Antimicrobial drug resistance in salmonella-infected aortic aneurysms.
Salmonella infection of the aorta and adjacent arteries is rare, but life-threatening. There is an increasing number of infections caused by antimicrobial drug resistant Salmonella. This study sought to assess the association between antimicrobial drug resistance and clinical outcomes of patients with Salmonella-infected aortic aneurysm. Data were collected by retrospective chart review. Between October 1995 and October 2004, 34 patients with Salmonella-infected aortic aneurysm were included. Aneurysm-related deaths were defined as hospital deaths and late deaths due to prosthetic graft infection. Analysis was performed using the chi2 test, Fisher's exact test, and Mann-Whitney test. Nineteen patients had a suprarenal and 15 patients had an infrarenal aortic infection. The most common responsible pathogen was group C Salmonella (47%). Ciprofloxacin-resistant Salmonella infection occurred since March 2001 and the rate increased from 0 per 15 in the years before March 2001 to 5 per 19 in the years after March 2001 (p = 0.005 by Fisher's exact test). Among the 26 patients who had combined medical and surgical therapy, 4 died in the hospital and 4 died of late prosthetic graft infection 3 to 6 months after operation, whereas 4 of the 8 who had medical therapy alone died of aneurysm rupture during hospitalization. The actuarial survival rates by the Kaplan-Meier method were 64% at 6 months, 61% at 1 year, and 56% at 5 years. The risk factors for aneurysm-related death were old age (78.5 +/- 9.7 years vs 63.5 +/- 11.4 years; p < 0.001) and ciprofloxacin-resistant Salmonella infection (4 of 5 vs 8 of 29; p = 0.042). There was an increased mortality associated with ciprofloxacin resistance in infected aortic aneurysms with Salmonella. With an increasing incidence of ciprofloxacin resistant Salmonella, third generation cephalosporin is the antibiotic of choice for Salmonella-infected aneurysm.


Chinese SLE Treatment and Research group (CSTAR) registry: Clinical significance of thrombocytopenia in Chinese patients with systemic lupus erythematosus.
To investigate the prevalence, clinical characteristics, and prognosis of thrombocytopenia (TP) in Chinese patients with systemic lupus erythematosus (SLE). The study was conducted based on the Chinese SLE Treatment and Research group (CSTAR) registry. Thrombocytopenia was defined as the platelet count<100,000/mm3 at enrollment. Severe thrombocytopenia was defined as the platelet count<50,000/mm3. The prevalence of SLE-related TP, the associations of thrombocytopenia with demographic data, organ involvements, laboratory findings, disease activity, damage, and mortality were investigated. Of 2104 patients with SLE, 342 patients (16.3%) were diagnosed with thrombocytopenia. The prevalence of neuropsychiatric SLE, vasculitis, myositis, nephritis, mucocutaneous lesions, pleuritis, fever, leukocytopenia and hypocomplementemia were significantly higher in patients with thrombocytopenia (p<0.05). SLE disease activity index (SLEDAI) was significantly higher in patients with thrombocytopenia (p<0.05). Multivariate analysis showed that leukocytopenia (OR = 2.644), lupus nephritis (OR = 1.539), hypocomplementemia (OR = 1.497) and elevated SLEDAI (OR = 1.318) were independently associated with thrombocytopenia (p<0.05). Long disease duration (OR = 1.006) was an independent risk factor of severe thrombocytopenia, while anti-rRNP (OR = 0.208) was an independent protective factor of severe thrombocytopenia (p<0.05). Long disease duration was an independent risk factor of mortality in patients with thrombocytopenia (RR = 1.006). The 6-year survival of patients with thrombocytopenia was significantly lower than patients without thrombocytopenia (88.2% vs. 95.5%). Thrombocytopenia was a common manifestation of SLE and was associated with leukocytopenia, nephritis and severe disease activity. Severe thrombocytopenia tended to occur in long-term and relatively inactive SLE. Patients with SLE-related thrombocytopenia has a decreased long-term survival rate. Long disease duration was an independent risk factor of mortality in patients with thrombocytopenia.


Effect of Ichnocarpus frutescens (L.) R.Br. hexane extract on preadipocytes viability and lipid accumulation in 3T3-L1 cells.
To investigate the crude extracts of Ichnocarpus frutescens (I. frutescens) for antiobesity effect. Leaves of I. frutescens were sequentially extracted with hexane, ethyl acetate, and methanol and their effect on viability of 3T3-L1 preadipocytes were evaluated. Based on this the apoptosis on preadipocytes was confirmed by DNA fragmentation and LDH (Lactate dehydrogenase) leakage assays. Anti-adipogenesis was performed by oil red O (ORO) staining and free glycerol release in the medium of differentiated adipocytes. The hexane extract of I. frutescens (IFHE) inhibited cell viability in a time- and dose-related manner. An increased release of LDH, as a marker of membrane integrity, was observed at a dose of 200 μg/mL. The discontinuous DNA fragments on agarose gel electrophoresis showed the apoptotic effect of the IFHE. Morphological observations of cells stained with ORO showed a decrease in cellular lipid content at the concentrations tested compared to the induced control cells. In the experiment of lipolytic activity, treatment with IFHE enhanced glycerol secretion with the rates of approximately 28%, 55%, and 46% at the concentrations of 100, 200 and 300 μg/mL, respectively. The observed properties clearly revealed the medicinal property of I. frutescens in the treatment of obesity.


Headache--defined.
Headache is one of man's most common afflictions. Increasing interest from the general population has contributed to the recent surge in research. This research relates to etiology or pathophysiology, treatment and impact of society. Headache can be a minor symptom or a symptom of serious underlying disease. As nurses, either in a health care facility or in our communities, we have a responsibility to keep abreast of current theories and treatments. Both presenters are currently involved in clinical trials of new headache medications for both children and adults. Behavioural Objectives: 1. Understand when a headache is a serious symptom and warrants further investigation. 2. Identify the different types of headache. 3. Describe the etiology of headache and its physical and psychological manifestations in child and adults with a particular emphasis on migraine. 4. Gain appreciation for the role of the clinical trials nurse.


Modelling HIV disease process and progression in seroconversion among South Africa women: using transition-specific parametric multi-state model.
HIV infected patients may experience many intermediate events including between-event transition throughout their follow up. Through modelling these transitions, we can gain a deeper understanding of HIV disease process and progression and of factors that influence the disease process and progression pathway. In this work, we present transition-specific parametric multi-state models to describe HIV disease process and progression. The data is from an ongoing prospective cohort study conducted amongst adult women who were HIV-infected in KwaZulu-Natal, South Africa. Participants were enrolled during the acute HIV infection phase and then followed up during chronic infection, up to ART initiation. Transition specific distributions for multi-state models, including a variety of accelerated failure time (AFT) models and proportional hazards (PH) models, were presented and compared in this study. The analysis revealed that women enrolling with a CD4 count less than 350 cells/mm3 (severe and advanced disease stages) had a far lower chance of immune recovery, and a considerably higher chance of immune deterioration, compared to women enrolling with a CD4 count of 350 cells/mm3 or more (normal and mild disease stages). Our analyses also showed that older age, higher educational levels, higher scores for red blood cell counts, higher mononuclear scores, higher granulocytes scores, and higher physical health scores, all had a significant effect on a shortened time to immunological recovery, while women with many sex partners, higher viral load and larger family size had a significant effect on accelerating time to immune deterioration. Multi-state modelling of transition-specific distributions offers a flexible tool for the study of demographic and clinical characteristics' effects on the entire disease progression pathway. It is hoped that the article will help applied researchers to familiarize themselves with the models, including interpretation of results.


Evaluation of retinal structure in unilateral amblyopia using spectral domain optical coherence tomography.
To investigate potential differences in the retinal nerve fiber layer (RNFL) thickness, macular thickness and foveal thickness between amblyopic eyes and normal fellow eyes on spectral domain optical coherence tomography (SD-OCT). A cross-sectional study of patients ≥10 years of age with unilateral amblyopia resulting from an anisometropic, strabismic or deprivative cause. Comprehensive ophthalmic examination was completed and the retinal structures of both eyes were measured using SD-OCT. We compared the measurements obtained between the amblyopic eye and the fellow normal eye in each subject. Twenty-six unilateral amblyopia patients with a mean age of 29.92 ± 14.19 years old participated in the study, of which 17 (65.4%) were classified as anisometropic, 7 (26.9%) as strabismic, and 2 (7.7%) as deprivative. For the amblyopic eye and fellow normal eye, respectively, the mean RNFL thickness was 95.87 ± 14.56 μm and 97.87 ± 14.56 μm (P = 0.628), the mean macular thickness was 270.87 ± 14.43 μm and 275.60 ± 14.43 μm (P = 0.251) and the mean foveal thickness was 250.59 ± 27.82 μm and 242.91 ± 27.82 μm (P = 0.332). SD-OCT assessments revealed no statistically significant differences between both eyes. Using SD-OCT, there were no significant changes in the retinal structure of amblyopic eyes. Therefore, amblyopia does not seem to have a profound structural effect on the retinal nerve fiber layer, the macula, or the fovea.


Reliable Functionalization of 5,6-Fused Bicyclic N-Heterocycles Pyrazolopyrimidines and Imidazopyridazines via Zinc and Magnesium Organometallics.
DFT-calculations allow prediction of the reactivity of uncommon N-heterocyclic scaffolds of pyrazolo[1,5-a]pyrimidines and imidazo[1,2-b]pyridazines and considerably facilitate their functionalization. The derivatization of these N-heterocycles was realized using Grignard reagents for nucleophilic additions to 5-chloropyrazolo[1,5-a]pyrimidines and TMP2 Zn ⋅ 2 MgCl2 ⋅ 2 LiCl allowed regioselective zincations. In the case of 6-chloroimidazo[1,2-b]pyridazine, bases such as TMP2 Zn ⋅ MgCl2 ⋅ 2 LiCl, in the presence or absence of BF3 ⋅ OEt2 , led to regioselective metalations at positions 3 or 8. Subsequent functionalizations were achieved with TMPMgCl ⋅ LiCl, producing various polysubstituted derivatives (up to penta-substitution). X-ray analysis confirmed the regioselectivity for key functional heterocycles.


Promoter analysis of cytolethal distending toxin genes (cdtA , B, and C ) and effect of a luxS mutation on CDT production in Campylobacter jejuni.
Quorum sensing is known to be related to regulation of virulence factors in some pathogens. We report transcriptional analysis of cdt genes (cdtA, B, and C ) encoding cytolethal distending toxin (CDT) in Campylobacter jejuni and demonstrate that a luxS mutation affects the cdt transcription in C. jejuni. The reverse transcriptase-polymerase chain reaction (RT-PCR) showed that cdtA, cdtB, and cdtC genes constitute a polycistronic operon in C. jejuni. A putative transcriptional start site was found at 81-bp upstream from the start codon of cdtA by the primer extension assay. A decrease in cdt transcription was observed in the luxS null mutant, which is defective in AI-2 production. The level of cdt transcription in the luxS mutant was approximately 61% of that in the wild-type. Flow cytometric analysis showed that the number of HeLa cells arrested in the G (2) /M phase, a common biological feature of CDT activity, was reduced by treatment with the cell-free supernatant of the luxS mutant as compared to that of the wild-type. Our observations suggest that the function of luxS is related to the regulation of cdt in C. jejuni.


