Age-associated chromatin relaxation is enhanced in Huntington's disease mice.
Expansion of polyglutamine stretch in the huntingtin (HTT) protein is a major cause of Huntington's disease (HD). The polyglutamine part in HTT interacts with various proteins implicated in epigenetic regulation of genes, suggesting that mutant HTT may disturb the integrity of the epigenetic system. Here, we used a PCRseq-based method to examine expression profile of 395 exonic segments from 260 "epi-driver" genes in splenic T lymphocytes from aged HD mice. We identified 67 exonic segments differentially expressed between young and aged HD mice, most of them upregulated in the aged. Polycomb-repressive complex (PRC)-regulated genes (PRGs) were markedly upregulated in aged HD mice, consistent with downregulation of PRC genes. Epi-driver gene categories of lysine-methylation, lysine-demethylation, arginine-methylation, and PRG showed differential age-associated changes between HD and control. Analyzing the pattern of change in epi-driver gene expressions hinted at an enhanced shift in HD chromatin to a more accessible state with age, which was experimentally demonstrated by DNase-I-hypersensitivity sequencing showing increased chromatin accessibility in HD cells compared to control. We suggest the global change can potentially relieve chromatin-induced repression of many genes, and the unintended expressions of some detrimental proteins could alter T cell function to a greater degree in aged HD mice.


Substantial differences in initiation of oral anticoagulant therapy and clinical outcome among non-valvular atrial fibrillation patients treated in inpatient and outpatient settings.
Patients with atrial fibrillation (AF) are encountered and treated in different healthcare settings, which may affect the quality of care. We investigated the use of oral anticoagulant (OAC) therapy and the risk of thrombo-embolism (TE) and bleeding, according to the healthcare setting. Using national Danish registers, we categorized non-valvular AF patients (2002-11) according to the setting of their first-time AF contact: hospitalization (inpatients), ambulatory (outpatients), or emergency department (ED). Event rates and hazard ratios (HRs), calculated using Cox regression analysis, were estimated for outcomes of TE and bleeding. We included 116 051 non-valvular AF patients [mean age 71.9 years (standard deviation 14.1), 51.3% males], of whom 55.2% were inpatients, 41.9% outpatients, and 2.9% ED patients. OAC therapy 180 days after AF diagnosis among patients with a CHADS2 ≥ 2 was 42.1, 63.0, and 32.4%, respectively. Initiation of OAC therapy was only modestly influenced by CHADS2 and HAS-BLED scores, regardless of the healthcare setting. The rate of TE was 4.30 [95% confidence interval (CI) 4.21-4.40] per 100 person-years for inpatients, 2.28 (95% CI 2.22-2.36) for outpatients, and 2.30 (95% CI 2.05-2.59) for ED patients. The adjusted HR of TE, with inpatients as reference, was 0.74 (95% CI 0.71-0.77) for outpatients and 0.89 (95% CI 0.79-1.01) for ED patients. In a nationwide cohort of non-valvular AF patients, outpatients were much more likely to receive OAC therapy and had a significantly lower risk of stroke/TE compared with inpatients and ED patients. However, across all settings investigated, OAC therapy was far from optimal.


Compatibilization by homopolymer: significant improvements in the modulus and tensile strength of PPC/PMMA blends by the addition of a small amount of PVAc.
Poly(propylene carbonate) (PPC), a polymer produced from CO2, has been melt-mixed with 30 wt % poly(methyl methacrylate) (PMMA) with the aim of enhancing the physical properties of PPC for practical use but keeping a relatively high CO2 fixing rate in the compound. The observation of a coarse phase structure with a large PMMA domain size and a large size distribution in the blend indicates the immiscibility between PPC and PMMA. The addition of a small amount of poly(vinyl acetate) (PVAc) not only shifts the glass transition temperatures (T(g)'s) of both PPC and PMMA markedly but also significantly increases the modulus and tensile strength of the blend. The prepared compound with 5 per hundred parts of resin PVAc shows a 26 times higher elastic modulus and an approximately 3.8 times higher tensile strength than pure PPC at room temperature. The morphological investigation indicates that the incorporation to PVAC not only induces the finer dispersion of PMMA in the PPC matrix but also results in the phase transformation from a sea-island to a co-continuous structure.


Role of dopamine transporter imaging in investigation of parkinsonian syndromes in routine clinical practice.
We discuss the potential role of dopamine transporter (DAT) imaging by single photon emission computed tomography (SPECT) as a biological marker for differentiating among parkinsonian disorders in routine clinical practice, and the implication for disease progression assessment is considered. Although clinical criteria enable accurate and reliable diagnosis of fully developed Parkinson's disease, there are several areas of diagnostic uncertainty relating to atypical parkinsonian disorders, isolated tremor symptoms not fulfilling essential tremor criteria, as well as drug-induced and psychogenetic parkinsonism. DAT-SPECT facilitates differential diagnosis of the different parkinsonian syndromes that cannot be reliably separated on clinical grounds and it can thus provide valuable diagnostic information in early disease.


In vitro characterization of TGF-beta1 release from genetically modified fibroblasts in Ca(2+)-alginate microcapsules.
This study was undertaken to develop an in situ source of transforming growth factor-beta1 (TGF-beta1), one of several molecules potentially useful for a tissue-engineered bioartificial cartilage. Primary human fibroblasts and murine NIH 3T3 cells were genetically modified via viral transfection to express human TGF-beta1. Two viral constructs were used, one expressing a gene encoding for the latent and the other for the constitutively active form of the growth factor. Unmodified cells served as controls. Four genetically modified cohorts and two controls were separately encapsulated in a 1.8% alginate solution using a vibrating nozzle and 0.15M calcium chloride crosslinking bath. Diameter of the spherical capsules was 410 +/- 87 microm. In vitro release rate measured over 168 hours varied with cell types and ranged from 2-17 pg/(milligram of capsules x 24 h) or 2-17 ng/(10(6) cells x 24 h). None of the formulations exhibited a large initial bolus release. Even when serum-supplemented medium was not replenished, cell viabilities remained over 55% after 1 week for all cell types. Microencapsulated genetically modified cells were capable of a constitutive synthesis and delivery of biologically significant quantity of TGF-beta1 for at least 168 hours and thus are of potential utility for artificial cartilage and other orthopedic tissue engineering applications.


Influence of Cervical Muscle Fatigue on Musculo-Tendinous Stiffness of the Head-Neck Segment during Cervical Flexion.
The aim of this study is to determine if the fatigue of cervical muscles has a significant influence on the head-neck segment musculo-tendinous stiffness. Ten men (aged 21.2 ± 1.9 years) performed four quick-release trials of flexion at 30 and 50% MVC before and after the induction of muscular fatigue on cervical flexors. Electromyographic activity was recorded on the sternocleidomastoids (SCM) and spinal erectors (SE), bilaterally. Musculo-tendinous stiffness was calculated through the quick-release method adapted to the head-neck segment. We noticed a significant linear increase of the head-neck segment musculo-tendinous stiffness with the increase of exertion level both before (P < 0.0001) and after the fatigue procedure (P < 0.0001). However, this linear relationship was not different before and after the fatigue procedure. EMG analysis revealed a significant increase of the root mean square for the right SCM (P = 0.0002), the left SCM (P < 0.0001), the right SE (P < 0.0001), and the left SE (P < 0.0001) and a significant decrease of the median power frequency only for the right (P = 0.0006) and the left (P = 0.0003) SCM with muscular fatigue. We did not find significant changes in the head-neck segment musculo-tendinous stiffness with fatigue of cervical muscles. We found a significant increase in EMG activity in the SCM and the SE after the induction of fatigue of the SCM. Our findings suggest that with fatigue of cervical flexors, neck muscle activity is modulated in order to maintain the musculo-tendinous stiffness at a steady state.


[The abdominal wall: an overlooked cause of pain].
Abdominal wall pain is frequently misdiagnosed as arising from visceral source, often resulting in inappropriate diagnostic tests, unsatisfactory treatment and high costs. The Authors describe the various causes of abdominal wall pain with particular regard to abdominal cutaneous nerve entrapment syndrome. They analyze the main features of abdominal wall pain: a localized tender trigger point can be frequentely identified, the Carnett's sign is positive and the local injection of an anesthetic agent into the trigger point can be diagnostic and therapeutic, while image techniques are useful when the pain results from structural conditions. At last they describe the therapeutic options.


[Subjective estimations of the treatment programmes offered in inpatient and outpatient orthopaedic rehabilitation].
The survey of psychosocial, somatic and economic outcomes is regarded as standard in establishing the effectiveness of various rehabilitative forms of medical care. Another important part is the patient's perspective for the subjective valuation of the entire measure or different facets of the rehabilitation measure. During a comparison of the effectiveness of different forms of care of orthopaedic rehabilitation (inpatient, outpatient in the hospital, outpatient) 1176 patients were questioned in writing at 4 different time points. The results concerning the general measurement of the satisfaction with the rehabilitation measure showed a high level and a high acceptance in all forms of medical care at the end of and after the measure. The result relating to the selection of the correct hospital for the specific troubles of the patient was positive as well. This can also be stated for the patients' estimation of the contacts between the doctors and the physiotherapists. At the end of measure, all the patients in every form of care viewed these contacts as being helpful. The outpatient offers were viewed a bit better by the patients concerning the contacts to doctors and physiotherapists. The extent of the care specific to the different occupational groups was estimated by almost all patients of all forms as being just about right. Additionally, the course organization and the work of the administration had a good evaluation - with slight advantages for the inpatient forms.


Densoviruses in oyster Crassostrea ariakensis.
Densoviruses have short ssDNA genomes and mainly infect arthropods. To characterize viral nucleic acid in shellfish, oysters (Crassostrea ariakensis) were analyzed using viral metagenomics. Two large de novo assembled contigs, CaaDV1 and CaaDV2, consisting of nearly complete densovirus genomes (5860 nucleotides (nt) and 4034 nt) with two major ambisense protein coding regions were identified. Several potential non-structural proteins and capsid proteins were encoded by these genomes, but these were divergent from the existing densoviral species. The NS1 protein of the two CaaDVs shared 43.3%~61.5% amino acid identities with the sea star-associated densovirus and cherax quadricarinatus densovirus, with the four species clustering by phylogenetic analysis. This is the first report of densovirus detection in shellfish, increasing the potential host range of densoviruses and the genetic diversity of the genus Ambidensovirus.


