk for mania, behavioral self-regulation, and risky sexual behavior were examined in a negative binomial hurdle model. For the hurdle portion, sensation-seeking was positively associated with the likelihood of engaging in risky sexual behavior. Effortful control was inversely associated with the likelihood of engaging in risky sexual behavior, but only among those high in risk for mania. Among those endorsing engagement in risky sex, urgency was positively, and effortful control negatively, associated with frequency of risky sex. Risk for mania was positively associated with frequency of risky sex, but only for those low in effortful control. Findings were among a homogeneous, young adult, nonclinical population, limiting generalizability. Examining these associations among a clinical population in an active manic episode is warranted. Results suggest high levels of effortful control may diminish the hallmark effects of mania on cognition thereby reducing engagement in risky sexual behavior. Treatments targeting emotion-based rash action and effortful decision making may be particularly important for those experiencing manic symptoms.


Abbreviated breast magnetic resonance protocol: Value of high-resolution temporal dynamic sequence to improve lesion characterization.
To evaluate the added value of ULTRAFAST-MR sequence to an abbreviated FAST protocol in comparison with FULL protocol to distinguish benign from malignant lesions in a population of women, regardless of breast MR imaging indication. From March 10th to September 22th, 2014, we retrospectively included a total of 70 consecutive patients with 106 histologically proven lesions (58 malignant and 48 benign) who underwent breast MR imaging for preoperative breast staging (n=38), high-risk screening (n=7), problem solving (n=18), and nipple discharge (n=4) with 12 time resolved imaging of contrast kinetics (TRICKS) acquisitions during contrast inflow interleaved in a regular high-resolution dynamic MRI protocol (FULL protocol). Two readers scored MR exams as either positive or negative and described significant lesions according to Bi-RADS lexicon with a TRICKS images (ULTRAFAST), an abbreviated protocol (FAST) and all images (FULL protocol). Sensitivity, specificity, positive and negative predictive values, and accuracy were calculated for each protocol and compared with McNemar's test. For all readers, the combined FAST-ULTRAFAST protocol significantly improved the reading with a specificity of 83.3% and 70.8% in comparison with FAST protocol or FULL protocol, respectively, without change in sensitivity. By adding ULTRAFAST protocol to FAST protocol, readers 1 and 2 were able to correctly change the diagnosis in 22.9% (11/48) and 10.4% (5/48) of benign lesions, without missing any malignancy, respectively. Both interpretation and image acquisition times for combined FAST-ULTRAFAST protocol and FAST protocol were shorter compared to FULL protocol (p<0.001). Compared to FULL protocol, adding ULTRAFAST to FAST protocol improves specificity, mainly in correctly reclassifying benign masses and reducing interpretation and acquisition time, without decreasing sensitivity.


Temporal patterns of immunoblot-reactive antibodies to cytomegalovirus in transplant recipients.
A total of 234 sera from 44 allograft recipients were compared with 12 sera from 9 immunocompetent patients with symptomatic cytomegalovirus (CMV) infection and with 20 sera of 20 healthy individuals with latent CMV infection. The presence of immunoreactive proteins was not associated with a specific transplant group or with different immunosuppressive regimens but rather with the kinetics of the immune response. Acute phase sera demonstrated early antibodies to proteins p38 and p48, followed by high or still rising antibodies to high molecular weight proteins, particularly p150, and their later decline to persistent lower levels. Convalescent phase sera were identified serologically by the transient appearance of IgG antibodies directed to 22-26 kDa polypeptides. Immunoreactive p44 was present in 85% of all patients with mild disease and in 40% of all patients with severe CMV disease. When tested in parallel, the immunoblot analysis was shown to be a more sensitive indicator of early CMV antibodies in allograft recipients than the ELISA technique.