Spectroscopic investigation of CaAl₁₂O₁₉:M³⁺ upon UV/vacuum-UV excitation: a comparison with SrAl₁₂O₁₉:M³⁺ (M = Pr,Cr).
In order to evaluate the possibility of using Cr³⁺ co-doping to modify the emission properties of Pr³⁺-based quantum cutting phosphors, which emit one ultraviolet (UV) and one visible photon from each vacuum-UV photon absorbed, into phosphors that emit two visible photons, the optical spectroscopies between 150 and 750 nm of CaAl₁₂O₁₉:M³⁺ (M = Pr,Cr) were investigated and compared with those of SrAl₁₂O₁₉:M³⁺ using synchrotron radiation as one of the excitation sources. When Pr³⁺ is excited to its 4f5d states, cascade emission of UV photons from the ¹S₀ state followed by visible photons from the ³P₀ state are both observed in (Ca,Sr)Al₁₂O₁₉:Pr³⁺. Similar to SrAl₁₂O₁₉:M³⁺, there exist desirable spectral overlaps between Pr³⁺ ¹S₀ emissions and the Cr³⁺ higher multiplet absorptions in CaAl₁₂O₁₉, which should be favourable to the energy transfer from Pr³⁺ ¹S₀ to Cr³⁺, converting the UV photon from Pr³⁺ ¹S₀ into the red Cr³⁺ emission. However, the host absorption band and the Cr³⁺-related charge transfer band have an unfavourable overlap with the Pr³⁺ 4f5d states in the vacuum-UV region, preventing efficient selective Pr³⁺ excitation under radiation of Xe discharge, a prerequisite for the quantum cutting process.


Bereavement Part 2: Breaking bad news.
Breaking bad news, whether telling a patient about a poor prognosis or informing relatives of the sudden death of a loved one, is one of the most daunting tasks facing nurses. It requires a sensitive approach, based on individuals' right to know the truth.


Assays for Measuring the Role of MIF in NLRP3 Inflammasome Activation.
Hallmarks of NLRP3 inflammasome activation include the cleavage and secretion of the mature forms of caspase-1, IL-1β, and IL-18 and aggregation of ASC into "specks." We have previously shown that macrophage migratory inhibitory factor (MIF) directly regulates activation of the NLRP3 inflammasome, inhibiting the release of interleukin (IL)-1α, IL-1β, and IL-18. Here we present protocols for studying activation of the NLRP3 inflammasome in human and mouse macrophages and peripheral blood mononuclear cells (PBMCs). These protocols can also be applied to different cell types, such as fibroblasts, neutrophils, endothelial cells, and epithelial cells, although further optimization may be required for each. We also cover the stimulation of macrophages with established NLRP3 inflammasome activators.


Cognitive impairment in Duchenne muscular dystrophy.
Cognitive function and dystrophin gene mutations were investigated in 50 DMD patients (mean age 11.1 yr; range 3.5-20.3). General intelligence assessment showed 31% of patients with Wechsler full intelligence quotient (FIQ) lower than 75 (normal values: 100 +/- 14), and only 24% with appropriate FIQ level. Modal distribution of Wechsler verbal, performance, and FIQs, and Raven IQs was normal. Verbal IQ was more affected than performance IQ (PIQ) only in the younger group of subjects. Low PIQ correlated with the presence of macroglossia, detected in 13 out of 50 patients. Impairment of productive language was of non-dysphasic nature and correlated with defects of short-term memory, which was also affected in non-verbal skills. DMD patients shared the same spectrum of neuropsychological defects, regardless of whether they were or were not mentally retarded. The proportion of patients with dystrophin gene deletions was 64%. No statistically significant correlations were found between genetic data and psychometric assessment. Finally, (18F)-fluorodeoxyglucose positron emission tomography studies demonstrated cerebellar hypometabolism in all the DMD patients examined and variable involvement of associative cortical areas. These findings suggest a possible role of the cerebral and cerebellar hypometabolism in the cognitive impairment of DMD.


Collybistin and gephyrin are novel components of the eukaryotic translation initiation factor 3 complex.
Collybistin (CB), a neuron-specific guanine nucleotide exchange factor, has been implicated in targeting gephyrin-GABAA receptors clusters to inhibitory postsynaptic sites. However, little is known about additional CB partners and functions. Here, we identified the p40 subunit of the eukaryotic translation initiation factor 3 (eIF3H) as a novel binding partner of CB, documenting the interaction in yeast, non-neuronal cell lines, and the brain. In addition, we demonstrated that gephyrin also interacts with eIF3H in non-neuronal cells and forms a complex with eIF3 in the brain. Together, our results suggest, for the first time, that CB and gephyrin associate with the translation initiation machinery, and lend further support to the previous evidence that gephyrin may act as a regulator of synaptic protein synthesis.


Removing Bacillus subtilis from fermentation broth using alumina nanoparticles.
In this study, an efficient separation technology using Al2O3 nanoparticles (NPs) was developed for removing Bacillus subtilis from fermentation broth. The dosage of alumina nanoparticles used for separating B. subtilis increased during the culture process and remained stable in the stationary phase of the culture process. The pH of the culture-broth was also investigated for its effects on flocculation efficiency, and showed an acidic pH could enhance the flocculation efficiency. The attachment mechanisms of Al2O3 NPs to the B. subtilis surface were investigated, and the zeta potential analysis showed that Al2O3 NPs could attach to B. subtilis via electrostatic attachment. Finally, the metabolite content and the antibacterial effect of the fermentation supernatants were detected and did not significantly differ between alumina nanoparticle separation and centrifugation separation. Together, these results indicate a great potential for a highly efficient and economical method for removing B. subtilis from fermentation broth using alumina nanoparticles.


Efficient extraction of antimony(III) by titanate nanosheets: Study on adsorption behavior and mechanism.
Antimony has been listed as a critical pollutant in many countries because of its toxic effects on earth organisms. In this study, titanate nanosheets (TNS) were prepared with a high specific surface area by alkaline hydrothermal method. The adsorption mechanism and adsorption capacity of removing Sb(III) from aqueous solutions with TNS as an adsorbent were investigated for the first time. The FTIR and XPS analysis indicated that the interlayer sodium ions of TNS were responsible for Sb(III) adsorption. The batch experiments were conducted on solution pH, adsorbent dosage, initial concentration and reaction time. The results exhibited that when pH was 2, the removal rate was about 90% with the dosage of TNS was 0.1 g/L. The adsorption reaction was exceedingly rapid in the initial 5 min, and then the reaction was in equilibrium after about 30 min. The experimental data were better fitted with Langmuir isotherm model, and the maximum adsorption amount could attain 232.56 mg/g. The experiments showed that TNS had outstanding anti-interference performance to common cations. Therefore, TNS were considered to be an excellent material for removing Sb(III) from aqueous solutions.


A case of aggressive multiple metachronous central giant cell granulomas of the jaws: differential diagnosis and management options.
We describe multiple metachronous central giant cell granulomas in a 62-year-old man who has a first degree relative with a history of a solitary central giant cell granulomas. The patient presented in 1997 with a large central giant cell granuloma of the right maxilla which was treated with a partial maxillectomy. A small recurrence was then identified and the successful management of this is described. The patient has also a histologically confirmed central giant cell granuloma previously removed from the right body of the mandible and the left angle of the mandible. The differential diagnosis of multiple central giant cell granulomas of the jaw is considered. It is possible that the present case may indeed represent a new syndrome or subtype of multiple central giant cell granulomas. The problem of treating such aggressive sub-types of giant cell granulomas is also addressed in the context of recent advances of surgical and medical management.


Chinese Pedigree of Chronic Mucocutaneous Candidiasis Due to STAT1 Gain-of-Function Mutation: A Case Study and Literature Review.
To further elucidate the clinical, immunological and genetic features of chronic mucocutaneous candidiasis (CMC) due to STAT1 GOF mutation in the Chinese population. Clinical data for a proband were collected, and pedigree analyses were performed. Whole-exome sequencing and targeted Sanger sequencing were conducted to explore genetic factors of a Chinese pedigree involving inherited CMC. An autosomal dominant CMC pedigree was identified, and both the proband and his father had mucocutaneous Candida infections without involvement of other systems. A rare mutation (c.T1175C) in STAT1 was detected in this CMC pedigree. Multiple sequence alignment revealed that the amino acid position of this mutation (p.M392T) is evolutionarily conserved in vertebrate species. Serum IFN-α was elevated in patients harbouring the mutation. A total of 10 publications reporting 26 CMC patients with STAT1 GOF mutations were retrieved by literature review, and the most common mutation found in previously reported Chinese patients is T385M in the DNA-binding domain. STAT1 GOF mutation at c.T1175C (p.M392T) may lead to mucocutaneous Candida infections and an increase in serum IFN-α. T385M in the DNA-binding domain is the most common STAT1 GOF mutation found in the Chinese population.


Reclassifying inconclusive diagnosis after newborn screening for cystic fibrosis. Moving forward.
Newborn screening for Cystic Fibrosis (CF) is associated with situations where the diagnosis of CF or CFTR related disorders (CFTR-RD) cannot be clearly ruled out. We report a case series of 23 children with unconclusive diagnosis after newborn screening for CF and a mean follow-up of 7.7 years (4-13). Comprehensive investigations including whole CFTR gene sequencing, in vivo intestinal current measurement (ICM), nasal potential difference (NPD), and in vitro functional studies of variants of unknown significance, helped to reclassify the patients. Extensive genetic testing identified, in trans with a CF causing mutation, variants with varying clinical consequences and 3 variants of unknown significance (VUS). Eighteen deep intronic variants were identified by deep resequencing of the whole CFTR gene in 13 patients and were finally considered as non-pathogenic. All patients had normal CFTR dependent chloride transport in ICM. NPD differentiated 3 different profiles: CF-like tracings qualifying the patients as CF, such as F508del/D1152H patients; normal responses, suggesting an extremely low likelihood of developing a CFTR-RD such as F508del/TG11T5 patients; partial CFTR dysfunction above 20% of the normal, highlighting a remaining risk of developing CFTR-RD such as F508del/F1052V patients. The 3 VUS were reclassified as variant with defective maturation (D537N), defective expression (T582I) or with no clinical consequence (M952T). This study demonstrates the usefulness of combining genetic and functional investigations to assess the possibility of evolving to CF or CFTR-RD in babies with inconclusive diagnosis at neonatal screening.


