Aminophylline Dosage In Asthma Exacerbations in Children: A Systematic Review.
Adequate asthma treatment of childhood exacerbations with IV aminophylline depends on appropriate dosage. Recommendations to aim for a target therapeutic range may be inappropriate as serum concentrations correlate poorly with clinical improvement. This review aims to evaluate the evidence for the optimum dosage strategy of intravenous aminophylline in children suffering an exacerbation of asthma. A systematic review comparing dosage regimens of intravenous aminophylline in children suffering an exacerbation of asthma. Primary outcomes were time until resolution of symptoms, mortality and need for mechanical ventilation. Secondary outcomes were date until discharge criteria are met, actual discharge and adverse effects. CENTRAL, CINAHL, MEDLINE and Web of Science. Search performed in March 2016. Studies using intravenous aminophylline in children with an acute exacerbation of asthma which reported the dosage and clinical outcomes. 14 RCTs were included. There is a poor relationship between the dosage administered to children and symptom resolution, length of stay or need for mechanical ventilation. This study is limited due to its use of indirect evidence. The currently recommended dosage regimens may not represent the optimum safety and efficacy of intravenous aminophylline. There is a need to develop the evidence base correlating dosage with patient centered clinical outcomes, to improve prescribing practices.


Prolactin modulation of immune and inflammatory responses.
Prolactin (PRL), a pituitary peptide hormone, is known to regulate diverse physiological functions via its effects on cellular processes such as proliferation, differentiation, and cell survival. All these activities are mediated by the PRL receptor (PRL-R), a member of the hematopoietin cytokine receptor superfamily. To understand PRL-dependent mitogenic signaling in T cells, we cloned PRL. PRL-R, one mediator of PRL signaling, signal transducer and activator of transcription (Stat) 5b, and a panel of PRL-inducible immediate early-response genes from T cells. We are employing one of these PRL-inducible genes, the transcription factor interferon regulatory factor-1 (IRF-1), a multifunctional immune regulator gene, as a tool to understand how PRL modulates T-cell proliferative responses. In investigating regulatory events along the PRL-R/Janus activating kinase (JAK)/Stat/IRF-1 signaling pathway, we show that Stat factors can activate as well as inhibit IRF-1 promoter activity and that cross talk between Stat and nuclear factor (NF)kappaB signaling pathways also regulates IRF-1 expression. In understanding how signaling pathways cross talk at the IRF-1 promoter, we obtained insights into how PRL can modulate immune and inflammatory responses. These findings have much broader implications, not only for cells in the immune system but also for other PRL-responsive cells and tissues.


IL5RA polymorphisms, smoking and eczema in Japanese women: the Kyushu Okinawa Maternal and Child Health Study.
The present case-control study examined the relationship between IL5RA SNPs and eczema in young adult Japanese women. Cases and control subjects were selected from pregnant women who participated in the baseline survey of the Kyushu Okinawa Maternal and Child Health Study, which is an ongoing prebirth cohort study. Cases comprised 188 women with eczema in the previous 12 months as defined according to the criteria of the International Study of Asthma and Allergies in Childhood (ISAAC), regardless of the presence of a doctor's diagnosis of atopic eczema. Control subjects comprised 1130 women without eczema as defined according to the ISAAC criteria who also had not been diagnosed with atopic eczema by a doctor. Compared with the AA genotype of IL5RA SNP rs17881144, the AT genotype, but not the TT genotype, was significantly associated with a decreased risk of eczema. The ATTAGA haplotype and the GTAGCA haplotype of rs17882210, rs3804797, rs334809, rs9831572, rs6771148 and rs17881144 were significantly associated with an increased risk of eczema. In contrast, the GCTGCA haplotype was significantly related to a decreased risk of eczema. Multiplicative interactions between IL5RA SNPs rs334809 and rs17881144 and smoking with respect to eczema were marginally significant (P = 0.07 and 0.07, respectively). This is the first study to show significant associations between IL5RA SNP rs17881144, the ATTAGA haplotype, the GTAGCA haplotype, and the GCTGCA haplotype and eczema. Smoking may modify the relationships between SNPs rs334809 and rs17881144 and eczema.


Characteristics associated with mobility limitation in long-term care residents with dementia.
This article describes the prevalence, assessment, and treatment of, as well as characteristics associated with, mobility limitation in 343 residents with dementia in 45 assisted living facilities and nursing homes. Overall, 89% of residents had some degree of mobility limitation. Mobility limitation was associated with fewer behavioral symptoms, low fluid intake, professional assessment, and professional and informal treatment.


Carbon-Silicon Bond Formation in the Synthesis of Benzylic Silanes.
Sterically encumbered organosilanes can be difficult to synthesize with conventional, strongly basic reagents; the harsh reaction conditions are often low yielding and not suitable for many functional groups. As an alternative to the typical anionic strategies to construct silanes, the coupling of benzylic halides and arylhalosilanes with sonication has been identified as a high yielding and general strategy to access bulky and functionalized benzylic silanes. This new methodology provides a solution for the synthesis of families of bulky benzylic silanes for study in catalysis and other areas of chemical synthesis.


A simplified clinical prediction rule for prognosticating independent walking after spinal cord injury: a prospective study from a Canadian multicenter spinal cord injury registry.
Traumatic spinal cord injury (SCI) is a debilitating condition with limited treatment options for neurologic or functional recovery. The ability to predict the prognosis of walking post injury with emerging prediction models could aid in rehabilitation strategies and reintegration into the community. To revalidate an existing clinical prediction model for independent ambulation (van Middendorp et al., 2011) using acute and long-term post-injury follow-up data, and to investigatethe accuracy of a simplified model using prospectively collected data from a Canadian multicenter SCI database, the Rick Hansen Spinal Cord Injury Registry (RHSCIR). Prospective cohort study. The analysis cohort consisted of 278 adult individuals with traumatic SCI enrolled in the RHSCIR for whom complete neurologic examination data and Functional Independence Measure (FIM) outcome data were available. The FIM locomotor score was used to assess independent walking ability (defined as modified or complete independence in walk or combined walk and wheelchair modality) at 1-year follow-up for each participant. A logistic regression (LR) model based on age and four neurologic variables was applied to our cohort of 278 RHSCIR participants. Additionally, a simplified LR model was created. The Hosmer-Lemeshow goodness of fit test was used to check if the predictive model is applicable to our data set. The performance of the model was verified by calculating the area under the receiver operating characteristic curve (AUC). The accuracy of the model was tested using a cross-validation technique. This study was supported by a grant from The Ottawa Hospital Academic Medical Organization ($50,000 over 2 years). The RHSCIR is sponsored by the Rick Hansen Institute and is supported by funding from Health Canada, Western Economic Diversification Canada, and the provincial governments of Alberta, British Columbia, Manitoba, and Ontario. ET and JP report receiving grants from the Rick Hansen Institute (approximately $60,000 and $30,000 per year, respectively). DMR reports receiving remuneration for consulting services provided to Palladian Health, LLC and Pacira Pharmaceuticals, Inc ($20,000-$30,000 annually), although neither relationship presents a potential conflict of interest with the submitted work. KEH received a grant for involvement in the present study from the Government of Canada as part of the Canada Summer Jobs Program ($3,000). JP reports receiving an educational grant from Medtronic Canada outside of the submitted work ($75,000 annually). TM reports receiving educational fellowship support from AO Spine, AO Trauma, and Medtronic; however, none of these relationships are financial in nature. All remaining authors have no conflicts of interest to disclose. The fitted prediction model generated 85% overall classification accuracy, 79% sensitivity, and 90% specificity. The prediction model was able to accurately classify independent walking ability (AUC 0.889, 95% confidence interval [CI] 0.846-0.933, p<.001) compared with the existing prediction model, despite the use of a different outcome measure (FIM vs. Spinal Cord Independence Measure) to qualify walking ability. A simplified, three-variable LR model based on age and two neurologic variables had an overall classification accuracy of 84%, with 76% sensitivity and 90% specificity, demonstrating comparable accuracy with its five-variable prediction model counterpart. The AUC was 0.866 (95% CI 0.816-0.916, p<.01), only marginally less than that of the existing prediction model. A simplified predictive model with similar accuracy to a more complex model for predicting independent walking was created, which improves utility in a clinical setting. Such models will allow clinicians to better predict the prognosis of ambulation in individuals who have sustained a traumatic SCI.


Interferon-alpha enhances neutrophil respiratory burst responses to stimulation with influenza A virus and FMLP.
Despite increasing therapeutic use of interferon (IFN)-alpha, its effects on human neutrophil function are not well characterized. In vitro preincubation of neutrophils with recombinant IFN-alpha and -gamma, tumor necrosis factor (TNF), or granulocyte-macrophage colony-stimulating factor (GM-CSF) enhanced neutrophil respiratory burst responses to stimulation with influenza A virus (IAV) and FMLP. The enhancing effects of IFNs were more subtle and required more prolonged incubation than those of TNF and GM-CSF. TNF and GM-CSF enhanced neutrophil binding of IAV and neutrophil intracellular calcium and membrane depolarization responses to IAV or FMLP stimulation, while IFNs did not. Inhibitors of neutrophil tyrosine kinase activation and protein synthesis blocked IFN-alpha-induced enhancement of respiratory burst responses. In addition to its other well-characterized effects, IFN-alpha may protect against viral infection indirectly by promoting neutrophil respiratory burst responses.


Syntheses of C12,N13 heterocyclic bridged fused indenopyrrolocarbazoles.
Tandem alkylation/cyclization of indenopyrrolocarbazole 4a, a C12 carbon analogue of indolocarbazole K252c, was carried out by general solid-phase and solution-phase methods. Alkylation of fused pyrroloindenylcarbazole 4a derivatives with appropriate monoacetals of diketones afforded the corresponding C12-substituted acetal alcohols. Acid-catalyzed cyclization of these adducts yielded C12,N13-bridged tetrahydrofuran, pyran, and dioxane compounds 10-13.


Rapid Detection of Gadolinium-Based Contrast Agents in Urine with a Chelated Europium Luminescent Probe.
Gadolinium-based contrast agents are widely used in magnetic resonance imaging procedures to enhance image contrast. Despite their ubiquitous use in clinical settings, gadolinium is not an innocuous element, as suggested by several disorders associated with its use. Therefore, novel analytical technologies capable of tracking contrast agent excretion through urine are necessary for optimizing patient safety after imaging procedures. Here, we describe an assay to detect and quantify contrast agents in urine based on the luminescence quenching of a metal chelate probe, Eu3+-3,4,3-LI(1,2-HOPO), which only requires 10 min incubation before measurement. Gadolinium-based contrast agents prevent the formation of the Eu3+-3,4,3-LI(1,2-HOPO) complex, subsequently decreasing the luminescence of the assay solution. Three commercial contrast agents, Magnevist, Multihance, and Omniscan, were used to demonstrate the analytical concept in synthetic human urine, and subsequent quantification of mouse urine samples. To the best of our knowledge, this is the first assay capable of detecting and quantifying gadolinium-based contrast agents in urine without sample preparation or digestion.


