Ki-67 immunolabelling index is a prognostic indicator in childhood posterior fossa ependymomas.
Conventional histological evaluation and subclassification of childhood ependymomas poorly predict their biological behaviour. The Ki-67 labelling index (Ki-67 LI), a measure of growth fraction, correlates with the biological behaviour of several neoplasms, and this retrospective study tested the hypothesis that Ki-67 LI is a prognostic indicator in childhood posterior fossa ependymomas. Immunocytochemistry using an antibody to Ki-67 was undertaken on 5 microns sections of formalin-fixed, paraffin-embedded tissue from 74 cases of childhood (age < 16 years.) posterior fossa ependymoma. A Ki-67 LI was established by counting the proportion of labelled nuclei in more than 1000 cells from several histological fields. Several clinical and histological variables (including Ki-67 LI) potentially associated with survival were entered into univariate and multivariate analyses using a Cox proportional hazards model. Variables that showed a significant and independent association with survival were Ki-67 LI (P < 0.002), whether total surgical resection had been achieved according to operation records (P < 0.03), and whether no adjuvant therapy had been given (P < 0.01). Age, sex, and the presence of necrosis or microvascular proliferation did not correlate with survival. In our defined population of patients with ependymomas, Ki-67 LI is a strong prognostic indicator. We recommend that Ki-67 LI is used in the histological evaluation of childhood posterior fossa ependymomas during trials of novel adjunctive therapies.


Structure and function come unglued in the visual cortex.
In this issue of Neuron, Chowdhury and DeAngelis report that training monkeys to perform a fine depth discrimination abolishes the contribution of signals from area MT to the execution of a different, coarse depth discrimination. This result calls into question the principle of associating particular visual areas with particular visual functions, by showing that such associations are modifiable by experience.


A robust clinical review process: the catalyst for clinical governance in an Australian tertiary hospital.
To determine if a robust clinical review process can influence an organisation's response to adverse patient outcomes. Retrospective analysis of the activity and outputs of the Clinical Review Committee (CRC) of a university-affiliated tertiary hospital from 1 September 2002 to 30 June 2006. Engagement of clinicians (number on CRC, number interviewed for the clinical review process, number of specific referrals from clinicians); and numbers of cases reviewed, system issues identified, recommendations made to the hospital board, and ensuing actions. A multidisciplinary CRC with 34 members established a robust clinical review process and identified 5925 cases for initial case review. Of these, 2776 (46.8%) fulfilled one or more of the specified criteria for adverse events and progressed to detailed review; 342 of these (12.3%) were classed as serious or major. A total of 317 staff (11%) were interviewed, and 881 system issues were identified, resulting in 98 specific recommendations being made to the Clinical Board and implementation of 81 practice changes (including seven hospital-wide projects) to improve patient care. A robust, multidisciplinary clinical review process with strong links to managers and policymakers can influence an organisation's response to adverse patient outcomes and underpin a clinical governance framework.


Uptake of 67Ga in the lung of mice during bleomycin treatment.
Changes of 67Ga uptake in the lungs and changes of components of the so-called ground substance of the lung connective tissues of mice were followed for 7 weeks after the start of bleomycin (BLM) administration (20 mg/kg body weight IP, twice weekly for 5 weeks; this treatment induced fibrosis of the lung). 67Ga uptake of the lung was elevated at 1 week, and reached a maximum at 5 weeks (3.00 +/- 0.11% dose/g lung), and then decreased slightly at 7 weeks. The uronic acid content in the 1.2 M NaCl-soluble fraction, which contained predominantly heparan sulfate (HS), was increased at 1 week, peaked at 3 weeks, and then remained unchanged up to 7 weeks. This pattern was similar to that of 67Ga accumulation in the lungs. The uronic acid content of the 0.4 M NaCl-fraction, which contained predominantly hyaluronic acid (HA), was decreased at 1 week, but increased to a maximum at 3 weeks, then decreased to about the initial level at 5 weeks and decreased further at 7 weeks. Lung hydroxyproline content, an index of collagen content, was increased at 3 weeks and continued to increased rapidly thereafter, reaching approximately 1.5 times the control value at 7 weeks. Serum iron, measured as an indicator of iron metabolism, was slightly increased at 3 weeks and there was a corresponding decrease of unsaturated iron-binding capacity (UIBC). No corresponding change of 67Ga uptake was apparent. These results indicate that HS increased before the collagen accumulation at an early stage of pulmonary fibrosis of the lung during BLM treatment of mice, and support our earlier proposal that HS is a major acceptor for 67Ga accumulation.


Comparative transcriptome and Lipidome analyses suggest a lipid droplet-specific response to heat exposure of brown adipose tissue in normal and obese mice.
In mammals, heat stress (HS) from high-temperature environments has multiple adverse effects on the well-being of the organism. Brown adipose tissue (BAT) is a thermogenesis tissue that protects against obesity, and as an endocrine organ that regulates the systemic metabolism, but it is unclear how heat stress affects BAT in normal and obese subjects. Understanding the transcriptomic profiles and lipidomics of BAT upon heat exposure provides insights into the adaptive changes associated with this process. We constructed heat treatment (40 °C, 4 h) models for normal and obese mice, observed the effect of heat treatment on interscapular BAT (iBAT) and performed an assay for iBAT with RNA-seq and lipidomics to compare transcriptional programs and lipid dynamics. In normal mice, heat treatment caused an iBAT damage by decreasing the expression of genes involved in thermogenesis, adipogenesis and lipid metabolism. Furthermore, HS disturbed the acyl-chain composition of triacylglycerols (TAGs) and glycerophospholipids (PEs, PCs and CLs), accelerated the production of cholesterol esters, and caused the formation of giant lipid droplets rich in cholesterol esters in iBAT. Unexpectedly, in obese mice, heat treatment had a smaller effect on iBAT by improving the composition of the saturated glycerolipids, PEs and PCs and increasing the proportion of oxidized lipid in lipid droplets. Our findings proved lipid droplets participated in the regulation of lipid components of iBAT in normal and obese mice after heat treatment, which provided a new view for the understanding of the adaptation of iBAT to high-temperature environments.


On the mechanism of 'escape' from desensitization of the cyclic AMP response to TSH in cultured human thyroid cells.
Studies were conducted to examine the mechanism by which 'escape' from TSH desensitization of the cyclic AMP response to TSH (Endocrinology 109, 1156, 1981) occurs in confluent cultured thyroid cells. At confluence, cell replication and DNA synthesis are suppressed. An attempt was therefore made to reproduce escape in sparse thyroid cell monolayers using inhibitors of DNA synthesis. The concurrent presence of TSH and mitomycin C (5 micrograms/ml) did not influence the induction of desensitization to TSH after 6 h of stimulation, but cAMP levels then rebounded by 24 h; that is, mitomycin C reproduced escape in sparse cells. Hydroxyurea (10 mM) did not reproduce escape in sparse cells. Adenylate cyclase activity was unaltered in plasma membranes prepared from sparse thyroid cells treated with mitomycin C for 24 h. These data suggest that 'escape' from TSH desensitization is related to events occurring during the cell cycle associated with DNA synthesis, and is caused by an alteration in adenylate cyclase substrate or co-factor availability rather than in enzyme activity itself.


Wnt isoform-specific interactions with coreceptor specify inhibition or potentiation of signaling by LRP6 antibodies.
β-Catenin-dependent Wnt signaling is initiated as Wnt binds to both the receptor FZD and coreceptor LRP5/6, which then assembles a multimeric complex at the cytoplasmic membrane face to recruit and inactivate the kinase GSK3. The large number and sequence diversity of Wnt isoforms suggest the possibility of domain-specific ligand-coreceptor interactions, and distinct binding sites on LRP6 for Wnt3a and Wnt9b have recently been identified in vitro. Whether mechanistically different interactions between Wnts and coreceptors might mediate signaling remains to be determined. It is also not clear whether coreceptor homodimerization induced extracellularly can activate Wnt signaling, as is the case for receptor tyrosine kinases. We generated monoclonal antibodies against LRP6 with the unexpected ability to inhibit signaling by some Wnt isoforms and potentiate signaling by other isoforms. In cell culture, two antibodies characterized further show reciprocal activities on most Wnts, with one antibody antagonizing and the other potentiating. We demonstrate that these antibodies bind to different regions of LRP6 protein, and inhibition of signaling results from blocking Wnt binding. Antibody-mediated dimerization of LRP6 can potentiate signaling only when a Wnt isoform is also able to bind the complex, presumably recruiting FZD. Endogenous autocrine Wnt signaling in different tumor cell lines can be either antagonized or enhanced by the LRP6 antibodies, indicating expression of different Wnt isoforms. As anticipated from the roles of Wnt signaling in cancer and bone development, antibody activities can also be observed in mice for inhibition of tumor growth and in organ culture for enhancement of bone mineral density. Collectively, our results indicate that separate binding sites for different subsets of Wnt isoforms determine the inhibition or potentiation of signaling conferred by LRP6 antibodies. This complexity of coreceptor-ligand interactions may allow for differential regulation of signaling by Wnt isoforms during development, and can be exploited with antibodies to differentially manipulate Wnt signaling in specific tissues or disease states.


[Neurological rehabilitation].
This article describes state of the art concepts of neurological rehabilitation in Germany. In parallel to enormous growth of knowledge in the neurosciences also neurological rehabilitation has made significant progress. The increasing use of concepts of evidence based medicine and an early translation of knowledge from the neurosciences into clinical rehabilitation practice contribute to therapeutic advances. It is now widely accepted, that rehabilitation should start early and should be organized in a multidisciplinary professional team. Therapeutic procedures selected should be evidence based and have to be modified to find custom tailored solutions for individual patients. General rules derived from neuroscientific knowledge have been shown to be useful to design new therapeutic techniques. Neuromodulatory stimulation and special pharmacological treatments provide further options for enhancing results of rehabilitation.


Altered mitogen- and alloantigen-induced lymphoproliferative responses in primary lymphoid organs of pregnant mice.
The effect of syngeneic murine pregnancy on the response of lymphocytes from the primary lymphoid organs to mitogenic and alloantigenic stimulation was investigated. Thymocytes and bone marrow cells from gravid animals were found to exhibit elevated reactivity to T cell mitogens and allogeneic stimulator cells. In contrast, the LPS response of bone marrow cells from pregnant mice did not differ significantly from that of virgin animals. These findings indicate that the immune reactivity of T cells derived from the primary lymphoid organs is altered during syngeneic murine pregnancy. Pregnancy-induced modifications in T lymphocyte reactivity may contribute to the ability of the maternal immune system to recognize and react against fetal antigens.


