DA strain of Theiler's murine encephalomyelitis virus induces demyelination in nude mice.
DA strain of Theiler's murine encephalomyelitis virus produces a chronic, progressive demyelinating disease in mice that resembles multiple sclerosis. An immunopathological mechanism for demyelination has been postulated, because there is a brisk immune response with low virus titers at the time of demyelination and because immunosuppression lessens the degree of demyelination. We inoculated Nude mice with DA virus to clarify the role of immune-mediated demyelination. Animals became paralyzed 3 weeks to 2 months after inoculation, usually dying within a week of appearance of signs. Demyelinated foci were present in the spinal cords, with evidence of degenerating myelin around intact axons as well as completely demyelinated, naked axons. Occasional macrophages were present, but none was seen actively stripping intact myelin lamellae. These results suggest that DA virus lytic infection, without a contribution from the T lymphocyte immune system, is sufficient to produce demyelination. It is likely that DA virus demyelination has varying mechanisms that may be active at different times.


The multitalented microbial sensory rhodopsins.
Sensory rhodopsins are photoactive, membrane-embedded seven-transmembrane helix receptors that use retinal as a chromophore. They are widespread in the microbial world in each of the three domains of life: Archaea, Bacteria and Eukarya. A striking characteristic of these photoreceptors is their different modes of signaling in different organisms, including interaction with other membrane proteins, interaction with cytoplasmic transducers and light-controlled Ca(2+) channel activity. More than two decades since the discovery of the first sensory rhodopsins in the archaeon Halobacterium salinarum, genome projects have revealed a widespread presence of homologous photosensors. New work on cyanobacteria, algae, fungi and marine proteobacteria is revealing how evolution has modified the common design of these proteins to produce a remarkably rich diversity in their signaling biochemistry.


Envelope solitons of acoustic plate modes and surface waves.
The problem of the existence of evelope solitons in elastic plates and at solid surfaces covered by an elastic film is revisited with special attention paid to nonlinear long-wave short-wave interactions. Using asymptotic expansions and multiple scales, conditions for the existence of envelope solitons are established and it is shown how their parameters can be expressed in terms of the elastic moduli and mass densities of the materials involved. In addition to homogeneous plates, weak periodic modulation of the plate's material parameters are also considered. In the case of wave propagation in an elastic plate, modulations of weakly nonlinear carrier waves are governed by a coupled system of partial differential equations consisting of evolution equations for the complex amplitude of the carrier wave (the nonlinear Schrödinger equation for envelope solitons and the Mills-Trullinger equations for gap solitons), and the wave equation for long-wavelength acoustic plate modes. In contrast to this situation, envelope solitons of surface acoustic waves in a layered structure are normally described by the nonlinear Schrödinger equation alone. However, at higher orders of the carrier wave amplitude, the envelope soliton is found to be accompanied by a quasistatic long-wavelength strain field, which may be localized at the surface with penetration depth into the substrate of the order of the inverse amplitude or which may radiate energy into the bulk. A new set of modulation equations is derived for the resonant case of the carrier wave's group velocity being equal to the phase velocity of long-wavelength Rayleigh waves of the uncoated substrate.


Exploring perceptions and beliefs about the cost of fruit and vegetables and whether they are barriers to higher consumption.
Fruit and vegetable (F&V) consumption is below recommendations, and cost may be a barrier to meeting recommendations. Limited evidence exists on individual perceptions about the cost, actual spending and consumption of F&V. This study investigated perceptions and beliefs about cost of F&V and whether this is a barrier to higher consumption. An online survey of Australian adults (n = 2474) measured F&V consumption; expenditure on F&V and food; and perceived barriers to consumption. Multivariable logistic regression examined associations between participants' responses about cost of F&V and demographic factors, and with actual consumption and expenditure on F&V. Cost was identified as a barrier for 29% of people not meeting recommended fruit servings and for 14% of people not meeting recommendations for vegetables. Cost was a more common barrier for those on lower incomes (fruit aOR 1.89; 95% CI 1.20-2.98 and vegetables aOR 2.94; 95% CI 1.97-4.39) and less common for older participants (fruit aOR 0.33; 95% CI 0.17-0.62 and vegetables aOR 0.31; 95% CI 0.18-0.52). There was no association between the perceived barriers and actual F&V spending. Twenty percent of participants said F&V were not affordable; 39% said cost made it difficult to buy F&V, and for 23% the cost of F&V meant they bought less than desired. A minority reported F&V were not affordable where they shopped and that cost was a barrier to higher consumption. However, it is apparent that young adults and those on low incomes eat less than they would like because of cost. Strategies that remove financial impediments to consumption are indicated for these population sub-groups.


[Chemical constituents from roots of Ixeris chinensis].
Silica gel column chromatography and preparative HPLC were applied to isolate the chemical constituents from the roots of Ixeris chinensis. Fifteen compounds were isolated and their structures were elucidated by the physicochemical properties and spectral analysis as chinensioide G(1), chinensioide B(2), 10α-hydroxy-guaia-12,6-lactone-3-keton(3), chinensioide C(4), 10α-hydroxy-11βH-guaia-4(5) -ene-12,6-lactone (5), 3β, 10α-dihydroxy-11βH-guaia-11 (13)-ene-12,6-lactone (6), 3β, 10α-dihydroxy-4βH, 11βH-guaia-12,6-lactone(7), 3β, 10α-dihydroxy-guaia-4 (15), 11 (13) -diene-12, 6-lactone (8), caffeic acid (9), p-hydorxyphenylacetic acid(10), methyl p-hydroxyphenylacetate (11), ethyl p-hydroxyphenylacetate (12), sitosterol (13), daucosterol (14), and ixerin D(15). Compound 1 was new, and 6 and 7 were isolated from I. chinensis for the first time.


Nursing implementation of smoking bans on psychiatric wards.
Although the prevalence of tobacco dependence among psychiatric inpatients far exceeds that of the general population, psychiatric inpatients are concerned about the health risks and financial impact of their addiction. Financial resources heretofore invested in supporting psychiatric patients' smoking and treatment of cigarette related illnesses can be reallocated to underwrite patient education. Comprehensive nursing care of tobacco dependent patients addresses knowledge deficits through individual and group treatment modalities.


Bone marrow disease detection with FDG-PET/CT and bone marrow biopsy during the staging of malignant lymphoma: results from a large multicentre study.
To compare the accuracy of bone marrow biopsy (BMb) and positron emission tomography (PET) in bone marrow disease (BMD) detection, in a large multicentre population of patients with new diagnosis of malignant lymphoma. PET and BMb were performed to complete disease staging in 337 consecutive patients: 130 Hodgkin's disease (HD), 207 aggressive non Hodgkin's lymphoma (NHL). Sensitivity, specificity and accuracy of both techniques in BMD detection were evaluated and compared. 87 patients with BMD (25 positives at both exams, 27 only at the BMb and 35 only at the PET study). PET vs. BMb were reordered: sensitivity: 69% vs. 59.8%; specificity: 99.2% vs. 100%; accuracy: 91.4% vs. 89.6%; positive predictive value: 96.8% vs. 100%; negative predictive value: 90.2% vs. 87.7%. The sensitivity of PET and BMb is similar (69% and 60%, respectively), PET and BMb are complementary: in fact out of 87 patients with confirmed BMD only 25 are positive at both exams, while 27 only at the BMb and 35 only at the PET exam; the integration of PET findings with BMb ones increases the diagnostic accuracy. Consequentially PET is essential during the staging of malignant lymphomas.


Subsets of T cells in healthy rhesus macaques (Macaca mulatta) infected with simian T-lymphotropic virus type 1.
Simian T-lymphotropic virus type 1 (STLV-1) is a C-type retrovirus of nonhuman primates that is genetically and antigenically related to human T-lymphotropic virus type 1 (HTLV-1). Infection with STLV-1 has been reported in many species of Old World monkeys and apes, including rhesus macaques (Macaca mulatta). Similar to HTLV infection in humans, STLV infection has been associated with T-cell lymphoproliferative disease or lymphoma in a small proportion of infected animals, predominantly African species. There are conflicting reports of T-cell subset alterations in healthy HTLV-1 carriers. To the authors' knowledge, analysis of T-cell subsets in healthy STLV-1 carrier rhesus macaques has not been reported. Subsets of T cells in peripheral blood from healthy, STLV-1-seropositive rhesus macaques (n = 17) and seronegative controls matched for age and sex (n = 17) were determined by use of fluorescence-activated cell sorter analysis. Parameters measured included CD3, CD4, CD8, CD25, CD28, CD38, and HLA-DR cell sets. Significant differences in T-cell subsets or hematologic parameters were not observed between healthy STLV-seropositive and seronegative groups.


Prevalence, geographic distribution, and genealogical investigation of Machado-Joseph disease in the Azores (Portugal).
Machado-Joseph disease (MJD) is an autosomal, dominantly inherited neurodegenerative disorder of adult onset. The prevalence of MJD reaches its highest values in the islands of the Azores. A research program was undertaken to study the origin and spread of the mutant gene in the Azorean populations. Here, we present the first results of such a study. The Azorean MJD patients are grouped in 34 families and are distributed on 4 of the 9 Azore islands. Values of prevalence, carrier rate, and number of individuals at risk are reported. The genealogies of the patients were reconstructed to identify the founders. An analysis of the geographic distribution of the birthplaces of the patients compared with the birthplaces of the founders revealed the existence of areas that are clusters for both, thus defining crucial sites for the origin of the disease. Preliminary results on the number of links between the affected families show that 64.7% of them have at least one link with another MJD family. So far, a single source for the introduction of the mutant gene in the Azores has not been identified.


Prevalence of alcohol and other drugs in injured drivers and their association with clinical outcomes.
Driving under the influence of alcohol or drugs is a risk factor for motor vehicle accidents (MVAs). This issue has become an increasing concern for the governments of many European and North American countries, thereby encouraging the adoption of preventive policies. The aim of this study was to investigate the associations between major clinical outcomes and alcohol or drug abuse among drivers involved in MVAs who were referred to an Italian Emergency Department. The study population consisted of consecutive injured drivers who were admitted to the Emergency Department following an MVA during a period of one year. The patients' blood alcohol concentrations (BACs) and the presence of the most common drugs of abuse [amphetamine, methamphetamine, methylenedioxymethamphetamine (MDMA), barbiturates, benzodiazepines, benzoylecgonine (cocaine main metabolite), cannabinoids, methadone, and opiates)] were determined and evaluated in association with major clinical outcomes and demographic data. Overall, 347 injured drivers were enrolled. Of the 347 enrolled patients, 164 (47.3%) had a positive BAC (greater than 5 mg/dL). A subgroup of 107 injured drivers was also screened for drugs of abuse. Thirty-seven of these subjects (34.5%) were positive for at least one drug. A statistically significant association was found between BAC and triage at admission (p<0.01), hospitalization (p<0.01), and lesions of internal organs (p=0.04). The results of this study show that a significant proportion of injured drivers had detectable levels of BAC and/or illegal drugs. Positive BACs were significantly associated with worse clinical outcomes. These findings suggest that the implementation of methods to prevent alcohol and drug abuse is of paramount importance in the effort to reduce the rates of MVAs and their dramatic consequences.


