A Pilot Study into the Association between Oral Health Status and Human Papillomavirus-16 Infection.
Over the next 20 years, oropharyngeal cancers (OPC) will represent the majority of head and neck cancers (HNCs) in the United States. It is estimated that human papillomavirus (HPV) may account for as much as 70% to 80% of OPCs in North America and in certain parts of Europe. It is hence crucial to understand the disease risk factors and natural history of oral HPV infections. We hypothesized that poor oral health (by measures such as poor oral hygiene and periodontal disease) leads to a higher degree of oral HPV-16 infections within a patient cohort from a dental school clinic. This study aims to test this hypothesis and gauge possible disease associations before larger scale studies. 223 participants were recruited in this study from the University of Queensland Dental School clinic. Clinical oral health parameters (such as oral hygiene measures and periodontal disease measurements) have been examined and determined by dental professionals. We have collected oral rinse samples from these volunteers. 10 (4.5%) out of 223 participants were found to have HPV-16 DNA in their oral rinse samples using NB2 endpoint PCR and Sanger sequencing. Within the HPV-16 DNA positive subjects, 7 (70%) and 3 (30%) were associated with poor oral hygiene and periodontal disease, respectively. Our results show a trend towards a positive correlation between oral HPV-16 infection and poor clinical oral health status.


Metabolism of N-methylcarbazole by rat lung microsomes.
N-methylcarbazole (NMC) is a procarcinogenic component of tobacco smoke particulate matter. It is metabolized by liver microsomes into some hydroxylated metabolites such as the potent mutagen N-hydroxymethylcarbazole (NHMC). Lung metabolism and toxicity of NMC is not known. Since the lung is the primary organ of inhalation of tobacco smoke, NMC metabolism by lung microsomes was studied in comparison with the metabolism by liver microsomes. Liver or lung microsomes (1 mg/mL) were incubated with 0.5 mM NMC for 30 min at 37 degrees C. NMC metabolites were extracted with ethyl acetate and analyzed by reversed-phase high-performance liquid chromatography. Rat lung microsomes metabolized NMC with a similar profile to liver microsomes, although lung microsomes produced greater number of metabolites. The potent mutagen NHMC was also the major NMC metabolite produced by lung microsomes, as confirmed by particle beam mass spectrometry. However, lung microsomes produced only 10% of NHMC produced by liver microsomes. Metabolism of NMC by lung microsomes also led to depletion of the endogenous antioxidant glutathione by 34% compared to controls, indicating a significant generation of some reactive intermediates during NMC metabolism by lung microsomes. The data show that the lung participates directly in producing the potent mutagen NHMC from NMC present in tobacco smoke.


Centromeric DNA characterization in the model grass Brachypodium distachyon provides insights on the evolution of the genus.
Brachypodium distachyon is a well-established model monocot plant, and its small and compact genome has been used as an accurate reference for the much larger and often polyploid genomes of cereals such as Avena sativa (oats), Hordeum vulgare (barley) and Triticum aestivum (wheat). Centromeres are indispensable functional units of chromosomes and they play a core role in genome polyploidization events during evolution. As the Brachypodium genus contains about 20 species that differ significantly in terms of their basic chromosome numbers, genome size, ploidy levels and life strategies, studying their centromeres may provide important insight into the structure and evolution of the genome in this interesting and important genus. In this study, we isolated the centromeric DNA of the B. distachyon reference line Bd21 and characterized its composition via the chromatin immunoprecipitation of the nucleosomes that contain the centromere-specific histone CENH3. We revealed that the centromeres of Bd21 have the features of typical multicellular eukaryotic centromeres. Strikingly, these centromeres contain relatively few centromeric satellite DNAs; in particular, the centromere of chromosome 5 (Bd5) consists of only ~40 kb. Moreover, the centromeric retrotransposons in B. distachyon (CRBds) are evolutionarily young. These transposable elements are located both within and adjacent to the CENH3 binding domains, and have similar compositions. Moreover, based on the presence of CRBds in the centromeres, the species in this study can be grouped into two distinct lineages. This may provide new evidence regarding the phylogenetic relationships within the Brachypodium genus.


Hermansky-Pudlak Syndrome: Identification of Novel Variants in the Genes HPS3, HPS5, and DTNBP1 (HPS-7).
Hermansky-Pudlak syndrome (HPS), a rare heterogeneous autosomal recessive disorder, is characterized by oculocutaneous albinism (OCA) and a bleeding diathesis due to a defect regarding melanosomes and platelet delta (δ)-granule secretion. Interestingly, patients with HPS type 2 (HPS-2) or HPS type 10 (HPS-10) present additionally with an immunological defect. We investigated three patients (IP1, IP2, and IP3) who suffer from a bleeding diathesis. Platelet aggregometry showed impaired platelet function and flow cytometry revealed a severely reduced platelet CD63 expression hinting to either a defect of platelet delta granule secretion or a decreased number of delta granules in these patients. However, only IP3 presents with an apparent OCA. We performed panel sequencing and identified a homozygous deletion of exon 6 in DTNBP1 for IP3. Western analysis confirmed the absence of the encoded protein dysbindin confirming the diagnosis of HPS-7. Interestingly, this patient reported additionally recurrent bacterial infections. Analysis of lymphocyte cytotoxicity showed a slightly reduced NK-degranulation previously documented in a more severe form in patients with HPS-2 or HPS-10. IP1 is carrier of two compound heterozygous variants in the HPS3 gene (c.65C > G and c.1193G > A). A homozygous variant in HPS5 (c.760G > T) was identified in IP2. The novel missense variants were classified as VUS (variant of uncertain significance) according to ACMG guidelines. For IP1 with the compound heterozygous variants in HPS3 a specialized ophthalmological examination showed ocular albinism. HPS3 and HPS5 encode subunits of the BLOC-2 complex and patients with HPS-3 or HPS-5 are known to present with variable/mild hypopigmentation.


Rheological studies of creams. I. Rheological functions and structure of creams.
Large number of washable (o/w type) creams were prepared for rheological investigation. The rheological functions known from the literature were determined in our studies. Rheological constants were determined by measurements and calculations. From these, we selected those ones which were applicable to characterize the energy status of the coherent structure and which gave the most information for practical work, elaboration of composition and evaluation of stability. These functions and parameters are the following: flow curves, viscosity vs shear time and viscosity vs temperature functions, Bingham-type yield value, plastic viscosity, structure breakdown rate constant, activation energy.


Hyperacute muscle weakness in an unusual coexistence of antisignal recognition particle and anti-Mi-2 antibodies.
Idiopathic inflammatory myopathies are a heterogeneous group of systemic diseases characterised by variable phenotypes of chronic progressive muscle weakness. Myositis-specific antibodies (MSAs) include antibodies to cytoplasmic signal recognition particle (SRP) and various tRNA synthetases as well as the nuclear helicase protein Mi-2. These antibodies are typically found only in a fraction of true myositis cases and they tend to be mutually exclusive. Few cases of coexistence of two MSAs in the same patient have been reported and these cases all involve an antisynthetase antibody coexisting with either anti-SRP or anti-Mi-2 antibody. Peculiar clinical manifestations may be associated with different combinations of MSAs but the rarity of these cases makes their characterisation difficult. We report the first ever case of anti-SRP and anti-Mi-2 copositive polymyositis in a 19-year-old boy who presented with a week history of profound muscle weakness that attained its peak within 24 hours of onset.


Virtual Screening Strategy and In Vitro Tests to Identify New Inhibitors of the Immunoproteasome.
Immunoproteasome inhibition is a promising strategy for the treatment of hematological malignancies, autoimmune diseases, and inflammatory diseases. The design of non-covalent inhibitors of the immunoproteasome β1i/β5i catalytic subunits could be a novel approach to avoid the drawbacks of the known covalent inhibitors, such as toxicity due to off-target binding. In this work, we report the biological evaluation of thirty-four compounds selected from a commercially available collection. These hit compounds are the outcomes of a virtual screening strategy including a dynamic pharmacophore modeling approach onto the β1i subunit and a pharmacophore/docking approach onto the β5i subunit. The computational studies were first followed by in vitro enzymatic assays at 100 μM. Only compounds capable of inhibiting the enzymatic activity by more than 50% were characterized in detail using Tian continuous assays, determining the dissociation constant (Ki) of the non-covalent complex where Ki is also the measure of the binding affinity. Seven out of thirty-four hits showed to inhibit β1i and/or β5i subunit. Compound 3 is the most active on the β1i subunit with Ki = 11.84 ± 1.63 µM, and compound 17 showed Ki = 12.50 ± 0.77 µM on the β5i subunit. Compound 2 showed inhibitory activity on both subunits (Ki = 12.53 ± 0.18 and Ki = 31.95 ± 0.81 on the β1i subunit and β5i subunit, respectively). The induced fit docking analysis revealed interactions with Thr1 and Phe31 of β1i subunit and that represent new key residues as reported in our previous work. Onto β5i subunit, it interacts with the key residues Thr1, Thr21, and Tyr169. This last hit compound identified represents an interesting starting point for further optimization of β1i/β5i dual inhibitors of the immunoproteasome.


Uterine sarcomas. A retrospective study of 17 cases.
Seventeen documented cases of uterine sarcoma were studied in an effort to establish the relationship between prognostic factors and patients' survival. The analysis of prognostic factors showed that there was a significant difference in survival between patients with stages I and II tumors and those with more advanced lesions. It has been also noted that prognosis was worse in patients with history of previous abortions and in patients who had abdominal or pelvic pain.


Ischemic Mitral Regurgitation: Repair, Replacement or Nothing.
The treatment strategy for ischemic mitral regurgitation (MR) continues to evolve with the completion of multicenter trials and the advancement of surgical and percutaneous interventional techniques. This review defines ischemic MR, outlines key clinical trials that assess surgical and interventional approaches, and reports the main elements of recent national guidelines for decision making in treatment of ischemic MR. New findings in percutaneous mitral valve repair and replacement for ischemic MR will also be described. Effective perioperative care of patients with ischemic MR requires clinicians to be well versed in the most up-to-date recommendations and emerging technological developments.