Nanoparticles for Manipulation of the Developmental Wnt, Hedgehog, and Notch Signaling Pathways in Cancer.
The Wnt, Hedgehog, and Notch signaling pathways play a crucial role in early development and the maintenance of adult tissues. When dysregulated, these developmental signaling pathways can drive the formation and progression of cancer by facilitating cell survival, proliferation, and stem-like behavior. While this makes these pathways promising targets for therapeutic intervention, their pharmacological inhibition has been challenging due to the substantial complexity that exists within each pathway and the complicated crosstalk that occurs between the pathways. Recently, several small molecule inhibitors, ribonucleic acid (RNA) molecules, and antagonistic antibodies have been developed that can suppress these signaling pathways in vitro, but many of them face systemic delivery challenges. Nanoparticle-based delivery vehicles can overcome these challenges to enhance the performance and anti-cancer effects of these therapeutic molecules. This review summarizes the mechanisms by which the Wnt, Hedgehog, and Notch signaling pathways contribute to cancer growth, and discusses various nanoparticle formulations that have been developed to deliver small molecules, RNAs, and antibodies to cancer cells to inhibit these signaling pathways and halt tumor progression. This review also outlines some of the challenges that these nanocarriers must overcome to achieve therapeutic efficacy and clinical translation.


Staging of extrahepatic cholangiocarcinoma.
Preoperative staging of extrahepatic cholangiocarcinoma is important in determining the best treatment plan. Several classification systems have been suggested to determine the operability and extent of surgery. Longitudinal tumor extent is especially important in extrahepatic cholangiocarcinoma because operative methods differ depending on the tumor extent. The Bismuth-Corlette classification system provides useful information when planning for surgery. However, this classification system is not adequate for selecting surgical candidates. Anatomic variation of the bile duct and gross morphology of the tumor must be considered simultaneously. Lateral spread of the tumor can be evaluated based on the TNM staging provided by American Joint Committee on Cancer (AJCC). However, there is a potential for ambiguity in the distinction of T1 and T2 cancer from one another. In addition, T stage does not necessarily mean invasiveness. Blumgart T staging is helpful for the assessment of resectability with the consideration of nodal status and distant metastasis as suggested by the AJCC cancer staging system. Computed tomography (CT) and magnetic resonance imaging (MRI) are the primary tools used in the assessment of longitudinal and lateral spread of a tumor when determining respectability. Diagnostic laparoscopy and positron emission tomography (PET) may play additional roles in this regard.


Identification and functional characterization of insulin-like peptides in a pine beetle.
Insulin - including insulin-like peptides (ILPs), relaxins and insulin-like growth factors (IGFs) - is an evolutionarily conserved hormone in all metazoans. It is involved in various physiological processes, such as metabolism, growth, reproduction, lifespan and stress resistance. However, there are no reports on the functional role of ILPs in the Chinese white pine beetle, Dendroctonus armandi. In this study, we have cloned and identified two ILP cDNAs in D. armandi. The expression levels of DaILP1 and DaILP2 were significantly changed in different developmental stages. Both ILPs were expressed mostly in the head and fat body. Moreover, starvation induces the reduction of ILP1 mRNA level in adults and larvae, while ILP2 only in larvae of D. armandi, respectively. Additionally, RNA-interference (RNAi) using double stranded RNA to knock down ILP1 and ILP2 reduced the mRNA levels of the target genes, and caused a significant reduction in body weight of D. armandi. Moreover, silencing ILP1 led to an increase of trehalose and glycogen and significantly enhanced starvation resistance in both adults and larvae. The results show that the ILP signaling pathway plays a significant role in growth and carbohydrate metabolism of D. armandi and may provide a potential molecular target for pest control.


The functioning of the Medical Council of India analysed by the Parliamentary Standing Committee of Health and Family Welfare.
On March 8, 2016, the 92nd report on the functioning of the Medical Council of India (MCI) (1) was placed before both Houses of Parliament by Professor Ram Gopal Yadav, Chairman of the Parliamentary Standing Committee of Health and Family Welfare.


Roles of acyl-CoA-binding proteins in plant reproduction.
Acyl-CoA-binding proteins (ACBPs) constitute a well-conserved family of proteins in eukaryotes that are important in stress responses and development. Past studies have shown that ACBPs are involved in maintaining, transporting and protecting acyl-CoA esters during lipid biosynthesis in plants, mammals, and yeast. ACBPs show differential expression and various binding affinities for acyl-CoA esters. Hence, ACBPs can play a crucial part in maintaining lipid homeostasis. This review summarizes the functions of ACBPs during the stages of reproduction in plants and other organisms. A comprehensive understanding on the roles of ACBPs during plant reproduction may lead to opportunities in crop improvement in agriculture.


A double jeopardy: COVID-19 impacts on the travel behavior and community living of people with disabilities.
The COVID-19 pandemic response has had a significant impact on the general population's ability to participate in their communities. Individuals with disabilities, an already socially disadvantaged population, are more vulnerable to and have likely been disproportionately impacted by COVID-19 response conditions. Yet, the extent to which the daily community living activities of people with disabilities have been impacted is unknown. Thus, this study assesses their travel behavior and community living during the COVID-19 pandemic conditions compared with those of the general population. A web survey was conducted using Qualtrics's online panel data (respondents included 161 people with any type of disability and 232 people without a disability). Regression models found that people with disabilities reduced their daily travel to a greater extent but at varying degrees, depending on the destination types and travel modes. Reductions in taxi rides (including ride-hailing services) were most significant among people with cognitive and sensory (e.g., vision and hearing) disabilities. By place type, cognitive disability was associated with a trip reduction for multiple destination types-grocery, restaurants, outdoor recreation, indoor recreation, and healthcare providers. Findings from this study could contribute to decision- and policy-making in planning, transportation, and community services during the remainder of the COVID-19 pandemic, in future major public health crises, and post-COVID, because the adjustments in travel behavior and community living might be longer-term.


An overview of limonoid synthetic derivatives as promising bioactive molecules.
Limonoids, a class of abundant natural tetracyclic triterpenoids, present diverse biological activity and provide a versatile platform amenable by chemical modifications for clinical use. Among all of the limonoids isolated from natural sources, obacunone, nomilin, and limonin are the primary hub of limonoid-based chemical modification research. To date, more than 800 limonoids analogs have been synthesized, some of which possess promising biological activities. This review not only discusses the synthesis of limonoid derivatives as promising therapeutic candidates and details the pharmacological studies of their underlying mechanisms from 2002 to 2022, but also proposes a preliminary limonoid synthetic structure-activity relationship (SAR) and provides future direction of limonoid derivatization research.


Differences in white blood cell proportions between schizophrenia cases and controls are influenced by medication and variations in time of day.
Cases with schizophrenia (SCZ) and healthy controls show differences in white blood cell (WBC) counts and blood inflammation markers. Here, we investigate whether time of blood draw and treatment with psychiatric medications are related to differences in estimated WBC proportions between SCZ cases and controls. DNA methylation data from whole blood was used to estimate proportions of six subtypes of WBCs in SCZ patients (n = 333) and healthy controls (n = 396). We tested the association of case-control status with estimated cell-type proportions and the neutrophil-to-lymphocyte ratio (NLR) in 4 models: with/without adjusting for time of blood draw, and then compared results from blood samples drawn during a 12-h (07:00-19:00) or 7-h (07:00-14:00) period. We also investigated WBC proportions in a subgroup of medication-free patients (n = 51). Neutrophil proportions were significantly higher in SCZ cases (mean=54.1%) vs. controls (mean=51.1%; p = <0.001), and CD8+T lymphocyte proportions were lower in SCZ cases (mean=12.1%) vs. controls (mean=13.2%; p = 0.001). The effect sizes in the 12-h sample (07:00-19:00) showed a significant difference between SCZ vs. controls for neutrophils, CD4+T, CD8+T, and B-cells, which remained significant after adjusting for time of blood draw. In the samples matched for time of blood draw during 07.00-14.00, we also observed an association with neutrophils, CD4+T, CD8+T, and B-cells that was unaffected by further adjustment for time of blood draw. In the medication-free patients, we observed differences that remained significant in neutrophils (p = 0.01) and CD4+T (p = 0.01) after adjusting for time of day. The association of SCZ with NLR was significant in all models (range: p < 0.001 to p = 0.03) in both medicated and unmedicated patients. In conclusion, controlling for pharmacological treatment and circadian cycling of WBC is necessary for unbiased estimates in case-control studies. Nevertheless, the association of WBC with SCZ remains, even after adjusting for the time of day.


Evaluation of health care costs and utilization patterns for patients with gout.
The prevalence of gout has been increasing. Serum uric acid (sUA) levels ≥6 mg/dL have been associated with high morbidity and increased health care utilization. To assess the costs and patterns of health care resource utilization for patients with gout, categorized into 3 cohorts based on sUA levels. We retrospectively analyzed laboratory, pharmacy, and medical service claims data (January 2005 to June 2010) for patients ≥18 years old. Inclusion criteria were at least 2 sUA levels and at least 1 primary gout diagnosis (International Classification of Disease-9th revision code 274.xx), and/or at least 1 prescription for gout-specific medications. Outcomes including costs, health care resource utilization, and medication adherence and persistence were assessed for the 1-year postindex period and summarized for the 3 cohorts based on sUA levels: <6 mg/dL, 6 to 8.99 mg/dL, and ≥9 mg/dL. Costs were adjusted based on preindex utilization and baseline characteristics. Three hundred fifty-two patients met the inclusion criteria: cohort 1 (sUA <6 mg/dL), n = 38, mean age 59 years; cohort 2 (sUA 6-8.99 mg/dL), n = 231, mean age 61 years; and cohort 3 (sUA ≥9 mg/dL), n = 83, mean age 62 years. Mean adjusted gout-related health care costs were $332, $353, and $663, respectively (P <0.05); mean adjusted all-cause health care costs were $11,365, $11,551, and $14,474, respectively, for the 3 cohorts (P <0.05). sUA levels were positively associated with the percent of patients who had at least 1 hospitalization and the mean number of hospitalizations and emergency department visits (P < 0.05). Significantly more patients with sUA <6 mg/dL achieved adherence rates of ≥80% and had a longer mean duration of continuous treatment compared with patients with sUA between 6 and 8.99 mg/dL or ≥9.0 mg/dL (P <0.05). Patients with high levels of sUA had higher gout-related and all-cause health care costs, more all-cause hospitalizations, and emergency department visits, but they also exhibited poorer adherence and persistence.