3-MCPD exposure enhances ovarian fibrosis and reduces oocyte quality in mice.
3-monochloro-1,2-propanediol (3-MCPD) is a food contaminant believed to be harmful to human health. Previous studies showed that 3-MCPD exerts toxic effects in multiple tissues, but whether 3-MCPD affects female reproductive function remained unknown. Here, using mouse gastric lavage models, we report that 3-MCPD exposure for four weeks affected body growth, decreased the ovary/body weight ratio, and increased atretic follicle numbers. Expression levels of follicular development-related factors decreased. Further studies found that ovaries from 3-MCPD exposed mice had activated the Transforming Growth Factor-β (TGF-β) signaling pathway and promoted ovarian fibrosis. Increased TNF-α, IL-1 and NF-κB expression also indicated the occurrence of ovarian inflammation. Exposure to 3-MCPD stimulated the caspase pathway and enhanced granulosa cell apoptosis. Consistent with disrupted ovarian homeostasis, 3-MCPD exposure interfered with mitochondrial function, generated more reactive oxygen species, increased ferrous ion and lipid peroxidation levels, and resulted in decreased oocyte development potential. Collectively, these findings indicated that 3-MCPD exposure induced ovarian inflammation and fibrosis, and caused disorders of mitochondrial function and ferrous ion homeostasis in oocytes, which consequently disturbed follicle maturation and reduced oocyte quality.


Evaluation of Carotid Space Schwannoma Using Ultrasonography: Characteristics and Role in Defining the Nerve of Origin.
We aimed to evaluate the ultrasonography (US) characteristics of carotid space schwannoma and their role in identifying the nerve of origin. This prospective study enrolled patients with cervical carotid space schwannoma accessible by US. The US characteristics of vagus nerve schwannomas (VNSs) and sympathetic nerve schwannomas (SNSs) were assessed; a carotid space schwannoma was defined as a VNS if the tumor originated in the mid-vagal region and an SNS if it arose posterior to the intact vagus nerve, displacing the vagus nerve anteriorly. Twenty patients with carotid space schwannoma were enrolled. The vagus and sympathetic nerves were identified as the nerve of origin in 12 and 8 patients, respectively. VNSs were centered at levels II, III, and IV in 5, 3, and 4 patients, respectively, while SNSs were centered at levels II (7 patients) and IV (1 patient) (P = .105). The maximal diameters were 3.2 and 4.8 cm for VNSs and SNSs, respectively (P = .011). Internal vascularity was absent and low in 9 and 3 VNSs, respectively, and low and intermediate in 4 SNSs each (P = .002). Twelve patients with VNSs underwent active surveillance without immediate surgery; no adverse events occurred during the 55.2-month follow-up period. Eight patients with potential SNSs underwent surgery, confirming the sympathetic nerve as the nerve of origin. US facilitates identification of the nerve of origin in cervical carotid space schwannoma. VNSs are more frequent in infrahyoid locations and tend to be smaller in size with lower vascularity compared with SNSs on US.


Evaluation of the clinical utility of extended non-invasive prenatal testing in the detection of chromosomal aneuploidy and microdeletion/microduplication.
With the development of whole-genome sequencing technology, non-invasive prenatal testing (NIPT) has been applied gradually to screen chromosomal microdeletions and microduplications that cannot be detected by traditional karyotyping. However, in NIPT, some false positives and false negatives occur. This study aimed to investigate the applicability of extended NIPT (NIPT-PLUS) in the detection of chromosomal aneuploidy and microdeletion/microduplication syndrome (MMS). A total of 452 pregnancies that underwent prenatal diagnostic testing (amniocentesis or chorionic villus sampling) by chromosomal microarray analysis (CMA), were screened by NIPT-PLUS from the peripheral blood sample of the pregnant women. The results of the two tested items were compared and analysed. Of the 452 cases, 335 (74.12%) had positive CMA results, and 117 (25.88%) had no abnormal results. A total of 86 cases of trisomy 21, 18 and 13 and sex chromosome aneuploidy (SCA) were detected by CMA and NIPT-PLUS, with a detection rate of 96.51% (83/86). Among them, the detection rates of T18, T13; 47, XXY; 47, XXX and 47 XYY were 100%, and the detection rates of T21 and 45 XO were 96.55% and 90%, respectively. The detection sensitivity of rare chromosomal trisomy (RAT) was 80% (4/5). The positive predictive values of NIPT-PLUS for chromosome aneuploidy T21, T18 and T13 and for SCA and RAT were 90.32%, 87.50%, 25.00%, 88.89% and 50%, respectively. A total of 249 cases (74.32%) of chromosomal MMS were detected by CMA. The detection rate of NIPT-PLUS was 63.86% (159/249), and 90 cases (36.14%) were missed. The larger the MMS fragment, the higher the NIPT-PLUS detection sensitivity. In addition, most small fragments were of maternal origin. The comparison between the CMA and NIPT-PLUS techniques shows that NIPT-PLUS has high sensitivity for detecting chromosomal aneuploidy and chromosomal copy number variations (CNVs) with fragments > 5 M. However, the sensitivity of CNV for fragments < 5 M is low, and the missed detection rate is high. Additionally, confined placental mosaicism and foetal mosaicism are the key factors causing false negatives in NIPT-PLUS, while maternal chromosomal abnormalities and confined placental mosaicism are key contributors to false positives, so appropriate genetic counselling is especially important for pregnant women before and after NIPT-PLUS testing.


Study on the correlation between cardiac function indices measured by velocity vector imaging and disease severity in patients with Parkinson disease.
This study aimed to evaluate cardiac function, particularly left ventricular systolic function, in patients with Parkinson disease (PD) using velocity vector imaging (VVI), and to determine whether a correlation exists between left ventricular global systolic function and PD severity. A case-control study design was used to select 56 PD patients and 30 healthy controls from January 2019 to December 2019. The characteristics of age, sex, BMI and course of disease were collected. The Hoehn-Yahr (H-Y) score was collected to record the grading of PD. The left ventricular systolic function of all patients was evaluated by variable vapor injection (VVI). The left ventricular systolic function was compared between the case group and the control group, and the correlation between cardiac dysfunction and the severity of PD symptoms was assessed using the modified H-Y scale. Compared with control group, left ventricular global systolic function18.22 (17.08, 19.12) vs 18.88 (18.12, 20.01) was lower in PD patients as indicated by left ventricular global longitudinal strain (GLS), and the difference was statistically significant (P = 0.039). Additionally, H-Y scores (r = -0.404) and PD duration(r = -0.323) were significantly correlated with reduced left ventricular ejection fraction (P < 0.01), GLS (P < 0.001), left ventricular global radial strain (GRS; P < 0.001), and left ventricular global circumferential strain (GCS; P < 0.001), along with their associated peak strain rates (GLSr, GRSr, and GCSr; P < 0.001). Subclinical left ventricular global systolic dysfunction in patients with PD can be detected using VVI, and reduced left ventricular systolic function correlates with the modified H-Y score and duration of the disease.


Efficacy, cost-effectiveness, and tolerability of mometasone furoate, levocabastine, and disodium cromoglycate nasal sprays in the treatment of seasonal allergic rhinitis.
Current guidelines recommend intranasal glucocorticosteroids as first-line therapy for seasonal allergic rhinitis. To compare the efficacy, cost-effectiveness, and tolerability of the topical glucocorticosteroid mometasone furoate, the topical antihistamine levocabastine hydrochloride, and the cromone disodium cromoglycate in seasonal allergic rhinitis. This study was performed during the 2003 grass pollen season as an open, randomized, parallel-group, single-center study of 123 patients assigned to receive mometasone furoate (200 microg once daily), levocabastine hydrochloride (200 microg twice daily), or disodium cromoglycate (5.6 mg 4 times daily). Symptom scores and nasal inspiratory peak flow measurements were recorded in a patient diary. The global efficacy of the study medication was evaluated by patients after treatment. Eosinophil cationic protein concentrations were measured in nasal secretions before and after treatment. Cost-effectiveness was evaluated as medication cost per treatment success. Mometasone furoate therapy was significantly superior to the use of levocabastine or disodium cromoglycate with respect to all nasal symptoms, the global evaluation of efficacy, and eosinophil cationic protein concentration. Furthermore, mometasone furoate therapy was significantly superior to disodium cromoglycate therapy with respect to nasal inspiratory peak flow. Medication cost per treatment success was lowest with mometasone furoate use and highest with levocabastine use. This is the first study to compare mometasone furoate nasal spray with nonsteroidal topical treatments for seasonal allergic rhinitis. Mometasone furoate nasal spray was confirmed as a first-choice topical treatment option for seasonal allergic rhinitis.


Electrocardiographic marker of the cardiac action potential triangulation induced by antiarrhythmic drugs in perfused guinea-pig heart.
What is the central question of this study? Can the triangular appearance of ventricular action potential, indicating proarrhythmic profile of antiarrhythmic agent, be approximated by specific changes on an electrocardiogram (ECG)? What are the main finding and its importance? The triangulation of the ventricular action potential seen when antiarrhythmic drugs induce a greater lengthening of the late repolarization compared to the initial repolarization in epicardium is closely approximated by a greater prolongation of the T wave upslope relative to the interval between the J point and the start of the T wave (the JTstart interval) on the ECG. These findings may improve the power of ECG assessments in predicting the drug-induced arrhythmia resulting from slowed phase 3 repolarization. Antiarrhythmic drugs prescribed to treat atrial fibrillation can occasionally precipitate ventricular tachyarrhythmia through a prominent slowing of the phase 3 repolarization. The latter results in the triangular shape of ventricular action potential, indicating high arrhythmic risk. However, clinically, the utility of triangulation assessments for predicting arrhythmia is limited owing to the invasive nature of the ventricular action potential recordings. This study examined whether the triangulation effect can be detected indirectly from electrocardiogram (ECG) analysis. Epicardial monophasic action potentials and the ECG were simultaneously recorded in perfused guinea-pig hearts. With antiarrhythmics (dofetilide, quinidine, procainamide and flecainide), a prolongation of the initial repolarization seen in the action potential recordings was closely approximated by lengthening of the interval between the J point and the start of the T wave (the JTstart interval) on the ECG, whereas a prolongation of the late repolarization was paralleled by widening of the T wave upslope. Dofetilide, quinidine and procainamide induced a prominent slowing of the phase 3 repolarization in epicardium, leading to triangulation of the action potential. These effects were accompanied by a greater prolongation of the T wave upslope compared to the JTstart interval. Flecainide elicited a proportional prolongation of the initial and the late ventricular repolarization, and therefore failed to induce triangulation, based on analysis of both epicardial action potential and ECG profiles. Collectively, these findings suggest that the ratio between the durations of the T wave upslope and the JTstart interval may represent the ECG metric of the ventricular action potential triangulation induced by antiarrhythmic drugs.