Identification of immune-related biomarkers in peripheral blood of schizophrenia using bioinformatic methods and machine learning algorithms.
Schizophrenia is a group of severe neurodevelopmental disorders. Identification of peripheral diagnostic biomarkers is an effective approach to improving diagnosis of schizophrenia. In this study, four datasets of schizophrenia patients' blood or serum samples were downloaded from the GEO database and merged and de-batched for the analyses of differentially expressed genes (DEGs) and weighted gene co-expression network analysis (WCGNA). The WGCNA analysis showed that the cyan module, among 9 modules, was significantly related to schizophrenia, which subsequently yielded 317 schizophrenia-related key genes by comparing with the DEGs. The enrichment analyses on these key genes indicated a strong correlation with immune-related processes. The CIBERSORT algorithm was adopted to analyze immune cell infiltration, which revealed differences in eosinophils, M0 macrophages, resting mast cells, and gamma delta T cells. Furthermore, by comparing with the immune genes obtained from online databases, 95 immune-related key genes for schizophrenia were screened out. Moreover, machine learning algorithms including Random Forest, LASSO, and SVM-RFE were used to further screen immune-related hub genes of schizophrenia. Finally, CLIC3 was found as an immune-related hub gene of schizophrenia by the three machine learning algorithms. A schizophrenia rat model was established to validate CLIC3 expression and found that CLIC3 levels were reduced in the model rat plasma and brains in a brain-regional dependent manner, but can be reversed by an antipsychotic drug risperidone. In conclusion, using various bioinformatic and biological methods, this study found an immune-related hub gene of schizophrenia - CLIC3 that might be a potential diagnostic biomarker and therapeutic target for schizophrenia.


Do children born before and after adequate birth intervals do better at school?
There are un-verified reports that adequate birth intervals are associated with better physical and mental development children in the school age. The objective of this study was to investigate the effect of preceding and succeeding birth intervals on the school performance of 9-10-year-old male Saudi children. This is a cross-sectional study of the performance of Saudi school children in relation to the length of the birth interval before and after the birth of the index child, conducted in Khobar, Eastern Saudi Arabia. A two-stage randomized sampling technique was adopted. Data were collected on scholastic achievements. Data was analyzed using SPSS software using chi-square, linear and logistic regression analysis. Children born after birth intervals longer than 31 months who scored grade A in the year of study, and the year before, were found to be significantly more than children born after intervals less than 17 months. There are more above-average students amongst those born after an interval of 31 months or more compared to those born after a shorter birth interval of 17 months or less according to teachers. Significantly more children born before birth interval longer than 35 months did better at school than children born before interval shorter intervals (less than 19 months). Logistic regression analysis showed that the possibility of classifying the index child as average or above in school performance increased as the succeeding birth interval increased. Results of the study verified previous findings that children born after adequate birth intervals do better at school. The study revealed that the succeeding birth interval in relation to school performance is more significant than the preceding birth interval. Apart from mother's education and breastfeeding, no other variables were found to be significantly related to the birth interval. These findings would enable us to advise couples that by observing a birth interval of around 3 years, their children are likely to do better at school.


Knocking down gene expression with dendritic vectors.
The aim of this review is to provide the reader with an overview on the potential of dendritic polymers in the antisense delivery technology. Special emphasis has been placed on the different types of dendritic structures that have been reported and the modifications performed to increase their efficacy and safety. Therefore the advances made in their chemistry and how it has been adapted to meet the specific requirements of the antisense delivery technology are reviewed and discussed.


Pain descriptors and determinants of pain sensitivity in knee osteoarthritis: a community-based cross-sectional study.
The aim was to explore pain characteristics in individuals with knee OA (KOA), to compare pain sensitivity across individuals with KOA, individuals with chronic back pain (CBP) and pain-free individuals (NP) and to examine the relationship between clinical characteristics and pain sensitivity and between pain characteristics and pain sensitivity in KOA. We carried out a cross-sectional, community-based online survey. Two data sets were combined, consisting of Dutch individuals ≥40 years of age, who were experiencing chronic knee pain (KOA, n = 445), chronic back pain (CBP, n = 504) or no pain (NP, n = 256). Demographic and clinical characteristics, global health, physical activity/exercise and pain characteristics, including intensity, spreading, duration, quality (short-form McGill pain questionnaire) and sensitivity (pain sensitivity questionnaire), were assessed. Differences between (sub)groups were examined using analyses of variance or χ2 tests. Regression analyses were performed to examine determinants of pain sensitivity in the KOA group. The quality of pain was most commonly described as aching, tender and tiring-exhausting. Overall, the KOA group had higher levels of pain sensitivity compared with the NP group, but lower levels than the CBP group. Univariately, pain intensity, its variability and spreading, global health, exercise and having co-morbidities were weakly related to pain sensitivity (standardized β: 0.12-0.27). Symptom duration was not related to pain sensitivity. Older age, higher levels of continuous pain, lower levels of global health, and exercise contributed uniquely, albeit modestly, to pain sensitivity (P < 0.05). Continuous pain, such as aching and tenderness, in combination with decreased physical activity might be indicative for a subgroup of individuals at risk for pain sensitivity and, ultimately, poor treatment outcomes.


Lifestyle Advice and Self-Care Integral to Acupuncture Treatment for Patients with Chronic Neck Pain: Secondary Analysis of Outcomes Within a Randomized Controlled Trial.
Lifestyle advice is widely considered as an integral component of acupuncture treatment. However, it is unclear whether lifestyle advice and related self-care are important for sustaining benefit over the longer term. In a novel secondary analysis of trial data, this paper explores the nature and impact of acupuncture-related diagnosis, and associated lifestyle advice and self-care, in patients with chronic neck pain. In a three-arm, randomized, controlled multicenter trial with 12 months of follow-up, a total of 517 patients with chronic neck pain were randomized in equal proportions to acupuncture, Alexander technique, or usual care alone. For each acupuncture patient, practitioners reported treatment components that included an acupuncture-related diagnosis and provision of associated lifestyle advice. Patients reported at baseline, 3, 6, and 12 months on variables related to treatment, which included aspects of self-care, self-efficacy, and lifestyle advice acted upon, as well as pain and disability scores. Congruence between practitioner advice and patient take-up was assessed using chi-squared test. Impact of lifestyle advice and self-efficacy on outcome was evaluated using regression models. Among patients randomized to acupuncture, the most common diagnostic framework involved the Zang-Fu syndromes for 139/160 (87%) patients. Lifestyle advice was provided by practitioners to 134/160 (84%) of patients, most commonly related to exercise, relaxation, diet, rest, and work. Significant congruence with patient take-up was found for diet, rest, and work. Moreover, patients in the acupuncture group improved their ability to use what they had learnt and increased their self-efficacy. In turn, these characteristics were associated with significant reductions in pain and disability scores at 12 months. Acupuncture-related lifestyle advice helped patients improve the way they live and care for themselves and enhanced self-efficacy and ability to use what they had learnt. These changes were associated with reductions in pain and disability at 12 months.


Nerve guidance channels as drug delivery vehicles.
Nerve guidance channels (NGCs) have been shown to facilitate regeneration after transection injury to the peripheral nerve or spinal cord. Various therapeutic molecules, including neurotrophic factors, have improved regeneration and functional recovery after injury when combined with NGCs; however, their impact has not been maximized partly due to the lack of an appropriate drug delivery system. To address this limitation, nerve growth factor (NGF) was incorporated into NGCs of poly(2-hydroxyethyl methacrylate-co-methyl methacrylate), P(HEMA-co-MMA). The NGCs were synthesized by a liquid-liquid centrifugal casting process and three different methods of protein incorporation were compared in terms of protein distribution and NGF release profile: (1) NGF was encapsulated (with BSA) in biodegradable poly(d,l-lactide-co-glycolide) 85/15 microspheres, which were combined with a PHEMA polymerization formulation and coated on the inside of pre-formed NGCs by a second liquid-liquid centrifugal casting technique; (2) pre-formed NGCs were imbibed with a solution of NGF/BSA and (3) NGF/BSA alone was combined with a PHEMA formulation and coated on the inside of pre-formed NGCs by a second liquid-liquid centrifugal casting technique. Using a fluorescently labelled model protein, the distribution of proteins in NGCs prepared with a coating of either protein-loaded microspheres or protein alone was found to be confined to the inner PHEMA layer. Sustained release of NGF was achieved from NGCs with either NGF-loaded microspheres or NGF alone incorporated into the inner layer, but not from channels imbibed with NGF. By day 28, NGCs with microspheres released a total of 220 pg NGF/cm of channel whereas those NGCs imbibed with NGF released 1040 pg/cm and those NGCs with NGF incorporated directly in a PHEMA layer released 8624 pg/cm. The release of NGF from NGCs with microspheres was limited by a slow-degrading microsphere formulation and by the maximum amount of microspheres that could be incorporated into the NGCs structure. Notwithstanding, the liquid-liquid centrifugal casting process is promising for localized and controlled release of multiple factors that are key to tissue regeneration.


Dimensionality of organizational justice in a call center context.
Summary.-Employees in three call centers were surveyed about their perceptions of organizational justice. Four factors were measured: distributive justice, procedural justice, interpersonal justice, and informational justice. Structural equation modeling was employed to test whether a two-, three-, or four-factor model best fit the call center data. A three-factor model of distributive, procedural, and informational justice provided the best fit to these data. The three-factor model that showed the best fit does not conform to any of the more traditional models identified in the organizational justice literature. This implies that the context in which organizational justice is measured may play a role in identifying which justice factors are relevant to employees. Findings add to the empirical evidence on the dimensionality of organizational justice and imply that dimensionality of organizational justice is more context-dependent than previously thought.