Correlation between CCL26 production by human bronchial epithelial cells and airway eosinophils: Involvement in patients with severe eosinophilic asthma.
High pulmonary eosinophil counts are associated with asthma symptoms and severity. Bronchial epithelial cells (BECs) produce CC chemokines, notably CCL26 (eotaxin-3), which recruits and activates eosinophils from asthmatic patients. This suggests that CCL26 production by BECs might be involved in persistent eosinophilia in patients with severe asthma despite treatment with high corticosteroid doses. We sought to determine whether CCL26 levels correlate with eosinophilia and asthma severity. Human CC chemokine expression was assessed by means of quantitative PCR or a quantitative PCR array in vehicle- or IL-13-treated BECs. CCL26 was quantitated by means of ELISA. Immunohistochemistry analyses of CCL26 and major basic protein were done on bronchial biopsy specimens. IL-13 selectively induced CCL26 expression by BECs. This increase was time-dependent and more prominent in BECs from patients with severe eosinophilic asthma. CCL26 levels measured in supernatants of IL-13-stimulated BECs also increased with asthma severity as follows: patients with severe eosinophilic asthma > patients with mild asthma ≈ healthy subjects. Immunohistochemistry analyses of bronchial biopsy specimens confirmed increased levels of CCL26 in the epithelium of patients with mild and those with severe eosinophilic asthma. Tissue eosinophil counts did not correlate with CCL26 staining. However, sputum CCL26 levels significantly correlated with sputum eosinophil counts (P < .0001), suggesting that CCL26 participates in the movement of eosinophils from the tissues to the airway lumen. These results show a relation between CCL26 production by IL-13-stimulated BECs, sputum eosinophil counts, and asthma severity. They also suggest a role for CCL26 in the sustained inflammation observed in patients with severe eosinophilic asthma and reveal CCL26 as a potential target for treating patients with eosinophilic asthma that are refractory to classic therapies.


Invasiveness of a Growth-Migration System in a Two-dimensional Percolation cluster: A Stochastic Mathematical Approach.
We developed a framework based on the software Unstructured Reaction-Diffusion Master Equation (URDME) to address tumor cells' proliferation and migration in a heterogeneous space, herein a 2D percolation cluster. A mitogenic paracrine signaling pathway is utilized phenomenologically to reveal how cells cooperate with one another. We modeled the emerging Allee effect using low seeding density culture (LSDC) assays to fit the model parameters. A Finite time scaling (FTS) function has been formulated to quantitatively analyze invasiveness of a virtual Growth-Migration (GM) system in mimicking the cancer cell growth. Through such simulation, we analyzed the GM dynamics of virtual model in mimicking the growth of BT-474 cancer cell populations in vitro in a 2D percolation cluster and calculated the successful penetration rate (SPR). By analyzing the temporal trajectories of the SPR, we could determine the critical exponents of the critical SPR scaling relation. The SPR transition point ([Formula: see text]), which is a fundamentally different from a conventional percolation transition point, is found to be negatively correlated with the invasiveness of this cancer cell. The [Formula: see text] of the three variations of the virtual GM system distinctly designated by varying paracrine-regulated Allee (PAllee) model phenotypes is 0.3408, 0.3675, and 0.4454, respectively. FTS algorithm thereon may serve as an approach to quantify invasiveness of tumor cells. Through a phenomenological paracrine model, inter-cell cooperation and mutual mitogenic boosting are enabled to elicit the Allee effect in the GM systems. The rationale behind such computationally tunable virtual mechanism can be applied to other circumstances concerning emerging processes.


Genetic influences on phase synchrony of brain oscillations supporting response inhibition.
Phase synchronization of neuronal oscillations is a fundamental mechanism underlying cognitive processing and behavior, including context-dependent response production and inhibition. Abnormalities in neural synchrony can lead to abnormal information processing and contribute to cognitive and behavioral deficits in neuropsychiatric disorders. However, little is known about genetic and environmental contributions to individual differences in cortical oscillatory dynamics underlying response inhibition. This study examined heritability of event-related phase synchronization of brain oscillations in 302 young female twins including 94 MZ and 57 DZ pairs performing a cued Go/No-Go version of the Continuous Performance Test (CPT). We used the Phase Locking Index (PLI) to assess inter-trial phase clustering (synchrony) in several frequency bands in two time intervals after stimulus onset (0-300 and 301-600ms). Response inhibition (i.e., successful response suppression in No-Go trials) was characterized by a transient increase in phase synchronization of delta- and theta-band oscillations in the fronto-central midline region. Genetic analysis showed significant heritability of the phase locking measures related to response inhibition, with 30 to 49% of inter-individual variability being accounted for by genetic factors. This is the first study providing evidence for heritability of task-related neural synchrony. The present results suggest that PLI can serve as an indicator of genetically transmitted individual differences in neural substrates of response inhibition.


Boron-neutron Capture on Activated Carbon for Hydrogen Storage.
This work investigates the effects of neutron irradiation on nitrogen and hydrogen adsorption in boron-doped activated carbon. Boron-neutron capture generates an energetic lithium nucleus, helium nucleus, and gamma photons, which can alter the surface and structure of pores in activated carbon. The defects introduced by fission tracks are modeled assuming the slit-shaped pores geometry. Sub-critical nitrogen adsorption shows that nitrogen molecules cannot probe the defects created by fission tracks. Hydrogen adsorption isotherms of irradiated samples indicate higher binding energies compared to their non-irradiated parent samples.


Isolation of TIR and non-TIR NBS--LRR resistance gene analogues and identification of molecular markers linked to a powdery mildew resistance locus in chestnut rose (Rosa roxburghii Tratt).
Toll and interleukin-1 receptor (TIR) and non-TIR nucleotide binding site-leucine rich repeat (NBS-LRR) resistance gene analogues (RGAs) were obtained from chestnut rose (Rosa roxburghii Tratt) by two PCR-based amplification strategies (direct amplification and overlap extension amplification) with degenerate primers designed to the conserved P-loop, kinase-2, and Gly-Leu-Pro-Leu (GLPL) motifs within the NBS domain of plant resistance gene (R gene) products. Thirty-four of 65 cloned PCR fragments contained a continuous open reading frame (ORF) and their predicted protein products showed homology to the NBS-LRR class R proteins in the GenBank database. These 34 predicted protein sequences exhibited a wide range (19.5--99.4%) of sequence identity among them and were classified into two distinct groups by phylogenetic analysis. The first group consisted of 23 sequences and seemed to belong to the non-TIR NBS-LRR RGAs, since they contained group specific motifs (RNBS-A-non-TIR motif) that are often present in the coiled-coil domain of the non-TIR NBS-LRR class R genes. The second group comprised 11 sequences that contained motifs found in the TIR domain of TIR NBS-LRR class R genes. Restriction fragment length polymorphic (RFLP) markers were developed from some of the RGAs and used for mapping powdery mildew resistance genes in chestnut rose. Three markers, RGA 22 C, RGA 4 A, and RGA 7 B, were identified to be linked to a resistance gene locus, designated CRPM 1 for chestnut rose powdery mildew resistance 1, which accounted for 72% of the variation in powdery mildew resistance phenotype in an F1 segregating population. To our knowledge, this is the first report on isolation, phylogenetic analysis and potential utilization as genetic markers of RGAs in chestnut rose.


Arthroscopic triple and modified double hindfoot arthrodesis.
Arthroscopic arthrodesis is an accepted technique for the ankle but less commonly reported for multiple hindfoot joints. We present a case series review to establish the feasibility of this surgery. In a consecutive series of 112 arthroscopic hindfoot arthrodeses, 18 involved decortication and fusion of 2 or 3 hindfoot joints. These were reviewed to identify complications, union rates and improvement over preoperative state. Mean age was 62 (45-78). Mean follow-up was 4.4 (1.75-7.5) years. There were no perioperative complications. The four patients with triple fusions united with good or excellent outcomes. Of 14 patients with subtalar and talonavicular arthrodeses there were three talonavicular non-unions. Arthroscopic double and triple arthrodeses appear feasible salvage options for pain and deformity. Decortication of all three joints and rotatory correction of deformity is possible whilst preserving the soft tissue envelope. Late adjacent joint pain and arthrosis can occur.


Central nervous system relapse of treated stage IV neuroblastoma.
Neuroblastoma is the most common extracranial solid tumor in pediatrics. The long-term survival of patients with advanced-stage neuroblastoma has remarkably improved secondary to aggressive treatment protocols including autologous bone marrow transplant (BMT). As a result, a different natural history of this disease is being reported with unusual, late manifestations. The central nervous system (CNS), once a rare site of disease, is being involved with increasing frequency. Appropriate neuroimaging in these patients is important. Two cases of patients with treated stage IV neuroblastoma who developed isolated CNS metastases are presented. The proposed pathogenesis and neuroradiologic manifestations of this complication are reviewed.


Therapeutic opportunities for pain medicines via targeting of specific translation signaling mechanisms.
As the population of the world ages and as more and more people survive diseases that used to be primary causes of mortality, the incidence of severe chronic pain in most of the world has risen dramatically. This type of pain is very difficult to treat and the opioid overdose epidemic that has become a leading cause of death in the United States and other parts of the world highlights the urgent need to develop new pain therapeutics. A common underlying cause of severe chronic pain is a phenotypic change in pain-sensing neurons in the peripheral nervous system called nociceptors. These neurons play a vital role in detecting potentially injurious stimuli, but when these neurons start to detect very low levels of inflammatory meditators or become spontaneously active, they send spurious pain signals to the brain that are significant drivers of chronic pain. An important question is what drives this phenotypic shift in nociceptors from quiescence under most conditions to sensitization to a broad variety of stimuli and spontaneous activity. The goal of this review is to discuss the critical role that specific translation regulation signaling pathways play in controlling gene expression changes that drive nociceptor sensitization and may underlie the development of spontaneous activity. The focus will be on advances in technologies that allow for identification of such targets and on developments in pharmacology around translation regulation signaling that may yield new pain therapeutics. A key advantage of pharmacological manipulation of these signaling events is that they may reverse phenotypic shifts in nociceptors that drive chronic pain thereby creating the first generation of disease modifying drugs for chronic pain.