Antimycin A induces apoptosis in As4.1 juxtaglomerular cells.
Antimycin A, an inhibitor of electron transport in mitochondria, has been used as reactive oxygen species (ROS) generator in the biological system. Here, we investigated the in vitro effect of antimycin A on apoptosis in As4.1 juxtaglomerular cells. Antimycin A efficiently induced apoptosis in As4.1 cells as evidenced by flow cytometric detection of sub-G(1) DNA content, annexin V binding assay and DAPI staining. This apoptotic process was accompanied by loss of mitochondrial transmembrane potential (DeltaPsi(m)), Bcl-2 decrease, caspase-3 activation and PARP cleavage. All of caspase inhibitors tested in this experiment failed to rescue As4.1 cells from antimycin A-induced cell death at the time of 48 h in view of sub-G(1) cells and annexin V positive staining cells. However, with regard to the mitochondrial membrane potential (DeltaPsi(m)), pan caspase inhibitor (Z-VAD-FMK) and caspase-3 inhibitor (Z-DEVD-FMK) at the concentration of 25 microM noticeably decreased the loss of mitochondrial membrane potential (DeltaPsi(m)) in antimycin A-treated cells. Taken together, we have demonstrated that antimycin A as an inhibitor of electron transport in mitochondria potently induces apoptosis in As4.1 juxtaglomerular cells.


The effect of nonperitonization and laparoscopic lymphadenectomy for minimizing the incidence of lymphocyst formation after radical hysterectomy for cervical cancer.
To determine the clinical effect of nonperitonization and laparoscopic lymphadenectomy using bipolar electrocautery after radical hysterectomy for cervical cancer compared with peritonization and open lymphadenectomy using monopolar electrocautery. This was a retrospective study of 180 patients who underwent a radical hysterectomy and pelvic lymph node dissection (PLND) for cervical cancer from August 1998 to August 2007. The patients were composed of the Peritonization + Laparotomy group (group A; n = 98, 196 PLND) and the Nonperitonization + Laparoscopy group (group B; n = 82, 164 PLND). Group B left the peritoneum in front of the PLND open. Two closed-suction drains were placed at each side of the PLND. Group B statistically showed a lesser total amount of lymphatic drainage (P = 0.001), shorter duration of inserted drains (P < 0.001), and shorter length of hospital stay (P < 0.001), compared with group A. The formation of lymphocysts occurred in 30 patients (41 lymphocysts) of group A and 5 patients (5 lymphocysts) of group B. Lymphocyst formation of group B had a statistically lower incidence than that of group A (P < 0.001). Lymphocyst formation was associated with an increase in the total amount of lymphatic drainage in group A (P = 0.090) and group B (P = 0.041) and a pathologic type of adenocarcinoma in group B (P = 0.016). Surgical experiences were not correlated with lymphocyst formation. The omission of peritonization and laparoscopic lymphadenectomy using bipolar electrocautery in early-stage cervical cancer were more effective than peritonization and open lymphadenectomy using monopolar electrocautery in minimizing the incidence of lymphocyst formation.


An unusual case of pneumocephalus.
The authors present an unusual cause of pneumocephalus in a previously fit and well female octogenarian who presented with acute onset altered level of consciousness and generalised weakness. Radiological imaging demonstrated widespread cerebritis with pneumocephalus and gas within the superior sagittal sinus. Blood culture grew Clostridium septicum, a virulent but rare organism that can infect normal tissues. The close association between C septicum and both haematological and bowel malignancies must be considered if this organism is cultured.


Evaluation of three recombinant outer membrane proteins, OmpA1, Tdr, and TbpA, as potential vaccine antigens against virulent Aeromonas hydrophila infection in channel catfish (Ictalurus punctatus).
A virulent clonal population of Aeromonas hydrophila (VAh) is recognized as the etiological agent in outbreaks of motile aeromonas septicemia (MAS) in catfish aquaculture in the southeastern United States since 2009. Genomic subtraction revealed three outer membrane proteins present in VAh strain ML09-119 but not in low virulence reference A. hydrophila strains: major outer membrane protein OmpA1, TonB-dependent receptor (Tdr), and transferrin-binding protein A (TbpA). Here, the genes encoding ompA1, tdr, and tbpA were cloned from A. hydrophila ML09-119 and expressed in Escherichia coli. The purified recombinant OmpA1, Tdr, and TbpA proteins had estimated molecular weights of 37.26, 78.55, and 41.67 kDa, respectively. Catfish fingerlings vaccinated with OmpA1, Tdr, and TbpA emulsified with non-mineral oil adjuvant were protected against subsequent VAh strain ML09-119 infection with 98.59%, 95.59%, and 47.89% relative percent survival (RPS), respectively. Furthermore, the mean liver, spleen, and anterior kidney bacterial concentrations were significantly lower in catfish vaccinated with the OmpA1 and Tdr than the sham-vaccinated control group. ELISA demonstrated that catfish immunized with OmpA1, Tdr, and TbpA produce significant antibody response by 21 days post-immunization. Therefore, OmpA1 and Tdr proteins could be used as potential candidates for vaccine development against virulent A. hydrophila infection. However, TbpA protein failed to provide strong protection.


Cytokines and the hypothalamic-pituitary-ovarian-endometrial axis.
Recently, the demarcating boundaries that allowed separation of the fields of reproductive biology, endocrinology, immunology and neurobiology have faded. The missing link that now ties these disciplines together is the understanding that the language by which cells communicate within these diverse systems is unanimous. This language is the network of products collectively called cytokines. The effect of these factors spans from the hypothalamus to the endometrium and is undoubtedly involved in the maintenance of the delicate balance within the hypothalamic-pituitary-gonadal-endometrial axis. Orchestrated networks of these cytokines also seem to be linked to the steroid hormone signals, an essential feature for maintenance of normal menstrual cycles. Evidence in favour of these emerging concepts is discussed. Major emphasis is placed on interferons, interleukins, tumour necrosis factor, transforming growth factors and colony-stimulating factors.


The occurrence of mountain hare mitochondrial DNA in wild brown hares.
If interspecific hybrids are fertile and backcross to either parental species, transmission of mitochondrial DNA over the species barrier can occur. To investigate if such transmission has occurred between the brown hare Lepus europeus Pall and the mountain hare L. timidus L. in Scandinavia, an analysis of genetic variation in mitochondrial DNA from 36 hares, collected from 15 localities, was performed. Sequence divergence of mtDNA between species was estimated at 8 +/- 1% (SD). Intraspecific mtDNA sequence divergence varied between 0.09 and 0.38% in brown hares and 0.10 and 1.44% in mountain hares. In six out of 18 brown hares examined, two different haplotypes of mountain hare origin were detected, demonstrating a transmission of mtDNA haplotypes from mountain hares to brown hares. The results indicate that interspecific hybridization between the two species occurs in wild populations.


Objective Assessment of Microsurgery Competency-In Search of a Validated Tool.
Microsurgical skill acquisition is an integral component of training in plastic surgery. Current microsurgical training is based on the subjective Halstedian model. An ideal microsurgery assessment tool should be able to deconstruct all the subskills of microsurgery and assess them objectively and reliably. For our study, to analyze the feasibility, reliability, and validity of microsurgery skill assessment, a video-based objective structured assessment of technical skill tool was chosen. Two blinded experts evaluated 40 videos of six residents performing microsurgical anastomosis for arteriovenous fistula surgery. The generic Reznick's global rating score (GRS) and University of Western Ontario microsurgical skills acquisition/assessment (UWOMSA) instrument were used as checklists. Correlation coefficients of 0.75 to 0.80 (UWOMSA) and 0.71 to 0.77 (GRS) for interrater and intrarater reliability showed that the assessment tools were reliable. Convergent validity of the UWOMSA tool with the prevalidated GRS tool showed good agreement. The mean improvement of scores with years of residency was measured with analysis of variance. Both UWOMSA ( p -value: 0.034) and GRS ( p -value: 0.037) demonstrated significant improvement in scores from postgraduate year 1 (PGY1) to PGY2 and a less marked improvement from PGY2 to PGY3. We conclude that objective assessment of microsurgical skills in an actual clinical setting is feasible. Tools like UWOMSA are valid and reliable for microsurgery assessment and provide feedback to chart progression of learning. Acceptance and validation of such objective assessments will help to improve training and bring uniformity to microsurgery education.


Simultaneous organics removal and bio-electrochemical denitrification in microbial fuel cells.
Simultaneous organics removal and bio-electrochemical denitrification using a microbial fuel cell (MFC) reactor were investigated in this study. The electrons produced as a result of the microbial oxidation of glucose in the anodic chamber were transferred to the anode, which then flowed to the cathode in the cathodic chamber through a wire, where microorganisms used the transferred electrons to reduce the nitrate. The highest power output obtained on the MFCs was 1.7 mW/m(2) at a current density of 15 mA/m(2). The maximum volumetric nitrate removal rate was 0.084 mg NO(3)(-)-N cm(-2) (electrode surface area) day(-1). The coulombic efficiency was about 7%, which demonstrated that a substantial fraction of substrate was lost without current generation.


Sintering photonic beads for multiplex biosensing.
Monodispersed silica nanoparticles were assembled into opaline photonic crystal beads and cemented together by sintering in order to enhance the mechanical stability of the beads, which simulates the formation of nature opal. The sintering temperatures and structures of the sintered beads were investigated. The results showed that by sintering treatment at temperatures between 700 degrees C and 1000 degrees C for 2 hours the beads were more reliable for multiplex bioassay applications in mechanical robustness, fluorescent background, sensitivity and encoding ability. It is anticipated that the opal-like beads have wide applications in multiplex protein and nucleic acid analysis.


Electrically injected GaN-based microdisk towards an efficient whispering gallery mode laser.
III-nitrides based microdisks with the mushroom-type shape are key components for integrated nanophotonic circuits. The air gap undercut in the mushroom-type microdisk is essential for maintaining vertical optical confinement, but this structure is still facing the difficulty of electrical injection. In this work, we demonstrate an electrically injected GaN-based microdisk of such structure. The device is featured with a copper substrate and copper supporting pedestal, through which current can be efficiently injected into the microdisk with low leakage current (less than 10 nA). Bright emission at ∼420 nm was demonstrated from the microdisk under current injection. The copper substrate and supporting pedestal can also extract thermal energy out of the microdisk effectively, and the structure in this work shows a low thermal resistance of ∼788.86 K/W. Low threshold lasing action at ∼405 nm was realized under the optically pumped condition and the threshold energy is ∼35 nJ/pulse. Clear whispering gallery modes were observed and the Q factor is as high as 4504, indicating the high quality of the microdisk cavity. This work is the first step towards low threshold efficient electrically injected microdisk laser with a mushroom-type shape.