Hypoxia reduces endothelin production by rat alveolar type II cells in primary culture.
The purpose of the study was to describe endothelin (ET) production and to characterize the effect of hypoxia on preproendothelin-1 (preproET-1) messenger ribonucleic acid (mRNA) expression and ET secretion by rat type II pneumocytes in vitro. Rat type II pneumocytes were incubated in a sealed chamber containing a normoxic (21% O2) or hypoxic (1% O2) atmosphere for increasing durations. Immunoreactive ET (irET) was measured in cell supernatants using a radioimmunoassay. Rat preproET-1 mRNA was detected by Northern blot. Rat type II pneumocytes expressed preproET-1 mRNA, contained irET and secreted irET in a time-dependent manner. ET secretion was dependent on de novo ribonucleic acid (RNA) and protein synthesis. Hypoxia decreased irET secretion by 27% and reduced the steady-state level of preproET-1 mRNA by 60% whereas intracellular irET concentration was unchanged. Inhibition was partially reversible with the return to a normoxic atmosphere. Inhibition of nitric oxide synthesis did not prevent the inhibitory effect of hypoxia. In conclusion, rat type II pneumocytes in primary culture secreted immunoreactive endothelin and expressed preproendothelin-1 messenger ribonucleic acid. Hypoxia reversibly reduced endothelin-1 production through a reduction of the steady-state preproendothelin-1 messenger ribonucleic acid level. Nitric oxide synthesis did not mediate the inhibitory effect of hypoxia.


Prevalence and diversity of carbapenem-resistant bacteria in untreated drinking water in Portugal.
We examined the prevalence and diversity of carbapenem-resistant bacteria (CRB) in untreated drinking water. Prevalence was estimated in plate count agar (PCA) and R2A media with or without antibiotics. Clonal relatedness of isolates was established by repetitive extragenic palindroitic (REP)-PCR. Phylogeny was based on the 16S rRNA gene. Antimicrobial susceptibility was assessed by disc diffusion methods. Genes encoding beta-lactamases and integrases were inspected by PCR. CRB ranged from 0.02% to 15.9% of cultivable bacteria, while ampicillin-resistant bacteria ranged from 1.5% to 31.4%. Carbapenem-resistant isolates affiliated with genera Stenotrophomonas, Pseudomonas, Janthinobacterium, Chryseobacterium, Sphingobacterium, Acidovorax, Caulobacter, Cupriavidus, and Sphingomonas. CRB were highly resistant to beta-lactams, but mostly susceptible to other classes. Transmissible beta-lactamase genes and integrase genes were not detected. The genus-specific bla(L1) was detected in 61% of the Stenotrophomonas isolates. Contrarily to what has been reported for extensively used antibiotics, low levels of carbapenem resistance were detected in untreated drinking water, often represented by intrinsically resistant genera. Production of chromosomal-encoded carbapenemases was the prevalent carbapenem resistance mechanism. Results suggest that the dissemination of anthropogenic-derived carbapenem resistance is at an early stage. This presents an opportunity to rationally develop monitoring strategies to identify dissemination routes and assess the impact of human actions in the environmental resistome.


Development of Pericardial Effusion in Non-small Cell Lung Cancer Is Associated with the Presence of EGFR/ALK Mutations.
No specific clinical or histological factors are recognized to be associated with the development of pericardial effusion in non-small cell lung cancer (NSCLC) other than a metastatic disease. To assess whether specific clinical and histological features are associated with development of pericardial effusion in patients with NSCLC. A consecutive cohort of patients with NSCLC who presented with symptomatic pericardial effusion 2014-2017 was compared to a control group of patients with advanced NSCLC without pericardial effusion. The 27 patients in the effusion group were generally younger, more often female, and with a higher percentage of never-smokers, compared to the 54 patients of the control group. Epidermal growth factor receptor/anaplastic lymphoma kinase (EGFR/ALK) mutation tumors were found in 48% of patients in the effusion group vs. 25% in the control group. In the multivariate analysis, the unadjusted odds ratio (OR) for the development of pericardial effusion in patients with somatic mutations was significantly higher compared to wild type tumors (OR 2.65, 95% confidence interval 1.00-7.00). However, a suspected association between pericardial effusion and mutation status was found to be confounded by age. While a high rate of recurrence was observed when pericardiocentesis was initially performed (9/17, 53%), no recurrence was documented when pericardial window procedure was performed (total of 17 patients). Patients with EGFR/ALK mutations may be at higher risk for the development of pericardial effusion; therefore, attending physicians need to be aware and have a high index of clinical suspicion.


[Development of a Scale for Alcohol Drinking Prevention Behavior in Early Elementary School Based on Ajzen's Theory of Planned Behavior].
This study aimed to develop a scale to measure variables related to alcohol drinking prevention behavior in early elementary school, based on the theory of planned behavior. A scale was developed to measure variables related to alcohol drinking prevention behavior. Initial items for direct evaluation were constructed through a literature review, and those for belief-based indirect measure were generated through interviews with 30 second- and third-grade elementary school students. The collected data from 286 third-grade elementary school students were then subjected to item analysis, exploratory and confirmative factor analysis, criterion-related validity testing, and internal consistency assessment. The final scale consisted of 35 items. Intention, attitudes, subjective norms, and perceived behavioral control explained 82.7% of the variance; behavioral beliefs, normative beliefs, and control beliefs explained 65.6% of the variance; and evaluation of outcome, motivation to comply, and power of control beliefs explained 72.8% of the variance. The confirmatory factor analysis indicated that the theoretical models had a satisfactory goodness of fit. Criterion-related validity was confirmed between the direct evaluation variables and the indirect measure variables (attitudes r=.64, p <.001; subjective norms r=.39, p <.001; perceived behavioral control r=.62, p <.001). Cronbach's a was .89 for the direct evaluation variables and .93 for the indirect measure variables. The scale developed in this study is valid and reliable. It could be used to measure and explain variables related to alcohol drinking prevention behavior in early elementary school.


A comprehensive review of oral cancer.
Oral squamous cell carcinomas comprise 2-3% of all new malignancies diagnosed in the United States, making it the 10th most common malignancy. However, for the last few decades, the average five-year survival rate of 50% has not changed significantly. This article reviews the risk factors associated with the development of oral cancer and how premalignant (leukoplakia and erythroplakia) and actual cancerous lesions may appear. Diagnostic tools and aids to diagnosis are discussed, as are treatment modalities. It is imperative that all dental professionals perform a simple head and neck examination in addition to an oral examination during each new patient visit and each six-month recall appointment. Early detection saves lives.


Cytosolic and mitochondrial ROS production resulted in apoptosis induction in breast cancer cells treated with Crocin: The role of FOXO3a, PTEN and AKT signaling.
Different groups have reported the Crocin anticancer activity. We previously showed Crocin-induced apoptosis in rat model of breast and gastric cancers, through the increased Bax/Bcl-2 ratio and caspases activity, as well as the cell cycle arrest in a p53-dependent manner. Since Crocin antioxidant activity has been shown under different conditions, it is interesting to elucidate its apoptotic mechanism. Here, we treated two breast cancer cell lines, MCF-7 and MDA-MB-231, with Crocin. MTT and ROS assays, cell cycle arrest, Bax/Bcl-2 ratio and caspase3 activity were determined. PARP cleavage and expression of some proteins were studied using Western blotting and immunofluorescence. The results indicated stepwise ROS generation in cytosol and mitochondria after Crocin treatment. Attenuating the early ROS level, using diphenyleneiodonium, diminished the sequent mitochondrial damage (decreasing Δψ) and downstream apoptotic signaling. Crocin induced ROS production, FOXO3a expression and nuclear translocation, and then, elevation of the expression of FOXO3a target genes (Bim and PTEN) and caspase-3 activation. Application of N-acetylcysteine blocked AKT/FOXO3a/Bim signaling. FOXO3a knockdown resulted in a decrease of Bim, PTEN and caspase 3, after Crocin treatment. PTEN knockdown caused a decrease in FOXO3a, Bim and caspase 3, in addition to an increase in p-AKT and p-FOXO3a, after Crocin treatment. In conclusion, Crocin induced apoptosis in MCF-7 and MDA-MB-231 human breast cancer cells. The ROS-activated FOXO3a cascade plays a central role in this process. FOXO3a-mediated upregulation of PTEN exerted a further inhibition of the AKT survival pathway. These data provide a new insight into applications of Crocin for cancer therapy.


Normalized cut-based saliency detection by adaptive multi-level region merging.
Existing salient object detection models favor over-segmented regions upon which saliency is computed. Such local regions are less effective on representing object holistically and degrade emphasis of entire salient objects. As a result, the existing methods often fail to highlight an entire object in complex background. Toward better grouping of objects and background, in this paper, we consider graph cut, more specifically, the normalized graph cut (Ncut) for saliency detection. Since the Ncut partitions a graph in a normalized energy minimization fashion, resulting eigenvectors of the Ncut contain good cluster information that may group visual contents. Motivated by this, we directly induce saliency maps via eigenvectors of the Ncut, contributing to accurate saliency estimation of visual clusters. We implement the Ncut on a graph derived from a moderate number of superpixels. This graph captures both intrinsic color and edge information of image data. Starting from the superpixels, an adaptive multi-level region merging scheme is employed to seek such cluster information from Ncut eigenvectors. With developed saliency measures for each merged region, encouraging performance is obtained after across-level integration. Experiments by comparing with 13 existing methods on four benchmark datasets, including MSRA-1000, SOD, SED, and CSSD show the proposed method, Ncut saliency, results in uniform object enhancement and achieves comparable/better performance to the state-of-the-art methods.