Chromosomal abnormalities and birth defects among couples with colchicine treated familial Mediterranean fever.
To determine whether colchicine prescribed for familial Mediterranean fever is teratogenic. Reproductive histories were analyzed from 326 couples referred for prenatal diagnosis because 1 partner was affected. Numbers of chromosomal abnormalities and birth defects were compared with numbers expected from published rates. There were 901 pregnancies, and amniocentesis had been performed in 566, all but 3 conceived while taking colchicine. Seven numerical chromosomal abnormalities were found, not statistically significantly greater than the 4.99 expected from maternal age and gestation of diagnosis (P = .24): unbalanced structural abnormalities were 6, compared with 3.22 expected (P = .11). There were 7 birth defects, a considerably lower rate than reported in local malformation registers. The current policy of routine amniocentesis in pregnancies of couples taking colchicine should not be changed until sufficient data accumulates to establish whether the higher number of chromosomal anomalies in this group is significant.


Microencapsulation of Streptococcus equi antigens in biodegradable microspheres and preliminary immunisation studies.
Streptococcus equi subspecies equi is the causative agent of strangles, a bacterial infection of the respiratory tract of equidae. Current strategies to prevent strangles rely on antimicrobial therapy or immunisation with inactivated bacteria, S. equi bacterin, or M-like protein (SeM) extract. The aim of this work was to investigate whether immunisation with whole killed S. equi or a bacterial lysate entrapped in poly(lactide-co-glycolide) (PLGA) microspheres might induce protective immunity to mice. Animals were treated with a dose of antigen equivalent to 25 microg of SeM. For intranasal route animals were primed on days 1, 2 and 3 and were boosted on day 29. For intramuscular route, primary immunisation was carried out with a single injection on day 1 and animals were boosted on day 29. On day 43 animals were submitted to a challenge with a virulent strain of S. equi. Vaccination with antigen-containing microspheres induced higher serum antibody levels in mice treated by the intranasal route, whereas intramuscular immunisation did not reveal any difference between control and treatment groups. Microencapsulated antigens achieved to fully protect mice against experimental infection irrespective of the route of administration used. Following intranasal or intramuscular administration soluble antigen failed to protect mice against challenge. These studies indicate that PLGA microspheres are a potential carrier system for the delivery of S. equi antigens.


Surgical considerations for glenoid bone loss in anterior glenohumeral instability: a narrative review.
Treatment algorithms may consider many factors like glenoid and humeral bone loss, or scores such as the instability severity index score (ISIS). As most studies only evaluate a part of these factors, there is still no evidence-based consensus estalished. Our study aims to summarize the surgical options for treatment of glenoid bone loss (GBL) in anterior shoulder instability. Based on the current available literature, surgical options including Bankart repair and glenoid bone augmentation should be considered while taking into consideration the degree of bone loss which has been divided into < 10%, 10-20% and > 20%. There are many new techniques evolving including arthroscopic anatomic glenoid reconstruction with bone blocks. Future long-term outcome studies and randomized controlled trials comparing established techniques will be needed for new evidence-based treatment algorithms.


Demyelinating peripheral neuropathy in a guinea hen associated with subacute lead intoxication.
In mammalian species lead acts primarily as a neurotoxin. Lead poisoning is common in avian species but lesions in the nervous system have not been associated with it. This paper describes a peripheral neuropathy with fragmentation and segmental demyelination of fibers in the sciatic nerves of an adult guinea hen (Numida meleagris) which died of lead poisoning.


Sequence-specific and/or stereospecific constraints of the U3 enhancer elements of MCF 247-W are important for pathogenicity.
The oncogenic potential of many nonacute retroviruses is dependent on the duplication of the enhancer sequences present in the unique 3' (U3) region of the long terminal repeat (LTR). In a molecular clone (MCF 247-W) of the murine leukemia virus MCF 247, a leukemogenic mink cell focus-inducing (MCF) virus, the U3 enhancer sequences are tandemly repeated in the LTR. We mutated the enhancer region of MCF 247-W to test the hypothesis that the duplicated enhancer sequences of this virus have a sequence-specific and/or a stereospecific role in enhancer function required for transformation. In one virus, we inserted 14 nucleotide bp into the novel sequence generated at the junction of the two enhancers to generate an MCF virus with an interrupted enhancer region. In the second virus, only one copy of the enhancer sequences was present. This second virus also lacked the junction sequence present between the two enhancers of MCF 247-W. Both viruses were less leukemogenic and had a longer mean latency period than MCF 247-W. These data indicate that the sequence generated at the junction of the two enhancers and/or the stereospecific arrangement of the two enhancer elements are required for the full oncogenic potential of MCF 247-W. We analyzed proviral LTRs within the c-myc locus in tumor DNAs from mice injected with the MCF virus with the interrupted enhancer region. Some of the proviral LTRs integrated upstream of c-myc contain enhancer regions that are larger than those of the injected virus. These results are consistent with the suggestion that the virus with an interrupted enhancer changes in vivo to perform its role in the transformation of T cells.


Nitrogen inputs to a river course in a heavily impacted watershed: a combined hydrochemical and isotopic evaluation (Oglio River Basin, N Italy).
This study aims at evaluating sources and processes affecting NO₃(-) concentrations in the Oglio River. Five sampling campaigns considered the main watercourse, tributaries, point pollution sources, springs, and groundwater. Physico-chemical parameters, N forms, B, Sr(2+), stable isotopes (δ(2)HH₂O, δ(18)OH₂O, δ(15)NNO₃, δ(18)ONO₃, δ(11)B) and discharge were measured. Hydrological modelling was performed using mass balance and End Member Mixing Analysis equations. During the irrigation period, in the upstream reach, up to 90% of the natural river flow is diverted for irrigation and industrial purposes; excess water drained from agricultural fields is returned to river in the downstream reach. Results evidenced, in the middle reach, a large input of NO₃(-)-rich groundwater which could be quantified using hydrological modelling. Groundwater inputs are responsible for the sharp, tenfold increase in NO₃(-) in the river water, from 2.2-4.4 up to 33.5 mgL(-1), and are more evident in summer, when discharge is lower. Nevertheless, river water preserves its natural B isotopic composition, indicating that the two tracers do not have a common origin and are not co-migrant. In the lower plain, surface-groundwater interconnections and human disturbances in the water cycle favour the recycling of the compounds in the environment, and lead to a similarity in composition of the different water bodies (Oglio River, tributaries and groundwater). The long lasting agronomical practices have profoundly modified the surface-groundwater equilibrium and chemical characteristics, resulting in a highly buffered system. Infiltrating irrigation water leaches down NO₃(-) which is subsequently denitrified; when returned to the Oglio River, groundwater modifies the river water composition by dilution, in the case of NO₃(-), or by addition, for other constituents (e.g. Cl(-), B). The results of this study indicate that, in order to reduce the NO3(-) transport towards the Adriatic Sea, groundwater contamination should be addressed first, with expected long recovery times.


Ecotoxicity of Lead to a Phytoplankton Community: Effects of pH and Phosphorus Addition and Implications for Risk Assessment.
Ecological risk assessment and water quality criteria for lead (Pb) are increasingly making use of bioavailability-based approaches to account for the impact of toxicity-modifying factors, such as pH and dissolved organic carbon. For phytoplankton, which are among the most Pb-sensitive freshwater species, a Pb bioavailability model has previously been developed based on standard single-species exposures at a high phosphorus (P) concentration and pH range of 6.0 to 8.0. It is well known that P can affect metal toxicity to phytoplankton and that the pH of many surface waters can be above 8.0. We aimed to test whether the single-species bioavailability model for Pb could predict the influence of pH on Pb toxicity to a phytoplankton community at both low and high P supply. A 10-species phytoplankton community was exposed to Pb for 28 days at two different pH levels (7.2 and 8.4) and two different P supply levels (low and high, i.e., total P input 10 and 100 µg/L, respectively) in a full factorial 2 × 2 test design. We found that the effects of total Pb on three community-level endpoints (biodiversity, community functioning, and community structure) were highly dependent on both pH and P supply. Consistent lowest-observed-effect concentrations (LOECs) ranged between 21 and >196 µg total Pb/L and between 10 and >69 µg filtered Pb/L. Long-term LOECs were generally higher, that is, 69 µg total Pb/L (42 µg filtered Pb/L) or greater, across all endpoints and conditions, indicating recovery near the end of the exposure period, and suggesting the occurrence of acclimation to Pb and/or functional redundancy. The highest toxicity of Pb for all endpoints was observed in the pH 7.2 × low P treatment, whereas the pH 8.4 × low P and pH 8.4 × high P treatment were the least sensitive treatments. At the pH 7.2 × high P treatment, the algal community showed an intermediate Pb sensitivity. The effect of pH on the toxicity of filtered Pb could not be precisely quantified because for many endpoints no effect was observed at the highest Pb concentration tested. However, the long-term LOECs (filtered Pb) at low P supply suggest a decrease in Pb toxicity of at least 1.6-fold from pH 7.2 to 8.4, whereas the single-species algal bioavailability model predicted a 2.5-fold increase. This finding suggests that bioavailability effects of pH on Pb toxicity cannot be extrapolated as such from the single species to the community level. Overall, our data indicate that, although the single-species algal Pb bioavailability model may not capture pH effects on Pb ecotoxicity in multispecies systems, the bioavailability-based hazardous concentration for 5% of the species was protective of long-term Pb effects on the structure, function, and diversity of a phytoplankton community in a relevant range of pH and P conditions. Environ Toxicol Chem 2023;42:2684-2700. © 2023 SETAC.


The kidney-ureter stone sexual paradox: a possible explanation.
The greater frequency of renal stones seen on excretory urograms in women, compared with the greater frequency of ureteral stones in men has been termed a sexual paradox. We assessed stone composition and weight, and sex as possible explanatory factors. A total of 4,014 renal and ureteral calculi was analyzed. For the 3,119 calculi in which only calcium oxalate and/or phosphate was detected by infrared and wet chemical analysis, there was a strong relationship between the oxalate-to-phosphate weight ratio and sex (p less than 0.0001). The mean weight for phosphate stones was 330 mg. but for oxalate stones it was 107 mg. Male-to-female ratios were 2.7, 2.2 and 1.8 for stone weight groups of 20 or less, 21 to 100 and more than 100 mg. The male-to-female ratio was 0.87 for the 171 stones containing magnesium ammonium phosphate; the average weight was 508 mg. for men and 1,560 mg. for women. The tendency for phosphate stones to be heavier and relatively more common in women compared to predominantly oxalate stones may partly account for the sexual paradox.