Integral cross section measurements and product recoil velocity distributions of Xe(2+) + N2 hyperthermal charge-transfer collisions.
Charge exchange from doubly charged rare gas cations to simple diatomics proceeds with a large cross section and results in populations of many vibrational and electronic product states. The charge exchange between Xe(2+) and N2, in particular, is known to create N2 (+) in both the A and B electronic states. In this work, we present integral charge exchange cross section measurements of the Xe(2+) + N2 reaction as well as axial recoil velocity distributions of the Xe(+) and N2 (+) product ions for collision energies between 0.3 and 100 eV in the center-of-mass (COM) frame. Total charge-exchange cross sections decrease from 70 Å(2) to about 40 Å(2) with increasing collision energy through this range. Analysis of the axial velocity distributions indicates that a Xe(2+) - N2 complex exists at low collision energies but is absent by 17.6 eV COM. Analysis of the axial velocity distributions reveals evidence for complexes with lifetimes comparable to the rotational period at low collision energies. The velocity distributions are consistent with quasi-resonant single charge transfer at high collision energies.


Sex differences in 90-day outcomes after mechanical thrombectomy for acute ischemic stroke.
It is largely unknown whether functional outcomes after mechanical thrombectomy for large vessel occlusion (LVO) ischemic strokes differ by sex in non-clinical trial populations. We investigated sex differences in 90-day outcomes among ischemic stroke patients receiving mechanical thrombectomy. This was a prospective cohort of adults treated with mechanical thrombectomy for LVO at a single academic comprehensive stroke center from July 2015 to April 2017. Data on independence (mRS ≤2) at hospital discharge and 90 days were collected prospectively. Multiple logistic regression was used to determine the association between sex and 90-day independence, first adjusting for demographics, pre-stroke mRS, and NIHSS, then by co-morbidities and time to thrombectomy, and finally by vessel recanalization and use of intravenous thrombolysis. We included 279 patients, 52% of whom were female. Compared with males, females were older (median years (IQR) 81 (75-88) vs. 71.5 (60-81), P<0.001) and had higher baseline NIHSS (mean SD 18.2±7.5 vs . 16.0±7.1, P=0.02). Similar proportions of males and females had pre-stroke mRS ≤2 (73.3% vs.67.1%, P=0.27). In multivariate analyses, males and females had a similar likelihood of being independent at discharge (aOR 0.71 (95%CI 0.32 to 1.58)), but females were less likely to be independent at 90 days (aOR 0.37 95% CI 0.16 to 0.87). In patients treated with mechanical thrombectomy for LVOs at a large comprehensive stroke center, females were less likely to be independent at 90 days. Future research should investigate contributors to poor outcomes post-discharge in females with LVOs, along with potential interventions to improve outcomes.


Stem cell therapies in preclinical models of stroke associated with aging.
Stroke has limited treatment options, demanding a vigorous search for new therapeutic strategies. Initial enthusiasm to stimulate restorative processes in the ischemic brain by means of cell-based therapies has meanwhile converted into a more balanced view recognizing impediments related to unfavorable environments that are in part related to aging processes. Since stroke afflicts mostly the elderly, it is highly desirable and clinically important to test the efficacy of cell therapies in aged brain microenvironments. Although widely believed to be refractory to regeneration, recent studies using both neural precursor cells and bone marrow-derived mesenchymal stem cells for stroke therapy suggest that the aged rat brain is not refractory to cell-based therapy, and that it also supports plasticity and remodeling. Yet, important differences exist in the aged compared with young brain, i.e., the accelerated progression of ischemic injury to brain infarction, the reduced rate of endogenous neurogenesis and the delayed initiation of neurological recovery. Pitfalls in the development of cell-based therapies may also be related to age-associated comorbidities, e.g., diabetes or hyperlipidemia, which may result in maladaptive or compromised brain remodeling, respectively. These age-related aspects should be carefully considered in the clinical translation of restorative therapies.


Immunogenicity and safety of a pediatric dose of a virosomal hepatitis A vaccine in healthy children in India.
As India is transitioning from high to intermediate hepatitis A endemicity, the need for hepatitis A vaccination programs increases. This study investigated the immunogenicity and safety of a virosomal hepatitis A vaccine (HAVpur Junior) compared with an aluminum-adsorbed hepatitis A vaccine (Havrix 720 Junior) in Indian children. Healthy children aged 18-47 months, stratified by age, were randomized to either HAVpur Junior or Havrix 720 Junior. The first dose of vaccine was administered on Day 1 and the second (booster) dose 6 months later. Antibodies against hepatitis A virus (HAV) were measured using a microparticle enzyme immunoassay. The primary objective assessed non-inferiority of HAVpur Junior to Havrix 720 Junior in terms of seroprotection rates (≥ 10 mIU/mL anti-HAV antibodies) at 1 month after the first vaccination. Non-inferiority was demonstrated if the lower limit of the 90% confidence interval of the group difference was greater than -10%. Local and systemic adverse events were recorded. The seroprotection rate at 1 month was 95.9% in the HAVpur Junior group and 96.6% in the Havrix 720 Junior group. As the lower limit of the 90% confidence interval of the group difference was greater than -10% (-4.7), non-inferiority of HAVpur Junior to Havrix 720 Junior was established. The overall incidence of adverse events (solicited and unsolicited) after each vaccination was similar in both groups. In conclusion, the aluminum-free virosomal vaccine HAVpur Junior induced a similar immune response to Havrix 720 Junior in healthy Indian children aged 18 to 47 months. Both vaccines were well tolerated. The study shows that the low-dose virosomal HAV vaccine is consistently efficacious and well tolerated in children of all age groups and is suitable for inclusion into Indian childhood vaccination schedules.


Inflammation as a therapeutic target in heart failure with preserved ejection fraction.
Heart failure with preserved ejection fraction (HFpEF) accounts for around half of all cases of heart failure and may become the dominant type of heart failure in the near future. Unlike HF with reduced ejection fraction there are few evidence-based treatment strategies available. There is a significant unmet need for new strategies to improve clinical outcomes in HFpEF patients. Inflammation is widely thought to play a key role in HFpEF pathophysiology and may represent a viable treatment target. In this review focusing predominantly on clinical studies, we will summarise the role of inflammation in HFpEF and discuss potential therapeutic strategies targeting inflammation.


Upgrade from ICD to CRT-D: clinical and haemodynamic impact of biventricular pacing in a patient with acquired long QT syndrome.
Long QT syndrome (LQTS) is characterised by both the depolarisation and repolarisation disorder of cardiac muscle cells. Cardiac resynchronising therapy (CRT) is an important treatment option for patients with chronic heart failure (CHF) when echocardiographic and electrocardiographic criteria are met. Although CRT was introduced in clinical practice 10 years ago, doubts related to application of this treatment method persist because of its potential proarrhythmogenic effect. This is a case describing a 66-year-old Caucasian female with LQTS coexisting with a left bundle branch branch block (LBBB) and an implantable single-cavity cardioverter-defibrillator (ICD VR), who had repeated appropriate high-energy treatments. The upgrade to resynchronisation therapy defibrillator (CRT-D) significantly reduced frequency of ventricular tachycardia and the need for electrical therapies. The normalisation of the left ventricle size, as seen on echo examination, and the improvement of heart failure symptoms were also observed.


Beta-blocker administration protocol for prospectively ECG-triggered coronary CT angiography.
The aim of this article is to discuss the protocol of beta-blockers that is commonly used for prospectively ECG-triggered coronary computed tomography angiography (CCTA). It is essential to ensure a low and regular heart rate in patients undergoing prospectively ECG-triggered CCTA for optimal visualization of coronary arteries. Although early generations of computed tomographyscanners are not applicable to be tailored according to patients' heart rate, a low and regular heart rate is possible to be achieved by the administration of medications according to the beta-blocker protocol. Beta-blocker can be safely administered to reduce patients' heart rate for CCTA examination if patients are screened for certain contraindications.


Poultices as biofilms of titanium dioxide nanoparticles/carboxymethyl cellulose/Phytagel for cleaning of infected cotton paper by Aspergillus sydowii and Nevskia terrae.
In this study, TiO2 nanoparticle (TiO2NP)-coated film was produced to protect manuscripts against microorganisms using ecofriendly benign materials. As a result, a simple method was created that uses poultice biofilm made of carboxymethyl cellulose (CMC) and Phytagel plant cell (PGP) loaded with TiO2NPs to preserve manuscripts against microbes in an environmentally responsible way. Three volumes (1, 2, 4 mL) of TiO2NPs were put into a biofilm combination to produce the poultices known as CMC/PGP/TiO2-1, CMC/PGP/TiO2-2, and CMC/PGP/TiO2-3. The synthesized TiO2NPs were nearly spherical in shape, small in size (98 nm), and stable (zeta potential value - 33 mV). The results showed that the unique deposition of TiO2NPs on the biofilm surface gave the produced films loaded with TiO2NPs a rough structure. The highest values of mechanical characteristics were determined to be in CMC/PGP/TiO2-1 with values of 25.4 g, 6.6 MPa, and 11.4%, for tensile strength, elongation at break, and tear strength, respectively. Based on molecular identification, the fungus Aspergillus sydowii and the bacterium Nevskia terrae, with accession numbers MG991624 and AB806800, respectively, were isolated and identified from an antiquated manuscript formed from cellulosic fibers. Before the experiments, the produced cotton paper samples were aged, and then, one group was infected for 6 months by A. sydowii and the second group with N. terrae. Following the preparation of a CMC/PGP biofilm loaded with various volumes of TiO2NPs, poultices were applied to infected cotton paper in order to clean it. The infected cotton paper was placed inside the sandwich-like poultices that were created. The poultice CMC/PGP/TiO2-2 demonstrated potential for preventing the growth of A. sydowii and N. terrae-infected cotton paper, when the fibers were saved, cleaned, and coated with CMC/PGP/TiO2-2 after absorbing the fungus and the bacterium and exhibiting exceptional antimicrobial activities. Finally, the novel biofilms have demonstrated their capacity to lessen microbial contamination of cotton paper. In order to generalize the usage of these poultices, it is also advised that they be produced on a large scale and tested on a variety of organic materials in the future.