Violence Against Paramedics: Protocol for Evaluating 2 Years of Reports Through a Novel, Point-of-Event Reporting Process.
Violence against paramedics has been described as a serious public health problem with the potential for significant physical and psychological harm, but the organizational culture within the profession encourages paramedics to consider violence as just "part of the job." Therefore, most incidents of violence are never formally documented. This limits the ability of researchers and policy makers to develop strategies that mitigate the risk and enhance paramedic safety. Following the development and implementation of a novel, point-of-event violence reporting process in February 2021, our objectives are to (1) estimate the prevalence of violence and generate a descriptive profile for incidents of reported violence; (2) identify potentially high-risk service calls based on characteristics of calls that are generally known to the responding paramedics at the point of dispatch; and (3) explore underpinning themes, including intolerance based on gender, race, and sexual orientation, that contribute to incidents of violence. Our work is situated in a single paramedic service in Ontario, Canada. Using a convergent parallel mixed methods approach, we will retrospectively review 2 years of quantitative and qualitative data gathered from the External Violence Incident Report (EVIR) system from February 1 2021 through February 28, 2023. The EVIR is a point-of-event reporting mechanism embedded in the electronic patient care record (ePCR) developed through an extensive stakeholder engagement process. When completing an ePCR, paramedics are prompted to file an EVIR if they experienced violence on the call. Our methods include using descriptive statistics to estimate the prevalence of violence and describe the characteristics of reported incidents (Objective 1), logistic regression modeling to identify high-risk service calls (Objective 2), and qualitative content analysis of incident report narratives to identify underpinning themes that contribute to violence (Objective 3). As of January 1, 2023, 377 paramedics-approximately 1 in 5 active-duty paramedics in the service-have filed a total of 975 violence reports. Early analysis suggests 40% of reports involved a physical assault on the reporting paramedic. Our team is continuing to collect data with more fulsome analyses beginning in March 2023. Our findings will provide much-needed epidemiological data on the prevalence of violence against paramedics in a single paramedic service, its contributing themes, and potential risk factors. Our findings will contribute to a growing body of literature demonstrating that violence against paramedics is a complex problem that requires a nuanced understanding of its scope, risk factors, and contributing circumstances. Collectively, our research will inform larger, multisite prospective studies already in the planning stage and inform organizational strategies to mitigate the risk of harm from violence. DERR1-10.2196/37636.


Incidence of new focal pulmonary emboli after routine cardiac catheterization comparing the brachial to the femoral approach.
The incidence of pulmonary perfusion defects after routine cardiac catheterization was assessed in 56 patients by comparing ventilation-perfusion (V/Q) lung scans obtained before and 1 day after catheterization. Patients were prospectively randomized in two groups, one in which the brachial approach was performed using an antecubital cutdown procedure, and one in which the percutaneous femoral approach was used. None of the patients with the brachial approach had any ventilation-perfusion mismatch on the V/Q scan; however, three patients (8.3%) with the femoral approach did. These two groups did not differ significantly in clinical characteristics, duration of catheterization, and hemodynamic variables. The data suggest that pulmonary emboli postcardiac catheterization is more frequent in the femoral than the brachial approach. Furthermore, since those pulmonary emboli are mostly asymptomatic, their clinical recognition would be underestimated.


A cross sectional analytic study of modes of delivery and caesarean section rates in a private health insured South African population.
Monitoring Caesarean Section (CS) rates is essential to ensure optimal use of the procedure. Information on CS rates in the South African private sector is limited and information from this study will assist in planning for the proposed NHI in South Africa. The objectives of this paper are to assess mode of delivery patterns and to determine CS rates amongst South African private health insurance scheme members; and to assess the extent to which CS rates are influenced by age and health status of the mother. The 2015 claims for members of 10 health insurance schemes were analysed to assess delivery type patterns. Mode of delivery patterns were assessed by 6 delivery types: emergency, elective and "other" for caesarean deliveries; and non-assisted, assisted and "other" for vaginal deliveries; as well as by age and health condition of the mother. Of a total of 6,542 births analysed, 4,815 were CS giving a CS rate of 73·6% (95% CI 72·5%;74·7%). Emergency CS were the most common mode of delivery (39·7%), followed by elective CS (39·5%). CS rates increased with increasing maternal age and were higher for women with a medical condition. CS rates for the South African private sector are considerably higher than the safe rates recommended by the WHO. The high CS rates is a cause for concern for the health system under the proposed NHI. To support initiatives encouraging evidence based practice, further research is required to understand the drivers for the high CS rates.


Positive effect of a new supplementation of vitamin D3 with myo-inositol, folic acid and melatonin on IVF outcomes: a prospective randomized and controlled pilot study.
To assess whether oral supplementation of vitamin D3, myo-inositol, folic acid and melatonin affects IVF outcomes. One hundred and twenty consecutive infertile women attending IVF treatment were 1:1 randomly distributed in two groups. Women in group A (control) were assigned to receive myo-inositol, alpha-lactalbumin and folic acid in the morning, and myo-inositol, folic acid and melatonin in the evening. Women in group B (treated) were assigned to receive analogous treatment, with the addition of cholecalciferol (vitamin D3) in the evening from the early beginning of the luteal phase. 50 patients in group A and 50 in group B underwent blastocyst transfer and were considered in the statistical analysis. Vitamin D3 levels significantly increased after 45 days of treatment: 33.2 ng/ml in group B Vs. 24.3 ng/ml in group A (p < .0001). The implantation rate increased as well: 37.1% in group B Vs. 19.2% in group A (p < .0151). Overall, the results indicate that increased vitamin D3 levels positively correlate with the implantation rate in IVF. Because of the low number of participants, these findings need to be confirmed with larger cohorts of patients.


Probabilistic Representation and Inverse Design of Metamaterials Based on a Deep Generative Model with Semi-Supervised Learning Strategy.
The research of metamaterials has achieved enormous success in the manipulation of light in a prescribed manner using delicately designed subwavelength structures, so-called meta-atoms. Even though modern numerical methods allow for the accurate calculation of the optical response of complex structures, the inverse design of metamaterials, which aims to retrieve the optimal structure according to given requirements, is still a challenging task owing to the nonintuitive and nonunique relationship between physical structures and optical responses. To better unveil this implicit relationship and thus facilitate metamaterial designs, it is proposed to represent metamaterials and model the inverse design problem in a probabilistically generative manner, enabling to elegantly investigate the complex structure-performance relationship in an interpretable way, and solve the one-to-many mapping issue that is intractable in a deterministic model. Moreover, to alleviate the burden of numerical calculations when collecting data, a semisupervised learning strategy is developed that allows the model to utilize unlabeled data in addition to labeled data in an end-to-end training. On a data-driven basis, the proposed deep generative model can serve as a comprehensive and efficient tool that accelerates the design, characterization, and even new discovery in the research domain of metamaterials, and photonics in general.


Mapping and organization of highly-repeated DNA sequences by means of simultaneous and sequential FISH and C-banding in 6x-triticale.
Three families of highly repeated sequences from rye and the rRNA multigenes (NOR and 5S) have been mapped by FISH and C-banding, in chromosomes of triticale. The pSc119.2 probe showed interstitial hybridization in chromosome arms 1RS, 1RL, 4RL, 5RL, 6RS, 6RL, 7RS and 7RL, and is very effective for chromosome identification of rye chromosomes in triticale. This sequence also hybridizes to the 4A, 5A and the seven B-genome wheat chromosomes. Simultaneous hybridization with the pSc119.2 and pTa794 (5S rRNA) is very useful to distinguish the metacentric chromosomes 2R and 3R. The pSc74 probe appears at interstitial sites in the long arm of the most heterobrachial chromosomes (5R and 6R). The three repetitive sequences of 120 bp, 480 bp, and 610 bp hybridize to telomeric regions in rye chromosomes. Different arrangements and complex organizations consisting of arrays of three or more family sequences were found. The results demonstrate a great variation in the relative arrangement of the repetitive sequences in the telomeres of the rye chromosomes. There were quantitative differences in each cytological marker between triticale lines in both in situ labelling and C-banding, probably as the result of differences in the number and/or kind of repeat sequence.


HOM-C evolution in Drosophila: is there a need for Hox gene clustering?
The conservation of Homeotic (Hox) gene clustering and colinearity in many metazoans indicates that functional constraints operate on this genome organization. However, several studies have questioned its relevance in Drosophila. Here, we analyse the genomic organization of Hox and Hox-derived genes in 13 fruitfly species and the mosquito Anopheles gambiae. We found that at least seven different Homeotic complex (HOM-C) arrangements exist among Drosophila species, produced by three major splits, five microinversions and six gene transpositions. This dynamism contrasts with the stable organization of the complex in many other taxa. Although there is no evidence of an absolute requirement for Hox gene clustering in Drosophila, we found that strong functional constraints act on the individual genes.


Co-existence of Alport syndrome and C3 glomerulonephritis in a proband with family history.
Alport syndrome and C3 glomerulonephritis (C3GN) are rare kidney diseases, frequently responsible for familial haematuria, proteinuria, and renal impairment. With the rapid development of molecular genetic testing, Alport syndrome causes have been restricted mostly to variants in the COL4A5 or COL4A3/COL4A4 genes. Moreover, a broad range of genetic contributors in the complement and complement-regulating proteins are definitely implicated in the pathogenesis of C3GN. We sought a family with persistent microscopic haematuria associated with renal failure. Clinicopathologic and follow-up data were obtained, and molecular genetic testing was used to screen for pathogenic variants. We describe a three-generation family with Alport syndrome showing a dominant maternal inheritance. Notably, renal biopsy showed the concurrent histological evidence of C3GN in the proband harbouring an uncommon heterozygous variation in CFHR5, c.508G > A. The alteration leads to replacement of a highly conserved residue at position 170 of the β-strand subunit of CFHR5 (p.Val170Met). In silico analysis showed that the variation was predicted to deregulate complement activation by altering the structural properties and enhancing C3b binding capacity to compete with Complement Factor H (CFH), which was in line with experimental data previously published. The comorbidity findings between Alport syndrome and C3GN indicate an underlying overlap and require further study.