Paroxysmal Sympathetic Hyperactivity in Adult Patients with Brain Injury: A Systematic Review and Meta-Analysis.
Paroxysmal sympathetic hyperactivity (PSH) is a syndrome of excessive sympathetic activity, mainly occurring in severe traumatic brain injury. However, few studies have reported the frequency of PSH and its related risk factors in adult patients with brain injury. We performed this systematic review and meta-analysis to estimate the combined incidence of PSH and the associated risk factors in adult patients with brain injury. This study was registered with the PROSPERO international prospective register of systematic reviews (https://www.crd.york. ac.uk/PROSPERO/Identifier: CRD 42021260493), and a systematic search was conducted of the scientific databases Embase, PubMed, Web of Science, Cochrane Library, and Google Scholar. All identified observational studies regarding the incidence and risk factors of PSH in adult patients with brain injury were included. Two authors extracted data independently; data were analyzed by STATA version 16. The search yielded 9 studies involving 1643 adult patients. PSH was detected in 438 patients. The combined incidence of PSH in adult patients with brain injury was 27.4% (95% confidence interval [CI], 0.190-0.358). The risk factors include patients' age (SMD = -0.592; I2 = 77.5%; 95% CI, -1.027 to -0.156; P = 0.008), traffic accident (odds ratio [OR], 1.783; I2 =18.0%; 95% CI, 1.128-2.820; P = 0.013), admission Glasgow Coma Scale score (SMD = -1.097; I2 =28.3%; 95% CI, -1.500 to -0.693; P = 0.000), hydrocephalus (OR, 3.936; I2 =67.9%; 95% CI, 1.144-13.540; P = 0.030), and diffuse axonal injury (OR, 4.747; I2 =71.1%; 95% CI, 1.221-18.463; P = 0.025) and were significantly associated with the presence of PSH after brain injury. PSH occurs in nearly a quarter of adult patients with brain injury. Patient's age, traffic accident, admission Glasgow Coma Scale score, hydrocephalus, and diffuse axonal injury were risk factors for PSH in adult patients with brain injury. These findings may contribute to novel strategies for early diagnosis and interventions that aid in the rehabilitation of patients with brain injury.


One thousand cases of severe occupational contact dermatitis.
Occupational contact dermatitis is frequent, and further understanding of the epidemiology will improve the basis of its prevention. Objectives. To identify occupations at risk for severe occupational contact dermatitis. The last 1000 cases of severe occupational contact dermatitis seen at our department were identified. The study population comprised 618 females and 382 males. The mean age at onset of irritant contact dermatitis was significantly lower than the mean age at onset of allergic contact dermatitis for both sexes, irrespective of the presence of atopic dermatitis. Females at high risk were cooks, butchers, beauticians, bakers, and hairdressers, ranging from 23.3 to 96.8 cases per 10 000 workers per year. Males at high risk were painters, cooks, mechanics, locksmiths, and bakers, ranging from 16.5 to 32.3 cases per 10000 workers per year. Occupational contact dermatitis remains frequent, even if only severe cases are considered. It is a concern that no effective, systematic interventions and prevention schemes have been launched in Europe, despite documentation of a significant problem over many years, and knowledge of risk occupations and risk factors. This study suggests new approaches for general and specific prevention of occupational contact dermatitis.


Characterization of basic proteins from goldfish myelin.
Myelin basic protein (MBP) from common goldfish (Carassius auratus) myelin was extracted with dilute mineral acid. Immunological cross-reactivity of the goldfish MBP, with polyclonal antisera raised against bovine MBP, suggested that the goldfish protein has epitopes for these antibodies. It also reacted with a monoclonal antibody specific for a seven amino acid epitope (130-137) conserved in the MBP of most mammalian species. To characterize the charge heterogeneity of this protein, we iodinated the protein with 125I and chromatographed it on a carboxymethyl cellulose-52 column together with a nonlabeled acid soluble fraction prepared from human white matter as a carrier protein. All of the goldfish protein was recovered in the unbound fraction, demonstrating that it was less cationic than the carrier protein (human MBP). We have also examined the urea alkaline gel profile of the goldfish MBP together with the human C-1, C-2, C-3, C-4, and C-8 components. The results from these experiments indicated that this MBP extracted from goldfish brain myelin lacked the microheterogeneity that is associated with MBPs from higher vertebrates. The MBPs from goldfish myelin were separated into their isoforms by reversed-phase HPLC. Amino acid compositions were determined for both the 17- and 14-kDa goldfish proteins. Amino acid analysis revealed similarities with the compositions of other MBPs; however, the serine content in both the 17- and 14-kDa proteins was higher than that of the human C-1, the mouse C-1 protein, and the shark proteins. The HPLC-purified 14-kDa goldfish protein was chemically cleaved with CNBr for partial sequence analysis.(ABSTRACT TRUNCATED AT 250 WORDS)


[Open reduction and internal fixation of supracondylar fractures of the humerus in children. Analysis of results at ten-year of follow-up].
The aim of this study was to evaluate the long term results of the surgical treatment by means of open reduction and internal fixation of displaced supracondylar humerus fractures in a paediatric population. Descriptive retrospective study conducted between 1996-2003, which included 21 patients who underwent open reduction and internal fixation for the treatment of displaced, supracondylar humerus fractures according to the Gartland classification, which were irreducible by closed methods. The patients were clinically evaluated according to the Flynn criteria (functional and cosmetic). Data collection also included postoperative radiological evaluation, range of movement, the presence of post-operative complications, and a questionnaire on satisfaction with treatment received. The mean age of the patients was 5.8 years. Mean follow-up was 11.52 years. The average post-operative Baumann angle was 17.6°. Final loss of flexion averaged 5.1° (range: 0-20°), and loss of extension 0.71° (range: 0-10°), with 90% of patients demonstrating an elbow range of movement within normal limits. According to the Flynn criteria, functional and cosmetic results were satisfactory in 85.5%. Superficial wound infection and metal work migration were the most common post-operative complications. At the final follow-up all patients, except two, were very happy with the result, and no patient complained of difficulties in carrying out normal living activities or their favourite sports. In cases of unsatisfactory reduction or failure to maintain a stable closed reduction, open reduction and internal fixation demonstrates equivalent results to closed procedures.


Hepatic secretion and turnover of serum phosphatidylcholine-cholesterol acyltransferase in male and female rats.
The activity of serum phosphatidylcholine-cholesterol acyltransferase (LCAT), output of the enzyme by the perfused rat liver, and the effect of pretreatment with colchicine on LCAT were studied in male and female rats. It was observed that: 1. Serum LCAT activity in the female exceeded that of the male in fasted animals, whereas in fed animals, LCAT activity was higher in the male than the female. With both sexes, however, serum LCAT activity in fed animals was greater than that in fasted animals. Data are presented which suggest that the observed sex differences were due to concentration and/or composition of the substrate rather than to differences in the serum concentration of the enzyme. 2. The release of LCAT by perfused livers from fasted female rats exceeded that of the male animals. The output of LCAT was inhibited by pretreatment (male) with colchicine, which suggests that hepatic secretion of LCAT is dependent on vesicular transport. 3. The decay of serum LCAT activity in vivo following injection of colchicine was more rapid in fasted female rats than in male animals. These observations lead us to postulate that the turnover rate of LCAT is higher in female rats than in male animals.


Design of a titering assay for lentiviral vectors utilizing direct extraction of DNA from transduced cells in microtiter plates.
Using lentiviral vector products in clinical applications requires an accurate method for measuring transduction titer. For vectors lacking a marker gene, quantitative polymerase chain reaction is used to evaluate the number of vector DNA copies in transduced target cells, from which a transduction titer is calculated. Immune Design previously described an integration-deficient lentiviral vector pseudotyped with a modified Sindbis virus envelope for use in cancer immunotherapy (VP02, of the ZVex platform). Standard protocols for titering integration-competent lentiviral vectors employ commercial spin columns to purify vector DNA from transduced cells, but such columns are not optimized for isolation of extrachromosomal (nonintegrated) DNA. Here, we describe a 96-well transduction titer assay in which DNA extraction is performed in situ in the transduction plate, yielding quantitative recovery of extrachromosomal DNA. Vector titers measured by this method were higher than when commercial spin columns were used for DNA isolation. Evaluation of the method's specificity, linear range, and precision demonstrate that it is suitable for use as a lot release assay to support clinical trials with VP02. Finally, the method is compatible with titering both integrating and nonintegrating lentiviral vectors, suggesting that it may be used to evaluate the transduction titer for any lentiviral vector.


Use of a 3D Virtually Reconstructed Patient-Specific Model to Examine the Effect of Acetabular Labral Interference on Hip Range of Motion.
The labrum is likely to influence impingement, which may also depend on acetabular coverage. Simulating impingement using 3-dimensional (3D) computed tomography (CT) is a potential solution to evaluating range of motion (ROM); however, it is based on bony structures rather than on soft tissue. To examine ROM when the labrum is considered in a 3D dynamic simulation. A particular focus was evaluation of maximum flexion and internal rotation angles before occurrence of impingement, comparing them in cases of cam-type femoroacetabular impingement (FAI) and borderline developmental dysplasia of the hip (BDDH). Descriptive laboratory study. Magnetic resonance imaging (MRI) and CT scans of 40 hips (20 with cam-type FAI and 20 with BDDH) were reviewed retrospectively. The thickness and width of the labrum were measured on MRI scans. A virtual labrum was reconstructed based on patient-specific sizes measured on MRI scans. The impingement point was identified using 3D dynamic simulation and was compared with the internal rotation angle before and after labral reconstruction. The thickness and width of the labrum were significantly larger in BDDH than in FAI (P < .001). In FAI, the maximum internal rotation angles without the labrum were 30.3° at 90° of flexion and 56.9° at 45° of flexion, with these values decreasing to 18.7° and 41.4°, respectively, after labral reconstruction (P < .001). In BDDH, the maximum internal rotation angles were 48.0° at 90° of flexion and 76.7° at 45° of flexion without the labrum, decreasing to 31.1° and 55.3°, respectively, after labral reconstruction (P < .001). The differences in the angles before and after labral reconstruction were larger in BDDH than in FAI (90° of flexion, P = .03; 45° of flexion, P = .01). As the labrum was significantly more hypertrophic in BDDH than in FAI, the virtual labral model revealed that the labrum's interference with the maximum internal rotation angle was also significantly larger in BDDH. The labrum has a significant effect on impingement; this is more significant for BDDH than for FAI.