Transient Expression of Foreign Genes in Insect Cells (sf9) for Protein Functional Assay.
The transient gene expression system is one of the most important technologies for performing protein functional analysis in the baculovirus in vitro cell culture system. This system was developed to express foreign genes under the control of the baculoviral promoter in transient expression plasmids. Furthermore, this system can be applied to a functional assay of either the baculovirus itself or foreign proteins. The most widely and commercially available transient gene expression system is developed based on the immediate-early gene (IE) promoter of Orgyia pseudotsugata multicapsid nucleopolyhedrovirus (OpMNPV). However, a low expression level of foreign genes in insect cells was observed. Therefore, a transient gene expression system was constructed for improving protein expression. In this system, recombinant plasmids were constructed to contain the target sequence under the control of the Drosophila heat shock 70 (Dhsp70) promoter. This protocol presents the application of this heat shock-based pDHsp/V5-His (V5 epitope with 6 histidine)/Spodoptera frugiperda cell (sf9 cell) system; this system is available not only for gene expression but also for evaluating the anti-apoptotic activity of candidate proteins in insect cells. Furthermore, this system can be either transfected with one recombinant plasmid or co-transfected two potentially functionally antagonistic recombinant plasmids in insect cells. The protocol demonstrates the efficiency of this system and provides a practical case of this technique.


Longitudinal Analysis of Female Authorship of Psychiatry Articles in Turkey.
The number of women with careers in medicine and with academic positions at medical schools has increased substantially since the 1980s; however, women remain underrepresented in medical academia, which may be because of the fewer research publications authored by women. This study aimed to determine the gender distribution among Turkish authors of psychiatry articles published in international scientific journals during a 30-year period. The ISI Web of Science database was searched for all psychiatry publications between 1980 and 2009 using the search term Turkey. All articles were classified according to publication period (1980-1989, 1990-1999, 2000-2004, and 2005-2009), gender of the first and last authors, first author title, total number of authors, and type of article. In all, 1961 articles meet the study criteria. The first author of 36.5% of the articles and 34.9% of last authors were women. The percentage of female first and last authors did not differ according to publication period (p=0.57). To the best of our knowledge this is the first study to examine gender and authorship of psychiatric research in Turkey. In total, 33% of academic positions in Turkish university psychiatry departments were occupied by women, which is comparable to the percentage of female first authors of psychiatric research papers from Turkey. It could be concluded that women academics in psychiatry departments from state universities are as reproductive as their male counterparts, but there is still a "gender gap" in psychiatry field in our country.


Existence of the natural antibody against human-gamma-globulin in bovine sera.
The natural antibody against human gamma-globulins has been found in 2 out of 26 bovine sera. The bovine sera were absorbed with human erythrocytes of group O and tested with human red cells coated with incomplete antibodies. Two of 26 sera studied displayed evident agglutinating properties similar to those of anti-human globulin used in Coombs test.


Multicomponent Condensation Reactions via ortho-Quinone Methides.
Iron(III) salts promote the condensation of aldehydes or acetals with electron-rich phenols to generate ortho-quinone methides that undergo Diels-Alder condensations with alkenes. The reaction sequence occurs in a single vessel to afford benzopyrans in up to 95% yield. The reaction was discovered while investigating a two-component strategy using 2-(hydroxy(phenyl)methyl)phenols to access the desired ortho-quinone methide in a Diels-Alder condensation. The two-component condensation also afforded the corresponding benzopyran products in yields up to 97%. Taken together, the two- and three-component strategies using ortho-quinone methide intermediates provide efficient access to benzopyrans in good yields and selectivities.


Cardiovascular risk from water arsenic exposure in Vietnam: Application of systematic review and meta-regression analysis in chemical health risk assessment.
A systematic review (SR) and meta-analysis cannot provide the endpoint answer for a chemical risk assessment (CRA). The objective of this study was to apply SR and meta-regression (MR) analysis to address this limitation using a case study in cardiovascular risk from arsenic exposure in Vietnam. Published studies were searched from PubMed using the keywords of arsenic exposure and cardiovascular diseases (CVD). Random-effects meta-regression was applied to model the linear relationship between arsenic concentration in water and risk of CVD, and then the no-observable-adverse-effect level (NOAEL) were identified from the regression function. The probabilistic risk assessment (PRA) technique was applied to characterize risk of CVD due to arsenic exposure by estimating the overlapping coefficient between dose-response and exposure distribution curves. The risks were evaluated for groundwater, treated and drinking water. A total of 8 high quality studies for dose-response and 12 studies for exposure data were included for final analyses. The results of MR suggested a NOAEL of 50 μg/L and a guideline of 5 μg/L for arsenic in water which valued as a half of NOAEL and guidelines recommended from previous studies and authorities. The results of PRA indicated that the observed exposure level with exceeding CVD risk was 52% for groundwater, 24% for treated water, and 10% for drinking water in Vietnam, respectively. The study found that systematic review and meta-regression can be considered as an ideal method to chemical risk assessment due to its advantages to bring the answer for the endpoint question of a CRA.


Correlates of sexually transmitted infection knowledge among late adolescents.
Background Accurate knowledge about sexually transmitted infections (STIs) is imperative for young people's development and sexual health outcomes, but STI knowledge has been found to be inadequate among youth. Little is known about the factors that are associated with STI knowledge. This study therefore comprehensively assessed correlates of STI knowledge among late adolescents. Undergraduate students (n = 419) at a large public Midwestern university completed an online survey that assessed general STI knowledge using an established modified scale, demographics, sexual health and behavioural factors, and sources of STI information. Exploratory bivariate analyses were first conducted followed by a multiple linear regression examining the correlates initially identified as significantly and strongly associated with STI knowledge. Although many factors were significantly correlated with STI knowledge, gender, nationality, sexual identity, STI testing history, knowing someone diagnosed with an STI, prior school-based STI education, and receiving STI information from a healthcare provider were most strongly associated (P < 0.001 with medium or large effect sizes). All but prior school-based STI education were predictive of STI knowledge score (P = 0.103), with nationality (β = 0.172, P = 0.003) and gender (β = 0.147, P = 0.002) being the strongest predictors. Late adolescents' STI knowledge was universally low, but disparities existed and were related to a variety of characteristics. These findings expand the current literature on young people's STI knowledge and provide needed information to prioritise populations and methods for educational interventions in order to enhance STI knowledge among youth.


Subcutaneous methotrexate for symptomatic control of severe recalcitrant psoriasis: safety, efficacy, and patient acceptability.
Although oral methotrexate is an effective first-line traditional systemic therapy for psoriasis, the use of the subcutaneous form of methotrexate for the treatment of psoriasis has not been fully established. This study is a literature review of the research related to the safety, efficacy, and patient acceptability of subcutaneous methotrexate for its application in the treatment of severe recalcitrant psoriasis. Systematic literature searches were conducted of the PubMed, Ovid, and ClinicalTrials.gov databases. Only three relevant sources of literature were found studying subcutaneous methotrexate specifically in the context of psoriasis. Of these, only one clinical trial was found to directly study the use of subcutaneous methotrexate in psoriasis patients; however, results of this study have not been published. The other two literature sources involved a cost-effectiveness analysis and a literature review for subcutaneous methotrexate. Otrexup™ and Rasuvo™ are two particular single-use auto-injector modalities of subcutaneous methotrexate that are approved by the US Food and Drug Administration. The equivalents of Rasuvo available in countries outside of the USA are advertised as Metoject® or Metex®. Much more research has been conducted on the use of subcutaneous methotrexate in rheumatoid arthritis patients. There is a lack of original evidence-based studies evaluating the use of subcutaneous methotrexate specifically for the treatment of psoriasis. Based on the more extensively researched data on the safety, efficacy, and patient acceptability of subcutaneous methotrexate in rheumatoid arthritis patients, its application for the treatment of moderate-to-severe psoriasis is promising. More evidence-based studies on psoriasis subjects are needed to explore the practical application of subcutaneous methotrexate as a treatment option for severe recalcitrant psoriasis.


Isolation and characterization of novel variants of BBI coding genes from the legume Lathyrus sativus.
A pool of twelve cDNA sequences coding for Bowman-Birk inhibitors (BBIs) was identified in the legume grass pea (Lathyrus sativus L.). The corresponding amino acid sequences showed a canonical first anti-trypsin domain, predicted according to the identity of the determinant residue P(1). A more variable second binding loop was observed allowing to identify three groups based on the identity of residue P(1): two groups (Ls_BBI_1 and Ls_BBI_2) carried a second reactive site specific for chymotrypsin, while a third group (Ls_BBI_3) was predicted to inhibit elastase. A fourth variant carrying an Asp in the P(1) position of the second reactive site was identified only from genomic DNA. A phylogenetic tree constructed using grass pea BBIs with their homologs from other legume species revealed grouping based on taxonomy and on specificity of the reactive sites. Five BBI sequences, representing five different second reactive sites, were heterologously expressed in the yeast Pichia pastoris. The recombinant proteins demonstrated to be active against trypsin, while three of them were also active against chymotrypsin, and one against human leukocyte elastase. Comparative modeling and protein docking were used to further investigate interactions between two grass pea BBI isoforms and their target proteases. Thus two reliable 3D models have been proposed, representing two potential ternary complexes, each constituted of an inhibitor and its target enzymes.


De novo focal glomerulosclerosis after kidney transplantation.
A transplanted kidney in a patient developed focal and segmental glomerulosclerosis, associated with severe systemic hypertension, proteinuria, progressive azotemia, and allograft hypertrophy. A pediatric kidney with two main arteries was used, and occlusion of the artery supplying the upper pole resulted in infarction of this portion of the allograft. Because other known factors predisposing to focal sclerosis were absent, it is postulated that renal hemodynamic changes associated with reduction in functioning renal mass, attended by striking stimuli for renal hypertrophy, resulted in progressive damage. The implications of these concepts are discussed in relation to the progression of renal diseases.


Perforin-deficient CD8+ T cells provide immunity to Listeria monocytogenes by a mechanism that is independent of CD95 and IFN-gamma but requires TNF-alpha.
CD8+ T cells are effective mediators of immunity against Listeria monocytogenes, but the mechanisms by which they provide antilisterial immunity are poorly understood. CD8+ T cells efficiently lyse target cells in vitro by at least two independent pathways. To test the hypothesis that CD8+ T cell-mediated immunity to L. monocytogenes is dependent on perforin or CD95 (Fas, Apo-1), we used C57BI/6 (B6) and perforin-deficient (PO) mice to generate CD8+ T cell lines specific for the L. mono cytogenes-encoded Ag listeriolysin O (LLO). Both lines specifically produce IFN-gamma and TNF-alpha, and mediate target cell lysis in vitro. Cytolysis mediated by the PO-derived CD8+ T cell line is delayed relative to the B6-derived line and is completely inhibited by anti-CD95 Abs. In vivo, PO-derived CD8+ T cells provide specific antilisterial immunity in B6 hosts, CD95-deficient hosts, and IFN-gamma-depleted hosts. However, PO-derived CD8+ T cells fail to provide antilisterial immunity in hosts depleted of TNF-alpha. These results indicate that single Ag-specific CD8+ T cells derived from PO mice can mediate antilisterial immunity by a mechanism that is independent of CD95 or IFN-gamma, but requires TNF-alpha.