Compact Genetic Algorithm-Based Feature Selection for Sequence-Based Prediction of Dengue-Human Protein Interactions.
Dengue Virus (DENV) infection is one of the rapidly spreading mosquito-borne viral infections in humans. Every year, around 50 million people get affected by DENV infection, resulting in 20,000 deaths. Despite the recent experiments focusing on dengue infection to understand its functionality in the human body, several functionally important DENV-human protein-protein interactions (PPIs) have remained unrecognized. This article presents a model for predicting new DENV-human PPIs by combining different sequence-based features of human and dengue proteins like the amino acid composition, dipeptide composition, conjoint triad, pseudo amino acid composition, and pairwise sequence similarity between dengue and human proteins. A Learning vector quantization (LVQ)-based Compact Genetic Algorithm (CGA) model is proposed for feature subset selection. CGA is a probabilistic technique that simulates the behavior of a Genetic Algorithm (GA) with lesser memory and time requirements. Prediction of DENV-human PPIs is performed by the weighted Random Forest (RF) technique as it is found to perform better than other classifiers. We have predicted 1013 PPIs between 335 human proteins and 10 dengue proteins. All predicted interactions are validated by literature filtering, GO-based assessment, and KEGG Pathway enrichment analysis. This study will encourage the identification of potential targets for more effective anti-dengue drug discovery.


Pilomatrix carcinoma with pulmonary metastasis. Report of a case.
A 67-year-old white man developed a locally recurrent pilomatrix carcinoma of the back. Within a 4-year period bilateral pulmonary metastases developed. This to the knowledge of the authors is the first reported case of a metastasizing pilomatrix carcinoma in the medical literature.


Mutations in the connection domain of HIV-1 reverse transcriptase increase 3'-azido-3'-deoxythymidine resistance.
We previously proposed that a balance between nucleotide excision and template RNA degradation plays an important role in nucleoside reverse transcriptase inhibitor (NRTI) resistance. To explore the predictions of this concept, we analyzed the role of patient-derived C-terminal domains of HIV-1 reverse transcriptase (RT) in NRTI resistance. We found that when the polymerase domain contained previously described thymidine analog resistance mutations, mutations in the connection domain increased resistance to 3'-azido-3'-deoxythymidine (AZT) from 11-fold to as much as 536-fold over wild-type RT. Mutational analysis showed that amino acid substitutions E312Q, G335C/D, N348I, A360I/V, V365I, and A376S were associated strongly with the observed increase in AZT resistance; several of these mutations also decreased RT template switching, suggesting that they alter the predicted balance between nucleotide excision and template RNA degradation. These results indicate that mutations in the C-terminal domain of RT significantly enhance clinical NRTI resistance and should be considered in genotypic and phenotypic drug resistance studies.


Effect of a BMI chart on weight management discussions in a primary care setting.
To measure whether the addition of a BMI chart to a patient's medical record at the time of the office visit would increase the likelihood of a physician discussing weight management with the patient. Office staff were instructed to place a BMI chart on the front of medical charts of all patients aged 21 years to 65 years who were seen during a 2-month period in two urban university-affiliated clinics. The staff were to plot the BMI on the chart. The medical records were audited for the presence of the BMI chart and any documentation of a discussion of weight management. Of the 961 charts that were audited, 44% contained the BMI chart. A discussion of weight management issues was documented in 19% of those that contained a BMI chart and in 15% of those that did not contain a BMI chart. Data presented here suggest that adding a BMI chart to the patient medical record may increase the attention of a physician to weight management issues.


Use of fiberoptic bronchoscopy in experimental production of bovine respiratory tract disease.
Fourteen 6-month-old calves were infected with Pasteurella haemolytica or infectious bovine rhinotracheitis (IBR) virus. Four calves were inoculated sequentially with IBR virus followed by P haemolytica at a 5-day interval. Calves were inoculated by allowing them to inhale an aerosol of the organism or by placing an inoculum in the right lung, using fiberoptic bronchoscopy. Clinical signs of infection were recorded, and the calves, if they survived, were killed and necropsied 3 days after inoculation with P haemolytica (or 8 days after inoculation with IBR virus). The extent of pulmonary lesions was determined, and the lower respiratory tract (lungs and lower trachea) was examined for both organisms. Inoculation of the calves by aerosolization with IBR virus alone resulted in mild respiratory tract disease. Mild-to-moderately severe respiratory tract disease developed as a result of sequential inoculations by aerosolization with IBR virus and P haemolytica. However, respiratory tract disease did not develop in calves exposed by aerosol to P haemolytica alone. Large numbers of these organisms were recovered from the lower respiratory tract of the dually inoculated calves, only indicating delayed pulmonary clearance. Mild clinical signs of disease but substantial, though localized, pneumonic lesions developed in calves inoculated with P haemolytica by fiberoptic bronchoscopy. Calves inoculated with IBR virus by the latter procedure developed moderately severe respiratory tract disease involving 25% to 30% of the total lung volume. Lesions occurred mainly in the right lung, but the left lung also had marked lesions in these calves.(ABSTRACT TRUNCATED AT 250 WORDS)


Observation of the asymmetric Bessel beams with arbitrary orientation using a digital micromirror device.
Recently, V. V. Kotlyar et al. [Opt. Lett.39, 2395 (2014)] have theoretically proposed a novel kind of three-parameter diffraction-free beam with a crescent profile, namely, the asymmetric Bessel (aB) beam. The asymmetry degree of such nonparaxial modes was shown to depend on a nonnegative real parameter c. We present a more generalized asymmetric Bessel mode in which the parameter c is a complex constant. This parameter controls not only the asymmetry degree of the mode but also the orientation of the optical crescent, and affects the energy distribution and orbital angular momentum (OAM) of the beam. As a proof of concept, the high-quality generation of asymmetric Bessel-Gauss beams was demonstrated with the super-pixel method using a digital micromirror device (DMD). We investigated the near-field properties as well as the far field features of such beams, and the experimental observations were in good agreement with the theoretical predictions. Additionally, we provided an effective way to control the beam's asymmetry and orientation, which may find potential applications in light-sheet microscopy and optical manipulation.


Histidine decarboxylase activity in trauma-resistant rats.
Studies have been carried out to determine the possible role of nascent histamine in the development of traumatic shock. This was done by examining histidine decarboxylase (HD) activity of the lung, spleen, and plasma following exposure to trauma in normal and trauma-resistant rats. In normal rats, there was a significant increase in lung HD activity at 15 min and 4 h; and in the spleen the HD activity increased significantly at 4 h. In trauma-resistant rats exposed to trauma, there were no changes in enzyme activity in the lung and less pronounced changes in the spleen. The plasma HD activity remained stable in normal and resistant rats following episodes of trauma. Changes in total erythrocyte hemoglobin were observed in both normal and trauma-adapted rats following exposure to this stress, increasing significantly in normal rats, but decreasing in trauma-resistant rats. Blood volume decreased significantly at 4 h after trauma in normal animals; whereas only a slight decrease was noted in resistant animals. The data support the concept that newly formed histamine contributes to the pathogenesis of shock. It is also proposed that the increased resistance, characteristic of trauma-adapted rats, could be partly due to an inhibition of enzyme activation following trauma.


A review of existing and emerging digital technologies to combat the global trade in fake medicines.
The globalization of the pharmaceutical supply chain has introduced new challenges, chief among them, fighting the international criminal trade in fake medicines. As the manufacture, supply, and distribution of drugs becomes more complex, so does the need for innovative technology-based solutions to protect patients globally. Areas covered: We conducted a multidisciplinary review of the science/health, information technology, computer science, and general academic literature with the aim of identifying cutting-edge existing and emerging 'digital' solutions to combat fake medicines. Our review identified five distinct categories of technology including mobile, radio frequency identification, advanced computational methods, online verification, and blockchain technology. Expert opinion: Digital fake medicine solutions are unifying platforms that integrate different types of anti-counterfeiting technologies as complementary solutions, improve information sharing and data collection, and are designed to overcome existing barriers of adoption and implementation. Investment in this next generation technology is essential to ensure the future security and integrity of the global drug supply chain.


RamA, the transcriptional regulator of acetate metabolism in Corynebacterium glutamicum, is subject to negative autoregulation.
The RamA protein represents a LuxR-type transcriptional activator of genes involved in acetate metabolism of Corynebacterium glutamicum. Here we analyze the expression of the respective ramA gene and its regulation. Transcription was found to start 71 nucleotides upstream of the translational start codon and to be two- to threefold up-regulated in the presence of acetate in the growth medium. Accordingly, about twofold higher amounts of RamA were observed in C. glutamicum cells grown on acetate instead of glucose. Using cell extracts of C. glutamicum and employing DNA affinity chromatography, we found RamA itself as the main protein which binds to the ramA promoter region. By electrophoretic mobility shift analysis with the ramA promoter region and His-tagged RamA protein, multiple RamA-binding sites were identified in front of the ramA transcriptional start site. Transcriptional cat fusion experiments revealed that ramA promoter activity was about threefold higher in a RamA-deficient mutant of C. glutamicum than in the wild-type, however, acetate-dependent up-regulation of ramA expression was not affected in the RamA-negative mutant. These results indicate that RamA negatively controls the expression of its own gene, but is not involved in acetate-dependent up-regulation of ramA expression.


Multiwavelength Raman Spectroscopic Analysis of Superficial Iron-Chromium Oxides Generated Using Laser Irradiation.
In order to characterize iron-chromium oxides generated by laser irradiation on the surface of stainless steel plates, an ultraviolet-visible (UV-Vis) near-infrared (NIR) multiwavelength excitation Raman analysis has been performed using both austenitic SS304 and ferritic SS430 stainless steel samples. Raman spectra were obtained using five different excitation wavelengths from blue (455 nm) to NIR (830 nm). These measurements have allowed us to observe and identify four Raman bands, among which two have not been previously observed for iron-chromium oxides, and characterize the existence of different resonant excitation conditions for the different excitation wavelengths. For example, when using 455 nm as excitation wavelength the band at 485 cm-1 did not show up, although that when using 830 nm as excitation wavelength is a clear characteristic band for iron-chromium oxide. In addition, the dependence of the spectra profile with the excitation wavelength for films and microspheres features was observed. This experimental Raman analysis shows the importance of the excitation wavelength for the characterization of metallic oxides with different features.