Pneumodissection for skin protection in image-guided cryoablation of superficial musculoskeletal tumours.
Pneumodissection is described as a simple method for preventing skin injury during cryoablation of superficial musculoskeletal tumours. Superficial tumour cryoablations performed from 2009 to 2015 were retrospectively reviewed. Pneumodissection was performed in 13 patients when the shortest tumour-skin distance was less than 25 mm. Indications were pain palliation (n = 9) and local tumour control (n = 4). Patients, target tumours, technical characteristics and complications up to 60 days post ablation were reviewed. The ice ball-skin distances with and without pneumodissection were compared by a paired t-test and further assessed for association with covariates using ANCOVA. Technical success for ablation was 12 of 13. The mean shortest tumour-skin distance was 15.0 mm (3.2-24.5 mm). The mean thickness of pneumodissection was 9.6 mm (5.2-16.6 mm) resulting in mean elevation of skin of 3.4 mm (1.2-5.3 mm). Mean shortest ice ball-skin distance after pneumodissection was 10.5 mm (4.2-19.7 mm). No infection or systemic air embolism was noted. No intraprocedural frostbite was observed. Pneumodissection is feasible, effective and safe in protecting the skin during image-guided cryoablation of superficial tumours. • Frostbite during image-guided cryoablation of superficial tumours is commonly under-reported. • Frostbites are painful and may introduce infection into the superficial ablation zone. • Warm compress, saline and CO 2 have shortcomings in protecting the skin. • Pneumodissection is free, readily available, easy to use and safe and effective.


Shortening of pulse-width for immediately succeeding trigger signals in the use of logic pulse shapers for nuclear experiments.
If a second succeeding pulse arrives immediately after a first preceding pulse in the output from a non-retrigerable monostable multivibrator, the width of the succeeding pulse is somewhat shortened. Using a time-to-amplitude converter followed by a multi channel analyzer, the pulse-width shortening of the succeeding pulse was measured as a function of the time interval between the two pulses. It was found that this effect was highly dependent on the resistance of an external RC time constant circuit. Similar measurements were also carried out for nuclear instrument modules involving the monostable multivibrator circuits.


Unconventional monetary policy and disaster risk: Evidence from the subprime and COVID-19 crises.
We compare the interventions conducted by the Federal Reserve in response to the subprime and COVID-19 crises with respect to their effectiveness in reducing disaster risk. Using model-free measures of disaster risk derived from daily options data, we document that interventions in response to both crises reduced tail risks in domestic equity markets. The spillover effects of the two crises have been markedly dissimilar. While subprime interventions are generally characterized by negative spillovers to international equity markets, policy responses to the COVID-19 crisis are generally associated with positive spillovers. We interpret these results as consistent with the different degrees of protagonism by central banks in the two episodes, emphasizing the importance of a broader participation of monetary authorities in expanding their balance sheets to counteract the effects of major crises.


Sequence variation in primer targets affects the accuracy of viral quantitative PCR.
This study was designed to assess the effect of sequence mismatches between primers and their targets on viral quantitative PCR. Numerous primers were constructed incorporating various mismatches with a target sequence on the BKV T antigen gene. When using these primers in standard Taqman two-step cycling conditions, as few as two mismatches in a single primer increased cycle threshold values and significantly influenced the calculation of viral load.


Radix Scrophulariae extracts (harpagoside) suppresses hypoxia-induced microglial activation and neurotoxicity.
Hypoxia could lead to microglia activation and inflammatory mediators' overproduction. These inflammatory molecules could amplify the neuroinflammatory process and exacerbate neuronal injury. The aim of this study is to find out whether harpagoside could reduce hypoxia-induced microglia activation. In this study, primary microglia cells harvested from neonatal ICR mice were activated by exposure to hypoxia (1 % O2 for 3 h). Harpagoside had been shown to be no cytotoxicity on microglia cells by MTT assay. The scavenger effect of harpagoside on hypoxia-enhanced microglial cells proliferation, associated inflammatory genes expression (COX-II, IL-1β and IL-6 genes) and NO synthesis were also examined. Hypoxia enhances active proliferation of microglial cells, while harpagoside can scavenge this effect. We find that harpagoside could scavenge hypoxia-enhanced inflammatory genes expression (COX-2, IL-1β and IL-6 genes) and NO synthesis of microglial cells. Under 3 h' hypoxic stimulation, the nuclear contents of p65 and hypoxia inducible factor-1α (HIF-1α) significantly increase, while the cytosol IκB-α content decreases; these effects can be reversed by 1 h's pre-incubation of 10(-8) M harpagoside. Harpagoside could decrease IκB-α protein phosphorylation and inhibit p65 protein translocation from the cytosol to the nucleus, thus suppress NF-κB activation and reduce the HIF-1α generation. These results suggested that the anti-inflammatory mechanism of harpagoside might be associated with the NF-κB signaling pathway. Harpagoside protect against hypoxia-induced toxicity on microglial cells through HIF-α pathway.


Identification of a second G-C-rich promoter conserved in the human, murine and rat tumor suppressor genes HIC1.
The BTB/POZ transcriptional repressor HIC1 (Hypermethylated in Cancer 1) is a tumor suppressor gene located at chromosome 17p13.3, a region frequently hypermethylated or deleted in human tumors and in a contiguous-gene syndrome, the Miller-Dieker syndrome. The human and murine HIC1 genes are composed of two alternative 5' exons, 1a and 1b fused to a large second coding exon 2. Exon 1a is a noncoding exon associated with a major G-C-rich promoter whereas exon 1b is a downstream coding exon associated with a minor TATA box promoter. By human-mouse genome comparison, we have identified a short upstream conserved sequence containing G-C boxes which were shown to be functional. Transcripts initiating from this new promoter were detected in various human and mouse tissues and contained a long 5'-UTR sequence, called 1c which encompass the G-C-rich promoter associated with exon 1a and uses the same splice donor site. RT-PCR analyses of two primary breast epithelial cell lines identified two other 5'-UTRs generated by alternative splicing within exon 1c. Our results thus highlight the existence of an unexpected complex transcriptional regulation of HIC1.


Two class Bayes point machines in repayment prediction of low credit borrowers.
Decision-making in the peer-to-peer loan market has not been studied as extensively as traditional lending mostly because of the perceived risk in dealing with low credit borrowers seeking funding alternatives. We develop a machine learning-based approach to test the viability and usefulness in peer-to-peer loan repayment predictions among low credit borrowers. This analysis provides potential benefits that could strengthen the lending market with a more reliable method of identifying applications from promising candidates with low credit. Here an experiment will be performed to measure the performance of a model used for classifying peer-to-peer loan data. The aim is to aid the repayment prediction capabilities of peer lenders when analyzing low credit applicants. A binary classification algorithm is used to build the model and applied to actual historical loan data to evaluate performance. Experiment results, visualizations, and key performance indicators are discussed in the work to influence confidence in using the method proposed.


Assessment of corrected flow time in carotid artery via point-of-care ultrasonography: Reference values and the influential factors.
Assessment of Corrected Flow Time (FTc) in carotid artery has been suggested recently as a measure of intravascular volume status. This study aimed to determine the reference values of FTc in carotid artery in a normal population. A total number of 142 healthy volunteers (73 females and 69 males) with a mean age of 36.65±10.52years were included. The mean FTc in carotid artery was 325.18±22.15ms0.5. The mean value of FTc differed significantly between females and males both before and after passive leg raise (PLR) (330.18±21.61ms0.5 vs. 319.88±21.62, P=0.005 before PLR, and 336.89±22.95ms0.5 vs. 326.51±21.21, P=0.006 after PLR). This study would potentially pave the way to determine clinically significant cutoff points in order to assess the diagnostic accuracy of FTc in predicting intravascular volume status and fluid therapy responsiveness.


The role of mucins in gastrointestinal barrier function during health and disease.
Mucins are the gatekeepers of the mucosal barrier of the gastrointestinal tract and are aberrantly expressed in various gastrointestinal pathologies, including pathogen infection, inflammation, and uncontrolled growth and spread of abnormal cells. Although several studies have emphasised the role of mucins in dysfunction of the gastrointestinal mucosal barrier, they are often still considered to be passive mediators of this barrier instead of regulators or modulators. In this Review, we discuss the interactions between mucins and gastrointestinal barrier function during health and disease. We will focus on the bidirectional relationship between mucins and the gut microbiota and will also address the molecular mechanisms involved in key cell signalling pathways, such as inflammation, cell interactions, and cell differentiation, proliferation, and survival. Additionally, we highlight the potential use of mucins in the diagnosis, follow-up, and treatment of gastrointestinal diseases, such as chronic inflammatory diseases and cancer.


A mixture model approach to multiple testing for the genetic analysis of gene expression.
With the availability of very dense genome-wide maps of markers, multiple testing has become a major difficulty for genetic studies. In this context, the false-discovery rate (FDR) and related criteria are widely used. Here, we propose a finite mixture model to estimate the local FDR (lFDR), the FDR, and the false non-discovery rate (FNR) in variance-component linkage analysis. Our parametric approach allows empirical estimation of an appropriate null distribution. The contribution of our model to estimation of FDR and related criteria is illustrated on the microarray expression profiles data set provided by the Genetic Analysis Workshop 15 Problem 1.


The Taiwanese hepatitis C virus genome: sequence determination and mapping the 5' termini of viral genomic and antigenomic RNA.
The complete nucleotide sequence of hepatitis C virus (HCV) cloned from the liver tissue of a Taiwanese patient with post-transfusion type C hepatitis was determined. The 5' end of HCV genomic RNA was located 341 nucleotides upstream from the initiation codon for the viral polyprotein open reading frame. The 5' end of the viral antigenomic RNA was shown to have 13 consecutive As. Thus the 3' terminus of the viral genome is a stretch of U which ends about 50 nucleotides downstream from the stop codon of the large open reading frame. The nucleotide sequence homology between this HCV strain and two Japanese isolates was 90.5 and 90.7%, respectively. Homology with the United States strain, however, was only 77.8%. Accordingly, the indigenous Taiwanese HCV strain is of the same subtype as the Japanese isolates. Novel features of the viral genome termini are possibly relevant to HCV genome replication.


Association of In Vivo Adipose Tissue Cellular Kinetics With Markers of Metabolic Health in Humans.
Adipose tissue (AT) expansion occurs by hypertrophy and hyperplasia. Impaired hyperplasia, or adipogenesis, has been associated with obesity-related diseases. We examined how in vivo adipogenesis in the subcutaneous abdominal (scABD) and femoral (scFEM) depots (via 8-week incorporation of deuterium) correlates with markers of metabolic health. Data from 52 women with obesity [27 black and 25 white; 29.7 ± 5.5 years; body mass index (BMI) 32.2 ± 2.8 kg/m2; 44.3% ± 4.0% body fat] were analyzed at Pennington Biomedical Research Center. A linear repeated measure model was used to assess the fraction of new adipose cells and the associated covariates. Akaike information criterion determined the covariates that best described the data. Simple associations were examined using Spearman's correlation. The covariates that were associated with adipose kinetics included BMI, visceral AT/total abdominal AT (VAT/TAT) ratio, and the Matsuda index. Simple correlations demonstrated that adipocyte and preadipocyte formation in scABD (P = 0.02 and P = 0.16, trend, respectively) and scFEM (P = 0.01 and P = 0.24, trend, respectively) depots correlated positively with VAT/TAT. Preadipocyte and adipocyte formation in the scABD (P < 0.0001 and P = 0.02, respectively) and scFEM (P = 0.0001 and P = 0.003, respectively) was negatively associated with insulin sensitivity. Our results challenge the AT expandability hypothesis and suggest that higher in vivo adipose cell turnover is positively associated with BMI and VAT/TAT and negatively associated with insulin sensitivity, all correlates of impaired metabolic health.