Clinical and demographic predictors of long-term disability in patients with relapsing-remitting multiple sclerosis: a systematic review.
To identify clinical and demographic factors associated with long-term disability in patients with relapsing-remitting multiple sclerosis. We searched the MEDLINE (1966-May 2005), EMBASE, CINAHL, Cochrane, and PsycINFO computerized databases, and reviewed reference lists of retrieved articles. We included studies that examined predictors of long-term disability in patients with relapsing-remitting multiple sclerosis. We excluded studies that did not distinguish relapsing-remitting multiple sclerosis from primary progressive multiple sclerosis, enrolled fewer than 40 subjects, observed subjects for less than 5 years, or collected follow-up information in less than 80% of the inception cohort. Two reviewers assessed study quality in 4 domains: cohort assembly, definitions and assessments of prognostic factors and outcomes, and statistical methods. One reviewer extracted data on the direction, magnitude, precision, and statistical significance of the effect of each predictor on prognosis. Heterogeneity of study designs precluded us from pooling the results of 27 eligible studies. Study quality was limited by cross-sectional design, enrollment of prevalent cases from referral centers, and lack of multivariate adjustment. Sphincter symptoms at onset (hazard ratio, 1.1-3.1), incomplete recovery from the first attack (hazard ratio, 1.3-3.3), and a short interval between the first and second attack (hazard ratio, 1.6-1.9) were most strongly and consistently associated with poor prognosis. Other factors widely believed to be of prognostic importance, including sex and age at onset, demonstrated inconsistent or weak effects on prognosis. The most robust predictors of long-term physical disability in relapsing-remitting multiple sclerosis are sphincter symptoms at onset and early disease course outcomes. These factors can be used to guide treatment decisions for drugs with significant toxicities.


Which paradigm for managing the risk of ionizing radiation?
This article tackles the problem of controversies expressed by experts in the field of estimating and managing ionizing radiation risks. We analyze the paradigms that were conceived on this subject, in particular the studies carried out by the International Commission on Radiological Protection (ICRP), as well as the papers stating either that the effect of low doses is relatively weak or, on the contrary, relatively serious. Uncertainties, which taint the risk estimations, assume a particular importance because they are at the origin of the request for expert and value judgments and represent the critical point of the discussions on the ionizing radiation risks. Our study allows us to look further into the problem of the paradigm's formation, uncertainties, and expert and value judgments, and provides areas for consideration that may contribute to a better understanding of certain gridlocks in the decision-making process, as regards to environmental, health, and energy policies.


IMPACT is a developmentally regulated protein in neurons that opposes the eukaryotic initiation factor 2α kinase GCN2 in the modulation of neurite outgrowth.
The product of the mouse Imprinted and Ancient gene, IMPACT, is preferentially expressed in neurons. We have previously shown that IMPACT overexpression inhibits the activation of the protein kinase GCN2, which signals amino acid starvation. GCN2 phosphorylates the α-subunit of eukaryotic translation initiation factor 2 (eIF2α), resulting in inhibition of general protein synthesis but increased translation of specific messages, such as ATF4. GCN2 is also involved in the regulation of neuronal functions, controlling synaptic plasticity, memory, and feeding behavior. We show here that IMPACT abundance increases during differentiation of neurons and neuron-like N2a cells, whereas GCN2 displays lowered activation levels. Upon differentiation, IMPACT associates with translating ribosomes, enhances translation initiation, and down-regulates the expression of ATF4. We further show that endogenous IMPACT promotes neurite outgrowth whereas GCN2 is a strong inhibitor of spontaneous neuritogenesis. Together, these results uncover the participation of the GCN2-IMPACT module of translational regulation in a highly controlled step in the development of the nervous system.


Ovarian cancer has frequent loss of heterozygosity at chromosome 12p12.3-13.1 (region of TEL and Kip1 loci) and chromosome 12q23-ter: evidence for two new tumour-suppressor genes.
Identification of the key genetic alterations leading to ovarian cancer is in its infancy. Polymerase chain reaction (PCR)-based analysis of loss of heterozygosity (LOH) is a powerful method for detecting regions of altered tumour-suppressor genes. Focusing on chromosome 12, we examined 23 ovarian cancer samples for LOH using 31 highly polymorphic microsatellite markers and found the chromosomal localization of two putative tumour-suppressor genes. Two commonly deleted regions were 12p12.3-13.1 in 6/23 (26%) and 12q23-ter in 7/23 (30%) samples. LOH on chromosome 12 was more common in late-stage ovarian carcinomas. The region of LOH at 12p12.3-13.1 includes the genes that code for the ETS-family transcriptional factor, known as TEL, and the cyclin-dependent kinase inhibitor, known as p27Kip1. Mutational analysis of both TEL and p27Kip1 using single-strand conformation polymorphism (SSCP) showed no abnormalities, suggesting that the altered gene in this region is neither of these genes. Taken together, our data suggest that new tumour-suppressor genes in the region of chromosomes 12p12.3-13.1 and 12q23-ter may be involved in the development of ovarian cancer.


Effects of endurance training on superoxide dismutase activity, content and mRNA expression in rat muscle.
1. The purpose of the present study was to investigate the changes in superoxide dismutase (SOD) isoenzyme (Mn(2+)-SOD and Cu2+, Zn(2+)-SOD) activities, contents and mRNA expressions in rat skeletal muscle during endurance training and a single bout of exercise. 2. Thirty-eight male Wistar rats were divided into untrained (U) and trained (T) groups. The T group rats were treadmill-trained for 9 weeks. The activity, content and mRNA expression of Mn(2+)-SOD and Cu2+, Zn(2+)-SOD were determined in the soleus muscle of each rat. 3. Mn(2+)-SOD activity and content in the T group were significantly higher than in the U group, both at rest (22 and 21%, respectively) and after exercise (24 and 46%, respectively), while a single bout of exercise affected neither the activity nor content of Mn(2+)-SOD in either group. 4. The content of Cu2+,Zn(2+)-SOD in both groups was not different at rest and after exercise, although its activity at rest was significantly higher in the T group than in the U group (by 29%). 5. After exercise, the expression of Mn(2+)-SOD mRNA was markedly attenuated only in the U group (49%); the expression of Cu2+,Zn(2+)-SOD mRNA was not influenced by exercise. 6. Our results suggest that adequate endurance training increases both the activity and content of Mn(2+)-SOD and that untrained rats are rather susceptible to oxidative stress during physical exercise. It thus appears that Mn(2+)-SOD provides a reliable index of physical training. 7. The results obtained in the present study also suggest that muscle has the capacity of responding to training in such a manner as to reduce the potential harm arising from the accumulation of oxygen free radicals resulting from enhanced metabolic activity.


An outbreak investigation of parechovirus-A3 in a newborn nursery.
To investigate parechovirus-A3 (PeV-A3) transmission in a newborn nursery, after encountering 3 neonates with fever and rash. An observational study. At a newborn nursery at the general hospital in Hyogo, Japan. Symptomatic neonates and their family members, and asymptomatic neonates born during the same period. PCR assays for PeV-A and genotyping were used for the investigation of PeV-A3. Preserved umbilical cords were used to identify the route of transmission. PeV-A3 infection was confirmed in the three symptomatic neonates. The index case had fever and rash, and the 2 neonates treated later became symptomatic and had serum, cerebrospinal fluid, and stool specimens that were positive for PeV-A3 on PCR. The umbilical cord of the index case was positive for PeV-A3 on PCR. The family members of the index case, including the mother, were asymptomatic before delivery. The older sister and cousin of the PeV-A3-infected neonate had positive PCR results. The sequence analysis suggested 2 possible transmission routes: vertical and horizontal transmission in a newborn nursery and/or a family outside the hospital. The incubation period of PeV-A3 infection was estimated to be 1-3 days (maximum, 7 days). Horizontal transmission of PeV-A3 was confirmed in a newborn nursery. Vertical transmission was suggested by the detection of RNA in an umbilical cord sample from the index case. These observations indicate that PeV-A3 can be horizontally transmitted in a newborn nursery and that special caution is required to prevent healthcare-associated transmission of PeV-A3.


Spectroscopic identification of isomeric jet-cooled benzyl-type radicals generated from 4-fluoro-o-xylene.
Vibronically excited but jet-cooled benzyl-type radicals were generated by the corona discharge of precursor 4-fluoro-o-xylene seeded in a large amount of inert carrier gas helium using a pinhole-type glass nozzle, from which the vibronic emission spectra were observed with a long-path monochromator in the visible region. From an analysis of the spectra observed, we identified the existence of two isomeric benzyl-type radicals, 2-methyl-4-fluorobenzyl and 2-methyl-5-fluorobenzyl radicals in corona discharge, and determined the electronic energy of the D1 → D0 transition and several vibrational mode frequencies in the D0 state of both isomers for the first time.


Roquefortine C in blue-veined and soft-ripened Cheeses in the USA.
Certain fungi can produce secondary metabolites that are toxic, mycotoxins. Two groups of cheeses where fungi are used for ripening are the blue-veined cheeses (Penicillium roqueforti) and the "soft-ripened" cheeses (P. camemberti). An enzyme-linked immunosorbent assay was used to screen for the mycotoxin roquefortine C (ROQC) in 202 samples of cheeses sold in the United States. Of these 152 were blue-veined cheeses, 46 were soft-ripened cheeses and 4 were other varieties of mould-ripened cheeses. ROQC was not detected in any of the soft-ripened cheeses, at a limit of detection of 1.8 µg/kg. ROQC was found in 151 of 152 blue-veined cheeses. The maximum level found was 6,630 µg/kg (median 903 µg/kg, average of positives 1430 µg/kg, limit of quantitation 6.9 µg/kg). These levels are consistent with the levels found previously in blue-veined cheeses in the United Kingdom and Europe, which have generally been considered non-hazardous for human consumption.


Osteonecrosis in patients treated with definitive radiotherapy for squamous cell carcinomas of the oral cavity and naso-and oropharynx.
A group of 381 patients with squamous cell carcinoma of the oral cavity and naso-and oropharynx treated with definitive radiotherapy were analyzed with respect to the incidence and precipitating factors of mandibular osteonecrosis. Elective dental extraction prior to therapy increased the incidence, and dental conservation decreased it. Spontaneous osteonecrosis did not occur with doses less than 6,000 rads in 6 weeks, and was uncommon (1.8%) at doses under 7,000 rads in 7 weeks. At doses over 7,000 rads, osteonecrosis developed in 9%. The incidence was greater in patients with tumors near bone (9.4%) than in those with tumors not next to bone (2.1%).


Infiltrating orbital granular cell tumour: a case report and literature review.
A surgical biopsy of an infiltrative retrobulbar mass in a 44-year-old man was diagnosed as granular cell tumour. Electron microscopy and immunoperoxidase stains were used to confirm the diagnosis and to study the histogenesis of this rare soft tissue neoplasm. S-100 stain was positive, while neuron-specific enolase and myoglobin stains were negative, suggesting a non-specific neural origin for the cells. The capability of this tumour to invade surrounding tissues has seldom been described in the orbit and is demonstrated by this case.