Protein kinase C activation enhances K+-stimulated endogenous dopamine release from rat striatal synaptosomes in the absence of an increase in cytosolic Ca2+.
The possibility that protein kinase C modulates neurotransmitter release in brain was investigated by examining the effects of 12-O-tetradecanoylphorbol 13-acetate (TPA) on Ca2+ transport and endogenous dopamine release from rat striatal synaptosomes. TPA (0.16 and 1.6 microM) significantly increased dopamine release by 24 and 33%, respectively, after a 20-min preincubation with TPA followed by 60 s of depolarization with 30 mM KCl. Depolarization-induced 45Ca2+ uptake, measured simultaneously with dopamine release, was not significantly increased by TPA. Neither 45Ca2+ uptake nor dopamine release was altered under resting conditions. When the time course of K+-stimulated 45Ca2+ uptake and dopamine release was examined, TPA (1.6 microM) enhanced dopamine release after 15, 30, and 60 s, but not 1, 3, or 5 s, of depolarization. A slight increase in 45Ca2+ uptake after 60 s of depolarization was also seen. The addition of 30 mM KCl to synaptosomes which had been preloaded with the Ca2+-sensitive fluorophore fura-2 increased the cytosolic free Ca2+ concentration ([Ca2+]i) from 445 nM to 506 nM after 10 s of depolarization and remained elevated after 60 s. TPA had no effect on [Ca2+]i under depolarizing or resting conditions. Replacing extracellular Ca2+ with 100 microM EGTA reduced K+-stimulated (60 s) endogenous dopamine release by 53% and decreased [Ca2+]i to 120 nM. In Ca2+-free medium, 30 mM KCl did not produce an increase in the [Ca2+]i. TPA (1.6 microM) did not alter the [Ca2+]i under resting or depolarizing conditions, but did increase K+-stimulated dopamine release in Ca2+-free medium.(ABSTRACT TRUNCATED AT 250 WORDS)


The effect of sulphonylurea on the in vivo tissue uptake of glucose in normal rats.
To evaluate the effect of sulphonylurea on in vivo tissue uptake of glucose, the arterial injection tissue-sampling technique of Oldendorf was used to measure the glucose uptake of brain; liver; subcutaneous fat; and of three skeletal muscles, the masseter, femoris and soleus. Rats gavaged with glipizide 5 mg/kg daily for 5 days were compared to vehicle-treated rats. The serum glucose levels at the time of the experiment were identical in the two groups (10.36 +/- 0.42 mmol/l vs 10.38 +/- 0.36 mmol/l). Glipizide treatment did not result in an increase in glucose uptake by the various tissues studied. It is concluded that, under physiological conditions in non-fasted rats, sulphonylureas do not significantly alter tissue uptake of glucose.


The development of a peptide SRM-based tandem mass spectrometry assay for prenatal screening of Down syndrome.
Two new biomarkers, serum amyloid-P (SAP) and plasma C1-inhibitor protein are elevated in the maternal circulation of mothers carrying Down syndrome foetuses. Much emphasis of late\ has been put on the lack of translational tests being developed following the identification of new biomarkers. We have created a single-reaction-monitoring (SRM) tandem mass spectrometry-based assay for the quantitation of these biomarkers and compared these results with an in-house developed immunofluorescence-based technique (IF). This MS-based assay is a rapid 5 min test and a simple "one pot reaction," requiring only 5μl of plasma. To evaluate the potential of SRM-based quantitation in a clinical setting, SAP and C1-inhibitor were quantitated in 38 normal and Down syndrome affected pregnancies. Plasma SAP levels in the Down's group were significantly raised at 10-14 weeks (p<0.0015) and 14-20 weeks (p<0.0001). Plasma C1-inhibitor levels were also observed significantly elevated in the Down's group (10-14 weeks, p<0.0193, 14-20 weeks, p<0.0001). Analysis using the IF technique did not show any significant elevation of plasma SAP levels or C1-inhibitor levels. This rapid and sensitive assay demonstrates the potential of multiplexed tandem MS-based quantitation of proteins in chemical pathology labs and in a more cost-effective, accurate manner than conventionally used antibody methods.


An acidic sphingomyelinase Type C activity from Mycobacterium tuberculosis.
Sphingomyelinases (SMases) catalyze the hydrolysis of sphingomyelin to ceramide and phosphorylcholine. Sphingolipids are recognized as diverse and dynamic regulators of a multitude of cellular processes mediating cell cycle control, differentiation, stress response, cell migration, adhesion, and apoptosis. Bacterial SMases are virulence factors for several species of pathogens. Whole cell extracts of Mycobacterium tuberculosis strains H37Rv and CDC1551 were assayed using [N-methyl-(14)C]-sphingomyelin as substrate. Acidic Zn(2+)-dependent SMase activity was identified in both strains. Peak SMase activity was observed at pH 5.5. Interestingly, overall SMase activity levels from CDC1551 extracts are approximately 1/3 of those of H37Rv. The presence of exogenous SMase produced by M. tuberculosis during infection may interfere with the normal host inflammatory response thus allowing the establishment of infection and disease development. This Type C activity is different from previously identified M. tuberculosis SMases. Defining the biochemical characteristics of M. tuberculosis SMases helps to elucidate the roles that these enzymes play during infection and disease.