Comparative carcinogenic potencies of 7H-dibenzo[c,g]carbazole, dibenz[a,j]acridine and benzo[a]pyrene in mouse skin.
The relative carcinogenic potencies of three combustion products of fossil fuels, 7H-dibenzo[c,g]carbazole (7H-DB[c,g]C), dibenz[a,j]acridine (DB[a,j]A) and benzo[a] pyrene (B[a]P) were compared using complete carcinogenicity C3H mouse skin bioassays. Both 7H-DB[c,g]C and B[a]P produced tumors in 48 of 50 mice with latency periods of 36.6 and 32.4 weeks, respectively. DB[a,j]A produced tumors in 25 of 50 mice with a latency period of 80 weeks. 7H-DB[c,g]C was found to be as potent a carcinogen as B[a]P when applied to mouse skin. These results have important implications in the determination of relative carcinogenic potencies of complex mixtures.


Patterns of trace element deposition in beluga whale teeth reflect early life history.
Determination of trace element concentrations in continuously growing biological structures such as otoliths, whiskers, and teeth can provide important insight into physiological and ontogenetic processes. We examined concentrations of 11 trace elements (Li, Mg, Mn, Cu, Zn, Se, Rb, Sr, Cs, Ba, Pb) in the annual dentine growth layer groups (GLGs) of teeth of 66 Eastern Canadian Arctic belugas (Delphinapterus leucas). Several of these trace elements displayed clear and consistent patterns in early life, though few longer term trends or signals were present in trace element data for either females or males. Large changes in Sr and Ba concentrations in fetal dentine reflected in utero shifts in element deposition in the teeth of developing belugas. Marked changes in these elements during the first years after birth were likely associated with the onset of nursing and subsequent weaning. Mg, Mn, and Zn also displayed clear and consistent patterns in early life that correlated strongly with dentine stable nitrogen isotope (δ15N) data, suggesting these elements merit further study as potential tools for studying nursing and weaning. Depositional patterns of Zn and Pb, which have been linked to sexual maturation in female Pacific walruses (Odobenus rosmarus divergens), were inconsistent in beluga teeth. Some individuals (including males) displayed patterns strongly resembling those observed in female walruses, whereas many animals did not, perhaps because they had not yet reached sexual maturity. The lack of clear patterns in trace element deposition after the first few years of life may have resulted from pooling samples from multiple populations/regions collected across more than two decades, but may also indicate that elemental concentrations are primarily driven by other, extrinsic processes later in life, and might be useful as biomonitors of environmental element concentrations or tools for delineating population structure.


Modulation of cartilage destruction in murine arthritis with anti-IL-1 antibodies.
One of the early events in murine antigen-induced arthritis is the generation of IL-1 in the inflamed joint. We investigated the role of IL-1 in the acute phase of the arthritic process by selective blockage of IL-1 bioactivity by treatment with neutralizing antibodies. Pretreatment with anti-IL-1 antibodies moderately suppressed joint swelling. The decrease in chondrocyte proteoglycan synthesis seen in the acute phase of arthritis was prevented by treatment with anti-IL-1 antibodies. IL-1 does not appear to be a major contributor to the accelerated breakdown of articular cartilage in this model. The major impact of anti-IL-1 antibodies was the prevention of proteoglycan synthesis inhibition which clearly reduced articular cartilage depletion by maintaining normal proteoglycan synthesis.


Phenylphenalenones and oxabenzochrysenones from the Australian plant Haemodorum simulans.
Chemical investigation of the Australian plant Haemodorum simulans (Haemodoraceae) resulted in the isolation of two new phenylphenalenones, haemoxiphidone and haemodordioxolane from the bulbs together with the first report of an oxabenzochrysenone glycoside, haemodoroxychrysenose from the aerial parts of the plant. Also isolated were two previously described phenylphenalenones 5,6-dimethoxy-7-phenyl-1H,3H-naphtho[1,8-cd]pyran-1,3-dione and haemodorone and two oxabenzochrysenones 5-hydroxyl-2-methoxy-1H-naphtho[2,1,8-mna]xanthen-1-one and 5-methoxy-1H-naphtho[2,1,8-mna]xanthen-1-one. The X-ray structure of the phenylphenalenone 5,6-dimethoxy-7-phenyl-1H,3H-naphtho[1,8-cd]pyran-1,3-dione was secured for the first time. All compounds were deduced by detailed spectroscopic analyses. HPLC-NMR chemical profiling of an enriched fraction containing a mixture of haemodordioxolane and 5,6-dimethoxy-7-phenyl-1H,3H-naphtho[1,8-cd]pyran-1,3-dione facilitated the partial identification of these secondary metabolites. The structure previously assigned as xiphidone in our initial studies of this plant was re-assigned as the new isomer haemoxiphidone.


The role of protein-protein interactions mediated by the PB1 domain of NLP transcription factors in nitrate-inducible gene expression.
NIN-LIKE PROTEIN (NLP) transcription factors are master regulators of nitrate-inducible gene expression in higher plants. NLP transcription factors contain a nitrate signal-responsive domain in the amino-terminal region, an RWP-RK-type DNA-binding domain in the middle, and a Phox and Bem1 (PB1) domain at the carboxy terminus. Although the PB1 domain of NLP transcription factors appears to mediate protein-protein interactions associated with nitrate-inducible gene expression in higher plants, its precise role in nitrate-inducible gene expression has not previously been characterized. Yeast two-hybrid assays with the PB1 domain of the Arabidopsis transcription factor NLP7 revealed NLP-NLP interactions that required the core amino acid residues (K867, D909, D911, and E913) within the PB1 domain. Consistent with previous speculation on redundant and overlapping functions between different Arabidopsis NLP transcription factors, NLP-NLP interactions were observed between a variety of combinations of different NLP transcription factors. Furthermore, a mutated form of NLP7 that harbored amino acid substitutions at K867, D909, D911, and E913 required a far higher level of expression than wild-type NLP7 to restore nitrate-responsive gene expression and growth of nlp6 nlp7-1 double mutants. Surprisingly, however, the ability to transactivate nitrate-responsive promoters in protoplast transient expression assays was similar between wild-type and mutant forms of NLP7, suggesting that the PB1 domain was not required for transcription from naked DNA. Protein-protein interactions mediated by the PB1 domain of NLP transcription factors are necessary for full induction of nitrate-dependent expression of target genes in planta. The PB1 domains of NLP transcription factors may act on gene expression from chromosomal DNA via homo- and hetero-oligomerization in the presence of nitrate.


Duodenal intussusception of Brunner's gland adenoma mimicking a pancreatic tumour.
Brunner's gland adenoma is a rare benign tumour of the duodenum. It is usually asymptomatic but may occasionally present with gastrointestinal haemorrhage and obstruction. We report a 40-year old lady, presenting with upper gastrointestinal bleeding and was found to have prolapsed and intussuscepted Brunner's gland adenoma of the duodenum, which mimicked the appearance of a tumour in the head of pancreas.


Neuropsychological and psychiatric changes following treatment of ARC patients with zidovudine.
Six homosexual men with a diagnosis of acquired immunodeficiency syndrome (AIDS)-related complex (ARC- CDC IVA/C2) were assessed with a series of neuropsychological and psychiatric tests prior to commencing treatment with zidovudine and again after 5-6 months. Significant improvements were seen in cognitive functioning, mental state and physical health at the second assessment.


Effect of vitamin E supplementation on lipid peroxidation in blood and lung of influenza virus infected mice.
The influenza virus infection (A/Aichi/2/68) was associated with development of oxidative stress in lung and blood of mice, accompanied by an increase in levels of lipid peroxidation products (conjugated dienes and total malondialdehyde) and a decrease in endogenous amounts of natural antioxidant vitamin E. These effects were most pronounced on the 5th day after virus inoculation, in comparison with those on the 7th. Supplementation of mice with exogenous vitamin E before virus inoculation lead to lung and blood protection against lipid peroxidation. A marked decrease in lipid peroxidation products and an increase in vitamin E content was established in blood and lung on the 5th and 7th day after virus inoculation. The stabilizing effect of vitamin E is dose-dependent in blood and dose-independent in lung, and was most pronounced on the 5th day after virus inoculation in comparison with the 7th day.


Chaotic advection mixer for capturing transient states of diverse biological macromolecular systems with time-resolved small-angle X-ray scattering.
Advances in time-resolved structural techniques, mainly in macromolecular crystallography and small-angle X-ray scattering (SAXS), allow for a detailed view of the dynamics of biological macromolecules and reactions between binding partners. Of particular promise, are mix-and-inject techniques, which offer a wide range of experimental possibility as microfluidic mixers are used to rapidly combine two species just prior to data collection. Most mix-and-inject approaches rely on diffusive mixers, which have been effectively used within crystallography and SAXS for a variety of systems, but their success is dependent on a specific set of conditions to facilitate fast diffusion for mixing. The use of a new chaotic advection mixer designed for microfluidic applications helps to further broaden the types of systems compatible with time-resolved mixing experiments. The chaotic advection mixer can create ultra-thin, alternating layers of liquid, enabling faster diffusion so that even more slowly diffusing molecules, like proteins or nucleic acids, can achieve fast mixing on timescales relevant to biological reactions. This mixer was first used in UV-vis absorbance and SAXS experiments with systems of a variety of molecular weights, and thus diffusion speeds. Careful effort was also dedicated to making a loop-loading sample-delivery system that consumes as little sample as possible, enabling the study of precious, laboratory-purified samples. The combination of the versatile mixer with low sample consumption opens the door to many new applications for mix-and-inject studies.