Immunoregulation of SLE-like disease by the IL-1 receptor: disease modifying activity on BDF1 hybrid mice and MRL autoimmune mice.
Due to the immunopharmacological profile of the recombinant IL-1 receptor (IL-1-R) and its potential to modulate biological activity in various inflammatory autoimmune disease models, we further elucidated its disease modifying activity on the development of a systemic lupus erythematosus (SLE)-like disease in BDF1 hybrid mice and in MRL/lpr autoimmune mice. Treatment of BDF1 mice with the IL-1-R during the induction phase resulted in a strong inhibition of the development of a glomerulonephritis, prolonged the survival time and improved the survival rate. Even a therapeutic effect was demonstrated when this receptor was given after the appearance of clinical symptoms. Treating MRL/lpr mice, which develop spontaneously a SLE-like disease, with the IL-1-R resulted in an inhibition of the developing glomerulonephritis and splenomegaly, in a reduction of swollen lymph nodes and in a decrease of autoantibody formation. Even in the established autoimmune disease of MRL/1 pr mice the IL-1-R reduced proteinuria, the levels of autoantibodies and also improved the survival rate.


Evidence that the contractile response of the guinea-pig ileum to capsaicin is due to substance P release.
The mechanism of action of capsaicin on the guinea-pig isolated ileum was studied. Capsaicin (1.5 x 10(-6) mol 1(-1) produced a large contractile response of the ileum which exhibited marked tachyphylaxis. The response was reduced by treatment of preparations with atropine, 5 x 10(-6) mol 1(-1), and by substance P-autodesensitization, and was abolished by a combination of these treatments. It was concluded that capsaicin released both substance P and acetylcholine from the guinea-pig ileum. Evidence for a cholinergic component in the action of high concentrations of substance P was also obtained and therefore it is proposed that capsaicin releases substance P from neurones in the ileum, and the released substance P in turn stimulates cholinergic neurones to release acetylcholine, as well as producing direct muscle contraction.


Quantification of HIV-1 viral RNA in the blood in needles used for venous puncture in HIV-infected individuals.
Occupational HIV infection among healthcare workers is an important issue in exposures involving blood and body fluids. There are few data in the literature regarding the potential and the duration of infectivity of HIV type 1 (HIV-1) in contaminated material under adverse conditions. We quantified HIV-1 viral RNA in 25×8mm calibre hollow-bore needles, after punctures, in 25 HIV-1-infected patients selected during the sample collection. All of the patients selected were between the ages of 18 and 55. Five samples were collected from 16 patients: one sample for the immediate quantification of HIV-1 RNA in the plasma and blood samples from the interior of 4 needles to be analyzed at 0 h, 6 h, 24 h, and 72 h after collection. In nine patients, another test was carried out in the blood from one additional needle, in which HIV-1 RNA was assessed 168 h after blood collection. The method used to assess HIV-1 RNA was nucleic acid sequence-based amplification. Up to 7 days after collection, HIV-1 RNA was detected in all of the needles. The viral RNA remained stable up to 168 h, and there were no statistically significant differences among the needle samples. Although the infectivity of the viral material in the needles is unknown, the data indicate the need to re-evaluate the practices in cases of occupational accidents in which the source is not identified.


TME-Responsive Polyprodrug Micelles for Multistage Delivery of Doxorubicin with Improved Cancer Therapeutic Efficacy in Rodents.
It is of great significance to develop multifunctional biomaterials to effectively deliver anticancer drug to tumor cells for cancer therapy. Here, inspired by the specific tumor microenvironment (TME) cues, a unique multistage pH/redox-responsive polyprodrug composed of amphiphilic pH-sensitive diblock copolymer poly(ethylene glycol) methyl ether-b-poly(β-amino esters) conjugated with doxorubicin (DOX) via redox-sensitive disulfide bonds (mPEG-b-PAE-ss-DOX) is designed and developed. This polyprodrug can self-assemble into micelles (DOX-ss@PMs) at low concentration with high serum stability, indicating that DOX-ss@PMs have prolonged circulation time. The dual pH/redox-responsiveness of the multistage platform is thoroughly evaluated. In vitro results demonstrate that DOX-ss@PMs can highly accumulate at tumor site, followed by responding to the acidity for disassembly and effectively penetrating into the tumor cells. DOX is released from the platform due to the cleavage of disulfide bonds induced by high glutathione (GSH) concentration, thereby inducing the apoptosis of tumor cells. In vivo studies further reveal that multistage DOX-ss@PMs can more efficiently inhibit the growth of tumors and improve the survival of tumor-bearing mice in comparison to the free drug and control. These results imply that multistage delivery system might be a potential and effective strategy for drug delivery and DOX-ss@PMs could be a promising nanomedicine for cancer chemotherapy.


Left and right ventricular deformation in patients with severe mitral stenosis and pulmonary hypertension undergoing percutaneous balloon mitral valvuloplasty: A two dimensional speckle-tracking echocardiographic study.
Seventy-five patients with isolated severe MS (mitral valve area: 1.10 ± 0.15 cm2) and pulmonary hypertension underwent regional and global longitudinal strain (GLS) measurements of left (LV) and right ventricle (RV) at baseline and within 48 h after percutaneous balloon mitral valvuloplasty (PBMV). PBMV resulted in significant improvement in LV GLS (-16.35 ± 1.67% vs -19.98 ± 2.17%) and RV GLS (-10.34 ± 2.38% vs -13.83 ± 2.04%), p < 0.001 for both. Absolute increase in strain of basal segments of LV was more compared to mid and apical segments. We also found significant positive correlation between decrease in mean LA pressure (pre PBMV 28.91 ± 4.21 mm Hg vs post PBMV 10.55 ± 3.04 mm Hg, difference of 16.36 mm Hg; p < 0.001) obtained invasively during PBMV for 62 patients with improvement in LV GLS (r = 0.257, p = 0.048), RV GLS (r = 0.267, p = 0.043), and fall in right ventricular systolic pressure (r = 0.308, p = 0.022) that occurred post PBMV. The LV dysfunction is predominantly because of altered hemodynamics due to restricted LV filling with additional contribution from rheumatic involvement of basal LV myocardial segments. The improvement in LV deformation after PBMV is likely due to increase in preload. RV afterload reduction because of LA pressure decrease improved RV deformation.


Early neonatal deaths associated with perinatal asphyxia in infants ≥2500g in Brazil.
To assess the annual burden of early neonatal deaths associated with perinatal asphyxia in infants weighing ≥2500g in Brazil from 2005 to 2010. The population study enrolled all live births of infants with birth weight ≥2500g and without malformations who died up to six days after birth with perinatal asphyxia, defined as intrauterine hypoxia, asphyxia at birth, or meconium aspiration syndrome. The cause of death was written in any field of the death certificate, according to International Classification of Diseases, 10th Revision (P20.0, P21.0, and P24.0). An active search was performed in 27 Brazilian federative units. The chi-squared test for trend was applied to analyze early neonatal mortality ratios associated with perinatal asphyxia by study year. A total of 10,675 infants weighing ≥2500g without malformations died within six days after birth with perinatal asphyxia. Deaths occurred in the first 24h after birth in 71% of the infants. Meconium aspiration syndrome was reported in 4076 (38%) of these deaths. The asphyxia-specific early neonatal mortality ratio decreased from 0.81 in 2005 to 0.65 per 1000 live births in 2010 in Brazil (p<0.001); the meconium aspiration syndrome-specific early neonatal mortality ratio remained between 0.20 and 0.29 per 1000 live births during the study period. Despite the decreasing rates in Brazil from 2005 to 2010, early neonatal mortality rates associated with perinatal asphyxia in infants in the better spectrum of birth weight and without congenital malformations are still high, and meconium aspiration syndrome plays a major role.


Improving bioavailability and biodistribution of anti-HIV chemotherapy.
In the context of the treatment of HIV/AIDS, many improvements have been achieved since the introduction of the combination therapy (HAART). Nevertheless, no cure for this disease has been so far possible, because of some particular features of the therapies. Among them, two important ones have been selected and will be the subject of this review. The first main concern in the treatments is the poor drug bioavailability, resulting in repeated administrations and therefore a demanding compliance (drug regimens consist of multiple drugs daily intake, and non-adherence to therapy is among the important reasons for treatment failure). A second important challenge is the need to target the drugs into the so-called reservoirs and sanctuaries, i.e. cells or body compartments where drugs cannot penetrate or are distributed in sub-active concentrations. The lack of antiviral action in these regions allows the virus to lie latent and start to replicate at any moment after therapy suspension. Recent drug delivery strategies addressing these two limitations will be presented in this review. In the first part, strategies to improve the bioavailability are proposed in order to overcome the absorption or the target cell barrier, or to extend the efficacy time of drugs. In the second section, the biodistribution issues are considered in order to target the drugs into the reservoirs and the sanctuaries, in particular the mononuclear phagocyte system and the brain.


Methamphetamine antagonistic property of (+)- and (-)-4-phenyltetrahydroisoquinoline in rat anococcygeus muscle.
The antagonistic effects of (+)- and (-)-4-phenyl-1,2,3,4-tetrahydroisoquinoline (4PTIQ) on methamphetamine in the rat anococcygeus muscle were compared with those of cocaine and nomifensine. Methamphetamine contracted the anococcygeus muscle through the release of norepinephrine from noradrenergic nerve terminals. (+)-4PTIQ inhibited the methamphetamine-induced contractions more strongly than cocaine and nomifensine. (+)-4PTIQ had no potentiating effects on exogenous norepinephrine-induced contraction, which was considered to be an index of amine neuronal uptake blockade. On the other hand, (-)-4PTIQ, cocaine and nomifensine produced a significant leftward shift of the norepinephrine concentration-response curve, i.e. they showed a strong blocking effect on amine neuronal uptake. These results suggest that the inhibitory effects of (+)-4PTIQ on the action of methamphetamine are mediated by a mechanism other than inhibition of amine neuronal uptake.


Effects of an advocacy intervention to reduce smoking among teenagers.
To test whether high school students' participation in advocacy activities related to the advertising, availability, and use of tobacco in their communities would prevent or reduce their own tobacco use. Ten continuation high schools in northern California, randomly assigned to a semester-long program in which students either carried out advocacy activities to counter environmental-level smoking influences in their communities (treatment) or learned about drug and alcohol abuse prevention (control). Eleventh and 12th grade high school students; 5 (advocacy) treatment and 5 control schools over 4 semesters from 2000 through 2002. Self-reported smoking defined as nonsmokers (those who had never smoked tobacco or those who were former smokers), light smokers (those who smoked <1 pack per week), or regular smokers (those who smoked >or=1 pack per week), and confirmed by carbon monoxide level readings. The following 3 constructs related to social cognitive theory- perceived incentive value, perceived self-efficacy, and outcome expectancies-were assessed. There was a significant net change from baseline to the end of the semester (after the intervention) between treatment and control schools for students who were regular smokers, but not for students who were nonsmokers or light smokers. Regular smoking decreased 3.8% in treatment schools and increased 1.5% in control schools (P<.001). Regular smoking continued to decrease at 6 months after the intervention in treatment schools, with a total change in prevalence from 25.1% to 20.3%. Involvement in community-advocacy activities and the 3 social constructs-perceived incentive value, perceived self-efficacy, and outcome expectancies-also showed significant net changes between treatment and control schools (all P values <.01). Student engagement in community-advocacy activities that addressed environmental influences of cigarette smoking resulted in significant decreases in regular smoking.