Viability of sublethally injured indicator and pathogenic coliform bacteria on fresh-cut cabbage during storage in an active MAP of 10% CO2.
Shredded cabbage treated with either tap water or electrolyzed water was stored in an active modified atmosphere packaging (MAP) of 10% CO2 for 5 d at 10℃, 7 d at 5℃, and 8 d at 1℃ to evaluate the occurrence and viability of sublethally injured coliform bacteria. The CO2 and O2 concentrations in the packages approached an equilibrium of 10% CO2 and 10% O2 during storage at all temperatures tested. Coliforms in shredded cabbage increased during storage at all three temperatures, with the increase being greater at 10℃. Sublethal injury at 65% to 69% for the coliforms was detected only on cabbage samples treated with electrolyzed water and stored at 5℃ for 4 and 7 d. Enterobacter cloacae was one of the injured species of coliform bacteria in shredded cabbage. Shredded cabbage was inoculated with chlorine-injured Escherichia coli O157:H7 and stored at 5℃ for 6 d in an active MAP of 10% CO2. Counts of E. coli O157:H7 remained almost constant during storage, and injured E. coli O157:H7 ranging from 50% to 70% were found on shredded cabbage throughout the storage period. These results indicate that sublethally injured indicator and pathogenic bacteria would be found on fresh-cut cabbage in the realistic MAP storage at 5℃.


Inducible acid tolerance mechanisms in enteric bacteria.
Enteric micro-organisms have developed several inducible mechanisms for surviving transient periods of extreme acid stress. Salmonella typhimurium possesses an acid tolerance response (ATR) induced in minimal medium by short exposures to mild acid stress. More than 50 acid shock proteins (ASPs) are induced during adaptation. Eight ASPs are regulated by the major iron regulatory protein, Fur, in an unusual iron-independent manner. The two-component regulator, PhoP, is an autoinduced ASP that controls the induction of three additional ASPs. The stress sigma factor sigma S is an ASP that regulates induction of eight ASPs. Acid induction of sigma S is due to its decreased proteolytic turnover via the ClpXP protease in conjunction with the two-component-type response regulator MviA (RssB in Escherichia coli). Mutations in any of these three regulators leads to a defective ATR. Repair of pH stress-induced DNA damage appears to require the Ada protein (O6-methylguanine methyltransferase) since an ada mutant is both acid and alkaline sensitive. In contrast to S. typhimurium, E. coli and Shigella have acid resistance systems induced in complex media that include a glucose-repressed system protective at pH 2.5 without amino acid supplementation, a glutamate decarboxylase system that requires glutamate and an arginine decarboxylase system unique to E. coli.


Genetic mapping in (Populus tomentosa x Populus bolleana) and P. tomentosa Carr. using AFLP markers.
The AFLP genetic linkage maps for two poplar cultivars were constructed with the pseudo-test-cross mapping strategy. The hybrids were derived from an interspecific backcross between the female hybrid clone "TB01" (Populus tomentosa x Populus bolleana) and the male clone "LM50" ( P. tomentosa). A total of 782 polymorphic fragments were obtained with a PCR-based strategy using 49 enzyme-nested ( EcoRI/ MseI) primer combinations. Six hundred and thirty two of these fragments segregated in a 1:1 ratio ( P<0.01), indicating that these DNA polymorphisms are heterozygous in one parent and null in the other. The linkage analysis was performed using Mapmaker version 3.0 with LOD 5.0 and a maximum recombination fraction (theta) of 0.3. Map distances were estimated using the Kosambi mapping function. In the framework map for "LM50" (P. tomentosa), 218 markers were aligned in 19 major linkage groups. The linked loci spanned approximately 2,683 cM of the poplar genome, with an average distance of 12.3 cM between adjacent markers. For "TB01" (P. tomentosa x P. bolleana), the analysis revealed 144 loci, which were mapped to 19 major linkage groups and covered about 1,956 cM, with an average distance of 13.6 cM between adjacent markers. These maps covered about 87% and 77% of the estimated genome size of parents "LM50" and "TB01", respectively. The maps developed in this study lay an important foundation for future genomics research in poplar, providing a means for localizing genes controlling economically important traits in P. tomentosa.


Immunosuppressive levels of glucocorticoid block extrauterine luteolysins in the rat.
Leukocytes, normal constituents of the corpus luteum, release prostaglandins (PGs), superoxide, and hydrogen peroxide (H2O2) upon activation. These products appear to mediate luteolysis, and it has been postulated that activated leukocytes serve a role in corpus luteum regression. Glucocorticoids prevent leukocyte infiltration and activation by inhibiting cytokine production, secretion, and action, and also inhibit eicosanoid synthesis. The objective of the present studies was therefore to assess whether glucocorticoid would influence luteal regression in the rat. Ovulation and pseudopregnancy were synchronized in prepubertal rats by gonadotropin treatment. In uterine-intact rats, functional luteal regression, assessed from serum progesterone levels, began on Day 10 and was complete by Day 14. Dexamethasone blocked luteal regression in uterine-intact animals when administered daily from early in pseudopregnancy for as long as treatment was continued (up to Day 17). Immunosuppressive effects of dexamethasone were evident in the inhibition of estrogen-induced infiltration of eosinophils, as shown by abrogation of estrogen-induced uterine peroxidase activity, and high continuous levels of dexamethasone were necessary to block luteolysis. Hysterectomy extended luteal function by several days, with maintenance of maximal serum progesterone levels up to Day 12; but serum progesterone levels were reduced about 50% by Day 16 and completely depressed by Day 19. Dexamethasone treatment of hysterectomized rats from Day 12 until Day 15 or 18 blocked the decline in serum progesterone levels. Dexamethasone treatment did not block the decrease in serum progesterone levels induced within 24 h by PGF2 alpha in uterine-intact animals on Day 9 or in hysterectomized animals on Day 19.(ABSTRACT TRUNCATED AT 250 WORDS)


Hypertrophic osteopathy associated with renal pelvis transitional cell carcinoma in a dog.
A 6-year-old male, Belgian shepherd dog was presented with lethargy, oliguria, hematuria, and reluctance to move. The dog developed hypertrophic osteopathy secondary to renal pelvis transitional cell carcinoma. A nephrectomy was performed and after a year, the dog was completely asymptomatic, and no evidence of metastatic disease was present.


Zoophthora radicans (Entomophthorales), a fungal pathogen of Bagrada hilaris and Bactericera cockerelli (Hemiptera: Pentatomidae and Triozidae): Prevalence, pathogenicity, and interplay of environmental influence, morphology, and sequence data on fungal identification.
The exotic bagrada bug or painted bug, Bagrada hilaris, and the native potato/tomato psyllid, Bactericera (=Paratrioza) cockerelli, are key pests of horticulture in western North America. In 2014-2015, adult and juvenile B. hilaris and B. cockerelli killed by fungi in the genus Zoophthora were detected near Saltillo, northeastern Mexico. We report the field prevalence and observations of Zoophthora on these hosts. The morphology and growth characteristics of field-collected specimens and pure in vitro cultures, as well as molecular markers (ITS1 and ITS4) were analyzed to identify these Zoophthora populations. Although there were morphological spore differences detected among field collections from both insect hosts, the fungi causing these mycoses can be identified as the same species (Zoophthora radicans), according to morphometric data from in vitro cultures (where differences observed in field material were attenuated) and sequence data (96-99% identity for ITS1 and 4). These results underscore the plasticity of field collections and in vitro cultures, and the relevance of comprehensive morphological and molecular analysis from cultures under standard conditions. Dose-response bioassays were conducted with one Z. radicans strain against bagrada bug nymphs. Exposure to conidial showers from cultures induced 30-90% mortality. This is the first report of a natural enemy of bagrada bug in Mexico, and the first published report of entomophthoralean fungi naturally attacking bagrada bugs and potato psyllids. Z. radicans should be further investigated as a tool in the biological control of hemipterans.


Protein synthesis studies in skeletal muscle of aging rats. I. Alterations in nitrogen composition and protein synthesis using a crude polyribosome and pH 5 enzyme system.
The effect of aging on rat skeletal muscle protein synthesis was studied using a cell-free system. The activity of crude polyribosomes from hind-limb skeletal muscle was reduced by 40% in aged animals (22 to 24 months) and by 20% in the mature (12 months) animal compared with young (2 month) rats. In a poly Uridylic-acid-directed incorporation system the ribosomes from aged and mature animals showed a decrease in activity. Sucrose density gradient analysis also demonstrated a loss of heavy polyribosomes in aged and mature animals. The pH 5 enzyme fraction from aged and mature animals was less efficient than that from young rats in support of protein synthesis, suggesting a decreased activity of soluble factors. In conclusion, aging leads to a progressive decline in the efficiency of protein synthesis, associated with both the ribosome and soluble fractions of the cell.


A correlation of the endoscopic and pathological changes in subclinical pathology of the horse's larynx.
The larynges of 6 horses were examined endoscopically and the findings correlated with the gross and histological appearance of the intrinsic laryngeal muscles and their nerve supply. In all cases it appeared that the balance between abductor and adductor muscle groups had been lost due to preferential atrophy of individual muscles or groups of muscles. The laryngeal abnormalities recorded were asymmetry of the larynx with asynchronous left sided abduction and fluttering or trembling of the left vocal cord and arytenoid cartilage. It is suggested that these changes represent the early signs of a progressive lesion which may result in left sided laryngeal hemiplegia.


Paid Sick Leave Benefits and Adherence to Recommended Screening Tests Among Male Labor Workers in the United States.
We examined the association between availability of paid sick leave and health care utilization and screenings in male labor workers in the United States, and hypothesize that workers with paid sick leave benefits would be more likely to utilize health services. Using the 2013 to 2016 National Health Interview Survey (NHIS), labor workers (n = 8553), aged 18 to 64 years, were examined. Logistic regression analyses assessed the association between availability of paid sick leave and the use of preventive services. Thirty-five percent indicated paid sick leave benefits. Participants with available sick leave were more likely to have received screenings and to have utilized heath care services or had a dental visit in the past year. Availability of paid sick leave to labor workers may increase their use of preventive health care services. Policy that mandates paid sick leave is warranted.