Breast cancer following multiple chest fluoroscopies among tuberculosis patients. A case-control study in Denmark.
A case-control study of breast cancer among tuberculosis (TB) patients in Denmark (1937-1954) was conducted to provide additional information on the radiation risk associated with low-dose chest fluoroscopy exposures. Records of 46013 TB patients were linked to the Danish Cancer Registry and 125 subsequent female breast cancers identified. Medical records were located for 89 (71%) of these women who developed breast cancer and on 390 controls, who were individually matched to cases on age and calendar year of TB diagnosis, and survival. Common risk factors for breast cancer such as nulliparity (relative risk (RR) = 2.5) and high relative weight (RR = 2.6) were also identified in this population of TB patients. However no risk was evident with exposure to any type of fluoroscopy (RR = 0.6; 95% CI = 0.2-1.4), or to fluoroscopies performed to monitor lung collapse therapy (RR = 0.8; 95% CI = 0.5-1.4). Although based on only 7 breast cancers, there was a suggestion of an increased risk among women who received greater than 1 Gy to their breasts (RR = 1.6; 95% CI = 0.4-6.3). Because of the infrequent use of fluoroscopy in our study, the breast doses were too low, 0.27 Gy on average, to expect to detect a significant elevation in breast cancer risk overall. The findings do suggest, however, that current estimates of breast cancer risk following radiation are not greater than presently accepted, and that a relative excess of 40 per cent can be excluded with reasonable confidence following breast doses on the order of 0.3 Gy.


Few-photon transport in low-dimensional systems: interaction-induced radiation trapping.
We present a detailed analysis of the dynamics of photon transport in waveguiding systems in the presence of a two-level system. In these systems, quantum interference effects generate a strong effective optical nonlinearity on the few-photon level. We clarify the relevant physical mechanisms through an appropriate quantum many-body approach. Based on this, we demonstrate that a single-particle photon-atom bound state with an energy outside the band can be excited via multiparticle scattering processes. We further show that these trapping effects are robust and, therefore, will be useful for the control of photon entanglement in solid-state based quantum-optical systems.


Attitudes about research among Allied Medical Students enrolled in speech and hearing undergraduate program.
To investigate students' attitudes toward research during their pre-professional training. The study collected survey data from 31 undergraduate students enrolled in speech and hearing undergraduate program at the College of Applied Medical Sciences at King Saud University, Riyadh, Saudi Arabia. The data were collected at the beginning of a research methodology course over two consecutive terms. The study used a 32-item questionnaire listed in the Likert scale, and it measured students' perspectives about research across five sub-scales: usefulness of research, research anxiety, research difficulty, life relevancy of research, and attitude toward research. The findings showed that students favorably perceived research with average factor ratings ranging from 4.10 to 5.54 out of 7. Also, the study found that the usefulness of research, life relevancy of research, and attitude toward research were correlated highly. The current study suggests that students' favorable attitudes toward research may be due, in part, to perceiving research as relevant and useful to their lives and careers.


Nicotinamide enhances natural killer cell function and yields remissions in patients with non-Hodgkin lymphoma.
Allogeneic natural killer (NK) cell adoptive transfer has shown the potential to induce remissions in relapsed or refractory leukemias and lymphomas, but strategies to enhance NK cell survival and function are needed to improve clinical efficacy. Here, we demonstrated that NK cells cultured ex vivo with interleukin-15 (IL-15) and nicotinamide (NAM) exhibited stable induction of l-selectin (CD62L), a lymphocyte adhesion molecule important for lymph node homing. High frequencies of CD62L were associated with elevated transcription factor forkhead box O1 (FOXO1), and NAM promoted the stability of FOXO1 by preventing proteasomal degradation. NK cells cultured with NAM exhibited metabolic changes associated with elevated glucose flux and protection against oxidative stress. NK cells incubated with NAM also displayed enhanced cytotoxicity and inflammatory cytokine production and preferentially persisted in xenogeneic adoptive transfer experiments. We also conducted a first-in-human phase 1 clinical trial testing adoptive transfer of NK cells expanded ex vivo with IL-15 and NAM (GDA-201) combined with monoclonal antibodies in patients with relapsed or refractory non-Hodgkin lymphoma (NHL) and multiple myeloma (MM) (NCT03019666). Cellular therapy with GDA-201 and rituximab was well tolerated and yielded an overall response rate of 74% in 19 patients with advanced NHL. Thirteen patients had a complete response, and 1 patient had a partial response. GDA-201 cells were detected for up to 14 days in blood, bone marrow, and tumor tissues and maintained a favorable metabolic profile. The safety and efficacy of GDA-201 in this study support further development as a cancer therapy.


Aberrant expression of β-catenin in CD4+ T cells isolated from primary progressive multiple sclerosis patients.
Primary progressive multiple sclerosis (PP-MS) is a less common progressive form of MS in approximately 10% of patients that manifest increasingly neurological disability from disease onset. To date, there are no approved treatments for the progressive stage. Therefore, identifying new therapeutic targets could open a new opportunity for PP-MS management. Several lines of evidence suggest the critical role of the Wnt/β-catenin pathway in immune-mediated diseases, like MS. This study was aimed to investigate whether aberrant expression of β-catenin is involved in PP-MS progression. By western blot analysis the expression of β-catenin was evaluated in CD4+ cells purified from peripheral blood of PP-MS patients. Specifically, nuclear expression of β-catenin was detected in CD4+ T cells purified from peripheral blood lymphocytes of PP-MS, and not of other neuromuscular diseases. In addition, no relevant expression of Wnt-1 was found in PP-MS patients, suggesting that the increase in nuclear β-catenin expression in these cells could be independent from canonical Wnt pathway. Taken together, our observations demonstrate that the deregulation of the β-catenin expression is involved in CD4+ T cells of PP-MS patients. Therefore, inhibitors of β-catenin pathway could be proposed as a promising candidate strategy for PP-MS cure.


[Effects and mechanism of iron overload on hematopoiesis in mice with bone marrow injury].
To explore effects of iron overload on hematopoiesis in mice with bone marrow injury and its possible mechanism (s). C57BL/6 mice were divided into control, iron, irradiation, irradiation+iron groups. The iron-overloaded model of bone marrow injury was set up after mice were exposed to the dose of 4 Gy total body irradiation and (or) were injected iron dextran intraperitoneally. Iron overload was confirmed by observing iron deposits in mice and bone marrow labile iron pool. Additionally, the number of peripheral blood and bone marrow mononuclear cells and the frequency of erythroid cells and myeloid cells were counted and hematopoietic function was assessed. (1)Iron overload occurred by bone marrow biopsy and flow cytometry analysis. (2)Compared with control group, the number of platelets [(801.9±81.2)×10⁹/L vs (926.0±28.2)×10⁹/L] and BMMNC and the frequency of erythroid cells and myeloid cells decreased. Moreover, hematopoietic colony forming units and single-cell cloning counts decreased significantly in irradiation group (P<0.05). (3)Compared with irradiation group, the number of platelets [(619.0±60.9)×10⁹/L vs (801.9±81.2)×10⁹/L] and the frequency of erythroid cells and myeloid cells decreased; moreover, hematopoietic colony forming units and single-cell cloning counts decreased significantly in irradiation+iron group (P<0.05). (4)Compared with irradiation group, ROS level increased by 1.94 fold in BMMNC, 1.93 fold in erythroid cells and 2.70 fold in myeloid cells, respectively (P<0.05). The dose of 4 Gy total body irradiation caused bone marrow damage and iron overload based on this injury model, which could damage bone marrow hematopoietic function aggravatingly. And further study found that iron overload was closely related to increased ROS level in BMMNC. The findings would be helpful to further study the injury mechanism of iron overload on the hematopoiesis of bone marrow.


Measles seroprevalence in persons over one year of age in Chandigarh, India.
Measles continues to result in focal outbreaks in India, despite over three decades of universal infant vaccination. The aims of this study were to examine measles immunity in the population of Chandigarh, India, and to compare immunity by vaccination vs. natural infection. In a cross-sectional study of individuals 1-60 years selected from 30 communities within Chandigarh during 2017-2018, measles immunity was assessed using serological surveys. Seropositivity was compared across demographic groups, and by prior history of vaccination and natural history of infection. Among those 1-20 years old, measles seropositivity, and histories of measles vaccination or prior measles diagnosis were separately assessed as outcomes in logistic regression models, with demographic factors as independent variables. Among 1690 participants, 94% were seropositive, and 6% had borderline or negative antibody levels. Of those positive, 30% had prior vaccination, 16% had a history of natural infection, and 54% had an unknown history. Over 50% of individuals among those >20 years old, had unknown history of immunity. In the multivariable regression models, vaccination was more common in younger ages (P < .0001), and in males compared to females (P = .0220), and in those with more education (P < .0001). The majority of the population was seropositive, and seropositivity increased with age. Older age groups were more likely to be protected because of previous natural infection, whereas younger age groups were protected by vaccination. There was inequity in vaccination coverage by gender, and maternal education status.


Monitoring of carbon dioxide and equilibrium moisture content for early detection of physicochemical and morphological changes in soybeans stored in vertical silos.
In the context of grain storage, impurities and soybeans defects in soybeans can significantly impact the equilibrium moisture content. This, cause moisture migration and heating of the stored product, leading to increased respiratory activity. Furthermore, temperature measurements within stored grain mass do not provide sufficient information for effective grain quality monitoring, primarily due to the grains excellent thermal insulating properties. To address this issue, we propose a different approach: monitoring the equilibrium moisture content and CO2 concentration as indicators of soybean respiration within the intergranular spaces of the stored grain mass. This study propose monitoring the CO2 concentration in the intergranular air along with environmental variables for early detection of physicochemical and morphological changes in soybeans stored in vertical silos using near infrared spectroscopy, X-ray diffraction and scanning electron microscopy. Thermogravimetry and spectrometry analyses revealed that the interrelationships among variables had a direct impact on soybean quality attributes. Specifically, the presence of soybeans with 5.2 % impurities led to an increased in respiration rates, resulting in a CO2 concentration of up to 5000 ppm and the consumption of up to 3.6 % of dry matter. Consequently, there were changes in the percentage of ash, proteins, fibers, and oils compositions. These findings highlight the potential for indirect assessments, enabling the prediction of physicochemical quality and contamination of soybeans stored in vertical silos through continuous monitoring of CO2 concentration and equilibrium moisture content.