Spectral and kinetic studies on the binding of trithiomolybdate to bovine and canine serum albumin in vitro: the interaction with copper.
Spectral studies showed that copper and trithiomolybdate participated in a three-way interaction with bovine and canine serum albumin. The interaction with the proteins was affected by increased pH and ionic strength. Kinetic studies of binding equilibria indicated that [35S] trithiomolybdate bound to both albumins at a single site. The affinity of the site, but not the capacity of the protein, was increased by copper. It was concluded that the site was distinct from the N-terminal copper (and nickel) binding site, which is present on BSA but absent from CSA. Whether or not the N-terminal site has a role in copper transport is discussed. Reversible thiomolybdate-copper-protein interactions of this type may play a fundamental role in the pathogenesis of Mo-induced syndromes, since as the normal binding patterns are perturbed the interprotein equilibria are altered and the copper distribution patterns are modified.


Genetic variations associated with six-white-point coat pigmentation in Diannan small-ear pigs.
A common phenotypic difference among domestic animals is variation in coat color. Six-white-point is a pigmentation pattern observed in varying pig breeds, which seems to have evolved through several different mechanistic pathways. Herein, we re-sequenced whole genomes of 31 Diannan small-ear pigs from China and found that the six-white-point coat color in Diannan small-ear pigs is likely regulated by polygenic loci, rather than by the MC1R locus. Strong associations were observed at three loci (EDNRB, CNTLN, and PINK1), which explain about 20 percent of the total coat color variance in the Diannan small-ear pigs. We found a mutation that is highly differentiated between six-white-point and black Diannan small-ear pigs, which is located in a conserved noncoding sequence upstream of the EDNRB gene and is a putative binding site of the CEBPB protein. This study advances our understanding of coat color evolution in Diannan small-ear pigs and expands our traditional knowledge of coat color being a monogenic trait.


Reaction of monosubstituted hydrazines and diazenes with rat-liver cytochrome P450. Formation of ferrous-diazene and ferric sigma-alkyl complexes.
The alkyldiazenes RN = NH (R = CH3 or C2H5) react with reduced microsomal cytochrome P450 leading to complexes exhibiting a Soret peak at 446 nm. Upon oxidation of the [cytochrome P450-Fe(II)(CH3N = NH)] complex with limited amounts of dioxygen, a new complex characterized by a Soret peak at 486 nm is formed. The latter complex was also formed upon slow reaction of methyldiazene with microsomal cytochrome P450-Fe(III) or in situ oxidation of methylhydrazine by limited amounts of O2 or ferricyanide. This complex is rapidly destroyed by O2 or ferricyanide in excess and more slowly by excess dithionite in the presence of CO. Reactions of ethyldiazene or benzyldiazene with cytochrome P450-Fe(III) afforded similar complexes characterized by Soret peaks around 480 nm. These results, when compared to those recently described on reactions of monosubstituted hydrazines RNHNH2 and diazenes RN = NH with hemoglobin and iron-porphyrins, are consistent with a [cytochrome P450-Fe(II)(RN = NH)] structure for the 446-nm-absorbing complexes and a sigma-alkyl cytochrome P450-Fe(III)-R structure for the complexes characterized by a Soret peak around 480 nm. They also suggest a sigma-cytochrome P450-Fe(III)-Ph structure for the complex derived from phenylhydrazine oxidation, recently described in the literature. Finally, they provide the first evidence that cytochrome P450-Fe(III)-R complexes are formed upon microsomal oxidation of alkyl or phenylhydrazines.


Kidney transplantation from elderly donors: a prospective randomized study comparing celsior and UW solutions.
The aim of present study was to assess the effect of Celsior as compared with University of Wisconsin (UW) solution on immediate and long-term function of kidney transplants harvested from elderly donors. A prospective multicenter randomized study was designed to evaluate the efficacy of Celsior versus UW solution for the clinical preservation of the kidney. Fifty renal transplants were performed from donors over 60 years old. Twenty-five kidneys were stored in Celsior and 25 in UW solution. The groups were comparable with regard to donor and recipient characteristics. Renal function outcomes were compared by evaluating delayed graft function rates, daily urinary output, as well as the evolution of mean serum creatinine at 1, 3, 5, 7, and 15 days. The warm ischemia time was 42.4 +/- 11 minutes among Celsior vs 46.9 +/- 17.9 minutes in the UW cohort (P = NS). The cold ischemia time was 18 +/- 4.5 hours in Celsior and 19 +/- 6.5 hours in UW (P = NS). Delayed graft function occurred in 48% of the Celsior group and in 52% of the UW group (P = NS). Mean serum creatinine levels and mean daily urinary output were also similar. One- and 5-year graft survivals of kidneys preserved with Celsior were 91.8% and 79.3% compared with 96% and 87.4% for UW without any significant statistical difference. Our data show that the preservation of kidneys from elderly donors in Celsior solution is equivalent to that of UW solution.


Evaluation of the performance of Abbott Panbio™ COVID-19 antigen rapid diagnostic test for the detection of severe acute respiratory syndrome coronavirus 2 at Harar, Eastern Ethiopia.
Rapid antigen tests can help in the effective isolation of symptomatic cases and the systematic tracing of close contacts. However, their reliability must be validated before implementing them widely. A cross-sectional study was conducted on 236 COVID-19-suspected patients visiting four different health institutions in Harari Regional State, Harar, Eastern Ethiopia, from June to July 2021. Two nasopharyngeal samples were collected and processed by the Panbio™ Ag-RDT kit and qRT-PCR. The collected data were analyzed using SPSS version 25.0. The Panbio tests had a sensitivity of 77.5% (95% CI: 61.6-89.2%) and a specificity of 98.5% (95% CI: 95.6-99.7%). It also had a positive predictive value of 91.2% (95% CI: 76.9-96.9%), a negative predictive value of 95.5% (95% CI: 92.3-97.4%), and a kappa of 0.81 (95% CI: 0.7-0.9). The test had a sensitivity of 94.4%, 100%, 100%, and 90% in the samples collected from patients within the 1-5 days post-onset of COVID-19 signs and symptoms, of age group ≤18 years old, with cycle threshold values of <20, and with household contact, respectively. This test can be used as point-of-care testing for the diagnosis of symptomatic patients with short clinical courses and contact with patients in households.


In vivo evaluation of copper release and acute local tissue reactions after implantation of copper-coated titanium implants in rats.
Copper (Cu) based coatings can reduce infections for titanium (Ti) implants. However, Cu is also cytotoxic. To examine the balance of antibacterial versus adverse tissue effects, this study aimed at evaluating a Cu coating regarding in vivo Cu release and local inflammatory reactions for 72 h. TiAl6V4 plates received either plasma electrolytic oxidation only (Ti), or an additional galvanic Cu deposition (Ti-Cu). No Staphylococcus aureus were found in vitro on Ti-Cu after 24 h. Following simultaneous intramuscular implantation of two Ti and two Ti-Cu plates into nine rats, serum Cu was elevated until 48 h and residual Cu on explanted samples reduced accordingly after 48 h. Total and tissue macrophages around implants increased until 72 h for both series, and were increased for Ti-Cu. As numbers of total and tissue macrophages were comparable, macrophages were probably tissue-derived. MHC-class-II-positive cells increased for Ti-Cu only. T-lymphocytes had considerably lower numbers than macrophages, did not increase or differ between both series, and thus had minor importance. Tissue reactions increased beyond Cu release, indicating effects of either surface-bound Cu or more likely the implants themselves. Altogether, Ti-Cu samples possessed antibacterial effectiveness in vitro, released measurable Cu amounts in vivo and caused a moderately increased local inflammatory response, demonstrating anti-infective potential of Cu coatings.


Intermittent Fasting versus Continuous Calorie Restriction: Which Is Better for Weight Loss?
We conducted a systematic review and meta-analysis of randomized clinical trials and pilot trial studies to compare the effectiveness of intermittent fasting (IF) and continuous calorie restriction (CCR) in overweight and obese people. The parameters included body mass index (BMI), body weight, and other metabolism-related indicators. A systematic search in PubMed, Embase, Cochrane Library, and Web of Science was conducted up to January 2022. Standardized mean differences (SMDs) with 95% confidence intervals (CIs) were used to measure the effectiveness. Publication bias was assessed using Egger's test. The stability of the results was evaluated using sensitivity analyses. The significance of body weight change (SMD = -0.21, 95% CI (-0.40, -0.02) p = 0.028) was more significant after IF than CCR. There was no significant difference in BMI (SMD = 0.02, 95% CI (-0.16, 0.20) p = 0.848) between IF and CCR. These findings suggest that IF may be superior to CCR for weight loss in some respects.


The ovalbumin gene: transcriptional regulation by estrogen.
De novo synthesis of RNA sequences corresponding to intervening as well as to structural sequences of the ovalbumin gene have been detected in isolated oviduct nuclei. Their presence in the nuclear transcripts and their time course of induction support the hypothesis that transcription of structural and intervening sequences of the natural ovalbumin gene are regulated by steroid hormones. These results are in agreement with out previous demonstration of high-molecular-weight species of ovalbumin RNA in nuclei that contain structural as well as intervening RNA sequences and are thus likely precursors to mature cytoplasmic mRNAov. Analysis of the size of in vivo nuclear RNA by gel electrophoresis under denaturing conditions, revealed that withdrawal of hormone depletes the level of high molecular weight ovalbumin RNA as well as that of nature mRNAov and that readministration of estrogen induces the accumulation of both species. These results are consistent also with transcriptional regulation of the ovalbumin gene. In addition, they rule out the possibility that the rapid accumulation of mature mRNAov after secondard stimulation results from processing of ovalbumin RNA precursors that might have been stored in the withdrawn oviduct. We conclude that steroid hormones exert a primary effect at the level of gene transcription. Following this event, a series of coordinated cellular responses may occur which involve RNA processing, mRNA transport to the cytoplasm, protein synthesis and mRNA degradation. The final consequence of this network of molecular reactions is the induced cellular function inherent to a specific steroid hormone.


Kinetic studies of the copper nitrite reductase from Achromobacter cycloclastes and its interaction with a blue copper protein.
Transient state, burst and steady state kinetics of reactions of the blue copper nitrite reductase (NIR) and blue copper protein from Achromobacter cycloclastes are investigated. The two copper-containing species are reacted with each other and where possible with dithionite, ascorbate and nitrite. Both copper proteins are fully reduced by dithionite with both S2O4(2-) and SO2-. species active. NIR is only partially reduced by ascorbate in an unusual biphasic reaction consistent with complete reduction of type-one copper followed by partial reduction of type-two copper. The rate of reduction of the type-one copper is accelerated using phenazine methosulfate as mediator. Nitrite can oxidize dithionite-reduced NIR but cannot reduce oxidized NIR. Rate constants were determined for all observed reactions.