Clinical workflow for MR-only simulation and planning in prostate.
To describe the details and experience of implementing a MR-only workflow in the clinic for simulation and planning of prostate cancer patients. Forty-eight prostate cancer patients from June 2016 - Dec 2016 receiving external beam radiotherapy were scheduled to undergo MR-only simulation. MR images were acquired for contouring (T2w axial, coronal, sagittal), synthetic-CT generation (3D FFE-based) and fiducial identification (3D bFFE-based). The total acquisition time was 25 min. Syn-CT was generated at the console using commercial software called MRCAT. As part of acceptance testing of the MRCAT package, external laser positioning system QA (< 2 mm) and geometric fidelity QA (< 2 mm within 50 cm LR and 30 cm AP) were performed and baseline values were set. Our current combined CT + MR simulation process was modified to accommodate a MRCAT-based MR-only simulation workflow. An automated step-by-step process using a MIM™ workflow was created for contouring on the MR images. Patient setup for treatment was achieved by matching the MRCAT DRRs with the orthogonal KV radiographs based on either fiducial ROIs or bones. 3-D CBCTs were acquired and compared with the MR/syn-CT to assess the rectum and bladder filling compared to simulation conditions. Forty-two patients successfully underwent MR-only simulation and met all of our institutional dosimetric objectives that were developed based on a CT + MR-based workflow. The remaining six patients either had a hip prosthesis or their large body size fell outside of the geometric fidelity QA criteria and thus they were not candidates for MR-only simulation. A total time saving of ~15 min was achieved with MR-based simulation as compared to CT + MR-based simulation. An automated and organized MIM workflow made contouring on MR much easier, quicker and more accurate compared with combined CT + MR images because the temporal variations in normal structure was minimal. 2D and 3D treatment setup localization based on bones/fiducials using a MRCAT reference image was successfully achieved for all cases. MR-only simulation and planning with equivalent or superior target delineation, planning and treatment setup localization accuracy is feasible in a clinical setting. Future work will focus on implementing a robust 3D isotropic acquisition for contouring.


Hexagonal boron nitride exfoliation and dispersion.
Research on hexagonal boron nitride (hBN) 2-dimensional nanostructures has gained traction due to their unique chemical, thermal, and electronic properties. However, to make use of these exceptional properties and fabricate macroscopic materials, hBN often needs to be exfoliated and dispersed in a solvent. In this review, we provide an overview of the many different methods that have been used for dispersing hBN. The approaches that will be covered in this review include solvents, covalent functionalization, acids and bases, surfactants and polymers, biomolecules, intercalating agents, and thermal expansion. The properties of the exfoliated sheets obtained and the dispersions are discussed, and an overview of the work in the field throughout the years is provided.


Plasma Ghrelin Levels Are Associated with Anorexia but Not Cachexia in Patients with NSCLC.
Background and Aims: The ghrelin receptor is one of the new therapeutic targets in the cancer anorexia-cachexia syndrome. Previous studies revealed that plasma ghrelin levels were high in patients with anorexia nervosa and low in obese subjects. We studied to what extent ghrelin levels are related with anorexia and cachexia in patients with cancer. Materials and Methods: Fasted ghrelin levels were determined as well as anorexia and cachexia in patients with stage III/IV non-small cell lung cancer before chemotherapy. Total plasma ghrelin was measured by radioimmunoassay. Anorexia was measured with the FAACT-A/CS questionnaire (cut-off value ≤ 37). Cachexia was determined as >5% weight loss (WL) in 6 months or >2% WL in 6 months in combination with low BMI or low muscle mass. The Kruskal-Wallis test was performed to assess differences in plasma ghrelin levels between four groups: patients with (+) or without (-) anorexia (A) or cachexia (C). Multiple regression analyses were performed to assess differences in plasma ghrelin levels between patients C+ and C- and patients with A+ and A- (adjusted for age and sex). Results: Forty patients with stage III (33%) or stage IV (68%) were recruited, of which 50% was male. Mean age was 59.6 ± 10.3 years. Sixteen patients had no anorexia or cachexia (A-C-), seven patients had both anorexia and cachexia (A+C+), ten patients had anorexia without cachexia (A+C-) and seven patients had cachexia without anorexia (A-C+). The levels of total plasma ghrelin were significantly different between the four groups of patients with or without anorexia or cachexia (p = 0.032): the A+C- patients had significantly higher ghrelin levels [median (IQR): 1,754 (1,404-2,142) compared to the A-C+ patients 1,026 (952-1,357), p = 0.003]. A+ patients had significantly higher ghrelin levels compared A- patients (C+ and C- combined, β: 304, p = 0.020). Plasma ghrelin levels were not significantly different in C+ patients compared to C- patients (A+ and A- combined, β: -99, p = 0.450). Conclusions: Patients with anorexia had significantly higher ghrelin levels compared to patients without anorexia. We therefore hypothesize that patients with cancer anorexia might benefit from treatment with a ghrelin receptor agonist to prevent WL and deterioration in physical functioning.


Setting standards for high-quality placements.
As part of a project undertaken by a local education and training board, a wide range of stakeholders across South London were asked what makes a high-quality practice placement for student nurses, and how that quality could be effectively measured. This article outlines the drafting and testing of a set of quality standards in a mix of provider settings. Although further refinement is required, the standards enabled placement sites to question themselves about their own education and training processes, strengthened their partnership with the training and education board and facilitated the assurance that student nurses receive safe, effective and compassionate preparation when they are on placement.


Effects of Eu3+ concentration on structural, optical and vibrational properties of multifunctional Ce(1-x)Eu(x)O2-delta) nanoparticles synthesized by thermolysis of 2,4-pentanedione complexes.
The 5-10 nm Ce(1-x)Eu(x)O(2-delta) (0 < or = x < or = 0.30) nanoparticles with fluorite structure were synthesized by thermal decomposition of Eu- and Ce-2,4-pentanedione complexes mixtures. X-ray line broadening analysis of mixed samples Ce(1-x)Eu(x)O(2-delta) (0.05 < or = x < or = 0.30) showed that the crystallite size was lower and root mean square strain higher than in pure ceria. However, within mixed samples Ce(1-x)Eu(x)O(2-delta) (0.05 < or = x < or = 0.30) crystallite size and root mean square strain were independent of Eu3+ concentration. Raman spectroscopy results indicated that europium ions yield disorder by breaking the phonon propagation and therefore making the non-centre Brillouin zone modes Raman active. The absorption bands in the spectra of mixed oxides were blue-shifted in comparison to pure CeO(2-delta) nanopowder. The samples show red emission typical for Eu ions. The biggest photoluminescent intensity was observed for the highest Eu3+ concentration (x = 0.30) and further enhanced with the increase in crystallinity.


[Roles of VEGF-C and its receptor Flt-4 in proliferation and metastasis of primary breast cancer].
Vascular endothelial growth factor-C(VEGF-C) is a member of VEGF family and the only factor that can combine receptor VEGFR-3 (fms-like tyrosine kinase, Flt-4) located at endothelium of lymphatic vessel and modulates the physiological function of lymphatic vessel. Previous study showed that VEGF-C/Flt-4 system play a modulating role in metastasis of many kinds of tumors, but there were few reports about its function for primary breast cancer at home and abroad. The objective of this study was to identify the function of VEGF-C/Flt-4 system in proliferation and metastasis of primary breast cancer and its significance. A series of 101 primary breast cancer specimens were detected for the expression of VEGF-C, Flt-4,and PCNA by Immunohistochemical methods. Among 101 cases of breast cancer, the positive rate of VEGF-C was 93.1% (94/101), the positive rate of flt-4 was 86.1% (87/101). With the increase of the expression of VEGF-C, the positive index of flt-4 increased (r=0.816,P< 0.001). The positive rate of PCNA was 88.8% (89/101). With the increase of the expression of VEGF-C, the proliferation activity of PCNA was stronger (r=0.673,P< 0.001). The positive index of VEGF-C in lymph node metastases group (61.89+/-17.79) was significantly higher than that of no lymph node metastasis group (44.28+/-17.87)(P< 0.05). With the increase of VEGF-C protein level, the number of flt-4 positive vessels increased and significant differences among these groups were observed (P< 0.001). The number of flt-4 positive vessels in lymph node metastases group (15.55+/-3.63)was significantly higher than that of no lymph node metastasis group (10.71+/-2.90 ) (P< 0.05). VEGF-C and Flt-4 are overexpressed in primary breast cancer and related to lymph node metastasis. VEGF-C can promote proliferation of breast cancer cell. VEGF-C/flt-4 system can promote vasculogenesis in stroma of breast cancer. The number of Flt-4 positive vessels is closely related to lymph node metastasis.


Gated myocardial perfusion tomography versus gated blood pool tomography for the calculation of left ventricular volumes and ejection fraction.
Left ventricular (LV) volume, and not only ejection fraction (EF), is a crucial parameter for assessing the severity of cardiac disease and determining the patient's prognosis. The purpose of this study was to compare LV volumes and EF computed automatically from gated blood pool tomography (gBPT), using QUBE, and from gated myocardial perfusion tomography (gMPT), using QGS, in the same patients with a known history of myocardial infarction. The effects of the extent and severity of the myocardial perfusion defects were investigated. Thirty-seven patients were injected in a random sequence with 740 MBq of technetium-99m human serum albumin and 925 MBq of (99m)Tc-tetrofosmin, within an interval of 2 days. gBPT and gMPT were acquired on the same triple-head gamma camera using the following acquisition parameters: 360 degrees step-and shoot rotation, 32 stops (96 projections), 30 s per stop, 64x64 matrix (pixel size 5.8 mm), 8 time bins (75% forward/backward framing). Projection data were reconstructed by filtered back-projection using a Butterworth filter. LV volumes calculated from gBPT correlated well with LV volumes measured on gMPT ( r=0.93 for end-diastolic volume and 0.95 for end-systolic volume). Volumes above 200 ml, however, were substantially higher with gMPT than with gBPT. These discrepancies were related to the severity, but not the extent, of the perfusion defects. There was also good agreement between gBPT and gMPT for the LVEF ( r=0.91). On the Bland-Altman plot, no trend but a systematic error of 5.57% and a random error of 6.85% could be found. For the LVEF, the differences between the gated tomographic techniques were related neither to the extent nor to the severity of the perfusion defects. In conclusion, LV volumes and EF computed on gMPT correlated well with those measured on gBPT. Discrepancies were observed for large volumes presumably because of inaccuracies of gMPT in patients with severe perfusion defects.


A peroperative test of the function of the sphincter of Oddi.
A simple peroperative flow test has been developed to help detect organic stenosis of the Ampulla of Vater. The influence of glucagon and propantheline bromide on the flow of saline through the Ampulla during operation in 79 patients was measured. By measuring the flow rate of saline before and after the administration of glucagon to patients the effective diameter of the sphincter of Oddi and its ability to relax could be deduced. Glucagon was found to be most effective in relaxing the Ampulla. For the test to be successful impacted stones must be excluded by cholangiography, but free lying stones do not affect the test. In 7 of the 62 patients receiving glucagon flow was slow and the sphincter failed to relax. Two of these patients had impacted stones and were treated by ampullary dilatation and the other 5 (who had no stones showing on X-rays) were treated by trans-duodenal sphincterotomy; 2 of these patients were found to have small non-obstructing stones impacted at the Ampulla.