AML1-ETO positive AML: first report from India.
Translocation (8;21) is associated with few typical morphological features and favorable prognosis. All patients of AML and MDS with increased blasts (N = 35) according to FAB criteria, presenting (between Jan 2004 to June 2005) to the Department of Hematology, AIIMS were studied. RT-PCR was done for the AML1-ETO fusion transcript in all cases. Overall incidence of AML1-ETO was 28.57% and no correlation was found between AML1-ETO positivity and clinical or hematological parameters except for a direct correlation with absolute blast count (ABC) (a lower ABC in the AML1-ETO positive cases). Interestingly, 1/3 MDS cases were positive for the same fusion transcript and thus, it appears worthwhile to look for AML1-ETO in all cases of MDS with increased blasts. Objective morphological evaluation using a scoring system based on morphological features was not helpful in predicting positivity for AML1-ETO. The effect of this translocation on long-term survival could not be determined by the present study.


Constitutive production of interleukin-6 and tumor necrosis factor-alpha from spontaneously proliferating T cells in patients with human T-cell lymphotropic virus type-I/II.
The human T-cell lymphotropic viruses (HTLV) type I and type II are capable of inducing a variety of cellular genes, including many of the cytokines that regulate cell proliferation. To determine if the spontaneous proliferation of peripheral blood mononuclear cells from patients infected with HTLV-I and HTLV-II was related to coordinate expression of cytokines, we analyzed the levels of interleukin-1 beta (IL-1 beta), IL-2, IL-3, IL-4, IL-6, tumor necrosis factor-alpha (TNF-alpha) and interferon-tau (IFN-tau) in culture supernatants derived from spontaneously proliferating cells. Significantly elevated levels of IL-6 and TNF-alpha were present in culture supernatants from HTLV-I/II-infected individuals when compared with normal controls (P less than .01). Kinetic experiments showed that both IL-6 and TNF-alpha were elevated by day 5. None of the other cytokines (IL-1 beta, IL-2, IL-3, IL-4, and IFN-tau) were detectable in any of the culture. These data suggest that release of IL-6 and TNF-alpha may regulate lymphocyte proliferation in HTLV-I/II-infected individuals.


Pathological Validity of Using Near-infrared Fluorescence Imaging for Securing Surgical Margins During Liver Resection.
This study investigated the use of near-infrared fluorescent imaging for securing safe margins during liver resection. This study included 125 patients who underwent liver tumor resection in 2014-2018. Indocyanine green testing was performed 2-14 days before surgery. Histopathological specimens of hepatocellular carcinoma (HCC) and colorectal liver metastasis (CRLM) were evaluated using fluorescent microscopy. Fluorescence microscopy identified signals in 26/53 (49.0%) and 36/72 (50%) cases of HCC and CRLM, respectively. HCC demonstrated total, partial, rim, and combined fluorescence patterns; CRLM uniformly demonstrated rim fluorescence. Although rim fluorescence was seen in both HCC and CRLM, no malignancy was confirmed pathologically in the peritumoral area demonstrating fluorescence. The median widths of fluorescence from the tumor edge in HCC and CRLM were 1227.5 μm and 1608 μm, respectively, with no significant difference. Near-infrared fluorescent imaging can reliably detect safe surgical margins intraoperatively during liver resection.


[Culture-independent digging of cellulases and genes from natural environments].
There is a great diversity for cellulolytic microbes in nature and the strategies they use to digest cellulose. In addition to the cultured cellulolytic microbes, there are still a great number of microbes being not readily culturable in natural environments, which may represent great potential for identifying novel cellulases and their encoding genes. The rise of metagenomics and metaproteomics provides essential technologic tools to dig up these resources and significant progress has been made so far. This review gives an insight into some relative results that have arisen from the meta-genomic or proteomic analysis of definitive uncultured microbe communities. Their potential role in elucidating the process and mechanisms of cellulose degradation in natural environment from the point of "community system microbiology" is also discussed.


Benign Rabbit Calicivirus in New Zealand.
The Czech v351 strain of rabbit hemorrhagic disease virus (RHDV1) is used in Australia and New Zealand as a biological control agent for rabbits, which are important and damaging introduced vertebrate pests in these countries. However, nonpathogenic rabbit caliciviruses (RCVs) can provide partial immunological cross-protection against lethal RHDV infection and thus interfere with effective rabbit biocontrol. Antibodies that cross-reacted against RHDV antigens were found in wild rabbits before the release of RHDV1 in New Zealand in 1997, suggesting that nonpathogenic RCVs were already present in New Zealand. The aim of this study was to confirm the presence of nonpathogenic RCV in New Zealand and describe its geographical distribution. RCV and RHDV antibody assays were used to screen serum samples from 350 wild rabbits from 14 locations in New Zealand. The serological survey indicated that both RCV and RHDV are widespread in New Zealand wild rabbits, with antibodies detected in 10 out of 14 and 12 out of 14 populations, respectively. Two closely related RCV strains were identified in the duodenal tissue from a New Zealand wild rabbit (RCV Gore-425A and RCV Gore-425B). Both variants are most closely related to Australian RCV strains, but with 88% nucleotide identity, they are genetically distinct. Phylogenetic analysis revealed that the New Zealand RCV strains fall within the genetic diversity of the Australian RCV isolates, indicating a relatively recent movement of RCVs between Australia and New Zealand.IMPORTANCE Wild rabbits are important and damaging introduced vertebrate pests in Australia and New Zealand. Although RHDV1 is used as a biological control agent, some nonpathogenic RCVs can provide partial immunological cross-protection against lethal RHDV infection and thus interfere with its effectiveness for rabbit control. The presence of nonpathogenic RCVs in New Zealand wild rabbits has been long hypothesized, but earlier attempts to isolate a New Zealand RCV strain have been unsuccessful. Therefore, it is important to determine if such nonpathogenic viruses exist in New Zealand rabbits, especially considering the proposed introduction of new RHDV strains into New Zealand as biocontrols.


Two-Photon Microscopy (TPM) and Fluorescence Lifetime Imaging Microscopy (FLIM) of Retinal Pigment Epithelium (RPE) of Mice In Vivo.
Retinal pigment epithelium (RPE), a monolayer of epithelial cells located between the neural retina and the choroid, plays a significant role in the maintenance of retinal function. Its in vivo imaging is still technically challenging in human eye. With the mouse eye, there is a possibility to look into the RPE through the sclera using two-photon microscopy (TPM). TPM is a two photon-excited nonlinear fluorescence microscopy that enables the observation of deep tissues up to several hundred micrometers. Since the simultaneous absorption of two photons occurs only at the focal plane, spatial resolution of the TPM is quite high, such that pinhole as used in a confocal microscope is not necessary. TPM enables observation of autofluorescence at the cellular level, and thus may provide new insights into the fluorescent molecules in/around RPE cells.The combination of TPM with fluorescence lifetime imaging microscopy (FLIM) may expand the breadth of information about cells and tissues. Fluorescence lifetime is a fluorophore-specific property, which is independent of fluorescence intensity and changes with the alteration of molecular environment. FLIM may have therefore the potentials to distinguish different fluorophores and to indicate the change in the environment of a fluorophore. Some energy metabolisms-related intracellular fluorophores, such as NADH (nicotinamide adenine dinucleotide) and FAD (flavin adenine dinucleotide), show characteristic fluorescence lifetimes that shift under different molecular environments, and thus their fluorescence lifetime have been used to indicate cell energy metabolic states. These nonlabeling imaging methods offer us the opportunity to engage in the study of the RPE in vivo as well as in vitro both in morphological as well as metabolic aspects.


Hypofibrinolytic phenotype in Tsumura Suzuki Obese Diabetes (TSOD) mice unrelated to hyperglycemia.
Obesity and diabetes mellitus are associated with increased risk of arterial thrombosis and venous thromboembolism. Tsumura Suzuki Obese Diabetes (TSOD) mice are useful models for elucidating the molecular mechanisms of these diseases. We investigated normoglycemic [Ng]-TSOD mice with a metabolic abnormality that was accompanied by a coagulative and fibrinolytic state with a phenotype that distinctly differed from that of standard TSOD mice. As in TSOD mice, plasminogen activation inhibitor-1 (PAI-1) that inhibits fibrinolysis was substantially augmented in Ng-TSOD mice, suggesting that they are hypofibrinolytic. However, blood clotting parameters were within the normal range in Ng-TSOD mice. These findings indicated that Ng-TSOD mice are novel models with a hypofibrinolytic phenotype that is not associated with hyperglycemia.


Compositions of royal jelly II. Organic acid glycosides and sterols of the royal jelly of honeybees (Apis mellifera).
Two organic acid glycosides (1, 2) and 16 sterols were isolated from the royal jelly of honeybees (Apis mellifera). The former two were monoglucosides of 10-hydroxy-2E-decenoic and 10-hydroxydecanoic acids. They are the first examples of glycosides isolated from royal jelly. The latter 16 were sterols mainly composed of 28 or 29 carbons. Among them, four compounds were new isofucosterol derivatives, and their structures were characterized as (24Z)-stigmasta-5,24(28)-dien-3beta-ol-7-one (3), (24Z)-stigmasta-5,24(28)-diene-3beta,7beta-diol (4), (24Z)-stigmasta-5,24(28)-diene-3beta,7alpha-diol (5), and (24Z)-stigmast-24(28)-ene-3beta,5alpha,6beta-triol (6) on the basis of various NMR spectroscopic data.


A micro-CT evaluation of the performance of rotary and reciprocating single-file systems in shaping ability of curved root canals.
To compare the shaping ability of different single-file systems in the preparation of mesial curved canals of mandibular molars using micro-CT technology. Fifteen mesial roots of mandibular molars with two independent and curved canals (n = 30) were selected, scanned at a resolution of 26.7 μm anatomically matched, and distributed into three groups (n = 10), according to the preparation system: WaveOne 25.08, Reciproc 25.08, and OneShape 25.06. A final micro-CT scanning was performed, data sets were registered with their respective counterparts, and compared regarding the three-dimensional (volume, surface area, and structure model index - SMI) and two-dimensional (perimeter, area, roundness, major and minor diameters) parameters, as well as, canal transportation, using ANOVA and post hoc Tukey tests (α = 5%). Overall, no difference was observed between groups regarding area, perimeter, volume, surface area, and canal transportation (p > 0.05). Within group, no canal transportation was significantly higherobserved in the apical third (0.10 ± 0.05 mm) compared to coronal (0.08±0.040 mm) and middle (0.07 ± 0.03 mm) thirds (p < 0.05). Structure model index (SMI) was statistically higher after preparation with OneShape instrument (0.36 ± 0.26) compared to other systems (p < 0.05). Within the parameters of this study, similar shaping ability was observed in the preparation of mesial curved root canals of mandibular molars with Reciproc, OneShape and WaveOne systems.