One-pot preparation of a mixed-mode organic-silica hybrid monolithic capillary column and its application in determination of endogenous gibberellins in plant tissues.
A newly improved one-pot method, based on "thiol-ene" click chemistry and sol-gel approach in microemulsion system, was developed for the preparation of C8/PO(OH)2-silica hybrid monolithic capillary column. The prepared monolith possesses large specific surface area, narrow mesopore size distribution and high column efficiency. The monolithic column was demonstrated to have cation exchange/reversed-phase (CX/RP) mixed-mode retention for analytes on nano-liquid chromatography (nano-LC). On the basis of the developed nano-LC system with MS detector coupled to pipette tip solid phase extraction (PT-SPE) and derivatization process, we then realized simultaneous determination of 10 gibberellins (GAs) with low limits of detection (LODs, 0.003-0.025 ng/mL). Furthermore, 6 endogenous GAs in only 5mg rice leaves (fresh weight) were successfully detected and quantified. The developed PT-SPE-nano-LC-MS strategy may offer promising applications in the determination of low abundant bioactive molecules from complex matrix.


Correlations between cardiac troponin I and nonsustained ventricular tachycardia in hypertrophic obstructive cardiomyopathy.
Nonsustained ventricular tachycardia (NSVT) is an independent risk factor for sudden cardiac death (SCD) in patients with hypertrophic obstructive cardiomyopathy (HOCM). However, data concerning the correlations of cardiac biomarkers and NSVT in HOCM are rather limited. Our study aimed to investigate the associations between the occurrence of NSVT and circulating biomarkers representing myocardial injury (cardiac troponin I, cTnI), cardiac function (N-terminal pro-brain natriuretic peptide, NT-pro BNP), and inflammation (high-sensitivity C-reactive protein) in a large Chinese HOCM cohort. A total of 755 consecutive HOCM patients were recruited. Systematic cardiac evaluations and circulating biomarkers were examined routinely in all subjects under the clinically stable status. According to the results of 24-hour Holter monitoring, patients were divided into the NSVT group (n = 138) and the nonventricular tachycardia (non-VT) group (n = 617). Compared with the non-VT group, circulating levels of both cTnI and NT-pro BNP elevated significantly in patients with positive NSVT episodes (P < .001). Multivariable analyses demonstrated that cTnI was independently associated with the presence of NSVT (OR = 1.675, 95% CI: 1.406-1.994, P < .001). Concentrations of cTnI increased progressively not only with the aggravation of ventricular arrhythmic events (P < .001), but also with the growing risk of SCD in HOCM patients (P < .001). Serum cTnI ≥ 0.0265 ng/mL indicated predictive value for the occurrence of NSVT in the HOCM cohort (area under the curve = 0.707, 95% CI: 0.660-0.754, P < .001). Elevated cTnI was an independent determinant of NSVT, and it seemed to be valuable for assessing the clinical status of ventricular arrhythmias and the risk of SCD in patients with HOCM.


Reciprocal thalamo-hippocampal EEG augmenting and muscle responses in rabbits.
Waxing and waning electrographic responses (augmenting) and primary evoked responses could be induced in restricted regions of hippocampus, thalamus, and skeletal muscle by bipolar, low-frequency (7-10 Hz), low-amplitude (35 mV-4V) stimulation of selected sites within the hippocampus or thalamus of rabbits. Induction of the immobility reflex (IR) (animal hypnosis) lowered the threshold and increased the amplitude of both kinds of responses. An additive enhancement of both kinds of responses was often produced by concurrent treatment with a tranquilizer and the immobility reflex. These results suggest the thalamus and the hippocampus have interacting modulating mechanisms which affect motor activity.


Brief report: the factor structure of mood states in an early adolescent sample.
The purpose of this study was to examine the structure of negative mood states among young adolescents. Students (N=216) aged 11-15 years from a secondary school in Melbourne, Australia, completed the Depression, Anxiety, Stress Scales (DASS) [Lovibond, S. H., & Lovibond, P. F. (1996). Depression anxiety stress scales. Sydney: The Psychology Foundation of Australia Inc.]. Confirmatory factor analyses (CFA) failed to find support for a three-factor model. Further analyses suggested that items from the DASS were best represented by two factors, namely a generalized negativity factor and a factor comprising items indicating physiological arousal.


Sacbrood viruses cross-infection between Apis cerana and Apis mellifera: Rapid detection, viral dynamics, evolution and spillover risk assessment.
Recent outbreaks of sacbrood virus (SBV) have caused serious epizootic disease in Apis cerana populations across Asia including Taiwan. Earlier phylogenetic analyses showed that cross-infection of AcSBV and AmSBV in both A. cerana and A. mellifera seems common, raising a concern of cross-infection intensifying the risk of disease resurgence in A. cerana. In this study, we analyzed the dynamics of cross-infection in three different types of apiaries (A. mellifera-only, A. cerana-only and two species co-cultured apiaries) over one year in Taiwan. Using novel, genotype-specific primer sets, we showed that SBV infection status varies across apiaries: AmSBV-AM and AcSBV-AC were the major genotype in the A. mellifera-only and the A. cerana-only apiaries, respectively, while AmSBV-AC and AcSBV-AC were the dominant genotypes in the co-cultured apiaries. Interestingly, co-cultured apiaries were among the only apiary type that harbored all variants and dual infections (i.e., AC and AM genotype co-infection in a single sample), indicating the interactions between hosts may form a conduit for cross-infection. The cross-infection between the two honey bee species appears to occur in a regular cycle with temporal fluctuation of AmSBV-AC and AcSBV-AC prevalence synchronized to each other in the co-cultured apiaries. Artificial infection of AcSBV in A. mellifera workers showed the suppression of viral replication, suggesting the potential of A. mellifera serving as a AcSBV reservoir that may contribute to virus spillover. Furthermore, the survival rate of A. cerana larvae was significantly reduced after artificial infections of both SBVs, indicating fitness costs of cross-infection on A. cerana and thus a high risk of disease resurgence in co-cultured apiaries. Our field and laboratory data provide baseline information that facilitates understanding of the risk of SBV cross-infection, and highlights the urgent need of SBV monitoring in co-cultured apiaries.


Fluorescence properties and quantum-chemical modeling of tert-butyl-substituted porphyrazines: Structural and ionization effect.
Synthesis and identification of tetrakis-[5,6-bis(4-tert-butylphenyl)pyrazino] porphyrazine, tetra-(4-tert-butyl)phthalocyanine and octakis-(4-tert-butylphenyl)porphyrazine were carried out. Spectrophotometric method was used to study the spectral, acidic and fluorescence properties of the synthesized compounds. It was determined that the synthesized tert-butyl-substituted porphyrazines exhibit a high sensitivity of fluorescence to the molecule ionization. To understand the features of the spectral properties the geometry optimization and an analysis of energy levels and localization of highest occupied and lowest unoccupied molecular orbitals of the studied compounds were performed on the basis of density functional theory with the BP86 functional and the def2-TZVP basis set. The effect of substituents in molecular fragments of the macrocycle on the acidic and electro-optical properties of the studied compounds is revealed. Materials with pH-tunable fluorescence were designed.


International Validation of a Methicillin-Resistant Staphylococcus aureus Risk Assessment Tool for Skin and Soft Tissue Infections.
To promote judicious prescribing of methicillin-resistant Staphylococcus aureus (MRSA)-active therapy for skin and soft tissue infections (SSTI), we previously developed an MRSA risk assessment tool. The objective of this study was to validate this risk assessment tool internationally. A multicenter, prospective cohort study of adults with purulent SSTI was performed at seven international sites from July 2016 to March 2018. Patient MRSA risk scores were computed as follows: MRSA infection/colonization history (2 points); previous hospitalization, previous antibiotics, chronic kidney disease, intravenous drug use, human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS), diabetes with obesity (1 point each). Predictive performance of MRSA surveillance percentage, MRSA risk score, and estimated MRSA probability (surveillance percentage adjusted by risk score) were quantified using the area under the receiver operating characteristic curves (aROC) and compared. Performance characteristics of different risk score thresholds across varying baseline MRSA prevalence were examined. Two hundred three patients were included. Common SSTI were wounds (28.6%), abscess (25.1%), and cellulitis with abscess (20.7%). Patients with higher risk scores were more likely to have MRSA (P < 0.001). The MRSA risk score aROC (95%CI) [0.748 (0.678-0.819)] was significantly greater than MRSA surveillance percentage [0.646 (0.569-0.722)] (P = 0.016). Estimated MRSA probability aROC [0.781 (0.716-0.845)] was significantly greater than surveillance percentage (P < 0.001) but not the risk score (P = 0.192). The estimated negative predictive value (NPV) of an MRSA score ≥ 1 (i.e., a score of 0) was greater than 90% when MRSA prevalence was 30% or less. The MRSA risk score and estimated MRSA probability were significantly more predictive of MRSA compared with surveillance percentage. An MRSA risk score of zero had high predictive value and could help avoid unnecessary empiric MRSA coverage in low-acuity patients. Further study, including impact of such risk assessment tools on prescribing patterns and outcomes are required before implementation.


Muscarinic cholinergic receptors modulate vagal cardiac responses in man.
Respiratory sinus arrhythmia (peak-valley P-P interval changes during controlled breathing) and carotid baroreceptor-cardiac reflex responses (provoked by neck suction) were studied before and after low (0.725 microgram/kg) or high (0.043 mg/kg) dose atropine sulfate infusions in 22 healthy young adults. There was a highly significant (r = 0.78, P = 0.002) correlation between resting respiratory sinus arrhythmia and baroreflex responses. Low dose atropine increased the magnitude of sinus arrhythmia and baroreflex responses. Large dose atropine reduced sinus arrhythmia and baroreflex responses in an exponential fashion. Our results link respiratory sinus arrhythmia with baroreflex responsiveness and provide inferential evidence that vagal cardiac efferent activity is modulated by inhibitory cholinergic receptors. We speculate that blockade of these receptors by low doses of atropine amplifies vagal motoneuron responses to incoming baroreceptor information, and thereby increases average maximum and minimum levels of vagal cardiac outflow during breathing.


A blended sensor restores chronotropic response more favorably than an accelerometer alone in pacemaker patients: the LIFE study results.
Adaptive rate sensors used in permanent pacemakers incorporate an accelerometer (XL) to increase heart rate with activity. Limited data exists regarding the relative benefit of a blended sensor (BS) (XL and minute ventilation) versus XL alone in restoring chronotropic response (CR) in chronotropically incompetent (CI) patients. One thousand five hundred thirty-eight patients from the limiting chronotropic incompetence for pacemaker recipients (LIFE) study were implanted with a pacemaker and 1,256 patients had data collected at 1 month. Patients performed a treadmill test 1-month postimplant while programmed in nonrate responsive mode (DDD-60) to determine CI. Only patients who completed at least three exercise stages and achieved a peak perceived exertion >or=16 were included in the analyses. The metabolic chronotropic relationship (MCR) slope was used to evaluate CR in 547 patients. Patients were randomized to XL or BS with a conservative fixed rate response factor (XL = 8, MV = 4). CI patients performed a follow-up 6-month treadmill test. CI prevalence in this patient population (n = 547) was 34%. No differences in baseline characteristics existed between groups. Although both groups showed significant within-group improvements in MCR slope from 1 to 6 months (both P < 0.001), the BS group had a significantly higher MCR slope at 6 months compared to the XL group (P = 0.011). Improvement in quality of life (QOL) did not differ between groups. In this general pacemaker population with CI, a BS programmed empirically restores CR more favorably than an XL sensor programmed nominally. Further studies are needed to determine if individual sensor optimization would lead to improvement in functional capacity, higher MCR slopes, and QOL.