Currarino syndrome: variable imaging features in three siblings with HLXB9 gene mutation.
Currarino syndrome (CS) is characterized by the triad of partial sacral defect, anorectal malformation, and presacral mass and has been recently reported to be associated with mutations in the HLXB9 gene, which have been suggested to be the genetic background of CS. Phenotypic expression of the HLXB9 gene mutation in a CS family varies from an incomplete to a complete triad. We present variable clinical and imaging features of CS in three siblings with genetically identified HLXB9 mutation. Clinical presentation, management and outcome were also reviewed, and we suggest that magnetic resonance imaging should be used as a screening tool in the members of a CS family with genetic mutation in order to avoid morbidity and mortality from an undiagnosed presacral mass.


Engineered protein function by selective amino acid diversification.
Almost all protein engineering methods rely upon making changes to naturally occurring proteins that already possess some of the desired properties. This will probably remain the case as long as we lack a complete understanding of the way that an amino acid sequence gives rise to a protein with a precisely defined biological function. Common to all methods for altering an existing protein is the selection of a subset of amino acids in the protein for variation and a choice of which substitutions to make at each position. Variants are then tested empirically and further variants are created based upon their performance. Differences between protein engineering methods are the ways in which amino acids are chosen for variation, the protocols followed for creating the variants, and how information regarding variant properties is used in creating subsequent variants. In this article, we describe these differences and provide examples of how the experimental parameters of specific projects determine which method is most suitable.


Rationale for sequential use of both maxillary and mandibular orthopedic appliances in the treatment of TMJ disorders.
This paper describes how the use of a combination of maxillary and mandibular orthopedic appliances by TMJ patients can reduce iatrogenic stress and improve patient compliance with 24-hour use. This combination provides the patient with a proper appliance for anterior repositioning when sleeping and eliminates the fear of iatrogenic tooth depression or movement.


Characterization and pathogenicity of a novel mammalian orthoreovirus from wild short-nosed fruit bats.
Mammalian orthoreoviruses (MRVs) have a wide range of geographic distribution and have been isolated from humans and various animals. This study describes the isolation, molecular characterization and analysis of pathogenicity of MRV variant B/03 from wild short-nosed fruit bats. Negative stain electron microscopy illustrated that the B/03 strain is a non-enveloped icosahedral virus with a diameter of 70nm. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) migration patterns showed that the B/03 viral genome contains 10 segments in a 3:3:4 arrangement. The isolate belongs to MRV serotype 1 based on S1 gene nucleotide sequence data. BALB/c mice experimentally infected with B/03 virus by intranasal inoculation developed severe respiratory distress with tissue damage and inflammation. Lastly, B/03 virus has an increased transmission risk between bats and humans or animals.


Genetic Studies in Autism.
Autism is a complex neurodevelopmental disorder, which has captured the attention of not only pediatricians but also the parents. From the symptoms until the final diagnosis, parents undergo a diagnostic odyssey that involves a battery of tests without much yield. This has led to an increase in the referrals to the clinical geneticists to rule out the possible genetic etiology that can have implications for the parents for future pregnancy. This chapter focuses on the various genetic causes and their appropriate application in the evaluation of a child with Autism Spectrum Disorders (ASDs).


Effects of opioid drugs on capsaicin-sensitive neurones in guinea-pig atria.
Transmural nerve stimulation of isolated guinea-pig atria in the presence of atropine induced a biphasic positive inotropic effect but only a slow increase in contractility (NANC response) in atria obtained from 6-hydroxy-dopamine-pretreated animals. The latter effect disappeared after exposure of the preparations to capsaicin. The effects of some opioid peptides were investigated on NANC responses. [D-Ala2,D-Leu5]enkephalin (DADLE) and [D-Ala2,N-Me-Phe4,Gly5-ol]enkephalin (DAGO, 0.1-10 microM) inhibited the cardiac response to transmural nerve stimulation in a dose-dependent and naloxone-sensitive manner. Dynorphin-(1-13) and morphine, at 10-fold higher concentrations (1-10 microM), reduced the response in a naloxone-sensitive manner. Naloxone alone however did not affect the response. Opioid peptides were not able to reduce the positive inotropic effect induced by calcitonin gene-related peptide (CGRP), or the increase in cardiac contractility produced by capsaicin. These results suggest that opioid receptors exert a modulatory role on peripheral terminals of capsaicin-sensitive sensory nerves.


Prognostic value of pretransplant FDG-PET in refractory/relapsed Hodgkin lymphoma treated with autologous stem cell transplantation: systematic review and meta-analysis.
This study aimed to systematically review the prognostic value of pretransplant (18)F-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) in refractory/relapsed Hodgkin lymphoma treated with autologous stem cell transplantation (SCT). MEDLINE was systematically searched for appropriate studies. Included studies were methodologically appraised. Results of individual studies were meta-analyzed, if possible. Eleven studies, comprising a total of 745 refractory/relapsed Hodgkin lymphoma patients who underwent FDG-PET before autologous SCT, were included. The overall methodological quality of these studies was moderate. The proportion of pretransplant FDG-PET positive patients ranged between 25 and 65.2 %. Progression-free survival ranged between 0 and 52 % in pretransplant FDG-PET positive patients, and between 55 and 85 % in pretransplant FDG-PET negative patients. Overall survival ranged between 17 and 77 % in pretransplant FDG-PET positive patients, and between 78 and 100 % in FDG-PET negative patients. Based on five studies that provided sufficient data for meta-analysis, pooled sensitivity and specificity of pretransplant FDG-PET in predicting treatment failure (i.e., either progressive, residual, or relapsed disease) were 67.2 % (95 % confidence interval [CI] 58.2-75.3 %) and 70.7 % (95 % CI 64.2-76.5 %), respectively. Based on two studies that provided sufficient data for meta-analysis, pooled sensitivity and specificity of pretransplant FDG-PET in predicting death during follow-up were 74.4 % (95 % CI 58.8-86.5 %) and 58.0 % (95 % CI 49.3-66.3 %), respectively. In conclusion, the moderate quality evidence suggests pretransplant FDG-PET to have value in predicting outcome in refractory/relapsed Hodgkin lymphoma patients treated with autologous SCT. Nevertheless, a considerable proportion of pretransplant FDG-PET positive patients remains disease free and a considerable proportion of pretransplant FDG-PET negative patients develops disease relapse after autologous SCT.


Butyrylcholinesterase and lipid metabolism: Possible dual role in metabolic disorders.
Butyrylcholinesterase (BChE), an enzyme primarily found in the liver, plasma, and brain, has been recognized for its role in the hydrolysis of choline esters. Recent studies have shed light on its involvement in lipid metabolism, revealing its potential as a crucial player in maintaining lipid homeostasis. However, the interactions between external factors and BChE activity in lipid metabolic pathways remain a complex subject of study. This review summarizes the current knowledge regarding BChE activity and lipid metabolism and seeks to clarify the nature of this relationship as causal or consequential. Evidence supports the role of BChE in energy homeostasis disruption, such as obesity and related metabolic disorders, where it exhibits lipolytic activity and mediates fatty acid use and storage. The unexpected functions of BChE in lipoprotein synthesis and the impact of polymorphic variants of the BCHE gene suggest a central role in lipid metabolism; however, further investigation is needed to confirm and describe these functions, especially considering the metabolic context. Furthermore, exploring therapeutic interventions in lipid metabolism disorders contributes to elucidating their implications on BChE activity, but attention to the metabolic status and genotypes as possible factors in this interaction is needed. In summary, further research in this field holds promise for improving our understanding of the complex interplay between BChE and lipid metabolism, and its potential clinical applications. However, the available data corroborate the dual role of BChE activity, both as a critical responsive element to metabolic challenges and as a predisposition factor to metabolic diseases.


Testing trivializing maps in the Hybrid Monte Carlo algorithm.
We test a recent proposal to use approximate trivializing maps in a field theory to speed up Hybrid Monte Carlo simulations. Simulating the CPN-1 model, we find a small improvement with the leading order transformation, which is however compensated by the additional computational overhead. The scaling of the algorithm towards the continuum is not changed. In particular, the effect of the topological modes on the autocorrelation times is studied.


Effects of different types of isocaloric parenteral nutrients on food intake and metabolic concomitants.
Whether spontaneous food intake (SFI) is controlled by infused nutrient type or its caloric content, irrespective of nutrient type, was investigated. Rats were infused for 4 days with isocaloric solutions of different nutrient type but sharing the same intermediary metabolic oxidative pathway, providing 25% of daily caloric needs. One parenteral solution was a glucose, fat and amino acid mix (TPN-25%); the other provided ketone bodies (TRI-3.5%). Effects of parenteral infusions on SFI and metabolic concomitants were compared and contrasted to that in a group of orally fed rats. Both infusions reduced SFT by 50%. Rats receiving TRI-3.5% had lower blood glucose and insulin concentrations, but increased hepatic glycogen content compared to TPN-25% or orally fed rats. No differences in hepatic triglycerides occurred between the three groups. However, serum free fatty acids were significantly lower in TRI-3.5% and in TPN-25% groups vs. fed rats. Data indicate food intake suppression is mediated by caloric content rather than nutrient type, suggesting that a mediator of SFI regulation could be at the citric acid cycle level.


Lipolysosomes in human liver: distribution in livers with fatty infiltration.
In this study we investigated whether lipolysosomes--lysosomes containing large lipid droplets--were present in livers of patients with various forms of hepatic injury. Organelles which displayed the same morphological characteristics and enzymatic activity as those originally described in the hamster and those found in the hepatocytes of patients with Wolman's or Wilson's disease were also found in hepatocytes of 13 of 14 randomly selected biopsy specimens from patients with minimal to severe fatty infiltration of the liver. The numbers and sizes of the lipolysosomes seemed to increase with the degree of fatty infiltration while their proportion in relation to the total number of lipid droplets remained below 5%. Based on these observations of a virtually constant association of lipolysosomes with excess lipid accumulation in liver cells we suggest that lysosomes probably play an important role in hepatic lipid metabolism and that various pathogenetic mechanisms may trigger their proliferation.


Serum regulation of collagen biosynthesis in human diploid fibroblasts.
The mechanism by which serum stimulates collagen production by fibroblasts was examined. Fibroblasts were exposed to various concentrations of serum and collagen production and mRNA levels were measured. Collagen production was determined as collagenase digestible radioactivity and collagen mRNA levels were measured using a [35S]UTP-labelled pro alpha 1[I] probe. The results showed that increased collagen production correlated with enhanced mRNA levels. Extra- and intracellular collagen degradation was similar in control and serum treated cultures, and "G1" and "S" phase fibroblasts contained similar levels of collagen mRNA. We conclude that serum regulation of collagen synthesis occurs primarily at the transcriptional level and that activation of collagen synthesis is not coupled to mitogenic stimulation.