Population growth and natural-resources pressures in the Mekong River Basin.
The Mekong River Basin possesses the region's largest potential water source and related resources, which support ongoing economic development and basin community livelihoods. It is currently witnessing a major demographic transition that is creating both opportunities and challenges. An analysis of the complex relationship between demographic changes and impacts on the natural-resource base confirms that resource exploitation is occurring not only to meet growing domestic needs but also for other vested interests. Population, together with other major drivers, such as institutions, markets, and technology, will have a very strong bearing on the way in which the rich resources of the Mekong River Basin are developed and distributed in the present and future. The Mekong River Basin's rich resources, and the benefits derived from them, are unevenly distributed both in time and geographically. Moreover, since the causes and impacts do not respect political boundaries, the Mekong countries need to jointly develop alternative management strategies to meet projected demands within the sustainable capacity of the Mekong River Basin natural-resource base.


Release from proactive interference in short-term memory in mentally retarded persons.
Results of this study indicated that the accumulation of and release from proactive interference in mentally retarded persons parallels that observed in nonretarded subjects. Release from proactive interference in mentally retarded subjects suggests that they can organize and discriminate between items in short-term memory.


Peptide modification results in the formation of a dimer with a 60-fold enhanced antimicrobial activity.
Cationic antimicrobial peptides (CAMPs) occur naturally in numerous organisms and are considered as a class of antibiotics with promising potential against multi-resistant bacteria. Herein, we report a strategy that can lead to the discovery of novel small CAMPs with greatly enhanced antimicrobial activity and retained antibiofilm potential. We geared our efforts towards i) the N-terminal cysteine functionalization of a previously reported small synthetic cationic peptide (peptide 1037, KRFRIRVRV-NH2), ii) its dimerization through a disulfide bond, and iii) a preliminary antimicrobial activity assessment of the newly prepared dimer against Pseudomonas aeruginosa and Burkholderia cenocepacia, pathogens responsible for the formation of biofilms in lungs of individuals with cystic fibrosis. This dimer is of high interest as it does not only show greatly enhanced bacterial growth inhibition properties compared to its pep1037 precursor (up to 60 times), but importantly, also displays antibiofilm potential at sub-MICs. Our results suggest that the reported dimer holds promise for its use in future adjunctive therapy, in combination with clinically-relevant antibiotics.


The specificity of 130-kDa leech sensory afferent proteins is encoded by their carbohydrate epitopes.
From early development through adulthood in the leech, sensory afferents, glial cells, and connective tissue express different epitopes located on a group of 130-kDa glycoproteins. The sensory epitope [reactive with monoclonal antibody (mAb) Lan3-2] is shared by the peripheral sensory afferents of different sensory modalities. In contrast, three other immunocytochemically distinct epitopes (reactive with mAbs Laz2-369, Laz7-79, and Laz6-212) differentiate these sensory afferents according to their sensory modalities. The glial epitope (mAb Laz6-297) is expressed on all macroglial processes, and the connective tissue epitope (mAb Laz9-84) is located on connective tissue surrounding the CNS, as well as in the peripheral tissues. The hydrophilic-hydrophobic nature of the 130-kDa sensory afferent and glial proteins was determined by phase separation with Triton X-114 and hypoosmotic extraction. They behave as peripheral membrane proteins. Deglycosylation of 130-kDa glycoproteins with N-Glycanase or preincubation of their respective mAbs with alpha-methylmannoside showed that the sensory epitope contains mannose, whereas the modality epitopes are of an undefined carbohydrate character. Immunoprecipitation and a peptide mapping experiment confirmed the existence of four distinct sensory afferent epitopes. Previous studies provided evidence that the mannose-containing Lan3-2 epitope mediates normal sensory afferent growth in the synaptic neuropile. We, therefore, postulate that the carbohydrate epitopes on sensory afferent glycoproteins participate in synapse formation.


Resveratrol attenuates hIAPP amyloid formation and restores the insulin secretion ability in hIAPP-INS1 cell line via enhancing autophagy.
It has been proved that human islet amyloid polypeptide (hIAPP), the main constituent of islet amyloid deposition, is one of the important factors that can induce type 2 diabetes or graft failure after islet transplantation. As there is no research on whether resveratrol degrading the amyloid deposition by its special chemical structure or enhancing autophagy had been published, we decided to detect the function of resveratrol in degrading the amyloid deposition in pancreatic beta cells. We established stable hIAPP-INS1 cell line via transfecting INS1 cells by lentivirus that overexpresses hIAPP. Our research demonstrates that amyloid deposition existed in hIAPP-INS1 cell by the thioflavin S fluorescent staining, meanwhile the function of insulin secretion of hIAPP-INS1 cells was decreased significantly (p < 0.01). After treatment with resveratrol (20 μM) for 24 h, amyloid deposition in hIAPP-INS1 cells was decreased significantly, and the insulin secretion was restored significantly (p < 0.01). Once inhibited the autophagy of hIAPP-INS1 cells by 3-methyladenine for 24 h, resveratrol does not effectively remove hIAPP deposits again, and cannot improve the function of insulin secretion. These results provide a novel thought that resveratrol can degrade the amyloid deposition in type 2 diabetes and the graft after islet transplantation.


Sodium oleate induced rapid gelation of silk fibroin.
Silk fibroin has acquired increasing interest in the last years for application in medicine and namely in tissue engineering. Several methods have been developed to process fibroin and for the fabrication of nets, sponges, films and gels. This paper deals with the fabrication and characterization of fibroin hydrogels obtained by using sodium oleate as gelation agent. Gels have been prepared by mixing Silk fibroin (SF) and Sodium oleate (SO) water solutions in different concentrations, and a quite wide frame of compositions have been explored. Rheological tests have been performed to determine the gelation times, scanning electron microscopies have been made to evaluate morphologies, FTIR analysis has been done to determine the conformation of the starting materials and of the resulting gels, water content has been measured and cytotoxicity tests have been performed to validate the potential biomedical use of the hydrogels. Depending on the SF and SO different gelation times have been obtained thanks to the formation of intermolecular bonds between the fibroin chains. The obtained fastest gelation of about 80 s could make this specific formulation compatible with in situ gelation. By changing composition, gels with different morphologies, rheological properties and water contents have been prepared.


Yellow fever epizootics in non-human primates, São Paulo state, Brazil, 2008-2009.
Since 2000, the expansion of Sylvatic Yellow Fever (YF) has been observed in the southeast of Brazil, being detected in areas considered silent for decades. Epizootics in non-human primates (NHPs) are considered sentinel events for the detection of human cases. It is important to report epizootic events that could have impact on the conservation status of susceptible species. We describe the epizootics in NHPs, notified in state of São Paulo, Brazil, between September 2008 to August 2009. Ninety-one epizootic events, involving 147 animals, were reported in 36 counties. Samples were obtained from 65 animals (44.2%). Most of the epizootics (46.6%) were reported between March and April, the same period during which human cases of YF occurred in the state. Biological samples were collected from animals found dead and were sent to Instituto Adolfo Lutz, in São Paulo. Two samples, collected in two counties without an indication for YF vaccination, were positive for the virus. Another 48 animals were associated with YF by clinical-epidemiological linkage with laboratory confirmed cases. Because the disease in human and NHPs occurred in the same period, the detection of the virus in NHPs did not work as sentinel, but aided in the delineation of new areas of risk.


Decreased short-term renal graft survival in Maghrebian recipients.
The influence of race on renal allograft survival is disputed. We studied 16 cadaveric renal transplants in 14 Maghrebian patients, each matched with two controls of local origin. Patient survival at 12 months was 93% in the Maghreb group and 97% in the control group (NS). Graft survivals at 3 months for these two groups were 73% and 97%, respectively (P<0.01). At 6 months, graft survival in the control group remained unchanged at 97%, whereas in the case group it declined further to 59% (P<0.01). Overall graft failure in the Maghreb group amounted to 44% (seven of 16 transplants). In each case, failure was due to biopsy-proven acute rejection. Overall graft failure amongst the controls was only 6% (two of 32 transplants) (P=0.004) (only one case of acute rejection, or 3%) (P=0.01). This study provides evidence for significantly lower short-term renal graft survival in Maghrebian recipients of a Caucasian graft. Acute rejection seems to play a major causative role in graft loss in this group.


Bruises, blood coagulation tests and the battered child syndrome.
Cutaneous bruises are a common symptom and a sign of injury and blood coagulation disorders in childhood. A carefully-taken history, coupled with a thorough physical examination, would lead to the diagnosis, or guide the clinician to the necessary laboratory investigations. Most children suffering from non-accidental injury can have their diagnosis established on clinical grounds alone and do not require laboratory investigation. An initial screening with full blood counts, prothrombin time and activated partial thromboplastin time will be adequate in most cases if laboratory investigation is indicated, but the clinician must be aware of the limitations of these tests. The finding of an abnormal coagulation test does not exclude child abuse as it can be a consequence of maltreatment, or the two conditions may coexist. Whenever necessary, the opinion of a haematologist should be sought in order to obtain an accurate diagnosis, which is essential for subsequent management and the prevention of further injury in the case of child abuse.


[A case of tetanus showing limited mobility of the bilateral vocal cords].
Patients with tetanus complaining of common signs such as lockjaw, voice disturbance, and difficulty in swallowing, etc, should never be forgotten. A 71-year old woman complained of dyspnea and difficulty in swallowing. She had lockjaw with tongue bite soon after a tracheostomy, and she was diagnosed as having tetanus. She showed the redundant gag reflex even to a slight stimulus and limited mobility of bilateral vocal cords, which improved following intravenous administration of diazepam. This case suggests that the mobility of the vocal cords and the movement of the larynx could be limited in tetanus because even a slight stimulus caused a strong gag reflex, resulting in dyspnea or difficulty in swallowing.