[Genotypic resistance of human immunodeficiency virus type 1 in patients with therapeutic failure].
The aim of the present study is to analyse both the frequency of resistances to the different antiretrovirals and the implication of the mayor associated resistance mutations in a group of patients with therapeutic failure. He sequence of protease (pr) and retrotranscriptase (rt) of HIV-1 isolated from blood were analysed in 284 patients. The viral load level was between 500 and 106 copies/ml. The genotype was made with TRUGENETM HIV-1 kit, which is based in the synthesis of cDNA by RT-PCR and sequenciation of this cDNA by PCR. 39,78% of the patients have not associated resistance mutations in the antiretrovirales used in the treatment, including 73 patients who have not associated resistance mutations to antiretrovirales. 60,2% of the patients have associated resistance mutations in the antiretrovirales used in the treatment. In the patients multitreated, 88,2% presented resistance to some and 53% presented genotypic resistance or possible resistance to some of the TARGA treatment. The prevalence of resistance mutations in patients with therapeutic failure is bigger than 50% with both genes.


Roles of NKT cells in resistance against infection with Toxoplasma gondii and in expression of heat shock protein 65 in the host macrophages.
We investigated the roles of gamma delta T, NK, and NK1.1(+) T-like (NKT) cells in protective immunity against infection with Toxoplasma gondii. gamma delta T cells, NKT and NK cells, and NK cells in BALB/c mice were depleted by treatment with anti-TCR-gamma delta monoclonal antibody (mAb), anti-interleukin-2 receptor beta chain (IL-2R beta) mAb, and anti-asialoGM1 Ab, respectively, and these mice were infected with T. gondii. Treatment of mice with anti-TCR-gamma delta mAb aggravated toxoplasmosis, while treatment with anti-asialoGM1 Ab had no effects. Treatment with anti-IL-2R beta mAb enhanced the expression of heat shock protein 65 (HSP65) and gamma interferon (IFN-gamma) mRNA, while it inhibited interleukin-4 (IL-4) mRNA expression, ameliorating toxoplasmosis. In addition to NK cells, anti-IL-2R beta mAb eliminated cells expressing IL-2R beta and intermediate levels of CD3 (IL-2R beta(+) CD3(int)). Mice treated with anti-IL-2R beta mAb decreased the number of DX5(+) CD3(int) cells, which are considered to be equivalent to NK1.1(+)T cells in NK1.1 allele-negative strains. IL-2R beta(+) CD3(int) cells isolated from splenic and hepatic lymphoid cells were confirmed to express the TCR-V alpha 14 transcript. The magnitude of HSP65 induction in macrophages correlated with the protective potential against T. gondii infection after treatment with the antibodies, supporting our previous finding that gamma delta T cells play an essential role in the induction of HSP65 in host macrophages. Interestingly, NKT cells suppressed the expression of gamma delta T cell-induced HSP65 and IFN-gamma. Furthermore, depletion of IL-2R beta(+) CD3(int) cells suppressed the IL-4 mRNA expression. These results suggest that NKT cells may be the cells responsible for suppression of protective immunity against T. gondii infection by interfering with the gamma delta T cell-induced HSP65 expression, possibly through the generation of IL-4.


Potential roles for Homer1 and Spinophilin in the preventive effect of electroconvulsive seizures on stress-induced CA3c dendritic retraction in the hippocampus.
Electroconvulsive therapy (ECT) remains the treatment of choice for patients with severe or drug-resistant depressive disorders, yet the mechanism behind its efficacy remains poorly characterized. In the present study, we used electroconvulsive seizures (ECS), an animal model of ECT, to identify proteins possibly involved in the preventive effect of ECS on stress-induced neuronal atrophy in the hippocampus. Rats were stressed daily using the 21-day 6h daily restraint stress paradigm and subjected to sham seizures, a single ECS on the last day of the restraint period or daily repeated seizures for 10 consecutive days during the end of the restraint period. Consistent with previous findings, dendritic atrophy was observed in the CA3c hippocampal region of chronically stressed rats. In addition, we confirmed our recent findings of increased spine density in the CA1 region following chronic restraint stress. The morphological alterations in the CA3c area were prevented by treatment with ECS. On the molecular level, we showed that the synaptic proteins Homer1 and Spinophilin are targeted by ECS. Repeated ECS blocked stress-induced up-regulation of Spinophilin protein levels and further increased the stress-induced up-regulation of Homer1. Given the roles of Spinophilin in the regulation of AMPA receptors and Homer1 in the regulation of metabotropic glutamate receptors (mGluRs), our data imply the existence of a mechanism where ECS regulate cell excitability by modulating AMPA receptor function and mGluR related calcium homeostasis. These molecular changes could potentially contribute to the mechanism induced by ECS which prevents the stress-induced morphological changes in the CA3c region.


Inflatable splints: do they cause tissue ischaemia?
The effect of increasing pneumatic splint pressure on cutaneous oxygen tension measured transcutaneously (TcPO2) was investigated in 12 subjects. The mean initial TcPO2 was 70.6 mmHg. TcPO2 decreased linearly on increasing the pressure within the splint. TcPO2 became zero at a mean splint pressure of 28 mmHg. Second, three accepted methods used by the ambulance crew to assess inflation pressures of the splint were investigated and found to be unreliable. In the light of these findings the risk of ischaemic complications as a result of applying pneumatic splints to a fractured limb is discussed. We advocate a recommended maximum splint pressure of 15 mmHg and that the splint should be manufactured with a security blow-off valve set at 15 mmHg.


Craniofacial and temporal bone CT findings in cleidocranial dysplasia.
Cleidocranial dysplasia (CCD) is a multistructural polyostotic genetic disorder that results from mutation of the CBFA1 gene. Hearing loss is a frequent finding in CCD. We describe the CT craniofacial findings in CCD and provide a comprehensive discussion of the CT temporal bone findings in these patients.


Histone Monoubiquitination in Chromatin Remodelling: Focus on the Histone H2B Interactome and Cancer.
Chromatin remodelling is a major mechanism by which cells control fundamental processes including gene expression, the DNA damage response (DDR) and ensuring the genomic plasticity required by stem cells to enable differentiation. The post-translational modification of histone H2B resulting in addition of a single ubiquitin, in humans at lysine 120 (K120; H2Bub1) and in yeast at K123, has key roles in transcriptional elongation associated with the RNA polymerase II-associated factor 1 complex (PAF1C) and in the DDR. H2Bub1 itself has been described as having tumour suppressive roles and a number of cancer-related proteins and/or complexes are recognised as part of the H2Bub1 interactome. These include the RING finger E3 ubiquitin ligases RNF20, RNF40 and BRCA1, the guardian of the genome p53, the PAF1C member CDC73, subunits of the switch/sucrose non-fermenting (SWI/SNF) chromatin remodelling complex and histone methyltransferase complexes DOT1L and COMPASS, as well as multiple deubiquitinases including USP22 and USP44. While globally depleted in many primary human malignancies, including breast, lung and colorectal cancer, H2Bub1 is selectively enriched at the coding region of certain highly expressed genes, including at p53 target genes in response to DNA damage, functioning to exercise transcriptional control of these loci. This review draws together extensive literature to cement a significant role for H2Bub1 in a range of human malignancies and discusses the interplay between key cancer-related proteins and H2Bub1-associated chromatin remodelling.


Postmortem vitreous chemistry--an evaluation of sodium, potassium and chloride levels in estimation of time since death (during the first 36 h after death).
Estimation of time since death is a paramount medico-legal issue in any postmortem examination. The present study is intended to study the correlation between postmortem interval and vitreous humor chemistry for sodium, potassium, and chlorides. The study is aimed to find male-female differences and differences between right and left eyes in vitreous chemistry. The vitreous humor samples were collected in 114 autopsies conducted in the study center and analyzed biochemically. All the cases where exact time of death was known and where the time since death ranged between 0 and 36 h were included in the study. Data obtained was analyzed statistically using spss version 11.0. The present research did not find a significant correlation between vitreous chemistry and postmortem interval. The differences in vitreous sodium, potassium, chloride levels and the sodium potassium ratio among males and females and between right and left eyes were not found to be statistically significant.


Similar feeding preferences of Anopheles gambiae and A. arabiensis in Senegal.
This study in Senegal compared the feeding preferences of Anopheles gambiae and A. arabiensis while controlling for equal accessibility to hosts located outdoors under bed net traps. All fed A. gambiae complex females were identified with the aid of the polymerase chain reaction and their blood meal sources were identified by enzyme-linked immunosorbent assay. A total of 605 anophelines, including 281 A. gambiae and 301 A. arabiensis, were captured, 32.2% in the human-baited traps and 67.8% in bovine-baited traps. 30.3% of A. gambiae fed in the former and 69.7% fed in the latter; the corresponding figures for A. arabiensis were 29.6% and 70.4%. Thus, when the hosts were located outdoors and made equally available, the feeding preferences of A. gambiae and A. arabiensis were similar (P = 0.81). These results suggest that biases existed in previous studies, most of which suggested that A. arabiensis was more zoophilic than A. gambiae. Alternatively, the feeding behaviour of these 2 species may differ in various parts of Africa.


Canonical Wnt signaling negatively modulates regulatory T cell function.
Foxp3 is crucial for both the development and function of regulatory T (Treg) cells; however, the posttranslational mechanisms regulating Foxp3 transcriptional output remain poorly defined. Here, we demonstrate that T cell factor 1 (TCF1) and Foxp3 associates in Treg cells and that active Wnt signaling disrupts Foxp3 transcriptional activity. A global chromatin immunoprecipitation sequencing comparison in Treg cells revealed considerable overlap between Foxp3 and Wnt target genes. The activation of Wnt signaling reduced Treg-mediated suppression both in vitro and in vivo, whereas disruption of Wnt signaling in Treg cells enhanced their suppressive capacity. The activation of effector T cells increased Wnt3a production, and Wnt3a levels were found to be greatly increased in mononuclear cells isolated from synovial fluid versus peripheral blood of arthritis patients. We propose a model in which Wnt produced under inflammatory conditions represses Treg cell function, allowing a productive immune response, but, if uncontrolled, could lead to the development of autoimmunity.