Botulinum toxin type A for genitofemoral neuralgia: A case report.
Genitofemoral neuralgia is an uncommon pain disorder that could be resistant to conventional treatment. A 78-year-old woman with refractory right genitofemoral neuralgia was treated with BoNT/A subcutaneous injections; the treatment was performed three times with significant pain improvement, although temporary, and without adverse events. BoNT/A may be a promising alternative intervention in the setting of genitofemoral neuralgia refractory to oral and/or topical treatment.


Modification in the composition and metabolic properties of human low density and high density lipoproteins by different dietary fats.
The chemical composition and metabolism of lipoproteins in a population of Benedictine nuns were studied after 5-month periods during which the predominant dietary fats were sunflower oil, peanut oil, palm oil, or milk fats (butter and cream). The population was divided into three groups. The control group (C) included twelve subjects selected at random by taking two subjects per age pool among those with plasma cholesterol less than 230 mg/dl. Groups H1 and H2 were selected at random in the same way, among those with plasma cholesterol greater than 230 mg/dl. Each group comprised six subjects and differed from each other in the amount of plasma cholesteryl esters, i.e., below and above the mean value of group C, for H1 and H2, respectively. Changes in the degree of saturation of the predominant fat of the diet were associated with changes in both the chemical composition of lipoproteins and their cellular metabolism studied in fibroblast cultures. No significant difference between the normocholesterolemic subjects of group C and the "high risk" subjects of groups H1 and H2 was found.


Optimizing concentration of titanium tetrafluoride solution for human dentine remineralization.
The aim of the present study was to select the optimal concentration of TiF4 solution to facilitate the remineralization of early dentine caries lesions. Sixty human dentine specimens were cut and randomly divided into 6 groups (1%, 2%, 3%, 4% TiF4 groups, 2.712% NaF group and distilled deionized water (DDW) control group). Artificial dentine caries-like lesions were created. After being subjected to fluoride treatment and immersed in remineralizing solution for 2weeks, the specimens were observed by microCT, scanning electron microscopy (SEM) and X-ray photoelectron spectroscopy (XPS). Data were analysed using linear regression analysis (P<0.05). The lesion depths of the specimens treated by 2% TiF4 solution were statistically less than those of the other groups. Further, the greyscale values of these lesion areas were greater. The 3% and 4% TiF4 solutions caused further lesion demineralization. The 2.712% NaF solution seemed to be detrimental to remineralization during the experimental time, as the subsurface area remained hypomineralized with a thick precipitation layer on the surface. The 2% TiF4 solution demonstrated better remineralizing potency than did the other treatments.


Internal energy build-up in matrix-assisted laser desorption/ionization.
This paper reports detailed studies on the internal energy of ions formed in matrix-assisted laser desorption/ionization (MALDI) using delayed extraction MALDI-time-of-flight (TOF) and atmospheric pressure (AP) MALDI mass spectrometric (MS) methods. We use benzylpyridinium cations as internal energy probes. Our study reveals three distinct contributions to internal energy build-up in vacuum-MALDI (classical MALDI-TOF), each having different effects on ion fragmentation. Some fragments are formed before ion extraction (i.e. no more than 100 ns after the laser impact), and they are therefore well resolved and recorded as sharp signals in the MALDI-TOFMS scan. This prompt fragmentation can have two origins: (i) in-plume thermal activation, presumably always present, and (ii) in-plume chemical activation, in the course of reactions with hydrogen radicals. In addition to early internal energy build-up associated with these well-resolved promptly formed fragments, a broad peak slightly offset to higher masses could be detected corresponding to fragments formed after the extraction has started. This second signal corresponds to a third source of internal energy in MALDI ions, (iii) the extraction-induced collisional activation of the ions with the neutral components of the plume. These three contributions are difficult to quantify in vacuum-MALDI, because of the combined influence of several parameters (nature of the matrix, spot-to-spot variability, total laser exposure, delay time, acceleration voltage) on extraction-induced fragmentation. AP-MALDI, on the other hand, has two advantages for comparative studies of analyte fragmentation. First, extraction-induced fragmentation is absent, and only the contributions of early plume activation remain. Second, the reproducibility is far better than in vacuum-MALDI. AP-MALDI is therefore expected to shed new light on the early steps of the MALDI process.


Implementing resources to support the diagnosis and management of Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) in primary care: A qualitative study.
Previous research has highlighted that many GPs lack the confidence and knowledge to diagnose and manage people with CFS/ME. Following the development of an online training module for GPs, and an information pack and DVD for patients, this study explored the extent to which these resources can be implemented in routine primary care. Semi structured qualitative interviews were completed with patients and GPs across North West England. All interviews were transcribed and analysed using open exploratory thematic coding. Following this thematic analysis, the authors conducted a further theory-driven analysis of the data guided by Normalisation Process Theory. When used in line with advice from the research team, the information resource and training were perceived as beneficial to both patients and GPs in the diagnosis and management of CFS/ME. However, 47 % of patients in this study did not receive the information pack from their GP. When the information pack was used, it was often incomplete, sent in the post, and GPs did not work with patients to discuss the materials. Only13 out of 21 practices completed the training module due to time pressures and the low priority placed on low prevalence, contentious, hard to manage conditions. When the module was completed, many GPs stated that it was not feasible to retain the key messages as they saw so few patients with the condition. Due to the complexity of the condition, GPs also believed that the diagnosis and management of CFS/ME should take place in a specialist care setting. While barriers to the implementation of training and resources for CFS/ME remain, there is a need to support CFS/ME patients to access reliable, evidence based information outside primary care. Our findings suggest that future research should develop an online resource for patients to support self-management.


[Postoperative treatment of malignant tumors of the parotid gland: radiotherapy, concomitant chemotherapy and radiation therapy?].
The low incidence, the wide histological spectrum and the natural, sometimes slow, evolution of malignant parotid gland tumours do not allow to easily establish the impact of their treatments. At present, clinical data come from retrospective cohort analysis, whereas randomized phase II-III trials are confidential. Moreover conclusions from these studies are controversial. We present here the therapeutic highlights of parotid cancers: surgery, with the particular concern of facial nerve preservation; and adjuvant treatment essentially based on radiotherapy. This review focused on adjuvant care explores the indications and the technical aspects of radiation, as well as the role of concurrent chemotherapy.


A monoclonal antibody directed against the HLA-Bw6 epitope.
A cytotoxic monoclonal antibody, SFR8-B6, produced by immunizing KGH rats with partially purified glycoprotein from JY, a human B lymphoblastoid cell line, detects HLA-Bw6, a unique public antigen on the HLA-B molecule. By cytotoxicity, SFR8-B6 has complete concordance with the presence of Bw6 as defined by alloantisera, and its reactivity segregates with HLA in families. Because sera detecting Bw4 and Bw6 are rare, this monoclonal antibody has value as a perpetual standard. In addition, SFR8-B6 offers potential as a probe for investigating the molecular relationships of HLA antigens.


Classical analysis of quantum phase transitions in a bilayer model.
In this Brief Report we extend the classical analysis performed on the schematic model proposed in [T. Moreira, G. Q. Pellegrino, J. G. Peixoto de Faria, M. C. Nemes, F. Camargo, and A. F. R. Toledo Piza, Phys. Rev. E 77, 051102 (2008)] concerning quantum phase transitions in a bilayer system. We show that appropriate integrations along the classical periodic orbits reproduce with excellent agreement both the quantum spectrum and the expected mean value for the number of excitons in the system, quantities which are directly related to the observed boson-fermion quantum phase transition.


Highly Efficient Degradation of Persistent Pollutants with 3D Nanocone TiO2-Based Photoelectrocatalysis.
Photoelectrocatalytic (PEC) degradation of organic pollutants into CO2 and H2O is a promising strategy for addressing ever-growing environmental problems. Titanium dioxide (TiO2) has been widely studied because of its good performance and environmental benignancy; however, the PEC activity of TiO2 catalyst is substantially limited due to its fast electron-hole recombination. Herein, we report a TiO2 nanocone-based photoelectrocatalyst with superior degradation performance and outstanding durability. The unique conical catalyst can boost the PEC degradation of 4-chlorophenol (4-CP) with 99% degradation efficiency and higher than 55% mineralization efficiency at a concentration of 20 ppm. The normalized apparent rate constant of a nanocone catalyst is 5.05 h-1 g-1 m2, which is 3 times that of a nanorod catalyst and 6 times that of an aggregated particle catalyst, respectively. Further characterizations reveal that the conical morphology of TiO2 can make photogenerated charges separate and transfer more efficiently, resulting in outstanding PEC activity. Moreover, computational fluid dynamics simulations indicate that a three-dimensional conical structure is beneficial for mass transfer. This work highlights that tuning the morphology of a photoelectrocatalyst at the nanometer scale not only promotes the charge transfer but also facilitates the mass transportation, which jointly enhance the PEC performance in the degradation of persistent pollutants.


Frequency and origin of haplotypes associated with the beta-globin gene cluster in individuals with trait and sickle cell anemia in the Atlantic and Pacific coastal regions of Colombia.
Sickle cell anemia is a genetic disease with high prevalence in people of African descent. There are five typical haplotypes associated with this disease and the haplotypes associated with the beta-globin gene cluster have been used to establish the origin of African-descendant people in America. In this work, we determined the frequency and the origin of haplotypes associated with hemoglobin S in a sample of individuals with sickle cell anemia (HbSS) and sickle cell hemoglobin trait (HbAS) in coastal regions of Colombia. Blood samples from 71 HbAS and 79 HbSS individuals were obtained. Haplotypes were determined based on the presence of variable restriction sites within the β-globin gene cluster. On the Pacific coast of Colombia the most frequent haplotype was Benin, while on the Atlantic coast Bantu was marginally higher than Benin. Eight atypical haplotypes were observed on both coasts, being more diverse in the Atlantic than in the Pacific region. These results suggest a differential settlement of the coasts, dependent on where slaves were brought from, either from the Gulf of Guinea or from Angola, where the haplotype distributions are similar. Atypical haplotypes probably originated from point mutations that lost or gained a restriction site and/or by recombination events.