Using neural networks to predict the effect of the preload location on the natural frequencies of a cantilever beam.
With the evolution of computational power of computers in 20th century, neural networks (NNs) are becoming more popular in different engineering applications because of its ability to approximate static and dynamic, linear and non-linear, multi-dimensional systems. For example, they are used in industrial processes to automate assembly lines which increases its productivity and in automotive to reduce gas consumption of an engine. In this paper, NNs are utilized to reduce the computational power needed for finite element methods (FEM) simulations. A case study is taken for which NNs are used to predict the effect of the preload position and magnitude on the natural frequencies of the prestressed cantilever beam. A simple FEM model is implemented to generate the data set required to train the NN. The steps done to construct the FEM are discussed and the FEM model results are verified. The effect of the preload position on the natural frequencies of the beam is studied. A NN is then implemented to predict the natural frequencies of the beam for different beam cross-section geometries and different preload magnitudes and positions. The NN architecture, data processing and training methodology are explained. The NN and FEM results are compared to show the accuracy of the NN predictions. The results are shown to be in good agreement.


Homocysteine: a risk factor for retinal venous occlusive disease.
Recent studies have shown a relationship between elevated levels of homocysteine and vascular disease including cerebrovascular accidents and myocardial infarctions. We evaluated patients with a recent retinal vein occlusion to determine if there was an associated elevation of homocysteine. Age and gender matched case-controlled study. Twenty patients with retinal venous occlusive disease within the previous 6-month period and 40 control patients without retinal venous occlusive disease were enrolled in the study. Twenty patients with a history of retinal vein occlusion underwent laboratory testing to determine serum homocysteine levels. In addition, a health survey was completed and several laboratory tests relating to vascular disease including cholesterol were checked. Two control groups were selected. The first group included patients with diabetes and no history of retinal vascular occlusive disease. The second control group included nondiabetic patients who also had no prior history of retinal vascular occlusive disease. The main parameter measured in this study is fasting homocysteine. Fifteen of 20 patients (75%) with retinal vein occlusion disease had an elevated fasting serum homocysteine level, whereas only 5 of 40 control patients (13%) had an abnormal homocysteine level (P < 0.0005). Patients with retinal venous occlusive disease have higher levels of homocysteine, which may serve as a modifiable risk factor.


Correlation of serum N-Acetylneuraminic acid with the risk and prognosis of acute coronary syndrome: a prospective cohort study.
N-acetylneuraminic acid (Neu5Ac) is a functional metabolite involved in coronary artery disease (CAD). We aimed to evaluate the relationship between serum Neu5Ac and the risk and prognosis of acute coronary syndrome (ACS) in a real-world prospective study. Patients with suspected ACS who underwent coronary angiography were included. Serum Neu5Ac was measured at admission. Coronary lesion severity was evaluated by Gensini Score. GRACE risk stratification was performed at admission. Major adverse cardiac events (MACEs) were recorded during follow-up. A total of 766 patients, including 537 with unstable angina (UAP), 100 with myocardial infarction (MI), and 129 without CAD were included. The circulating Neu5Ac level was significantly higher in patients with MI (median [1QR]: 297[220, 374] ng/ml) than in those with UAP (227 [114, 312] ng/ml) or without CAD (207 [114, 276] ng/ml; both p < 0.001). Serum level of Neu5Ac was positively correlated with age, hypertension, serum uric acid, creatinine, MB isoform of creatine kinase (CK-MB), and Gensini score (all p < 0.05). Receiver operating characteristic curve analysis showed that a higher serum Neu5Ac was potentially associated with MI and high-risk GRACE stratification in ACS patients. Logistic analysis identified only elevated serum Neu5Ac as an independent predictor of MACEs in these patients (odds ratio [OR]: 1.003, 95% confidence interval [CI]: 1.002-1.005, p < 0.001). Serum Neu5Ac is associated with myocardial injury, GRACE risk category, and prognosis in ACS patients.