[Research progress in magnetic thermosensitive polymeric microspheres].
As a new type of functional material, magnetic thermosensitive polymeric microspheres offer high potential application in various fields, particularly in bioengineering and biomedical fields. In this review, the development of synthesis and application of magnetic thermosensitive polymeric microspheres was summarized, and the research trends were also discussed.


Development of a Gold Nanoparticle-Based Immunochromatographic Strip for Rapid Detection of Porcine Circovirus Type 2.
Porcine circovirus type 2 (PCV2) is an important swine infectious pathogen that seriously threatens the global swine industry. PCV2 Cap protein is the only structural and the main immunogenic protein constituting the viral capsid. In this study, a gold nanoparticle-based immunochromatographic strip with high sensitivity and specificity was developed which could be used for rapid detection of PCV2 virions or Cap protein in research. The visual detection limit of the strip was 103.18 50% tissue culture infective does (TCID50)/mL for PCV2, and 2.03 μg/mL for PCV2 Cap protein. No cross-reactivity was observed with the PCV1 and PCV3 Cap proteins and other common swine pathogens such as porcine reproductive and respiratory syndrome virus, classical swine fever virus, pseudorabies virus, porcine epidemic diarrhea virus, porcine parvovirus, and swine influenza virus. The repeatability of the strip was good. The stability of the strip was perfect for 12 months in a dry state at room temperature. Visual results could be obtained within 5 min by simply inserting the strip into the diluted sample. The strip is a time-saving, labor-saving, and reliable tool for testing of PCV2 virions or Cap protein in research. The idea of this study might open a new perspective for the application of the strip. IMPORTANCE Porcine circovirus type 2 (PCV2) Cap protein is the only structural and the main immunogenic protein constituting the viral capsid. Although many methods can be used to identify PCV2 or PCV2 Cap protein in vaccine research, they usually require high workload and time. The developed strip can specifically detect PCV2 virions or Cap protein, and visual qualitative results can be obtained within 5 min by simply diluting the sample and inserting the strip into the sample. The final value of the strip is providing a simple and time-saving method for real-time monitoring of PCV2 antigen in vaccine research with reliable results, such as the different stages of PCV2 Cap protein expression and purification, as well as the different stages of PCV2 reproduction and purification.


Two genes encoding Arabidopsis halleri MTP1 metal transport proteins co-segregate with zinc tolerance and account for high MTP1 transcript levels.
The zinc hyperaccumulator plant Arabidopsis halleri is able to naturally accumulate 100-fold higher leaf zinc concentrations when compared with non-accumulator species such as the closely related A. lyrata and A. thaliana, without showing toxicity symptoms. A novel member of the cation diffusion facilitator (CDF) protein family, an A. halleri metal tolerance protein 1 (MTP1), and the homologous A. thaliana Zn transporter (ZAT)/AtMTP1 metal-specifically complement the zinc hypersensitivity of a Saccharomyces cerevisiae zrc1 cot1 mutant strain. A fusion of the AhMTP1 protein to green fluorescent protein (GFP) localizes to the vacuolar membrane of A. thaliana protoplasts. When compared with A. lyrata and A. thaliana, the total MTP1 transcript levels are substantially higher in the leaves and upregulated upon exposure to high zinc concentrations in the roots of A. halleri. The high MTP1 transcript levels in A. halleri can be primarily attributed to two genetically unlinked genomic AhMTP1 gene copies. The two corresponding loci co-segregate with zinc tolerance in the back-cross 1 generation of a cross between the zinc-tolerant species A. halleri and the zinc-sensitive species A. lyrata. In contrast, a third MTP1 gene in the genome of A. halleri generates only minor amounts of MTP1 transcripts and does not co-segregate with zinc tolerance. Our data suggests that zinc tolerance in A. halleri involves an expanded copy number of an ancestral MTP1 gene, encoding functional proteins that mediate the detoxification of zinc in the cell vacuole. At the transcript level, MTP1 gene copies of A. halleri are regulated differentially and in response to changes in zinc supply.


[Acute purulent Listeria seelingeri meningitis in an immunocompetent adult].
Within the genus Listeria, the species L. monocytogenes most frequently causes disease in animals and humans. L. Seeligeri, a species recently described, has been considered experimentally nonpathogenic so far. The authors report the first case of human infection in a previously healthy adult presenting with acute purulent meningitis due to L. seeligeri. The patient recovered promptly after a course of ampicillin and gentamicin, but developed severe neurological sequelae (epilepsy, hydrocephalus) one year after the acute episode. The pathogenic properties of this isolate were investigated in two experimental animal models and the results were as follows. The clinical isolate of L. seeligeri was able to colonize the spleens of adult mice without bacterial multiplication, in contrast to the type strain of L. seeligeri (no colonization) and to a L. monocytogenes strain (colonization and multiplication). Previous infection of adult mice with the clinical L. seeligeri isolate protected moderately against spleen colonization and bacterial multiplication after challenge with L. monocytogenes. No lethal effect was observed after inoculation of suckling mice with the clinical L. seeligeri isolate, in contrast to L. monocytogenes strains. Thus, L. seeligeri, previously described as experimentally nonpathogenic for mice, may in fact be a heterogeneous species regarding its pathogenicity, and include strains that may cause life-threatening diseases in humans.


Quantum polyamorphism in compressed distinguishable helium-4.
We demonstrate that two amorphous solid states can exist in 4He consisting of distinguishable Boltzmann atoms under compressed conditions. The isothermal compression of normal or supercritical fluid 4He was conducted at 3-25 K using the isobaric-isothermal path integral centroid molecular dynamics simulation. The compression of fluid first produced the low-dispersion amorphous (LDA) state possessing modest extension of atomic necklaces. Further isothermal compression up to the order of 10 kbar to 1 Mbar or an isobaric cooling of LDA induced the transition to the high-dispersion amorphous (HDA) state. The HDA was characterized by long quantum wavelengths of atoms extended over several Angstroms and the promotion of atomic residual diffusion. They were related to the quantum tunneling of atoms bestriding the potential saddle points in this glass. The change in pressure or temperature induced the LDA-HDA transition reversibly with hysteresis, while it resembled the coil-globule transition of classical polymers. The HDA had lower kinetic and higher Gibbs free energies than the LDA at close temperature. The HDA was absent at T ≥ 13 K, while the LDA-HDA transition pressure significantly decreased with lowering temperature. The LDA and HDA correspond to the trapped and tunneling regimes proposed by Markland et al. [J. Chem. Phys. 136, 074511 (2012)], respectively. The same reentrant behavior as they found was observed for the expansion factor of the quantum wavelength as well as for atomic diffusivity.


Knockout of the two evolutionarily conserved peroxisomal 3-ketoacyl-CoA thiolases in Arabidopsis recapitulates the abnormal inflorescence meristem 1 phenotype.
A specific function for peroxisomal β-oxidation in inflorescence development in Arabidopsis thaliana is suggested by the mutation of the abnormal inflorescence meristem 1 gene, which encodes one of two peroxisomal multifunctional proteins. Therefore, it should be possible to identify other β-oxidation mutants that recapitulate the aim1 phenotype. Three genes encode peroxisomal 3-ketoacyl-CoA thiolase (KAT) in Arabidopsis. KAT2 and KAT5 are present throughout angiosperms whereas KAT1 is a Brassicaceae-specific duplication of KAT2 expressed at low levels in Arabidopsis. KAT2 plays a dominant role in all known aspects of peroxisomal β-oxidation, including that of fatty acids, pro-auxins, jasmonate precursor oxophytodienoic acid, and trans-cinnamic acid. The functions of KAT1 and KAT5 are unknown. Since KAT5 is conserved throughout vascular plants and expressed strongly in flowers, kat2 kat5 double mutants were generated. These were slow growing, had abnormally branched inflorescences, and ectopic organ growth. They made viable pollen, but produced no seed indicating that infertility was due to defective gynaecium function. These phenotypes are strikingly similar to those of aim1. KAT5 in the Brassicaceae encodes both cytosolic and peroxisomal proteins and kat2 kat5 defects could be complemented by the re-introduction of peroxisomal (but not cytosolic) KAT5. It is concluded that peroxisomal KAT2 and KAT5 have partially redundant functions and operate downstream of AIM1 to provide β-oxidation functions essential for inflorescence development and fertility.


Evaluation of periprostatic neurovascular fibers before and after radical prostatectomy by means of 1.5 T MRI diffusion tensor imaging.
To evaluate if diffusion tensor imaging (DTI) is able to detect changes of periprostatic neurovascular fibers (PNFs) before and after radical prostatectomy (RP), and if these changes are related to post-surgical urinary incontinence and erectile dysfunction. 22 patients (mean age 62.6 years) with biopsy-proven prostate cancer underwent 1.5 T DTI before and after RP. The number, fractional anisotropy (FA) values and length of PNFs before and after RP were compared using Student's t-test. Each patient filled out two questionnaires before and after RP, one for the evaluation of urinary continence (ICIQ-SF) and one for the evaluation of erectile function (IIEF-5). The ratios of the number, FA values and length of PNFs before and after RP (DTI B-A RATIOs) and the ratios between the scores obtained before and after RP for both ICIQ-SF and IIEF-2 (ICIQ-SF B-A RATIOs and IIEF-2 B-A RATIOs) were calculated to perform the Kendall's τ-test between them. There was a statistically significant decrease of the number of PNFs after RP at base, midgland, and apex (p < 0.01) and of FA values at midgland (p < 0.05), with positive statistically significant correlation between the DTI B-A RATIOs of the number of PNFs and IIEF-2 B-A RATIOs (p < 0.05, ρ = 0.47). DTI was able to detect that the decrease of the number of the PNFs after RP was statistically related to the post-surgical erectile dysfunction (p < 0.05). Advances in knowledge: This work demonstrates that: (1) 1.5 T MRI DTI is able to detect the decrease of the number and of the FA of PNFs after prostatectomy; (2) the decrease of the number of PNFs after prostatectomy is related with the post-surgical erectile dysfunction; (3) 1.5 T MRI DTI has demonstrated to be a reproducible technique in detecting the changes of the PNFs induced by RP, with high interobserver agreement.