Spaced Noninvasive Brain Stimulation: Prospects for Inducing Long-Lasting Human Cortical Plasticity.
Neuroplasticity is critical for learning, memory, and recovery of lost function following neurological damage. Noninvasive brain stimulation (NIBS) techniques can induce neuroplastic changes in the human cortex that are behaviorally relevant, raising the exciting possibility that these techniques might be therapeutically beneficial for neurorehabilitation following brain injury. However, the short duration and instability of induced effects currently limits their usefulness. To date, trials investigating the therapeutic value of neuroplasticity-inducing NIBS have used either single or multiple treatment sessions, typically repeated once-daily for 1 to 2 weeks. Although multiple stimulation sessions are presumed to have cumulative effects on neuroplasticity induction, there is little direct scientific evidence to support this "once-daily" approach. In animal models, the repeated application of stimulation protocols spaced using relatively short intervals (typically of the order of minutes) induces long-lasting and stable changes in synaptic efficacy. Likewise, learning through spaced repetition facilitates the establishment of long-term memory. In both cases, the spacing interval is critical in determining the outcome. Emerging evidence in healthy human populations suggests that the within-session spacing of NIBS protocols may be an effective approach for significantly prolonging the duration of induced neuroplastic changes. Similar to findings in the animal and learning literature, the interval at which spaced NIBS is applied seems to be a critical factor influencing the neuroplastic response. In this Point of View article, we propose that to truly exploit the therapeutic opportunities provided by NIBS, future clinical trials should consider the optimal spacing interval for repeated applications.


EXPERIMENTAL STUDIES OF PLEIOTROPY AND EPISTASIS IN ESCHERICHIA COLI. I. VARIATION IN COMPETITIVE FITNESS AMONG MUTANTS RESISTANT TO VIRUS T4.
Mutants selected for novel phenotypes frequently exhibit maladaptive pleiotropic effects. One may reasonably ask whether these effects are properties of the novel phenotypes per se, or whether these effects depend upon the particular genotypes conferring the novel phenotypes. To address this issue, I examined an array of independent mutants, derived from Escherichia coli B, that were all completely resistant to the virus T4. Each resistant mutant had maladaptive pleiotropic effects, but there was highly significant variation in competitive fitness among mutants. The degree of reduction in competitive fitness was strongly associated with cross-resistance to virus T7 and with the inferred position of the mutated gene in a complex metabolic pathway. This variation in competitive fitness permits refinement of the resistant phenotype by selection among resistant genotypes. This mechanism complements refinement of the resistant phenotype by selection for epistatic modifiers of maladaptive pleiotropic effects.


Comparison of drug eluting stents (DESs) and bare metal stents (BMSs) with STEMI: who received BMS in the era of 2nd generation DES?
The aim of this study was to analyze the indications for using bare metal stents (BMSs) in hospitalizations with ST segment elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI). The study cohorts were identified from the National Inpatient Sample database from 2010-2014 using appropriate, International Classification of Diseases, 9th Revision, Clinical Modification, diagnostic and procedural codes. A total of 123,487 hospitalizations were identified for this study. Drug eluting stent (DES) use demonstrated lower in-hospital mortality (5.8% vs. 3.3%, P = < 0.01) and other in-hospital outcomes, thus resulting in lower hospitalization stay. Higher age, black race, greater comorbidity burden, inferior wall myocardial infarction, and the use of mechanical circulatory devices were all associated with BMS use. DES was the preferred standard of care in the era of 2nd generation DES; however, BMSs were used in hospitalizations with high-risk procedures and multiple risk factors.


CLINICAL EFFICACY OF DIETARY MANIPULATION AS COMPLEMENTARY AND ALTERNATIVE MEDICINE THERAPIES ON FEMALE INTERSTITIAL CYSTITIS PATIENTS.
(Objectives) We examined the clinical efficacy of dietary manipulation (DM) for female patients with interstitial cystitis (IC) in stable condition who were followed in our hospital. (Patients and methods) This study included 20 female patients with IC in rather stable condition who were followed at our hospital. In cooperation with the nutrition control team, we created a basic IC diet menu for 1 month (total daily calories, 1,500 kcal; protein, 65 g; fat, 40 g; carbohydrate, 220 g; water, 1,000 ml; salt, 7 g). Data regarding daily food intake and food-related symptoms were collected by detailed interview of each patient conducted by the doctors, nurses, and nutritionists at our hospital. In accordance with the abovementioned nutrition control, we set meal menu to control IC symptoms and advised the patients to reduce the intake of specific food items to the maximum possible extent.The following food items were removed from or restricted in the diet of patients: tomatoes, tomato products, soy, tofu product (seasoning was acceptable), spices (pepper, curry powder, mustard, horseradish, etc.), excessive potassium, citrus, high-acidity-inducing substances (caffeine, carbonate, and citric acid), etc. We evaluated the following factors to determine the efficacy of this diet menu 3 months after the start of the intervention: O'Leary-Sant symptom index (OSSI), O'Leary-Sant problem index (OSPI), urgency visual analogue scale (UVAS) score, (0, no urgency; 10, severe urgency), bladder or pelvic pain VAS (PVAS) score, (0, no pain; 10, worst possible pain), and numerical patient-reported quality of life (QOL) index (0, highly satisfied; 6, highly dissatisfied). (Results) OSSI and OSPI improved from 11.7 to 10.1 (p<0.0001), and from 10.7 to 8.8 (p=0.01), respectively. The UVAS score significantly reduced from 6.4 to 4.8, and the PVAS score significantly improved from 6.5 to 4.8 (p<0.0001). The patient-reported QOL index significantly improved from 5.1 to 3.9 (p<0.0001). (Conclusion) Although repeated notes were taken and patients who were followed up for a long term were consulted on the meal, as appropriate, at the time of visit, DM was found to alleviate the symptoms of IC. DM as a systematic treatment modality for IC should be attempted more aggressively because of its non-invasiveness, without alterations to the other IC treatments.


[Autosomal-dominant osteopetrosis in Chuvashiya].
A genetic epidemiological study of osteopetrosis was carried out in Chuvashiya. The major signs of this disorder are severe anemia developed in the prenatal or early postnatal life, hepatosplenomegaly, and a progressive loss of sight and hearing. Osteopetrosis showed the autosomal recessive inheritance with a somewhat increased proportion of affected patients in families. The lowest estimate of osteopetrosis frequency in Chuvashiya was 0.00026, one affected patient per 3879 newborns. The osteopetrosis gene occurred at a frequency of 0.016; the proportion of heterozygotes was 3.15%. The gene was shown to be evenly distributed throughout the republic.


Naive T-cell depletion related to infection by X4 human immunodeficiency virus type 1 in poor immunological responders to highly active antiretroviral therapy.
The reasons for poor CD4+ T-cell recovery in some human immunodeficiency virus (HIV)-infected subjects despite effective highly active antiretroviral therapy (HAART) remain unclear. We recently reported that CXCR4-using (X4) HIV-1 could be gradually selected in cellular reservoirs during sustained HAART. Because of the differential expression of HIV-1 coreceptors CCR5 and CXCR4 on distinct T-cell subsets, the residual replication of R5 and X4 viruses could have different impacts on T-cell homeostasis during immune reconstitution on HAART. We examined this hypothesis and the mechanisms of CD4+ T-cell restoration by comparing the virological and immunological features of 15 poor and 15 good immunological responders to HAART. We found a high frequency of X4 viruses in the poor immunological responders. But the levels of intrathymic proliferation of the two groups were similar regardless of whether they were infected by R5 or X4 virus. The frequency of recent thymic emigrants in the poor immunological responders was also similar to that found in the good immunological responders, despite their reduced numbers of naïve CD4+ T cells. Our data, rather, suggest that the naïve T-cell compartment is drained by a high rate of mature naïve cell loss in the periphery due to bystander apoptosis or activation-induced differentiation. X4 viruses could play a role in the depletion of naïve T cells in poor immunological responders to HAART by triggering persistent T-cell activation and bystander apoptosis via gp120-CXCR4 interactions.


Brief assessment of male depression in clinical care: Validation of the Male Depression Risk Scale short form in a cross-sectional study of Australian men.
To develop and validate a short form of the Male Depression Risk Scale (MDRS-22) for use in primary care, examining associations with prototypic depression symptoms, psychological distress and suicidality. Cross-sectional study with 8-month follow-up. Community-based. A community sample of younger (n=510; 18-64 years) and older (n=439; 65-93 years) men residing in Australia (M age=58.09 years, SD=17.77) participated in the study. A subset of respondents (n=159 younger men; n=169 older men) provided follow-up data approximately eight months later. Quantitative data were obtained through a survey comprising a range of validated measures, including the MDRS-22, the Patient Health Questionnaire (PHQ-9) and the Kessler Psychological Distress Scale (K10). The MDRS-22 was refined using exploratory and confirmatory factor analysis in line with best practice guidelines. Analysis of variance and generalised linear models were conducted to explore relationships between variables. The short-form MDRS consisted of seven items (MDRS-7) and captured all of the domains in the original tool. Participants with mixed symptoms (PHQ-9 ≥ 10 and MDRS-7 > 5) had significantly higher risk of mental illness (K10 ≥ 25) and current suicidality (PHQ-9 item 9 ≥ 1) than those with exclusively prototypic symptoms (PHQ-9 ≥ 10 and MDRS-7 ≤ 5). Furthermore, the MDRS-7 was shown to be effective at predicting elevated symptoms of depression at follow-up, after controlling for previous depression diagnosis. Findings provide preliminary evidence of the potential utility of the MDRS-7 as a screening tool for externalised and male-type symptoms associated with major depression in men. Field trials of the MDRS-7 in primary care settings may facilitate identification of men at risk of suicide and psychological distress who do not meet cut-off scores for existing measures of major depression symptoms.


Purification and characterization of pea thioredoxin f expressed in Escherichia coli.
The recently cloned cDNA for pea chloroplast thioredoxin f was used to produce, by PCR, a fragment coding for a protein lacking the transit peptide. This cDNA fragment was subcloned into a pET expression vector and used to transform E. coli cells. After induction with IPTG the transformed cells produce the protein, mainly in the soluble fraction of the broken cells. The recombinant thioredoxin f has been purified and used to raise antibodies and analysed for activity. The antibodies appear to be specific towards thioredoxin f and do not recognize other types of thioredoxin. The recombinant protein could activate two chloroplastic enzymes, namely NADP-dependent malate dehydrogenase (NADP-MDH) and fructose 1,6-bisphosphatase (FBPase), both using dithiothreitol as a chemical reductant and in a light-reconstituted/thylakoid assay. Recombinant pea thioredoxin f turned out to be an excellent catalyst for NADP-MDH activation, being the more efficient than a recombinant m-type thioredoxin of Chlamydomonas reinhardtii and the thioredoxin of E. coli. At the concentrations of thioredoxin used in the target enzyme activation assays only the recombinant thioredoxin f activated the FBPase.