Folding and ligand recognition of the TPP riboswitch aptamer at single-molecule resolution.
Thiamine pyrophosphate (TPP)-sensitive mRNA domains are the most prevalent riboswitches known. Despite intensive investigation, the complex ligand recognition and concomitant folding processes in the TPP riboswitch that culminate in the regulation of gene expression remain elusive. Here, we used single-molecule fluorescence resonance energy transfer imaging to probe the folding landscape of the TPP aptamer domain in the absence and presence of magnesium and TPP. To do so, distinct labeling patterns were used to sense the dynamics of the switch helix (P1) and the two sensor arms (P2/P3 and P4/P5) of the aptamer domain. The latter structural elements make interdomain tertiary contacts (L5/P3) that span a region immediately adjacent to the ligand-binding site. In each instance, conformational dynamics of the TPP riboswitch were influenced by ligand binding. The P1 switch helix, formed by the 5' and 3' ends of the aptamer domain, adopts a predominantly folded structure in the presence of Mg(2+) alone. However, even at saturating concentrations of Mg(2+) and TPP, the P1 helix, as well as distal regions surrounding the TPP-binding site, exhibit an unexpected degree of residual dynamics and disperse kinetic behaviors. Such plasticity results in a persistent exchange of the P3/P5 forearms between open and closed configurations that is likely to facilitate entry and exit of the TPP ligand. Correspondingly, we posit that such features of the TPP aptamer domain contribute directly to the mechanism of riboswitch-mediated translational regulation.


[Therapeutic perspective in hereditary polyneuropathies].
Hereditary motor and sensory neuropathies (HMSN) also called as Charcot-Marie-Tooth disorders (CMT) are extremely heterogeneous group of disorders of peripheral nervous system. Over 80 genes have been reported in different types of CMT. In all CMT affected patients the main symptoms are slowly progressive wasting of the distal muscles of the lower and upper limbs. To date no efficient therapeutic approach basing upon molecular pathology of CMT has been proposed. This review presents the current state of knowledge concerning clinical, molecular pathogenesis and experimental therapy aspects in CMT disorders. Additionally the possibilities resulting from the use of the yeast model to the identification of new therapeutic substances as well as of neurotoxins are also discussed.


Blockade of 5-HT(3) receptor with MDL 72222 and Y 25130 reduces beta-amyloid protein (25--35)-induced neurotoxicity in cultured rat cortical neurons.
The present study was performed to examine neuroprotective effects of 5-hydroxytryptamine (5-HT)(3) receptor antagonists against beta-amyloid protein (25--35)-, a synthetic 25--35 amyloid peptide, induced neurotoxicity using cultured rat cortical neurons. beta-Amyloid protein (25--35) produced a concentration-dependent reduction of cell viability, which was significantly reduced by (5R,10S)-(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d] cyclohepten-5,10-imine (MK-801), an N-methyl-d-aspartate (NMDA) receptor antagonist, verapamil, an L-type Ca(2+) channel blocker, and N(G)-nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase inhibitor. The 5-HT(3) receptor antagonists, tropanyl-3,5-dichlorobenzoate (MDL-72222, 0.1--10 microM) and N-(1-azabicyclo[2.2.2.]oct-3-yl)-6-chloro-4-ethyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazine-8-carboxamide hydrochloride (Y 25130, 0.05--5 microM), decreased the beta-amyloid protein (25--35) (10 microM)-induced neuronal cell death as assessed by a colorimetric 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay and the number of apoptotic nuclei, evidenced by Hoechst 33342 staining. MDL 72222 and Y 25130 inhibited the beta-amyloid protein (25--35) (10 microM)-induced elevation of cytosolic Ca(2+) concentration ([Ca(2+)](c)) and glutamate release, generation of reactive oxygen species, and caspase-3 activity. These neuroprotective effects of MDL 72222 (10 microM) and Y 25130 (5 microM) were completely blocked by the simultaneous treatment with 100 microM 1-phenylbiguanide, a 5-HT(3) receptor agonist, indicating that the protective effects of these compounds were due to 5-HT(3) receptor blockade. These results suggest that the activation of the 5-HT(3) receptor may be partially involved in beta-amyloid protein-induced neurotoxicity, by membrane depolarization for Ca(2+) influx. Therefore, the blockade of 5-HT(3) receptor with MDL 72222 and Y 25130, may ameliorate the beta-amyloid protein-induced neurotoxicity by interfering with the increase of [Ca(2+)](c), and then by inhibiting glutamate release, generation of reactive oxygen species and caspase-3 activity.


Individual investment decision behaviors based on demographic characteristics: Case from China.
Predicting and analyzing behaviors of investors is of great value to financial institutions. This paper uses survey data from about 9,000 individual investors across China to explore the predictability of decision behaviors by studying demographic characteristics that are relatively easy to obtain. After applying Pearson's chi-squared test, Spearman rank correlation test, and several data mining methods, we verified that demographic characteristics are closely linked to decision behaviors, and it would be an economical and feasible solution for financial organizations to build initial behavioral prediction models especially when investors' behavioral data are insufficient.


Binding properties of mechanically and enzymatically isolated hepatocytes for IgG and C3.
The presence of Fc and C3 receptors was studied on mechanically and enzymatically isolated rabbit, mouse and rat hepatocytes as well as on hepatocytes derived from primary cultures. The same cell preparations were used for studying the uptake of an antibody against nuclear antigens. Mechanically isolated hepatocytes were able to bind AIgG and activate complement. However, the same cells were not able to form rosettes with EA or with EAC. Enzymatically isolated hepatocytes did not bind AIgG or activate complement nor did they form rosettes with EA or with EAC. The mechanically isolated cells and the nonviable fraction of the enzymatically isolated cells showed a nuclear fluorescence when incubated with an antibody against nuclear antigens. We conclude that enzymatically isolated hepatocytes lack Fc and C3 binding sites. Furthermore, the damage to the plasma membrane of the non-viable cells allows the penetration of antibodies against intracellular antigens.


Work Demands-Burnout and Job Engagement-Job Satisfaction Relationships: Teamwork as a Mediator and Moderator.
Few studies have examined teamwork as mediator and moderator of work demands-burnout and job engagement-job satisfaction relationships in healthcare workers (HCWs) in South-East Europe. To assess mediation and moderation effect of teamwork on the relationship between independent (work demands or job engagement) and dependent (burnout or job satisfaction) variables. Work demands, burnout, job engagement, and job satisfaction were measured with Hospital Experience Scale, Maslach Burnout Inventory, Utrecht Work Engagement Scale, and Job Satisfaction Survey, respectively. Hospital Survey on Patient Safety Culture was used for assessment of teamwork. In order to examine role of teamwork as a mediating variable we fit series of regression models for burnout and job satisfaction. We also fit regression models predicting outcome (burnout or job satisfaction) from predictor (work demands or job engagement) and moderator (teamwork) variable. Teamwork was partial mediator of work demands-burnout relationship and full mediator of job engagement-job satisfaction relationship. We found that only job engagement-job satisfaction relationship was moderated by teamwork. Occupational health services should target detection of burnout in HCWs and implementation of organizational interventions in hospitals, taking into account findings that teamwork predicted reduced burnout and higher job satisfaction.


Nanoparticle-based CT visualization of pulmonary vasculature for minimally-invasive thoracic surgery planning.
To evaluate CF800, a novel lipid-based liposomal nanoparticle that co-encapsulates indocyanine green (ICG) and iohexol, for CT imaging of pulmonary vasculature in minimally-invasive thoracic surgery planning. CF800 was intravenously administered to 7 healthy rabbits. In vivo CT imaging was performed 15 min post-injection, with a subset of animals imaged at 24h, 48h, and 72h post injection. Signal-to-background ratios (SBR) were calculated at the inferior vena cava and compared across time-points. A similar protocol was applied to 2 healthy pigs to evaluate the feasibility and efficacy in a large animal model. To evaluate the feasibility of clinical application, a survey was completed by 7 surgical trainees to assess pre- and post-injection CT images of rabbits and pigs. Responses on the discernibility of pulmonary vasculature sub-branches and comfort level to use the images for pre-operative planning were collected and analyzed. CF800 injection improved visualization of pulmonary vessels in both rabbit and pig models. The SBR of rabbit pulmonary vasculature was significantly higher after CF800 injection (range 3.7-4.4) compared to pre-injection (range 3.3-3.8, n = 7; p<0.05). SBR remained significantly different up to 24 hours after injection (range 3.7-4.3, n = 4; p<0.05). Trainees' evaluation found the post-injection CT images had significantly higher discernibility at the second vessel branch generation in both rabbit and pig models. Trainees identified smaller vasculature branch generations in the post-injection images compared to the pre-treatment images in both rabbit (mean 6.7±1.8 vs 5.4±2.1; p<0.05) and pig (mean 6.7±1.8 vs 5.4±2.1; p<0.05). Trainees were significantly more comfortable using post-injection images for surgical planning compared to the pre-injection images (rabbit: 8.1±1.1 vs. 4.7±2.1; pig: 7.6±2.1 vs. 4.9±2.2; p<0.05). CF800 provides SBR and contrast enhancement of pulmonary vasculature which may assist in pre-surgical CT planning of minimally invasive thoracic surgery.


Intestinal perforation as an early complication in Wegener's granulomatosis.
We present the case of a young man with involvement of the gastrointestinal tract in the early phase of Wegener's granulomatosis. The patient presented at the emergency department with sudden onset of abdominal pain, nausea and vomiting. Radiography work up was negative for free air although ultrasound examination showed extraluminal intra-abdominal fluid. Exploratory laparotomy showed perforation of the jejunum. The bowel was vital except for this small segment of jejunum. A 5-cm long segment of jejunum was resected which revealed ulcerative inflammation accompanied by occluded arteries of the small intestine. Although intestinal perforation in Wegener's granulomatosis is uncommon, several cases have been previously reported. Intestinal involvement in the early phase of the disease is even more uncommon. This case combined with previously reported cases emphasizes the possibility of gastrointestinal manifestation early in Wegener's disease.


Emerging complexities and rising omission: Contrasts among socio-ecological contexts of infectious diseases, research and policy in Brazil.
In this article, we explore elements that highlight the interdependent nature of demands for knowledge production and decision-making related to the appearance of emerging diseases. To this end, we refer to scientific production and current contextual evidence to verify situations mainly related to the Brazilian Amazon, which suffers systematic disturbances and is characterized as a possible source of pathogenic microorganisms. With the acceleration of the Anthropocene's environmental changes, socio-ecological instabilities and the possibility of the emergence of infectious diseases merge into a background of a ´twin insurgency´. Furthermore, there is a tendency to impose economic hegemony in the current Brazilian context, corroborating discourses and pressures to a scientific simplification and denial. With this, we assert that developmental sectoral actions and monoculture of knowledge characterize an agenda of omission, that is, a process of decision making that indirectly reinforces ecological degradation and carelessness in the face of the possibility of the emergence and spreading of new diseases, such as COVID-19. Tackling the socio-ecological complexity inherent in the risk of the emergence of infectious diseases requires robust co-construction of scientific knowledge, eco-social approaches, and corresponding governance and sophisticated decision-making arrangements.