Post-traumatic Sacral Epidermoid Cyst Masquerading as Chordoma on Imaging: A Case Report.
Intradural spinal epidermoid cysts are rare, benign lesions either acquired from trauma, surgery, lumbar puncture or arise as congenital lesions, particularly associated with spinal dysraphism. Epidermoid cyst arising from the spine with expansile destruction of vertebrae has not been reported yet in the literature. We report a case of 36-years male presented with history of fall 8 years back with progressive symptoms of lower back pain, weakness of left lower limb and bladder/bowel incontinence. Computed tomography revealed large lytic expansile, midline sacral vertebral lesion with soft tissue component and multiple calcific foci. Magnetic resonance imaging demonstrated large non-enhancing heterogeneous mass showing restricted diffusion on diffusion weighted images. The patient underwent biopsy confirming the diagnosis of an epidermoid cyst. The possibility of an epidermoid tumor should be kept in the differential diagnosis in patients presenting with post-traumatic sacral mass.


Ubiquitin hubs in oncogenic networks.
Ubiquitin is an important regulator of diverse biological functions including cell cycle progression, apoptosis, cell proliferation, and DNA damage responses. Crucial proteins involved in the control of such diverse functions are modified by ubiquitin and are frequently altered during oncogenesis. Here, we define such proteins as key-nodes regulated by ubiquitin, discuss examples of their oncogenic aberrations, and indicate how pharmacologic manipulation of such molecular hubs might improve anticancer therapy.


RV to PA conduits: impact of transcatheter pulmonary valve replacement in adults - a national register study.
The use of a conduit is an established surgical method for reconstruction of the right ventricular outflow tract in congenital heart disease; however, its limited durability makes reintervention almost inevitable. We studied the trends in new implantation, reoperation, and transcatheter pulmonary valve replacement (TPVR) from a Swedish national perspective. The Swedish registry of congenital heart disease (SWEDCON) was used to collect data. From 2000-2014, there was an increase in adult patients with conduits from 122 to 536. There were 60 surgical conduit replacements, 40 TPVRs and 176 new conduit implantations in the study period. Perioperative mortality was <1%. The yearly number of new implantations and reoperations both doubled over the study period. Patients with new implantations were older (mean age, 36 years) compared with the reoperation and TPVR groups (mean age, 26 years) with the majority of patients having tetralogy of Fallot. The majority of conduit reinterventions were surgical also after the introduction of TPVR in 2007, with no significant difference regarding diagnosis, gender, age, or previous number or longevity of conduits. The number of adults with conduits increased steadily with most conduit-related operations being new implantations in patients with tetralogy of Fallot. Surgical conduit replacements increased significantly and represented the majority of conduit reinterventions after the introduction of TPVR, indicating that TPVR is not used for the majority of patients with conduit failure. Diagnosis, gender, age, or previous number or longevity of conduits had no impact on choosing surgical replacement vs. TPVR.


Cloning and molecular characterization of the delta6-desaturase from two echium plant species: production of GLA by heterologous expression in yeast and tobacco.
The synthesis of GLA (delta6,9,12-1-8:3) is carried out in a number of plant taxa by introducing a double bond at the delta6 position of its precursor, linoleic acid (delta9,12-18:2), through a reaction catalyzed by a delta6-desaturase enzyme. We have cloned genes encoding the delta6-desaturase (D6DES) from two different Macaronesian Echium species, E. pitardii and E. gentianoides (Boraginaceae), which are characterized by the accumulation of high amounts of GLA in their seeds. The Echium D6DES genes encode proteins of 438 amino acids bearing the prototypical cytochrome b(5) domain at the N-terminus. Cladistic analysis of desaturases from higher plants groups the Echium D6DES proteins together with other delta6-desaturases in a different cluster from that of the highly related delta8-desaturases. Expression analysis carried out in E. pitardii shows a positive correlation between the D6DES transcript level and GLA accumulation in different tissues of the plant. Although a ubiquitous expression in all organs is observed, the transcript is particularly abundant in developing fruits, whereas a much lower level is present in mature leaves. Functional characterization of the D6DES gene from E. gentianoides has been achieved by heterologous expression in tobacco plants and in the yeast Saccharomyces cerevisiae. In both cases, overexpression of the gene led to the synthesis of GLA. Biotechnological application of these results can be envisaged as an initial step toward the generation of transgenic oleaginous plants producing GLA.


Must colposuspension be associated with sacropexy to prevent postoperative urinary incontinence?
This prospective, randomised study investigated whether a prophylactic procedure, performed during colposacropexy for prolapse repair, prevents ex novo postoperative incontinence. Sixty-six consecutive continent patients with advanced prolapse were randomised into two groups: group A underwent sacropexy combined with a Burch colposuspension; no anti-incontinence procedure was performed in group B patients. Work-up included clinical assessment (Halfway System and International Continence Society [ICS] classification for prolapse and Ingelman Sunderberg scale for incontinence), the Urogenital Distress Inventory and Impact Incontinence Quality of Life questionnaires, urogynaecologic ultrasound scans, and complete urodynamic testing that included the urethral pressure profile and Valsalva leak point pressure with reduced prolapse. Check-ups were done at 3, 6, 12 mo postoperatively and then yearly. Mean follow-up time was 39.5 mo. The mean age (+/- standard deviation) was 62+/-9 yr. All patients presented with grade (G) 3-4 prolapse. Postoperative incontinence was present in 12 of the 34 patients in group A: 7 G1; 4 G2, and 1 G3. Postoperative incontinence was present in 3 of the 32 patients in group B: 2 G1, 1 G3. The frequency of postoperative incontinence was significantly greater in patients who had undergone colposuspension (p<0.05). These preliminary data cast doubt on whether colposuspension should be performed during sacropexy for severe urogenital prolapse as prophylaxis for postoperative incontinence because it seems to emerge as overtreatment. Incontinence developed ex novo in 35% of continent patients treated with colposuspension combined with sacropexy.


An empirical test of the estimation of historical effective population size using Drosophila melanogaster.
The availability of a large number of high-density markers (SNPs) allows the estimation of historical effective population size (Ne ) from linkage disequilibrium between loci. A recent refinement of methods to estimate historical Ne from the recent past has been shown to be rather accurate with simulation data. The method has also been applied to real data for numerous species. However, the simulation data cannot encompass all the complexities of real genomes, and the performance of any estimation method with real data is always uncertain, as the true demography of the populations is not known. Here, we carried out an experimental design with Drosophila melanogaster to test the method with real data following a known demographic history. We used a population maintained in the laboratory with a constant census size of about 2800 individuals and subjected the population to a drastic decline to a size of 100 individuals. After a few generations, the population was expanded back to the previous size and after a few further generations again expanded to twice the initial size. Estimates of historical Ne were obtained with the software GONE both for autosomal and X chromosomes from samples of 17 individuals sequenced for the whole genome. Estimates of the historical effective size were able to infer the patterns of changes that occurred in the populations showing generally good performance of the method. We discuss the limitations of the method and the application of the software carried out so far.


Qualitative Scoring of the Pentagon Test: A Tool for the Identification of Subtle Cognitive Deficits in Isolated REM Sleep Behavior Disorder Patients.
Isolated rapid eye movement (REM) sleep behavior disorder (iRBD) frequently represents the prodromal stage of alpha-synucleinopathies, and similar to these pathologies, iRBD patients show neuropsychological deficits, particularly in the domain of visuospatial abilities and executive functions. We hypothesized that the qualitative scoring of the Mini-Mental State Examination pentagon test (QSPT) may detect subtle visuospatial deficits in these subjects, and we evaluated its relationship with indexes of sleep quality, as measured by polysomnography. A total of 80 polysomnography-confirmed iRBD patients and 40 healthy controls (HCs) were retrospectively recruited. Global and specific qualitative performances were evaluated according to QSPT procedure. Comparisons between iRBD and HC regarding all QSPT parameters, neuropsychological tests, and polysomnographic recordings were performed. Patients displayed significantly lower scores in both "closing-in" and total score parameters in comparison to HC. The QSPT total score exhibited significant positive correlations with verbal comprehension, fluency, visuospatial abilities, and executive functions. Notably, iRBD patients with impaired performance at QSPT showed decreased neuropsychological performances and higher percentages of slow wave sleep (SWS). In addition, SWS percentages negatively correlated with verbal comprehension, fluency, visuospatial abilities, executive functions, and QSPT total score. QSPT may represent a brief and easy to administer tool for the detection of subtle visuospatial changes in iRBD patients. Furthermore, polysomnographic findings suggest a possible slowdown of electroencephalographic pattern during non-REM sleep in iRBD patients in line with the presence of cognitive decline.


Jointly Composite Feature Learning and Autism Spectrum Disorder Classification Using Deep Multi-Output Takagi-Sugeno-Kang Fuzzy Inference Systems.
Autism spectrum disorder (ASD) is characterized by poor social communication abilities and repetitive behaviors or restrictive interests, which has brought a heavy burden to families and society. In many attempts to understand ASD neurobiology, resting-state functional magnetic resonance imaging (rs-fMRI) has been an effective tool. However, current ASD diagnosis methods based on rs-fMRI have two major defects. First, the instability of rs-fMRI leads to functional connectivity (FC) uncertainty, affecting the performance of ASD diagnosis. Second, many FCs are involved in brain activity, making it difficult to determine effective features in ASD classification. In this study, we propose an interpretable ASD classifier DeepTSK, which combines a multi-output Takagi-Sugeno-Kang (MO-TSK) fuzzy inference system (FIS) for composite feature learning and a deep belief network (DBN) for ASD classification in a unified network. To avoid the suboptimal solution of DeepTSK, a joint optimization procedure is employed to simultaneously learn the parameters of MO-TSK and DBN. The proposed DeepTSK was evaluated on datasets collected from three sites of the Autism Brain Imaging Data Exchange (ABIDE) database. The experimental results showed the effectiveness of the proposed method, and the discriminant FCs are presented by analyzing the consequent parameters of Deep MO-TSK.


Analysis of early region 4 of porcine adenovirus type 3.
The early region 4 (E4) of porcine adenovirus (PAdV)-3, located at the right-hand end of the genome is transcribed in a leftward direction and has the potential to encode seven (p1-p7) open reading frames (ORFs). To determine the role of each protein in viral replication, we constructed full-length PAdV-3 genomic clones containing deletions of individual E4 ORF or combined deletions of the neighboring ORFs. Transfection of swine testicular (ST) cells with individual E4 mutant plasmid DNAs generated PAdV-3 E4 mutant viruses except with plasmids containing a deletion of ORF p3, ORF p2+ p3 or ORF p3+ p4. Each of the mutants was further analyzed for growth kinetics, and early/late protein synthesis. Mutant viruses carrying deletions in ORF p1, ORF p2 or ORF p4 showed growth characteristics similar to that of wild-type PAdV-3. Early/late protein synthesis was also indistinguishable from that of wild-type PAdV-3. However, mutant viruses carrying deletions in ORF p5, ORF p6 or ORF p7 showed a modest effect in their ability to grow in porcine cells and express early proteins. These results suggest that the E4 ORF p3 (showing low homology with non-essential human adenovirus (HAdV)-9-E4 ORF1 encoded proteins) is essential for the replication of PAdV-3 in vitro. In contrast, the E4 ORF p7 (showing homology to essential HAdV-2 34 kDa protein) is not essential for replication of PAdV-3 in vitro. Moreover, successful deletion of 1.957 kb fragment in E4 region increased the available capacity of replication-competent PAdV-3 (E3 + E4 deleted) to approximately 4.3 kb and that of replication-defective PAdV-3 (E1 + E3 + E4 deleted) to approximately 7 kb. This is extremely useful for the construction of PAdV-3 vectors that express multiple genes and/or regulatory elements for gene therapy and vaccination.