Effect of a high phosphorus diet on indicators of renal health in cats.
Objectives High phosphorus intake may further impair renal health in cats with chronic kidney disease (CKD). The hypothesis that a high phosphorus (HP) diet might be nephrotoxic for healthy animals was tested in cats, a species with a high incidence of naturally occurring CKD. Methods Thirteen healthy adult cats were fed a phosphorus excess diet (about five times maintenance requirements), and this HP group was compared with cats on a balanced control diet (CON). The trial lasted for 29 days (10 days of faeces and urine collection). Endogenous creatinine clearance was determined towards the end of the trial. Fresh urine was tested for glucose and proteins. Results Glucosuria and microalbuminuria were observed exclusively in the HP group in 9/13 cats. Creatinine clearance was significantly decreased after feeding HP. In the HP group phosphorus was highly available (apparent digestibility around 60%). Renal phosphorus excretion was significantly increased in the HP group (115 mg/kg body weight/d vs 16 mg/kg body weight/d in the CON group). Conclusions and relevance The intake of a diet with an excessive content of highly available phosphorus may have adverse effects on parameters of kidney function in healthy cats.


Prosthetic Replacement of the Ocular Surface Ecosystem Treatment for Ocular Surface Disease in Pediatric Patients With Stevens-Johnson Syndrome.
To report the outcomes of prosthetic replacement of the ocular surface ecosystem (PROSE) treatment in pediatric patients with chronic ocular surface disease associated with Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN). Retrospective, interventional case series. Patients aged 18 years or younger seen in consultation for PROSE treatment at a single center between January 1992 and December 2016 with a history of SJS/TEN were reviewed. Demographics, etiology of SJS/TEN, age at treatment milestones, best-corrected visual acuity (BCVA) at treatment milestones, and treatment failures were recorded. BCVA at the initial presentation visit was compared to BCVA at the time of PROSE device dispense and at the last recorded visit. Twenty-seven female and 22 male patients were reviewed. Reported etiology was antibiotic (n = 19), antiepileptic (n = 9), antipyretic (n = 9), other (n = 3), and unknown (n = 9). The mean age was 6.4 years at disease onset and 9.3 years at time of initial presentation. The mean duration of follow-up was 5.45 years. The median BCVA at the initial presentation was 0.6 logMAR (20/80 Snellen), and was significantly improved to 0.18 logMAR (20/30 Snellen) at the time a PROSE device was dispensed (P < .0001). The median BCVA at the last recorded visit was significantly improved to 0.18 logMAR (20/30 Snellen, P = .0004). There were 15 patients who failed PROSE treatment (30.6%). PROSE treatment is feasible in over two thirds of pediatric patients with chronic ocular surface disease related to SJS/TEN and results in significant improvement in vision that is durable over a period of many years.


Laser-induced forward transfer based laser bioprinting in biomedical applications.
Bioprinting is an emerging field that utilizes 3D printing technology to fabricate intricate biological structures, including tissues and organs. Among the various promising bioprinting techniques, laser-induced forward transfer (LIFT) stands out by employing a laser to precisely transfer cells or bioinks onto a substrate, enabling the creation of complex 3D architectures with characteristics of high printing precision, enhanced cell viability, and excellent technical adaptability. This technology has found extensive applications in the production of biomolecular microarrays and biological structures, demonstrating significant potential in tissue engineering. This review briefly introduces the experimental setup, bioink ejection mechanisms, and parameters relevant to LIFT bioprinting. Furthermore, it presents a detailed summary of both conventional and cutting-edge applications of LIFT in fabricating biomolecule microarrays and various tissues, such as skin, blood vessels and bone. Additionally, the review addresses the existing challenges in this field and provides corresponding suggestions. By contributing to the ongoing development of this field, this review aims to inspire further research on the utilization of LIFT-based bioprinting in biomedical applications.


A Milestone: Approval of CEUS for Diagnostic Liver Imaging in Adults and Children in the USA.
The approval of microbubbles with the inert gas sulfur hexafluoride (SF6) and a palmitic acid shell (SonoVue(®), Bracco Geneva, CH) for the diagnostic imaging of liver tumors in adults and children by the FDA in the United States represents a milestone for contrast-enhanced ultrasound (CEUS).This warrants a look back at the history of the development of CEUS. The first publications based on echocardiographic observations of right ventricular contrast phenomena caused by tiny air bubbles following i. v. injection of indocyanine green appeared around 1970 1 2 3. A longer period of sporadic publications but no real progress then followed since, in contrast to X-ray methods, ultrasound works quite well without a contrast agent.It is noteworthy that the foundations for further development were primarily laid in Europe. The development and approval (1991) of the contrast agent Echovist(®) by a German contrast manufacturer for echocardiography unsuitable for passing through lungcapillaries 4 5 resulted in the first extracardiac indications, e. g. for detecting retrovesical reflux and tubal patency, in the mid-1980 s 6 7 8. The sensitivity of color Doppler was not able to compensate for the lack of an ultrasound contrast agent compared to CT with its obligatory contrast administration.Studies of SHU 508 - microbubbles of air moderately stabilized with galactose and palmitic acid - began in 1990 9 10 11 12 13 14 15 and the contrast agent was then introduced in 1995 in Germany as Levovist(®). The most important publications by Blomley, Cosgrove, Leen, and Albrecht are named here on a representative basis 16 17 18 19 20.SHU 508 along with other US contrast agents provided impressive proof of the superiority of CEUS for the diagnosis of liver metastases. However, practical application remained complicated and required skill and technical know-how because of a lack of suitable software on US units 21 22 23 24 25. The monograph regarding the use of contrast agent in the liver by Wermke and Gaßmann is impressive but unfortunately only available in German 26. In addition to being applied in the heart and the liver, CEUS was first used in transcranial applications 27 and in vessels 28, the kidneys 29, and the breast 30. Measurements at transit times were also of particular interest 31. It was difficult to convince ultrasound device manufacturers of the need to adapt US units to US contrast agents and not vice versa.The breakthrough came with low MI phase contrast inversion and the introduction of SonoVue(®) in many European countries in 2001. This more stable US contrast agent is easy to use and is becoming indispensable in diagnostic imaging of the liver 32 33 34 35 36 37 38 39 40. Studies have shown its excellent tolerability 41 and diagnostic reliability comparable to that of MDCT and MRI in the liver 42 43. Today it would be unimaginable to diagnose liver tumors without CEUS 44. This also applies to very small lesions 45 46.EFSUMB published the first CEUS guidelines in 2004 47 which have since been reissued and divided into hepatic 48 and extrahepatic applications 49. The first recommendations regarding quantitative assessment have also been published 50.The increasing scientific interest in CEUS is evident based on the greater number of PubMed hits for Echovist(®) (ca. 130), Levovist(®) (ca. 500) and SonoVue(®) (ca. 1500) as well as on the fact that publications regarding CEUS comprise almost 20 % of UiM/EJU articles in the last 10 years. The number of CEUS articles in UiM/EJU continues to be high 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 71 72 73 74 75.In the clinical reality, CEUS has been able to become established alongside CT and MRI according to the saying "better is the enemy of good" 76 as the method of choice after B-mode ultrasound in the evaluation of liver tumor malignancy in Germany, where the technically challenging method is promoted. In the case of unclear CT and MRI findings, CEUS performed by an experienced examiner/clinician often provides the solution, particularly in the case of small lesions, and is the last resort before US-guided biopsy 45 46. However, there is a lack of competent CEUS examiners and Germany continues to be the world champion of X-ray examinations with no noticeable reverse trend. In almost every doctor's office and hospital, ultrasound costs are by far not fully covered, resulting in an extremely high frequency of CT use with CT being available to everyone regardless of insurance status.The USA is now in the starting position for CEUS. It will be exciting to see how the method will develop there. The FDA's decision to approve sulfur hexafluoride (Lumason(®) = SonoVue(®)) should be considered against the background of the radiation exposure caused by CT examinations and the fact that MRI using gadolinium-containing contrast agents is no longer considered noninvasive because of nephrogenic systemic fibrosis (NSF) and the accumulation of the agent in the cerebrum. An essential point of the campaign regarding the avoidance of diagnostic radiation exposure triggered in the USA by the publications of Brenner et al. 77 78 was that the agent was approved for use in the liver even for children 79 80 - still off label in Europe - without additional comprehensive studies due to the available scientific results and the very low side effects profile of Lumason(®) (= SonoVue(®)). It is admittedly unclear why other indications (except the heart which has been approved since 2014) are excluded even though the microbubbles as a pure blood pool contrast agent can be diagnostically used in the entire vascular system and bed of all organs. To our knowledge, there is no such restriction on the approval of X-ray contrast agents.Like echocardiography and emergency ultrasound, CEUS began in Europe but will probably only establish its final diagnostic value as a "reimport".This is a major opportunity to permanently define the role of Ultrasound as a highly valuable, patient-centered imaging method in the German health care system.This may prompt some of our international readers to reflect upon the role of CEUS in their own countries.


Ocular HSV-1 latency, reactivation and recurrent disease.
Ocular infection with HSV-1 continues to be a serious clinical problem despite the availability of effective antivirals. Primary infection with HSV-1 can involve ocular and adenaxial sites and can manifest as blepharitis, conjunctivitis, or corneal epithelial keratitis. After initial ocular infection, HSV-1 can establish latent infection in the trigeminal ganglia for the lifetime of the host. During latency, the viral genome is retained in the neuron without producing viral proteins. However, abundant transcription occurs at the region encoding the latency-associated transcript, which may play significant roles in the maintenance of latency as well as neuronal reactivation. Many host and viral factors are involved in HSV-1 reactivation from latency. HSV-1 DNA is shed into tears and saliva of most adults, but in most cases this does not result in lesions. Recurrent disease occurs as HSV-1 is carried by anterograde transport to the original site of infection, or any other site innervated by the latently infected ganglia, and can reinfect the ocular tissues. Recurrent corneal disease can lead to corneal scarring, thinning, stromal opacity and neovascularization and, eventually, blindness. In spite of intensive antiviral and anti-inflammatory therapy, a significant percentage of patients do not respond to chemotherapy for herpetic necrotizing stromal keratitis. Therefore, the development of therapies that would reduce asymptomatic viral shedding and lower the risks of recurrent disease and transmission of the virus is key to decreasing the morbidity of ocular herpetic disease. This review will highlight basic HSV-1 virology, and will compare the animal models of latency, reactivation, and recurrent ocular disease to the current clinical data.