Biosynthesis and production of polysialic acids in bacteria.
Polysialic acids (PA) are protective capsular sialohomopolymers present in some bacteria which can invade the mammalian host and cause lethal bacteremia and meningitis. Biosynthesis and translocation of PA to the cell surface are equivalent in different species and bacterial strains which are produced. The diversity in PA structure is derived from the PA linkages and is a consequence of the specific sialyltransferase activities. The monomer acetylation and the polymer length could be important factors in the potential virulence. In vivo PA production is affected by different physical and chemical factors. The temperature of cellular growth strictly regulates PA genesis through a molecular complex and multifactorial mechanism that operate to transcription level.


Multichannel silk protein/laminin grafts for spinal cord injury repair.
The physical, chemical, and bioactive cues provided by biomaterials are critical for spinal cord regeneration following injury. In this study, we investigated the bioactivity of a silk-based scaffold for nerve tissue remodeling that featured morphological guidance in the form of ridges as well as bioactive molecules. Multichannel/laminin (LN) silk scaffolds stimulated growth, development, and the extension of primary hippocampal neurons after 7 days of culture in vitro. And then, the multichannel/LN silk scaffolds were implanted into 2-mm-long hemisection defects in Sprague-Dawley rat spinal cords for 70 days to evaluate their bioactivities of spinal cord remolding. Our results demonstrated that animal behavior was significantly improved in the multichannel/LN group, as evaluated by Basso-Beattie-Bresnahan score, whereas the implantation of multichannels and random pores groups resulted in recurring limps. Moreover, histology and immunohistochemical staining revealed an increase in blood vessels and expression of growth associated protein-43 and neurofilament-200 as well as reduced expression of glial fibrillary acidic protein in the multichannel/LN group, which contributed to the rebuilding of spinal cord defects. Thus, multichannel/LN silk scaffolds mediated cell migration, stimulated blood capillary formation, and promoted axonal extension, suggesting the utility of these scaffolds for spinal cord reconstruction. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 3045-3057, 2016.


Nicardipine inhibits axon conduction but causes dual changes of acetylcholine release in the mouse motor nerve.
The effects of nicardipine, a dihydropyridine Ca2(+)-channel antagonist, on neuromuscular transmission and impulse-evoked release of acetylcholine were compared with those of nifedipine. In the isolated mouse phrenic nerve diaphragm, nicardipine (50 microM), but not nifedipine (100 microM), induced neuromuscular block, fade of tetanic contraction, and dropout or all-or-none block of end-plate potentials. Nicardipine had no significant effect on the resting membrane potential and the amplitude of miniature end-plate potentials but increased the frequency and caused the appearance of large size miniature potentials. The quantal contents of evoked end-plate potentials were increased. In the presence of tubocurarine, however, nicardipine depressed the amplitude of end-plate potentials. The compound nerve action potential was also decreased. It is concluded that nicardipine blocks neuromuscular transmission by acting on Na+ channels and inhibits axonal conduction. Nicardipine appeared to affect the evoked release of acetylcholine by dual mechanisms, i.e., an enhancement presumably by an agonist action on Ca2+ channels, like Bay K 8644 and nifedipine, and inhibition by an effect on Na+ channels, like verapamil and diltiazem. In contrast with its inactivity on the amplitude of miniature end-plate potentials, depolarization of the end plate in response to succinylcholine was greatly depressed. The contractile response of baby chick biventer cervicis muscle to exogenous acetylcholine was noncompetitively antagonized by nicardipine (10 microM), but was unaffected by nifedipine (30 microM). These results may implicate that nicardipine blocks the postsynaptic acetylcholine receptor channel by enhancing receptor desensitization or by a use-dependent effect.


Role of the major antigenic membrane protein in phytoplasma transmission by two insect vector species.
Phytoplasmas are bacterial plant pathogens (class Mollicutes), transmitted by phloem feeding leafhoppers, planthoppers and psyllids in a persistent/propagative manner. Transmission of phytoplasmas is under the control of behavioral, environmental and geographical factors, but molecular interactions between membrane proteins of phytoplasma and vectors may also be involved. The aim of the work was to provide experimental evidence that in vivo interaction between phytoplasma antigenic membrane protein (Amp) and vector proteins has a role in the transmission process. In doing so, we also investigated the topology of the interaction at the gut epithelium and at the salivary glands, the two barriers encountered by the phytoplasma during vector colonization. Experiments were performed on the 'Candidatus Phytoplasma asteris' chrysanthemum yellows strain (CYP), and the two leafhopper vectors Macrosteles quadripunctulatus Kirschbaum and Euscelidius variegatus Kirschbaum. To specifically address the interaction of CYP Amp at the gut epithelium barrier, insects were artificially fed with media containing either the recombinant phytoplasma protein Amp, or the antibody (A416) or both, and transmission, acquisition and inoculation efficiencies were measured. An abdominal microinjection protocol was employed to specifically address the interaction of CYP Amp at the salivary gland barrier. Phytoplasma suspension was added with Amp or A416 or both, injected into healthy E. variegatus adults and then infection and inoculation efficiencies were measured. An internalization assay was developed, consisting of dissected salivary glands from healthy E. variegatus exposed to phytoplasma suspension alone or together with A416 antibody. The organs were then either observed in confocal microscopy or subjected to DNA extraction and phytoplasma quantification by qPCR, to visualize and quantify possible differences among treatments in localization/presence/number of CYP cells. Artificial feeding and abdominal microinjection protocols were developed to address the two barriers separately. The in vivo interactions between Amp of 'Candidatus Phytoplasma asteris' Chrysanthemum yellows strain (CYP) and vector proteins were studied by evaluating their effects on phytoplasma transmission by Euscelidius variegatus and Macrosteles quadripunctulatus leafhoppers. An internalization assay was developed, consisting of dissected salivary glands from healthy E. variegatus exposed to phytoplasma suspension alone or together with anti-Amp antibody. To visualize possible differences among treatments in localization/presence of CYP cells, the organs were observed in confocal microscopy. Pre-feeding of E. variegatus and M. quadripunctulatus on anti-Amp antibody resulted in a significant decrease of acquisition efficiencies in both species. Inoculation efficiency of microinjected E. variegatus with CYP suspension and anti-Amp antibody was significantly reduced compared to that of the control with phytoplasma suspension only. The possibility that this was due to reduced infection efficiency or antibody-mediated inhibition of phytoplasma multiplication was ruled out. These results provided the first indirect proof of the role of Amp in the transmission process. Protocols were developed to assess the in vivo role of the phytoplasma native major antigenic membrane protein in two phases of the vector transmission process: movement through the midgut epithelium and colonization of the salivary glands. These methods will be useful also to characterize other phytoplasma-vector combinations. Results indicated for the first time that native CYP Amp is involved in vivo in specific crossing of the gut epithelium and salivary gland colonization during early phases of vector infection.


An investigation into the allylic imidate rearrangement of trichloroacetimidates catalysed by cobalt oxazoline palladacycles.
Dimeric palladacycles, di-mu-X-bis[{eta(5)-(S)-((p)R)-2-[2'-(4'-methylethyl)oxazolinyl]cyclopentadienyl,1-C,3'-N}(eta(4)-tetraphenylcyclobutadiene)cobalt]dipalladium (COP-X), containing bridging groups X=OAc, Cl, Br, I, O(2)CCF(3), p-O(2)CC(6)H(4)F, were synthesised and compared as catalysts for the asymmetric allylic imidate rearrangement of (E)-Cl(3)CC(=NH)OCH(2)CH=CHR with R=nPr. The enantiomeric excess of the product (S)-Cl(3)CC(=O)NHCHRCH=CH(2) was essentially invariant of X (93-96%) and the yield increased in the sequence I<p-O(2)CC(6)H(4)F<OAc<O(2)CCF(3) approximately Br approximately Cl. With X=Cl (COP-Cl), the catalyst loading was reduced to 0.25 mol% (CH(3)CN/70 degrees C/48 h) and these conditions applied to various trichloroacetimidates (R=nPr, Me, CH(2)Ph, CH(2)CH=CH(2), CH(2)OTBDMS) to give the corresponding (S)-trichloroacetamides (68-88% yield, 84-94% ee; ee=enantiomeric excess). Addition of COP-Cl to triphenylphosphinobenzoyl NovaGel AM resin gave a recyclable catalyst in which the ee was maintained over three cycles (89-94%). Catalysis with COP-OAc displayed a small positive non-linear effect. The factors responsible for the activity of COP-X are discussed.


Metabolic markers or conditions preceding Parkinson's disease: a case-control study.
Several metabolic markers or conditions have been explored as possible risk or protective factors for Parkinson's disease (PD); however, results remain conflicting. We further investigated these associations using a case-control study design. We used the medical records-linkage system of the Rochester Epidemiology Project to identify 196 subjects who developed PD in Olmsted County, Minnesota, from 1976 through 1995. Each incident case was matched by age (±1 year) and sex to a general population control. We reviewed the complete medical records of cases and controls in the medical records-linkage system to abstract information about body mass index (BMI), cholesterol level, hypertension, and diabetes mellitus preceding the onset of PD (or the index year). There were no significant differences between cases and controls for the metabolic markers or conditions investigated. No significant associations were found using 2 cutoffs for BMI level (BMI ≥ 25 or BMI ≥ 30 kg/m(2) ) and 3 cutoffs for cholesterol levels (>200, >250, or >300 mg/dL). Neither a diagnosis of hypertension or the documented use of antihypertensive medications was significantly associated with the subsequent risk of PD (odds ratio [OR], 1.00; 95% confidence interval [CI], 0.65-1.54; P = .99) nor was a diagnosis of diabetes mellitus or the use of glucose-lowering medications (OR, 0.77; 95% CI, 0.37-1.57; P = .47). Our study, based on historical information from a records-linkage system, does not support an association between BMI, cholesterol level, hypertension, or diabetes mellitus with later development of PD.