Economic outcomes with antidepressant pharmacotherapy: a retrospective intent-to-treat analysis.
Herein we describe a retrospective intent-to-treat evaluation designed to compare the natural course of antidepressant utilization and direct health service expenditures for the treatment of a single episode of major depression among patients enrolled in a multistate network-model health maintenance organization and initially prescribed either a tricyclic antidepressant (amitriptyline or nortriptyline) or the serotonin selective reuptake inhibitor (SSRI) fluoxetine. Patient-level paid-claims data for the period July 1, 1988, through December 31, 1991, were abstracted. During the above time frame, fluoxetine was the only SSRI available in the United States. Patients prescribed amitriptyline were more than three times as likely to require a change in antidepressant pharmacotherapy (OR = 3.27, 95% CI = 2.31 to 5.49), while patients prescribed nortriptyline were nearly four times more likely to change medication (OR = 3.82, 95% CI = 2.74 to 6.83) relative to patients initially prescribed fluoxetine. Consistent with our intent-to-treat design, all accrued health service expenditures were assigned to the pharmacotherapeutic option initially prescribed. Multivariate analyses revealed that initiation of antidepressant pharmacotherapy with amitriptyline resulted in a 25.7% increase in per capita depression-related health service expenditures per year, while initiation of antidepressant pharmacotherapy with nortriptyline resulted in a 28.1% increase in per capita depression-related health service expenditures per year relative to patients initially prescribed fluoxetine. A financial break-even point was achieved at the conclusion of Month 5, at which time all three intent-to-treat cohorts had comparable health service expenditures in total. From a financial perspective, results stemming from this inquiry suggest that the initiation of antidepressant pharmacotherapy with an SSRI is warranted.


Distressing belching and neuroacanthocytosis.
We report on an uncommon manifestation of molecularly proven neuroacanthocytosis in a 32-year-old man in whom dyspnea with desaturation while awake accompanied by continuous involuntary belching were the major consequences of the disease.


Longitudinal bidirectional associations between diabetic retinopathy and diagnosed depression: Results from a Danish nationwide registry-based cohort study.
Diabetic retinopathy (DR) is a feared complication and a leading course of visual impairment, but the connection between DR and depression including the direction has never been studied in a nationwide cohort. We aimed to assess, whether the associations between DR and diagnosed depression are bidirectional. We performed a national register-based cohort study of individuals with type 2 diabetes, who attended diabetic eye screening between January 2013 and June 2022. Level of DR was extracted from the Danish Registry of Diabetic Retinopathy. The severity of DR was assessed according to the International Clinical Diabetic Retinopathy severity scale. Diagnosed depression was ascertained by physician diagnostic codes of unipolar depression (F32), recurrent depression (F33) or dysthymia (F34.1) from the Danish National Patient Register. We estimated presence of diagnosed depression according to DR level at index date and risk of diagnosed depression during follow-up using multivariable logistic and Cox regression, respectively. Secondly, we assessed whether diagnosed depression at index date could predict incident DR. We included 240,893 individuals with type 2 diabetes with baseline rates of diagnosed depression ranging from 5.2 to 6.0 % for DR level 1-4. At index date, individuals with type 2 diabetes and DR were less likely to have a history of diagnosed depression (multivariable adjusted OR, 0.77 [95 % CI 0.73-0.82]). In 226,523 individuals with type 2 diabetes followed for 1,159,755 person-years, 1.7 % developed at least one episode of diagnosed depression. In a model adjusted for age and sex, individuals with DR at index date had an increased risk of incident diagnosed depression compared to those without DR (HR 1.25 [95 % CI 1.16-1.36]). Adjusting for marital status, use of glucose-, lipid- and blood pressure lowering medication, HbA1c, diabetic neuropathy and Charlson comorbidity index waived the above risk (multivariable adjusted HR 1.02 [95 % CI 0.93-1.12]). Furthermore a previous history of diagnosed depression was not associated with increased risk of incident DR (multivariable adjusted HR 0.89 [95 % CI 0.77-1.03]). In this nationwide cohort study, individuals with DR at first screening were 23 % less likely to have a history of depression, but our data did not support a bidirectional association between DR and depression. Selection bias may have occurred as diagnosed depression is a known barrier for attending DR-screening.


Copper activates HIF-1α/GPER/VEGF signalling in cancer cells.
Copper promotes tumor angiogenesis, nevertheless the mechanisms involved remain to be fully understood. We have recently demonstrated that the G-protein estrogen receptor (GPER) cooperates with hypoxia inducible factor-1α (HIF-1α) toward the regulation of the pro-angiogenic factor VEGF. Here, we show that copper sulfate (CuSO4) induces the expression of HIF-1α as well as GPER and VEGF in breast and hepatic cancer cells through the activation of the EGFR/ERK/c-fos transduction pathway. Worthy, the copper chelating agent TEPA and the ROS scavenger NAC prevented the aforementioned stimulatory effects. We also ascertained that HIF-1α and GPER are required for the transcriptional activation of VEGF induced by CuSO4. In addition, in human endothelial cells, the conditioned medium from breast cancer cells treated with CuSO4 promoted cell migration and tube formation through HIF-1α and GPER. The present results provide novel insights into the molecular mechanisms involved by copper in triggering angiogenesis and tumor progression. Our data broaden the therapeutic potential of copper chelating agents against tumor angiogenesis and progression.


A prospective clinical trial comparing metrizamide and iohexol for equine myelography.
A prospective clinical trial comparing adverse postmyelographic effects and myelographic quality of metrizamide and iohexol was conducted. Using a predetermined, randomized assignment, 24 horses exhibiting neurologic signs were administered either metrizamide (180 mgl/ml) or iohexol (180 mgl/ml) via cerebellomedullary puncture. Each horse was evaluated postmyelographically for adverse effects. Myelographic quality was assessed by a numerical scoring method. Adverse effects were observed more frequently with metrizamide (21) compared with iohexol (6) myelography (p < 0.05). Seizures, intensification of preexisting neurologic signs and prolonged anesthetic recovery were the most common complications after myelography. There was no difference in myelographic quality (p > 0.05). We conclude that iohexol is safer than metrizamide for equine myelography and that quality myelograms can be obtained with either contrast medium.


Edge shadow projection method for measuring the brightness of electron guns.
The performance of an electron gun is evaluated in terms of the gun brightness. The brightness of an electron gun is typically measured by dividing the angular current density by the virtual source area. An electron gun brightness measurement system was constructed without an electron lens. The system consists of movable apertures (∅ 30, 50, 100, 200 μm), a Faraday cup, and a phosphor screen. The Faraday cup is employed to measure the angular current density. The electron beam passes through an aperture and its shade is projected onto the phosphor screen. The virtual source position is determined by measuring the displacement of the aperture shade made by the movement of the aperture. The blurring width of the edge of the shadow on the screen is measured by a charged-coupled device camera to calculate the virtual source size. Brightness values of a tungsten filament electron gun were obtained and compared to reported values.


Control of growth hormone receptor and insulin-like growth factor-I expression by cortisol in ovine fetal skeletal muscle.
Insulin-like growth factor (IGF)-I has an important role in myogenesis but its developmental regulation in skeletal muscle before birth remains unknown. In other tissues, cortisol modulates IGF gene expression and is responsible for many of the prepartum maturational changes essential for neonatal survival. Hence, using RNase protection assays and ovine riboprobes, expression of the IGF-I and growth hormone receptor (GHR) genes was examined in ovine skeletal muscle during late gestation and after experimental manipulation of fetal plasma cortisol levels by fetal adrenalectomy and exogenous cortisol infusion. Muscle IGF-I, but not GHR, mRNA abundance decreased with increasing gestational age in parallel with the prepartum rise in plasma cortisol. Abolition of this cortisol surge by fetal adrenalectomy prevented the prepartum fall in muscle IGF-I mRNA abundance. Conversely, raising cortisol levels by exogenous infusion earlier in gestation prematurely lowered muscle IGF-I mRNA abundance but had no effect on GHR mRNA. When all data were combined, plasma cortisol and muscle IGF-I mRNA abundance were inversely correlated in individual fetuses. Cortisol is, therefore, a developmental regulator of IGF-I gene expression and is responsible for suppressing expression of this gene in ovine skeletal muscle near term. These observations have important implications for muscle development both before and after birth, particularly during conditions which alter intrauterine cortisol exposure.


Conformal prostate brachytherapy guided by realtime dynamic dose calculations using permanent 125iodine implants: technical description and preliminary experience.
Low dose rate (LDR) prostate brachytherapy (permanent 125I or 103Pd seeds) is an accepted treatment option for low risk prostate cancer patients. However, differences in prostate spatial location, volume and gland deformation between the images obtained during pre-planning and later on during the implant procedure prevent the pre-planned intended dose to be accurately delivered. We are reporting on a new technique based on interactive real-time dynamic intra-operative dose calculation with avoidance of postimplant CT for final dosimetry. The reasons leading us to implementing this new technique are discussed and preliminary results reported. 47-78 years). For the real time intra-operative dosimetric analysis the following values were obtained: a median of 98% (90%-100%) for V90, of 60% (22%-76%) for V150 and 24% (9%-34%) for V200. The median intro-operative D90 obtained was 16,817 cGy with a range of 13,743 to 19,553 cGy. The median dose point calculation to the rectum maximum was 12,936 cGy and for the maximum in urethra was 21,880 cGy. For the real-time dynamic planning, the acute GU grade 1&2 toxicity was reduced from 28% and 2 1% to 16% and 6% respectively. Acute urinary retention was seen in 2/63 or 3% requiring a temporary post-implant bladder catheter. In addition, a decrease in chronic GU grade 1-2 toxicity was also seen from 16% and 17% to 1 1% and 2% respectively. No change in GI toxicity pattern was noted. No severe grade 3-4 intra-operative complications were noted. Real-time intra-operative planning was successfully implemented in our center. It avoids the possible implant quality and dose delivery disadvantages of the standard post-implant CT-based dosimetry by improving the accuracy of seed placement on real time, which was translated in lower rates of acute and chronic GU morbidity. In addition, avoids the unnecessary time, effort and cost of post-implant CT-based dosimetry.