Polymeric monolith column composited with multiwalled carbon nanotubes-β-cyclodextrin for the selective extraction of psoralen and isopsoralen.
A polymeric column that contains multiwalled carbon nanotubes-β-cyclodextrin composite was developed. The composite was wrapped into the poly(butyl methacrylate-ethylene dimethacrylate) monolith column (0.76 mm id and 10 cm in length). The column was then applied for the online solid-phase microextraction of psoralen and isopsoralen from Fructus Psoraleae. Following microextraction, the coumarins were quantified by high-performance liquid chromatography with C18 separation column and UV detection. The effects of sample flow rate, sample volume, and pH value were optimized. The method showed low limits of detection (20 pg/mL, S/N = 3) for both psoralen and isopsoralen. Finally the method was successfully applied to the determination of psoralen and isopsoralen in spiked herb extracts and rat plasma where it gave recoveries that ranged between 93.2 and 102.1%. The empty hydrophobic cavities of β-cyclodextrin and the hydrophobicity of multiwalled carbon nanotubes provided specific extraction capability for psoralen and isopsoralen.


Nanomechanical properties of alginate-recovered chondrocyte matrices for cartilage regeneration.
Tissue-engineered cartilage constructs designed for in-vivo applications intuitively should mimic the mechanical properties of native cartilage. The objective of the present work was to characterize the nanomechanical properties of alginate-recovered chondrocyte matrices as a function of ex-vivo incubation time. Chondrocytes isolated from the articular cartilage of the mature bovine metacarpophalangeal joints were cultured with alginate hydrogel to allow for the formation of extracellular matrices. The recovered chondral constructs after 2, 4, 8, and 12 weeks of ex-vivo incubation were analysed using nanoindentation with atomic force microscopy to determine their mechanical properties. Chondral constructs had average Young's moduli of 123 +/- 22 kPa, 174 +/- 31 kPa, 373 +/- 40 kPa, and 564 +/- 79 kPa after incubation for 2, 4, 8, and 12 weeks respectively, indicating the gradual attainment of mechanical stiffness. This escalating trend of micromechanical properties as a function of increasing ex-vivo incubation time suggests that chondral constructs via a tissue-engineering approach are capable of elaborating extracellular matrices and increase mechanical stiffness. The relationship between Young's modulus and incubation time of the chondral constructs is useful in the design and fabrication of tissue-engineered cartilage constructs.


Cardiovascular complications of acute cocaine poisoning: a clinical case report.
We present a case of an accidental cocaine overdose with various cardiovascular and neurological complications and ECG features of Brugada syndrome. It is imperative that clinicians know how to recognise and manage the symptoms of cocaine overdose because of the exceedingly rapid progression of the 'cocaine reaction' to a fatal outcome.


[The relationship between TSH response to TRH and GH response to dopaminergic agents in patients with acromegaly].
The role of dopaminergic agents (DA) in the regulation of growth hormone (GH) secretion was investigated in patients with untreated acromegaly. TRH (0.5 mg iv), bromocriptine (Br) (2.5 mg orally) or L-Dopa (500 mg orally) loading tests were performed, and serum levels of TSH, GH and prolactin (PRL) were measured. Patients were defined as responders to TRH when peak TSH level after TRH test was higher than 5 microU/ml. Br or L-Dopa was considered to be effective when serum GH or PRL levels were suppressed more than 50% of the basal value. The patients were classified into large adenoma group with suprasellar extension or cisternal herniation (L group, n = 7) and intrasellar small adenoma group (S group, n = 11) which was further divided into TRH responder (Sr group, n = 4) and TRH non-responder with suppressed TSH (Ss group, n = 7). Br was effective in 7 or 100% of 7 patients in the Ss group but only in one or 25% of 4 patients in the Sr group. Br was also effective in 5 or 71% of 7 patients in the L group, although most of them were responders to TRH. Percent inhibition of serum GH levels by Br was significantly higher in the Ss group (82.3 +/- 12.3%, p less than 0.001) and in the L group (64.7 +/- 20.5%, p less than 0.05) compared with that in the Sr group (29.3 +/- 21.6%). Suppression of serum GH level by L-Dopa was also observed in the Ss group. In contrast to the difference in the response of GH, serum PRL level was equally suppressed by Br or L-Dopa in each group. Suppression of TSH by administration of exogenous T4 had no effect on the GH suppression effect of Br in the Sr group. Considering the dual effects of DA to enhance growth hormone-releasing hormone (GHRH) secretion in the hypothalamus and to suppress GH secretion in the pituitary gland, these findings suggest that the paradoxical effect of DA to suppress serum GH level is observed when the hypothalamo-pituitary axis is disturbed mechanically by large adenoma in the L group or functionally in the Ss group probably due to enhanced secretion of somatostatin which suppresses TSH secretion and impairs the effect of GHRH.


Intraocular adenoviral vector-mediated gene transfer in proliferative retinopathies.
The purpose of this study was to compare levels and patterns of expression of reporter genes achieved with an E1-deleted and partially E3-deleted type 5 adenoviral (Ad) vector after intravitreous or subretinal injections, or after intravitreous injections in mouse eyes with proliferative retinopathies. Ad vectors containing reporter gene constructs were injected into the vitreous cavity or subretinal space of wild-type mice or mice with proliferative retinopathies, and quantitative comparisons were made of expression of transgenes. In normal eyes, peak Ad-mediated expression of luciferase, driven by a cytomegalovirus (CMV) promoter, occurred after injection of 10(7) to 10(8) viral particles and was 10 times greater after subretinal injections than after intravitreous injections. Intravitreous injections of Ad containing beta-galactosidase (LacZ) expression constructs (AdLacZ.10) resulted in strong expression of LacZ in epithelial cells of the iris and ciliary body and focal expression in the retina. Subretinal injections of AdLacZ.10 resulted in strong expression in RPE cells. Expression of LacZ after intravitreous injection of AdLacZ.10 was significantly greater in mice with two types of proliferative retinopathy (ischemic retinopathy or transgenic mice with retina-specific expression of platelet-derived growth factor (PDGF)-BB or PDGF-AB) than littermate control animals. Cells within epiretinal membranes and activated Müller cells were preferentially transduced in eyes with proliferative retinopathy. These data suggest that although higher intraocular expression levels can be achieved after subretinal injection of adenoviral vectors, intravitreous injections provide good transduction of cells lining the vitreous cavity. Compared with normal eyes, eyes with proliferative retinopathy showed increased transduction, which occurred preferentially in cells participating in the disease process. Intravitreous injection of adenoviral vectors containing appropriate expression constructs may provide a good strategy for acute treatment of proliferative retinopathies, such as diabetic retinopathy and proliferative vitreoretinopathy.


A follow-up study of infants with intracranial hemorrhage at full-term.
To determine physical and cognitive outcomes of full-term infants who suffered intracranial hemorrhage (ICH) at birth. A retrospective hospital-based, follow-up study of infants treated in London, Ontario between 1985 and 1996. Follow-up was conducted by telephone interviews and clinic visits. Outcome was measured according to physical and cognitive scales. Perinatal risk factors and hemorrhage characteristics were correlated with final outcome. For this study 66 infants with ICH were identified, of which seven died during the first week of life. We obtained follow-up in all but ten cases (median = 3-years; range 1.0 to 10.9 years). Overall, 57% of infants had no physical or cognitive deficits at follow-up. Death occurred most frequently among those with primarily subarachnoid hemorrhage (19%) and the most favorable outcomes occurred among those with subdural hemorrhage (80% had no disability). In univariate models, thrombocytopenia (platelet count < or = 70 x 10(9)/L), increasing overall hemorrhage severity, frontal location and spontaneous vaginal delivery as opposed to forceps-assisted delivery increased risk for poor outcome. In multivariate models, all these factors tended towards increased risk, but only thrombocytopenia remained significant for physical disability (OR = 7.6; 95% CI = 1.02 - 56.6); thrombocytopenia was borderline significant in similar models for cognitive disability (OR = 4.6; 95% CI = 0.9 - 23.9). Although forceps-assisted delivery may contribute to ICH occurrence, our study found better outcomes among these infants than those who had ICH following a spontaneous vaginal delivery. Hemorrhage in the frontal lobe was the most disabling hemorrhage location and if multiple compartments were involved, disability was also more likely to occur. However, in this report we found that the factor that was most likely to contribute to poor outcome was thrombocytopenia and this remained important in multivariate analysis.


Suffocation From Balloon Bronchoplasty.
Negative pressure pulmonary edema is a well-described complication of upper airway obstruction. However, the simultaneous occurrence of blood-stained secretions and petechial tracheobronchial hemorrhage are rarely recognized and a potential complication of transient intentional occlusion of the airways. We described a case of "hemorrhagic bronchial mucosa syndrome" and asymptomatic blood-tinged pulmonary edema after balloon bronchoplasty for a concentric tracheal stenosis using a flexible bronchoscopy. This was characterized by interval appearance of diffuse petechial tracheobronchial bleeding and a persistent blood-tinged alveolar effluent after sustained occlusion of the airway. The simultaneous occurrence of both phenomena in this patient suggests different degrees of injury in a common pathogenic spectrum. We postulate that sustained, complete occlusion of the airway produces variable degrees of mechanical disruption of the bronchial and alveolar vasculature that lead to the development of negative pressure pulmonary edema and tracheobronchial hemorrhage. In this case, the syndrome was self-limited and without major consequences but highlights an unrecognized potential complication of balloon bronchoplasty.


Use of hybridot assay to screen for BK and JC polyomaviruses in non-immunosuppressed patients.
Urine samples from 50 patients attending a genitourinary outpatient clinic and from 13 renal allograft recipients were investigated for evidence of infection with human BK and JC polyomaviruses using cytology and a new DNA hybridot assay. Forty four per cent of samples from the renal allograft recipients were positive by cytology and 75% by DNA hybridisation, indicating that hybridot assay is more sensitive than cytological screening. BK and JC viral DNA was found in 20% of the patients attending the genitourinary clinic, showing infection with BK virus and JC virus in a group of patients with clinical conditions not normally associated with immunological deficiency-a finding that has not been reported before.


Bilayer-forming synthetic lipids: drugs or carriers?
Since their introduction as bilayer-forming synthetic compounds in the eighties, dioctadecyldimethylammonium (DODA) and dihexadecylphosphate (DHP) salts have found many uses in strategic, applied areas. In particular, DODA chloride or bromide vesicles interacted with negatively charged prokaryotic or eukaryotic cells, yielding adsorption isotherms of high affinity for the cell surface, causing cell adhesion and flocculation, changing the cell surface charge from negative to positive, and causing loss of cell viability over DODA concentration ranges that depended on the cell type being tested. This work reviews data on DODA effects on cell viability (bacteria, fungus and cultured mammalian cells) to propose DODA salts as effective anti-microbial agents that exhibit differential cytotoxicity in vitro and, therefore, deserve to be investigated as potential drugs. The full utility of these inexpensive synthetic bilayers and bilayer fragments able to act as drugs themselves and, simultaneously, as drug, gene or vaccine carriers remains hitherto unexplored.