Focal organizing pneumonia: CT and pathologic findings.
The purpose of this study was to describe the CT findings of focal organizing pneumonia and to compare the findings with pathology. CT findings of histologically proven focal organizing pneumonias in 26 consecutive patients were analyzed. In 17 patients who had undergone surgical resections, the findings were correlated with pathology. Focal organizing pneumonias appeared as a nodule (n= 13) or a mass (n=13), ranging from 9 mm to 66 mm in diameter. Ground-glass opacity was seen in 6/13 (46%) nodules and 6.5/13 (50%) masses (k=.48) with an extent ranging from 5% to 75% (mean, 16%). In 4/26 (15%) patients, the extent was more than 50% of the lesion. They showed smooth (n=4), lobulated (n=8), spiculated (n=1), or lobulated and spiculated margin (n=13). On correlative analysis, nodule or mass on CT consisted histologically of intraalveolar exudate or microabscess, chronic inflammatory cell infiltration, fibrotic nodules, and polypoid granulation tissue in the alveolar or bronchiolar spaces. Ground-glass opacity consisted of interstitial fibrosis and chronic inflammatory cell infiltration and intraalveolar polypoid granulation tissue. Focal organizing pneumonia may simulate a lung cancer with variable appearances on CT and the findings reflect underlying histopathology of the disease.


Pseudohypoparathyroidism Type 1A with Normocalcaemia, due to the Novel C.389A>G Variant of Exon 5 of the Guanine Nucleotide-Binding Protein, α-Stimulating Gene.
Pseudohypoparathyroidism type 1A (PHP1A) is a rare disease caused by molecular defects in the maternally-inherited allele of the guanine nucleotide-binding protein, α-stimulating (GNAS) gene. The GNAS gene encodes the stimulatory G-protein α-subunit that regulates production of the second messenger cyclic adenosine monophosphate. Heterozygous inactivating mutations in these specific loci are responsible for a spectrum of phenotypic characteristics of the disease, including clinical features of the Albright's hereditary osteodystrophy, due to resistance to parathyroid hormone (PTH). We report a case of PHP1A and explore the underlying novel point mutation of the GNAS gene that leads to an atypical PHP1A phenotype. A male patient with a round face, short stature, and brachydactyly accompanied by normocalcaemia and mild PTH resistance consulted at our center. The GNAS encoding region from the patient and both of his parents were amplified and sequenced directly in a sample of peripheral blood leukocytes. A novel c.389A>G point mutation in exon 5 of the GNAS gene, resulting in a p.Tyr130Cys peptidic chain change of the Gsα protein, detected in the proband, in heterozygous state. Sequencing of the GNAS gene from his parents did not reveal the c.389A>G mutation, confirming a de novo proband genotype. The maternal origin of the affected GNAS allele, along with mild PTH resistance, confirmed the PHP1A diagnosis. PHP1A, caused by inactivating GNAS mutations, presents a range of complex clinical phenotypes. The novel c.389A>G GNAS mutation presented in this case expands the spectrum of known PHP1A molecular defects and describes the associated phenotype.


Boosting GABA improves impaired auditory temporal resolution in the gerbil.
Elderly humans often not only experience peripheral hearing loss but also suffer from more central deficits in temporal auditory processing affecting speech perception. Impaired auditory temporal resolution has also been observed in old rodents. Other studies have demonstrated a reduction of GABAergic function in the auditory pathway of old animals. Here we test the hypothesis that deficits in the GABAergic system affect central auditory processing. Our data suggests that pharmacological augmentation of the GABAergic system ameliorates impaired temporal auditory processing in the gerbil and might be a strategy for the treatment of at least some forms of central hearing loss in humans.


Dilated cardiomyopathy and limb-girdle muscular dystrophy-dystroglycanopathy due to novel pathogenic variants in the DPM3 gene.
Deficiency of Dolichol-P-mannose synthase subunit 3 (DPM3) affects the N-glycosylation and O-mannosylation pathways that are respectively involved in congenital disorders of glycosylation (CDG) and alpha-dystroglycanopathies. Herein, we describe novel pathogenic variants in the DPM3 gene in two unrelated male patients. They developed dilated cardiomyopathy in their late teens, limb-girdle muscular dystrophy - one patient in childhood and the other in adulthood. In both patients, next generation sequencing found in the DPM3 gene a heterozygous deletion and a heterozygous pathogenic missense mutation in exon 2 (c.41T>C, p.Leu14Pro). Electrophoresis of serum transferrin found an abnormal N-glycosylation profile suggestive of CDG type 1 (decreased tetrasialotransferrin, increased disialo- and asialotransferrin). Only two cases of DPM3 gene mutations with limb-girdle muscular dystrophy-dystroglycanopathy have been reported previously. The present study highlights several aspects related to DPM3 gene mutations such as mild to moderately severe limb-girdle muscular dystrophy, dilated cardiomyopathy, and abnormal N-glycosylation profile suggestive of CDG type 1.


Note: Efficient diode laser line narrowing using dual, feed-forward + feed-back laser frequency control.
We have achieved distributed feedback laser diode line narrowing by simultaneously acting on the diode current via a feed-back loop and on an external electrooptic phase modulator in feed-forward actuator. This configuration turns out to be very efficient in reaching large bandwidth in the phase correction: up to 15 MHz with commercial laser control units. About 98% of the laser power undergoes narrowing. The full width at half maximum of the narrowed optical spectrum is of less than 4 kHz. This configuration appears to be very convenient as the delay in the feed-forward control electronics is easily compensated for by a 20 m optical fiber roll.


Measuring Sexual and Gender Minority Populations in Health Surveillance.
Sexual and gender minorities (SGMs) are underrepresented and information about SGMs is difficult to locate in national health surveillance data, and this limits identification and resolution of SGM health disparities. It is also not known how measures of sexual orientation and transgender-inclusive gender identity in health surveillance compare with best practice recommendations. This article reviews and summarizes the publicly available, English language, large-scale, rigorously sampled, national, international, and regional data sources that include sexual orientation or transgender-inclusive gender identity and compares measures with best practice guidelines. A systematic review was undertaken of national, international, state, and regional health surveillance data sources. Data sources that measured sexual orientation or transgender-inclusive gender identity and met seven inclusion criteria were included. Forty-three publicly accessible national, international, and regional data sources included measures of sexual orientation and transgender-inclusive gender identity and health. For each data source, sampling design, sample characteristics, study years, survey questions, contact persons, and data access links are provided. Few data sources met best practice recommendations for SGM measurement: 14% measured all three dimensions of sexual orientation (identity, behavior, attraction) as recommended by the Sexual Minority Assessment Research Team. No data sources measured transgender-inclusive gender identity according to the Gender Identity in U.S. Surveillance-recommended two-step method of measuring sex assigned at birth and current gender identity. This article provides a much needed detailed summary of extant health surveillance data sources that can be used to inform research about health risks and disparities among SGM populations. Future recommendations are for more rigorous measurement and oversampling to advance what is known about SGM health disparities and guide development of interventions to reduce disparities.


CoRSeqV3-C: a novel HIV-1 subtype C specific V3 sequence based coreceptor usage prediction algorithm.
The majority of HIV-1 subjects worldwide are infected with HIV-1 subtype C (C-HIV). Although C-HIV predominates in developing regions of the world such as Southern Africa and Central Asia, C-HIV is also spreading rapidly in countries with more developed economies and health care systems, whose populations are more likely to have access to wider treatment options, including the CCR5 antagonist maraviroc (MVC). The ability to reliably determine C-HIV coreceptor usage is therefore becoming increasingly more important. In silico V3 sequence based coreceptor usage prediction algorithms are a relatively rapid and cost effective method for determining HIV-1 coreceptor specificity. In this study, we elucidated the V3 sequence determinants of C-HIV coreceptor usage, and used this knowledge to develop and validate a novel, user friendly, and highly sensitive C-HIV specific coreceptor usage prediction algorithm. We characterized every phenotypically-verified C-HIV gp120 V3 sequence available in the Los Alamos HIV Database. Sequence analyses revealed that compared to R5 C-HIV V3 sequences, CXCR4-using C-HIV V3 sequences have significantly greater amino acid variability, increased net charge, increased amino acid length, increased frequency of insertions and substitutions within the GPGQ crown motif, and reduced frequency of glycosylation sites. Based on these findings, we developed a novel C-HIV specific coreceptor usage prediction algorithm (CoRSeqV3-C), which we show has superior sensitivity for determining CXCR4 usage by C-HIV strains compared to all other available algorithms and prediction rules, including Geno2pheno[coreceptor] and WebPSSMSINSI-C, which has been designed specifically for C-HIV. CoRSeqV3-C is now openly available for public use at http://www.burnet.edu.au/coreceptor. Our results show that CoRSeqV3-C is the most sensitive V3 sequence based algorithm presently available for predicting CXCR4 usage of C-HIV strains, without compromising specificity. CoRSeqV3-C may be potentially useful for assisting clinicians to decide the best treatment options for patients with C-HIV infection, and will be helpful for basic studies of C-HIV pathogenesis.


Successful reimplantation of a passive-fixation ventricle lead perforating the chest wall.
Delayed perforation of a passive fixed pacemaker lead is a rare complication after pacemaker implantation and is associated with increased morbidity and mortality. We report the case of an 82-year-old patient who presented with a delayed perforation of the right heart wall, the pericardium, and the chest wall by a passive-fixation ventricular lead 14 months after pacemaker implantation. The lead was uneventfully extracted transvenously and repositioned in the right ventricle with good pacing and sensing.


N-Glycosidase-carbohydrate-binding module fusion proteins as immobilized enzymes for protein deglycosylation.
A carbohydrate-binding module (CBM) was fused to the N-termini of mannosyl-glycoprotein endo-beta-N-acetylglucosaminidase (EndoF1) and peptide N-glycosidase F (PNGaseF), two glycosidases from Chryseobacterium meningosepticum that are used to remove N-linked glycans from glycoproteins. The fusion proteins CBM-EndoF1 and CBM-PNGaseF also carry a hexahistidine tag for purification by immobilized metal affinity chromatography after production by Escherichia coli. CBM-EndoF1 is as effective as native EndoF1 at deglycosylating RNaseB; the glycans released by both enzymes are identical. Like native PNGaseF, CBM-PNGaseF is active on denatured but not on native RNaseB. Both fusion proteins are as active on RNaseB when immobilized on cellulose as they are in solution. They retain activity in the immobilized state for at least 1 month at 4 degrees C. The hexahistidine tag can be removed with thrombin, leaving the CBM as the only affinity tag. The CBM can be removed with factor Xa if required.