Phylogeny, expression patterns and regulation of DNA Methyltransferases in early development of the flatfish, Solea senegalensis.
The identification of DNA methyltransferases (Dnmt) expression patterns during development and their regulation is important to understand the epigenetic mechanisms that modulate larval plasticity in marine fish. In this study, dnmt1 and dnmt3 paralogs were identified in the flatfish Solea senegalensis and expression patterns in early developmental stages and juveniles were determined. Additionally, the regulation of Dnmt transcription by a specific inhibitor (5-aza-2'-deoxycytidine) and temperature was evaluated. Five paralog genes of dnmt3, namely dnmt3aa, dnmt3ab, dnmt3ba, dnmt3bb.1 and dnmt3bb.2 and one gene for dnmt1 were identified. Phylogenetic analysis revealed that the dnmt gene family was highly conserved in teleosts and three fish-specific genes, dnmt3aa, dnmt3ba and dnmt3bb.2 have evolved. The spatio-temporal expression patterns of four dnmts (dnmt1, dnmt3aa, dnmt3ab and dnmt3bb.1) were different in early larval stages although all of them reduced expression with the age and were detected in neural organs and dnmt3aa appeared specific to somites. In juveniles, the four dnmt genes were expressed in brain and hematopoietic tissues such as kidney, spleen and gills. Treatment of sole embryos with 5-aza-2'-deoxycytidine down-regulated dntm1 and up-regulated dntm3aa. Moreover, in lecithotrophic larval stages, dnmt3aa and dnmt3ab were temperature sensitive and their expression was higher in larvae incubated at 16 °C relative to 20 °C. Five dnmt3 and one dnmt1 paralog were identified in sole and their distinct developmental and tissue-specific expression patterns indicate that they may have different roles during development. The inhibitor 5-aza-2'-deoxycytidine modified the transcript abundance of dntm1 and dntm3aa in embryos, which suggests that a regulatory feedback mechanism exists for these genes. The impact of thermal regime on expression levels of dnmt3aa and dnmt3ab in lecithotrophic larval stages suggests that these paralogs might be involved in thermal programing.


Epidural spinal cavernous hemangioma.
A 28-year-old woman presented with a rare primary epidural hemangioma without adjacent vertebral involvement manifesting as progressive paraparesis. Magnetic resonance imaging of the thoracic spine showed an epidural lesion at T4-5 space appearing as isointense on T1-weighted images with enhancement by contrast medium and hyperintense on T2-weighted images. The lesion was totally removed microsurgically. Histological examination revealed cavernous hemangioma. She made a complete recovery from her symptoms and has remained asymptomatic for 9 years.


Cytomegalovirus infection in Systemic Lupus Erythematosus: report of four cases challenging the management of the disease, and literature review.
Cytomegalovirus (CMV) is particularly dangerous in systemic lupus erythematosus (SLE), being a problem both for the differential diagnosis with disease flare and for the management of SLE flare with immunosuppressive drugs. We report on four cases of SLE with concomitant CMV infection, having some common clinical and laboratory characteristics. Our data suggest that lupus patients presenting with symptoms such as fever, diarrhea, and respiratory symptoms, alone or in combination, and laboratory evidence of leukopenia, elevated transaminases, and hyponatremia, especially in the setting of recent immunosuppressive treatments, should be screened for CMV.


Extraction of maxillary central incisors: an orthodontic-restorative treatment.
Malformed central incisors with poor prognosis could be candidates for extraction especially in crowded dental arches. This case report refers to a 12-year-old boy who suffered from malformed upper central incisors associated with severe attrition. Upper lateral incisors were positioned palatally and canines were rotated and positioned in the high buccal area. The patient had class II malocclusion and space deficiency in both dental arches. Due to incisal wear and malformed short maxillary central incisors and the need for root canal therapy with a major crown build-up, these teeth were extracted. The maxillary lateral incisors were substituted. Thus the maxillary canines were substituted for lateral incisors and the first premolars were substituted for canines. In the lower dental arch the first bicuspids were extracted. Composite resin build-up was performed on the maxillary lateral incisors and canines. This allowed for the crowding and the malocclusion to be corrected. Subsequent gingivectomy improved the patient's gingival margins and smile esthetics one month after orthodontic therapy.


Prognostic value of microphthalmia-associated transcription factor and tyrosinase as markers for circulating tumor cells detection in patients with melanoma.
The aim of this study was to analyze microphthalmia-associated transcription factor (MITF) as a marker for the detection of circulating melanoma cells, determine its prognostic value in melanoma patients, and compare it with tyrosinase. Blood samples from 201 melanoma patients in all stages of the disease and 40 healthy volunteers were analyzed. RNA was isolated from mononuclear cell fraction of the blood and assayed by reverse transcription-PCR for the expression of MITF and tyrosinase. All samples from healthy volunteers were negative for both MITF and tyrosinase. Out of 201 blood samples from melanoma patients 32 were positive for MITF, 20 for tyrosinase, and four for both MITF and tyrosinase. Analysis of MITF as an additional marker to tyrosinase allowed for detection of circulating melanoma cells in a larger number of melanoma patients in comparison to tyrosinase analysis alone (48 vs. 20 positive). A positive value of MITF was associated with shorter progression-free (P=0.005) and overall survival (P=0.042). A positive value of tyrosinase was associated with shorter overall survival (P=0.012), whereas there was no significant association between the value of tyrosinase and progression-free survival. The value of MITF was selected with multivariate analysis as the independent prognostic factor for progression-free survival, whereas the only independent prognostic factor for overall survival was the stage of disease. This study has shown that MITF is a specific marker for detection of circulating melanoma cells that has a prognostic value in melanoma patients. Determination of MITF in addition to tyrosinase improved the detection of circulating melanoma cells in melanoma patients.


Direct and indirect injuries of the pharynx and larynx.
Direct and indirect injuries of the pharynx and larynx. The neck is characterized by a relatively complex anatomy and a very compact content. It therefore forms an extremely vulnerable part of the human body. Although uncommon, aero-digestive tract injuries caused by trauma present a challenging situation for both the emergency doctor and the head and neck surgeon. Clinical presentations may vary from severe acute distress with immediate life-threatening airway obstruction to apparently more reassuring situations. However, the latter turn out to be frequently misleading, since patients may deteriorate suddenly as the result of unrecognized injuries. In such cases, delayed diagnosis is often associated with increased morbidity and mortality. Due to its role in phonation, breathing and alimentation, injuries to the aero-digestive tract also expose the patient to severe later impairment and a poorer quality of life. Comprehensive airway control remains the highest and often most challenging priority for the emergency physician. Careful clinical examination combined with endoscopy and computed tomography imaging form the key elements in diagnosis and early recognition of patients who may require surgical management.


Control methods for invasive mosquitoes of Aedes aegypti and Aedes albopictus (Diptera: Culicidae) in Indonesia.
The two invasive mosquito species in Indonesia are Aedes aegypti and Ae. albopictus. These mosquitoes are a serious nuisance to humans and are also the primary vectors of several foreign pathogens, such as dengue, Zika, and chikungunya viruses. Efforts must be made to reduce the possibility of mosquito bites and the potential for disease transmission. Given the invasion of these two Aedes species, this approach should be considered as part of an integrated strategy to manage them. This review discusses existing and developing control techniques for invasive Ae. aegypti and Ae. albopictus, with an emphasis on those that have been and are being used in Indonesia. Environmental, mechanical, biological (e.g., Bacillus thuringiensis and Wolbachia), and chemical (e.g., insect growth regulators and pyrethroids) approaches are discussed in this review, considering their effectiveness, sustainability, and control methods.


NMR investigation on the DNA binding and B-Z transition pathway of the Zα domain of human ADAR1.
Human ADAR1, which has two left-handed Z-DNA binding domains, preferentially binds Z-DNA rather than B-DNA with a high binding affinity. Z-DNA can be induced in long genomic DNA by Z-DNA binding proteins through the formation of two B-Z junctions with the extrusion of one base pair from each junction. We performed NMR experiments on complexes of Zα(ADAR1) with three DNA duplexes at a variety of protein-to-DNA molar ratios. This study confirmed that the Zα(ADAR1) first binds to an 8-bp CG-rich DNA segment via a unique conformation during B-Z transition and the neighboring AT-rich region becomes destabilized. We also found that, when DNA duplexes have only 6-bp CG-rich segment, the interaction with Zα(ADAR1) did not affect the thermal stabilities of the 6-bp CG-rich segment as well as the neighboring two A·T base pairs. These results indicate that four Zα(ADAR1) proteins interact with the 8-bp DNA sequence containing a 6-bp CG-repeat segment as well as a dinucleotide step, even though the dinucleotid step contains A∙T base pairs. Thus this study suggests that the length of the CG-rich region is more important than the specific DNA sequence for determining which base-pair is extruded from the B-Z junction structure. This study also found that the Zα(ADAR1) in complex with a 11-bp DNA duplex exhibits a Z-DNA-bound conformation distinct from that of free Zα(ADAR1) and the initial contact conformations of Zα(ADAR1) complexed with 13-bp DNA duplexes.


Evaluation of chalcones--a flavonoid subclass, for, their anxiolytic effects in rats using elevated plus maze and open field behaviour tests.
The clinical applications of benzodiazepines as anxiolytics are limited because of their unwanted side effects. Therefore, the development of new pharmacological agents is well justified. Eight variably substituted chalcones were investigated for their effects on central nervous system if they have anxiolytic effects in rats. Anxiolytic effects of chalcones were also compared with standard anxiolytic drug (diazepam, DZP). Rats were injected intraperitoneally with chalcones, their derivatives and DZP for 3 days. Chalcones and their derivatives were injected at the dose of 25 mg/kg body weight and DZP was injected at the dose of 1 and 2 mg/kg body weight. Rats were then subjected to various anxiety paradigms including the open field behaviour and elevated plus maze tests. In addition, their effects on rota rod performance and grip strength were also examined. Variably substituted chalcones and DZP showed differential pattern of activities.


AIRWAY VISUALIZATION: EYES SEE WHAT MIND KNOWS.
Airway management is basic for anesthesia practice, and sometimes it can represent a really dramatic scenario for both the patient and the physicians. Laryngoscopy has been the gold standard of airway visualization for more than 60 years, showing its limitations and failure rates with time. New technology has made available an opportunity to move the physician's eye inside patient airways thanks to video laryngoscopy and video assisted airway management technique. Undoubtedly, we have entered a new era of high resolution airway visualization and different approach in airway instrumentation. Nevertheless, each new technology needs time to be tested and considered reliable, and pitfalls and limitations may come out with careful and long lasting analysis, so it is probably not the right time yet to promote video assisted approach as a new gold standard for airway visualization, despite the fact that it certainly offers some new prospects. In any case, whatever the visualization approach, no patient dies because of missed airway visualization or failed intubation, but due to failed ventilation, which remains without doubt the gold standard of any patient safety goal and airway management technique.