[Transitory episode of laughter as the initial symptom of an ischemic stroke].
Pathological laughter occurs in pseudobulbar paralysis, in psychiatric disorders and as a sign of convulsions (gelastic crisis). An extremely rare form is the "fou rire prodromique' a pathological episode of laughter preceding a stroke. The pathogenesis is unknown and classically differentiated from gelastic crises. "Fou rire prodromique' has been described in subcortical ischaemic or haemorrhagic strokes, not in cortical strokes. We describe a patient with an ischaemic cerebrovascular accident due to embolism of the left Sylvian artery. The clinical picture started with a short episode of pathological laughter which preceded sensitive aphasia and weakness of the right limbs. We suggest that in the case described it is impossible to differentiate between the "fou rire prodromique' and a gelastic crisis as a first sign of an embolic cerebrovascular accident.


Microencapsulation and Stimuli-Responsive Controlled Release of Particles Using Water-in-Air Powders.
In this work, we report a facile, one-step method to encapsulate hydrophilic particles (HP) (micro- or nanosize) using water-in-air powders. Hydrophobic silica nanoparticles were mixed with an aqueous phase containing HP in the presence of air under high shear, resulting in the self-assembly of silica nanoparticles on water droplets to make water-in-air powders with HP encapsulated in the aqueous phase within the silica shell. The encapsulated HP can be released on the basis of an external stimulus such as adding an external aqueous phase of a certain pH or a surfactant solution that alters the wettability of the encapsulating silica nanoparticles. A contact angle study was performed using surface-hydrophobized glass slides, which acted as a proxy for hydrophobic silica nanoparticles, to investigate the effect of these stimuli on surface hydrophobicity. Such encapsulation and a stimuli-responsive controlled release system has promising potential in subsurface petroleum engineering such as the delayed swelling of particles for conformance control and delayed acid stimulation.


Genetic variants associated with persistent central obesity and the metabolic syndrome in a 12-year longitudinal study.
Central obesity predisposes to various cardiometabolic diseases and is a key component of the metabolic syndrome (MetS). We have previously demonstrated that three obesity-susceptible single nucleotide polymorphisms (SNPs), rs10938397 (GNPDA2), rs8050136 (FTO) and rs17782313 (MC4R), were associated with obesity and waist circumference in cross-sectional studies in the Chinese population. In this study, we investigate whether these SNPs could also predict the persistence of central obesity and MetS in subjects from the Hong Kong Cardiovascular Risk Factors Prevalence Study (CRISPS) cohort. We genotyped these SNPs in i) 354 subjects with and 994 subjects without central obesity at both baseline and a 12-year follow-up, ii) 2214 subjects (816 cases and 1398 controls) in an MetS cross-sectional case-control study and iii) 225 subjects with and 1221 subjects without MetS at both baseline and the 12-year follow-up. Both FTO rs8050136 (P(age, sex-adjusted)=0.019; odds ratio (OR) (95% confidence intervals (CI)): 1.35 (1.05, 1.73)) and GNPDA2 rs10938397 (P(age, sex-adjusted)=3 × 10(-3); OR (95% CI): 1.34 (1.11, 1.63)) were significantly associated with persistent central obesity. GNPDA2 rs10938397 was also significantly associated with MetS (P(age, sex-adjusted)=0.011, OR (95% CI): 1.20 (1.04, 1.38)) in the case-control study. However, none of these SNPs showed an individual association with persistent MetS. In the combined genetic risk analyses for persistent central obesity and persistent MetS, the combined genetic risk score of the three SNPs showed an OR of 1.25 (95% CI: 1.10, 1.42; P(age, sex-adjusted)=4.92 × 10(-3)) and 1.19 (95% CI: 1.03, 1.38; P(age, sex-adjusted)=0.019) for each additional risk allele respectively. This study demonstrated that FTO and GNPDA2 variants predicted persistent central obesity in the Chinese population, further supporting their importance as obesity-susceptible genes.


[Surgeons not interested in smoking?]
Smoking worsens surgical treatment outcomes: Smokers have more complications, spent longer time at postoperative wards / intensive care units, have longer overall hospitalization time after surgery, healing process is slower. In addition to the deterioration of patient comfort, it is also an economic burden for the health care unit. The surgery results are significantly better especially if the patient stops smoking at least 3-6 weeks before the surgery - but every day without cigarettes is a benefit.Except of acute cases, the preoperative preparation should include recommendation to quit smoking as long as possible before elective surgery and to offer treatment of tobacco dependence to the patient.


Classification of Maxillofacial Morphology by Artificial Intelligence Using Cephalometric Analysis Measurements.
The characteristics of maxillofacial morphology play a major role in orthodontic diagnosis and treatment planning. While Sassouni's classification scheme outlines different categories of maxillofacial morphology, there is no standardized approach to assigning these classifications to patients. This study aimed to create an artificial intelligence (AI) model that uses cephalometric analysis measurements to accurately classify maxillofacial morphology, allowing for the standardization of maxillofacial morphology classification. This study used the initial cephalograms of 220 patients aged 18 years or older. Three orthodontists classified the maxillofacial morphologies of 220 patients using eight measurements as the accurate classification. Using these eight cephalometric measurement points and the subject's gender as input features, a random forest classifier from the Python sci-kit learning package was trained and tested with a k-fold split of five to determine orthodontic classification; distinct models were created for horizontal-only, vertical-only, and combined maxillofacial morphology classification. The accuracy of the combined facial classification was 0.823 ± 0.060; for anteroposterior-only classification, the accuracy was 0.986 ± 0.011; and for the vertical-only classification, the accuracy was 0.850 ± 0.037. ANB angle had the greatest feature importance at 0.3519. The AI model created in this study accurately classified maxillofacial morphology, but it can be further improved with more learning data input.


Identification of a unique transgenic mouse line that develops megabladder, obstructive uropathy, and renal dysfunction.
Urinary tract malformations, obstructive uropathy, and hypoplasia/dysplasia are extremely important in terms of pediatric health care costs, with end-stage renal failure in children estimated to cost >$15 billion annually in the United States alone. Even so, little is known regarding the mechanisms that control these processes. Identified was a unique mutant mouse model that develops in utero megabladder, resulting in variable hydroureteronephrosis and chronic renal failure secondary to obstructive uropathy. These animals, designated mgb for megabladder, possess a primary defect in bladder smooth muscle development that is apparent by embryonic day 15. The mgb mouse represents an excellent model for the study of normal and pathogenic bladder development, including the postnatal progression of chronic renal failure that results from the development of in utero obstructive uropathy.


Viral Prototypes for Pandemic Preparedness: The Road Ahead.
The coronavirus disease 2019 (COVID-19) pandemic demonstrated how rapidly vaccines and monoclonal antibodies (mAbs) could be deployed when the field is prepared to respond to a novel virus, serving as proof of concept that the prototype pathogen approach is feasible. This success was built upon decades of foundational research, including the characterization of protective antigens and coronavirus immunity leading to the development and validation of a generalizable vaccine approach for multiple coronaviruses. For other virus families of pandemic concern, the field is less prepared. The articles in this special issue have highlighted research gaps that need to be addressed to accelerate the development of effective vaccines and mAbs, to identify generalizable vaccine and mAb strategies, and to increase preparedness against other pandemic threats. Successful implementation of the prototype pathogen approach will require a systematic, multidisciplinary, coordinated approach with expertise and crosstalk among researchers of different virus families.


Antiprotozoal activities of organic extracts from French marine seaweeds.
Marine macrophytes contain a variety of biologically active compounds, some reported to have antiprotozoal activity in vitro. As a part of a screening program to search for new natural antiprotozoals, we screened hydroalcoholic and ethyl acetate extracts of 20 species of seaweeds from three phyla (Rhodophyta, Heterokontophyta and Chlorophyta), sampled along the Normandy (France) coast. We tested them in vitro against the protozoa responsible for three major endemic parasitic diseases: Plasmodium falciparum, Leishmania donovani and Trypanosoma cruzi. The selectivity of the extracts was also evaluated by testing on a mammalian cell line (L6 cells). Ethyl acetate extracts were more active than hydroalcoholic ones. Activity against T. cruzi and L. donovani was non-existent to average, but almost half the extracts showed good activity against P. falciparum. The ethyl acetate extract of Mastocarpus stellatus showed the best antiplasmodial activity as well as the best selectivity index (IC(50) = 2.8 μg/mL; SI > 30). Interestingly, a red algae species, which shares phylogenetic origins with P. falciparum, showed the best antiplasmodial activity. This study is the first to report comparative antiprotozoal activity of French marine algae. Some of the species studied here have not previously been biologically evaluated.


Stereological-ultrastructural study of pancreatic B cells in metabolic alkalosis.
The secretion of insulin in response to glucose and the changes in the B cell at the ultrastructural level were studied in rat pancreas perfused at pH 7.4 and 7.8 with different concentrations of glucose. Raising the extracellular pH from 7.4 to 7.8 significantly inhibits glucose-induced insulin secretion. Coincidentally, morphometric studies showed significant evidences of low secretory activity in B cells from pancreas submitted to high glucose stimulation under alkalosis, namely lower number of emiocytotic figures and microtubules as well as a decrease in the volume density of the granular endoplasmic reticulum and the Golgi complex. On the other hand, a significant increment in the number of images of granulolysis was also demonstrated. These secretory and ultrastructural results confirm the inhibitory effect of pH 7.8 upon B cell secretory activity induced by glucose. Moreover, they lend further support to the role of intracellular hormone degradation as a regulator of B cell insulin content.


A Cost-Effectiveness Analysis of Plasmodium falciparum Malaria Elimination in Hainan Province, 2002-2012.
In Hainan Province, China, great achievements in elimination of falciparum malaria have been made since 2010. There have been no locally acquired falciparum malaria cases since that time. The cost-effectiveness of elimination of falciparum malaria has been analyzed in Hainan Province. There were 4,422 falciparum malaria cases reported from 2002 to 2012, more cases occurred in males than in females. From 2002 to 2012, a total of 98.5 disability-adjusted life years (DALYs) were reported because of falciparum malaria. Populations in the age ranges of 15-25 and 30-44 years had higher incidences and DALYs than other age groups. From 2002 to 2012, malaria-related costs for salaries of staff, funds from the provincial government, national government, and the GFATM were US$3.02, US$2.24, US$1.44, and US$5.08 million, respectively. An estimated 9,504 falciparum malaria cases were averted during the period 2003-2012. The estimated cost per falciparum malaria case averted was US$116.5. The falciparum malaria elimination program in Hainan was highly effective and successful. However, funding for maintenance is still needed because of imported cases.