Dietary Protein, Kidney Function and Mortality: Review of the Evidence from Epidemiological Studies.
The World Health Organization recommends a minimum requirement of 0.8 g/day protein/kg ideal weight. Low protein diets are used against kidney failure progression. Efficacy and safety of these diets are uncertain. This paper reviews epidemiological studies about associations of protein intake with kidney function decline and mortality. Three studies investigated these associations; two reported data on mortality. Protein intake averaged >60 g/day and 1.2 g/day/kg ideal weight. An association of baseline protein intake with long-term kidney function decline was absent in the general population and/or persons with normal kidney function but was significantly positive in persons with below-normal kidney function. Independent of kidney function and other confounders, a J-curve relationship was found between baseline protein intake and mortality due to ≈35% mortality excess for non-cardiovascular disease in the lowest quintile of protein intake, a quintile where protein intake averaged <0.8 g/day/kg ideal weight. Altogether, epidemiological evidence suggests that, in patients with reduced kidney function, protein intakes of ≈0.8 g/d/kg ideal weight could limit kidney function decline without adding non-renal risks. Long-term lower protein intake could increase mortality. In most patients, an intake of ≈0.8 g/day/kg would represent a substantial reduction of habitual intake considering that average intake is largely higher.


[Correlation between allergic rhinitis and childhood obstructive sleep apnea-hypopnea syndrome].
To investigate the correlation between allergic rhinitis and obstructive sleep apnea-hypopnea (OSAHS) syndrome in children. (1) According to medical history, physical signs, skin-prick test, serum sIgE, endoscopic examination and polysomnography, the incidence of allergic rhinitis was confirmed in 574 cases of childhood obstructive sleeping apnea-hypopnea syndrome in our hospital between July in 2008 to June in 2010. (2) Effects of anti-allergic drugs were observed on 78 children with OSAHS and allergic rhinitis meanwhile. (1) 258 cases of allergic rhinitis were confirmed in 574 cases of OSAHS, accounting for 44.9% of the OSAHS cases and 50.4% of all cases of allergic rhinitis during the same period. Most of them were perennial allergic rhinitis (223 cases, 86.4%), and 72.5% of them were aroused by fungal allergen. Compared with other allergen, statistically significant difference was found (P < 0.05). (2) After receiving anti-allergic drugs regularly for 3 weeks, 40 cases suffering from mild and moderate OSAHS and allergic rhinitis, 3 cases out of 38 cases suffering from serious OSAHS and allergic rhinitis showed satisfactory results, while other cases had little improvement. Allergic rhinitis is closely related to childhood OSAHS, and perennial allergic rhinitis dominates. The most common allergen is fungal allergen, the second is house and flour dust mites. So for patients of mild and moderate OSAHS with allergic rhinitis, regular anti-allergic drugs can lighten OSAHS effectively and may make patients avoid surgery. Severe OSAHS cases can receive surgical intervention if prior anti allergic therapy fails. Anti allergic therapy should be adopted routinely after tonsillectomy and adenoidectomy in case of hypopnea due to hypertrophy of inferior turbinate or tubal torus in allergic rhinitis.


Massive pulmonary embolism with haemodynamic collapse.
Massive pulmonary embolism with shock remains a highly fatal disease. We present twelve cases of massive embolism over the last seven years that required emergent surgery. Five patients suffered haemodynamic collapse and all died despite heroic attempts at salvage. A better outcome can only be achieved in this sub-category of patients with a rapid confirmatory diagnosis and appropriate thrombolysis and early referral to a cardiothoracic surgeon.


Younger and older adults show non-linear, stimulus-dependent performance during early stages of auditory training for non-native English.
Older adults often report difficulty understanding speech produced by non-native talkers. These listeners can achieve rapid adaptation to non-native speech, but few studies have assessed auditory training protocols to improve non-native speech recognition in older adults. In this study, a word-level training paradigm was employed, targeting improved recognition of Spanish-accented English. Younger and older adults were trained on Spanish-accented monosyllabic word pairs containing four phonemic contrasts (initial s/z, initial f/v, final b/p, final d/t) produced in English by multiple male native Spanish speakers. Listeners completed pre-testing, training, and post-testing over two sessions. Statistical methods, such as growth curve modeling and generalized additive mixed models, were employed to describe the patterns of rapid adaptation and how they varied between listener groups and phonemic contrasts. While the training protocol failed to elicit post-test improvements for recognition of Spanish-accented speech, examination of listeners' performance during the pre-testing period showed patterns of rapid adaptation that differed, depending on the nature of the phonemes to be learned and the listener group. Normal-hearing younger and older adults showed a faster rate of adaptation for non-native stimuli that were more nativelike in their productions, while older adults with hearing impairment did not realize this benefit.


The neuroendocrine and neural profiles of neuroblastomas, ganglioneuroblastomas, and ganglioneuromas.
To establish the neuroendocrine and neural features of peripheral neuroblastic tumors, a prospectively collected group of 12 neuroblastomas (NB), 2 ganglioneuroblastomas (GNB), and 4 ganglioneuromas (GN) was probed with a panel of monoclonal antibodies (MAbs) to neuroendocrine and neural antigens. All tumors expressed the pan-neuroendocrine markers synaptophysin and chromogranin A. They also showed extensive expression of neuronal antigens, ie, of each of the neurofilament (NF) triplet proteins and of the microtubule-associated proteins (MAPs) MAP2 and tau-protein. However, only in the GNBs and GNs was the pattern of NF phosphoisoforms relatively mature. In the latter tumors glial fibrillary acidic protein (GFAP) and myelin basic protein (MBP) could be demonstrated as well, suggesting the presence of nonmyelinating and myelinating Schwann cells, respectively. The glial markers did not colocalize with the neural markers. On the basis of these data, it was concluded that all peripheral neuroblastic tumors manifest molecular characteristics of neuroendocrine cells and of neurons. The latter were most developed in GNBs and GNs, in which they were accompanied by Schwann cell differentiation in a separate population of cells. The above-outlined neuronal profile of peripheral neuroblastic tumors, including NBs, distinguishes this group of tumors from the much-less neuronally differentiated primitive neuroectodermal tumors of the central nervous system.


Migration patterns of Gentiana crassicaulis, an alpine gentian endemic to the Himalaya-Hengduan Mountains.
The Himalaya-Hengduan Mountain region is one of the hotspots of biodiversity research. The uplift of the Qinghai-Tibetan Plateau (QTP) and the Quaternary glaciation caused great environmental changes in this region, and the responses of many species in the QTP to the Quaternary climate are still largely unknown. The genetic structure and phylogeographical history of Gentiana crassicaulis Duthie ex Burk, an endemic Chinese alpine species in this area, were investigated based on four chloroplast fragments and internal transcribed spacer region of the nuclear ribosomal DNA (nrITS) sequences of 11 populations. The populations with highly diverse chloroplast haplotypes were mainly found at the edge of the QTP. There were two main haplotypes of nrITS clones, one shared by the Yunnan and Guizhou populations, and the other by the remaining populations. The population with the highest diversity was the Gansu population, located at the edge of the plateau. Based on molecular dating, the diversification of G. crassicaulis at the edge of the plateau occurred before the Last Glacial Maximum (LGM), and the species may have completed its expansion from the edge to the platform. Ecological niche models were conducted to predict the distributional ranges of G. crassicaulis at present, during the LGM, and during the last interglacial (LIG) period. The results demonstrated that G. crassicaulis survived on the QTP platform and at the edge during the LGM but afterward retreated from the platform to the southern edge, followed by expansion to the platform.


Chemoprevention by Quercetin of Oral Squamous Cell Carcinoma by Suppression of the NF-κB Signaling Pathway in DMBA-treated Hamsters.
The aim of this study was to investigate the effects of the flavonoid quercetin on chemoprevention of oral squamous cell carcinoma (OSCC). The study involved molecular signaling pathways in 7,12-dimethylbenz(a) anthracene (DMBA)-induced hamster buccal pouch (HBP) carcinogenesis. DMBA (0.5%) was painted at the right buccal pouches of hamsters for 14 weeks to induce carcinoma. DMBA-treated hamsters received simultaneous doses of quercetin. Animals without DMBA induction were used as normal controls. The incidence of OSCC and the severity of pre-malignant lesions were determined histologically. Apoptosis in the pouch tissue was determined by TUNEL staining. The mRNA and protein expression of NF-κB p50 and p65, as well as Bcl-2 and Bax genes were analyzed using RT-PCR and Western blotting, respectively. Quercetin, at various doses, significantly reduced OSCC incidence and severity of hyperplasia and dysplasia compared to the DMBA-induction-only group (p<0.01). Apoptosis was induced by quercetin treatment compared to the DMBA-induction-only group (p<0.01). mRNA and protein expression of NF-κB p50, p65 as well as Bcl-2 genes were significantly suppressed by quercetin at high doses compared to DMBA induction only (p<0.05). However, mRNA and protein expression of the Bax gene was increased by quercetin treatment at medium and high doses, compared to the DMBA-induction-only group (p<0.05). Quercetin significantly reduced body-weight loss compared to the DMBA-induction-only group (p<0.05). Quercetin reduced tumor incidence and induced apoptosis through modulation of NF-κB signaling and its target genes Bcl-2 and Bax in the DMBA-induced carcigenesis hamster model, suggesting the potential of quercetin as a candidate for OSCC chemoprevention.


Quartz-enhanced photoacoustic spectroscopy for multi-gas detection: A review.
Multi-gas detection represents a suitable solution in many applications, such as environmental and atmospheric monitoring, chemical reaction and industrial process control, safety and security, oil&gas and biomedicine. Among optical techniques, Quartz-Enhanced Photoacoustic Spectroscopy (QEPAS) has been demonstrated to be a leading-edge technology for addressing multi-gas detection, thanks to the modularity, ruggedness, portability and real time operation of the QEPAS sensors. The detection module consists in a spectrophone, mounted in a vacuum-tight cell and detecting sound waves generated via photoacoustic excitation within the gas sample. As a result, the sound detection is wavelength-independent and the volume of the absorption cell is basically determined by the spectrophone dimensions, typically in the order of few cubic centimeters. In this review paper, the implementation of the QEPAS technique for multi-gas detection will be discussed for three main areas of applications: i) multi-gas trace sensing by exploiting non-interfering absorption features; ii) multi-gas detection dealing with overlapping absorption bands; iii) multi-gas detection in fluctuating backgrounds. The fundamental role of the analysis and statistical tools will be also discussed in detail in relation with the specific applications. This overview on QEPAS technique, highlighting merits and drawbacks, aims at providing ready-to-use guidelines for multi-gas detection in a wide range of applications and operating conditions.