Torpor-like Hypothermia Induced by A1 Adenosine Receptor Agonist: A Novel Approach to Protect against Neuroinflammation.
Hypothermia is a promising clinical therapy for acute injuries, including neural damage, but it also faces practical limitations due to the complexities of the equipment and procedures required. This study investigates the use of the A1 adenosine receptor (A1AR) agonist N6-cyclohexyladenosine (CHA) as a more accessible method to induce steady, torpor-like hypothermic states. Additionally, this study investigates the protective potential of CHA against LPS-induced sepsis and neuroinflammation. Our results reveal that CHA can successfully induce a hypothermic state by activating a neuronal circuit similar to the one that induces physiological torpor. This state is characterized by maintaining a steady core body temperature below 28 °C. We further found that this torpor-like state effectively mitigates neuroinflammation and preserves the integrity of the blood-brain barrier during sepsis, thereby limiting the infiltration of inflammatory factors into the central nervous system. Instead of being a direct effect of CHA, this protective effect is attributed to inhibiting pro-inflammatory responses in macrophages and reducing oxidative stress damage in endothelial cells under systemic hypothermia. These results suggest that A1AR agonists such as CHA could potentially be potent neuroprotective agents against neuroinflammation. They also shed light on possible future directions for the application of hypothermia-based therapies in the treatment of sepsis and other neuroinflammatory conditions.


In vitro and in vivo Human Metabolism of (S)-[18F]Fluspidine - A Radioligand for Imaging σ1 Receptors With Positron Emission Tomography (PET).
(S)-[18F]fluspidine ((S)-[18F]1) has recently been explored for positron emission tomography (PET) imaging of sigma-1 receptors in humans. In the current report, we have used plasma samples of healthy volunteers to investigate the radiometabolites of (S)-[18F]1 and elucidate their structures with LC-MS/MS. For the latter purpose additional in vitro studies were conducted by incubation of (S)-[18F]1 and (S)-1 with human liver microsomes (HLM). In vitro metabolites were characterized by interpretation of MS/MS fragmentation patterns from collision-induced dissociation or by use of reference compounds. Thereby, structures of corresponding radio-HPLC-detected radiometabolites, both in vitro and in vivo (human), could be identified. By incubation with HLM, mainly debenzylation and hydroxylation occurred, beside further mono- and di-oxygenations. The product hydroxylated at the fluoroethyl side chain was glucuronidated. Plasma samples (10, 20, 30 min p.i., n = 5-6), obtained from human subjects receiving 250-300 MBq (S)-[18F]1 showed 97.2, 95.4, and 91.0% of unchanged radioligand, respectively. In urine samples (90 min p.i.) the fraction of unchanged radioligand was only 2.6% and three major radiometabolites were detected. The one with the highest percentage, also found in plasma, matched the glucuronide formed in vitro. Only a small amount of debenzylated metabolite was detected. In conclusion, our metabolic study, in particular the high fractions of unchanged radioligand in plasma, confirms the suitability of (S)-[18F]1 as PET radioligand for sigma-1 receptor imaging.


Art therapy for schizophrenia or schizophrenia-like illnesses.
Many people with schizophrenia or schizophrenia-like illnesses continue to experience symptoms in spite of medication. In addition to medication, creative therapies, such as art therapy, may be helpful. Art therapy allows exploration of the patient's inner world in a non-threatening way through a therapeutic relationship and the use of art materials. It was mainly developed in adult psychiatric inpatient units and was designed for use with people for whom verbal psychotherapy would be impossible. To review the effects of art therapy as an adjunctive treatment for schizophrenia compared with standard care and other psychosocial interventions. We updated the search of the Cochrane Schizophrenia Group's Register (February 2005), hand searched reference lists and 'Inscape' (the Journal of the British Association of Art Therapists), and contacted relevant authors. We included all randomised controlled trials that compared art therapy with standard care or other psychosocial interventions for schizophrenia. We reliably selected, quality assessed and extracted data from the studies. We excluded data where more than 50% of participants in any group were lost to follow up. For continuous outcomes we calculated a weighted mean difference and its 95% confidence interval. For binary outcomes we calculated a fixed effects risk ratio (RR), its 95% confidence interval (CI) and a number needed to treat (NNT). The search identified 61 reports but only two studies (total n=137) met the inclusion criteria. Both compared art therapy plus standard care with standard care alone. More people completed the therapy if allocated to the art therapy group compared with standard care in the short (n=90, 1 RCT, RR 0.97 CI 0.41 to 2.29), medium (n=47, 1 RCT, RR 0.34 CI 0.15 to 0.80) and long term (n=47, 1 RCT, RR 0.96 CI 0.57 to 1.60). Data from one mental state measure (SANS) showed a small but significant difference favouring the art-therapy group (n=73, 1 RCT, WMD -2.3 CI -4.10 to -0.5). In the short term, a measure of social functioning (SFS) showed no clear difference between groups in endpoint scores (n=70, 1 RCT, WMD 7.20 CI -2.53 to 16.93) and quality of life, as measured by the PerQoL, did not indicate effects of art therapy (n=74, 1 RCT, WMD 0.1 CI -2.7 to 0.47). Randomised studies are possible in this field. Further evaluation of the use of art therapy for serious mental illnesses is needed as its benefits or harms remain unclear.


Mesoporous hybrid material composed of Mn3O4 nanoparticles on nitrogen-doped graphene for highly efficient oxygen reduction reaction.
The hybrid material composed of Mn3O4 nanoparticles on nitrogen-doped graphene was prepared via a solvothermal process and investigated for the first time as a catalyst for oxygen reduction reaction (ORR). Its high ORR activity, excellent durability and tolerance to methanol make this hybrid material a promising candidate for highly efficient ORR in fuel cells and metal-air batteries.


Roles of methylation and phosphorylation in the bacterial sensing system.
Chemotaxis is an intriguing model system for the study of second-messenger pathways. One of the puzzles of second-messenger pathways in eukaryotic cells has been that many of these pathways interact, with one pathway either desensitizing or sensitizing an alternate messenger pathway. The chemotaxis system offered a particularly interesting chance to analyze such systems, because one of them is a methylation pathway and the other a phosphorylation pathway. The above description indicates that these two pathways interact with each other in a highly sophisticated way to produce an extremely important survival system. The stimulus on a receptor activates an excitation system that operates through phosphorylation, or the inhibition of phosphorylation, depending on whether the stimulus is a repellent or an attractant. That system ultimately generates or inhibits phosphorylation of a small peptide, the CheY protein, which apparently is the response regulator. The instant that this fast excitation is generated by a change in gradient, the change in conformation of the protein sets in motion a second process, i.e., the adaptation. That is a device which, over a longer period of time, has two functions: It serves as the comparator, which allows the comparison of the past with the present, essential for deletion of a gradient; it also sets in motion the reset to zero, so that the bacterium will not be overwhelmed by any one stimulus but can use all of its receptors to optimize its environment. These two systems by themselves are adequate for chemotaxis, but there is a further elegent complexity: The excitation system feeds back into the adaptation system to produce an asymmetry in the responses. The reason for that asymmetry is that the bacterium wishes to travel in the wrong direction only long enough to produce a detectable signal that it is migrating incorrectly. It wishes to keep swimming in the positive direction as long as the signals indicate that the direction is favorable. Hence, the feedback between the phosphorylation and methylation system involves further fine tuning.


[A forty-five-years-old woman suffered from Sjögren syndrome with progressive tetraparesis].
We herein report the finding of a 45-year-old woman suffered from Sjögren syndrome with progressive tetraparesis, who later developed systemic muscle atrophy and respiratory failure with a one-year clinical history. Neurological examinations revealed progressive tetraparesis with absent deep tendon reflexes, whereas no upper motor neuron signs were observed. The motor and sensory nerve conduction velocity and sensory nerve action potential (SNAP) were both completely normal, but the prolongation of distal motor latency in the median nerve and a decrease in the compound muscle action potential (CMAP) amplitude were observed. We ascertained that a spontaneous discharge was detected in her upper and lower limbs on electromyography (EMG). Her neurological findings as well as the EMG findings closely correlated with those of motor neuron disease; however, she showed a motor paralytic bladder and also demonstrated a serum antibody reaction with 50 kDa spinal cord protein of the rat. A lumbar MR image showed an increased signal intensity of the cauda equina on a gadolinium-enhanced T1 weighted image. We consider the immune-mediated impairment of the motor nerve associated with Sjögren syndrome to be the cardinal pathogenesis of the present patient, even though treatment with oral corticosteroids did not ameliorate her symptoms.


Meta-analysis reveals up-regulation of cholesterol processes in non-alcoholic and down-regulation in alcoholic fatty liver disease.
To compare transcriptomes of non-alcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD) in a meta-analysis of liver biopsies. Employing transcriptome data from patient liver biopsies retrieved from several public repositories we performed a meta-analysis comparing ALD and NAFLD. We observed predominating commonalities at the transcriptome level between ALD and NAFLD, most prominently numerous down-regulated metabolic pathways and cytochrome-related pathways and a few up-regulated pathways which include ECM-receptor interaction, phagosome and lysosome. However some pathways were regulated in opposite directions in ALD and NAFLD, for example, glycolysis was down-regulated in ALD and up-regulated in NAFLD. Interestingly, we found rate-limiting genes such as HMGCR, SQLE and CYP7A1 which are associated with cholesterol processes adversely regulated between ALD (down-regulated) and NAFLD (up-regulated). We propose that similar phenotypes in both diseases may be due to a lower level of the enzyme CYP7A1 compared to the cholesterol synthesis enzymes HMGCR and SQLE. Additionally, we provide a compendium of comparative KEGG pathways regulation in ALD and NAFLD. Our finding of adversely regulated cholesterol processes in ALD and NAFLD draws the focus to regulation of cholesterol secretion into bile. Thus, it will be interesting to further investigate CYP7A1-mediated cholesterol secretion into bile - also as possible drug targets. The list of potential novel biomarkers may assist differential diagnosis of ALD and NAFLD.