Relationship between donated kidney volume determined by ultrasound adjusted for clinical factors and 1-month and 1-year creatinine clearance: A retrospective study.
Graft volume as a surrogate of nephron numbers correlates with allograft function. The primary aim of this study was to correlate renal volume determined by ultrasound, adjusted to recipient clinical parameters in order to determine post-transplant renal function at the end of the first year. A total of 140 patients were enrolled in this study, including 75 males, with a total mean age of 41.2 ± 13.5 years. Clinical data of all donors and recipients undergoing kidney transplantation at our institution between 2003 and 2019 were reviewed. The volume of transplanted kidney was measured by ultrasonography on the fifth day after the operation and correlated with recipients' clinical parameters and then adjusted with first-month and first-year post-transplantation creatinine clearance. The mean allograft volume measured using ultrasonography was 175.0 ± 37.2 mL. Absolute donor kidney volume had a non-significant correlation with creatinine clearance at 1 month and at 1 year after transplantation. The kidney volume/recipient body weight ratio had a positive, and significant, correlation with creatinine clearance at 1 month and at 1 year after transplantation (r = 0.326, p < 0.001, and r = 0.183, p = 0.038, respectively). Our data demonstrated that 12-month creatinine clearance is influenced by ratio of donated kidney volume/recipient body weight.


Experience in the urologic management in 120 early spinal cord injury patients.
More than 120 patients with recent spinal cord injuries have been admitted to our hospital during the last 3 years. Intermittent catheterization has been the preliminary step in the urologic management of these patients. The transcutaneous suprapubic cystocath with intermittent aspiration of urine also has been used in 7 cases. A bladder outlet operation after 3 months was indicated 3 times more often in patients with complete than in those with incomplete neurologic lesions. Results and indications are discussed.


Effects of BAY l 5240, a fixed combination of low dose nifedipine and acebutolol on hypertension: comparison with standard dose nifedipine.
116 patients from 4 clinics participated in a double blind study to assess the efficacy of (BAY l 5240), a nifedipine-acebutolol fixed combination (10 mg + 100 mg), as compared to nifedipine 20 mg in essential hypertension. During the 10 week study, the mean recumbent blood pressure decreased 1 to 3 h after treatment from 175.5/105.2 to 148.3/88.0 mmHg in the BAY l 5240 group and from 174.3/102.9 to 150.3/86.5 mmHg in the nifedipine group. The results also showed a comparable decrease in the mean systolic (SBP) and diastolic (DBP) blood pressures before treatment (24 h after last tablet) and after physical exertion before and after either drug given for 4 weeks. Doubling of the dose for 4 additional weeks produced a moderate and similar additional decrease in blood pressure. The results show the possibility of treating essential hypertension with a low dose of a beta-adrenergic blocking agent in combination with 10 mg nifedipine. Both regimens were well tolerated. One patient in the BAY l 5240 group and 2 in the nifedipine group, all treated by the same investigator, were withdrawn from the study because of headache during the nifedipine pre-period.


Preparation and Ion Recognition Characteristics of a Trichloroacetic Acid Surface-Imprinted Material.
In this work, a trichloroacetic acid (TCAA) surface-imprinted material with high performance was prepared. In an aqueous solution, the molecules of the cationic monomer acryloyloxyethyl-trimethyl ammonium chloride (DAC) arranged around the template TCAA anion via electrostatic interaction. By initiating of the surface-initiating system of -NH2/S2O8(2-), the graft/cross-linking polymerization of DAC and the crosslinker N,N'-Methylenebisacrylamide and the TCAA surface-imprinting were simultaneously carried out on SiO2 particles, forming TCAA anion surface-imprinted material IIP-PDAC/ SiO2. With monochloroacetic acid (MCAA) and phenylacetic acid (PAA) as two contrast acids, the recognition character of the imprinted material IIP-PDAC/SiO2 was investigated. This imprinted material possesses special recognition selectivity and excellent binding affinity for TCAA anion. The binding amount of IIP-PDAC/SiO2 particles for TCAA reaches 0.93 mmol/g, whereas their binding amounts for MCAA and PAA are only 0.48 mmol/g and 0.15 mmol/g, respectively. The selectivity coefficients of IIP-PDAC/SiO2 for TCAA relative to MCAA and PAA anions are 3.61 and 9.12, respectively.


New Approaches to Biological Pacemakers: Links to Sinoatrial Node Development.
Irreversible degeneration of the cardiac conduction system is a common disease that can cause activity intolerance, fainting, and death. While electronic pacemakers provide effective treatment, alternative approaches are needed when long-term indwelling hardware is undesirable. Biological pacemakers comprise electrically active cells that functionally integrate with the heart. Recent findings on cardiac pacemaker cells (PCs) within the sinoatrial node (SAN), along with developments in stem cell technology, have opened a new era in biological pacing. Recent experiments that have derived PC-like cells from non-PCs have brought the field closer than ever before to biological pacemakers that can faithfully recapitulate SAN activity. In this review, I discuss these approaches in the context of SAN biology and address the potential for clinical translation.


A theoretical model for perceived intensity in human taste and smell. II. Temporal integration and reaction times.
The theoretical model for perceived intensity in human taste and smell published previously was extended by incorporating the concept of signal detectability and temporal integration phenomena at low and high stimulus levels. The processes involved in human taste and smell perception are divided into three stages: a) An "internal meter" registers outside signals. Adaptation occurs at this stage. b) The meter is read for two possible purposes: to detect a weak signal or to estimate the signal's intensity. Both tasks require the smoothing of noise, which is accomplished by integration of the meter over time. c) The internal estimate is expressed through the use of a scaling method.


Idiopathic pulmonary fibrosis.
Idiopathic pulmonary fibrosis is defined as a chronic progressive fibrosing interstitial pneumonia of unknown etiology. There are intrinsic and extrinsic risk factors that could favor the development of the disease in individuals with a genetic predisposition. The diagnosis is made by characteristic radiological and/or histological findings on high-resolution computed tomography and lung biopsy, respectively, in the absence of a specific identifiable cause. The median survival of the disease for patients without treatment is 3-5years from the onset of symptoms, although its natural history is variable and unpredictable. Currently, there are two antifibrotic drugs that reduce disease progression. The multidisciplinary approach will consider the nutritional and emotional status, physical conditioning, and treatment of comorbidities, as well as lung transplantation and palliative care in advanced stages. The following article reviews the fundamental aspects for the diagnosis and treatment of idiopathic pulmonary fibrosis.


The effects of vitamin A, pentoxyfylline and methylprednisolone on experimentally induced amyloid arthropathy in brown layer chicks.
The effects of vitamin A, pentoxyfylline and methylprednisolone on experimentally induced amyloid arthropathy were investigated. In this study, 175 1-day-old brown layer chicks were used. Throughout the study Group II (vitamin A) received high doses of vitamin A (75,000 IU/kg), whereas Group I (negative control), Group III (positive control), Group IV (pentoxyfylline) and Group V (methylprednisolone) received normal levels of vitamin A in the diet. At the fifth week, the experimental Groups II, III, IV and V were injected with Freund's adjuvant intra-articularly to induce amyloid arthropathy. Group IV received pentoxyfylline and Group V received methylprednisolone (10 mg/kg, intramuscularly) once. Joint and blood samples were examined 13 weeks after the injections. The values in Groups I, II, III, IV and V, respectively, were as follows: amyloid arthropathy formation (%), 0, 100, 87, 76, 66; serum amyloid A (ng/ml), 166+/-17, 607+/-40, 423+/-39, 342+/-27, 293+/-22; serum retinol (microg/dl): 59.75+/-3.8, 42.72+/-3, 59.24+/-3.6, 102+/-9.1, 101.3+/-12.3; heterophil/lymphocyte ratio: 0.504, 0.75, 0.75, 0.087, 0.44. In conclusion, it was observed that vitamin A enhanced the development of amyloid arthropathy and there were positive associations between amyloidosis, increased levels of serum amyloid A and increased numbers of tissue infiltrating macrophages. Methylprednisolone had a more successful inhibitory effect on amyloid arthropathy than pentoxyfylline.


Inverting the therapeutic pyramid: observations and recommendations on new directions in rheumatoid arthritis therapy based on the author's experience.
In evaluating current therapy for rheumatoid arthritis (RA), it is increasingly being recognized that sequential single-drug treatment, as exemplified by the traditional therapeutic pyramid, is often too little, too late, and ineffective in preventing disease progression or joint damage in patients with "at-risk," aggressive synovitis or what might be called type 2 RA. Designation of drugs as either antiinflammatory or disease-modifying is not supported by the author's experience. Evidence exists that prevention of joint damage correlates best with control of clinical and laboratory measures of inflammation, regardless of the medication used. The earlier and more effective the control of the inflammation, the better the patient response. Until a major breakthrough occurs, the author recommends that patients with aggressive RA be treated with a combination of fast-acting and slow-acting medications to achieve early control and then "bridge down" to a simplified maintenance program. Retrospective observation by the author of 54 patients with early, intermediate, and late disease treated with combinations of prednisone, methotrexate, auranofin, hydroxychloroquine, and azathioprine showed maximum response in patients with disease duration of less than 2 years, minimal toxicity, and lack of erosions in patients with control of inflammation. Twelve patients with inflammation not initially suppressed by prednisone and methotrexate had improved control with additional drugs in combination, including auranofin, hydroxychloroquine, and azathioprine. After inflammation was controlled, reduction of prednisone and methotrexate doses was possible in 60% of patients, primarily those with early disease.(ABSTRACT TRUNCATED AT 250 WORDS)


Interstitial brachytherapy for soft tissue sarcoma: A single institution experience.
Soft tissue sarcomas (STSs) are an uncommon, histologically diverse group of malignancies, which are primarily treated with surgery. Depending on location and grade, radiation therapy may be used as adjuvant treatment. In this single institution, retrospective series, we examine treatment outcome for STS treated with surgery and adjuvant interstitial brachytherapy (BTX). Forty-three patients were treated from 1997 to 2005 with adjuvant BTX for primary or recurrent STS. Thirty-four patients were treated for primary and nine for recurrent disease in locations including upper and lower extremity, pelvis, superficial trunk, and retroperitoneum. Twelve patients had low-grade and 31 had high-grade tumors. Most patients had lesions larger than 5 cm. Patients with low-grade tumors received 2500 cGy with BTX, followed by 4500 cGy with external beam radiation therapy (EBRT). High-grade tumors were treated with BTX alone to 4500 cGy if they were considered resectable at the time of diagnosis. For concern about resectability with conservative surgery, patients received 4500 cGy EBRT preoperatively, followed by a 2500 cGy BTX boost. Median followup was 39 months (range, 12-120). Thirty-four patients were known to be alive at last followup. The overall local control rate was 88%; local control was 87% for high-grade tumors and 92% for low-grade tumors. Disease-free survival was 75% overall with 88% free from distant metastases. No patient with low-grade sarcoma developed distant metastasis. Overall survival was 79%. The rate of long-term musculoskeletal or neurologic toxicity >Grade 3 was 7%, with all but a single case occurring in patients treated with EBRT plus BTX. Adjuvant interstitial BTX seemed to provide acceptable local control with well tolerated treatment in patients with low- and high-grade STS.