Evidence that dopamine is involved in neuroendocrine regulation, gill intracellular signaling pathways and ion regulation in Litopenaeus vannamei.
The transport of ions and ammonia in gills may be regulated by neuroendocrine factors. In order to explore the mechanism of dopamine (DA) regulation, we investigated hemolymph neuroendocrine hormones, gill intracellular signaling pathways, ion and ammonia transporters, hemolymph osmolality and ammonia concentration in Litopenaeus vannamei after injection of 10-7 and 10-6 mol DA per shrimp. The data showed a significant increase in crustacean hyperglycemic hormone (CHH) concentration at 1-12 h and a transient significant decrease in corticotrophin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH) and cortisol concentration under DA stimulation. The up-regulation of guanylyl cyclase (GC) mRNA, cyclic guanosine monophosphate (cGMP) and protein kinase G (PKG) concentration, together with the down-regulation of DA receptor D4 mRNA and up-regulation of cyclic adenosine monophosphate (cAMP), protein kinase A (PKA), diacylglycerol (DAG) and protein kinase C (PKC) concentration suggested the activation of complicated intracellular signaling pathways. The expression of cAMP response element-binding protein (CREB), FXYD2 and 14-3-3 protein mRNA was significantly increased by PKA regulation. The increase in Na+/K+-ATPase (NKA) activity and the stabilization of V-type H+-ATPase (V-rATPase) activity were accompanied by an up-regulation of K+ channel, Na+/K+/2Cl- cotransporter (NKCC), Rh protein and vesicle associated membrane protein (VAMP) mRNA, resulting in an increase in hemolymph osmolality and a decrease in hemolymph ammonia concentration. These results suggest that DA stimulates the secretion of CHH and inhibits the release of cortisol, which activates intracellular signaling factors to facilitate ion and ammonia transport across the gills, and may not affect intracellular acidification.


Insights into material and structural basis of bone fragility from diseases associated with fractures: how determinants of the biomechanical properties of bone are compromised by disease.
Minimal trauma fractures in bone diseases are the result of bone fragility. Rather than considering bone fragility as being the result of a reduced amount of bone, we recognize that bone fragility is the result of changes in the material and structural properties of bone. A better understanding of the contribution of each component of the material composition and structure and how these interact to maintain whole bone strength is obtained by the study of metabolic bone diseases. Disorders of collagen (osteogenesis imperfecta and Paget's disease of bone), mineral content, composition and distribution (fluorosis and osteomalacia); diseases of high remodeling (postmenopausal osteoporosis, hyperparathyroidism, and hyperthyroidism) and low remodeling (osteopetrosis, pycnodysostosis); and other diseases (idiopathic male osteoporosis, corticosteroid-induced osteoporosis) produce abnormalities in the material composition and structure that lead to bone fragility. Observations in patients and in animal models provide insights on the biomechanical consequences of these illnesses and the nature of the qualities of bone that determine its strength.


Electron diffraction and high resolution transmission electron microscopy in the characterization of calcium phosphate precipitation from aqueous solutions under biomineralization conditions.
Calcium phosphate precipitation obtained from aqueous solutions at room and body temperature and pH 5.5-7.5 were investigated by high-resolution transmission electron microscopy (HRTEM), transmission electron diffraction, scanning electron microscopy (SEM) and X-ray diffraction (XRD). Supersaturated solutions of calcium phosphates were prepared by different methods of mixing of the stock solutions: diffusion-controlled mixing in space, convection-controlled mixing on earth and forced mixing on earth and with typical physiological parameters (pH and temperature). Concentrations of the stock solutions, rate of solution mixing and duration of precipitation influence very strongly the chemical composition of the precipitation, the phase composition of individual crystals, their sizes, morphology and structure. Microdiffraction and HRTEM techniques showed an incontestable advantage on other techniques like SEM and XRD in the investigation of small particles and mixtures of calcium phosphates (hydroxyapatite and octacalcium phosphate) with different proportions.


Characteristics and experiences of professionals providing 9/11 mental health services.
After disasters, mental health professionals might be called upon to help address the emotional consequences of the disaster among survivors and other affected groups, but the clinicians themselves could be affected. This exploratory study examined the experiences of 60 mental health professionals, most of whom provided mental health care to individuals affected by the September 11, 2001 terrorist attacks (9/11), and/or experienced 9/11 sequelae themselves. Participants completed structured interviews 3 and/or 6 years after the disaster, with full diagnostic assessment of psychiatric disorders and questions specific to their personal and professional post-9/11 experience. Providing postdisaster care was somewhat stressful initially, but long-term effects were more positive than negative, with overall benefit to many personal lives. Most found their clients' 9/11 stories emotionally upsetting, yet characterized their 9/11 mental health work as positive. Work satisfaction increased by 3-fold, but this effect was transitory. One-third had postdisaster psychopathology, but most was pre-existing and therefore not a product of disaster-related stressors. Although most mental health professionals initially found the emotional difficulty of their work increased after 9/11, this negative effect had largely dissipated over the years. Opportunities for disaster mental health training and initial logistical support could benefit these professionals.


Flexible near-infrared diffuse optical tomography with varied weighting functions of edge-preserving regularization.
In this paper, a flexible edge-preserving regularization algorithm based on the finite element method is proposed to reconstruct the optical-property images of near-infrared diffuse optical tomography. This regularization algorithm can easily incorporate with varied weighting functions, such as a generalized Lorentzian function, an exponential function, or a generalized total variation function. To evaluate the performance, results obtained from Tikhonov or edge-preserving regularization are compared with each other. As found, the edge-preserving regularization with the generalized Lorentzian function is more attractive than that with other functions for the estimation of absorption-coefficient images concerning functional tomographic images to discover functional information of tested phantoms/tissues.


Concentrations of faecal immunoreactive progestagen metabolites during the oestrous cycle and pregnancy in the black rhinoceros (Diceros bicornis michaeli).
The analysis of reproductive hormones in faecal samples is a possibility for non-invasive monitoring of reproductive status in free-ranging or intractable species. In the present study, faecal samples from three black rhinoceroses (Diceros bicornis michaeli) were collected at about weekly intervals during oestrous cycles and pregnancy. Daily samples were taken during the week after parturition. Total immunoreactive progestagens in faecal extracts were analysed with three different enzymeimmunoassays (EIA) that had considerable specificity for progestagens containing either a 20 alpha-hydroxyl or a 20-keto group. With each EIA it was possible to distinguish between the follicular and luteal phases of the oestrous cycle. Mating corresponded with low concentrations of faecal progestagens. Samples from five and six consecutive cycles were available from two rhinoceroses and cycle lengths of 24 and 26.5 days were calculated. All three animals became pregnant and the duration of gestation ranged from 440 to 470 days. After fertilization, the concentration of progestagens increased continuously, as in the luteal phase, reaching values 5-10 times higher between days 60 and 250. During the two weeks before parturition faecal progestagens declined and within 3-4 days post partum had reached follicular phase values. It was concluded that several immunoreactive progestagens are present in the faeces of black rhinoceroses and that their measurement with EIA enables non-invasive monitoring of the oestrous cycle and pregnancy.


A Case Report of Acute Hepatitis Involving the Medicinal Herb Tinospora cordifolia Along with Other Variables.
This is a 54-year-old woman from Germany of central European origin who developed an acute hepatitis while orally taking Ayurvedic herbal remedies, among those was the medicinal herb Tinospora cordifolia. She took the plant powders from July 1, 2021, to October 1, 2021, with the intention of relieving the symptoms of her subjectively irritated gastrointestinal tract. The patient's main symptoms of acute hepatitis were progressively increasing general fatigue, nausea, and exhaustion. During an inpatient hospital admission from November 4, 2021, to November 9, 2021, she was under clinical observation, but no specific therapeutic measures were deemed necessary; however, blood chemistry showed an acute toxic hepatitis. There was no clinical or laboratory evidence of acute liver failure. Aminotransferase values decreased to normal values on December 14, 2021, by themselves. This case report contributes to the ongoing discussion about the potential risks of triggering an acute hepatitis due to the intake of herbal remedies from the Tinospora genus in rare cases, differentiating other involved risk factors. The case also shows that causality assignments are not trivial in the context of multivariate clinical scenarios. In the case of known hepatic metabolism-associated risk factors, T. cordifolia should be used with more caution based on available case reports. At the same time, no hasty and exaggerated prejudgments should be made about this medicinal herb, which has been very successfully used in traditional South Asian systems of medicine for many centuries.


Dosimetric and radiobiological comparison between conventional and hypofractionated breast treatment plans using the Halcyon system.
The objective of this research is to compare the efficacy of conventional and hypofractionated radiotherapy treatment plans for breast cancer patients, with a specific focus on the unique features of the Halcyon system. The study collected and analyzed dose volume histogram (DVH) data for two groups of treatment plans implemented using the Halcyon system. The first group consisted of 19 patients who received conventional fractionated (CF) treatment with a total dose of 50 Gy in 25 fractions, while the second group comprised 9 patients who received hypofractionated (HF) treatment with a total dose of 42.56 Gy in 16 fractions. The DVH data was used to calculate various parameters, including tumor control probability (TCP), normal tissue complication probability (NTCP), and equivalent uniform dose (EUD), using radiobiological models. The results indicated that the CF plan resulted in higher TCP but lower NTCP for the lungs compared to the HF plan. The EUD for the HF plan was approximately 49 Gy (114% of its total dose) while that for the CF plan was around 53 Gy (107% of its total dose). The analysis suggests that while the CF plan is better at controlling tumors, it is not as effective as the HF plan in minimizing side effects. Additionally, it is suggested that there may be an optimal configuration for the HF plan that can provide the same or higher EUD than the CF plan.


Sequence analysis of the novel HLA-B35 (B*3576) allele in an African individual.
A novel human leucocyte antigen (HLA)-B35 (HLA-B*3576) allele has been described in an African individual by polymerase chain reaction sequence-based typing. This new allele contains six nucleotide substitutions and is homologous to B*3501 with the exception of residues 66-74 resulting in five amino acid mutations.